{"id": "0", "text": "IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase .", "annotated_text": "<dna>IL-2 gene</dna> expression and <protein>NF-kappa B</protein> activation through <protein>CD28</protein> requires reactive oxygen production by <protein>5-lipoxygenase</protein> ."}
{"id": "1", "text": "Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 ( IL-2 ) and cell proliferation .", "annotated_text": "Activation of the <protein>CD28 surface receptor</protein> provides a major costimulatory signal for T cell activation resulting in enhanced production of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) and cell proliferation ."}
{"id": "2", "text": "In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates ( ROIs ) which are required for CD28 -mediated activation of the NF-kappa B / CD28-responsive complex and IL-2 expression .", "annotated_text": "In <cell_type>primary T lymphocytes</cell_type> we show that <protein>CD28</protein> ligation leads to the rapid intracellular formation of reactive oxygen intermediates ( ROIs ) which are required for <protein>CD28</protein> -mediated activation of the <protein>NF-kappa B</protein> / <protein>CD28-responsive complex</protein> and <protein>IL-2</protein> expression ."}
{"id": "3", "text": "Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity , followed by the activation of phospholipase A2 and 5-lipoxygenase .", "annotated_text": "Delineation of the <protein>CD28</protein> signaling cascade was found to involve <protein>protein tyrosine kinase</protein> activity , followed by the activation of <protein>phospholipase A2</protein> and <protein>5-lipoxygenase</protein> ."}
{"id": "4", "text": "Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation .", "annotated_text": "Our data suggest that <protein>lipoxygenase metabolites</protein> activate ROI formation which then induce <protein>IL-2</protein> expression via <protein>NF-kappa B</protein> activation ."}
{"id": "5", "text": "These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway .", "annotated_text": "These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the <protein>CD28</protein> costimulatory pathway ."}
{"id": "6", "text": "The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells .", "annotated_text": "The <dna>peri-kappa B site</dna> mediates <dna>human immunodeficiency virus type 2 enhancer</dna> activation in <cell_type>monocytes</cell_type> but not in <cell_type>T cells</cell_type> ."}
{"id": "7", "text": "Human immunodeficiency virus type 2 ( HIV-2 ) , like HIV-1 , causes AIDS and is associated with AIDS cases primarily in West Africa .", "annotated_text": "Human immunodeficiency virus type 2 ( HIV-2 ) , like HIV-1 , causes AIDS and is associated with AIDS cases primarily in West Africa ."}
{"id": "8", "text": "HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease .", "annotated_text": "HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease ."}
{"id": "9", "text": "Consistent with these differences , we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1 .", "annotated_text": "Consistent with these differences , we have previously demonstrated that the <dna>enhancer/promoter region</dna> of HIV-2 functions quite differently from that of HIV-1 ."}
{"id": "10", "text": "Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat , activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements : a single kappa B site , two purine-rich binding sites , PuB1 and PuB2 , and a pets site .", "annotated_text": "Whereas activation of the <dna>HIV-1 enhancer</dna> following T-cell stimulation is mediated largely through binding of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> to two adjacent <dna>kappa B sites</dna> in the <dna>HIV-1 long terminal repeat</dna> , activation of the <dna>HIV-2 enhancer</dna> in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> is dependent on four <dna>cis-acting elements</dna> : a single <dna>kappa B site</dna> , two <dna>purine-rich binding sites</dna> , <dna>PuB1</dna> and <dna>PuB2</dna> , and a <dna>pets site</dna> ."}
{"id": "11", "text": "We have now identified a novel cis-acting element within the HIV-2 enhancer , immediately upstream of the kappa B site , designated peri-kappa B .", "annotated_text": "We have now identified a novel <dna>cis-acting element</dna> within the <dna>HIV-2 enhancer</dna> , immediately upstream of the <dna>kappa B site</dna> , designated <dna>peri-kappa B</dna> ."}
{"id": "12", "text": "This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus , and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines .", "annotated_text": "This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus , and transfection assays show this site to mediate <dna>HIV-2 enhancer</dna> activation following stimulation of <cell_line>monocytic</cell_line> but not <cell_line>T-cell lines</cell_line> ."}
{"id": "13", "text": "This is the first description of an HIV-2 enhancer element which displays such monocyte specificity , and no comparable enhancer element has been clearly defined for HIV-1 .", "annotated_text": "This is the first description of an <dna>HIV-2 enhancer element</dna> which displays such monocyte specificity , and no comparable <dna>enhancer element</dna> has been clearly defined for HIV-1 ."}
{"id": "14", "text": "While a nuclear factor ( s ) from both peripheral blood monocytes and T cells binds the peri-kappa B site , electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells , thus supporting the transfection data .", "annotated_text": "While a <protein>nuclear factor</protein> ( s ) from both <cell_type>peripheral blood monocytes</cell_type> and <cell_type>T cells</cell_type> binds the <dna>peri-kappa B site</dna> , electrophoretic mobility shift assays suggest that either a different protein binds to this site in <cell_type>monocytes</cell_type> versus <cell_type>T cells</cell_type> or that the protein recognizing this <dna>enhancer element</dna> undergoes differential modification in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> , thus supporting the transfection data ."}
{"id": "15", "text": "Further , while specific constitutive binding to the peri-kappa B site is seen in monocytes , stimulation with phorbol esters induces additional , specific binding .", "annotated_text": "Further , while specific constitutive binding to the <dna>peri-kappa B site</dna> is seen in <cell_type>monocytes</cell_type> , stimulation with phorbol esters induces additional , specific binding ."}
{"id": "16", "text": "Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis .", "annotated_text": "Understanding the monocyte-specific function of the <protein>peri-kappa B factor</protein> may ultimately provide insight into the different role <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> play in HIV pathogenesis ."}
{"id": "17", "text": "E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells .", "annotated_text": "<dna>E1A gene</dna> expression induces susceptibility to killing by <cell_type>NK cells</cell_type> following immortalization but not adenovirus infection of <cell_type>human cells</cell_type> ."}
{"id": "18", "text": "Adenovirus ( Ad ) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells .", "annotated_text": "Adenovirus ( Ad ) infection and <protein>E1A</protein> transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable <protein>E1A</protein> expression in <cell_type>human cells</cell_type> ."}
{"id": "19", "text": "Only stably transfected target cells exhibited cytolytic susceptibility , despite expression of equivalent levels of E1A proteins in Ad-infected targets .", "annotated_text": "Only stably <cell_line>transfected target cells</cell_line> exhibited cytolytic susceptibility , despite expression of equivalent levels of <protein>E1A proteins</protein> in <cell_line>Ad-infected targets</cell_line> ."}
{"id": "20", "text": "The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells .", "annotated_text": "The inability of <dna>E1A gene</dna> products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible <cell_type>target cells</cell_type> or by <dna>viral gene</dna> effects on <protein>class I MHC antigen</protein> expression on <cell_type>target cells</cell_type> ."}
{"id": "21", "text": "This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host .", "annotated_text": "This differential effect of <protein>E1A</protein> expression on the cytolytic phenotypes of infected and stably transfected <cell_type>human cells</cell_type> suggests that <cell_type>human NK cells</cell_type> provide an effective immunologic barrier against the in vivo survival and neoplastic progression of <cell_line>E1A-immortalized cells</cell_line> that may emerge from the reservoir of <cell_type>persistently infected cells</cell_type> in the human host ."}
{"id": "22", "text": "Distinct signaling properties identify functionally different CD4 epitopes .", "annotated_text": "Distinct signaling properties identify functionally different <protein>CD4 epitopes</protein> ."}
{"id": "23", "text": "The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation .", "annotated_text": "The <protein>CD4 coreceptor</protein> interacts with <protein>non-polymorphic regions</protein> of <protein>major histocompatibility complex class II molecules</protein> on <cell_type>antigen-presenting cells</cell_type> and contributes to T cell activation ."}
{"id": "24", "text": "We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies ( mAb ) which recognize different CD4 epitopes .", "annotated_text": "We have investigated the effect of <protein>CD4</protein> triggering on T cell activating signals in a lymphoma model using <protein>monoclonal antibodies</protein> ( <protein>mAb</protein> ) which recognize different <protein>CD4 epitopes</protein> ."}
{"id": "25", "text": "We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression .", "annotated_text": "We demonstrate that <protein>CD4</protein> triggering delivers signals capable of activating the <protein>NF-AT transcription factor</protein> which is required for <protein>interleukin-2</protein> gene expression ."}
{"id": "26", "text": "Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein , which mediates signals to Ras , they differed significantly in their ability to activate NF-AT .", "annotated_text": "Whereas different <protein>anti-CD4 mAb</protein> or <protein>HIV-1 gp120</protein> could all trigger activation of the <protein>protein tyrosine kinases</protein> <protein>p56lck</protein> and <protein>p59fyn</protein> and phosphorylation of the <protein>Shc adaptor protein</protein> , which mediates signals to <protein>Ras</protein> , they differed significantly in their ability to activate <protein>NF-AT</protein> ."}
{"id": "27", "text": "Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore .", "annotated_text": "Lack of full activation of <protein>NF-AT</protein> could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore ."}
{"id": "28", "text": "The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways .", "annotated_text": "The results identify functionally distinct <protein>epitopes</protein> on the <protein>CD4 coreceptor</protein> involved in activation of the <protein>Ras/protein kinase C</protein> and calcium pathways ."}
{"id": "29", "text": "Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor .", "annotated_text": "Ligand-dependent repression of the <protein>erythroid transcription factor</protein> <protein>GATA-1</protein> by the <protein>estrogen receptor</protein> ."}
{"id": "30", "text": "High-dose estrogen administration induces anemia in mammals .", "annotated_text": "High-dose estrogen administration induces anemia in mammals ."}
{"id": "31", "text": "In chickens , estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation .", "annotated_text": "In chickens , estrogens stimulate outgrowth of <cell_type>bone marrow-derived erythroid progenitor cells</cell_type> and delay their maturation ."}
{"id": "32", "text": "This delay is associated with down-regulation of many erythroid cell-specific genes , including alpha- and beta-globin , band 3 , band 4.1 , and the erythroid cell-specific histone H5 .", "annotated_text": "This delay is associated with down-regulation of many <dna>erythroid cell-specific genes</dna> , including <dna>alpha- and beta-globin</dna> , band 3 , band 4.1 , and the <protein>erythroid cell-specific histone</protein> <protein>H5</protein> ."}
{"id": "33", "text": "We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures .", "annotated_text": "We show here that estrogens also reduce the number of <cell_type>erythroid progenitor cells</cell_type> in <cell_line>primary human bone marrow cultures</cell_line> ."}
{"id": "34", "text": "To address potential mechanisms by which estrogens suppress erythropoiesis , we have examined their effects on GATA-1 , an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes .", "annotated_text": "To address potential mechanisms by which estrogens suppress erythropoiesis , we have examined their effects on <protein>GATA-1</protein> , an <protein>erythroid transcription factor</protein> that participates in the regulation of the majority of <dna>erythroid cell-specific genes</dna> and is necessary for full maturation of <cell_type>erythrocytes</cell_type> ."}
{"id": "35", "text": "We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor ( ER ) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen .", "annotated_text": "We demonstrate that the transcriptional activity of <protein>GATA-1</protein> is strongly repressed by the <protein>estrogen receptor</protein> ( <protein>ER</protein> ) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen ."}
{"id": "36", "text": "ER -mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site , as well as in the context of an intact promoter which is normally regulated by GATA-1 .", "annotated_text": "<protein>ER</protein> -mediated repression of <protein>GATA-1</protein> activity occurs on an <dna>artificial promoter</dna> containing a single <dna>GATA-binding site</dna> , as well as in the context of an <dna>intact promoter</dna> which is normally regulated by <protein>GATA-1</protein> ."}
{"id": "37", "text": "GATA-1 and ER bind to each other in vitro in the absence of DNA .", "annotated_text": "<protein>GATA-1</protein> and <protein>ER</protein> bind to each other in vitro in the absence of DNA ."}
{"id": "38", "text": "In coimmunoprecipitation experiments using transfected COS cells , GATA-1 and ER associate in a ligand-dependent manner .", "annotated_text": "In coimmunoprecipitation experiments using transfected <cell_line>COS cells</cell_line> , <protein>GATA-1</protein> and <protein>ER</protein> associate in a ligand-dependent manner ."}
{"id": "39", "text": "Mapping experiments indicate that GATA-1 and the ER form at least two contacts , which involve the finger region and the N-terminal activation domain of GATA-1 .", "annotated_text": "Mapping experiments indicate that <protein>GATA-1</protein> and the <protein>ER</protein> form at least two contacts , which involve the finger region and the <protein>N-terminal activation domain</protein> of <protein>GATA-1</protein> ."}
{"id": "40", "text": "We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER .", "annotated_text": "We speculate that estrogens exert effects on erythropoiesis by modulating <protein>GATA-1</protein> activity through protein-protein interaction with the <protein>ER</protein> ."}
{"id": "41", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "42", "text": "Mouse interleukin-2 receptor alpha gene expression .", "annotated_text": "<dna>Mouse interleukin-2 receptor alpha gene</dna> expression ."}
{"id": "43", "text": "Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements .", "annotated_text": "<protein>Interleukin-1</protein> and <protein>interleukin-2</protein> control transcription via distinct <dna>cis-acting elements</dna> ."}
{"id": "44", "text": "We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors .", "annotated_text": "We have shown that <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) and <protein>IL-2</protein> control <dna>IL-2 receptor alpha ( IL-2R alpha ) gene</dna> transcription in <cell_line>CD4-CD8- murine T lymphocyte precursors</cell_line> ."}
{"id": "45", "text": "Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma ( PC60 ) .", "annotated_text": "Here we map the <dna>cis-acting elements</dna> that mediate interleukin responsiveness of the <dna>mouse IL-2R alpha gene</dna> using a <cell_line>thymic lymphoma-derived hybridoma</cell_line> ( <cell_line>PC60</cell_line> ) ."}
{"id": "46", "text": "The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic .", "annotated_text": "The transcriptional response of the <dna>IL-2R alpha gene</dna> to stimulation by <protein>IL-1</protein> + <protein>IL-2</protein> is biphasic ."}
{"id": "47", "text": "IL-1 induces a rapid , protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation .", "annotated_text": "<protein>IL-1</protein> induces a rapid , protein synthesis-independent appearance of <rna>IL-2R alpha mRNA</rna> that is blocked by inhibitors of <protein>NF-kappa B</protein> activation ."}
{"id": "48", "text": "It also primes cells to become IL-2 responsive and thereby prepares the second phase , in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts .", "annotated_text": "It also primes cells to become <protein>IL-2</protein> responsive and thereby prepares the second phase , in which <protein>IL-2</protein> induces a 100-fold further increase in <rna>IL-2R alpha transcripts</rna> ."}
{"id": "49", "text": "Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness , most importantly an NF-kappa B site conserved in the human and mouse gene .", "annotated_text": "Transient transfection experiments show that several elements in the <dna>promoter-proximal region</dna> of the <dna>IL-2R alpha gene</dna> contribute to <protein>IL-1</protein> responsiveness , most importantly an <dna>NF-kappa B site</dna> conserved in the <dna>human and mouse gene</dna> ."}
{"id": "50", "text": "IL-2 responsiveness , on the other hand , depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site .", "annotated_text": "<protein>IL-2</protein> responsiveness , on the other hand , depends on a <dna>78-nucleotide segment</dna> 1.3 kilobases upstream of the <dna>major transcription start site</dna> ."}
{"id": "51", "text": "This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced .", "annotated_text": "This segment functions as an <dna>IL-2-inducible enhancer</dna> and lies within a region that becomes <protein>DNase I</protein> hypersensitive in normal <cell_type>T cells</cell_type> in which <protein>IL-2R alpha</protein> expression has been induced ."}
{"id": "52", "text": "IL-2 responsiveness requires three distinct elements within the enhancer .", "annotated_text": "<protein>IL-2</protein> responsiveness requires three distinct <dna>elements</dna> within the <dna>enhancer</dna> ."}
{"id": "53", "text": "Two of these are potential binding sites for STAT proteins .", "annotated_text": "Two of these are potential binding sites for <protein>STAT proteins</protein> ."}
{"id": "54", "text": "Hematopoietic lineage commitment : role of transcription factors .", "annotated_text": "<cell_type>Hematopoietic lineage</cell_type> commitment : role of <protein>transcription factors</protein> ."}
{"id": "55", "text": "This review focuses on the roles of transcription factors in hematopoietic lineage commitment .", "annotated_text": "This review focuses on the roles of <protein>transcription factors</protein> in hematopoietic lineage commitment ."}
{"id": "56", "text": "A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types .", "annotated_text": "A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify <protein>transcription factors</protein> important in specifying <cell_type>hematopoietic cell types</cell_type> ."}
{"id": "57", "text": "Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis .", "annotated_text": "Next is presented a discussion of the use of <cell_type>embryonic stem cells</cell_type> in the analysis of <dna>hematopoietic gene</dna> expression and the use of targeted gene disruption to analyze the role of <protein>transcription factors</protein> in hematopoiesis ."}
{"id": "58", "text": "Finally , the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid , myeloid and lymphoid cell types is summarized .", "annotated_text": "Finally , the status of our current knowledge concerning the roles of <protein>transcription factors</protein> in the commitment to <cell_type>erythroid , myeloid and lymphoid cell types</cell_type> is summarized ."}
{"id": "59", "text": "Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes : simultaneous early expression of BZLF-1 and its repressor RAZ .", "annotated_text": "Epstein-Barr virus replicative gene transcription during de novo infection of <cell_type>human thymocytes</cell_type> : simultaneous early expression of <protein>BZLF-1</protein> and its repressor <protein>RAZ</protein> ."}
{"id": "60", "text": "Epstein-Barr virus ( EBV ) is known to infect B cells and epithelial cells .", "annotated_text": "Epstein-Barr virus ( EBV ) is known to infect <cell_type>B cells</cell_type> and <cell_type>epithelial cells</cell_type> ."}
{"id": "61", "text": "We and others have shown that EBV can also infect a subset of thymocytes .", "annotated_text": "We and others have shown that EBV can also infect a subset of <cell_type>thymocytes</cell_type> ."}
{"id": "62", "text": "Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection .", "annotated_text": "Infection of <cell_type>thymocytes</cell_type> was accompanied by the appearance of <dna>linear EBV genome</dna> within 8 hr of infection ."}
{"id": "63", "text": "Circularization of the EBV genome was not detected .", "annotated_text": "Circularization of the <dna>EBV genome</dna> was not detected ."}
{"id": "64", "text": "This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection .", "annotated_text": "This is in contrast to the infection in <cell_type>B cells</cell_type> where the genome can circularize within 24 hr of infection ."}
{"id": "65", "text": "The appearance of the BamHI ZLF-1 gene product , ZEBRA , by RT-PCR , was observed within 8 hr of infection .", "annotated_text": "The appearance of the <protein>BamHI ZLF-1 gene product</protein> , <protein>ZEBRA</protein> , by RT-PCR , was observed within 8 hr of infection ."}
{"id": "66", "text": "The appearance of a novel fusion transcript ( RAZ ) , which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus , was detected by RT-PCR .", "annotated_text": "The appearance of a novel <protein>fusion transcript</protein> ( <protein>RAZ</protein> ) , which comprised regions of the <dna>BZLF-1 locus</dna> and the adjacent <dna>BRLF-1 locus</dna> , was detected by RT-PCR ."}
{"id": "67", "text": "ZEBRA protein was also identified in infected thymocytes by immunoprecipitation .", "annotated_text": "<protein>ZEBRA protein</protein> was also identified in infected <cell_type>thymocytes</cell_type> by immunoprecipitation ."}
{"id": "68", "text": "In addition , we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter , rather than from the Cp/Wp promoter which is used in latently infected B cells .", "annotated_text": "In addition , we demonstrated that the <dna>EBNA-1 gene</dna> in infected <cell_type>thymocytes</cell_type> was transcribed from the <dna>Fp promoter</dna> , rather than from the <dna>Cp/Wp promoter</dna> which is used in <cell_type>latently infected B cells</cell_type> ."}
{"id": "69", "text": "Transcripts encoding gp350/220 , the major coat protein of EBV , were identified , but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes .", "annotated_text": "Transcripts encoding <protein>gp350/220</protein> , the <protein>major coat protein</protein> of EBV , were identified , but we did not find any evidence of transcription from the <dna>LMP-2A</dna> or <dna>EBER-1 loci</dna> in infected <cell_type>thymocytes</cell_type> ."}
{"id": "70", "text": "These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells .", "annotated_text": "These observations suggest that de novo EBV infection of <cell_type>thymocytes</cell_type> differs from infection of <cell_type>B cells</cell_type> ."}
{"id": "71", "text": "The main difference is that with thymocytes , no evidence could be found that the virus ever circularizes .", "annotated_text": "The main difference is that with <cell_type>thymocytes</cell_type> , no evidence could be found that the virus ever circularizes ."}
{"id": "72", "text": "Rather , EBV remains in a linear configuration from which replicative genes are transcribed .", "annotated_text": "Rather , EBV remains in a linear configuration from which <dna>replicative genes</dna> are transcribed ."}
{"id": "73", "text": "Identification and purification of human Stat proteins activated in response to interleukin-2 .", "annotated_text": "Identification and purification of <protein>human Stat proteins</protein> activated in response to <protein>interleukin-2</protein> ."}
{"id": "74", "text": "A key cytokine induced during the immune response is IL-2 .", "annotated_text": "A key <protein>cytokine</protein> induced during the immune response is <protein>IL-2</protein> ."}
{"id": "75", "text": "Following T cell activation , the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced .", "annotated_text": "Following T cell activation , the genes encoding <protein>IL-2</protein> and the various chains of its receptor are transcriptionally induced ."}
{"id": "76", "text": "In turn , secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes .", "annotated_text": "In turn , secreted <protein>IL-2</protein> serves to stimulate the proliferation and differentiation of <cell_type>T lymphocytes</cell_type> ."}
{"id": "77", "text": "Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2 .", "annotated_text": "Several recent studies have implicated Jak kinases in the signaling pathway induced by <protein>IL-2</protein> ."}
{"id": "78", "text": "Following this lead , we set out to identify transcription factors induced in response to IL-2 .", "annotated_text": "Following this lead , we set out to identify <protein>transcription factors</protein> induced in response to <protein>IL-2</protein> ."}
{"id": "79", "text": "Human peripheral blood lymphocytes were observed to contain several IL-2 -inducible DNA binding activities .", "annotated_text": "<cell_type>Human peripheral blood lymphocytes</cell_type> were observed to contain several <protein>IL-2</protein> -inducible DNA binding activities ."}
{"id": "80", "text": "Similar activities were also observed in a transformed human lymphocyte line , termed YT .", "annotated_text": "Similar activities were also observed in a <cell_line>transformed human lymphocyte line</cell_line> , termed <cell_line>YT</cell_line> ."}
{"id": "81", "text": "We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue .", "annotated_text": "We have purified these activities and found that the principal <protein>IL-2-inducible component</protein> bears significant relatedness to a <protein>prolactin-induced transcription factor</protein> first identified in <cell_type>sheep mammary gland tissue</cell_type> ."}
{"id": "82", "text": "We hypothesize that activation of this protein , designated hStat5 , helps govern the biological effects of IL-2 during the immune response .", "annotated_text": "We hypothesize that activation of this protein , designated <protein>hStat5</protein> , helps govern the biological effects of <protein>IL-2</protein> during the immune response ."}
{"id": "83", "text": "E2F-1 and a cyclin-like DNA repair enzyme , uracil-DNA glycosylase , provide evidence for an autoregulatory mechanism for transcription .", "annotated_text": "<protein>E2F-1</protein> and a <protein>cyclin-like DNA repair enzyme</protein> , <protein>uracil-DNA glycosylase</protein> , provide evidence for an autoregulatory mechanism for transcription ."}
{"id": "84", "text": "The cell cycle-dependent transcription factor , E2F-1 , regulates the cyclin -like species of the DNA repair enzyme uracil-DNA glycosylase ( UDG ) gene in human osteosarcoma ( Saos-2 ) cells .", "annotated_text": "The <protein>cell cycle-dependent transcription factor</protein> , <protein>E2F-1</protein> , regulates the <protein>cyclin</protein> -like species of the <protein>DNA repair enzyme</protein> <dna>uracil-DNA glycosylase ( UDG ) gene</dna> in <cell_line>human osteosarcoma ( Saos-2 ) cells</cell_line> ."}
{"id": "85", "text": "We demonstrate , through the deletion of the human UDG promoter sequences , that expression of E2F-1 activates the UDG promoter through several E2F sites .", "annotated_text": "We demonstrate , through the deletion of the <dna>human UDG promoter sequences</dna> , that expression of <protein>E2F-1</protein> activates the <dna>UDG promoter</dna> through several <dna>E2F sites</dna> ."}
{"id": "86", "text": "The major putative downstream site for E2F , located in the first exon , serves as a target for E2F-1/DP1 complex binding in vitro .", "annotated_text": "The <dna>major putative downstream site</dna> for <protein>E2F</protein> , located in the <dna>first exon</dna> , serves as a target for <protein>E2F-1/DP1 complex</protein> binding in vitro ."}
{"id": "87", "text": "We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F .", "annotated_text": "We also provide evidence for the functional relationship between the <protein>cyclin-like UDG gene product</protein> and <protein>E2F</protein> ."}
{"id": "88", "text": "High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F -mediated transcription .", "annotated_text": "High levels of <protein>UDG</protein> expression in a transient transfection assay result in the down-regulation of transcriptional activity through <dna>elements</dna> specific for <protein>E2F</protein> -mediated transcription ."}
{"id": "89", "text": "Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase .", "annotated_text": "Overexpression of <protein>UDG</protein> in <cell_line>Saos 2 cells</cell_line> was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase ."}
{"id": "90", "text": "This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription , likely through E2F .", "annotated_text": "This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription , likely through <protein>E2F</protein> ."}
{"id": "91", "text": "This implicates E2F as a multifunctional target for proteins and enzymes , possibly , responsive to DNA damage through the negative effect of UDG on E2F -mediated transcriptional activity .", "annotated_text": "This implicates <protein>E2F</protein> as a multifunctional target for proteins and enzymes , possibly , responsive to DNA damage through the negative effect of <protein>UDG</protein> on <protein>E2F</protein> -mediated transcriptional activity ."}
{"id": "92", "text": "Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line .", "annotated_text": "Cellular and molecular mechanisms of <protein>IFN-gamma</protein> production induced by <protein>IL-2</protein> and <protein>IL-12</protein> in a <cell_line>human NK cell line</cell_line> ."}
{"id": "93", "text": "Interferon-gamma ( IFN-gamma ) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes ( LGL ) in response to different extracellular signals .", "annotated_text": "<protein>Interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) is an important <protein>immunoregulatory protein</protein> produced predominantly by <cell_type>T cells</cell_type> and <cell_type>large granular lymphocytes</cell_type> ( <cell_type>LGL</cell_type> ) in response to different extracellular signals ."}
{"id": "94", "text": "In particular , two interleukins ( ILs ) , IL-2 and IL-12 , have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL .", "annotated_text": "In particular , two <protein>interleukins</protein> ( <protein>ILs</protein> ) , <protein>IL-2</protein> and <protein>IL-12</protein> , have been shown to be potent inducers of <protein>IFN-gamma</protein> gene expression in both <cell_type>T cells</cell_type> and <cell_type>LGL</cell_type> ."}
{"id": "95", "text": "Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation , there has as yet been no report of a natural killer ( NK ) cell line that responds in a similar manner .", "annotated_text": "Although it has been reported that there are some <cell_line>T cell lines</cell_line> that produce <protein>IFN-gamma</protein> in response to IL-2 and IL-12 stimulation , there has as yet been no report of a <cell_line>natural killer ( NK ) cell line</cell_line> that responds in a similar manner ."}
{"id": "96", "text": "In this report we present evidence that the cell line NK3.3 derived from human NK cells , responds to both IL-2 and IL-12 , as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) cytoplasmic mRNA and protein expression .", "annotated_text": "In this report we present evidence that the <cell_line>cell line NK3.3</cell_line> derived from <cell_type>human NK cells</cell_type> , responds to both <protein>IL-2</protein> and <protein>IL-12</protein> , as measured by increases in <protein>IFN-gamma</protein> and <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) cytoplasmic mRNA and protein expression ."}
{"id": "97", "text": "In addition , when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF mRNAs .", "annotated_text": "In addition , when used together <protein>IL-2</protein> and <protein>IL-12</protein> synergized in the induction of <protein>IFN-gamma</protein> and <protein>GM-CSF</protein> and this synergy was attributed to an increased accumulation and stability of the <rna>IFN-gamma and GM-CSF mRNAs</rna> ."}
{"id": "98", "text": "To investigate the signaling pathways involved in the gene induction , five inhibitors , cyclosporin A ( CsA ) , transforming growth factor-beta , cycloheximide , genistein , and staurosporine A , were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells .", "annotated_text": "To investigate the signaling pathways involved in the gene induction , five inhibitors , cyclosporin A ( CsA ) , <protein>transforming growth factor-beta</protein> , cycloheximide , genistein , and staurosporine A , were used in analyzing the effects of <protein>IL-2</protein> and <protein>IL-12</protein> on <cell_line>NK3.3 cells</cell_line> ."}
{"id": "99", "text": "The results suggest that activation of protein kinase C , but not new protein synthesis , is required for IL-2 induction of IFN-gamma and GM-CSF cytoplasmic mRNA .", "annotated_text": "The results suggest that activation of <protein>protein kinase C</protein> , but not new protein synthesis , is required for <protein>IL-2</protein> induction of <rna>IFN-gamma and GM-CSF cytoplasmic mRNA</rna> ."}
{"id": "100", "text": "In contrast , IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C .", "annotated_text": "In contrast , <protein>IL-12</protein> induction of <rna>IFN-gamma cytoplasmic mRNA</rna> appears to only partially depend on activation of <protein>protein kinase C</protein> ."}
{"id": "101", "text": "Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive .", "annotated_text": "Furthermore , both <protein>transforming growth factor-beta</protein> and genistein , a tyrosine kinase inhibitor , could suppress <protein>IL-2</protein> and <protein>IL-12</protein> signaling but CsA was generally inactive ."}
{"id": "102", "text": "It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation .", "annotated_text": "It also was observed that suppression of <dna>cytokine gene</dna> expression by these agents was independent of the inhibition of proliferation ."}
{"id": "103", "text": "In addition , IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1 , and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression .", "annotated_text": "In addition , <protein>IL-2</protein> but not <protein>IL-12</protein> induced <protein>nuclear factors</protein> <protein>NF-kappa B</protein> and <protein>AP1</protein> , and regulation of the nuclear levels of these two <protein>DNA binding protein complexes</protein> is correlated with IFN-gamma and GM-CSF gene expression ."}
{"id": "104", "text": "These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression , and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways .", "annotated_text": "These data indicate that <protein>IL-2</protein> and <protein>IL-12</protein> may have distinct signaling pathways leading to the induction of <protein>IFN-gamma</protein> and <protein>GM-CSF</protein> gene expression , and that the <cell_line>NK3.3 cell line</cell_line> may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways ."}
{"id": "105", "text": "A functional T-cell receptor signaling pathway is required for p95vav activity .", "annotated_text": "A functional <protein>T-cell receptor</protein> signaling pathway is required for <protein>p95vav</protein> activity ."}
{"id": "106", "text": "Stimulation of the T-cell antigen receptor ( TCR ) induces activation of multiple tyrosine kinases , resulting in phosphorylation of numerous intracellular substrates .", "annotated_text": "Stimulation of the <protein>T-cell antigen receptor</protein> ( <protein>TCR</protein> ) induces activation of multiple <protein>tyrosine kinases</protein> , resulting in phosphorylation of numerous intracellular substrates ."}
{"id": "107", "text": "One substrate is p95vav , which is expressed exclusively in hematopoietic and trophoblast cells .", "annotated_text": "One substrate is <protein>p95vav</protein> , which is expressed exclusively in <cell_type>hematopoietic and trophoblast cells</cell_type> ."}
{"id": "108", "text": "It contains a number of structural motifs , including Src homology 2 , Src homology 3 , and pleckstrin homology domains and a putative guanine nucleotide exchange domain .", "annotated_text": "It contains a number of <protein>structural motifs</protein> , including <protein>Src homology 2 , Src homology 3 , and pleckstrin homology domains</protein> and a <protein>putative guanine nucleotide exchange domain</protein> ."}
{"id": "109", "text": "The role of p95vav in TCR -mediated signaling processes is unclear .", "annotated_text": "The role of <protein>p95vav</protein> in <protein>TCR</protein> -mediated signaling processes is unclear ."}
{"id": "110", "text": "Here , we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors , including NFAT , involved in interleukin-2 expression .", "annotated_text": "Here , we show that overexpression of <protein>p95vav</protein> alone in Jurkat <cell_type>T cells</cell_type> leads to activation of the <protein>nuclear factors</protein> , including <protein>NFAT</protein> , involved in <protein>interleukin-2</protein> expression ."}
{"id": "111", "text": "Furthermore , p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription .", "annotated_text": "Furthermore , <protein>p95vav</protein> synergizes with <protein>TCR</protein> stimulation in inducing NFAT- and interleukin-2-dependent transcription ."}
{"id": "112", "text": "In contrast , NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression , suggesting that the effect is specific to the TCR signaling pathways .", "annotated_text": "In contrast , <protein>NFAT</protein> activation by a <protein>G-protein-coupled receptor</protein> is not modulated by <protein>p95vav</protein> overexpression , suggesting that the effect is specific to the <protein>TCR</protein> signaling pathways ."}
{"id": "113", "text": "Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells , this region appears to be required for its function in T cells .", "annotated_text": "Although removal of the <protein>first 67 amino acids</protein> of <protein>p95vav</protein> activates its transforming potential in <cell_line>NIH 3T3 cells</cell_line> , this region appears to be required for its function in <cell_type>T cells</cell_type> ."}
{"id": "114", "text": "We further demonstrate that the p95vav -induced NFAT activation is not mimicked by Ras activation , though its function is dependent upon Ras and Raf .", "annotated_text": "We further demonstrate that the <protein>p95vav</protein> -induced <protein>NFAT</protein> activation is not mimicked by <protein>Ras</protein> activation , though its function is dependent upon <protein>Ras</protein> and <protein>Raf</protein> ."}
{"id": "115", "text": "Furthermore , the activating function of p95vav is blocked by FK506 , suggesting that its activity also depends on calcineurin .", "annotated_text": "Furthermore , the activating function of <protein>p95vav</protein> is blocked by FK506 , suggesting that its activity also depends on <protein>calcineurin</protein> ."}
{"id": "116", "text": "To further dissect p95vav involvement in TCR signaling , we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function .", "annotated_text": "To further dissect <protein>p95vav</protein> involvement in <protein>TCR</protein> signaling , we analyzed various <cell_line>Jurkat mutants</cell_line> deficient in <protein>TCR</protein> signaling function or <protein>TCR</protein> expression and showed that an intact <protein>TCR</protein> signaling pathway is required for <protein>p95vav</protein> to function ."}
{"id": "117", "text": "However , overexpression of p95vav does not appear to influence TCR -induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium .", "annotated_text": "However , overexpression of <protein>p95vav</protein> does not appear to influence <protein>TCR</protein> -induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium ."}
{"id": "118", "text": "Taken together , our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade .", "annotated_text": "Taken together , our data suggest that <protein>p95vav</protein> plays an important role at an yet unidentified proximal position in the <protein>TCR</protein> signaling cascade ."}
{"id": "119", "text": "Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor , PEBP2 .", "annotated_text": "Positive and negative regulation of <protein>granulocyte-macrophage colony-stimulating factor</protein> promoter activity by <protein>AML1-related transcription factor</protein> , <protein>PEBP2</protein> ."}
{"id": "120", "text": "The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter contains a consensus sequence for the polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor , which consists of alpha and beta subunits .", "annotated_text": "The <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter</dna> contains a consensus sequence for the <protein>polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor</protein> , which consists of <protein>alpha and beta subunits</protein> ."}
{"id": "121", "text": "There are at least two genes , alpha A and alpha B , encoding the alpha subunit .", "annotated_text": "There are at least two genes , <dna>alpha A</dna> and <dna>alpha B</dna> , encoding the <protein>alpha subunit</protein> ."}
{"id": "122", "text": "alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t ( 8 ; 21 ) and t ( 3 ; 21 ) myeloid leukemias .", "annotated_text": "<dna>alpha B</dna> is the <dna>mouse homologue</dna> of <dna>human AML1 gene</dna> detected at the breakpoints of t ( 8 ; 21 ) and t ( 3 ; 21 ) myeloid leukemias ."}
{"id": "123", "text": "We examined alpha A1 ( an alpha A-gene product ) and alpha B1 and alpha B2 ( two alpha B-encoded isomers ) for their effects on the GM-CSF promoter .", "annotated_text": "We examined <protein>alpha A1</protein> ( an <protein>alpha A-gene product</protein> ) and <protein>alpha B1</protein> and <protein>alpha B2</protein> ( two <protein>alpha B-encoded isomers</protein> ) for their effects on the <dna>GM-CSF promoter</dna> ."}
{"id": "124", "text": "PEBP2 alpha A1 , alpha B1 , and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter .", "annotated_text": "<protein>PEBP2 alpha A1</protein> , <protein>alpha B1</protein> , and <protein>alpha B2 proteins</protein> bound the <dna>PEBP2 site</dna> within the <dna>mouse GM-CSF promoter</dna> ."}
{"id": "125", "text": "PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells .", "annotated_text": "<protein>PEBP2 alpha A1</protein> and <protein>alpha B1</protein> enhanced the expression of the <dna>GM-CSF promoter-driven reporter plasmid</dna> in <cell_line>unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells</cell_line> ."}
{"id": "126", "text": "In contrast , the promoter activity was suppressed by alpha B2 .", "annotated_text": "In contrast , the promoter activity was suppressed by <protein>alpha B2</protein> ."}
{"id": "127", "text": "Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1 /alpha B2 ratio .", "annotated_text": "Coexpression of <protein>alpha B1</protein> and <protein>alpha B2</protein> showed that the promoter activity could be determined by the <protein>alpha B1</protein> <protein>/alpha B2</protein> ratio ."}
{"id": "128", "text": "Jurkat cell extract contained PEBP2 site-binding protein ( s ) that cross-reacted with antimouse alpha A1 antibodies .", "annotated_text": "Jurkat cell extract contained <protein>PEBP2 site-binding protein</protein> ( s ) that cross-reacted with <protein>antimouse alpha A1 antibodies</protein> ."}
{"id": "129", "text": "Northern blot analysis indicated the expression of human PEBP2 alpha A , alpha B ( AML1 ) , and beta genes in Jurkat cells .", "annotated_text": "Northern blot analysis indicated the expression of human <protein>PEBP2 alpha A</protein> , <dna>alpha B</dna> ( <dna>AML1</dna> ) , and <dna>beta genes</dna> in <cell_line>Jurkat cells</cell_line> ."}
{"id": "130", "text": "Although further studies are required to determine the precise role of PEBP2 in the GM-CSF promoter activity , the present findings suggested the importance of the relative ratio of different PEBP2 isoforms in regulating the levels of the promoter activity .", "annotated_text": "Although further studies are required to determine the precise role of <protein>PEBP2</protein> in the <protein>GM-CSF</protein> promoter activity , the present findings suggested the importance of the relative ratio of different <protein>PEBP2 isoforms</protein> in regulating the levels of the promoter activity ."}
{"id": "131", "text": "IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability .", "annotated_text": "<protein>IFN-gamma</protein> priming of <cell_type>monocytes</cell_type> enhances LPS-induced <protein>TNF</protein> production by augmenting both transcription and MRNA stability ."}
{"id": "132", "text": "The induction of cytokine expression in monocytes / macrophages by bacterial endotoxin or lipopolysaccharide is a critical , highly regulated host defence response .", "annotated_text": "The induction of <protein>cytokine</protein> expression in <cell_type>monocytes</cell_type> / <cell_type>macrophages</cell_type> by <protein>bacterial endotoxin</protein> or lipopolysaccharide is a critical , highly regulated host defence response ."}
{"id": "133", "text": "The augmentation of LPS responses by interferon gamma ( IFN-gamma ) , referred to as priming , is well established .", "annotated_text": "The augmentation of LPS responses by <protein>interferon gamma</protein> ( <protein>IFN-gamma</protein> ) , referred to as priming , is well established ."}
{"id": "134", "text": "However , the mechanism ( s ) by which priming occurs is poorly defined .", "annotated_text": "However , the mechanism ( s ) by which priming occurs is poorly defined ."}
{"id": "135", "text": "Using tumour necrosis factor ( TNF ) induction as a model , experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes .", "annotated_text": "Using <protein>tumour necrosis factor</protein> ( <protein>TNF</protein> ) induction as a model , experiments were designed to analyse in detail the priming effect on the LPS response in <cell_type>human monocytes</cell_type> ."}
{"id": "136", "text": "Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation .", "annotated_text": "Priming by <protein>IFN-gamma</protein> was primarily manifested at the level of <rna>TNF mRNA</rna> accumulation ."}
{"id": "137", "text": "IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response .", "annotated_text": "<protein>IFN-gamma</protein> pre-treatment affected the magnitude rather than the sensitivity of the LPS response ."}
{"id": "138", "text": "Priming occurred after several hours of treatment , and the primed state was induced by either IFN-gamma or GM-CSF , but not M-CSF .", "annotated_text": "Priming occurred after several hours of treatment , and the primed state was induced by either <protein>IFN-gamma</protein> or <protein>GM-CSF</protein> , but not <protein>M-CSF</protein> ."}
{"id": "139", "text": "Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS .", "annotated_text": "Primed <cell_type>monocytes</cell_type> transcribed <rna>TNF mRNA</rna> at a higher rate than freshly isolated <cell_type>monocytes</cell_type> upon activation with LPS ."}
{"id": "140", "text": "The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide .", "annotated_text": "The increased transcriptional rate correlated with a marked increase in <protein>nuclear factor-kappa B</protein> activity in these cells as determined by electrophoretic mobility shift assay using a <dna>consensus NF-kappa B oligonucleotide</dna> ."}
{"id": "141", "text": "An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells ( T1/2 increased 6-8-fold ) .", "annotated_text": "An additional significant finding was than <rna>TNF mRNA</rna> induced in <cell_line>primed cells</cell_line> was much more stable than in <cell_line>unprimed cells</cell_line> ( T1/2 increased 6-8-fold ) ."}
{"id": "142", "text": "Consistent with the increased mRNA stability , the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes , in addition to being of greater magnitude .", "annotated_text": "Consistent with the increased <rna>mRNA</rna> stability , the duration of <rna>mRNA</rna> accumulation was longer following LPS stimulation in primed <cell_type>monocytes</cell_type> , in addition to being of greater magnitude ."}
{"id": "143", "text": "Finally , primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89 .", "annotated_text": "Finally , primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89 ."}
{"id": "144", "text": "H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells , but had no effect on primed monocytes following LPS stimulation .", "annotated_text": "H-89 substantially suppressed LPS-induced <rna>TNF mRNA</rna> accumulation in <cell_line>unprimed cells</cell_line> , but had no effect on <cell_line>primed monocytes</cell_line> following LPS stimulation ."}
{"id": "145", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "146", "text": "A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter .", "annotated_text": "A <dna>Myc-associated zinc finger protein binding site</dna> is one of four important <dna>functional regions</dna> in the <dna>CD4 promoter</dna> ."}
{"id": "147", "text": "The CD4 promoter plays an important role in the developmental control of CD4 transcription .", "annotated_text": "The <dna>CD4 promoter</dna> plays an important role in the developmental control of <protein>CD4</protein> transcription ."}
{"id": "148", "text": "In this report , we show that the minimal CD4 promoter has four factor binding sites , each of which is required for full function .", "annotated_text": "In this report , we show that the minimal <dna>CD4 promoter</dna> has four <dna>factor binding sites</dna> , each of which is required for full function ."}
{"id": "149", "text": "Using biochemical and mutagenesis analyses , we determined that multiple nuclear factors bind to these independent sites .", "annotated_text": "Using biochemical and mutagenesis analyses , we determined that multiple <protein>nuclear factors</protein> bind to these independent sites ."}
{"id": "150", "text": "We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function .", "annotated_text": "We determined that an <dna>initiator-like sequence</dna> present at the <dna>cap site</dna> and an <dna>Ets consensus sequence</dna> are required for full <dna>promoter</dna> function ."}
{"id": "151", "text": "We also demonstrate that the Myc-associated zinc finger protein ( MAZ ) appears to be the predominant factor binding to one of these sites .", "annotated_text": "We also demonstrate that the <protein>Myc-associated zinc finger protein</protein> ( <protein>MAZ</protein> ) appears to be the <protein>predominant factor</protein> binding to one of these sites ."}
{"id": "152", "text": "This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene .", "annotated_text": "This last site closely resembles the <dna>ME1a1 G3AG4AG3 motif</dna> previously shown to be a critical element in the <dna>P2 promoter</dna> of the <dna>c-myc gene</dna> ."}
{"id": "153", "text": "We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene .", "annotated_text": "We therefore believe that the <protein>MAZ transcription factor</protein> is also likely to play an important role in the control of developmental expression of the <dna>CD4 gene</dna> ."}
{"id": "154", "text": "Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products .", "annotated_text": "<protein>Erythropoietin</protein> stimulates transcription of the <dna>TAL1/SCL gene</dna> and phosphorylation of its <protein>protein products</protein> ."}
{"id": "155", "text": "Activation of the TAL1 ( or SCL ) gene , originally identified through its involvement by a recurrent chromosomal translocation , is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia .", "annotated_text": "Activation of the <dna>TAL1 ( or SCL ) gene</dna> , originally identified through its involvement by a recurrent chromosomal translocation , is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia ."}
{"id": "156", "text": "The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers .", "annotated_text": "The <protein>protein products</protein> of this gene contain the <protein>basic-helix-loop-helix motif</protein> characteristic of a large family of <protein>transcription factors</protein> that bind to the <dna>canonical DNA sequence CANNTG</dna> as <protein>protein heterodimers</protein> ."}
{"id": "157", "text": "TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation .", "annotated_text": "<protein>TAL1</protein> expression by <cell_type>erythroid cells</cell_type> in vivo and in <cell_line>chemical-induced erythroleukemia cell lines</cell_line> in vivo suggested the gene might regulate aspects of erythroid differentiation ."}
{"id": "158", "text": "Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin ( Epo ) , we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus ( FVA cells ) .", "annotated_text": "Since the terminal events of erythropoiesis are controlled by the <protein>glycoprotein hormone erythropoietin</protein> ( <protein>Epo</protein> ) , we investigated whether the expression or activity of the <dna>TAL1 gene</dna> and its <protein>protein products</protein> were affected by <protein>Epo</protein> in <cell_type>splenic erythroblasts</cell_type> from mice infected with an anemia-inducing strain of Friend virus ( FVA cells ) ."}
{"id": "159", "text": "Epo elicited a rapid , dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs .", "annotated_text": "<protein>Epo</protein> elicited a rapid , dose-related increase in <rna>TAL1 mRNA</rna> by increasing transcription of the gene and stabilizing one of its <rna>mRNAs</rna> ."}
{"id": "160", "text": "An Epo -inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein .", "annotated_text": "An <protein>Epo</protein> -inducible <protein>TAL1</protein> DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating <rna>mRNA</rna> and protein ."}
{"id": "161", "text": "Induction of DNA binding activity was associated temporally with Epo -induced phosphorylation of nuclear TAL1 protein .", "annotated_text": "Induction of DNA binding activity was associated temporally with <protein>Epo</protein> -induced phosphorylation of <protein>nuclear TAL1 protein</protein> ."}
{"id": "162", "text": "These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages .", "annotated_text": "These results indicate that <protein>Epo</protein> acts at both transcriptional and posttranscriptional levels on the <protein>TAL1</protein> locus in <cell_line>Friend virus-induced erythroblasts</cell_line> and establish a link between <protein>Epo</protein> signaling mechanisms and a member of a family of <protein>transcription factors</protein> involved in the differentiation of <cell_type>diverse cell lineages</cell_type> ."}
{"id": "163", "text": "Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells ( U937 ) .", "annotated_text": "Nonradioactive quantification of <protein>glucocorticoid receptor</protein> expression during differentiation of human <cell_type>monocytic cells</cell_type> ( <cell_line>U937</cell_line> ) ."}
{"id": "164", "text": "We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon ( probe ) and unlabeled amplicon ( target ) during hybridization .", "annotated_text": "We describe a method for relative quantification of specific <rna>mRNA</rna> using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon ( probe ) and unlabeled amplicon ( target ) during hybridization ."}
{"id": "165", "text": "As the target quantity increased , that of the double-labeled probe decreased in accordance with the mass action law .", "annotated_text": "As the target quantity increased , that of the double-labeled probe decreased in accordance with the mass action law ."}
{"id": "166", "text": "This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers : 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and a combination of all-trans retinoic acid ( RA ) and 1 , 25-dihydroxyvitamin D2 ( VD ) .", "annotated_text": "This technique was successfully applied to evaluate differences in <protein>glucocorticoid receptor</protein> expression in <cell_line>U937 cells</cell_line> before and after the addition of potent differentiation inducers : 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and a combination of all-trans retinoic acid ( RA ) and 1 , 25-dihydroxyvitamin D2 ( VD ) ."}
{"id": "167", "text": "We observed that TPA treatment was associated with an increase in specific binding of [ 3H ] dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment .", "annotated_text": "We observed that TPA treatment was associated with an increase in specific binding of [ 3H ] dexamethasone and up-regulation of <rna>GR mRNA</rna> while no enhanced <protein>GR</protein> expression was perceived with RA/VD treatment ."}
{"id": "168", "text": "Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid .", "annotated_text": "Induction of <protein>Sp1</protein> phosphorylation and <dna>NF-kappa B-independent HIV promoter</dna> domain activity in <cell_type>T lymphocytes</cell_type> stimulated by okadaic acid ."}
{"id": "169", "text": "In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region ( LTR ) , we observed that okadaic acid ( OKA ) activates HIV transcription through both the enhancer , responding to the factor NF-kappa B , and the promoter domain of the LTR .", "annotated_text": "In contrast to the purely enhancer-dependent effect of <protein>cytokines</protein> such as <protein>TNF</protein> on the activity of the <dna>HIV regulatory region</dna> ( <dna>LTR</dna> ) , we observed that okadaic acid ( OKA ) activates HIV transcription through both the enhancer , responding to the factor <protein>NF-kappa B</protein> , and the <dna>promoter domain</dna> of the <dna>LTR</dna> ."}
{"id": "170", "text": "The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP .", "annotated_text": "The inducibility of <dna>HIV LTR-driven luciferase expression constructs</dna> in <cell_type>lymphoblastoid cells</cell_type> stimulated by OKA depended on both <dna>functional Sp1 binding elements</dna> and the ability of the <dna>TATA box</dna> to bind the protein <protein>TBP</protein> ."}
{"id": "171", "text": "In both transformed and normal lymphocytes , OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus , a property of OKA not shared by TNF , phorbol ester , or PHA and interleukin 2 .", "annotated_text": "In both <cell_type>transformed and normal lymphocytes</cell_type> , OKA stimulation induced intense phosphorylation of the constitutively expressed <protein>Sp1 protein</protein> in the nucleus , a property of OKA not shared by <protein>TNF</protein> , phorbol ester , or <protein>PHA</protein> and <protein>interleukin 2</protein> ."}
{"id": "172", "text": "Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation .", "annotated_text": "Responsiveness of <dna>LTR constructs</dna> deleted of <dna>kappa B elements</dna> to <protein>HIV Tat</protein> expression was increased upon OKA but not <protein>TNF</protein> stimulation ."}
{"id": "173", "text": "Our results suggest that SP1 phosphorylation induced by OKA , a selective inhibitor of the serine-threonine phosphatase PP2A , facilitates the formation of a transcription complex involving general transcription factors , HIV Tat , and Sp1 proteins .", "annotated_text": "Our results suggest that <protein>SP1</protein> phosphorylation induced by OKA , a selective inhibitor of the <protein>serine-threonine phosphatase</protein> <protein>PP2A</protein> , facilitates the formation of a <protein>transcription complex</protein> involving general <protein>transcription factors</protein> , <protein>HIV Tat</protein> , and <protein>Sp1 proteins</protein> ."}
{"id": "174", "text": "The formation of this complex would increase , independently of an in synergy with NF-kappa B , the low basal activity of the HIV LTR observed in normal T lymphocytes .", "annotated_text": "The formation of this complex would increase , independently of an in synergy with <protein>NF-kappa B</protein> , the low basal activity of the <dna>HIV LTR</dna> observed in <cell_type>normal T lymphocytes</cell_type> ."}
{"id": "175", "text": "The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2 , IL-4 , IL-7 , IL-13 , and IL-15 .", "annotated_text": "The role of <protein>shared receptor motifs</protein> and <protein>common Stat proteins</protein> in the generation of <protein>cytokine</protein> pleiotropy and redundancy by <protein>IL-2</protein> , <protein>IL-4</protein> , <protein>IL-7</protein> , <protein>IL-13</protein> , and <protein>IL-15</protein> ."}
{"id": "176", "text": "To understand the molecular bases for cytokine redundancy and pleiotropy , we have compared the Stat proteins activated in peripheral blood lymphocytes ( PBLs ) by cytokines with shared and distinct actions .", "annotated_text": "To understand the molecular bases for cytokine redundancy and pleiotropy , we have compared the <protein>Stat proteins</protein> activated in <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBLs</cell_type> ) by <protein>cytokines</protein> with shared and distinct actions ."}
{"id": "177", "text": "Interleukin-2 ( IL-2 ) rapidly activated Stat5 in fresh PBL , and Stat3 and Stat5 in preactivated PBL .", "annotated_text": "<protein>Interleukin-2</protein> ( <protein>IL-2</protein> ) rapidly activated <protein>Stat5</protein> in fresh <cell_type>PBL</cell_type> , and <protein>Stat3</protein> and <protein>Stat5</protein> in <cell_type>preactivated PBL</cell_type> ."}
{"id": "178", "text": "IL-7 and IL-15 induced the same complexes as IL-2 , a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins .", "annotated_text": "<protein>IL-7</protein> and <protein>IL-15</protein> induced the same complexes as <protein>IL-2</protein> , a feature explained by the existence of similar <protein>tyrosine-phosphorylated motifs</protein> in the <protein>cytoplasmic domains</protein> of <protein>IL-2R beta</protein> and <protein>IL-7R</protein> that can serve as docking sites for <protein>Stat proteins</protein> ."}
{"id": "179", "text": "IL-13 Induced the same complexes as IL-4 , a finding explained by our studies implicating IL-4R as a shared component of the receptors .", "annotated_text": "<protein>IL-13</protein> Induced the same complexes as <protein>IL-4</protein> , a finding explained by our studies implicating <protein>IL-4R</protein> as a shared component of the <protein>receptors</protein> ."}
{"id": "180", "text": "These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions , and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein .", "annotated_text": "These studies demonstrate that a single <protein>cytokine</protein> can activate different combinations of <protein>Stat proteins</protein> under different physiological conditions , and also indicate two mechanisms by which distinct <protein>cytokines</protein> can activate the same <protein>Stat protein</protein> ."}
{"id": "181", "text": "Control of I kappa B-alpha proteolysis by site-specific , signal-induced phosphorylation .", "annotated_text": "Control of <protein>I kappa B-alpha</protein> proteolysis by site-specific , signal-induced phosphorylation ."}
{"id": "182", "text": "I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm .", "annotated_text": "<protein>I kappa B-alpha</protein> inhibits <protein>transcription factor</protein> <protein>NF-kappa B</protein> by retaining it in the cytoplasm ."}
{"id": "183", "text": "Various stimuli , typically those associated with stress or pathogens , rapidly inactivate I kappa B-alpha .", "annotated_text": "Various stimuli , typically those associated with stress or pathogens , rapidly inactivate <protein>I kappa B-alpha</protein> ."}
{"id": "184", "text": "This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism .", "annotated_text": "This liberates <protein>NF-kappa B</protein> to translocate to the nucleus and initiate transcription of <dna>genes</dna> important for the defense of the organism ."}
{"id": "185", "text": "Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor .", "annotated_text": "Activation of <protein>NF-kappa B</protein> correlates with phosphorylation of <protein>I kappa B-alpha</protein> and requires the proteolysis of this inhibitor ."}
{"id": "186", "text": "When either serine-32 or serine-36 of I kappa B-alpha was mutated , the protein did not undergo signal-induced phosphorylation or degradation , and NF-kappa B could not be activated .", "annotated_text": "When either serine-32 or serine-36 of <protein>I kappa B-alpha</protein> was mutated , the protein did not undergo signal-induced phosphorylation or degradation , and <protein>NF-kappa B</protein> could not be activated ."}
{"id": "187", "text": "These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B .", "annotated_text": "These results suggest that phosphorylation at one or both of these residues is critical for activation of <protein>NF-kappa B</protein> ."}
{"id": "188", "text": "Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs .", "annotated_text": "Regulation of transcription of the <dna>human erythropoietin receptor gene</dna> by proteins binding to <dna>GATA-1 and Sp1 motifs</dna> ."}
{"id": "189", "text": "Erythropoietin ( Epo ) , the primary regulator of the production of erythroid cells , acts by binding to a cell surface receptor ( EpoR ) on erythroid progenitors .", "annotated_text": "<protein>Erythropoietin</protein> ( <protein>Epo</protein> ) , the primary regulator of the production of <cell_type>erythroid cells</cell_type> , acts by binding to a <protein>cell surface receptor</protein> ( <protein>EpoR</protein> ) on <cell_type>erythroid progenitors</cell_type> ."}
{"id": "190", "text": "We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5 ' flanking region of the human EpoR gene .", "annotated_text": "We used deletion analysis and transfection assays with <dna>reporter gene constructs</dna> to examine the <dna>transcription control elements</dna> in the <dna>5 ' flanking region</dna> of the <dna>human EpoR gene</dna> ."}
{"id": "191", "text": "In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2 , Sp1 and the erythroid-specific GATA-1 .", "annotated_text": "In <cell_type>erythroid cells</cell_type> most of the transcription activity was contained in a <dna>150 bp promoter</dna> fragment with <dna>binding sites</dna> for <protein>transcription factors</protein> <protein>AP2</protein> , <protein>Sp1</protein> and the <protein>erythroid-specific GATA-1</protein> ."}
{"id": "192", "text": "The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells , respectively , reflecting the high and low levels of constitutive hEpoR expression .", "annotated_text": "The <dna>150 bp hEpoR promoter</dna> exhibited high and low activity in erythroid <cell_line>OCIM1</cell_line> and <cell_line>K562 cells</cell_line> , respectively , reflecting the high and low levels of constitutive <protein>hEpoR</protein> expression ."}
{"id": "193", "text": "The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation .", "annotated_text": "The <dna>GATA-1 and Sp1 binding sites</dna> in this promoter lacking a <dna>TATA sequence</dna> were necessary for a high level of transcription activation ."}
{"id": "194", "text": "Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif .", "annotated_text": "Protein-DNA binding studies suggested that <protein>Sp1</protein> and two other <protein>CCGCCC binding proteins</protein> from <cell_type>erythroid and non-erythroid cells</cell_type> could bind to the <dna>Sp1 binding motif</dna> ."}
{"id": "195", "text": "By increasing GATA-1 levels via co-transfection , we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells , but not in the highly active OCIM1 cells , although GATA-1 mRNA levels were comparable in OCIM1 and K562 .", "annotated_text": "By increasing <protein>GATA-1</protein> levels via co-transfection , we were able to transactivate the <dna>hEpoR promoter</dna> in <cell_line>K562 cells</cell_line> and <cell_type>non-erythroid cells</cell_type> , but not in the highly active <cell_type>OCIM1 cells</cell_type> , although <rna>GATA-1 mRNA</rna> levels were comparable in <cell_line>OCIM1</cell_line> and <cell_line>K562</cell_line> ."}
{"id": "196", "text": "Interestingly , when we mutated the Sp1 site , resulting in a marked decrease in hEpoR promoter activity , we could restore transactivation by increasing GATA-1 levels in OCIM1 cells .", "annotated_text": "Interestingly , when we mutated the <dna>Sp1 site</dna> , resulting in a marked decrease in <dna>hEpoR promoter</dna> activity , we could restore transactivation by increasing <protein>GATA-1</protein> levels in <cell_type>OCIM1 cells</cell_type> ."}
{"id": "197", "text": "These data suggest that while GATA-1 can transactivate the EpoR promoter , the level of hEpoR gene expression does not depend on GATA-1 alone .", "annotated_text": "These data suggest that while <protein>GATA-1</protein> can transactivate the <dna>EpoR promoter</dna> , the level of <dna>hEpoR gene</dna> expression does not depend on <protein>GATA-1</protein> alone ."}
{"id": "198", "text": "Rather , hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors , including possibly other Sp1-like binding proteins , to provide high level , tissue-specific expression .", "annotated_text": "Rather , <protein>hEpoR</protein> transcription activity depends on coordination between <protein>Sp1</protein> and <protein>GATA-1</protein> with other <protein>cell-specific factors</protein> , including possibly other <protein>Sp1-like binding proteins</protein> , to provide high level , tissue-specific expression ."}
{"id": "199", "text": "Overexpression of DR-nm23 , a protein encoded by a member of the nm23 gene family , inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells .", "annotated_text": "Overexpression of <protein>DR-nm23</protein> , a protein encoded by a member of the <dna>nm23 gene family</dna> , inhibits <cell_type>granulocyte</cell_type> differentiation and induces apoptosis in <cell_line>32Dc13 myeloid cells</cell_line> ."}
{"id": "200", "text": "Chronic myelogenous leukemia evolves in two clinically distinct stages : a chronic and a blast crisis phase .", "annotated_text": "Chronic myelogenous leukemia evolves in two clinically distinct stages : a chronic and a blast crisis phase ."}
{"id": "201", "text": "The molecular changes associated with chronic phase to blast crisis transition are largely unknown .", "annotated_text": "The molecular changes associated with chronic phase to blast crisis transition are largely unknown ."}
{"id": "202", "text": "We have identified a cDNA clone , DR-nm23 , differentially expressed in a blast-crisis cDNA library , which has approximately 70 % sequence similarity to the putative metastatic suppressor genes , nm23-H1 and nm23-H2 .", "annotated_text": "We have identified a <dna>cDNA clone</dna> , <protein>DR-nm23</protein> , differentially expressed in a <dna>blast-crisis cDNA library ,</dna> which has approximately 70 % sequence similarity to the <dna>putative metastatic suppressor genes</dna> , <dna>nm23-H1</dna> and <dna>nm23-H2</dna> ."}
{"id": "203", "text": "The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65 % and includes domains and amino acid residues ( the leucine zipper-like and the RGD domain , a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein , respectively ) postulated to be important for nm23 function .", "annotated_text": "The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65 % and includes domains and amino acid residues ( the <protein>leucine zipper-like</protein> and the <protein>RGD domain</protein> , a serine and a histidine residue in the <protein>NH2-</protein> and in the <protein>COOH-terminal portion</protein> of the protein , respectively ) postulated to be important for <protein>nm23</protein> function ."}
{"id": "204", "text": "DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells .", "annotated_text": "<rna>DR-nm23 mRNA</rna> is preferentially expressed at early stages of myeloid differentiation of <cell_line>highly purified CD34+ cells</cell_line> ."}
{"id": "205", "text": "Its constitutive expression in the myeloid precursor 32Dc13 cell line , which is growth-factor dependent for both proliferation and differentiation , results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death .", "annotated_text": "Its constitutive expression in the <cell_line>myeloid precursor 32Dc13 cell line</cell_line> , which is growth-factor dependent for both proliferation and differentiation , results in inhibition of granulocytic differentiation induced by <protein>granulocyte colony-stimulating factor</protein> and causes apoptotic cell death ."}
{"id": "206", "text": "These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest , a feature of blastic transformation in chronic myelogenous leukemia .", "annotated_text": "These results are consistent with a role for <protein>DR-nm23</protein> in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest , a feature of blastic transformation in chronic myelogenous leukemia ."}
{"id": "207", "text": "An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma .", "annotated_text": "An <dna>interferon-gamma activation sequence</dna> mediates the transcriptional regulation of the <dna>IgG Fc receptor type IC gene</dna> by <protein>interferon-gamma</protein> ."}
{"id": "208", "text": "Expression of the IgG Fc receptor type I ( Fc gamma RI ) on myeloid cells is dramatically increased by treatment with interferon-gamma ( IFN-gamma ) .", "annotated_text": "Expression of the <protein>IgG Fc receptor type I</protein> ( <protein>Fc gamma RI</protein> ) on <cell_type>myeloid cells</cell_type> is dramatically increased by treatment with <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) ."}
{"id": "209", "text": "We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma .", "annotated_text": "We observed that <protein>Fc gamma RI</protein> transcript levels in <cell_line>monoblast-like U937 cells</cell_line> were elevated within 3 hr and peaked 12 hr after exposure to <protein>IFN-gamma</protein> ."}
{"id": "210", "text": "Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression .", "annotated_text": "Treatment of <cell_line>U937</cell_line> with <protein>IFN-gamma</protein> for 9 hr in the presence of cycloheximide led to super-induction of <protein>Fc gamma RI</protein> expression ."}
{"id": "211", "text": "Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma .", "annotated_text": "Nuclear run-on analysis revealed that the rate of <protein>Fc gamma RI</protein> transcription was increased by <protein>IFN-gamma</protein> ."}
{"id": "212", "text": "Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis , which demonstrated a single transcription initiation site without a TATA box .", "annotated_text": "Genomic sequence upstream of the <dna>Fc gamma RIC gene</dna> was cloned and subjected to primer extension analysis , which demonstrated a single <dna>transcription initiation site</dna> without a <dna>TATA box</dna> ."}
{"id": "213", "text": "Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site ( -7 to +13 ) was capable of mediating transcription initiation and that an IFN-gamma responsive element ( GIRE ) was present within 74 bp upstream of the transcription initiation site .", "annotated_text": "Transient transfections of <dna>CAT reporter gene constructs</dna> containing various <dna>Fc gamma RIC promoter sequences</dna> into <cell_line>U937 cells</cell_line> revealed that a <dna>20-bp region</dna> surrounding the <dna>transcription start site</dna> ( -7 to +13 ) was capable of mediating transcription initiation and that an <dna>IFN-gamma responsive element</dna> ( <dna>GIRE</dna> ) was present within <dna>74 bp upstream</dna> of the <dna>transcription initiation site</dna> ."}
{"id": "214", "text": "A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter .", "annotated_text": "A <dna>17-bp sequence</dna> between positions -51 and -35 conferred <protein>IFN-gamma</protein> responsiveness on a <dna>heterologous promoter</dna> ."}
{"id": "215", "text": "Double-stranded GIRE sequence , but not a scrambled sequence , was specifically bound by nuclear proteins from IFN-gamma treated U937 cells .", "annotated_text": "<dna>Double-stranded GIRE sequence</dna> , but not a <dna>scrambled sequence</dna> , was specifically bound by <protein>nuclear proteins</protein> from <cell_line>IFN-gamma treated U937 cells</cell_line> ."}
{"id": "216", "text": "Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells .", "annotated_text": "Gel shift experiments further showed that the <protein>STAT1 alpha protein</protein> bound to the <dna>Fc gamma RIC GIRE</dna> in response to <protein>IFN-gamma</protein> treatment of <cell_line>U937 cells</cell_line> ."}
{"id": "217", "text": "The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence ( GAS ) of the guanylate binding protein and to X box elements of class II MHC genes .", "annotated_text": "The <dna>Fc gamma RIC GIRE</dna> is homologous to the <dna>IFN-gamma activation sequence</dna> ( <dna>GAS</dna> ) of the <protein>guanylate binding protein</protein> and to <dna>X box elements</dna> of <dna>class II MHC genes</dna> ."}
{"id": "218", "text": "Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter .", "annotated_text": "Our results demonstrate that transcriptional regulation of the <dna>Fc gamma RIC gene</dna> by <protein>IFN-gamma</protein> involves the binding of <protein>STAT1 alpha</protein> to a <dna>17-bp GAS homology</dna> in the <dna>proximal promoter</dna> ."}
{"id": "219", "text": "Constitutively activated Jak -STAT pathway in T cells transformed with HTLV-I .", "annotated_text": "Constitutively activated <protein>Jak</protein> <protein>-STAT</protein> pathway in <cell_type>T cells</cell_type> transformed with HTLV-I ."}
{"id": "220", "text": "Human T cell lymphotropic virus I ( HTLV-I ) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis ( also termed HTLV-I-associated myelopathy ) .", "annotated_text": "Human T cell lymphotropic virus I ( HTLV-I ) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis ( also termed HTLV-I-associated myelopathy ) ."}
{"id": "221", "text": "HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 ( IL-2 ) -dependent growth ; over time , by an unknown mechanism , the cells become IL-2 -independent .", "annotated_text": "<cell_type>HTLV-I-infected peripheral blood T cells</cell_type> exhibit an initial phase of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) -dependent growth ; over time , by an unknown mechanism , the cells become <protein>IL-2</protein> -independent ."}
{"id": "222", "text": "Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2 , this signaling pathway was constitutively activated in HTLV-I-transformed cells .", "annotated_text": "Whereas the <protein>Jak kinases</protein> <protein>Jak1</protein> and <protein>Jak3</protein> and the signal transducer and activator of <protein>transcription proteins</protein> <protein>Stat3</protein> and <protein>Stat5</protein> are activated in <cell_type>normal T cells</cell_type> in response to <protein>IL-2</protein> , this signaling pathway was constitutively activated in <cell_line>HTLV-I-transformed cells</cell_line> ."}
{"id": "223", "text": "In HTLV-I-infected cord blood lymphocytes , the transition from IL-2 -dependent to IL-2 -independent growth correlated with the acquisition of a constitutively activated Jak -STAT pathway , which suggests that this pathway participates in HTLV-I-mediated T cell transformation .", "annotated_text": "In <cell_line>HTLV-I-infected cord blood lymphocytes</cell_line> , the transition from <protein>IL-2</protein> -dependent to <protein>IL-2</protein> -independent growth correlated with the acquisition of a constitutively activated <protein>Jak</protein> <protein>-STAT</protein> pathway , which suggests that this pathway participates in HTLV-I-mediated T cell transformation ."}
{"id": "224", "text": "Nitric oxide decreases cytokine -induced endothelial activation .", "annotated_text": "Nitric oxide decreases <protein>cytokine</protein> -induced endothelial activation ."}
{"id": "225", "text": "Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines .", "annotated_text": "Nitric oxide selectively reduces endothelial expression of <protein>adhesion molecules</protein> and <protein>proinflammatory cytokines</protein> ."}
{"id": "226", "text": "To test the hypothesis that nitric oxide ( NO ) limits endothelial activation , we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 ( VCAM-1 ) .", "annotated_text": "To test the hypothesis that nitric oxide ( NO ) limits endothelial activation , we treated <cell_line>cytokine-stimulated human saphenous vein endothelial cells</cell_line> with several NO donors and assessed their effects on the inducible expression of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) ."}
{"id": "227", "text": "In a concentration-dependent manner , NO inhibited interleukin ( IL ) -1 alpha-stimulated VCAM-1 expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry .", "annotated_text": "In a concentration-dependent manner , NO inhibited <protein>interleukin ( IL ) -1</protein> alpha-stimulated <protein>VCAM-1</protein> expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry ."}
{"id": "228", "text": "This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays , was unaffected by cGMP analogues , and was quantitatively similar after stimulation by either IL-1 alpha , IL-1 beta , IL-4 , tumor necrosis factor ( TNF alpha ) , or bacterial lipopolysaccharide .", "annotated_text": "This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays , was unaffected by cGMP analogues , and was quantitatively similar after stimulation by either <protein>IL-1 alpha</protein> , <protein>IL-1 beta</protein> , <protein>IL-4</protein> , <protein>tumor necrosis factor</protein> ( <protein>TNF alpha</protein> ) , or bacterial lipopolysaccharide ."}
{"id": "229", "text": "NO also decreased the endothelial expression of other leukocyte adhesion molecules ( E-selectin and to a lesser extent , intercellular adhesion molecule-1 ) and secretable cytokines ( IL-6 and IL-8 ) .", "annotated_text": "NO also decreased the endothelial expression of other <protein>leukocyte adhesion molecules</protein> ( <protein>E-selectin</protein> and to a lesser extent , <protein>intercellular adhesion molecule-1</protein> ) and secretable <protein>cytokines</protein> ( <protein>IL-6</protein> and <protein>IL-8</protein> ) ."}
{"id": "230", "text": "Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1 , but did not augment cytokine-induced VCAM-1 expression .", "annotated_text": "Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of <protein>VCAM-1</protein> , but did not augment cytokine-induced <protein>VCAM-1</protein> expression ."}
{"id": "231", "text": "Nuclear run-on assays , transfection studies using various VCAM-1 promoter reporter gene constructs , and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription , in part , by inhibiting NF-kappa B .", "annotated_text": "Nuclear run-on assays , transfection studies using various <dna>VCAM-1 promoter reporter gene constructs</dna> , and electrophoretic mobility shift assays indicated that NO represses <protein>VCAM-1</protein> gene transcription , in part , by inhibiting <protein>NF-kappa B</protein> ."}
{"id": "232", "text": "We propose that NO 's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall .", "annotated_text": "We propose that NO 's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall ."}
{"id": "233", "text": "MIP1 alpha nuclear protein ( MNP ) , a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene .", "annotated_text": "<protein>MIP1 alpha nuclear protein</protein> ( <protein>MNP</protein> ) , a novel <protein>transcription factor</protein> expressed in hematopoietic cells that is crucial for transcription of the <dna>human MIP-1 alpha gene</dna> ."}
{"id": "234", "text": "Murine macrophage inflammatory protein 1 alpha ( MIP-1 alpha ) and its human equivalent ( GOS19 , LD78 , or AT464 ) are members of the -C-C family of low-molecular-weight chemokines .", "annotated_text": "<protein>Murine macrophage inflammatory protein 1 alpha</protein> ( <protein>MIP-1 alpha</protein> ) and its <protein>human equivalent</protein> ( <protein>GOS19</protein> , <protein>LD78</protein> , or <protein>AT464</protein> ) are members of the <protein>-C-C family</protein> of <protein>low-molecular-weight chemokines</protein> ."}
{"id": "235", "text": "Secreted from activated T cells and macrophages , bone marrow-derived MIP-1 alpha/GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation .", "annotated_text": "Secreted from <cell_type>activated T cells</cell_type> and <cell_type>macrophages</cell_type> , bone <protein>marrow-derived MIP-1 alpha/GOS19</protein> inhibits <cell_type>primitive hematopoietic stem cells</cell_type> and appears to be involved in the homeostatic control of <cell_type>stem cell</cell_type> proliferation ."}
{"id": "236", "text": "It also induces chemotaxis and inflammatory responses in mature cell types .", "annotated_text": "It also induces chemotaxis and inflammatory responses in <cell_type>mature cell types</cell_type> ."}
{"id": "237", "text": "Therefore , it is important to understand the mechanisms which control the expression of MIP-1 alpha /GOS19 .", "annotated_text": "Therefore , it is important to understand the mechanisms which control the expression of <protein>MIP-1 alpha</protein> <protein>/GOS19</protein> ."}
{"id": "238", "text": "Previous work has shown that in Jurkat T cells , a set of widely expressed transcription factors ( the ICK-1 family ) affect the GOS19 promoter .", "annotated_text": "Previous work has shown that in <cell_line>Jurkat T cells</cell_line> , a set of widely expressed <protein>transcription factors</protein> ( the <protein>ICK-1 family</protein> ) affect the <dna>GOS19 promoter</dna> ."}
{"id": "239", "text": "One member , ICK-1A , behaves as a strong negative regulator .", "annotated_text": "One member , <protein>ICK-1A</protein> , behaves as a <protein>strong negative regulator</protein> ."}
{"id": "240", "text": "In this communication , we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells .", "annotated_text": "In this communication , we provide evidence that the pathway of induction in the <cell_line>macrophage cell line</cell_line> <cell_line>U937</cell_line> is different from that in <cell_line>Jurkat cells</cell_line> ."}
{"id": "241", "text": "Furthermore , we show that the ICK-1 binding site does not confer negative regulation in U937 cells .", "annotated_text": "Furthermore , we show that the <dna>ICK-1 binding site</dna> does not confer negative regulation in <cell_line>U937 cells</cell_line> ."}
{"id": "242", "text": "We provide evidence for an additional binding site , the MIP-1 alpha nuclear protein ( MNP ) site , which overlaps the ICK-1 site .", "annotated_text": "We provide evidence for an additional <dna>binding site</dna> , the <dna>MIP-1 alpha nuclear protein ( MNP ) site</dna> , which overlaps the <dna>ICK-1 site</dna> ."}
{"id": "243", "text": "Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities .", "annotated_text": "Interaction of nuclear extracts from <cell_line>various cell lines</cell_line> and tissue with the <dna>MNP site</dna> leads to the formation of <protein>fast-migrating protein-DNA complexes</protein> with similar but distinct electrophoretic mobilities ."}
{"id": "244", "text": "A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells .", "annotated_text": "A mutation of the <dna>MNP site</dna> which does not abrogate ICK-1 binding inactivates the <dna>GOS19.1 promoter</dna> in <cell_line>U937 cells</cell_line> and reduces its activity by fourfold in <cell_line>Jurkat cells</cell_line> ."}
{"id": "245", "text": "We propose that the MNP protein ( s ) binding at the MNP site constitutes a novel transcription factor ( s ) expressed in hematopoietic cells .", "annotated_text": "We propose that the <protein>MNP protein</protein> ( s ) binding at the <dna>MNP site</dna> constitutes a novel <protein>transcription factor</protein> ( s ) expressed in <cell_type>hematopoietic cells</cell_type> ."}
{"id": "246", "text": "The effect of Toremifene on the expression of some genes in human mononuclear cells .", "annotated_text": "The effect of Toremifene on the expression of some genes in <cell_type>human mononuclear cells</cell_type> ."}
{"id": "247", "text": "Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells .", "annotated_text": "Toremifene exerts multiple and varied effects on the gene expression of <cell_type>human peripheral mononuclear cells</cell_type> ."}
{"id": "248", "text": "After short-term , in vitro exposure to therapeutical levels , distinct changes in P-glycoprotein , steroid receptors , p53 and Bcl-2 expression take place .", "annotated_text": "After short-term , in vitro exposure to therapeutical levels , distinct changes in P-glycoprotein , steroid receptors , p53 and Bcl-2 expression take place ."}
{"id": "249", "text": "In view of the increasing use of antiestrogens in cancer therapy and prevention , there is obvious merit in long-term in vivo studies to be conducted .", "annotated_text": "In view of the increasing use of antiestrogens in cancer therapy and prevention , there is obvious merit in long-term in vivo studies to be conducted ."}
{"id": "250", "text": "The interleukin-5 /receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak -STAT pathways in eosinophils .", "annotated_text": "The <protein>interleukin-5</protein> /receptor interaction activates <protein>Lyn and Jak2 tyrosine kinases</protein> and propagates signals via the <protein>Ras-Raf-1-MAP kinase</protein> and the <protein>Jak</protein> <protein>-STAT</protein> pathways in <cell_type>eosinophils</cell_type> ."}
{"id": "251", "text": "We have shown that the interaction of interleukin ( IL ) -5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min .", "annotated_text": "We have shown that the interaction of <protein>interleukin ( IL ) -5</protein> with the receptor activates <protein>Lyn tyrosine kinase</protein> within 1 min and <protein>Jak2 tyrosine kinase</protein> within 1-3 min ."}
{"id": "252", "text": "IL-5 also stimulates GTP binding to p21ras .", "annotated_text": "<protein>IL-5</protein> also stimulates GTP binding to <protein>p21ras</protein> ."}
{"id": "253", "text": "The signal is subsequently propagated through the activation of Raf-1 , MEK , and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ .", "annotated_text": "The signal is subsequently propagated through the activation of <protein>Raf-1</protein> , <protein>MEK</protein> , and <protein>MAP kinases</protein> as shown by their increased autophosphorylation in vitro and phosphorylation in situ ."}
{"id": "254", "text": "Jak2 kinase has been shown to phosphorylate STAT nuclear proteins .", "annotated_text": "<protein>Jak2 kinase</protein> has been shown to phosphorylate <protein>STAT nuclear proteins</protein> ."}
{"id": "255", "text": "The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site ( GAS ) probe .", "annotated_text": "The activation of <protein>STAT nuclear factors</protein> was studied by electrophoretic mobility shift assay using a <dna>gamma activation site</dna> ( <dna>GAS</dna> ) probe ."}
{"id": "256", "text": "We found that IL-5 induces two GAS-binding proteins in eosinophils , one of which is STAT1 .", "annotated_text": "We found that <protein>IL-5</protein> induces two <protein>GAS-binding proteins</protein> in <cell_type>eosinophils</cell_type> , one of which is <protein>STAT1</protein> ."}
{"id": "257", "text": "We conclude that IL-5 induced signals are propagated through two distinct pathways : ( 1 ) Lyn -- > Ras -- > Raf-1 -- > MEK -- > MAP kinase and ( 2 ) Jak2 -- > STAT1 .", "annotated_text": "We conclude that <protein>IL-5</protein> induced signals are propagated through two distinct pathways : ( 1 ) <protein>Lyn</protein> -- > <protein>Ras</protein> -- > <protein>Raf-1</protein> -- > <protein>MEK</protein> -- > <protein>MAP kinase</protein> and ( 2 ) <protein>Jak2</protein> -- > <protein>STAT1</protein> ."}
{"id": "258", "text": "The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein .", "annotated_text": "The <protein>retinoblastoma gene product</protein> negatively regulates transcriptional activation mediated by the <protein>human cytomegalovirus IE2 protein</protein> ."}
{"id": "259", "text": "The IE2 gene product of human cytomegalovirus ( HCMV ) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell .", "annotated_text": "The <protein>IE2 gene product</protein> of human cytomegalovirus ( HCMV ) is one of a few <protein>viral regulatory proteins</protein> expressed immediately upon infection of the <cell_type>host cell</cell_type> ."}
{"id": "260", "text": "It is a potent transcriptional activator of many viral and cellular promoters .", "annotated_text": "It is a potent <protein>transcriptional activator</protein> of many <dna>viral and cellular promoters</dna> ."}
{"id": "261", "text": "We found that the retinoblastoma susceptibility gene product ( Rb ) dramatically suppressed this IE2 transactivation of various promoters .", "annotated_text": "We found that the <protein>retinoblastoma susceptibility gene product</protein> ( <protein>Rb</protein> ) dramatically suppressed this <protein>IE2</protein> transactivation of <dna>various promoters</dna> ."}
{"id": "262", "text": "However , unlike another tumor suppressor protein , p53 , Rb did not have any significant effect on basal levels of transcription , suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery .", "annotated_text": "However , unlike another <protein>tumor suppressor protein</protein> , <protein>p53</protein> , <protein>Rb</protein> did not have any significant effect on basal levels of transcription , suggesting that <protein>Rb</protein> specifically interacts with <protein>IE2</protein> rather than other <protein>cellular factors</protein> involved in the general transcription machinery ."}
{"id": "263", "text": "We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2 .", "annotated_text": "We found by protein-affinity chromatography that <protein>Rb</protein> in nuclear extracts or produced by in vitro translation directly bound to <protein>IE2</protein> ."}
{"id": "264", "text": "Our results suggest that Rb may regulate the life cycle of HCMV , which is endemic in the human population .", "annotated_text": "Our results suggest that <protein>Rb</protein> may regulate the life cycle of HCMV , which is endemic in the human population ."}
{"id": "265", "text": "Furthermore , these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis .", "annotated_text": "Furthermore , these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis ."}
{"id": "266", "text": "Expression of the nucleoside diphosphate kinase in human skin cancers : an immunohistochemical study .", "annotated_text": "Expression of the <protein>nucleoside diphosphate kinase</protein> in human skin cancers : an immunohistochemical study ."}
{"id": "267", "text": "Expression of nucleoside diphosphate ( NDP ) kinase , which is homologous to the nm23 gene product in a variety of species , has been found to be inversely associated with metastatic potential .", "annotated_text": "Expression of <protein>nucleoside diphosphate ( NDP ) kinase</protein> , which is homologous to the <protein>nm23 gene product</protein> in a variety of species , has been found to be inversely associated with metastatic potential ."}
{"id": "268", "text": "However , the relationship remains controversial according to the tumor cell types and experimental system , with conflicting results from different research groups .", "annotated_text": "However , the relationship remains controversial according to the <cell_type>tumor cell types</cell_type> and experimental system , with conflicting results from different research groups ."}
{"id": "269", "text": "In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer , we assessed the levels of NDP kinase expression in 9 keratoacanthomas ( KAs ) , 26 squamous cell carcinomas ( SCCs ) , and 25 basal cell carcinomas ( BCCs ) using immunohistochemistry .", "annotated_text": "In order to determine whether <protein>NDP kinase</protein> expression serves as a marker for metastatic potential in human skin cancer , we assessed the levels of <protein>NDP kinase</protein> expression in 9 keratoacanthomas ( KAs ) , 26 squamous cell carcinomas ( SCCs ) , and 25 basal cell carcinomas ( BCCs ) using immunohistochemistry ."}
{"id": "270", "text": "The expression of NDP kinase was intense in KA and SCC compared with BCC .", "annotated_text": "The expression of <protein>NDP kinase</protein> was intense in KA and SCC compared with BCC ."}
{"id": "271", "text": "However , the difference of NDP kinase expression between KA and SCC was not statistically significant .", "annotated_text": "However , the difference of <protein>NDP kinase</protein> expression between KA and SCC was not statistically significant ."}
{"id": "272", "text": "And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis .", "annotated_text": "And there was no statistically significant difference in <protein>NDP kinase</protein> expression between SCC with metastasis and SCC without metastasis ."}
{"id": "273", "text": "Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer .", "annotated_text": "Our results contradict the hypothesis concerning the possible role of <dna>nm23 gene</dna> as a metastatic suppressor gene in human skin cancer ."}
{"id": "274", "text": "The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined .", "annotated_text": "The mechanism of overexpression in various <cell_type>tumor cell types</cell_type> and its biological significance in cutaneous carcinogenesis remain to be determined ."}
{"id": "275", "text": "RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB-defective tumor lines .", "annotated_text": "<protein>RB</protein> and a novel <protein>E2F-1 binding protein</protein> in <cell_line>MHC class II deficient B-cell lines</cell_line> and normal <protein>IFN-gamma</protein> induction of the <dna>class IL transactivator</dna> <dna>CIITA</dna> in <cell_line>class II non-inducible RB-defective tumor lines</cell_line> ."}
{"id": "276", "text": "The major histocompatibility ( MHC ) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells .", "annotated_text": "The <dna>major histocompatibility ( MHC ) class II genes</dna> encode <protein>cell surface proteins</protein> that bind antigenic peptide for presentation to <cell_type>T-cells</cell_type> ."}
{"id": "277", "text": "The class II proteins are expressed constitutively on B-cells and EBV-transformed B-cells , and are inducible by IFN-gamma on a wide variety of cell types .", "annotated_text": "The <protein>class II proteins</protein> are expressed constitutively on <cell_type>B-cells</cell_type> and <cell_line>EBV-transformed B-cells ,</cell_line> and are inducible by <protein>IFN-gamma</protein> on a wide variety of <cell_type>cell types</cell_type> ."}
{"id": "278", "text": "Retinoblastoma protein ( RB ) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I .", "annotated_text": "<protein>Retinoblastoma protein</protein> ( <protein>RB</protein> ) is a tumor suppressor and functions as a <protein>transcriptional repressor</protein> by binding and inactivating the <dna>transactivator E2F-I</dna> ."}
{"id": "279", "text": "RB-defective tumor lines are non-inducible for MHC class II by IFN-gamma , or very weakly inducible , but transfection of 2 different lines with RB expression vectors re-establishes or substantially enhances class II inducibility .", "annotated_text": "<cell_line>RB-defective tumor lines</cell_line> are non-inducible for <protein>MHC class II</protein> by <protein>IFN-gamma</protein> , or very weakly inducible , but transfection of 2 different lines with <dna>RB expression vectors</dna> re-establishes or substantially enhances class II inducibility ."}
{"id": "280", "text": "Therefore , we examined the RB status of a series of B-cell mutants that are defective in class II expression , generated either in vitro or derived from Bare Lymphocyte Syndrome ( BLS ) patients .", "annotated_text": "Therefore , we examined the <protein>RB</protein> status of a series of B-cell mutants that are defective in class II expression , generated either in vitro or derived from Bare Lymphocyte Syndrome ( BLS ) patients ."}
{"id": "281", "text": "Nuclear matrix-bound RB was detectable in all cases , indicating that loss of RB is not responsible for decreased class II expression in these lines .", "annotated_text": "Nuclear matrix-bound <protein>RB</protein> was detectable in all cases , indicating that loss of <protein>RB</protein> is not responsible for decreased class II expression in these lines ."}
{"id": "282", "text": "A second E2F-I binding protein , most likely DP-I , was also apparently normal in both class II-positive and -negative B-cell lines .", "annotated_text": "A second E2F-I binding protein , most likely DP-I , was also apparently normal in both class II-positive and -negative B-cell lines ."}
{"id": "283", "text": "We also examined the IFN-gamma induction of CIITA in RB -defective lines .", "annotated_text": "We also examined the <protein>IFN-gamma</protein> induction of <dna>CIITA</dna> in <protein>RB</protein> -defective lines ."}
{"id": "284", "text": "CIITA is a class II gene transactivator known to be defective in one form of BLS and to be required for the induction of MHC class II by IFN-gamma .", "annotated_text": "<dna>CIITA</dna> is a <dna>class II gene transactivator</dna> known to be defective in one form of BLS and to be required for the induction of <protein>MHC class II</protein> by <protein>IFN-gamma</protein> ."}
{"id": "285", "text": "CIITA mRNA is normally inducible by IFN-gamma in class II non-inducible , RB-defective lines , and in one line , re-expression of RB has no effect on CIITA mRNA induction levels .", "annotated_text": "<rna>CIITA mRNA</rna> is normally inducible by <protein>IFN-gamma</protein> in <cell_line>class II non-inducible , RB-defective lines</cell_line> , and in one line , re-expression of <protein>RB</protein> has no effect on <rna>CIITA mRNA</rna> induction levels ."}
{"id": "286", "text": "Thus , the block in MHC class II inducibility in RB-defective cells is not due to a block in CIITA inducibility .", "annotated_text": "Thus , the block in MHC class II inducibility in <cell_line>RB-defective cells</cell_line> is not due to a block in <dna>CIITA</dna> inducibility ."}
{"id": "287", "text": "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes .", "annotated_text": "<protein>Interleukin 12</protein> induces tyrosine phosphorylation and activation of <protein>STAT4</protein> in <cell_type>human lymphocytes</cell_type> ."}
{"id": "288", "text": "Interleukin 12 ( IL-12 ) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily .", "annotated_text": "<protein>Interleukin 12</protein> ( <protein>IL-12</protein> ) is an important <protein>immunoregulatory cytokine</protein> whose receptor is a member of the <protein>hematopoietin receptor superfamily</protein> ."}
{"id": "289", "text": "We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2 , implicating these kinases in the immediate biochemical response to IL-12 .", "annotated_text": "We have recently demonstrated that stimulation of <cell_type>human T and natural killer cells</cell_type> with <protein>IL-12</protein> induces tyrosine phosphorylation of the <protein>Janus family tyrosine kinase</protein> <protein>JAK2</protein> and <protein>Tyk2</protein> , implicating these <protein>kinases</protein> in the immediate biochemical response to <protein>IL-12</protein> ."}
{"id": "290", "text": "Recently , transcription factors known as STATs ( signal transducers and activators of transcription ) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases .", "annotated_text": "Recently , <protein>transcription factors</protein> known as <protein>STATs</protein> ( <protein>signal transducers and activators of transcription</protein> ) have been shown to be tyrosine phosphorylated and activated in response to a number of <protein>cytokines</protein> that bind <protein>hematopoietin receptors</protein> and activate <protein>JAK kinases</protein> ."}
{"id": "291", "text": "In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member , STAT4 , and show that STAT4 expression is regulated by T-cell activation .", "annotated_text": "In this report we demonstrate that <protein>IL-12</protein> induces tyrosine phosphorylation of a recently identified <protein>STAT family member</protein> , <protein>STAT4</protein> , and show that <protein>STAT4</protein> expression is regulated by T-cell activation ."}
{"id": "292", "text": "Furthermore , we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4 .", "annotated_text": "Furthermore , we show that <protein>IL-12</protein> stimulates formation of a <protein>DNA-binding complex</protein> that recognizes a DNA sequence previously shown to bind <protein>STAT proteins</protein> and that this complex contains <protein>STAT4</protein> ."}
{"id": "293", "text": "These data , and the recent demonstration of JAK phosphorylation by IL-12 , identify a rapid signal-transduction pathway likely to mediate IL-12 -induced gene expression .", "annotated_text": "These data , and the recent demonstration of <protein>JAK</protein> phosphorylation by <protein>IL-12</protein> , identify a rapid signal-transduction pathway likely to mediate <protein>IL-12</protein> -induced gene expression ."}
{"id": "294", "text": "Temperature-induced down-regulation of the glucocorticoid receptor in peripheral blood mononuclear leucocyte in patients with sepsis or septic shock .", "annotated_text": "Temperature-induced down-regulation of the <protein>glucocorticoid receptor</protein> in <cell_type>peripheral blood mononuclear leucocyte</cell_type> in patients with sepsis or septic shock ."}
{"id": "295", "text": "OBJECTIVE : Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness .", "annotated_text": "OBJECTIVE : Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness ."}
{"id": "296", "text": "We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock .", "annotated_text": "We have studied the adaptive mechanisms which occur at the level of the <protein>glucocorticoid receptor</protein> in glucocorticoid target tissues in patients with sepsis or septic shock ."}
{"id": "297", "text": "DESIGN : The effects of hypercortisolaemia , hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their affinity were evaluated , both in vitro and in vivo , in peripheral blood mononuclear leucocytes of control subjects and in patients with sepsis or septic shock .", "annotated_text": "DESIGN : The effects of hypercortisolaemia , hyperthermia and cellular composition on number of <protein>glucocorticoid receptors</protein> per cell and their affinity were evaluated , both in vitro and in vivo , in <cell_type>peripheral blood mononuclear leucocytes</cell_type> of control subjects and in patients with sepsis or septic shock ."}
{"id": "298", "text": "SUBJECTS : Fifteen patients ( age 25-79 ) with sepsis or septic shock who were admitted to an intensive care unit were studied .", "annotated_text": "SUBJECTS : Fifteen patients ( age 25-79 ) with sepsis or septic shock who were admitted to an intensive care unit were studied ."}
{"id": "299", "text": "The control group consisted of 24 healthy laboratory employees .", "annotated_text": "The control group consisted of 24 healthy laboratory employees ."}
{"id": "300", "text": "MEASUREMENTS : The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma cortisol concentrations .", "annotated_text": "MEASUREMENTS : The binding capacity and affinity of the <protein>glucocorticoid receptors</protein> were measured and compared to clinical data and the plasma cortisol concentrations ."}
{"id": "301", "text": "RESULTS : Hypercortisolaemia , in vitro , resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor .", "annotated_text": "RESULTS : Hypercortisolaemia , in vitro , resulted in a decreased affinity and a decreased binding capacity of the <protein>glucocorticoid receptor</protein> ."}
{"id": "302", "text": "In vitro , hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor .", "annotated_text": "In vitro , hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor ."}
{"id": "303", "text": "In vivo , there was no change in the number of receptors per cell in patients with sepsis or septic shock as compared to healthy controls .", "annotated_text": "In vivo , there was no change in the number of receptors per cell in patients with sepsis or septic shock as compared to healthy controls ."}
{"id": "304", "text": "However , a decreased affinity of the glucocorticoid receptor was observed .", "annotated_text": "However , a decreased affinity of the <protein>glucocorticoid receptor</protein> was observed ."}
{"id": "305", "text": "There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors in the patient group .", "annotated_text": "There was a weak but significant negative correlation between body temperature and the number of <protein>glucocorticoid receptors</protein> in the patient group ."}
{"id": "306", "text": "There was no relation between circulating cortisol concentrations and glucocorticoid receptor affinity and number .", "annotated_text": "There was no relation between circulating cortisol concentrations and <protein>glucocorticoid receptor</protein> affinity and number ."}
{"id": "307", "text": "CONCLUSIONS : There is no obvious regulation of the number of glucocorticoid receptors by plasma cortisol concentrations in vivo .", "annotated_text": "CONCLUSIONS : There is no obvious regulation of the number of <protein>glucocorticoid receptors</protein> by plasma cortisol concentrations in vivo ."}
{"id": "308", "text": "The decreased affinity of the glucocorticoid receptor together with the negative correlation between hyperthermia and the number of glucocorticoid receptors in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in glucocorticoid receptor number and affinity .", "annotated_text": "The decreased affinity of the <protein>glucocorticoid receptor</protein> together with the negative correlation between hyperthermia and the number of <protein>glucocorticoid receptors</protein> in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in <protein>glucocorticoid receptor</protein> number and affinity ."}
{"id": "309", "text": "Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells .", "annotated_text": "Integrin-mediated tyrosine phosphorylation and <protein>cytokine</protein> message induction in <cell_type>monocytic cells</cell_type> ."}
{"id": "310", "text": "A possible signaling role for the Syk tyrosine kinase .", "annotated_text": "A possible signaling role for the <protein>Syk tyrosine kinase</protein> ."}
{"id": "311", "text": "Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins .", "annotated_text": "Activation of <protein>cytoplasmic tyrosine kinases</protein> is an important aspect of signal transduction mediated by <protein>integrins</protein> ."}
{"id": "312", "text": "In the human monocytic cell line THP-1 , either integrin -dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa .", "annotated_text": "In the <cell_line>human monocytic cell line THP-1</cell_line> , either <protein>integrin</protein> -dependent cell adhesion to <protein>fibronectin</protein> or ligation of beta 1 integrins with <protein>antibodies</protein> causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about <protein>65-75 and 120-125 kDa</protein> ."}
{"id": "313", "text": "In addition , integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor , to activation of a reporter gene driven by a promoter containing NF-kappa B sites , and to increased levels of mRNAs for immediate-early genes , including the cytokine interleukin ( IL ) -1 beta .", "annotated_text": "In addition , <protein>integrin</protein> ligation leads to nuclear translocation of the <protein>p50</protein> and <protein>p65 subunits</protein> of the <protein>NF-kappa B transcription factor</protein> , to activation of a <dna>reporter gene</dna> driven by a <dna>promoter</dna> containing <dna>NF-kappa B sites</dna> , and to increased levels of <rna>mRNAs</rna> for <dna>immediate-early genes</dna> , including the <protein>cytokine interleukin ( IL ) -1 beta</protein> ."}
{"id": "314", "text": "The tyrosine kinase inhibitors genistein and herbimycin A block both integrin -mediated tyrosine phosphorylation and increases in IL-1 beta message levels , indicating a causal relationship between the two events .", "annotated_text": "The tyrosine kinase inhibitors genistein and herbimycin A block both <protein>integrin</protein> -mediated tyrosine phosphorylation and increases in <protein>IL-1 beta</protein> message levels , indicating a causal relationship between the two events ."}
{"id": "315", "text": "The components tyrosine phosphorylated subsequent to cell adhesion include paxillin , pp125FAK , and the SH2 domain containing tyrosine kinase Syk .", "annotated_text": "The components tyrosine phosphorylated subsequent to cell adhesion include <protein>paxillin</protein> , <protein>pp125FAK</protein> , and the <protein>SH2 domain containing tyrosine kinase Syk</protein> ."}
{"id": "316", "text": "In contrast , integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin .", "annotated_text": "In contrast , <protein>integrin</protein> ligation with <protein>antibodies</protein> induces tyrosine phosphorylation of <protein>Syk</protein> but not of <protein>FAK</protein> or <protein>paxillin</protein> ."}
{"id": "317", "text": "In adhering cells , pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk , while IL-1 beta message induction is unaffected .", "annotated_text": "In <cell_type>adhering cells</cell_type> , pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of <protein>FAK</protein> and <protein>paxillin</protein> but not of <protein>Syk</protein> , while <protein>IL-1 beta</protein> message induction is unaffected ."}
{"id": "318", "text": "These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells , leading to activation of NF-kappa B and to increased levels of cytokine messages .", "annotated_text": "These observations indicate that the <protein>Syk</protein> tyrosine kinase may be an important component of an <protein>integrin</protein> signaling pathway in <cell_type>monocytic cells</cell_type> , leading to activation of <protein>NF-kappa B</protein> and to increased levels of <protein>cytokine</protein> messages ."}
{"id": "319", "text": "Inhibition of dexamethasone binding to human glucocorticoid receptor by New World primate cell extracts .", "annotated_text": "Inhibition of dexamethasone binding to <protein>human glucocorticoid receptor</protein> by New World primate cell extracts ."}
{"id": "320", "text": "To determine if New World primates express an inhibitor that influences glucocorticoid receptor ( GR ) binding characteristics , we examined [ 3H ] dexamethasone binding in cytosol prepared from B95-8 lymphoid cells , derived from the cotton top tamarin ( Saguinus oedipus ) , in combination with cytosol prepared from human or rat tissues .", "annotated_text": "To determine if New World primates express an inhibitor that influences <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding characteristics , we examined [ 3H ] dexamethasone binding in cytosol prepared from <cell_line>B95-8 lymphoid cells</cell_line> , derived from the cotton top tamarin ( Saguinus oedipus ) , in combination with cytosol prepared from human or rat tissues ."}
{"id": "321", "text": "B95-8 cytosol inhibited specific binding of [ 3H ] dexamethasone ( P < 0.01 ) when mixed with cytosol prepared from either a human lymphoid cell line ( HL ) or rat thymus .", "annotated_text": "B95-8 cytosol inhibited specific binding of [ 3H ] dexamethasone ( P < 0.01 ) when mixed with cytosol prepared from either a <cell_line>human lymphoid cell line</cell_line> ( <cell_line>HL</cell_line> ) or rat thymus ."}
{"id": "322", "text": "The inhibitory activity was heat labile and trypsin sensitive .", "annotated_text": "The inhibitory activity was heat labile and <protein>trypsin</protein> sensitive ."}
{"id": "323", "text": "Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration .", "annotated_text": "Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration ."}
{"id": "324", "text": "Scatchard analysis of [ 3H ] dexamethasone binding using mixed cytosol showed a diminished GR apparent binding affinity when compared to HL cytosol .", "annotated_text": "Scatchard analysis of [ 3H ] dexamethasone binding using mixed cytosol showed a diminished <protein>GR</protein> apparent binding affinity when compared to HL cytosol ."}
{"id": "325", "text": "Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [ 3H ] dexamethasone .", "annotated_text": "Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [ 3H ] dexamethasone ."}
{"id": "326", "text": "These data demonstrate that B95-8 cells contain a competitive inhibitor that prevents binding of dexamethasone to its cognate receptor .", "annotated_text": "These data demonstrate that <cell_type>B95-8 cells</cell_type> contain a competitive inhibitor that prevents binding of dexamethasone to its <protein>cognate receptor</protein> ."}
{"id": "327", "text": "Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals .", "annotated_text": "Disruption of a <dna>GATA motif</dna> in the <dna>Duffy gene promoter</dna> abolishes <dna>erythroid gene</dna> expression in Duffy-negative individuals ."}
{"id": "328", "text": "The mRNA for the Duffy blood group antigen , the erythrocyte receptor for the Plasmodium vivax malaria parasite , has recently been cloned and shown to encode a widely expressed chemokine receptor .", "annotated_text": "The <rna>mRNA</rna> for the <protein>Duffy blood group antigen</protein> , the <protein>erythrocyte receptor</protein> for the Plasmodium vivax malaria parasite , has recently been cloned and shown to encode a widely expressed <protein>chemokine receptor</protein> ."}
{"id": "329", "text": "Here , we show that the Duffy antigen/chemokine receptor gene ( DARC ) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46 .", "annotated_text": "Here , we show that the <dna>Duffy antigen/chemokine receptor gene</dna> ( <dna>DARC</dna> ) is composed of a single <dna>exon</dna> and that most Duffy-negative blacks carry a <dna>silent FY*B allele</dna> with a single T to C substitution at nucleotide -46 ."}
{"id": "330", "text": "This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor .", "annotated_text": "This mutation impairs the promoter activity in <cell_type>erythroid cells</cell_type> by disrupting a <dna>binding site</dna> for the <protein>GATA1 erythroid transcription factor</protein> ."}
{"id": "331", "text": "With the recent characterization of the FY*A and FY*B alleles , these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals .", "annotated_text": "With the recent characterization of the <dna>FY*A and FY*B alleles</dna> , these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the <dna>DARC gene</dna> in Duffy-negative individuals ."}
{"id": "332", "text": "Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells .", "annotated_text": "Activation of <protein>pp90rsk</protein> and <dna>early growth response-1 gene</dna> expression by <protein>pokeweed mitogen</protein> in <cell_type>human B cells</cell_type> ."}
{"id": "333", "text": "The present studies have examined the effects of pokeweed mitogen ( PWM ) on the induction of early growth response-1 gene ( EGR-1 ) in normal human B cells .", "annotated_text": "The present studies have examined the effects of <protein>pokeweed mitogen</protein> ( <protein>PWM</protein> ) on the induction of <dna>early growth response-1 gene</dna> ( <dna>EGR-1</dna> ) in <cell_type>normal human B cells</cell_type> ."}
{"id": "334", "text": "PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms .", "annotated_text": "<protein>PWM</protein> regulates <dna>EGR-1</dna> gene expression by both transcriptional and post-transcriptional mechanisms ."}
{"id": "335", "text": "Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase ( CAT ) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif ( C C [ AT ] 6GG ) in the EGR-1 promoter .", "annotated_text": "Transient transfection assays with <dna>EGR-1 promoter fragments</dna> linked to the <dna>chloramphenicol acetyltransferase ( CAT ) gene</dna> demonstrated that <protein>PWM</protein> induced <dna>EGR-1</dna> transcription is conferred by the <dna>CArG motif</dna> ( <dna>C C [ AT ] 6GG</dna> ) in the <dna>EGR-1 promoter</dna> ."}
{"id": "336", "text": "The results further demonstrated the activation of S6 kinase ( pp90rsk ) , evidenced by phosphorylation of S6 and serum response factor ( SRF ) peptides , in PWM treated B cells .", "annotated_text": "The results further demonstrated the activation of <protein>S6 kinase</protein> ( <protein>pp90rsk</protein> ) , evidenced by phosphorylation of <protein>S6</protein> and serum response factor ( SRF ) peptides , in <cell_line>PWM treated B cells</cell_line> ."}
{"id": "337", "text": "Taken together , these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells .", "annotated_text": "Taken together , these findings suggest that <protein>PWM</protein> is able to initiate an intracytoplasmic signalling cascade and <dna>EGR-1</dna> induction in <cell_type>normal human B cells</cell_type> ."}
{"id": "338", "text": "A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes .", "annotated_text": "A <dna>conserved motif</dna> in the <dna>promoters</dna> of several <protein>cytokines</protein> expressed by <cell_line>human Th2-type lymphocytes</cell_line> ."}
{"id": "339", "text": "We have recently found a novel conserved motif in the promoters of several T-cell-expressed cytokines [ human interleukin-2 , -4 , -5 and -13 and human and mouse granulocyte/macrophage-colony stimulating factor ( GM-CSF ) ] .", "annotated_text": "We have recently found a novel <dna>conserved motif</dna> in the <dna>promoters</dna> of several <protein>T-cell-expressed cytokines</protein> [ <protein>human interleukin-2 , -4 , -5 and -13</protein> and <protein>human and mouse granulocyte/macrophage-colony stimulating factor</protein> ( <protein>GM-CSF</protein> ) ] ."}
{"id": "340", "text": "It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene .", "annotated_text": "It contains a <dna>core sequence</dna> CTTGG ... CCAAG which is present as part of larger <dna>palindromic sequences</dna> in each gene ."}
{"id": "341", "text": "This suggest that they may interact with a new family of trans-acting factors .", "annotated_text": "This suggest that they may interact with a new family of <protein>trans-acting factors</protein> ."}
{"id": "342", "text": "In transfection assays , the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation .", "annotated_text": "In transfection assays , the <dna>human GM-CSF element</dna> has a strong positive effect on the expression of a <dna>reporter gene</dna> by the <cell_line>human T cell line</cell_line> <cell_line>Jurkat J6</cell_line> upon stimulation ."}
{"id": "343", "text": "In DNA mobility shift assays , this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats , depending on the reconstitution conditions .", "annotated_text": "In DNA mobility shift assays , this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats , depending on the reconstitution conditions ."}
{"id": "344", "text": "In different genes , the core sequences are separated by integer numbers of helical turns .", "annotated_text": "In different <dna>genes</dna> , the <dna>core sequences</dna> are separated by integer numbers of helical turns ."}
{"id": "345", "text": "Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed cytokine genes , it may be crucial to the coordinated expression of these cytokines in T helper cells .", "annotated_text": "Considering the strong positive regulatory effect of this <dna>element</dna> and its presence in several <dna>T-cell-expressed cytokine genes</dna> , it may be crucial to the coordinated expression of these <protein>cytokines</protein> in <cell_type>T helper cells</cell_type> ."}
{"id": "346", "text": "cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line .", "annotated_text": "<dna>cDNA</dna> cloning of a <protein>NGFI-B/nur77-related transcription factor</protein> from an <cell_line>apoptotic human T cell line</cell_line> ."}
{"id": "347", "text": "A human T lymphoid cell line , PEER , dies by apoptosis in the presence of PMA and calcium ionophore .", "annotated_text": "A <cell_line>human T lymphoid cell line</cell_line> , <cell_line>PEER</cell_line> , dies by apoptosis in the presence of PMA and calcium ionophore ."}
{"id": "348", "text": "A new gene , TINUR , was cloned from apoptotic PEER cells .", "annotated_text": "A new <dna>gene</dna> , <dna>TINUR</dna> , was cloned from <cell_line>apoptotic PEER cells</cell_line> ."}
{"id": "349", "text": "The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex .", "annotated_text": "The expression of the <dna>TINUR gene</dna> is induced within 1 h after the cross-linking of the <protein>T cell Ag receptor complex</protein> ."}
{"id": "350", "text": "TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor .", "annotated_text": "<dna>TINUR</dna> belongs to the <protein>NGFI-B/nur77 family</protein> of the <protein>steroid receptor superfamily</protein> and is an <protein>orphan receptor</protein> ."}
{"id": "351", "text": "TINUR binds to the same DNA sequence as NGFI-B/nur77 .", "annotated_text": "<dna>TINUR</dna> binds to the same <dna>DNA sequence</dna> as <protein>NGFI-B/nur77</protein> ."}
{"id": "352", "text": "We also propose that the NGFI-B/nur77 family can be classified into two subtypes .", "annotated_text": "We also propose that the <protein>NGFI-B/nur77 family</protein> can be classified into two subtypes ."}
{"id": "353", "text": "Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells .", "annotated_text": "Aspirin inhibits <protein>nuclear factor-kappa B</protein> mobilization and monocyte adhesion in <cell_line>stimulated human endothelial cells</cell_line> ."}
{"id": "354", "text": "BACKGROUND : The induction of vascular cell adhesion molecule-1 ( VCAM-1 ) and E-selectin by tumor necrosis factor-alpha ( TNF ) is mediated by mobilization of the transcription factor nuclear factor-kappa B ( NF-kappa B ) .", "annotated_text": "BACKGROUND : The induction of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) and <protein>E-selectin</protein> by <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF</protein> ) is mediated by mobilization of the <protein>transcription factor</protein> <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) ."}
{"id": "355", "text": "Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B , we studied a potential inhibition of this pathway by acetylsalicylate ( aspirin ) in human umbilical vein endothelial cells ( HUVECs ) .", "annotated_text": "Since salicylates have been reported to inhibit <protein>NF-kappa B</protein> activation by preventing the degradation of its inhibitor <protein>I kappa B</protein> , we studied a potential inhibition of this pathway by acetylsalicylate ( aspirin ) in <cell_line>human umbilical vein endothelial cells</cell_line> ( <cell_line>HUVECs</cell_line> ) ."}
{"id": "356", "text": "METHODS AND RESULTS : Gel-shift analyses demonstrated dose-dependent inhibition of TNF -induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L .", "annotated_text": "METHODS AND RESULTS : Gel-shift analyses demonstrated dose-dependent inhibition of <protein>TNF</protein> -induced <protein>NF-kappa B</protein> mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L ."}
{"id": "357", "text": "Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range , while induction of intercellular adhesion molecule-1 ( ICAM-1 ) was hardly affected .", "annotated_text": "Induction of <protein>VCAM-1</protein> and <protein>E-selectin</protein> surface expression by <protein>TNF</protein> was dose-dependently reduced by aspirin over the same range , while induction of <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) was hardly affected ."}
{"id": "358", "text": "Aspirin appeared to prevent VCAM-1 transcription , since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF .", "annotated_text": "Aspirin appeared to prevent <protein>VCAM-1</protein> transcription , since it dose-dependently inhibited induction of <rna>VCAM-1 mRNA</rna> by <protein>TNF</protein> ."}
{"id": "359", "text": "As a functional consequence , adhesion of U937 monocytes to TNF-stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation .", "annotated_text": "As a functional consequence , adhesion of <cell_line>U937 monocytes</cell_line> to <cell_line>TNF-stimulated HUVECs</cell_line> was markedly reduced by aspirin due to suppression of <protein>VCAM-1</protein> and <protein>E-selectin</protein> upregulation ."}
{"id": "360", "text": "These effects of aspirin were not related to the inhibition of cyclooxygenase activity , since indomethacin was ineffective .", "annotated_text": "These effects of aspirin were not related to the inhibition of <protein>cyclooxygenase</protein> activity , since indomethacin was ineffective ."}
{"id": "361", "text": "CONCLUSIONS : Our data suggest that aspirin inhibits NF-kappa B mobilization , induction of VCAM-1 and E-selectin , and subsequent monocyte adhesion in endothelial cells stimulated by TNF , thereby providing an additional mechanism for therapeutic effects of aspirin .", "annotated_text": "CONCLUSIONS : Our data suggest that aspirin inhibits <protein>NF-kappa B</protein> mobilization , induction of <protein>VCAM-1</protein> and <protein>E-selectin</protein> , and subsequent monocyte adhesion in <cell_type>endothelial cells</cell_type> stimulated by <protein>TNF</protein> , thereby providing an additional mechanism for therapeutic effects of aspirin ."}
{"id": "362", "text": "Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites .", "annotated_text": "Activation of <protein>NF-kappa B</protein> by <protein>phosphatase</protein> inhibitors involves the phosphorylation of <protein>I kappa B alpha</protein> at <protein>phosphatase 2A-sensitive sites</protein> ."}
{"id": "363", "text": "Activation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor , I kappa B alpha , although the underlying mechanism remains unclear .", "annotated_text": "Activation of <protein>NF-kappa B</protein> by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor , <protein>I kappa B alpha</protein> , although the underlying mechanism remains unclear ."}
{"id": "364", "text": "In the present study , the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated .", "annotated_text": "In the present study , the role of <protein>serine/threonine phosphatases</protein> in the regulation of <protein>I kappa B alpha</protein> phosphorylation was investigated ."}
{"id": "365", "text": "Our studies demonstrate that incubation of human T cells with low concentrations ( approximately 1-5 nM ) of calyculin A or okadaic acid , potent inhibitors of protein phosphatase type 1 ( PP-1 ) and type 2A ( PP-2A ) , induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus .", "annotated_text": "Our studies demonstrate that incubation of <cell_type>human T cells</cell_type> with low concentrations ( approximately 1-5 nM ) of calyculin A or okadaic acid , potent inhibitors of <protein>protein phosphatase type 1 ( PP-1 ) and type 2A</protein> ( <protein>PP-2A</protein> ) , induces the phosphorylation of <protein>I kappa B alpha</protein> even in the absence of any cellular stimulus ."}
{"id": "366", "text": "This action of the phosphatase inhibitors , which is associated with the activation of the RelA.p50 NF-kappa B heterodimer , is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha ( TNF-alpha ) .", "annotated_text": "This action of the phosphatase inhibitors , which is associated with the activation of the <protein>RelA.p50 NF-kappa B heterodimer</protein> , is not affected by agents that block the induction of <protein>I kappa B alpha</protein> phosphorylation by <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) ."}
{"id": "367", "text": "Furthermore , the phosphorylated I kappa B alpha from calyculin A-treated cells , but not that from TNF-alpha-stimulated cells , is sensitive to PP-2A in vitro , suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers .", "annotated_text": "Furthermore , the <protein>phosphorylated I kappa B alpha</protein> from <cell_line>calyculin A-treated cells</cell_line> , but not that from <cell_line>TNF-alpha-stimulated cells</cell_line> , is sensitive to <protein>PP-2A</protein> in vitro , suggesting the existence of fundamental differences in the phosphorylation of <protein>I kappa B alpha</protein> induced by the two different <protein>NF-kappa B</protein> inducers ."}
{"id": "368", "text": "However , induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha .", "annotated_text": "However , induction of <protein>I kappa B alpha</protein> phosphorylation by both <protein>TNF-alpha</protein> and the phosphatase inhibitors is associated with the subsequent degradation of <protein>I kappa B alpha</protein> ."}
{"id": "369", "text": "We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor .", "annotated_text": "We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor ."}
{"id": "370", "text": "Together , these results suggest that phosphorylation of I kappa B alpha , mediated through both the TNF-alpha -inducible and the PP-2A-opposing kinases , may serve to target I kappa B alpha for proteasome -mediated degradation .", "annotated_text": "Together , these results suggest that phosphorylation of <protein>I kappa B alpha</protein> , mediated through both the <protein>TNF-alpha</protein> -inducible and the <protein>PP-2A-opposing kinases</protein> , may serve to target <protein>I kappa B alpha</protein> for <protein>proteasome</protein> -mediated degradation ."}
{"id": "371", "text": "Sp1 functions in a chromatin -dependent manner to augment human alpha-globin promoter activity .", "annotated_text": "<protein>Sp1</protein> functions in a <dna>chromatin</dna> -dependent manner to augment <dna>human alpha-globin promoter</dna> activity ."}
{"id": "372", "text": "The 5 ' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site .", "annotated_text": "The <dna>5 ' flanking region</dna> of the <dna>human alpha-globin gene</dna> is highly G + C rich and contains multiple copies of the <dna>consensus sequence</dna> for the <dna>Sp1 binding site</dna> ."}
{"id": "373", "text": "We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer , HS-40 .", "annotated_text": "We investigated the role of this <dna>G + C-rich region</dna> in augmenting <dna>alpha-globin promoter</dna> activity in the presence of the <dna>far-upstream alpha-globin enhancer</dna> , <dna>HS-40</dna> ."}
{"id": "374", "text": "We show that in transiently transfected erythroid cells , deletion of the alpha-globin G + C-rich 5 ' flanking region has no effect on alpha-globin promoter activity .", "annotated_text": "We show that in <cell_line>transiently transfected erythroid cells</cell_line> , deletion of the <dna>alpha-globin G + C-rich 5 ' flanking region</dna> has no effect on <dna>alpha-globin promoter</dna> activity ."}
{"id": "375", "text": "However , upon stable integration into chromatin , deletion of this region causes a nearly 90 % decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region .", "annotated_text": "However , upon stable integration into <dna>chromatin</dna> , deletion of this region causes a nearly 90 % decrease in promoter activity compared with expression from an <dna>alpha-globin promoter</dna> retaining this region ."}
{"id": "376", "text": "These results suggest that the alpha-globin G + C-rich 5 ' flanking region augments alpha-globin promoter activity in a chromatin -dependent manner .", "annotated_text": "These results suggest that the <dna>alpha-globin G + C-rich 5 ' flanking region</dna> augments <dna>alpha-globin promoter</dna> activity in a <dna>chromatin</dna> -dependent manner ."}
{"id": "377", "text": "We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation .", "annotated_text": "We further show that this <dna>G + C-rich region</dna> is required for the activation of <dna>alpha-globin gene</dna> expression during erythroid differentiation ."}
{"id": "378", "text": "Finally , we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1 .", "annotated_text": "Finally , we show by both footprint analysis and functional assays that the ability of the <dna>G + C-rich region</dna> to increase <dna>alpha-globin promoter</dna> activity from a stably integrated <dna>alpha-globin gene</dna> is mediated by its <dna>multiple binding sites</dna> for the <protein>transcription factor</protein> <protein>Sp1</protein> ."}
{"id": "379", "text": "Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors .", "annotated_text": "Costimulation of <cell_line>human CD4+ T cells</cell_line> with <protein>LFA-3</protein> and <protein>B7</protein> induce distinct effects on AP-1 and <protein>NF-kappa B</protein> <protein>transcription factors</protein> ."}
{"id": "380", "text": "We have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary ( CHO ) -DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles .", "annotated_text": "We have earlier shown that stimulation of <cell_line>human CD4+ T cells</cell_line> with SEA presented on <cell_line>Chinese hamster ovary ( CHO ) -DR transfectants</cell_line> coexpressing either <protein>B7</protein> or <protein>LFA-3</protein> resulted in distinct <protein>cytokine</protein> profiles ."}
{"id": "381", "text": "We now demonstrate that B7 , but not LFA-3 , strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells .", "annotated_text": "We now demonstrate that <protein>B7</protein> , but not <protein>LFA-3</protein> , strongly costimulated <protein>IL-2</protein> transcription and mRNA expression in <cell_line>CD4+ T cells</cell_line> ."}
{"id": "382", "text": "Maximal increase in IL-2 transcription was recorded with CHO-DR/B7/LFA-3 , suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level .", "annotated_text": "Maximal increase in <protein>IL-2</protein> transcription was recorded with <protein>CHO-DR/B7/LFA-3</protein> , suggesting a cooperative effect of <protein>B7</protein> and <protein>LFA-3</protein> at the transcriptional level ."}
{"id": "383", "text": "Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins , whereas induction of AP-1 binding proteins required costimulation .", "annotated_text": "Gel-shift analysis demonstrated that stimulation of <cell_line>CD4+ T cells</cell_line> with <protein>CHO-DR</protein> and staphylococcal enterotoxin A was sufficient to induce significant amounts of <protein>NF-kappa B</protein> binding proteins , whereas induction of <protein>AP-1 binding proteins</protein> required costimulation ."}
{"id": "384", "text": "LFA-3 induced moderate levels of AP-1 , but did not influence the levels of NF-kappa B , while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins .", "annotated_text": "<protein>LFA-3</protein> induced moderate levels of <protein>AP-1</protein> , but did not influence the levels of <protein>NF-kappa B</protein> , while <protein>B7</protein> costimulation strongly induced both <protein>AP-1</protein> and substantially enhanced <protein>NF-kappa B binding proteins</protein> ."}
{"id": "385", "text": "The CHO-DR/B7/LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants .", "annotated_text": "The <cell_line>CHO-DR/B7/LFA-3 triple transfectant</cell_line> induced a further increase in <protein>AP-1</protein> and <protein>NF-kappa B</protein> <protein>binding proteins</protein> compared with the <cell_line>double transfectants</cell_line> ."}
{"id": "386", "text": "The level of Oct-1 binding proteins remained similar in all samples .", "annotated_text": "The level of <protein>Oct-1 binding proteins</protein> remained similar in all samples ."}
{"id": "387", "text": "Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50 , substantial amounts of p65 , and marginal levels of c-Rel proteins .", "annotated_text": "Super-shift analysis revealed that the <protein>NF-kappa B complex</protein> of <cell_line>costimulated CD4+ T cells</cell_line> contained large amounts of <protein>p50</protein> , substantial amounts of <protein>p65</protein> , and marginal levels of <protein>c-Rel proteins</protein> ."}
{"id": "388", "text": "The AP-1 binding proteins contained c-Jun , Jun-D , and Fra-1 , but marginal amounts of Jun-B and c-Fos .", "annotated_text": "The <protein>AP-1 binding proteins</protein> contained <protein>c-Jun</protein> , <protein>Jun-D</protein> , and <protein>Fra-1</protein> , but marginal amounts of <protein>Jun-B</protein> and <protein>c-Fos</protein> ."}
{"id": "389", "text": "Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B .", "annotated_text": "Our results indicate distinct effects of <protein>B7</protein> and <protein>LFA-3</protein> costimulation on the activity of <protein>AP-1</protein> and <protein>NF-kappa B</protein> ."}
{"id": "390", "text": "These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression .", "annotated_text": "These may partly account for the differential effects of <protein>B7</protein> and <protein>LFA-3</protein> costimulation on <protein>IL-2</protein> expression ."}
{"id": "391", "text": "The Ah receptor recognizes DNA binding sites for the B cell transcription factor , BSAP : a possible mechanism for dioxin-mediated alteration of CD19 gene expression in human B lymphocytes .", "annotated_text": "The <protein>Ah receptor</protein> recognizes <dna>DNA binding sites</dna> for the <protein>B cell transcription factor</protein> , <protein>BSAP</protein> : a possible mechanism for dioxin-mediated alteration of <dna>CD19 gene</dna> expression in <cell_type>human B lymphocytes</cell_type> ."}
{"id": "392", "text": "2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism .", "annotated_text": "2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism ."}
{"id": "393", "text": "This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line .", "annotated_text": "This study investigated the effect of TCDD on expression of the <dna>CD19 gene</dna> in a <cell_line>human B lymphocyte cell line</cell_line> ."}
{"id": "394", "text": "Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67 % in the IM-9 cell line .", "annotated_text": "Northern blot analysis showed that TCDD treatment decreased steady state levels of <rna>CD19 mRNA</rna> by 67 % in the <cell_line>IM-9 cell line</cell_line> ."}
{"id": "395", "text": "Using a gel mobility shift assay , we identified a DNA-binding complex in IM-9 nuclear extracts that by several criteria appears to be the Ah receptor .", "annotated_text": "Using a gel mobility shift assay , we identified a <protein>DNA-binding complex</protein> in IM-9 nuclear extracts that by several criteria appears to be the <protein>Ah receptor</protein> ."}
{"id": "396", "text": "In addition , the Ah receptor complex recognized a DNA binding site for B cell lineage-specific activator protein ( BSAP ) in the promoter region of the human CD19 gene which is similar to the consensus Ah receptor DNA binding site .", "annotated_text": "In addition , the <protein>Ah receptor complex</protein> recognized a <dna>DNA binding site</dna> for <protein>B cell lineage-specific activator protein</protein> ( <protein>BSAP</protein> ) in the <dna>promoter region</dna> of the human <dna>CD19 gene</dna> which is similar to the <dna>consensus Ah receptor DNA binding site</dna> ."}
{"id": "397", "text": "These results suggest that the AhR could interfere with BSAP -stimulated CD19 gene transcription by competition for a common DNA binding site .", "annotated_text": "These results suggest that the <protein>AhR</protein> could interfere with <protein>BSAP</protein> -stimulated <dna>CD19 gene</dna> transcription by competition for a common <dna>DNA binding site</dna> ."}
{"id": "398", "text": "Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells .", "annotated_text": "Inhibitory action of <protein>nm23 proteins</protein> on induction of erythroid differentiation of <cell_type>human leukemia cells</cell_type> ."}
{"id": "399", "text": "We recently identified a differentiation inhibitory factor ( I-factor ) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product .", "annotated_text": "We recently identified a <protein>differentiation inhibitory factor</protein> ( <protein>I-factor</protein> ) in <cell_line>mouse myeloid leukemia M1 cells</cell_line> as a <protein>murine homolog</protein> of the <protein>human nm23-H2 gene product</protein> ."}
{"id": "400", "text": "nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes , although their mechanisms of action are still unknown .", "annotated_text": "<dna>nm23 genes</dna> encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes , although their mechanisms of action are still unknown ."}
{"id": "401", "text": "Although all nm23 proteins contain nucleoside diphosphate ( NDP ) kinase activity , it has not been established that the enzyme activity mediated the various functions of nm23 proteins .", "annotated_text": "Although all <protein>nm23 proteins</protein> contain <protein>nucleoside diphosphate ( NDP ) kinase</protein> activity , it has not been established that the enzyme activity mediated the various functions of <protein>nm23 proteins</protein> ."}
{"id": "402", "text": "In the present experiment , we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60 , U937 , HEL/S , KU812F , K562 , and HEL cells .", "annotated_text": "In the present experiment , we examined the effect of <protein>nm23 proteins</protein> on various differentiation induction systems of <cell_type>human leukemic cells</cell_type> including <cell_line>HL-60 , U937 , HEL/S , KU812F , K562 , and HEL cells</cell_line> ."}
{"id": "403", "text": "Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL , KU812 and K562 cells , but not the induction of monocytic or granulocytic differentiation of HL-60 , U937 and HEL/S cells .", "annotated_text": "<protein>Native human erythrocyte NDP kinase protein</protein> inhibited the induction of erythroid differentiation of <cell_line>HEL , KU812 and K562 cells</cell_line> , but not the induction of monocytic or granulocytic differentiation of <cell_line>HL-60 , U937 and HEL/S cells</cell_line> ."}
{"id": "404", "text": "The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1 , -H2 , mouse nm23-M1 , and -M2 proteins .", "annotated_text": "The erythroid differentiation of <cell_line>HEL cells</cell_line> was inhibited by <protein>recombinant human nm23-H1 , -H2 , mouse nm23-M1 , and -M2 proteins</protein> ."}
{"id": "405", "text": "Moreover , both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal ( 1-60 ) peptide , which do not have NDP kinase activity , also inhibited erythroid differentiation of HEL cells .", "annotated_text": "Moreover , both the <protein>mutant nm23-H2His protein</protein> and <protein>truncated nm23-H2 protein</protein> containing <protein>N-terminal ( 1-60 ) peptide</protein> , which do not have <protein>NDP kinase</protein> activity , also inhibited erythroid differentiation of <cell_line>HEL cells</cell_line> ."}
{"id": "406", "text": "These results suggest that ( 1 ) the differentiation inhibitory activity of I-factor/nm23 protein is not restricted to monocytic differentiation of M1 cells , ( 2 ) the inhibitory activity is exhibited without species specificity , and ( 3 ) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides .", "annotated_text": "These results suggest that ( 1 ) the differentiation inhibitory activity of <protein>I-factor/nm23 protein</protein> is not restricted to monocytic differentiation of <cell_line>M1 cells</cell_line> , ( 2 ) the inhibitory activity is exhibited without species specificity , and ( 3 ) the differentiation inhibitory activity of the <protein>nm23/NDP kinase protein</protein> is independent of its enzyme activity and requires the presence of N-terminal peptides ."}
{"id": "407", "text": "Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein .", "annotated_text": "Lipopolysaccharide-induced <protein>E-selectin</protein> expression requires continuous presence of LPS and is inhibited by <protein>bactericidal/permeability-increasing protein</protein> ."}
{"id": "408", "text": "Endothelial cells stimulated by LPS express E-selectin , which plays an important role in mediating neutrophil adhesion during inflammation .", "annotated_text": "<cell_type>Endothelial cells</cell_type> stimulated by LPS express <protein>E-selectin</protein> , which plays an important role in mediating <cell_type>neutrophil</cell_type> adhesion during inflammation ."}
{"id": "409", "text": "E-selectin is induced within 1-2 h , peaks at 4-6 h , and gradually returns to basal level by 24 h .", "annotated_text": "<protein>E-selectin</protein> is induced within 1-2 h , peaks at 4-6 h , and gradually returns to basal level by 24 h ."}
{"id": "410", "text": "rBPI21 , a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein ( BPI ) , inhibited LPS-induced E-selectin expression when added at the same time as , and up to 6 h after , LPS .", "annotated_text": "<protein>rBPI21</protein> , a <protein>recombinant N-terminal fragment</protein> of <protein>human bactericidal/permeability-increasing protein</protein> ( <protein>BPI</protein> ) , inhibited LPS-induced <protein>E-selectin</protein> expression when added at the same time as , and up to 6 h after , LPS ."}
{"id": "411", "text": "Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor , NF-kappa B .", "annotated_text": "Delayed administration of <protein>rBPI21</protein> also affected LPS-mediated activation of the <protein>nuclear factor</protein> , <protein>NF-kappa B</protein> ."}
{"id": "412", "text": "Two to 4 h following LPS addition to endothelial cells , when NF-kappa B was already activated , addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h .", "annotated_text": "Two to 4 h following LPS addition to <cell_type>endothelial cells</cell_type> , when <protein>NF-kappa B</protein> was already activated , addition of <protein>rBPI21</protein> resulted in marked reduction of <protein>NF-kappa B</protein> detectable at 4 or 6 h ."}
{"id": "413", "text": "These results indicate that endothelial activation requires continuous presence of LPS , and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal .", "annotated_text": "These results indicate that endothelial activation requires continuous presence of LPS , and <protein>rBPI21</protein> acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal ."}
{"id": "414", "text": "GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells .", "annotated_text": "<protein>GM-CSF</protein> and <protein>IL-2</protein> share common control mechanisms in response to costimulatory signals in <cell_type>T cells</cell_type> ."}
{"id": "415", "text": "Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor ( TCR ) on the surface of T cells and initiates an activation cascade .", "annotated_text": "Antigen complexed with <protein>major histocompatibility complex class I or II molecules</protein> on the surface of <cell_type>antigen presenting cells</cell_type> interacts with the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) on the surface of <cell_type>T cells</cell_type> and initiates an activation cascade ."}
{"id": "416", "text": "So called costimulatory signals , mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells , are also required for complete T cell activation .", "annotated_text": "So called costimulatory signals , mediated by other cell surface interactions or <protein>soluble cytokines</protein> produced by <cell_type>antigen presenting cells</cell_type> , are also required for complete T cell activation ."}
{"id": "417", "text": "High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals .", "annotated_text": "High levels of <protein>cytokine</protein> gene expression in <cell_type>T cells</cell_type> also required both <protein>TCR</protein> and costimulatory signals ."}
{"id": "418", "text": "The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR -like signals .", "annotated_text": "The <protein>granulocyte-macrophage colony-stimulating factor</protein> requires sequences in the <dna>promoter</dna> as well as a powerful <dna>enhancer</dna> located 3kb upstream to respond to <protein>TCR</protein> -like signals ."}
{"id": "419", "text": "These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells ( NFAT ) .", "annotated_text": "These <dna>promoter and enhancer regions</dna> are mainly activated by the <protein>transcription factor nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) ."}
{"id": "420", "text": "The activation of NFAT by TCR signals has been well described for interleukin-2 ( IL-2 ) and IL-4 gene transcription in T cells .", "annotated_text": "The activation of <protein>NFAT</protein> by <protein>TCR</protein> signals has been well described for interleukin-2 ( <protein>IL-2</protein> ) and IL-4 gene transcription in <cell_type>T cells</cell_type> ."}
{"id": "421", "text": "Costimulatory signals , such as activation of the CD28 cell surface molecule on T cells , lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter .", "annotated_text": "Costimulatory signals , such as activation of the <protein>CD28 cell surface molecule</protein> on <cell_type>T cells</cell_type> , lead to activation through a distinct region of the <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter</dna> ."}
{"id": "422", "text": "This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-kappa B family of transcription factors .", "annotated_text": "This region is termed the <dna>CK-1</dna> or <dna>CD28RE</dna> and appears to bind specific members of the <protein>NF-kappa B family</protein> of <protein>transcription factors</protein> ."}
{"id": "423", "text": "Human T leukemia virus type 1 ( HTLV-1 ) infects T cells and can lead to increase GM-CSF expression .", "annotated_text": "Human T leukemia virus type 1 ( HTLV-1 ) infects <cell_type>T cells</cell_type> and can lead to increase <protein>GM-CSF</protein> expression ."}
{"id": "424", "text": "We have found that the HTLV-1 transactivator protein , tax , acts as a costimulatory signal for GM-CSF and IL-2 gene transcription , in that it can cooperate with TCR signals to mediate high level gene expression .", "annotated_text": "We have found that the <protein>HTLV-1 transactivator protein</protein> , <protein>tax</protein> , acts as a costimulatory signal for GM-CSF and IL-2 gene transcription , in that it can cooperate with <protein>TCR</protein> signals to mediate high level gene expression ."}
{"id": "425", "text": "Tax activates the GM-CSF promoter through the CK-1 /CD28RE region and also activates nuclear factor-kappa B binding to this region .", "annotated_text": "Tax activates the <dna>GM-CSF promoter</dna> through the <dna>CK-1</dna> <dna>/CD28RE</dna> region and also activates <protein>nuclear factor-kappa B</protein> binding to this region ."}
{"id": "426", "text": "However , other transcription factors or coactivators of NF-kappa B are required for tax activation but these remain to be identified .", "annotated_text": "However , other <protein>transcription factors</protein> or coactivators of <protein>NF-kappa B</protein> are required for <protein>tax</protein> activation but these remain to be identified ."}
{"id": "427", "text": "The CK-1 /CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region .", "annotated_text": "The <dna>CK-1</dna> <dna>/CD28RE</dna> of <protein>GM-CSF</protein> shows a high degree of similarity to the <protein>IL-2</protein> <dna>CD28RE</dna> and the <dna>IL-3 gene</dna> also contains a related region ."}
{"id": "428", "text": "This observation , together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT , implies a high degree of conservation in the regulation of cytokine gene expression in T cells .", "annotated_text": "This observation , together with the fact that both <protein>GM-CSF</protein> and <protein>IL-2</protein> respond to <protein>TCR</protein> signals via <protein>NFAT</protein> , implies a high degree of conservation in the regulation of <protein>cytokine</protein> gene expression in <cell_type>T cells</cell_type> ."}
{"id": "429", "text": "Danazol decreases transcription of estrogen receptor gene in human monocytes .", "annotated_text": "Danazol decreases transcription of <dna>estrogen receptor gene</dna> in <cell_type>human monocytes</cell_type> ."}
{"id": "430", "text": "1. Administration of danazol for over one month reduced the levels of estrogen receptor ( ER ) and its mRNA to approximately 50 and 20 % , respectively in monocytes .", "annotated_text": "1. Administration of danazol for over one month reduced the levels of <protein>estrogen receptor</protein> ( <protein>ER</protein> ) and its <rna>mRNA</rna> to approximately 50 and 20 % , respectively in <cell_type>monocytes</cell_type> ."}
{"id": "431", "text": "2. Danazol did not alter the degradation rate of ER mRNA in monocytes .", "annotated_text": "2. Danazol did not alter the degradation rate of <rna>ER mRNA</rna> in <cell_type>monocytes</cell_type> ."}
{"id": "432", "text": "3. Danazol decreased the transcription rate of ER gene to approximately 50 % in monocytes in a run-on assay .", "annotated_text": "3. Danazol decreased the transcription rate of <dna>ER gene</dna> to approximately 50 % in <cell_type>monocytes</cell_type> in a run-on assay ."}
{"id": "433", "text": "4. Danazol may release estrogen predominance via the reduction of transcription for ER gene , which leads to the reduction of ER mRNA and ER expressions in monocytes .", "annotated_text": "4. Danazol may release estrogen predominance via the reduction of transcription for <dna>ER gene</dna> , which leads to the reduction of <rna>ER mRNA</rna> and <protein>ER</protein> expressions in <cell_type>monocytes</cell_type> ."}
{"id": "434", "text": "Functional characterization of novel IL-2 transcriptional inhibitors .", "annotated_text": "Functional characterization of novel <protein>IL-2</protein> transcriptional inhibitors ."}
{"id": "435", "text": "IL-2 -mediated T cell proliferation is a critical early event in the inflammatory process .", "annotated_text": "<protein>IL-2</protein> -mediated <cell_type>T cell</cell_type> proliferation is a critical early event in the inflammatory process ."}
{"id": "436", "text": "Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription .", "annotated_text": "Formation of the <protein>NFAT-1 transcriptional complex</protein> on the <dna>IL-2 promoter</dna> is essential for <protein>IL-2</protein> transcription ."}
{"id": "437", "text": "Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene , we screened for inhibitors of NFAT -1-mediated beta-galactosidase activity .", "annotated_text": "Using a cell line that is stably transfected with a trimer of the <dna>NFAT-1 regulatory element</dna> linked to a <dna>lac-Z reporter gene</dna> , we screened for inhibitors of <protein>NFAT</protein> -1-mediated <protein>beta-galactosidase</protein> activity ."}
{"id": "438", "text": "WIN 61058 and WIN 53071 were identified as microM inhibitors .", "annotated_text": "WIN 61058 and WIN 53071 were identified as microM inhibitors ."}
{"id": "439", "text": "These compounds also inhibited beta-galactosidase mRNA levels .", "annotated_text": "These compounds also inhibited <rna>beta-galactosidase mRNA</rna> levels ."}
{"id": "440", "text": "Similar inhibition of NFAT -1-mediated gene expression was observed in a second cell line , which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8 .", "annotated_text": "Similar inhibition of <protein>NFAT</protein> -1-mediated gene expression was observed in a second <cell_line>cell line</cell_line> , which is stably transfected with <dna>NFAT-1 regulatory elements</dna> linked to the <dna>reporter gene for sCD8</dna> ."}
{"id": "441", "text": "At 10 microM , both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants , and in human lymphocytes .", "annotated_text": "At 10 microM , both compounds inhibited IL-2 mRNA and protein levels in the <cell_line>NFAT-1-linked lac-Z transfectants</cell_line> , and in <cell_type>human lymphocytes</cell_type> ."}
{"id": "442", "text": "Both compounds inhibited the mixed lymphocyte reaction , and this inhibition was reversed by exogenous IL-2 .", "annotated_text": "Both compounds inhibited the mixed lymphocyte reaction , and this inhibition was reversed by exogenous <protein>IL-2</protein> ."}
{"id": "443", "text": "WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway .", "annotated_text": "WIN 53071 inhibited <protein>IL-2</protein> production induced in the calcium-dependent PMA and ionomycin pathway ."}
{"id": "444", "text": "Conversely , calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant .", "annotated_text": "Conversely , <protein>calcium-independent anti-CD28 Ab</protein> and PMA-induced <protein>IL-2</protein> production was resistant ."}
{"id": "445", "text": "Both compounds altered the NFAT-1 transcriptional complex , causing its retarded mobility on gels .", "annotated_text": "Both compounds altered the <protein>NFAT-1 transcriptional complex</protein> , causing its retarded mobility on gels ."}
{"id": "446", "text": "By these functional criteria , we believe we have identified two structurally distinct , novel inhibitors of NFAT -1-mediated transcription .", "annotated_text": "By these functional criteria , we believe we have identified two structurally distinct , novel inhibitors of <protein>NFAT</protein> -1-mediated transcription ."}
{"id": "447", "text": "Transcriptional regulation of the vacuolar H ( + ) -ATPase B2 subunit gene in differentiating THP-1 cells .", "annotated_text": "Transcriptional regulation of the <dna>vacuolar H ( + ) -ATPase B2 subunit gene</dna> in <cell_line>differentiating THP-1 cells</cell_line> ."}
{"id": "448", "text": "Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H ( + ) -ATPase ( V-ATPase ) .", "annotated_text": "Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the <protein>human vacuolar H ( + ) -ATPase</protein> ( <protein>V-ATPase</protein> ) ."}
{"id": "449", "text": "We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1 , and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content .", "annotated_text": "We examined <rna>mRNA</rna> levels of various <protein>V-ATPase</protein> subunits during differentiation of both <cell_type>native monocytes</cell_type> and the <cell_line>cell line</cell_line> <cell_line>THP-1</cell_line> , and found that transcriptional and post-transcriptional mechanisms could account for increases in cell <protein>V-ATPase</protein> content ."}
{"id": "450", "text": "From nuclear runoff experiments , we found that one subunit in particular , the B2 isoform ( Mr = 56 , 000 ) , was amplified primarily by transcriptional means .", "annotated_text": "From nuclear runoff experiments , we found that one subunit in particular , the <protein>B2 isoform</protein> ( Mr = 56 , 000 ) , was amplified primarily by transcriptional means ."}
{"id": "451", "text": "We have begun to examine the structure of the B2 subunit promoter region .", "annotated_text": "We have begun to examine the structure of the <dna>B2 subunit promoter region</dna> ."}
{"id": "452", "text": "Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content .", "annotated_text": "Isolation and sequencing of the <dna>first exon</dna> and <dna>5'-flanking region</dna> of this gene reveal a <dna>TATA-less promoter</dna> with a high G + C content ."}
{"id": "453", "text": "Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site .", "annotated_text": "Primer extension and <protein>ribonuclease</protein> protection analyses indicate a single <dna>major transcriptional start site</dna> ."}
{"id": "454", "text": "We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation .", "annotated_text": "We transfected <dna>promoter-luciferase reporter plasmids</dna> into <cell_line>THP-1 cells</cell_line> to define sequences that mediate transcriptional control during monocyte differentiation ."}
{"id": "455", "text": "We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation .", "annotated_text": "We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during <cell_line>THP-1</cell_line> differentiation ."}
{"id": "456", "text": "DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions .", "annotated_text": "<protein>DNase I</protein> footprinting and sequence analysis revealed the existence of multiple <dna>AP2 and Sp1 binding sites</dna> in the <dna>5'-untranslated and proximal coding regions</dna> ."}
{"id": "457", "text": "Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines : implication for c-fos control via surface immunoglobulin and T cell antigen receptors .", "annotated_text": "Synergy between signal transduction pathways is obligatory for expression of <dna>c-fos</dna> in <cell_line>B and T cell lines</cell_line> : implication for <dna>c-fos</dna> control via <protein>surface immunoglobulin</protein> and <protein>T cell antigen receptors</protein> ."}
{"id": "458", "text": "Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C , cAMP , and calcium .", "annotated_text": "Expression of the <dna>protooncogene c-fos</dna> is controlled by three main regulatory pathways involving <protein>kinase C</protein> , cAMP , and calcium ."}
{"id": "459", "text": "Kinase C mediates its effects via phosphorylation of serum response factor ( SRF ) which interacts with the serum response element ( SRE ) ; cAMP and calcium mediate their effects via phosphorylation of CREB ( cAMP regulatory element binding protein ) presumably by activation of a protein kinase A or calmodulin-regulated kinase .", "annotated_text": "<protein>Kinase C</protein> mediates its effects via phosphorylation of <protein>serum response factor</protein> ( <protein>SRF</protein> ) which interacts with the <dna>serum response element</dna> ( <dna>SRE</dna> ) ; cAMP and calcium mediate their effects via phosphorylation of <protein>CREB</protein> ( <protein>cAMP regulatory element binding protein</protein> ) presumably by activation of a <protein>protein kinase A</protein> or <protein>calmodulin-regulated kinase</protein> ."}
{"id": "460", "text": "We have examined the function of these elements in Burkitt 's lymphoma cells ( Ramos and Daudi ) as well as a T lymphocytic cell line ( Jurkat ) .", "annotated_text": "We have examined the function of these elements in <cell_line>Burkitt 's lymphoma cells</cell_line> ( <cell_line>Ramos</cell_line> and <cell_line>Daudi</cell_line> ) as well as a <cell_line>T lymphocytic cell line</cell_line> ( <cell_line>Jurkat</cell_line> ) ."}
{"id": "461", "text": "We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction .", "annotated_text": "We have found that stimulation of any one of these pathways alone has little or no effect on <dna>c-fos</dna> induction ."}
{"id": "462", "text": "However , kinase C activation ( PMA stimulation ) combined with either cAMP ( forskolin plus MIX ) or calcium stimulation ( ionophore ) leads to greatly enhanced c-fos induction .", "annotated_text": "However , <protein>kinase C</protein> activation ( PMA stimulation ) combined with either cAMP ( forskolin plus MIX ) or calcium stimulation ( ionophore ) leads to greatly enhanced <dna>c-fos</dna> induction ."}
{"id": "463", "text": "By contrast , cAMP in the presence of calcium shows no synergy in c-fos induction .", "annotated_text": "By contrast , cAMP in the presence of calcium shows no synergy in <dna>c-fos</dna> induction ."}
{"id": "464", "text": "Okadaic acid augments PMA- as well as calcium-mediated activation of c-fos , and has little or no effect when combined with cAMP .", "annotated_text": "Okadaic acid augments PMA- as well as calcium-mediated activation of <dna>c-fos</dna> , and has little or no effect when combined with cAMP ."}
{"id": "465", "text": "The main difference between Ramos ( B cells ) and Jurkat ( T cells ) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos .", "annotated_text": "The main difference between <cell_line>Ramos</cell_line> ( <cell_type>B cells</cell_type> ) and <cell_line>Jurkat</cell_line> ( <cell_type>T cells</cell_type> ) in the regulation of <dna>c-fos</dna> is that cAMP plus calcium is strongly synergistic in <cell_line>Jurkat</cell_line> and is without effect in <cell_line>Ramos</cell_line> ."}
{"id": "466", "text": "Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity .", "annotated_text": "Analysis of <protein>AP-1</protein> activity using gel mobility shift assays confirms that the requirements for synergy in <rna>c-fos mRNA</rna> induction are paralleled by requirements for synergy in induction of <protein>AP-1</protein> activity ."}
{"id": "467", "text": "Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium , and results in c-fos mRNA induction .", "annotated_text": "Signaling in <cell_type>B cells</cell_type> due to <protein>anti-Ig</protein> stimulation involves both <protein>kinase C</protein> activation and release of intracellular calcium , and results in <rna>c-fos mRNA</rna> induction ."}
{"id": "468", "text": "Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well .", "annotated_text": "Our results indicate that synergy between the <protein>kinase C</protein> activation and calcium is needed for efficient <dna>c-fos</dna> induction since neither of these two alone induces <dna>c-fos</dna> well ."}
{"id": "469", "text": "That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig induction of c-fos .", "annotated_text": "That synergy of signaling pathways is relevant for the <protein>anti-Ig</protein> induction of <dna>c-fos</dna> is supported by the fact that cAMP-inducing agents and okadaic acid further enhance <protein>anti-Ig</protein> induction of <dna>c-fos</dna> ."}
{"id": "470", "text": "These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors .", "annotated_text": "These results suggest that cell-specific patterns of synergy are an essential feature for <dna>c-fos</dna> induction and may be relevant for <dna>c-fos</dna> control through <protein>B and T cell antigen receptors</protein> ."}
{"id": "471", "text": "Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells .", "annotated_text": "Multiple signals are required for function of the <dna>human granulocyte-macrophage colony-stimulating factor gene promoter</dna> in <cell_type>T cells</cell_type> ."}
{"id": "472", "text": "The human granulocyte-macrophage CSF ( GM-CSF ) gene is expressed in T cells in response to TCR activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore .", "annotated_text": "The <dna>human granulocyte-macrophage CSF ( GM-CSF ) gene</dna> is expressed in <cell_type>T cells</cell_type> in response to <protein>TCR</protein> activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore ."}
{"id": "473", "text": "The gene contains a proximal functional promoter region ( -620 to +34 ) , as well as a powerful enhancer located 3 kb upstream , both of which are involved in the response of the gene to TCR activation .", "annotated_text": "The gene contains a <dna>proximal functional promoter region</dna> ( <dna>-620 to +34</dna> ) , as well as a powerful <dna>enhancer</dna> located 3 kb upstream , both of which are involved in the response of the gene to <protein>TCR</protein> activation ."}
{"id": "474", "text": "The proximal promoter contains a region termed CLEO ( -54 to -31 ) that consists of a purine-rich element abutting an activator protein-1 ( AP-1 ) -like site , as well as an upstream nuclear factor-kappa B ( NF-kappa B ) site ( -85 to -76 ) and a CK-1 element ( -101 to -92 ) .", "annotated_text": "The <dna>proximal promoter</dna> contains a region termed <dna>CLEO</dna> ( <dna>-54 to -31</dna> ) that consists of a <dna>purine-rich element</dna> abutting an <dna>activator protein-1 ( AP-1 ) -like site</dna> , as well as an <dna>upstream nuclear factor-kappa B ( NF-kappa B ) site</dna> ( <dna>-85 to -76</dna> ) and a <dna>CK-1 element</dna> ( <dna>-101 to -92</dna> ) ."}
{"id": "475", "text": "We show in this work that mutations in either the purine-rich region of the CLEO element or the NF-kappa B site result in reduced PMA/Ca2+ activation of a 620-bp human GM-CSF promoter-luciferase reporter construct in Jurkat T cells by 65 % and 50 % , respectively .", "annotated_text": "We show in this work that mutations in either the <dna>purine-rich region</dna> of the <dna>CLEO element</dna> or the <dna>NF-kappa B site</dna> result in reduced PMA/Ca2+ activation of a <dna>620-bp human GM-CSF promoter-luciferase reporter construct</dna> in <cell_line>Jurkat T cells</cell_line> by 65 % and 50 % , respectively ."}
{"id": "476", "text": "The major inducible protein complex that binds to the human CLEO ( hCLEO ) element is an AP-1-like complex that is inducible by PMA alone , but shows increased binding in response to PMA together with Ca2+ ionophore .", "annotated_text": "The major <protein>inducible protein complex</protein> that binds to the <dna>human CLEO ( hCLEO ) element</dna> is an <protein>AP-1-like complex</protein> that is inducible by PMA alone , but shows increased binding in response to PMA together with Ca2+ ionophore ."}
{"id": "477", "text": "Although the binding of this complex is not cyclosporin-sensitive , promoter induction is inhibited by cyclosporin treatment .", "annotated_text": "Although the binding of this complex is not cyclosporin-sensitive , promoter induction is inhibited by cyclosporin treatment ."}
{"id": "478", "text": "A second weak inducible complex resembling nuclear factor of activated T cells ( NF-AT ) was also observed binding to the hCLEO region .", "annotated_text": "A second weak inducible complex resembling <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) was also observed binding to the <dna>hCLEO region</dna> ."}
{"id": "479", "text": "By using recombinant proteins , we confirmed that AP-1 , NF-ATp , and a higher order NF-ATp/AP-1 complex could all form with the hCLEO element , and we have also defined the sequence requirements for binding of each of these complexes .", "annotated_text": "By using <protein>recombinant proteins</protein> , we confirmed that <protein>AP-1</protein> , <protein>NF-ATp</protein> , and a higher order <protein>NF-ATp/AP-1 complex</protein> could all form with the <dna>hCLEO element</dna> , and we have also defined the sequence requirements for binding of each of these complexes ."}
{"id": "480", "text": "We found that expression of a constitutively active form of calcineurin could substitute for Ca2+ ionophore and synergize with PMA to activate the GM-CSF promoter , and conversely that mutant-activated Ras could substitute for PMA and cooperate with Ca2+ ionophore .", "annotated_text": "We found that expression of a constitutively active form of <protein>calcineurin</protein> could substitute for Ca2+ ionophore and synergize with PMA to activate the <dna>GM-CSF promoter</dna> , and conversely that <protein>mutant-activated Ras</protein> could substitute for PMA and cooperate with Ca2+ ionophore ."}
{"id": "481", "text": "Co-expression of Ras and calcineurin , however , did not activate the GM-CSF promoter , but required the additional expression of NF-kappa B p65 .", "annotated_text": "Co-expression of <protein>Ras</protein> and <protein>calcineurin</protein> , however , did not activate the <dna>GM-CSF promoter</dna> , but required the additional expression of <protein>NF-kappa B p65</protein> ."}
{"id": "482", "text": "These results imply that at least three signals are required to activate the GM-CSF proximal promoter , and that the signals impinge on distinct transcription factors that bind to the hCLEO and NF-kappa B regions of the promoter .", "annotated_text": "These results imply that at least three signals are required to activate the <dna>GM-CSF proximal promoter</dna> , and that the signals impinge on distinct <protein>transcription factors</protein> that bind to the <dna>hCLEO and NF-kappa B regions</dna> of the <dna>promoter</dna> ."}
{"id": "483", "text": "IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes .", "annotated_text": "IL-10 induces the tyrosine phosphorylation of <protein>tyk2</protein> and <protein>Jak1</protein> and the differential assembly of <protein>STAT1 alpha</protein> and <protein>STAT3 complexes</protein> in <cell_type>human T cells</cell_type> and <cell_type>monocytes</cell_type> ."}
{"id": "484", "text": "IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate .", "annotated_text": "<protein>IL-10</protein> affects <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate ."}
{"id": "485", "text": "In this report , we show that in monocytes and T cells IL-10 stimulates tyrosine phosphorylation of the signal transducers and activators of transcription , STAT1 alpha and STAT3 , in a differential manner such that the relative formation of homo- and heterodimers varies between the two cell types .", "annotated_text": "In this report , we show that in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> <protein>IL-10</protein> stimulates tyrosine phosphorylation of the <protein>signal transducers</protein> and <protein>activators of transcription</protein> , <protein>STAT1 alpha</protein> and <protein>STAT3</protein> , in a differential manner such that the relative formation of <protein>homo- and heterodimers</protein> varies between the two cell types ."}
{"id": "486", "text": "Moreover , monocytes express a novel IL-10-stimulated STAT protein with an M ( r ) of 70 kDa that is recognized by the anti-STAT3 Ab but is not observed in T cells .", "annotated_text": "Moreover , <cell_type>monocytes</cell_type> express a novel <protein>IL-10-stimulated STAT protein</protein> with an M ( r ) of <protein>70 kDa</protein> that is recognized by the <protein>anti-STAT3 Ab</protein> but is not observed in <cell_type>T cells</cell_type> ."}
{"id": "487", "text": "IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1 , but not Jak2 or Jak3 .", "annotated_text": "<protein>IL-10</protein> treatment of both <cell_type>T cells</cell_type> and <cell_type>monocytes</cell_type> results in the ligand-induced tyrosine phosphorylation of <protein>tyk2</protein> and <protein>Jak1</protein> , but not <protein>Jak2</protein> or <protein>Jak3</protein> ."}
{"id": "488", "text": "Selective modulation of immune responsiveness by IL-10 in cells such as monocytes and T cells may result in part from the differential activation of STAT protein pairs .", "annotated_text": "Selective modulation of immune responsiveness by <protein>IL-10</protein> in cells such as <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> may result in part from the differential activation of <protein>STAT protein pairs</protein> ."}
{"id": "489", "text": "Use of new biologic markers in the ovulation induction .", "annotated_text": "Use of new biologic markers in the ovulation induction ."}
{"id": "490", "text": "Biological markers of ovulation , after a great in the past , have been fallen into disuse for the large diffusion of biochemical and biophysical ones .", "annotated_text": "Biological markers of ovulation , after a great in the past , have been fallen into disuse for the large diffusion of biochemical and biophysical ones ."}
{"id": "491", "text": "However , the real effect of hormones involved in ovulation is expressed by biological modifications on target tissues .", "annotated_text": "However , the real effect of hormones involved in ovulation is expressed by biological modifications on <cell_type>target tissues</cell_type> ."}
{"id": "492", "text": "To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia , Platelet Factor IV ( as indicator of Platelet Aggregation ) , Type II estrogenic receptors in 42 ovulation induced women , undergoing our observation .", "annotated_text": "To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia , <protein>Platelet Factor IV</protein> ( as indicator of Platelet Aggregation ) , <protein>Type II estrogenic receptors</protein> in 42 ovulation induced women , undergoing our observation ."}
{"id": "493", "text": "33 of them had ovulation and 9 developed a LUF syndrome , constituting two biological models of an opposite situation for the three markers observed .", "annotated_text": "33 of them had ovulation and 9 developed a LUF syndrome , constituting two biological models of an opposite situation for the three markers observed ."}
{"id": "494", "text": "All the markers considered were sufficiently sensitive , but among them , Platelet Factor IV was the most reliable to the hormonal ovulatory situation .", "annotated_text": "All the markers considered were sufficiently sensitive , but among them , <protein>Platelet Factor IV</protein> was the most reliable to the hormonal ovulatory situation ."}
{"id": "495", "text": "Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells-binding factor .", "annotated_text": "Abnormal regulation of the <dna>IL-2 promoter</dna> in lpr <cell_line>CD4-CD8- T lymphocytes</cell_line> results in constitutive expression of a <protein>novel nuclear factor of activated T cells-binding factor</protein> ."}
{"id": "496", "text": "The inert quality of MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation .", "annotated_text": "The inert quality of <cell_line>MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells</cell_line> manifests primarily as an inability to proliferate or produce <protein>IL-2</protein> in response to <protein>TCR</protein> or mitogenic stimulation ."}
{"id": "497", "text": "Yet these same cells do initiate early TCR -mediated signaling events , such as generation of inositol phosphates and increased intracellular calcium .", "annotated_text": "Yet these same cells do initiate early <protein>TCR</protein> -mediated signaling events , such as generation of inositol phosphates and increased intracellular calcium ."}
{"id": "498", "text": "They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation .", "annotated_text": "They also display constitutively high levels of <protein>p59fyn</protein> and <protein>CD3 zeta</protein> tyrosine phosphorylation ."}
{"id": "499", "text": "The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene .", "annotated_text": "The generation of second messengers in <cell_type>T cells</cell_type> normally leads to downstream signaling that results in transcriptional activation of the <dna>IL-2 gene</dna> ."}
{"id": "500", "text": "We , therefore , compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes .", "annotated_text": "We , therefore , compared the activation state of the <dna>IL-2 gene promoter region</dna> in freshly isolated and stimulated <cell_line>Ipr CD4-8- T cells</cell_line> with that of <cell_type>normal T lymphocytes</cell_type> ."}
{"id": "501", "text": "Levels of the octamer , NF-kappa B ( p50-p65 heterodimer ) , and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells , consistent with the activated phenotype of these cells .", "annotated_text": "Levels of the octamer , <protein>NF-kappa B</protein> ( <protein>p50-p65 heterodimer</protein> ) , and <protein>AP-1 transcriptional factors</protein> are constitutively elevated in freshly isolated <cell_line>Ipr CD4-8- T cells</cell_line> , consistent with the activated phenotype of these cells ."}
{"id": "502", "text": "Upon stimulation with mitogens , formation of the transactivating complex , nuclear factor of activated T cells ( NF-AT ) , occurs with normal kinetics in Ipr CD4-8- T cells .", "annotated_text": "Upon stimulation with mitogens , formation of the transactivating complex , <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) , occurs with normal kinetics in <cell_line>Ipr CD4-8- T cells</cell_line> ."}
{"id": "503", "text": "Yet , the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells .", "annotated_text": "Yet , the levels of the activating <protein>NF-AT complex</protein> never reach those observed in similarly stimulated normal <cell_type>T cells</cell_type> ."}
{"id": "504", "text": "Furthermore , nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site , which is present at much lower levels in freshly isolated normal T lymphocytes .", "annotated_text": "Furthermore , nuclear extracts from <cell_line>Ipr CD4-8- T cells</cell_line> display high levels of a novel specific binding activity at the <dna>NF-AT site</dna> , which is present at much lower levels in freshly isolated <cell_type>normal T lymphocytes</cell_type> ."}
{"id": "505", "text": "Upon mitogenic stimulation , the binding activity of the novel NF-AT-binding factor is rapidly down-regulated in normal T cells , but persists at high levels in Ipr CD4-8- T cells .", "annotated_text": "Upon mitogenic stimulation , the binding activity of the novel <protein>NF-AT-binding factor</protein> is rapidly down-regulated in normal <cell_type>T cells</cell_type> , but persists at high levels in <cell_line>Ipr CD4-8- T cells</cell_line> ."}
{"id": "506", "text": "These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells .", "annotated_text": "These two abnormalities at the <dna>NF-AT site</dna> provide a potential mechanism to account for the defect in <protein>IL-2</protein> production from <cell_line>Ipr CD4-8- T cells</cell_line> ."}
{"id": "507", "text": "Cross-linking of CD30 induces HIV expression in chronically infected T cells .", "annotated_text": "Cross-linking of <protein>CD30</protein> induces HIV expression in chronically infected <cell_type>T cells</cell_type> ."}
{"id": "508", "text": "CD30 , a member of the tumor necrosis factor ( TNF ) receptor family , is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type-1 ( HIV ) -1 .", "annotated_text": "<protein>CD30</protein> , a member of the tumor necrosis factor ( TNF ) receptor family , is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type-1 ( HIV ) -1 ."}
{"id": "509", "text": "We demonstrate that cross-linking CD30 with an anti- CD30 -specific monoclonal antibody , which mimics the described biological activities of the CD30 ligand ( CD30L ) , results in HIV expression .", "annotated_text": "We demonstrate that cross-linking <protein>CD30</protein> with an anti- <protein>CD30</protein> -specific monoclonal antibody , which mimics the described biological activities of the <protein>CD30 ligand</protein> ( <protein>CD30L</protein> ) , results in HIV expression ."}
{"id": "510", "text": "CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta .", "annotated_text": "<protein>CD30</protein> cross-linking does not alter proliferation of <cell_line>ACH-2 cells</cell_line> and the induction of HIV expression is not mediated by endogenous <protein>TNF alpha/beta</protein> ."}
{"id": "511", "text": "Furthermore , cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription .", "annotated_text": "Furthermore , cross-linking of <protein>CD30</protein> leads to <protein>NF-kappa B</protein> activation and enhanced HIV transcription ."}
{"id": "512", "text": "Thus , CD30 -CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF .", "annotated_text": "Thus , <protein>CD30</protein> <protein>-CD30L</protein> interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of <protein>TNF</protein> ."}
{"id": "513", "text": "This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells , especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions .", "annotated_text": "This mechanism may be important in the activation of HIV expression from latently infected <cell_line>CD4+ T cells</cell_line> , especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions ."}
{"id": "514", "text": "Human MHC class II gene transcription directed by the carboxyl terminus of CIITA , one of the defective genes in type II MHC combined immune deficiency .", "annotated_text": "Human <dna>MHC class II gene</dna> transcription directed by the <protein>carboxyl terminus</protein> of <dna>CIITA</dna> , one of the <dna>defective genes</dna> in type II <protein>MHC</protein> combined immune deficiency ."}
{"id": "515", "text": "Type II major histocompatibility complex combined immune deficiency ( type II MHC CID or bare lymphocyte syndrome ) is a congenital immunodeficiency disease characterized by absent MHC class II expression .", "annotated_text": "<protein>Type II major histocompatibility complex</protein> combined immune deficiency ( type II <protein>MHC</protein> CID or bare lymphocyte syndrome ) is a congenital immunodeficiency disease characterized by absent <protein>MHC class II</protein> expression ."}
{"id": "516", "text": "Four distinct complementation groups have been identified .", "annotated_text": "Four distinct complementation groups have been identified ."}
{"id": "517", "text": "Recently , the defective gene in group II type II MHC CID has been isolated and termed CIITA .", "annotated_text": "Recently , the <dna>defective gene</dna> in group II type II <protein>MHC</protein> CID has been isolated and termed <dna>CIITA</dna> ."}
{"id": "518", "text": "Here , we demonstrate that CIITA is an MHC class II gene-specific transcription activator .", "annotated_text": "Here , we demonstrate that <dna>CIITA</dna> is an <dna>MHC class II gene-specific transcription activator</dna> ."}
{"id": "519", "text": "The transcription activation function is provided by the N-terminal acidic domain ( amino acids 26-137 ) , which is experimentally exchangeable with a heterologous viral transcription-activating domain .", "annotated_text": "The transcription activation function is provided by the <protein>N-terminal acidic domain</protein> ( <protein>amino acids 26-137</protein> ) , which is experimentally exchangeable with a <protein>heterologous viral transcription-activating domain</protein> ."}
{"id": "520", "text": "The specificity of CIITA for three major MHC class II genes , DR , DQ and DP , is mediated by its remaining C-terminal residues ( amino acids 317-1130 ) .", "annotated_text": "The specificity of <protein>CIITA</protein> for three major <dna>MHC class II genes</dna> , <dna>DR</dna> , <dna>DQ</dna> and <dna>DP</dna> , is mediated by its remaining <protein>C-terminal residues</protein> ( <protein>amino acids 317-1130</protein> ) ."}
{"id": "521", "text": "The transactivation of multiple cis elements , especially S and X2 , of the DR alpha proximal promoter in group II CID cells is CIITA dependent .", "annotated_text": "The transactivation of <dna>multiple cis elements</dna> , especially <dna>S</dna> and <dna>X2</dna> , of the <dna>DR alpha proximal promoter</dna> in <cell_line>group II CID cells</cell_line> is <protein>CIITA</protein> dependent ."}
{"id": "522", "text": "Since CIITA overexpression in normal cells did not increase class II expression , we propose that initiation of CIITA expression serves as the on-off switch , while availability of downstream interactor ( s ) limits transcription .", "annotated_text": "Since <protein>CIITA</protein> overexpression in <cell_type>normal cells</cell_type> did not increase class II expression , we propose that initiation of <protein>CIITA</protein> expression serves as the on-off switch , while availability of downstream interactor ( s ) limits transcription ."}
{"id": "523", "text": "Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion .", "annotated_text": "Monocyte tethering by <protein>P-selectin</protein> regulates <protein>monocyte chemotactic protein-1</protein> and <protein>tumor necrosis factor-alpha</protein> secretion ."}
{"id": "524", "text": "Signal integration and NF-kappa B translocation [ see comments ]", "annotated_text": "Signal integration and <protein>NF-kappa B</protein> translocation [ see comments ]"}
{"id": "525", "text": "Adhesion molecules that tether circulating leukocytes to endothelial cells may also transduce or modulate outside-in signals for cellular activation , providing an initial regulatory point in the inflammatory response .", "annotated_text": "<protein>Adhesion molecules</protein> that tether <cell_type>circulating leukocytes</cell_type> to <cell_type>endothelial cells</cell_type> may also transduce or modulate outside-in signals for cellular activation , providing an initial regulatory point in the inflammatory response ."}
{"id": "526", "text": "Adhesion of human monocytes to P-selectin , the most rapidly expressed endothelial tethering factor , increased the secretion of monocyte chemotactic protein-1 ( MCP-1 ) and tumor necrosis factor-alpha ( TNF-alpha ) by the leukocytes when they were stimulated with platelet-activating factor .", "annotated_text": "Adhesion of <cell_type>human monocytes</cell_type> to <protein>P-selectin</protein> , the most rapidly expressed <protein>endothelial tethering factor</protein> , increased the secretion of <protein>monocyte chemotactic protein-1</protein> ( <protein>MCP-1</protein> ) and <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) by the <cell_type>leukocytes</cell_type> when they were stimulated with <protein>platelet-activating factor</protein> ."}
{"id": "527", "text": "Increased cytokine secretion was specifically inhibited by G1 , an anti-P-selectin mAb that prevents P-selectin from binding to its ligand ( P-selectin glycoprotein ligand-1 ) on myeloid cells .", "annotated_text": "Increased cytokine secretion was specifically inhibited by <protein>G1</protein> , an <protein>anti-P-selectin mAb</protein> that prevents <protein>P-selectin</protein> from binding to its ligand ( <protein>P-selectin glycoprotein ligand-1</protein> ) on <cell_type>myeloid cells</cell_type> ."}
{"id": "528", "text": "Moreover , tethering by P-selectin specifically enhanced nuclear translocation of nuclear factor-kappa B ( NF-kappa B ) , a transcription factor required for expression of MCP-1 , TNF-alpha , and other immediate-early genes .", "annotated_text": "Moreover , tethering by <protein>P-selectin</protein> specifically enhanced nuclear translocation of <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) , a <protein>transcription factor</protein> required for expression of <protein>MCP-1</protein> , <protein>TNF-alpha</protein> , and other <dna>immediate-early genes</dna> ."}
{"id": "529", "text": "These results demonstrate that P-selectin , through its ligands on monocytes , may locally regulate cytokine secretion in inflamed tissues .", "annotated_text": "These results demonstrate that <protein>P-selectin</protein> , through its ligands on <cell_type>monocytes</cell_type> , may locally regulate <protein>cytokine</protein> secretion in inflamed tissues ."}
{"id": "530", "text": "Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer .", "annotated_text": "Functional roles of <dna>in vivo footprinted DNA motifs</dna> within an <dna>alpha-globin enhancer</dna> ."}
{"id": "531", "text": "Erythroid lineage and developmental stage specificities .", "annotated_text": "Erythroid lineage and developmental stage specificities ."}
{"id": "532", "text": "Transcriptional regulation of the human alpha-like globin genes , embryonic zeta 2 and adult alpha , during erythroid development is mediated by a distal enhancer , HS-40 .", "annotated_text": "Transcriptional regulation of the <dna>human alpha-like globin genes</dna> , <dna>embryonic zeta 2</dna> and <dna>adult alpha</dna> , during erythroid development is mediated by a <dna>distal enhancer</dna> , <dna>HS-40</dna> ."}
{"id": "533", "text": "Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner .", "annotated_text": "Previous protein-DNA binding studies have shown that <dna>HS-40</dna> consists of multiple <dna>nuclear factor binding motifs</dna> that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner ."}
{"id": "534", "text": "We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures .", "annotated_text": "We have systematically analyzed the functional roles of these <dna>factor binding motifs</dna> of <dna>HS-40</dna> by site-directed mutagenesis and transient expression assay in <cell_line>erythroid cell cultures</cell_line> ."}
{"id": "535", "text": "Three of these HS-40 enhancer motifs , 5'NF-E2/AP1 , GT II , and GATA-1 ( c ) , positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells .", "annotated_text": "Three of these <dna>HS-40 enhancer motifs</dna> , <dna>5'NF-E2/AP1</dna> , <dna>GT II</dna> , and <dna>GATA-1 ( c )</dna> , positively regulate the <dna>zeta 2-globin promoter</dna> activity in <cell_line>embryonic/fetal erythroid K562 cells</cell_line> and the <dna>adult alpha-globin promoter</dna> activity in <cell_line>adult erythroid MEL cells</cell_line> ."}
{"id": "536", "text": "On the other hand , the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells , and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor .", "annotated_text": "On the other hand , the <dna>3'NF-E2/AP1 motif</dna> is able to exert both positive and negative regulatory effects on the <dna>zeta 2-globin promoter</dna> activity in <cell_line>K562 cells</cell_line> , and this dual function appears to be modulated through differential binding of the <protein>ubiquitous AP1 factors</protein> and the <protein>erythroid-enriched NF-E2 factor</protein> ."}
{"id": "537", "text": "Mutation in the GATA-1 ( d ) motif , which exhibits an adult erythroid-specific genomic footprint , decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells .", "annotated_text": "Mutation in the <dna>GATA-1 ( d ) motif</dna> , which exhibits an <dna>adult erythroid-specific genomic footprint</dna> , decreases the <dna>HS-40 enhancer</dna> function in <cell_line>dimethyl sulfoxide-induced MEL cells</cell_line> but not in <cell_line>K562 cells</cell_line> ."}
{"id": "538", "text": "These studies have defined the regulatory roles of the different HS-40 motifs .", "annotated_text": "These studies have defined the regulatory roles of the different <dna>HS-40 motifs</dna> ."}
{"id": "539", "text": "The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo .", "annotated_text": "The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of <dna>human alpha-like globin promoters</dna> is indeed modulated by stable binding of <protein>specific nuclear factors</protein> in vivo ."}
{"id": "540", "text": "Nitric oxide-stimulated guanine nucleotide exchange on p21ras .", "annotated_text": "Nitric oxide-stimulated guanine nucleotide exchange on <protein>p21ras</protein> ."}
{"id": "541", "text": "The protooncogene p21ras , a monomeric G protein family member , plays a critical role in converting extracellular signals into intracellular biochemical events .", "annotated_text": "The <dna>protooncogene p21ras</dna> , a <protein>monomeric G protein family member</protein> , plays a critical role in converting extracellular signals into intracellular biochemical events ."}
{"id": "542", "text": "Here , we report that nitric oxide ( NO ) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras .", "annotated_text": "Here , we report that nitric oxide ( NO ) activates <dna>p21ras</dna> in <cell_type>human T cells</cell_type> as evidenced by an increase in <protein>GTP-bound p21ras</protein> ."}
{"id": "543", "text": "In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible .", "annotated_text": "In vitro studies using <protein>pure recombinant p21ras</protein> demonstrate that the activation is direct and reversible ."}
{"id": "544", "text": "Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange .", "annotated_text": "Circular dichroism analysis reveals that NO induces a profound conformational change in <dna>p21ras</dna> in association with GDP/GTP exchange ."}
{"id": "545", "text": "The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange .", "annotated_text": "The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange ."}
{"id": "546", "text": "Furthermore , we demonstrate that p21ras is essential for NO-induced downstream signaling , such as NF-kappa B activation , and that endogenous NO can activate p21ras in the same cell .", "annotated_text": "Furthermore , we demonstrate that <protein>p21ras</protein> is essential for NO-induced downstream signaling , such as <protein>NF-kappa B</protein> activation , and that endogenous NO can activate <protein>p21ras</protein> in the same cell ."}
{"id": "547", "text": "These studies identify p21ras as a target of the same cell .", "annotated_text": "These studies identify <dna>p21ras</dna> as a target of the same cell ."}
{"id": "548", "text": "These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors .", "annotated_text": "These studies identify <dna>p21ras</dna> as a target of NO in <cell_type>T cells</cell_type> and suggest that NO activates <dna>p21ras</dna> by an action which mimics that of <protein>guanine nucleotide exchange factors</protein> ."}
{"id": "549", "text": "Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B .", "annotated_text": "<dna>Interleukin-2 promoter</dna> activity in <cell_line>Epstein-Barr virus-transformed B lymphocytes</cell_line> is controlled by <protein>nuclear factor-chi B</protein> ."}
{"id": "550", "text": "The regulation of interleukin ( IL ) -2 gene expression has been investigated mainly in T lymphocytes , the predominant producers of IL-2 .", "annotated_text": "The regulation of <dna>interleukin ( IL ) -2 gene</dna> expression has been investigated mainly in <cell_type>T lymphocytes</cell_type> , the predominant producers of <protein>IL-2</protein> ."}
{"id": "551", "text": "However , B cells can also synthesize IL-2 .", "annotated_text": "However , <cell_type>B cells</cell_type> can also synthesize <protein>IL-2</protein> ."}
{"id": "552", "text": "In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus ( EBV ) -transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin .", "annotated_text": "In the present study we analyzed the control of <dna>IL-2 promoter</dna> activity in <cell_line>Epstein-Barr virus ( EBV ) -transformed B cell clones</cell_line> which are capable of secreting <protein>IL-2</protein> at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin ."}
{"id": "553", "text": "Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [ distal nuclear factor ( NF ) -AT , proximal NF-AT , AP-1/Octamer ( UPS ) or NF-chi B ( TCEd ) sites ] were performed .", "annotated_text": "Transient transfections using <dna>reporter constructs</dna> with multiples of <dna>transcription factor binding sites</dna> from the <dna>IL-2 promoter</dna> [ <protein>distal nuclear factor ( NF ) -AT</protein> , <protein>proximal NF-AT</protein> , <protein>AP-1/Octamer</protein> ( <protein>UPS</protein> ) or <protein>NF-chi B</protein> ( <protein>TCEd</protein> ) sites ] were performed ."}
{"id": "554", "text": "In EBV-transformed B clones , the chi B site exerted the strongest inducible activity ; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells .", "annotated_text": "In <cell_line>EBV-transformed B clones</cell_line> , the <dna>chi B site</dna> exerted the strongest inducible activity ; the <dna>NF-AT binding sites</dna> showed either no or only weak activity compared to <cell_line>Jurkat T cells</cell_line> ."}
{"id": "555", "text": "An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells , while it still had activity in Jurkat T cells .", "annotated_text": "An <dna>IL-2 promoter</dna> bearing a defective <dna>NF-chi B site</dna> was completely inactive in <cell_line>EBV-transformed B cells</cell_line> , while it still had activity in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "556", "text": "In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2 , the activity of the IL-2 promoter correlated well with the status of IL-2 secretion .", "annotated_text": "In seven <cell_line>EBV-B cell clones</cell_line> or lines differing in their capacity to secrete <protein>IL-2</protein> , the activity of the <dna>IL-2 promoter</dna> correlated well with the status of <protein>IL-2</protein> secretion ."}
{"id": "557", "text": "Similarly , a human immunodeficiency virus promoter , whose activity is controlled through chi B factors , was found to be active in the IL-2 producing EBV-B cells , but inactive in the non-IL-2-producing cells .", "annotated_text": "Similarly , a <dna>human immunodeficiency virus promoter</dna> , whose activity is controlled through <protein>chi B factors</protein> , was found to be active in the <cell_line>IL-2 producing EBV-B cells</cell_line> , but inactive in the <cell_line>non-IL-2-producing cells</cell_line> ."}
{"id": "558", "text": "Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes .", "annotated_text": "Electrophoretic mobility shift assays using protein extracts from <cell_line>EBV-B cells</cell_line> and the <protein>IL-2</protein> <protein>NF-chi B</protein> probe revealed the constitutive generation of <protein>chi B complexes</protein> in <cell_line>IL-2-secreting cells</cell_line> consisting mainly of <protein>heterodimeric p50/p65 complexes</protein> ."}
{"id": "559", "text": "A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells .", "annotated_text": "A weaker <dna>chi B</dna> complex formation and faster-migrating complexes were detected in <cell_line>non-IL-2-secreting cells</cell_line> ."}
{"id": "560", "text": "These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells , whereas other transcription factors appear to be less important for IL-2 expression in these cells .", "annotated_text": "These results demonstrate that the <dna>IL-2 NF-chi B site</dna> is indispensable for the activity of the <dna>IL-2 promoter</dna> in <cell_line>EBV-transformed B cells</cell_line> , whereas other <protein>transcription factors</protein> appear to be less important for <protein>IL-2</protein> expression in these cells ."}
{"id": "561", "text": "Latent membrane protein-1 induces cyclin D2 expression , pRb hyperphosphorylation , and loss of TGF-beta 1 -mediated growth inhibition in EBV-positive B cells .", "annotated_text": "<protein>Latent membrane protein-1</protein> induces <protein>cyclin D2</protein> expression , <protein>pRb</protein> hyperphosphorylation , and loss of <protein>TGF-beta 1</protein> -mediated growth inhibition in <cell_type>EBV-positive B cells</cell_type> ."}
{"id": "562", "text": "The normal cell cycle is regulated by several molecules , such as the tumor-suppressor protein pRb , the G1 cyclins , the cyclin-dependent kinases , and their inhibitors .", "annotated_text": "The normal cell cycle is regulated by several molecules , such as the <protein>tumor-suppressor protein pRb</protein> , the <protein>G1 cyclins</protein> , the <protein>cyclin-dependent kinases</protein> , and their inhibitors ."}
{"id": "563", "text": "These regulators are targeted by negative growth regulatory signals , such as that provided by TGF-beta .", "annotated_text": "These regulators are targeted by negative growth regulatory signals , such as that provided by <protein>TGF-beta</protein> ."}
{"id": "564", "text": "Here , we show that the presence of either wild-type EBV or its transforming latent membrane protein-1 ( LMP-1 ) results in the loss of TGF-beta 1 -mediated growth inhibition in human B cells .", "annotated_text": "Here , we show that the presence of either wild-type EBV or its <protein>transforming latent membrane protein-1</protein> ( <protein>LMP-1</protein> ) results in the loss of <protein>TGF-beta 1</protein> -mediated growth inhibition in <cell_type>human B cells</cell_type> ."}
{"id": "565", "text": "Chemical cross-linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF-beta receptor profile in EBV-positive and EBV-negative Burkitt 's lymphoma cell lines , and these receptors were shown to be functional in transducing signals , as evidenced by the TGF-beta 1 -mediated modulation of junB gene expression .", "annotated_text": "Chemical cross-linking with <protein>125I-labeled TGF-beta 1</protein> showed an essentially normal <protein>TGF-beta receptor</protein> profile in <cell_line>EBV-positive and EBV-negative Burkitt 's lymphoma cell lines</cell_line> , and these receptors were shown to be functional in transducing signals , as evidenced by the <protein>TGF-beta 1</protein> -mediated modulation of <dna>junB gene</dna> expression ."}
{"id": "566", "text": "However , TGF-beta 1 did not induce dephosphorylation of pRb in EBV ( or LMP-1 ) -positive cells as opposed to EBV-negative cells , suggesting a dichotomy in the TGF-beta 1 signaling pathway leading to separable gene regulatory and growth inhibitory responses .", "annotated_text": "However , <protein>TGF-beta 1</protein> did not induce dephosphorylation of <protein>pRb</protein> in <cell_line>EBV ( or LMP-1 ) -positive cells</cell_line> as opposed to <cell_line>EBV-negative cells</cell_line> , suggesting a dichotomy in the <protein>TGF-beta 1</protein> signaling pathway leading to separable gene regulatory and growth inhibitory responses ."}
{"id": "567", "text": "Furthermore , LMP-1 was found to induce the expression of cyclin D2 ; normal B cells or EBV-negative Burkitt 's lymphoma cells do not express D-type cyclins .", "annotated_text": "Furthermore , <protein>LMP-1</protein> was found to induce the expression of <protein>cyclin D2</protein> ; normal <cell_type>B cells</cell_type> or <cell_line>EBV-negative Burkitt 's lymphoma cells</cell_line> do not express <protein>D-type cyclins</protein> ."}
{"id": "568", "text": "Taken together , these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of key cell cycle regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell proliferation .", "annotated_text": "Taken together , these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of <protein>key cell cycle regulators</protein> by <protein>LMP-1</protein> can lead to <protein>pRb</protein> hyperphosphorylation and uncontrolled cell proliferation ."}
{"id": "569", "text": "Does thyroidectomy , radioactive iodine therapy , or antithyroid drug treatment alter reactivity of patients ' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases ?", "annotated_text": "Does thyroidectomy , radioactive iodine therapy , or antithyroid drug treatment alter reactivity of patients ' <cell_type>T cells</cell_type> to epitopes of <protein>thyrotropin receptor</protein> in autoimmune thyroid diseases ?"}
{"id": "570", "text": "The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves ' disease ( GD ) before and after thyroidectomy , 19 patients with GD before and after radioactive iodine ( RAI ) therapy , and 9 patients maintained euthyroid on antithyroid drugs ( ATD ) .", "annotated_text": "The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves ' disease ( GD ) before and after thyroidectomy , 19 patients with GD before and after radioactive iodine ( RAI ) therapy , and 9 patients maintained euthyroid on antithyroid drugs ( ATD ) ."}
{"id": "571", "text": "Twenty subjects matched for age and sex without known thyroid disease served as controls .", "annotated_text": "Twenty subjects matched for age and sex without known thyroid disease served as controls ."}
{"id": "572", "text": "In GD patients , the responses of peripheral blood mononuclear cells ( PBMC ) and TSH receptor ( TSHR ) -specific T cell lines to recombinant human TSHR extracellular domain , thyroglobulin , and TSHR peptides were examined on the day of surgery or RAI therapy ( day 0 ) and also 6-8 weeks and 3-6 months thereafter .", "annotated_text": "In GD patients , the responses of <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) and <cell_line>TSH receptor ( TSHR ) -specific T cell lines</cell_line> to <protein>recombinant human TSHR extracellular domain</protein> , <protein>thyroglobulin</protein> , and <protein>TSHR</protein> peptides were examined on the day of surgery or RAI therapy ( day 0 ) and also 6-8 weeks and 3-6 months thereafter ."}
{"id": "573", "text": "Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain .", "annotated_text": "Reactivity to <protein>TSHR</protein> peptides before surgery was heterogeneous and spanned the entire <protein>extracellular domain</protein> ."}
{"id": "574", "text": "Six to 8 weeks after subtotal thyroidectomy , the number of patients ' PBMC responding to any peptide and the average number of recognized peptides decreased .", "annotated_text": "Six to 8 weeks after subtotal thyroidectomy , the number of patients ' <cell_type>PBMC</cell_type> responding to any peptide and the average number of recognized peptides decreased ."}
{"id": "575", "text": "A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery .", "annotated_text": "A further decrease in the T cell reactivity to <protein>TSHR</protein> peptides was observed 3-6 months after surgery ."}
{"id": "576", "text": "The responses of PBMC from Graves ' patients before RAI therapy were less than those in the presurgical group .", "annotated_text": "The responses of <cell_type>PBMC</cell_type> from Graves ' patients before RAI therapy were less than those in the presurgical group ."}
{"id": "577", "text": "Six to 8 weeks after RAI therapy , the number of patients responding to any peptide and the average number of recognized peptides increased .", "annotated_text": "Six to 8 weeks after RAI therapy , the number of patients responding to any peptide and the average number of recognized peptides increased ."}
{"id": "578", "text": "Three to 6 months after RAI , T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy , but still higher than the values on day 0 .", "annotated_text": "Three to 6 months after RAI , T cell responses to <protein>TSHR</protein> peptides were less than those 6-8 weeks after RAI therapy , but still higher than the values on day 0 ."}
{"id": "579", "text": "Responses of PBMC from patients with GD , maintained euthyroid on ATD , were lower than those before surgery or RAI therapy .", "annotated_text": "Responses of <cell_type>PBMC</cell_type> from patients with GD , maintained euthyroid on ATD , were lower than those before surgery or RAI therapy ."}
{"id": "580", "text": "The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment .", "annotated_text": "The reactivity of <cell_line>T cell lines</cell_line> in different groups reflected a pattern similar to <cell_type>PBMC</cell_type> after treatment ."}
{"id": "581", "text": "TSHR antibody and microsomal antibody levels decreased after surgery , but increased after RAI therapy .", "annotated_text": "<protein>TSHR antibody</protein> and <protein>microsomal antibody</protein> levels decreased after surgery , but increased after RAI therapy ."}
{"id": "582", "text": "The difference in the number of recognized peptides by patients ' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery .", "annotated_text": "The difference in the number of recognized peptides by patients ' <cell_type>PBMC</cell_type> before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery ."}
{"id": "583", "text": "The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells .", "annotated_text": "The decreased T cell reactivity to <protein>thyroid antigens</protein> after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer <cell_type>T cells</cell_type> ."}
{"id": "584", "text": "The increased T cell response after RAI therapy is probably epitope specific , rather than a response to the whole TSHR molecule .", "annotated_text": "The increased T cell response after RAI therapy is probably epitope specific , rather than a response to the whole <protein>TSHR</protein> molecule ."}
{"id": "585", "text": "Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD , and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism .", "annotated_text": "Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD , and the loss of recognition of one of these <protein>epitopes</protein> may be an early sign of immune remission and a predictor of euthyroidism ."}
{"id": "586", "text": "Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization of TCF-1 knock-out mice .", "annotated_text": "Circumvention of tolerance for the <protein>nuclear T cell protein</protein> <protein>TCF-1</protein> by immunization of <protein>TCF-1</protein> knock-out mice ."}
{"id": "587", "text": "Molecular events that underlie the well-defined phenotypic changes of the differentiating thymocyte are poorly understood .", "annotated_text": "Molecular events that underlie the well-defined phenotypic changes of the <cell_type>differentiating thymocyte</cell_type> are poorly understood ."}
{"id": "588", "text": "A candidate gene to control thymocyte differentiation , T cell factor-1 ( TCF-1 ) * encodes a DNA-binding protein .", "annotated_text": "A candidate gene to control <cell_type>thymocyte</cell_type> differentiation , <protein>T cell factor-1</protein> ( <protein>TCF-1</protein> ) * encodes a <protein>DNA-binding protein</protein> ."}
{"id": "589", "text": "Its mRNA expression pattern is complex during embryogenesis , yet restricted to lymphocytes postnatally .", "annotated_text": "Its mRNA expression pattern is complex during embryogenesis , yet restricted to <cell_type>lymphocytes</cell_type> postnatally ."}
{"id": "590", "text": "Expression studies on TCF-1 protein have been hampered by the difficulty to raise antibodies due to extreme evolutionary conservation .", "annotated_text": "Expression studies on <protein>TCF-1 protein</protein> have been hampered by the difficulty to raise <protein>antibodies</protein> due to extreme evolutionary conservation ."}
{"id": "591", "text": "TCF-1 knock-out mice , generated recently in our laboratory , have strongly decreased numbers of thymocytes , but are otherwise normal .", "annotated_text": "<protein>TCF-1</protein> knock-out mice , generated recently in our laboratory , have strongly decreased numbers of <cell_type>thymocytes</cell_type> , but are otherwise normal ."}
{"id": "592", "text": "We have used these mice to generate anti-TCF-1 antibodies .", "annotated_text": "We have used these mice to generate <protein>anti-TCF-1 antibodies</protein> ."}
{"id": "593", "text": "By immunization with a recombinant fusion protein , we show that TCF-1 knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein .", "annotated_text": "By immunization with a <protein>recombinant fusion protein</protein> , we show that <protein>TCF-1</protein> knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein ."}
{"id": "594", "text": "Wild-type littermates remain unresponsive to TCF-1 while they mount a high-titer antibody response to the fusion protein , Maltose Binding Protein ( MBP ) .", "annotated_text": "Wild-type littermates remain unresponsive to <protein>TCF-1</protein> while they mount a high-titer antibody response to the <protein>fusion protein</protein> , <protein>Maltose Binding Protein</protein> ( <protein>MBP</protein> ) ."}
{"id": "595", "text": "Subsequently , TCF-1-specific hybridomas could be prepared from the spleens of immunized knock-out mice .", "annotated_text": "Subsequently , <cell_line>TCF-1-specific hybridomas</cell_line> could be prepared from the spleens of immunized knock-out mice ."}
{"id": "596", "text": "This study illustrates the almost complete tolerance of mice for human TCF-1 and demonstrates that this tolerance is readily broken by gene knock-out .", "annotated_text": "This study illustrates the almost complete tolerance of mice for <protein>human TCF-1</protein> and demonstrates that this tolerance is readily broken by gene knock-out ."}
{"id": "597", "text": "Furthermore , the usefulness of knock-out mice for the generation of monoclonal antibodies against the gene product of interest is underscored .", "annotated_text": "Furthermore , the usefulness of knock-out mice for the generation of <protein>monoclonal antibodies</protein> against the gene product of interest is underscored ."}
{"id": "598", "text": "The transcription factor , Nm23H2 , binds to and activates the translocated c-myc allele in Burkitt 's lymphoma .", "annotated_text": "The <protein>transcription factor</protein> , <protein>Nm23H2</protein> , binds to and activates the translocated <dna>c-myc allele</dna> in Burkitt 's lymphoma ."}
{"id": "599", "text": "We have identified an in vivo footprint over the PuF site on the translocated c-myc allele in Burkitt 's lymphoma cells .", "annotated_text": "We have identified an in vivo footprint over the <dna>PuF site</dna> on the translocated <dna>c-myc allele</dna> in Burkitt 's lymphoma cells ."}
{"id": "600", "text": "The PuF site on the silent normal c-myc allele was unoccupied .", "annotated_text": "The <dna>PuF site</dna> on the <dna>silent normal c-myc allele</dna> was unoccupied ."}
{"id": "601", "text": "We demonstrated by electrophoretic mobility shift assay , electrophoretic mobility shift assay with antibody , UV cross-linking followed by SDS-gel electrophoresis , and Western analysis that Nm23H2 in B cell nuclear extracts bound to the c-myc PuF site .", "annotated_text": "We demonstrated by electrophoretic mobility shift assay , electrophoretic mobility shift assay with antibody , UV cross-linking followed by SDS-gel electrophoresis , and Western analysis that <protein>Nm23H2</protein> in B cell nuclear extracts bound to the c-myc <dna>PuF site</dna> ."}
{"id": "602", "text": "Transfection experiments with c-myc promoter constructs in both DHL-9 and Raji cells revealed that the PuF site functioned as a positive regulatory element in B cells with a drop in activity with mutation of this site .", "annotated_text": "Transfection experiments with <dna>c-myc promoter constructs</dna> in both <cell_line>DHL-9</cell_line> and <cell_line>Raji cells</cell_line> revealed that the <dna>PuF site</dna> functioned as a <dna>positive regulatory element</dna> in <cell_type>B cells</cell_type> with a drop in activity with mutation of this site ."}
{"id": "603", "text": "Access to this site is blocked in the normal silent c-myc allele ; these data suggest that the Nm23H2 protein is involved in deregulation of the translocated c-myc allele in Burkitt 's lymphoma cells .", "annotated_text": "Access to this site is blocked in the <dna>normal silent c-myc allele</dna> ; these data suggest that the <protein>Nm23H2</protein> protein is involved in deregulation of the translocated <dna>c-myc allele</dna> in <cell_line>Burkitt 's lymphoma cells</cell_line> ."}
{"id": "604", "text": "Identification of two novel regulatory elements within the 5'-untranslated region of the human A gamma-globin gene .", "annotated_text": "Identification of two novel <dna>regulatory elements</dna> within the <dna>5'-untranslated region</dna> of the <dna>human A gamma-globin gene</dna> ."}
{"id": "605", "text": "Interaction between the stage selector element ( SSE ) in the proximal gamma-globin promoter and hypersensitivity site 2 in the locus control region partly mediates the competitive silencing of the beta-globin promoter in the fetal developmental stage .", "annotated_text": "Interaction between the <dna>stage selector element</dna> ( SSE ) in the <dna>proximal gamma-globin promoter</dna> and <dna>hypersensitivity site 2</dna> in the <dna>locus control region</dna> partly mediates the competitive silencing of the <dna>beta-globin promoter</dna> in the fetal developmental stage ."}
{"id": "606", "text": "We have now demonstrated that a second SSE-like element in the 5'-untranslated region of the gamma-gene also contributes to this competitive silencing of the beta-gene .", "annotated_text": "We have now demonstrated that a second <dna>SSE-like element</dna> in the <dna>5'-untranslated region</dna> of the <dna>gamma-gene</dna> also contributes to this competitive silencing of the <dna>beta-gene</dna> ."}
{"id": "607", "text": "Utilizing transient transfection assays in the fetal erythroid cell line , K562 , we have shown that the core enhancer of hypersensitivity site 2 can preferentially interact with the proximal gamma-promoter in the absence of the SSE , completely silencing a linked beta-promoter .", "annotated_text": "Utilizing transient transfection assays in the <cell_line>fetal erythroid cell line</cell_line> , <cell_line>K562</cell_line> , we have shown that the <dna>core enhancer</dna> of <dna>hypersensitivity site 2</dna> can preferentially interact with the <dna>proximal gamma-promoter</dna> in the absence of the <dna>SSE</dna> , completely silencing a <dna>linked beta-promoter</dna> ."}
{"id": "608", "text": "Mutation of a 20-base pair sequence of the gamma-gene 5'-untranslated region ( UTR ) led to derepression of beta-promoter activity .", "annotated_text": "Mutation of a 20-base pair sequence of the <dna>gamma-gene 5'-untranslated region</dna> ( <dna>UTR</dna> ) led to derepression of <dna>beta-promoter</dna> activity ."}
{"id": "609", "text": "A marked activation of gamma-promoter activity was also observed with this mutation , suggesting the presence of a repressor .", "annotated_text": "A marked activation of <dna>gamma-promoter</dna> activity was also observed with this mutation , suggesting the presence of a repressor ."}
{"id": "610", "text": "Fine mutagenesis dissected these activities to different regions of the 5'-UTR .", "annotated_text": "Fine mutagenesis dissected these activities to different regions of the <dna>5'-UTR</dna> ."}
{"id": "611", "text": "The stage selector activity was localized to a region centered on nucleotides +13 to +15 .", "annotated_text": "The stage selector activity was localized to a region centered on <dna>nucleotides +13 to +15</dna> ."}
{"id": "612", "text": "Electromobility shift assays utilizing this sequence demonstrated binding of a fetal and erythroid-specific protein .", "annotated_text": "Electromobility shift assays utilizing this sequence demonstrated binding of a <protein>fetal and erythroid-specific protein</protein> ."}
{"id": "613", "text": "The repressor activity of the 5'-UTR was localized to tandem GATA-like sites , which appear to bind a complex of two proteins , one of which is the erythroid transcription factor GATA-1 .", "annotated_text": "The repressor activity of the <dna>5'-UTR</dna> was localized to tandem <dna>GATA-like sites</dna> , which appear to bind a complex of two proteins , one of which is the <protein>erythroid transcription factor</protein> <protein>GATA-1</protein> ."}
{"id": "614", "text": "These results indicate that the 5'-UTR of the gamma-gene contains sequences that may be important for its transcriptional and developmental regulation .", "annotated_text": "These results indicate that the <dna>5'-UTR</dna> of the <dna>gamma-gene</dna> contains sequences that may be important for its transcriptional and developmental regulation ."}
{"id": "615", "text": "Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation .", "annotated_text": "Coupling of a <protein>signal response domain</protein> in <protein>I kappa B alpha</protein> to multiple pathways for <protein>NF-kappa B</protein> activation ."}
{"id": "616", "text": "The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth .", "annotated_text": "The <protein>eukaryotic transcription factor</protein> <protein>NF-kappa B</protein> plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth ."}
{"id": "617", "text": "The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha .", "annotated_text": "The nuclear activity of <protein>NF-kappa B</protein> is tightly regulated from the cytoplasmic compartment by an <protein>inhibitory subunit</protein> called <protein>I kappa B alpha</protein> ."}
{"id": "618", "text": "This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents , including T-cell mitogens , proinflammatory cytokines , and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1 .", "annotated_text": "This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of <protein>NF-kappa B-inducing agents</protein> , including <protein>T-cell mitogens ,</protein> <protein>proinflammatory cytokines</protein> , and <protein>viral transactivators</protein> such as the <protein>Tax protein</protein> of human T-cell leukemia virus type 1 ."}
{"id": "619", "text": "To explore these I kappa B alpha -dependent mechanisms for NF-kappa B induction , we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes .", "annotated_text": "To explore these <protein>I kappa B alpha</protein> -dependent mechanisms for <protein>NF-kappa B</protein> induction , we identified novel mutants of <protein>I kappa B alpha</protein> that uncouple its inhibitory and signal-transducing functions in <cell_type>human T lymphocytes</cell_type> ."}
{"id": "620", "text": "Specifically , removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm .", "annotated_text": "Specifically , removal of the <protein>N-terminal 36 amino acids</protein> of <protein>I kappa B alpha</protein> failed to disrupt its ability to form latent complexes with <protein>NF-kappa B</protein> in the cytoplasm ."}
{"id": "621", "text": "However , this deletion mutation prevented the induced phosphorylation , degradative loss , and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells .", "annotated_text": "However , this deletion mutation prevented the induced phosphorylation , degradative loss , and functional release of <protein>I kappa B alpha</protein> from <protein>NF-kappa B</protein> in <cell_line>Tax-expressing cells</cell_line> ."}
{"id": "622", "text": "Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax -induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction , including those initiated from antigen and cytokine receptors .", "annotated_text": "Alanine substitutions introduced at two serine residues positioned within this <protein>N-terminal regulatory region</protein> of <protein>I kappa B alpha</protein> also yielded constitutive repressors that escaped from <protein>Tax</protein> -induced turnover and that potently inhibited immune activation pathways for <protein>NF-kappa B</protein> induction , including those initiated from <protein>antigen and cytokine receptors</protein> ."}
{"id": "623", "text": "In contrast , introduction of a phosphoserine mimetic at these sites rectified this functional defect , a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor .", "annotated_text": "In contrast , introduction of a phosphoserine mimetic at these sites rectified this functional defect , a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this <protein>cytoplasmic inhibitor</protein> ."}
{"id": "624", "text": "Together , these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli .", "annotated_text": "Together , these in vivo studies define a critical signal response domain in <protein>I kappa B alpha</protein> that coordinately controls the biologic activities of <protein>I kappa B alpha</protein> and <protein>NF-kappa B</protein> in response to viral and immune stimuli ."}
{"id": "625", "text": "Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte-conditioned medium .", "annotated_text": "Growth regulation and cellular changes during differentiation of <cell_line>human prostatic cancer LNCaP cells</cell_line> as induced by T lymphocyte-conditioned medium ."}
{"id": "626", "text": "Human prostatic epithelial cells from an androgen-dependent LNCaP cell line were examined in response to conditioned medium ( CM ) derived from phytohemagglutinin ( PHA ) -stimulated lymphocytes .", "annotated_text": "<cell_line>Human prostatic epithelial cells</cell_line> from an <cell_line>androgen-dependent LNCaP cell line</cell_line> were examined in response to conditioned medium ( CM ) derived from <cell_line>phytohemagglutinin ( PHA ) -stimulated lymphocytes</cell_line> ."}
{"id": "627", "text": "Addition of CM caused a greater than 70 % reduction of cell proliferation by cell counting and cell cycle .", "annotated_text": "Addition of CM caused a greater than 70 % reduction of cell proliferation by cell counting and cell cycle ."}
{"id": "628", "text": "These cells showed G1 phase arrest and the clonogenicity was reduced .", "annotated_text": "These cells showed G1 phase arrest and the clonogenicity was reduced ."}
{"id": "629", "text": "The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis .", "annotated_text": "The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis ."}
{"id": "630", "text": "The binding of androgen to androgen receptor on these cells showed approximately 50 % reduction , underlining a proliferation reduction mechanism .", "annotated_text": "The binding of androgen to <protein>androgen receptor</protein> on these cells showed approximately 50 % reduction , underlining a proliferation reduction mechanism ."}
{"id": "631", "text": "The prostate-specific antigen ( PSA ) was downregulated to approximately 75 % during the process .", "annotated_text": "The <protein>prostate-specific antigen</protein> ( <protein>PSA</protein> ) was downregulated to approximately 75 % during the process ."}
{"id": "632", "text": "Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics .", "annotated_text": "Cell morphology showed dendritic processes extending from cytoplasm and other <cell_type>neuroendocrine cell</cell_type> characteristics ."}
{"id": "633", "text": "The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures .", "annotated_text": "The expression of several <protein>cytoskeleton and intracellular proteins</protein> increased as determined by immunostaining on slides and by ELISA procedures ."}
{"id": "634", "text": "These included vimentin , correlating to cell shape changes , cytokeratins 8 and 18 , associated with differentiated cell types of prostate epithelia , and neuron-specific enolase and serotonin , associated with neuroendocrine cells .", "annotated_text": "These included <protein>vimentin</protein> , correlating to cell shape changes , <protein>cytokeratins 8 and 18</protein> , associated with <cell_type>differentiated cell types</cell_type> of prostate epithelia , and <protein>neuron-specific enolase</protein> and serotonin , associated with <cell_type>neuroendocrine cells</cell_type> ."}
{"id": "635", "text": "From these cellular changes , we can infer that the cell growth was modulated along with induction of terminal differentiation .", "annotated_text": "From these cellular changes , we can infer that the cell growth was modulated along with induction of terminal differentiation ."}
{"id": "636", "text": "Activated T cells were demonstrated to be important in providing the modulating activity .", "annotated_text": "Activated <cell_type>T cells</cell_type> were demonstrated to be important in providing the modulating activity ."}
{"id": "637", "text": "This growth modulator was semipurified and had an estimated molecular weight 13 , 000 to 24 , 000 Da .", "annotated_text": "This <protein>growth modulator</protein> was semipurified and had an estimated molecular weight 13 , 000 to 24 , 000 Da ."}
{"id": "638", "text": "The activity was determined to be distinct from TGF , TNF , and some commonly known lymphokines .", "annotated_text": "The activity was determined to be distinct from <protein>TGF</protein> , <protein>TNF</protein> , and some commonly known <protein>lymphokines</protein> ."}
{"id": "639", "text": "The interaction between lymphoid and prostatic cells in growth and development is described .", "annotated_text": "The interaction between <cell_type>lymphoid and prostatic cells</cell_type> in growth and development is described ."}
{"id": "640", "text": "Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes .", "annotated_text": "<protein>Platelet-activating factor</protein> stimulates transcription of the <protein>heparin-binding epidermal growth factor-like growth factor</protein> in <cell_type>monocytes</cell_type> ."}
{"id": "641", "text": "Correlation with an increased kappa B binding activity .", "annotated_text": "Correlation with an increased kappa B binding activity ."}
{"id": "642", "text": "Human peripheral blood monocytes responded to stimulation of platelet-activating factor ( PAF ) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) , a potent mitogen for vascular smooth muscle cells .", "annotated_text": "Human peripheral blood <cell_type>monocytes</cell_type> responded to stimulation of <protein>platelet-activating factor</protein> ( <protein>PAF</protein> ) with up-regulation of the transcript for <protein>heparin-binding epidermal growth factor-like growth factor</protein> ( <protein>HB-EGF</protein> ) , a <protein>potent mitogen</protein> for <cell_type>vascular smooth muscle cells</cell_type> ."}
{"id": "643", "text": "This function of PAF was observed at nanomolar concentrations of the ligand , starting at 30 min after stimulation .", "annotated_text": "This function of <protein>PAF</protein> was observed at nanomolar concentrations of the ligand , starting at 30 min after stimulation ."}
{"id": "644", "text": "The PAF -induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity .", "annotated_text": "The <protein>PAF</protein> -induced up-regulation of <rna>HB-EGF mRNA</rna> was accompanied by an increase in kappa B binding activity ."}
{"id": "645", "text": "These functions of PAF appeared to be mediated through the cell surface PAF receptors , as two PAF receptor antagonists , WEB 2086 and L-659 , 989 , blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF .", "annotated_text": "These functions of <protein>PAF</protein> appeared to be mediated through the <protein>cell surface PAF receptors</protein> , as two <protein>PAF</protein> receptor antagonists , WEB 2086 and L-659 , 989 , blocked both the up-regulation of <rna>HB-EGF mRNA</rna> and kappa B binding activity induced by <protein>PAF</protein> ."}
{"id": "646", "text": "The antagonists , however , had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity .", "annotated_text": "The antagonists , however , had no effect on phorbol ester-induced up-regulation of <rna>HB-EGF mRNA</rna> and kappa B binding activity ."}
{"id": "647", "text": "Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF , whereas cholera toxin had no inhibitory effect .", "annotated_text": "Pretreatment of <cell_type>monocytes</cell_type> with pertussis toxin inhibited these functions of <protein>PAF</protein> , whereas cholera toxin had no inhibitory effect ."}
{"id": "648", "text": "Pyrrolidine dithiocarbamate , an inhibitor for NF-kappa B activation , markedly reduced PAF -stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA .", "annotated_text": "Pyrrolidine dithiocarbamate , an inhibitor for <protein>NF-kappa B</protein> activation , markedly reduced <protein>PAF</protein> -stimulated kappa B binding activity as well as up-regulation of <rna>HB-EGF mRNA</rna> ."}
{"id": "649", "text": "These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity .", "annotated_text": "These results suggest a potential role of <protein>PAF</protein> in <protein>HB-EGF</protein> expression and provide evidence that this stimulation may occur through increased kappa B binding activity ."}
{"id": "650", "text": "Mapping of the interaction site of the defective transcription factor in the class II major histocompatibility complex mutant cell line clone-13 to the divergent X2-box .", "annotated_text": "Mapping of the <protein>interaction site</protein> of the <protein>defective transcription factor</protein> in the <cell_line>class II major histocompatibility complex mutant cell line clone-13</cell_line> to the <dna>divergent X2-box</dna> ."}
{"id": "651", "text": "We have previously described a mutant B lymphoblastoid cell line , Clone-13 , that expresses HLA-DQ in the absence of HLA-DR and -DP .", "annotated_text": "We have previously described a <cell_line>mutant B lymphoblastoid cell line</cell_line> , <cell_line>Clone-13 ,</cell_line> that expresses <protein>HLA-DQ</protein> in the absence of <protein>HLA-DR and -DP</protein> ."}
{"id": "652", "text": "Several criteria indicated that the defect in this cell line influences the activity of an isotype-specific transcription factor .", "annotated_text": "Several criteria indicated that the defect in this cell line influences the activity of an <protein>isotype-specific transcription factor</protein> ."}
{"id": "653", "text": "Indeed , transient transfection of HLA-DRA and DQB reporter constructs indicated that the affected factor operates via cis-elements located between -141 base pairs and the transcription initiation site .", "annotated_text": "Indeed , transient transfection of <dna>HLA-DRA and DQB reporter constructs</dna> indicated that the affected factor operates via <dna>cis-elements</dna> located between <dna>-141 base pairs</dna> and the <dna>transcription initiation site</dna> ."}
{"id": "654", "text": "A series of hybrid DRA/DQB reporter constructs was generated to further map the relevant cis-elements in this system .", "annotated_text": "A series of <dna>hybrid DRA/DQB reporter constructs</dna> was generated to further map the relevant <dna>cis-elements</dna> in this system ."}
{"id": "655", "text": "Insertion of oligonucleotides spanning the DQB X-box ( but not the DQB-W region or the DQB Y-box ) upstream of -141 in a DRA reporter plasmid rescued expression to nearly wild-type levels .", "annotated_text": "Insertion of oligonucleotides spanning the <dna>DQB X-box</dna> ( but not the <dna>DQB-W region</dna> or the <dna>DQB Y-box</dna> ) <dna>upstream of -141</dna> in a <dna>DRA reporter plasmid</dna> rescued expression to nearly wild-type levels ."}
{"id": "656", "text": "Substitution promoters were then generated where the entire X-box , or only the X1- or X2-boxes of HLA-DRA were replaced with the analogous regions of HLA-DQB .", "annotated_text": "Substitution promoters were then generated where the entire <dna>X-box</dna> , or only the <dna>X1- or X2-boxes</dna> of <dna>HLA-DRA</dna> were replaced with the analogous regions of <dna>HLA-DQB</dna> ."}
{"id": "657", "text": "The DQB X2-box was able to restore expression to the silent DRA reporter construct .", "annotated_text": "The <dna>DQB X2-box</dna> was able to restore expression to the <dna>silent DRA reporter construct</dna> ."}
{"id": "658", "text": "Moreover , replacement of the DQB X2-box with the DRA X2-box markedly diminished the activity of the DQB promoter in the mutant cell .", "annotated_text": "Moreover , replacement of the <dna>DQB X2-box</dna> with the <dna>DRA X2-box</dna> markedly diminished the activity of the <dna>DQB promoter</dna> in the <cell_line>mutant cell</cell_line> ."}
{"id": "659", "text": "of the hybrid reporter constructs were defective when transfected into the wild-type , HLA-DR/-DQ positive parental cell line , Jijoye .", "annotated_text": "of the <dna>hybrid reporter constructs</dna> were defective when transfected into the <protein>wild-type</protein> , <cell_line>HLA-DR/-DQ positive parental cell line</cell_line> , <cell_line>Jijoye</cell_line> ."}
{"id": "660", "text": "These studies suggest that the divergent X2-box of the class II major histocompatibility complex promoters plays an important role in influencing differential expression of the human class II isotypes .", "annotated_text": "These studies suggest that the <dna>divergent X2-box</dna> of the <dna>class II major histocompatibility complex promoters</dna> plays an important role in influencing differential expression of the <dna>human class II isotypes</dna> ."}
{"id": "661", "text": "Restoration of the Epstein-Barr virus ZEBRA protein 's capacity to disrupt latency by the addition of heterologous activation regions .", "annotated_text": "Restoration of the <protein>Epstein-Barr virus ZEBRA protein</protein> 's capacity to disrupt latency by the addition of <protein>heterologous activation regions</protein> ."}
{"id": "662", "text": "The ZEBRA protein has a unique biological function among herpesviral proteins .", "annotated_text": "The <protein>ZEBRA protein</protein> has a unique biological function among <protein>herpesviral proteins</protein> ."}
{"id": "663", "text": "It is responsible for the disruption of Epstein-Barr virus ( EBV ) latency and the induction of the lytic cycle .", "annotated_text": "It is responsible for the disruption of Epstein-Barr virus ( EBV ) latency and the induction of the lytic cycle ."}
{"id": "664", "text": "ZEBRA is a bZIP transcriptional activator which binds as a dimer to 7-bp response elements within EBV promoters and is directly involved in the stimulation of virus replication at the EBV lytic origin .", "annotated_text": "<protein>ZEBRA</protein> is a <protein>bZIP transcriptional activator</protein> which binds as a dimer to <dna>7-bp response elements</dna> within <dna>EBV promoters</dna> and is directly involved in the stimulation of virus replication at the <dna>EBV lytic origin</dna> ."}
{"id": "665", "text": "We have employed the ZEBRA /EBV biological system to test whether a heterologous activation domain can substitute for another activation domain ( the ZEBRA domain ) .", "annotated_text": "We have employed the <protein>ZEBRA</protein> /EBV biological system to test whether a <protein>heterologous activation domain</protein> can substitute for another activation domain ( the <protein>ZEBRA domain</protein> ) ."}
{"id": "666", "text": "The ZEBRA activation region was replaced with the potent acid activation region from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein .", "annotated_text": "The <protein>ZEBRA activation region</protein> was replaced with the potent <protein>acid activation region</protein> from the <protein>herpes simplex virus VP16 protein</protein> or with the <protein>activation region</protein> of the <protein>EBV R protein</protein> ."}
{"id": "667", "text": "Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself .", "annotated_text": "Both chimeras were found to transactivate model and native promoters at equivalent or better levels than <protein>ZEBRA</protein> itself ."}
{"id": "668", "text": "Activation was not target- or cell-type dependent , nor was it dependent on the presence of virus .", "annotated_text": "Activation was not target- or cell-type dependent , nor was it dependent on the presence of virus ."}
{"id": "669", "text": "These activation domains restored ZEBRA 's ability to induce early antigen and to stimulate origin replication to levels that were equal to or greater than those of wild type .", "annotated_text": "These activation domains restored <protein>ZEBRA</protein> 's ability to induce <protein>early antigen</protein> and to stimulate origin replication to levels that were equal to or greater than those of wild type ."}
{"id": "670", "text": "These studies suggest that the specificities of some of the known biological functions of ZEBRA are not dependent upon the nature of the activation domain present within ZEBRA .", "annotated_text": "These studies suggest that the specificities of some of the known biological functions of <protein>ZEBRA</protein> are not dependent upon the nature of the <protein>activation domain present</protein> within <protein>ZEBRA</protein> ."}
{"id": "671", "text": "Interleukin 4 activates a signal transducer and activator of transcription ( Stat ) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line .", "annotated_text": "<protein>Interleukin 4</protein> activates a signal transducer and activator of <protein>transcription ( Stat ) protein</protein> which interacts with an <dna>interferon-gamma activation site-like sequence</dna> upstream of the <dna>I epsilon exon</dna> in a <cell_line>human B cell line</cell_line> ."}
{"id": "672", "text": "Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat .", "annotated_text": "Evidence for the involvement of <protein>Janus kinase 3</protein> and <protein>interleukin-4 Stat</protein> ."}
{"id": "673", "text": "Germ line C transcripts can be induced by IL-4 in the human B cell line , BL-2 .", "annotated_text": "<rna>Germ line C transcripts</rna> can be induced by <protein>IL-4</protein> in the <cell_line>human B cell line</cell_line> , <cell_line>BL-2</cell_line> ."}
{"id": "674", "text": "Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon , we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells .", "annotated_text": "Utilizing a <dna>IFN-gamma activation site-like DNA sequence element</dna> located upstream of the <dna>I epsilon exon</dna> , we demonstrated by gel mobility shift assays that <protein>IL-4</protein> induced a binding activity in the cytosol and nucleus of <cell_line>BL-2 cells</cell_line> ."}
{"id": "675", "text": "This factor was designated IL-4 NAF ( IL-4-induced nuclear-activating factors ) and was identified as a tyrosine phosphoprotein , which translocates from the cytosol to the nucleus upon IL-4 treatment .", "annotated_text": "This factor was designated <protein>IL-4 NAF</protein> ( <protein>IL-4-induced nuclear-activating factors</protein> ) and was identified as a <protein>tyrosine phosphoprotein</protein> , which translocates from the cytosol to the nucleus upon <protein>IL-4</protein> treatment ."}
{"id": "676", "text": "Because these are the characteristics of a signal transducer and activator of transcription ( Stat ) protein , we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat , also known as Stat6 , but not antibodies to other Stat proteins , interfere with the formation of the IL-4 NAF complex .", "annotated_text": "Because these are the characteristics of a <protein>signal transducer and activator of transcription ( Stat ) protein</protein> , we determined whether <protein>antibodies to Stat proteins</protein> will interfere with gel mobility shift and found that <protein>antibodies to IL-4 Stat</protein> , also known as <protein>Stat6</protein> , but not <protein>antibodies</protein> to other <protein>Stat proteins</protein> , interfere with the formation of the <protein>IL-4 NAF complex</protein> ."}
{"id": "677", "text": "Congruous with the involvement of a Stat protein , IL-4 induced robust Janus kinase 3 ( JAK3 ) activity in BL-2 cells .", "annotated_text": "Congruous with the involvement of a <protein>Stat protein</protein> , <protein>IL-4</protein> induced robust <protein>Janus kinase 3</protein> ( <protein>JAK3</protein> ) activity in <cell_line>BL-2 cells</cell_line> ."}
{"id": "678", "text": "Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay .", "annotated_text": "Cotransfection of <protein>JAK3</protein> with <protein>IL-4 Stat</protein> into <cell_line>COS-7 cells</cell_line> produced an intracellular activity which bound the same <dna>IFN-gamma activation site-like sequence</dna> and comigrated with <protein>IL-4 NAF</protein> in electrophoretic mobility shift assay ."}
{"id": "679", "text": "These results show that IL-4 NAF is IL-4 Stat , which is activated by JAK3 in response to IL-4 receptor engagement .", "annotated_text": "These results show that <protein>IL-4 NAF</protein> is <protein>IL-4 Stat</protein> , which is activated by <protein>JAK3</protein> in response to <protein>IL-4</protein> receptor engagement ."}
{"id": "680", "text": "Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia ? A pediatric oncology group study .", "annotated_text": "Does activation of the <dna>TAL1 gene</dna> occur in a majority of patients with T-cell acute lymphoblastic leukemia ? A pediatric oncology group study ."}
{"id": "681", "text": "Almost 25 % of patients with T-cell acute lymphoblastic leukemia ( T-ALL ) have tumor-specific rearrangements of the TAL1 gene .", "annotated_text": "Almost 25 % of patients with T-cell acute lymphoblastic leukemia ( T-ALL ) have tumor-specific rearrangements of the <dna>TAL1 gene</dna> ."}
{"id": "682", "text": "Although TAL1 expression has not been observed in normal lymphocytes , TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele .", "annotated_text": "Although <protein>TAL1</protein> expression has not been observed in <cell_type>normal lymphocytes</cell_type> , <protein>TAL1 gene products</protein> are readily detected in <cell_type>leukemic cells</cell_type> that harbor a <dna>rearranged TAL1 allele</dna> ."}
{"id": "683", "text": "Hence , it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL .", "annotated_text": "Hence , it has been proposed that ectopic expression of <protein>TAL1</protein> promotes the development of T-ALL ."}
{"id": "684", "text": "In this report , we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL , including many that do not display an apparent TAL1 gene alteration .", "annotated_text": "In this report , we show that <protein>TAL1</protein> is expressed in the <cell_type>leukemic cells</cell_type> of most patients with T-ALL , including many that do not display an apparent <dna>TAL1 gene</dna> alteration ."}
{"id": "685", "text": "A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells .", "annotated_text": "A polymorphic dinucleotide repeat in the transcribed sequences of <protein>TAL1</protein> was used to determine the allele specificity of <protein>TAL1</protein> transcription in <cell_type>primary T-ALL cells</cell_type> ."}
{"id": "686", "text": "Monoallelic expression of TAL1 was observed in the leukemic cells of all patients ( 8 of 8 ) bearing a TAL1 gene rearrangement .", "annotated_text": "Monoallelic expression of <protein>TAL1</protein> was observed in the <cell_type>leukemic cells</cell_type> of all patients ( 8 of 8 ) bearing a <dna>TAL1 gene</dna> rearrangement ."}
{"id": "687", "text": "In the leukemic cells of patients without detectable TAL1 rearrangements , TAL1 transcription occurred in either a monoallelic ( 3 of 7 patients ) or a biallelic ( 4 of 7 patients ) fashion .", "annotated_text": "In the <cell_type>leukemic cells</cell_type> of patients without detectable <protein>TAL1</protein> rearrangements , <protein>TAL1</protein> transcription occurred in either a monoallelic ( 3 of 7 patients ) or a biallelic ( 4 of 7 patients ) fashion ."}
{"id": "688", "text": "Thus , TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences ( affecting expression of a single TAL1 allele ) or changes in trans-acting factors that control TAL1 transcription ( affecting expression of both TAL1 alleles ) .", "annotated_text": "Thus , <protein>TAL1</protein> activation in these patients may result from subtle alterations in <dna>cis-acting regulatory sequences</dna> ( affecting expression of a <dna>single TAL1 allele</dna> ) or changes in trans-acting factors that control <protein>TAL1</protein> transcription ( affecting expression of both <dna>TAL1 alleles</dna> ) ."}
{"id": "689", "text": "Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down 's syndrome .", "annotated_text": "Expression of <dna>erythroid-specific genes</dna> in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down 's syndrome ."}
{"id": "690", "text": "Acute megakaryoblastic leukaemia ( M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers .", "annotated_text": "Acute megakaryoblastic leukaemia ( M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of <cell_type>abnormal blast cells</cell_type> which express <protein>megakaryocytic markers</protein> ."}
{"id": "691", "text": "To clarify properties of the blast cells in M7 and TMD cases , we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study .", "annotated_text": "To clarify properties of the <cell_type>blast cells</cell_type> in M7 and TMD cases , we examined erythroid markers expression in <cell_type>blasts</cell_type> from six cases with M7 and seven cases with TMD in this study ."}
{"id": "692", "text": "Erythroid-specific mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were found to be expressed in blasts from most of these cases , indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes .", "annotated_text": "<rna>Erythroid-specific mRNAs</rna> encoding <protein>gamma-globin</protein> and <protein>erythroid delta-aminolevulinate synthase</protein> were found to be expressed in <cell_type>blasts</cell_type> from most of these cases , indicating that majorities of the <cell_type>blasts</cell_type> in M7 and TMD cases have erythroid and megakaryocytic phenotypes ."}
{"id": "693", "text": "We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases .", "annotated_text": "We also found that <rna>mRNAs</rna> encoding <protein>GATA-1</protein> and <protein>GATA-2</protein> are expressed in all these cases ."}
{"id": "694", "text": "These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells .", "annotated_text": "These results suggest that <cell_type>M7 blasts</cell_type> and <cell_type>TMD blasts</cell_type> correspond to the <cell_type>erythroid/megakaryocytic bipotential progenitor cells</cell_type> ."}
{"id": "695", "text": "Expression of Ah receptor ( TCDD receptor ) during human monocytic differentiation .", "annotated_text": "Expression of <protein>Ah receptor</protein> ( <protein>TCDD receptor</protein> ) during human monocytic differentiation ."}
{"id": "696", "text": "We have previously found a high expression of human Ah receptor ( TCDD receptor ) mRNA in peripheral blood cells of individuals .", "annotated_text": "We have previously found a high expression of <rna>human Ah receptor ( TCDD receptor ) mRNA</rna> in <cell_type>peripheral blood cells</cell_type> of individuals ."}
{"id": "697", "text": "In this paper , the expression of this gene in blood cells was first investigated in fractions of nucleated cells , revealing predominant expression of the Ah receptor gene in the monocyte fraction .", "annotated_text": "In this paper , the expression of this gene in <cell_type>blood cells</cell_type> was first investigated in fractions of <cell_type>nucleated cells</cell_type> , revealing predominant expression of the <dna>Ah receptor gene</dna> in the <cell_type>monocyte fraction</cell_type> ."}
{"id": "698", "text": "Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1 .", "annotated_text": "Then the expression levels of <rna>AhR mRNA</rna> in various <cell_line>hematopoietic cell lines</cell_line> were examined together with those of <protein>Arnt</protein> and <protein>P450IA1</protein> ."}
{"id": "699", "text": "AhR was expressed at high levels in monocytoid U937 , THP1 , and HEL/S cells , and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells .", "annotated_text": "<protein>AhR</protein> was expressed at high levels in <cell_line>monocytoid U937</cell_line> , <cell_line>THP1</cell_line> , and <cell_line>HEL/S cells</cell_line> , and at moderate levels in <cell_line>promyelocytic HL60 cells</cell_line> and <cell_line>erythroblastic HEL cells</cell_line> ."}
{"id": "700", "text": "However , it was not detected in lymphoid cells MOLT4 ( T cell ) and BALL1 ( B cell ) , nor in K562 erythroblasts .", "annotated_text": "However , it was not detected in <cell_type>lymphoid cells</cell_type> <cell_line>MOLT4</cell_line> ( <cell_type>T cell</cell_type> ) and <cell_line>BALL1</cell_line> ( <cell_type>B cell</cell_type> ) , nor in <cell_line>K562 erythroblasts</cell_line> ."}
{"id": "701", "text": "Furthermore , a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells .", "annotated_text": "Furthermore , a specific induction of <protein>AhR</protein> during monocytic differentiation was investigated in <cell_line>HL60</cell_line> and <cell_line>HEL cells</cell_line> ."}
{"id": "702", "text": "HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester , showing a 5- to 2-fold increase of AhR mRNA .", "annotated_text": "<cell_line>HL60 cells</cell_line> were induced to differentiate toward <cell_type>monocytes-macrophages</cell_type> by incubation with phorbol ester , showing a 5- to 2-fold increase of <rna>AhR mRNA</rna> ."}
{"id": "703", "text": "The incubation with transforming growth factor beta 1 and 1 alpha , 25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA .", "annotated_text": "The incubation with <protein>transforming growth factor beta 1</protein> and 1 alpha , 25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of <rna>AhR mRNA</rna> ."}
{"id": "704", "text": "The HEL cells also exhibited a similar elevation of AhR mRNA level , when they had differentiated toward monocyte-macrophage cells by these combined inducers , but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types .", "annotated_text": "The <cell_line>HEL cells</cell_line> also exhibited a similar elevation of <rna>AhR mRNA</rna> level , when they had differentiated toward <cell_type>monocyte-macrophage cells</cell_type> by these combined inducers , but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types ."}
{"id": "705", "text": "Treatment of the differentiated HL60 cells with 3-methylcholanthrene , a ligand of AhR , induced the expression of the P450IA1 gene .", "annotated_text": "Treatment of the <cell_line>differentiated HL60 cells</cell_line> with 3-methylcholanthrene , a ligand of <protein>AhR</protein> , induced the expression of the <protein>P450IA1</protein> gene ."}
{"id": "706", "text": "These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics .", "annotated_text": "These results indicated that expression of <rna>AhR mRNA</rna> was significantly induced during monocytic differentiation and that the <cell_type>differentiated cells</cell_type> were responsive to xenobiotics ."}
{"id": "707", "text": "Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens .", "annotated_text": "Our results suggest that <protein>AhR</protein> may play an important role in the function of <cell_type>monocytes</cell_type> and also in the eventual activation of environmental carcinogens ."}
{"id": "708", "text": "Neutrophils and monocytes express high levels of PU.1 ( Spi-1 ) but not Spi-B .", "annotated_text": "<cell_type>Neutrophils</cell_type> and <cell_type>monocytes</cell_type> express high levels of <protein>PU.1</protein> ( <protein>Spi-1</protein> ) but not <protein>Spi-B</protein> ."}
{"id": "709", "text": "PU.1 ( the Spi-1 oncogene ) and Spi-B are closely related members of the ets transcription factor family , sharing similar DNA binding specificities mediated by similar DNA binding domains .", "annotated_text": "<protein>PU.1</protein> ( the <dna>Spi-1 oncogene</dna> ) and <protein>Spi-B</protein> are closely related members of the <protein>ets transcription factor family</protein> , sharing similar DNA binding specificities mediated by similar <protein>DNA binding domains</protein> ."}
{"id": "710", "text": "PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells , but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated .", "annotated_text": "<protein>PU.1</protein> and <protein>Spi-B</protein> have been previously described as being predominantly expressed coordinately in <cell_type>macrophages</cell_type> and <cell_type>B cells</cell_type> , but their expression in early hematopoietic stages and during the course of myeloid differentiation to <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> or to <cell_type>neutrophils</cell_type> has not been extensively investigated ."}
{"id": "711", "text": "Here , we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34+ cells and murine multipotential FDCP-mix A4 cells , suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells .", "annotated_text": "Here , we report that <rna>PU.1 mRNA</rna> is upregulated during myeloid differentiation of <cell_line>human purified CD34+ cells</cell_line> and <cell_line>murine multipotential FDCP-mix A4 cells</cell_line> , suggesting that <protein>PU.1</protein> is upregulated as an early event during differentiation of <cell_type>multipotential progenitor cells</cell_type> ."}
{"id": "712", "text": "PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells .", "annotated_text": "<protein>PU.1</protein> expression is maintained at stable levels during differentiation of <cell_line>myeloid cell lines</cell_line> <cell_line>U937</cell_line> and <cell_line>HL-60</cell_line> to <cell_type>monocytic and neutrophilic cells</cell_type> ."}
{"id": "713", "text": "PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils .", "annotated_text": "<protein>PU.1</protein> is expressed at highest levels in <cell_type>mature human monocytes</cell_type> and <cell_type>human peripheral blood neutrophils</cell_type> ."}
{"id": "714", "text": "In contrast to PU.1 , significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines , neutrophils , or macrophages .", "annotated_text": "In contrast to <protein>PU.1</protein> , significant levels of <rna>Spi-B mRNA</rna> and protein are found only in some <cell_line>B-cell lines</cell_line> and spleen but are not found in <cell_line>myeloid cell lines</cell_line> , <cell_type>neutrophils</cell_type> , or <cell_type>macrophages</cell_type> ."}
{"id": "715", "text": "In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells .", "annotated_text": "In vitro translated <protein>Spi-B protein</protein> can bind to <dna>PU.1 binding sites</dna> in <dna>myeloid promoters</dna> and transactivate these <dna>promoters</dna> in <cell_type>nonmyeloid cells</cell_type> ."}
{"id": "716", "text": "Therefore , although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro , the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression .", "annotated_text": "Therefore , although <protein>PU.1</protein> and <protein>Spi-B</protein> may bind to similar DNA control elements and have redundancy of transactivation function in vitro , the lack of significant levels of <protein>Spi-B</protein> in <cell_type>myeloid cells</cell_type> makes it unlikely that <protein>Spi-B</protein> plays a significant role in myeloid lineage development and gene expression ."}
{"id": "717", "text": "In contrast , PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils , indicating that PU.1 can activate gene expression in both major myeloid lineages .", "annotated_text": "In contrast , <protein>PU.1</protein> is expressed at high levels not only in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> but also in <cell_type>neutrophils</cell_type> , indicating that <protein>PU.1</protein> can activate gene expression in both <cell_type>major myeloid lineages</cell_type> ."}
{"id": "718", "text": "Identification of a major positive regulatory element located 5 ' to the human zeta-globin gene .", "annotated_text": "Identification of a major <dna>positive regulatory element</dna> located 5 ' to the <dna>human zeta-globin gene</dna> ."}
{"id": "719", "text": "The function of the zeta-globin promoter was studied using a series of zeta-globin promoter deletion constructs to drive luciferase expression in transiently transfected human erythroleukemia cells .", "annotated_text": "The function of the <dna>zeta-globin promoter</dna> was studied using a series of <dna>zeta-globin promoter deletion constructs</dna> to drive <protein>luciferase</protein> expression in <cell_line>transiently transfected human erythroleukemia cells</cell_line> ."}
{"id": "720", "text": "The promoters were used without enhancers , or with enhancers derived from the beta-globin locus control region and the alpha-globin HS-40 enhancer .", "annotated_text": "The <dna>promoters</dna> were used without <dna>enhancers</dna> , or with <dna>enhancers</dna> derived from the <dna>beta-globin locus control region</dna> and the <dna>alpha-globin HS-40 enhancer</dna> ."}
{"id": "721", "text": "When transfected into K562 cells , which express zeta-globin , comparable amounts of activity were obtained from the -557 and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no enhancers or the alpha-globin locus enhancers were used .", "annotated_text": "When transfected into <cell_line>K562 cells</cell_line> , which express <protein>zeta-globin</protein> , comparable amounts of activity were obtained from the <dna>-557 and -417 zeta-luciferase constructs</dna> and the <dna>alpha-luciferase constructs</dna> when no <dna>enhancers</dna> or the <dna>alpha-globin locus enhancers</dna> were used ."}
{"id": "722", "text": "When the constructs were transfected into OCIM1 cells , which do not express zeta-globin , the zeta-globin promoters were at best 20 % as active as the alpha-globin promoters .", "annotated_text": "When the constructs were transfected into <cell_line>OCIM1 cells</cell_line> , which do not express <protein>zeta-globin</protein> , the <dna>zeta-globin promoters</dna> were at best 20 % as active as the <dna>alpha-globin promoters</dna> ."}
{"id": "723", "text": "When sequences from -417 to -207 5 ' to the zeta-globin mRNA cap site were deleted , up to 95 % of the zeta-globin promoter activity was lost in K562 cells .", "annotated_text": "When <dna>sequences from -417 to -207 5 '</dna> to the <rna>zeta-globin mRNA cap site</rna> were deleted , up to 95 % of the <dna>zeta-globin promoter</dna> activity was lost in <cell_line>K562 cells</cell_line> ."}
{"id": "724", "text": "Reinsertion of these sequences into zeta-luciferase constructs missing the -417 to -207 region showed that the sequences lack classical enhancer activity .", "annotated_text": "Reinsertion of these sequences into <dna>zeta-luciferase constructs</dna> missing the -417 to -207 region showed that the sequences lack classical enhancer activity ."}
{"id": "725", "text": "Point mutation of a GATA-1 site at -230 reduced promoter activity by 37 % .", "annotated_text": "Point mutation of a <dna>GATA-1 site</dna> at -230 reduced promoter activity by 37 % ."}
{"id": "726", "text": "Point mutation of a CCACC site at -240 had no effect .", "annotated_text": "Point mutation of a <dna>CCACC site</dna> at -240 had no effect ."}
{"id": "727", "text": "Electrophoretic mobility shift assays indicated that the -230 GATA-1 site has a relatively low affinity for GATA-1 .", "annotated_text": "Electrophoretic mobility shift assays indicated that the <dna>-230 GATA-1 site</dna> has a relatively low affinity for <protein>GATA-1</protein> ."}
{"id": "728", "text": "These experiments show the presence of a strong positive-acting element , located between -417 and -207 bp 5 ' to the zeta-globin mRNA cap site , is necessary for high-level promoter activity in K562 cells .", "annotated_text": "These experiments show the presence of a strong <dna>positive-acting element</dna> , located between <dna>-417 and -207 bp 5 '</dna> to the <dna>zeta-globin mRNA cap site</dna> , is necessary for high-level promoter activity in <cell_line>K562 cells</cell_line> ."}
{"id": "729", "text": "This element requires GATA-1 and additional unknown factors for maximal activity .", "annotated_text": "This element requires <protein>GATA-1</protein> and <protein>additional unknown factors</protein> for maximal activity ."}
{"id": "730", "text": "Analysis of the role of protein kinase C-alpha , -epsilon , and -zeta in T cell activation .", "annotated_text": "Analysis of the role of <protein>protein kinase C-alpha , -epsilon , and -zeta</protein> in T cell activation ."}
{"id": "731", "text": "T cells express multiple isotypes of protein kinase C ( PKC ) and although it is well accepted that PKCs have an important role in T cell activation , little is known about the function of individual PKC isotypes .", "annotated_text": "<cell_type>T cells</cell_type> express multiple isotypes of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) and although it is well accepted that <protein>PKCs</protein> have an important role in T cell activation , little is known about the function of individual <protein>PKC isotypes</protein> ."}
{"id": "732", "text": "To address this issue , mutationally active PKC-alpha , -epsilon , or -zeta have been transfected into T cells and the consequences for T cell activation determined .", "annotated_text": "To address this issue , mutationally active <protein>PKC-alpha , -epsilon , or -zeta</protein> have been transfected into <cell_type>T cells</cell_type> and the consequences for T cell activation determined ."}
{"id": "733", "text": "p21ras plays an essential role in T cell activation .", "annotated_text": "<protein>p21ras</protein> plays an essential role in T cell activation ."}
{"id": "734", "text": "Accordingly , the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21ras .", "annotated_text": "Accordingly , the effects of the <protein>constitutively active PKCs</protein> were compared to the effects of mutationally activated <protein>p21ras</protein> ."}
{"id": "735", "text": "The data indicate that PKC-epsilon and , to a lesser extent PKC-alpha but not -zeta , can regulate the transcription factors AP-1 and nuclear factor of activated T cells ( NF-AT-1 ) .", "annotated_text": "The data indicate that <protein>PKC-epsilon</protein> and , to a lesser extent <protein>PKC-alpha</protein> but not <protein>-zeta</protein> , can regulate the <protein>transcription factors</protein> <protein>AP-1</protein> and nuclear <protein>factor of activated T cells</protein> ( <protein>NF-AT-1</protein> ) ."}
{"id": "736", "text": "The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21ras .", "annotated_text": "The ability of <protein>PKC-epsilon</protein> to induce transactivation of <protein>NF-AT-1</protein> and <protein>AP-1</protein> was similar to the stimulatory effect of a <protein>constitutively activated p21ras</protein> ."}
{"id": "737", "text": "PKC-epsilon , but not PKC-alpha nor activated p21ras , was able to induce NF-KB activity .", "annotated_text": "<protein>PKC-epsilon</protein> , but not <protein>PKC-alpha</protein> nor activated <protein>p21ras</protein> , was able to induce <protein>NF-KB</protein> activity ."}
{"id": "738", "text": "Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect .", "annotated_text": "Phorbol esters induce expression of <protein>CD69</protein> whereas none of the <protein>activated PKC isotypes</protein> tested were able to have this effect ."}
{"id": "739", "text": "Activated Src and p21ras were able to induce CD69 expression .", "annotated_text": "Activated <protein>Src</protein> and <protein>p21ras</protein> were able to induce <protein>CD69</protein> expression ."}
{"id": "740", "text": "These results indicate selective functions for different PKC isotypes in T cells .", "annotated_text": "These results indicate selective functions for different <protein>PKC isotypes</protein> in <cell_type>T cells</cell_type> ."}
{"id": "741", "text": "Moreover , the data comparing the effects of activated Ras and PKC mutants suggest that PKC-alpha , p21ras , and PKC-epsilon are not positioned linearly on a single signal transduction pathway .", "annotated_text": "Moreover , the data comparing the effects of <protein>activated Ras</protein> and <protein>PKC mutants</protein> suggest that <protein>PKC-alpha</protein> , <protein>p21ras</protein> , and <protein>PKC-epsilon</protein> are not positioned linearly on a single signal transduction pathway ."}
{"id": "742", "text": "Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma .", "annotated_text": "Differences in binding of <protein>glucocorticoid receptor</protein> to DNA in steroid-resistant asthma ."}
{"id": "743", "text": "Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases , a small proportion of patients are resistant to their therapeutic effects .", "annotated_text": "Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases , a small proportion of patients are resistant to their therapeutic effects ."}
{"id": "744", "text": "The molecular mechanism for this steroid resistance is unclear .", "annotated_text": "The molecular mechanism for this steroid resistance is unclear ."}
{"id": "745", "text": "Steroid resistance can not be explained by pharmacokinetic mechanisms , by a defect in the binding of steroids to glucocorticoid receptors , nor by defective nuclear translocation of this receptor , thereby suggesting that the molecular abnormality lies distal to nuclear translocation .", "annotated_text": "Steroid resistance can not be explained by pharmacokinetic mechanisms , by a defect in the binding of steroids to <protein>glucocorticoid receptors</protein> , nor by defective nuclear translocation of this receptor , thereby suggesting that the molecular abnormality lies distal to nuclear translocation ."}
{"id": "746", "text": "We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites ( GRE ) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma .", "annotated_text": "We examined the ability of nuclear translocated <protein>glucocorticoid receptors</protein> to bind to their <dna>DNA binding sites</dna> ( <dna>GRE</dna> ) using electrophoretic mobility shift assays in <cell_type>PBMC</cell_type> from patients with steroid-sensitive and steroid-resistant asthma ."}
{"id": "747", "text": "The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis .", "annotated_text": "The binding of the <protein>glucocorticoid receptor</protein> to DNA in these patients was also studied using Scatchard analysis ."}
{"id": "748", "text": "Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals , but this was markedly reduced in steroid-resistant asthmatic patients .", "annotated_text": "Dexamethasone induced a significant rapid and sustained twofold increase in <dna>GRE</dna> binding in <cell_type>PBMCs</cell_type> from steroid-sensitive asthmatic patients and nonasthmatic individuals , but this was markedly reduced in steroid-resistant asthmatic patients ."}
{"id": "749", "text": "Scatchard analysis of glucocorticoid receptor - GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients .", "annotated_text": "Scatchard analysis of <protein>glucocorticoid receptor</protein> - <dna>GRE</dna> binding showed no change in binding affinity but did show a reduced number of <protein>receptors</protein> available for DNA binding in the steroid-resistant patients ."}
{"id": "750", "text": "These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA .", "annotated_text": "These results suggest that the ability of the <protein>glucocorticoid receptor</protein> to bind to <dna>GRE</dna> is impaired in steroid-resistant patients because of a reduced number of <protein>receptors</protein> available for binding to DNA ."}
{"id": "751", "text": "Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha .", "annotated_text": "<protein>Interleukin-5</protein> signaling in <cell_type>human eosinophils</cell_type> involves <protein>JAK2 tyrosine kinase</protein> and <protein>Stat1 alpha</protein> ."}
{"id": "752", "text": "Signaling by a wide variety of cytokines , including interferons , interleukins , and growth factors , involves activation of JAK kinases and Stat ( Signal transducers and activators of transcription ) proteins .", "annotated_text": "Signaling by a wide variety of <protein>cytokines</protein> , including <protein>interferons</protein> , <protein>interleukins</protein> , and <protein>growth factors</protein> , involves activation of <protein>JAK kinases</protein> and <protein>Stat ( Signal transducers and activators of transcription ) proteins</protein> ."}
{"id": "753", "text": "At present , not much is known about the molecular mechanisms by which interleukin-5 ( IL-5 ) exerts its diverse biologic effects .", "annotated_text": "At present , not much is known about the molecular mechanisms by which <protein>interleukin-5</protein> ( <protein>IL-5</protein> ) exerts its diverse biologic effects ."}
{"id": "754", "text": "Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell .", "annotated_text": "<cell_type>Human eosinophils</cell_type> are one of the most important <cell_type>target cells</cell_type> for <protein>IL-5</protein> and were used here to study <protein>IL-5</protein> signaling in a <cell_type>primary human cell</cell_type> ."}
{"id": "755", "text": "IL-5 induced rapid and transient tyrosine phosphorylation of JAK2 .", "annotated_text": "<protein>IL-5</protein> induced rapid and transient tyrosine phosphorylation of <protein>JAK2</protein> ."}
{"id": "756", "text": "Moreover , IL-5 induced at least two DNA-binding complexes , using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter ( ICAM-1 pIRE ) in an electromobility shift assay .", "annotated_text": "Moreover , <protein>IL-5</protein> induced at least two <protein>DNA-binding complexes</protein> , using nuclear extracts from normal <cell_type>human eosinophils</cell_type> and the <dna>IL-6/interferon-gamma response element</dna> of the <dna>ICAM-1 promoter</dna> ( <dna>ICAM-1 pIRE</dna> ) in an electromobility shift assay ."}
{"id": "757", "text": "From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha , probably as a homodimer .", "annotated_text": "From supershift experiments it was concluded that one <protein>DNA-binding complex</protein> contained <protein>Stat1 alpha</protein> , probably as a homodimer ."}
{"id": "758", "text": "Both DNA-binding complexes were inhibited by a phosphotyrosine antibody ( 4G10 ) , suggesting that tyrosine phosphorylation is required for complex formation .", "annotated_text": "Both <protein>DNA-binding complexes</protein> were inhibited by a <protein>phosphotyrosine antibody</protein> ( <protein>4G10</protein> ) , suggesting that tyrosine phosphorylation is required for complex formation ."}
{"id": "759", "text": "IL-3 and granulocyte-macrophage colony-stimulating factor induced , similar to IL-5 , two DNA-binding complexes in human eosinophils , including Stat1 alpha .", "annotated_text": "<protein>IL-3</protein> and <protein>granulocyte-macrophage colony-stimulating factor</protein> induced , similar to <protein>IL-5</protein> , two <protein>DNA-binding complexes</protein> in <cell_type>human eosinophils</cell_type> , including <protein>Stat1 alpha</protein> ."}
{"id": "760", "text": "These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family .", "annotated_text": "These data show for the first time that molecular mechanisms of <protein>IL-5</protein> signaling in <cell_type>human eosinophils</cell_type> involve members of the <protein>JAK kinase family</protein> as well as members of the <protein>Stat family</protein> ."}
{"id": "761", "text": "Infection and replication of Tat- human immunodeficiency viruses : genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells .", "annotated_text": "Infection and replication of Tat- human immunodeficiency viruses : genetic analyses of <dna>LTR</dna> and <protein>tat mutations</protein> in <cell_type>primary and long-term human lymphoid cells</cell_type> ."}
{"id": "762", "text": "Tat is an essential regulatory protein for the replication of human immunodeficiency virus ( HIV ) .", "annotated_text": "<protein>Tat</protein> is an essential <protein>regulatory protein</protein> for the replication of human immunodeficiency virus ( HIV ) ."}
{"id": "763", "text": "Mutations in the tat gene have been shown to block HIV replication in human T cells .", "annotated_text": "Mutations in the <dna>tat gene</dna> have been shown to block HIV replication in <cell_type>human T cells</cell_type> ."}
{"id": "764", "text": "Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat ( LTR ) ; however , it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent .", "annotated_text": "Several studies have established that <protein>Tat</protein> releases an <protein>elongation block</protein> to the transcription of <dna>HIV long terminal repeat</dna> ( <dna>LTR</dna> ) ; however , it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in <cell_type>human T cells</cell_type> when <protein>Tat</protein> is absent ."}
{"id": "765", "text": "It is possible that Tat is also needed for other functions during HIV replication .", "annotated_text": "It is possible that <protein>Tat</protein> is also needed for other functions during HIV replication ."}
{"id": "766", "text": "To test these hypotheses , we studied several tat mutants , including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites .", "annotated_text": "To test these hypotheses , we studied several <protein>tat mutants</protein> , including two <protein>stop codon mutants</protein> and one <protein>deletion mutant</protein> using <dna>replication-competent HIV-1 constructs</dna> carrying <dna>wild-type or mutant LTRs</dna> with modifications in the <dna>NF-kappa B and/or Sp1 binding sites</dna> ."}
{"id": "767", "text": "In this study , we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells , and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages .", "annotated_text": "In this study , we show that Tat- HIV-1 with <dna>wild-type LTRs</dna> can replicate in <cell_line>HeLa cells</cell_line> , and the virus produced from <cell_line>HeLa cells</cell_line> can infect primary <cell_type>peripheral blood lymphocytes</cell_type> and <cell_type>macrophages</cell_type> ."}
{"id": "768", "text": "It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants .", "annotated_text": "It was found that the propagation of the <protein>Tat mutants</protein> containing <dna>wild-type LTRs</dna> was less efficient than that of the <protein>LTR-modified Tat mutants</protein> ."}
{"id": "769", "text": "Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs .", "annotated_text": "Large amounts of <rna>viral RNA</rna> and particles were synthesized in infections established using the <protein>tat mutants</protein> that contain <dna>modified LTRs</dna> ."}
{"id": "770", "text": "However , this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses .", "annotated_text": "However , this efficient propagation of the <protein>LTR-modified tat mutants</protein> was restricted to some <cell_line>lymphoid cell lines</cell_line> that have been transformed with other viruses ."}
{"id": "771", "text": "Thus , despite its essential role for releasing an elongation block , Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles .", "annotated_text": "Thus , despite its essential role for releasing an <protein>elongation block</protein> , <protein>Tat</protein> is not otherwise absolutely required for synthesis of <rna>full-length HIV transcripts</rna> and assembly of virus particles ."}
{"id": "772", "text": "Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat -virus .", "annotated_text": "Direct sequencing of the <dna>viral genomes</dna> and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the <protein>Tat</protein> -virus ."}
{"id": "773", "text": "The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed .", "annotated_text": "The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative <protein>Tat</protein> function are discussed ."}
{"id": "774", "text": "Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression .", "annotated_text": "Functional roles of the <protein>transcription factor Oct-2A</protein> and the <protein>high mobility group protein</protein> <protein>I/Y</protein> in <dna>HLA-DRA gene</dna> expression ."}
{"id": "775", "text": "The class II major histocompatibility complex gene HLA-DRA is expressed in B cells , activated T lymphocytes , and in antigen-presenting cells .", "annotated_text": "The <dna>class II major histocompatibility complex gene</dna> <dna>HLA-DRA</dna> is expressed in <cell_type>B cells</cell_type> , activated <cell_type>T lymphocytes</cell_type> , and in <cell_type>antigen-presenting cells</cell_type> ."}
{"id": "776", "text": "In addition , HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma ( IFN-gamma ) .", "annotated_text": "In addition , <dna>HLA-DRA gene</dna> expression is inducible in a variety of cell types by <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) ."}
{"id": "777", "text": "Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines , and that the high mobility group protein ( HMG ) I/Y binds to multiple sites within the DRA promoter , including the Oct-2A binding site .", "annotated_text": "Here we show that the <protein>lymphoid-specific transcription factor Oct-2A</protein> plays a critical role in <dna>HLA-DRA gene</dna> expression in <cell_line>class II-positive B cell lines</cell_line> , and that the <protein>high mobility group protein</protein> ( <protein>HMG</protein> ) <protein>I/Y</protein> binds to multiple sites within the <dna>DRA promoter</dna> , including the <dna>Oct-2A binding site</dna> ."}
{"id": "778", "text": "Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression , and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter .", "annotated_text": "Coexpression of <protein>HMG I/Y</protein> and <protein>Oct-2</protein> in <cell_line>cell lines</cell_line> lacking <protein>Oct-2</protein> results in high levels of <dna>HLA-DRA gene</dna> expression , and in vitro DNA-binding studies reveal that HMG <protein>I/Y</protein> stimulates <protein>Oct-2A</protein> binding to the <dna>HLA-DRA promoter</dna> ."}
{"id": "779", "text": "Thus , Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells .", "annotated_text": "Thus , <protein>Oct-2A</protein> and <protein>HMG I/Y</protein> may synergize to activate <dna>HLA-DRA</dna> expression in <cell_type>B cells</cell_type> ."}
{"id": "780", "text": "By contrast , Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells , but antisense HMG I/Y dramatically decreases the level of induction .", "annotated_text": "By contrast , <protein>Oct-2A</protein> is not involved in the <protein>IFN-gamma</protein> induction of the <dna>HLA-DRA gene</dna> in <cell_line>HeLa cells</cell_line> , but <dna>antisense HMG I/Y</dna> dramatically decreases the level of induction ."}
{"id": "781", "text": "We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression , and that HMG I/Y may be important for B cell-specific expression , and is essential for IFN-gamma induction .", "annotated_text": "We conclude that distinct sets of <protein>transcription factors</protein> are involved in the two modes of <dna>HLA-DRA</dna> expression , and that <protein>HMG I/Y</protein> may be important for B cell-specific expression , and is essential for <protein>IFN-gamma</protein> induction ."}
{"id": "782", "text": "Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt 's lymphoma .", "annotated_text": "Heterogeneous expression of <protein>Epstein-Barr virus latent proteins</protein> in endemic Burkitt 's lymphoma ."}
{"id": "783", "text": "Epstein-Barr virus ( EBV ) -infected cells may sustain three distinct forms of virus latency .", "annotated_text": "<cell_type>Epstein-Barr virus ( EBV ) -infected cells</cell_type> may sustain three distinct forms of virus latency ."}
{"id": "784", "text": "In lymphoblastoid cell lines , six EBV-encoded nuclear antigens ( EBNA1 , 2 , 3A , 3B , 3C , -LP ) , three latent membrane proteins ( LMP1 , 2A , 2B ) , and two nuclear RNAs ( EBERs ) are expressed .", "annotated_text": "In <cell_line>lymphoblastoid cell lines</cell_line> , six <protein>EBV-encoded nuclear antigens</protein> ( <protein>EBNA1 , 2 , 3A , 3B , 3C , -LP</protein> ) , three <protein>latent membrane proteins</protein> ( <protein>LMP1</protein> , <protein>2A</protein> , <protein>2B</protein> ) , and two <rna>nuclear RNAs</rna> ( <rna>EBERs</rna> ) are expressed ."}
{"id": "785", "text": "This form of latency , termed latency III , is also encountered in some posttransplant lymphoproliferative disorders .", "annotated_text": "This form of latency , termed latency III , is also encountered in some posttransplant lymphoproliferative disorders ."}
{"id": "786", "text": "In EBV-positive cases of Hodgkin 's disease , the EBERs , EBNA1 , and the LMPs are expressed ( latency II ) , whereas in Burkitt 's lymphoma ( BL ) only the EBERs and EBNA1 have been detected ( latency I ) .", "annotated_text": "In EBV-positive cases of Hodgkin 's disease , the <rna>EBERs</rna> , <protein>EBNA1</protein> , and the <protein>LMPs</protein> are expressed ( latency II ) , whereas in Burkitt 's lymphoma ( BL ) only the <rna>EBERs</rna> and <protein>EBNA1</protein> have been detected ( latency I ) ."}
{"id": "787", "text": "We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology .", "annotated_text": "We have studied the expression of <protein>EBV proteins</protein> in 17 cases of EBV-positive endemic BL by immunohistology ."}
{"id": "788", "text": "Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases .", "annotated_text": "Expression of <protein>LMP1</protein> was seen in variable proportions of <cell_type>tumor cells</cell_type> in two cases and <protein>EBNA2</protein> was detected in some <cell_type>tumor cells</cell_type> in three other cases ."}
{"id": "789", "text": "Also , the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases , indicating entry into the lytic cycle .", "annotated_text": "Also , the <protein>BZLF1 trans-activator protein</protein> was expressed in a few <cell_type>tumor cells</cell_type> in 6 cases , indicating entry into the lytic cycle ."}
{"id": "790", "text": "A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines .", "annotated_text": "A phenotypic drift from latency I to latency III has been observed previously in some <cell_line>BL cell lines</cell_line> ."}
{"id": "791", "text": "Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors .", "annotated_text": "Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors ."}
{"id": "792", "text": "The activation of the Jak -STAT 1 signaling pathway by IL-5 in eosinophils .", "annotated_text": "The activation of the <protein>Jak</protein> <protein>-STAT 1</protein> signaling pathway by <protein>IL-5</protein> in <cell_type>eosinophils</cell_type> ."}
{"id": "793", "text": "The intracellular signal transduction of IL-5 in eosinophils is unknown .", "annotated_text": "The intracellular signal transduction of <protein>IL-5</protein> in <cell_type>eosinophils</cell_type> is unknown ."}
{"id": "794", "text": "The objective of this study was to investigate the involvement of the newly discovered Jak -STAT pathway in the IL-5 signal transduction mechanism .", "annotated_text": "The objective of this study was to investigate the involvement of the newly discovered <protein>Jak</protein> <protein>-STAT</protein> pathway in the <protein>IL-5</protein> signal transduction mechanism ."}
{"id": "795", "text": "Eosinophils were purified from peripheral blood by discontinuous Percoll gradients and stimulated with IL-5 .", "annotated_text": "<cell_type>Eosinophils</cell_type> were purified from peripheral blood by discontinuous Percoll gradients and stimulated with <protein>IL-5</protein> ."}
{"id": "796", "text": "The involvement of Jak 2 was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .", "annotated_text": "The involvement of <protein>Jak 2</protein> was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation ."}
{"id": "797", "text": "The activation of Jak 2 was studied by autophosphorylation of the immunoprecipitated kinase .", "annotated_text": "The activation of <protein>Jak 2</protein> was studied by autophosphorylation of the <protein>immunoprecipitated kinase</protein> ."}
{"id": "798", "text": "Jak 2 was tyrosine phosphorylated within 1 to 3 min after stimulation of eosinophils with IL-5 .", "annotated_text": "<protein>Jak 2</protein> was tyrosine phosphorylated within 1 to 3 min after stimulation of <cell_type>eosinophils</cell_type> with <protein>IL-5</protein> ."}
{"id": "799", "text": "Further , the immunoprecipitated Jak 2 obtained from IL-5-stimulated cells underwent autophosphorylation .", "annotated_text": "Further , the <protein>immunoprecipitated Jak 2</protein> obtained from <cell_line>IL-5-stimulated cells</cell_line> underwent autophosphorylation ."}
{"id": "800", "text": "Jak 2 coprecipitated with the beta-subunit of the IL-5 receptor , suggesting a physical association of the kinase with the receptor .", "annotated_text": "<protein>Jak 2</protein> coprecipitated with the beta-subunit of the <protein>IL-5 receptor</protein> , suggesting a physical association of the <protein>kinase</protein> with the receptor ."}
{"id": "801", "text": "The nuclear factor STAT-1 ( p91 ) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .", "annotated_text": "The <protein>nuclear factor STAT-1</protein> ( <protein>p91</protein> ) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation ."}
{"id": "802", "text": "STAT-1 was tyrosine phosphorylated within 15 min of IL-5 stimulation .", "annotated_text": "<protein>STAT-1</protein> was tyrosine phosphorylated within 15 min of <protein>IL-5</protein> stimulation ."}
{"id": "803", "text": "The presence of STAT-1 in the nuclear extract was studied by electrophoretic mobility shift assay .", "annotated_text": "The presence of <protein>STAT-1</protein> in the nuclear extract was studied by electrophoretic mobility shift assay ."}
{"id": "804", "text": "IL-5 induced two proteins that bound to the gamma-activating sequence .", "annotated_text": "<protein>IL-5</protein> induced two proteins that bound to the <dna>gamma-activating sequence</dna> ."}
{"id": "805", "text": "In the presence of an anti-STAT-1 Ab , the band was supershifted .", "annotated_text": "In the presence of an <protein>anti-STAT-1 Ab</protein> , the band was supershifted ."}
{"id": "806", "text": "Thus , we demonstrated that IL-5 activated the Jak 2 -STAT 1 signaling pathway in eosinophils .", "annotated_text": "Thus , we demonstrated that <protein>IL-5</protein> activated the <protein>Jak 2</protein> <protein>-STAT 1</protein> signaling pathway in <cell_type>eosinophils</cell_type> ."}
{"id": "807", "text": "We speculate that the Jak 2 -STAT 1 pathway may be involved in the activation of IL-5-inducible genes in eosinophils .", "annotated_text": "We speculate that the <protein>Jak 2</protein> <protein>-STAT 1</protein> pathway may be involved in the activation of <dna>IL-5-inducible genes</dna> in <cell_type>eosinophils</cell_type> ."}
{"id": "808", "text": "Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer : a prospective longitudinal study .", "annotated_text": "Reduced mitogenic stimulation of <cell_type>peripheral blood mononuclear cells</cell_type> as a prognostic parameter for the course of breast cancer : a prospective longitudinal study ."}
{"id": "809", "text": "Immunosuppression has been often associated with the course of malignant diseases .", "annotated_text": "Immunosuppression has been often associated with the course of malignant diseases ."}
{"id": "810", "text": "In the present study , the proliferation of peripheral blood mononuclear cells ( PBMCs ) in response to mitogenic stimulation with phytohaemagglutinin ( PHA ) was assessed prospectively in 90 patients with stage I-III breast cancer .", "annotated_text": "In the present study , the proliferation of <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) in response to mitogenic stimulation with <protein>phytohaemagglutinin</protein> ( <protein>PHA</protein> ) was assessed prospectively in 90 patients with stage I-III breast cancer ."}
{"id": "811", "text": "Whereas PHA -induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals ( P < 0.001 ) , the degree of the defect in PHA -induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement ( P < 0.003 in each case ) .", "annotated_text": "Whereas <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals ( P < 0.001 ) , the degree of the defect in <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement ( P < 0.003 in each case ) ."}
{"id": "812", "text": "PHA -induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide , methotrexate and fluorouracil ( CMF ) after an observation period of 6 months ( P < 0.01 ) , but not in patients under adjuvant treatment with tamoxifen only .", "annotated_text": "<protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide , methotrexate and fluorouracil ( CMF ) after an observation period of 6 months ( P < 0.01 ) , but not in patients under adjuvant treatment with tamoxifen only ."}
{"id": "813", "text": "After an additional 6 months ( i.e. 12 months after surgery ) , PHA -induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment ( P > 0.1 ) , but in all patients still significantly decreased as compared with healthy controls ( P < 0.001 ) .", "annotated_text": "After an additional 6 months ( i.e. 12 months after surgery ) , <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment ( P > 0.1 ) , but in all patients still significantly decreased as compared with healthy controls ( P < 0.001 ) ."}
{"id": "814", "text": "When data obtained preoperatively and after 12 months were compared , it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA -induced proliferation , 14 ( 61 % ) had developed metastatic disease within the subsequent 24 months ( i.e. 36 months after surgery ) .", "annotated_text": "When data obtained preoperatively and after 12 months were compared , it was found that out of 23 patients whose <cell_type>PBMCs</cell_type> had experienced a drop in their <protein>PHA</protein> -induced proliferation , 14 ( 61 % ) had developed metastatic disease within the subsequent 24 months ( i.e. 36 months after surgery ) ."}
{"id": "815", "text": "In contrast , out of 59 patients whose PBMCs showed an increase in their PHA -induced proliferation within the first 12 months after surgery , only one ( 2 % ) presented with disease progression .", "annotated_text": "In contrast , out of 59 patients whose <cell_type>PBMCs</cell_type> showed an increase in their <protein>PHA</protein> -induced proliferation within the first 12 months after surgery , only one ( 2 % ) presented with disease progression ."}
{"id": "816", "text": "We thus conclude that PHA -induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease .", "annotated_text": "We thus conclude that <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease ."}
{"id": "817", "text": "Activation of transcription by binding of NF-E1 ( YY1 ) to a newly identified element in the first exon of the human DR alpha gene .", "annotated_text": "Activation of transcription by binding of <protein>NF-E1</protein> ( <protein>YY1</protein> ) to a newly identified element in the first exon of the <dna>human DR alpha gene</dna> ."}
{"id": "818", "text": "A previously unrecognized element , located downstream of the start site of transcription in the first exon of the DR alpha gene , has been defined that enhances promoter activity up to eightfold in a position-dependent manner .", "annotated_text": "A previously unrecognized element , located downstream of the <dna>start site of transcription</dna> in the first <dna>exon</dna> of the <dna>DR alpha gene</dna> , has been defined that enhances promoter activity up to eightfold in a position-dependent manner ."}
{"id": "819", "text": "Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level .", "annotated_text": "Mutations in this <dna>DNA-binding site</dna> abolished binding of a <protein>nuclear factor</protein> in human B cell nuclear extract and decreased the activity of the <dna>DR alpha promoter</dna> to a basal level ."}
{"id": "820", "text": "Significant sequence homology of this element was found in the DNA of the DR beta , DP alpha and -beta , and DQ alpha genes , always located downstream of the transcriptional start site .", "annotated_text": "Significant sequence homology of this <dna>element</dna> was found in the DNA of the <dna>DR beta , DP alpha and -beta , and DQ alpha genes</dna> , always located downstream of the <dna>transcriptional start site</dna> ."}
{"id": "821", "text": "The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene .", "annotated_text": "The nuclear factor binds to the <dna>DR alpha and DP alpha element</dna> but not to the element in the <dna>DQ alpha gene</dna> ."}
{"id": "822", "text": "It was identified as NF-E1 ( YY1 ) .", "annotated_text": "It was identified as <protein>NF-E1</protein> ( <protein>YY1</protein> ) ."}
{"id": "823", "text": "This protein , previously identified by its binding to the Ig kappa 3 ' enhancer and the Ig heavy chain mu E1 site , thus also appears to be quite important in the regulation of MHC class II gene expression .", "annotated_text": "This protein , previously identified by its binding to the <dna>Ig kappa 3 ' enhancer</dna> and the <dna>Ig heavy chain mu E1 site</dna> , thus also appears to be quite important in the regulation of <dna>MHC class II gene</dna> expression ."}
{"id": "824", "text": "Transcriptional activity of core binding factor-alpha ( AML1 ) and beta subunits on murine leukemia virus enhancer cores .", "annotated_text": "Transcriptional activity of <protein>core binding factor-alpha ( AML1 ) and beta</protein> subunits on <dna>murine leukemia virus enhancer cores</dna> ."}
{"id": "825", "text": "Core binding factor ( CBF ) , also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1 , is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses .", "annotated_text": "<protein>Core binding factor</protein> ( <protein>CBF</protein> ) , also known as <protein>polyomavirus enhancer-binding protein 2</protein> and <protein>SL3 enhancer factor 1</protein> , is a <protein>mammalian transcription factor</protein> that binds to an element termed the core within the <dna>enhancers</dna> of the murine leukemia virus family of retroviruses ."}
{"id": "826", "text": "The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes .", "annotated_text": "The <dna>core elements</dna> of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the <dna>viral long terminal repeat</dna> in <cell_type>T lymphocytes</cell_type> ."}
{"id": "827", "text": "CBF consists of two subunits , a DNA binding subunit , CBF alpha , and a second subunit , CBF beta , that stimulates the DNA binding activity of CBF alpha .", "annotated_text": "<protein>CBF</protein> consists of two subunits , a <protein>DNA binding subunit</protein> , <protein>CBF alpha</protein> , and a second subunit , <protein>CBF beta</protein> , that stimulates the DNA binding activity of <protein>CBF alpha</protein> ."}
{"id": "828", "text": "One of the genes that encodes a CBF alpha subunit is AML1 , also called Cbf alpha 2 .", "annotated_text": "One of the genes that encodes a <protein>CBF alpha subunit</protein> is <protein>AML1</protein> , also called <protein>Cbf alpha 2</protein> ."}
{"id": "829", "text": "This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias .", "annotated_text": "This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias ."}
{"id": "830", "text": "An exogenously expressed Cbf alpha 2-encoded subunit ( CBF alpha 2-451 ) stimulated transcription from the SL3 enhancer in P19 and HeLa cells .", "annotated_text": "An exogenously expressed <protein>Cbf alpha 2-encoded subunit</protein> ( <protein>CBF alpha 2-451</protein> ) stimulated transcription from the <dna>SL3 enhancer</dna> in <protein>P19</protein> and <cell_line>HeLa cells</cell_line> ."}
{"id": "831", "text": "Activity was mediated through the core elements .", "annotated_text": "Activity was mediated through the <dna>core elements</dna> ."}
{"id": "832", "text": "Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer .", "annotated_text": "Three different isoforms of <protein>CBF beta</protein> were also tested for transcriptional activity on the <dna>SL3 enhancer</dna> ."}
{"id": "833", "text": "The longest form , CBF beta-187 , increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells , although it had no effect in P19 cells .", "annotated_text": "The longest form , <protein>CBF beta-187</protein> , increased the transcriptional stimulation by <protein>CBF alpha 2-451</protein> twofold in <cell_line>HeLa cells</cell_line> , although it had no effect in <cell_line>P19 cells</cell_line> ."}
{"id": "834", "text": "Transcriptional activation by CBF beta required binding to the CBF alpha subunit , as a form of CBF beta that lacked binding ability , CBF beta-148 , failed to increase activity .", "annotated_text": "Transcriptional activation by <protein>CBF beta</protein> required binding to the <protein>CBF alpha subunit</protein> , as a form of <protein>CBF beta</protein> that lacked binding ability , <protein>CBF beta-148</protein> , failed to increase activity ."}
{"id": "835", "text": "These results indicated that at least in certain cell types , the maximum activity of CBF required both subunits .", "annotated_text": "These results indicated that at least in certain cell types , the maximum activity of <protein>CBF</protein> required both subunits ."}
{"id": "836", "text": "They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores .", "annotated_text": "They also provided support for the hypothesis that <protein>CBF</protein> is a factor in <cell_type>T lymphocytes</cell_type> that is responsible for recognition of the <dna>SL3 cores</dna> ."}
{"id": "837", "text": "We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus , Akv .", "annotated_text": "We also examined whether <protein>CBF</protein> could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus , Akv ."}
{"id": "838", "text": "This difference strongly affects transcription in T cells and leukemogenicity of SL3 .", "annotated_text": "This difference strongly affects transcription in T cells and leukemogenicity of <dna>SL3</dna> ."}
{"id": "839", "text": "However , no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays .", "annotated_text": "However , no combination of <protein>CBF alpha</protein> and <protein>CBF beta</protein> subunits that we tested was able to distinguish the 1-bp difference in transcription assays ."}
{"id": "840", "text": "Thus , a complete understanding of how T cells recognize the SL3 core remains to be elucidated .", "annotated_text": "Thus , a complete understanding of how <cell_type>T cells</cell_type> recognize the <dna>SL3 core</dna> remains to be elucidated ."}
{"id": "841", "text": "Interleukin ( IL ) -10 inhibits nuclear factor kappa B ( NF kappa B ) activation in human monocytes .", "annotated_text": "<protein>Interleukin ( IL ) -10</protein> inhibits <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) activation in <cell_type>human monocytes</cell_type> ."}
{"id": "842", "text": "IL-10 and IL-4 suppress cytokine synthesis by different mechanisms .", "annotated_text": "<protein>IL-10</protein> and <protein>IL-4</protein> suppress <protein>cytokine</protein> synthesis by different mechanisms ."}
{"id": "843", "text": "Our previous studies in human monocytes have demonstrated that interleukin ( IL ) -10 inhibits lipopolysaccharide ( LPS ) -stimulated production of inflammatory cytokines , IL-1 beta , IL-6 , IL-8 , and tumor necrosis factor ( TNF ) -alpha by blocking gene transcription .", "annotated_text": "Our previous studies in <cell_type>human monocytes</cell_type> have demonstrated that <protein>interleukin ( IL ) -10</protein> inhibits lipopolysaccharide ( LPS ) -stimulated production of <protein>inflammatory cytokines</protein> , <protein>IL-1 beta</protein> , <protein>IL-6</protein> , <protein>IL-8</protein> , and <protein>tumor necrosis factor ( TNF ) -alpha</protein> by blocking gene transcription ."}
{"id": "844", "text": "Using electrophoretic mobility shift assays ( EMSA ) , we now show that , in monocytes stimulated with LPS or TNF alpha , IL-10 inhibits nuclear stimulation of nuclear factor kappa B ( NF kappa B ) , a transcription factor involved in the expression of inflammatory cytokine genes . Several other transcription factors including NF- IL-6 , AP-1 , AP-2 , GR , CREB , Oct-1 , and Sp-1 are not affected by IL-10 .", "annotated_text": "Using electrophoretic mobility shift assays ( EMSA ) , we now show that , in monocytes stimulated with LPS or <protein>TNF alpha</protein> , <protein>IL-10</protein> inhibits nuclear stimulation of <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) , a <protein>transcription factor</protein> involved in the expression of <dna>inflammatory cytokine genes</dna> . Several other <protein>transcription factors</protein> including NF- <protein>IL-6</protein> , <protein>AP-1</protein> , <protein>AP-2</protein> , <protein>GR</protein> , <protein>CREB</protein> , <protein>Oct-1</protein> , and <protein>Sp-1</protein> are not affected by <protein>IL-10</protein> ."}
{"id": "845", "text": "This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10 's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness .", "annotated_text": "This selective inhibition by <protein>IL-10</protein> of <protein>NF kappa B</protein> activation occurs rapidly and in a dose-dependent manner and correlates well with <protein>IL-10</protein> 's <protein>cytokine</protein> synthesis inhibitory activity in terms of both kinetics and dose responsiveness ."}
{"id": "846", "text": "Furthermore , compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes .", "annotated_text": "Furthermore , compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit <protein>NF kappa B</protein> activation block cytokine gene transcription in <cell_line>LPS-stimulated monocytes</cell_line> ."}
{"id": "847", "text": "Taken together , these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes .", "annotated_text": "Taken together , these results suggest that inhibition of <protein>NF kappa B</protein> activation may be an important mechanism for <protein>IL-10</protein> suppression of cytokine gene transcription in <cell_type>human monocytes</cell_type> ."}
{"id": "848", "text": "IL-4 , another cytokine that inhibits cytokine mRNA accumulation in monocytes , shows little inhibitory effect on LPS-induced NF kappa B activation .", "annotated_text": "<protein>IL-4</protein> , another <protein>cytokine</protein> that inhibits <rna>cytokine mRNA</rna> accumulation in <cell_type>monocytes</cell_type> , shows little inhibitory effect on LPS-induced <protein>NF kappa B</protein> activation ."}
{"id": "849", "text": "Further examination reveals that , unlike IL-10 , IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription .", "annotated_text": "Further examination reveals that , unlike <protein>IL-10</protein> , <protein>IL-4</protein> enhances <rna>mRNA</rna> degradation and does not suppress cytokine gene transcription ."}
{"id": "850", "text": "These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms .", "annotated_text": "These data indicate that <protein>IL-10</protein> and <protein>IL-4</protein> inhibit <protein>cytokine</protein> production by different mechanisms ."}
{"id": "851", "text": "LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha .", "annotated_text": "<protein>LMP-1</protein> activates <protein>NF-kappa B</protein> by targeting the <protein>inhibitory molecule I kappa B alpha</protein> ."}
{"id": "852", "text": "LMP-1 , an Epstein-Barr virus membrane protein expressed during latent infection , has oncogenic properties , as judged from its ability to transform B lymphocytes and rodent fibroblasts .", "annotated_text": "<protein>LMP-1</protein> , an <protein>Epstein-Barr virus membrane protein</protein> expressed during latent infection , has oncogenic properties , as judged from its ability to transform B <cell_type>lymphocytes</cell_type> and <cell_type>rodent fibroblasts</cell_type> ."}
{"id": "853", "text": "LMP-1 induces the expression of bcl2 , an oncogene which protects cells from apoptosis , as well as of genes encoding other proteins involved in cell regulation and growth control .", "annotated_text": "<protein>LMP-1</protein> induces the expression of <dna>bcl2</dna> , an <dna>oncogene</dna> which protects cells from apoptosis , as well as of genes encoding other proteins involved in cell regulation and growth control ."}
{"id": "854", "text": "The mechanisms by which LMP-1 upregulates these proteins is unknown , but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes .", "annotated_text": "The mechanisms by which <protein>LMP-1</protein> upregulates these proteins is unknown , but it is plausible that <protein>LMP-1</protein> modifies signal transduction pathways that result in the activation of one or more <protein>transcription factors</protein> that ultimately regulate transcription of <dna>oncogenic genes</dna> ."}
{"id": "855", "text": "NF-kappa B , a transcription factor controlling the expression of genes involved in cell activation and growth control , has been shown to be activated by LMP-1 .", "annotated_text": "<protein>NF-kappa B</protein> , a <protein>transcription factor</protein> controlling the expression of <dna>genes</dna> involved in cell activation and growth control , has been shown to be activated by <protein>LMP-1</protein> ."}
{"id": "856", "text": "The mechanism ( s ) regulating this activation remains unknown .", "annotated_text": "The mechanism ( s ) regulating this activation remains unknown ."}
{"id": "857", "text": "Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1 .", "annotated_text": "Our data indicate that increased <protein>NF-kappa B</protein> DNA binding and functional activity are present in <cell_type>B-lymphoid cells</cell_type> stably or transiently expressing <protein>LMP-1</protein> ."}
{"id": "858", "text": "I kappa B alpha is selectively modified in LMP-1-expressing B cells .", "annotated_text": "<protein>I kappa B alpha</protein> is selectively modified in <cell_line>LMP-1-expressing B cells</cell_line> ."}
{"id": "859", "text": "A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation .", "annotated_text": "A phosphorylated form of <protein>I kappa B alpha</protein> and increased protein turnover-degradation correlate with increased <protein>NF-kappa B</protein> nuclear translocation ."}
{"id": "860", "text": "This results in increased transcription of NF-kappa B-dependent-genes , including those encoding p105 and I kappa B alpha ( MAD3 ) .", "annotated_text": "This results in increased transcription of <dna>NF-kappa B-dependent-genes</dna> , including those encoding <protein>p105</protein> and <protein>I kappa B alpha</protein> ( <dna>MAD3</dna> ) ."}
{"id": "861", "text": "These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha .", "annotated_text": "These results indicate that <protein>LMP-1</protein> activates <protein>NF-kappa B</protein> in <cell_line>B-cell lines</cell_line> by targeting <protein>I kappa B alpha</protein> ."}
{"id": "862", "text": "Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis .", "annotated_text": "Identification of the pathways activated by <protein>LMP-1</protein> to result in posttranslational modifications of <protein>I kappa B alpha</protein> will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis ."}
{"id": "863", "text": "Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [ published erratum appears in J Biol Chem 1995 Nov 3 ; 270 ( 44 ) : 26721 ]", "annotated_text": "Identification of <dna>human TR2 orphan receptor response element</dna> in the <dna>transcriptional initiation site</dna> of the <dna>simian virus 40 major late promoter</dna> [ published erratum appears in J Biol Chem 1995 Nov 3 ; 270 ( 44 ) : 26721 ]"}
{"id": "864", "text": "A DNA response element ( TR2RE-SV40 ) for the TR2 orphan receptor , a member of the steroid-thyroid hormone receptor superfamily , has been identified in the simian virus 40 ( SV40 ) +55 region ( nucleotide numbers 368-389 , 5'-GTTAAGGTTCGTAGGTCATGGA-3 ' ) .", "annotated_text": "A <dna>DNA response element</dna> ( <dna>TR2RE-SV40</dna> ) for the <protein>TR2 orphan receptor</protein> , a member of the <protein>steroid-thyroid hormone receptor superfamily</protein> , has been identified in the <dna>simian virus 40 ( SV40 ) +55 region</dna> ( <dna>nucleotide numbers 368-389</dna> , 5'-GTTAAGGTTCGTAGGTCATGGA-3 ' ) ."}
{"id": "865", "text": "Electrophoretic mobility shift assay , using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons , showed a specific binding with high affinity ( dissociation constant = 9 nM ) for this DNA sequence .", "annotated_text": "Electrophoretic mobility shift assay , using in vitro translated <protein>TR2 orphan receptor</protein> with a molecular mass of <protein>67 kilodaltons</protein> , showed a specific binding with high affinity ( dissociation constant = 9 nM ) for this DNA sequence ."}
{"id": "866", "text": "DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor .", "annotated_text": "DNA-swap experiments using <protein>chloramphenicol acetyl-transferase</protein> assay demonstrated that androgen can suppress the transcriptional activities of <dna>SV40 early promoter</dna> via the interaction between this <dna>TR2RE-SV40</dna> and the <protein>chimeric receptor AR/TR2/AR</protein> with the <protein>DNA-binding domain</protein> of the <protein>TR2 orphan receptor</protein> flanked by the <protein>N-terminal and androgen-binding domains</protein> of the <protein>androgen receptor</protein> ."}
{"id": "867", "text": "In addition , this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters .", "annotated_text": "In addition , this <dna>TR2RE-SV40</dna> can function as a repressor to suppress the transcriptional activities of both <dna>SV40 early and late promoters</dna> ."}
{"id": "868", "text": "Together , these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression .", "annotated_text": "Together , these data suggest the <dna>TR2RE-SV40</dna> may represent the first identified natural <dna>DNA response element</dna> for the <protein>TR2 orphan receptor</protein> that may function as a repressor for the SV40 gene expression ."}
{"id": "869", "text": "Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias .", "annotated_text": "Detection of the <rna>chromosome 16 CBF beta-MYH11 fusion transcript</rna> in myelomonocytic leukemias ."}
{"id": "870", "text": "Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult .", "annotated_text": "Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult ."}
{"id": "871", "text": "Characterization of the two genes involved in the inv ( 16 ) ( p13q22 ) , CBF beta and MYH11 , has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .", "annotated_text": "Characterization of the two genes involved in the inv ( 16 ) ( p13q22 ) , <dna>CBF beta</dna> and <dna>MYH11</dna> , has allowed the detection of <rna>fusion transcripts</rna> by reverse-transcriptase polymerase chain reaction ( RT-PCR ) ."}
{"id": "872", "text": "We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias , with or without eosinophilia , to determine whether their presence correlates with morphology .", "annotated_text": "We have analyzed <rna>CBF beta-MYH11 fusion transcripts</rna> by RT-PCR in myelomonocytic leukemias , with or without eosinophilia , to determine whether their presence correlates with morphology ."}
{"id": "873", "text": "Fifty-three cases ( 11 AML M4Eo ; 1 AML M4 with atypical abnormal eosinophils ( AML M4 `` Eo '' ) ; 29 AML M4 ; 8 AML M5 ; 3 CMML ; and 1 AML M2 with eosinophilia ) were analyzed .", "annotated_text": "Fifty-three cases ( 11 AML M4Eo ; 1 AML M4 with <cell_type>atypical abnormal eosinophils</cell_type> ( AML M4 `` Eo '' ) ; 29 AML M4 ; 8 AML M5 ; 3 CMML ; and 1 AML M2 with eosinophilia ) were analyzed ."}
{"id": "874", "text": "All 11 typical AML M4Eo were CBF beta -MYH11 positive .", "annotated_text": "All 11 typical AML M4Eo were <dna>CBF beta</dna> <dna>-MYH11</dna> positive ."}
{"id": "875", "text": "The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype , RT-PCR and fluorescent in situ hybridization ( FISH ) .", "annotated_text": "The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype , RT-PCR and fluorescent in situ hybridization ( FISH ) ."}
{"id": "876", "text": "Three of 29 ( 10 % ) AML M4 without abnormal eosinophils were CBF beta -MYH11 positive , 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis ( 2 not tested ) .", "annotated_text": "Three of 29 ( 10 % ) AML M4 without <cell_type>abnormal eosinophils</cell_type> were <dna>CBF beta</dna> <dna>-MYH11</dna> positive , 1 of which did not show any apparent <dna>chromosome 16</dna> abnormalities by classical metaphase analysis ( 2 not tested ) ."}
{"id": "877", "text": "Both cases tested also showed MYH11 genomic rearrangement .", "annotated_text": "Both cases tested also showed <dna>MYH11</dna> genomic rearrangement ."}
{"id": "878", "text": "of the other leukemias were RT-PCR positive .", "annotated_text": "of the other leukemias were RT-PCR positive ."}
{"id": "879", "text": "Follow-up of three patient showed residual positivity in apparent complete remission .", "annotated_text": "Follow-up of three patient showed residual positivity in apparent complete remission ."}
{"id": "880", "text": "These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo , but also in approximately 10 % of AML M4 without eosinophilic abnormalities , a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest .", "annotated_text": "These data show that <rna>CBF beta-MYH11 fusion transcripts</rna> occur not only in the vast majority of typical AML M4Eo , but also in approximately 10 % of AML M4 without eosinophilic abnormalities , a much higher incidence than the sporadic reports of <dna>chromosome 16</dna> abnormalities in AML M4 would suggest ."}
{"id": "881", "text": "Taken together with the detection of CBF beta - MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques , these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4 , regardless of morphologic features , to allow accurate evaluation of the prognostic importance of this fusion transcript .", "annotated_text": "Taken together with the detection of <dna>CBF beta</dna> - <rna>MYH11 transcripts</rna> in the absence of apparent <dna>chromosome 16</dna> abnormalities by classical banding techniques , these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4 , regardless of morphologic features , to allow accurate evaluation of the prognostic importance of this <rna>fusion transcript</rna> ."}
{"id": "882", "text": "HIV-1 Tat potentiates TNF -induced NF-kappa B activation and cytotoxicity by altering the cellular redox state .", "annotated_text": "<protein>HIV-1 Tat</protein> potentiates <protein>TNF</protein> -induced <protein>NF-kappa B</protein> activation and cytotoxicity by altering the cellular redox state ."}
{"id": "883", "text": "This study demonstrates that human immunodeficiency virus type 1 ( HIV-1 ) Tat protein amplifies the activity of tumor necrosis factor ( TNF ) , a cytokine that stimulates HIV-1 replication through activation of NF-kappa B .", "annotated_text": "This study demonstrates that <protein>human immunodeficiency virus type 1 ( HIV-1 ) Tat protein</protein> amplifies the activity of <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , a cytokine that stimulates HIV-1 replication through activation of <protein>NF-kappa B</protein> ."}
{"id": "884", "text": "In HeLa cells stably transfected with the HIV-1 tat gene ( HeLa-tat cells ) , expression of the Tat protein enhanced both TNF -induced activation of NF-kappa B and TNF -mediated cytotoxicity .", "annotated_text": "In <cell_line>HeLa cells</cell_line> stably transfected with the <dna>HIV-1 tat gene</dna> ( <cell_line>HeLa-tat cells</cell_line> ) , expression of the <protein>Tat protein</protein> enhanced both <protein>TNF</protein> -induced activation of <protein>NF-kappa B</protein> and <protein>TNF</protein> -mediated cytotoxicity ."}
{"id": "885", "text": "A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein .", "annotated_text": "A similar potentiation of <protein>TNF</protein> effects was observed in Jurkat T cells and <cell_line>HeLa cells</cell_line> treated with soluble <protein>Tat protein</protein> ."}
{"id": "886", "text": "TNF -mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates .", "annotated_text": "<protein>TNF</protein> -mediated activation of <protein>NF-kappa B</protein> and cytotoxicity involves the intracellular formation of reactive oxygen intermediates ."}
{"id": "887", "text": "Therefore , Tat -mediated effects on the cellular redox state were analyzed .", "annotated_text": "Therefore , <protein>Tat</protein> -mediated effects on the cellular redox state were analyzed ."}
{"id": "888", "text": "In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase ( Mn-SOD ) , a mitochondrial enzyme that is part of the cellular defense system against oxidative stress .", "annotated_text": "In both <cell_type>T cells</cell_type> and <cell_line>HeLa cells</cell_line> <protein>HIV-1 Tat</protein> suppressed the expression of <protein>Mn-dependent superoxide dismutase</protein> ( <protein>Mn-SOD</protein> ) , a <protein>mitochondrial enzyme</protein> that is part of the cellular defense system against oxidative stress ."}
{"id": "889", "text": "Thus , Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat .", "annotated_text": "Thus , <protein>Mn-SOD</protein> RNA protein levels and activity were markedly reduced in the presence of <protein>Tat</protein> ."}
{"id": "890", "text": "Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced : oxidized glutathione .", "annotated_text": "Decreased <protein>Mn-SOD</protein> expression was associated with decreased levels of glutathione and a lower ratio of reduced : oxidized glutathione ."}
{"id": "891", "text": "A truncated Tat protein ( Tat1-72 ) , known to transactivate the HIV-1 long terminal repeat ( LTR ) , no longer affected Mn-SOD expression , the cellular redox state or TNF -mediated cytotoxicity .", "annotated_text": "A truncated <protein>Tat protein</protein> ( <protein>Tat1-72</protein> ) , known to transactivate the <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) , no longer affected <protein>Mn-SOD</protein> expression , the cellular redox state or <protein>TNF</protein> -mediated cytotoxicity ."}
{"id": "892", "text": "Thus , our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione ( GSH ) and the GSH : oxidized GSH ( GSSG ) ratio .", "annotated_text": "Thus , our experiments demonstrate that the <protein>C-terminal region</protein> of <protein>HIV-1 Tat</protein> is required to suppress <protein>Mn-SOD</protein> expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione ( <protein>GSH</protein> ) and the GSH : oxidized GSH ( GSSG ) ratio ."}
{"id": "893", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "894", "text": "The use of glucocorticoids in acute lymphoblastic leukemia of childhood .", "annotated_text": "The use of glucocorticoids in acute lymphoblastic leukemia of childhood ."}
{"id": "895", "text": "Molecular , cellular , and clinical considerations .", "annotated_text": "Molecular , cellular , and clinical considerations ."}
{"id": "896", "text": "Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades .", "annotated_text": "Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades ."}
{"id": "897", "text": "However , optimal agents , doses , and/or schedules have yet to be defined despite extensive clinical application .", "annotated_text": "However , optimal agents , doses , and/or schedules have yet to be defined despite extensive clinical application ."}
{"id": "898", "text": "New data on the pharmacokinetics , pharmacodynamics , and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL .", "annotated_text": "New data on the pharmacokinetics , pharmacodynamics , and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL ."}
{"id": "899", "text": "These suggest that prolonged , i.e. 28 day , glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of glucocorticoid receptors .", "annotated_text": "These suggest that prolonged , i.e. 28 day , glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of <protein>glucocorticoid receptors</protein> ."}
{"id": "900", "text": "Dexamethasone may be superior to prednisone in conventional equi-effective doses .", "annotated_text": "Dexamethasone may be superior to prednisone in conventional equi-effective doses ."}
{"id": "901", "text": "Blast sensitivity to glucocorticoids correlates closely with sensitivity to other , putatively non-cross-resisting agents and with outcome after multi-agent therapy , suggesting overlapping mechanisms of action , and focusing attention on the determinants of the threshold for apoptosis .", "annotated_text": "Blast sensitivity to glucocorticoids correlates closely with sensitivity to other , putatively non-cross-resisting agents and with outcome after multi-agent therapy , suggesting overlapping mechanisms of action , and focusing attention on the determinants of the threshold for apoptosis ."}
{"id": "902", "text": "Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy , especially in adolescent and young adult patients .", "annotated_text": "Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy , especially in adolescent and young adult patients ."}
{"id": "903", "text": "Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1 .", "annotated_text": "<protein>Epstein-Barr virus nuclear protein 2</protein> transactivation of the <dna>latent membrane protein 1 promoter</dna> is mediated by <protein>J kappa</protein> and <protein>PU.1</protein> ."}
{"id": "904", "text": "Expression of the Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene is regulated by the EBV nuclear protein 2 ( EBNA-2 ) transactivator .", "annotated_text": "Expression of the <dna>Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene</dna> is regulated by the <protein>EBV nuclear protein 2 ( EBNA-2 ) transactivator</protein> ."}
{"id": "905", "text": "EBNA-2 is known to interact with the cellular DNA-binding protein J kappa and is recruited to promoters containing the GTGGGAA J kappa recognition sequence .", "annotated_text": "<protein>EBNA-2</protein> is known to interact with the <protein>cellular DNA-binding protein</protein> <protein>J kappa</protein> and is recruited to <dna>promoters</dna> containing the GTGGGAA <dna>J kappa recognition sequence</dna> ."}
{"id": "906", "text": "The minimal EBNA-2-responsive LMP-1 promoter includes one J kappa-binding site , and we now show that mutation of that site , such that J kappa can not bind , reduces EBNA-2 responsiveness by 60 % .", "annotated_text": "The <dna>minimal EBNA-2-responsive LMP-1 promoter</dna> includes one <dna>J kappa-binding site</dna> , and we now show that mutation of that site , such that <protein>J kappa</protein> can not bind , reduces <protein>EBNA-2</protein> responsiveness by 60 % ."}
{"id": "907", "text": "To identify other factors which interact with the LMP-1 EBNA-2 response element ( E2RE ) , a -236/-145 minimal E2RE was used as a probe in an electrophoretic mobility shift assay .", "annotated_text": "To identify other factors which interact with the <dna>LMP-1 EBNA-2 response element</dna> ( <dna>E2RE</dna> ) , a <dna>-236/-145 minimal E2RE</dna> was used as a probe in an electrophoretic mobility shift assay ."}
{"id": "908", "text": "The previously characterized factors J kappa , PU.1 , and AML1 bind to the LMP-1 E2RE , along with six other unidentified factors ( LBF2 to LBF7 ) .", "annotated_text": "The previously characterized factors <protein>J kappa</protein> , <protein>PU.1</protein> , and <protein>AML1</protein> bind to the <dna>LMP-1 E2RE</dna> , along with six other unidentified factors ( <protein>LBF2</protein> to <protein>LBF7</protein> ) ."}
{"id": "909", "text": "Binding sites were mapped for each factor .", "annotated_text": "Binding sites were mapped for each factor ."}
{"id": "910", "text": "LBF4 is B- and T-cell specific and recognizes the PU.1 GGAA core sequence as shown by methylation interference .", "annotated_text": "<protein>LBF4</protein> is B- and T-cell specific and recognizes the <dna>PU.1 GGAA core sequence</dna> as shown by methylation interference ."}
{"id": "911", "text": "LBF4 has a molecular mass of 105 kDa and is probably unrelated to PU.1 .", "annotated_text": "<protein>LBF4</protein> has a molecular mass of 105 kDa and is probably unrelated to <protein>PU.1</protein> ."}
{"id": "912", "text": "LBF2 was found only in epithelial cell lines , whereas LBF3 , LBF5 , LBF6 , and LBF7 were not cell type specific .", "annotated_text": "<protein>LBF2</protein> was found only in <cell_line>epithelial cell lines</cell_line> , whereas <protein>LBF3</protein> , <protein>LBF5</protein> , <protein>LBF6</protein> , and <protein>LBF7</protein> were not cell type specific ."}
{"id": "913", "text": "Mutations of the AML1- or LBF4-binding sites had no effect on EBNA-2 transactivation , whereas mutation of the PU.1-binding site completely eliminated EBNA-2 responses .", "annotated_text": "Mutations of the <dna>AML1- or LBF4-binding sites</dna> had no effect on <protein>EBNA-2</protein> transactivation , whereas mutation of the <dna>PU.1-binding site</dna> completely eliminated <protein>EBNA-2</protein> responses ."}
{"id": "914", "text": "A gst-EBNA-2 fusion protein specifically depleted PU.1 from nuclear extracts and bound in vitro translated PU.1 , providing biochemical evidence for a direct EBNA-2 -PU.1 interaction .", "annotated_text": "A <protein>gst-EBNA-2 fusion protein</protein> specifically depleted <protein>PU.1</protein> from nuclear extracts and bound in vitro translated <protein>PU.1</protein> , providing biochemical evidence for a direct <protein>EBNA-2</protein> <protein>-PU.1</protein> interaction ."}
{"id": "915", "text": "Thus , EBNA-2 transactivation of the LMP-1 promoter is dependent on interaction with at least two distinct sequence-specific DNA-binding proteins , J kappa and PU.1 .", "annotated_text": "Thus , <protein>EBNA-2</protein> transactivation of the <dna>LMP-1 promoter</dna> is dependent on interaction with at least two distinct sequence-specific <protein>DNA-binding proteins</protein> , <protein>J kappa</protein> and <protein>PU.1</protein> ."}
{"id": "916", "text": "LBF3 , LBF5 , LBF6 , or LBF7 may also be involved , since their binding sites also contribute to EBNA-2 responsiveness .", "annotated_text": "<protein>LBF3</protein> , <protein>LBF5</protein> , <protein>LBF6</protein> , or <protein>LBF7</protein> may also be involved , since their binding sites also contribute to <protein>EBNA-2</protein> responsiveness ."}
{"id": "917", "text": "Lymphocyte glucocorticoid receptor : predictor of sertraline response in adolescent major depressive disorder ( MDD ) .", "annotated_text": "<protein>Lymphocyte glucocorticoid receptor</protein> : predictor of sertraline response in adolescent major depressive disorder ( MDD ) ."}
{"id": "918", "text": "Major depressive disorder ( MDD ) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia .", "annotated_text": "Major depressive disorder ( MDD ) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia ."}
{"id": "919", "text": "The efficacy of serotonin reuptake inhibitors ( SRIs ) is uncertain , and response predictors are unavailable .", "annotated_text": "The efficacy of serotonin reuptake inhibitors ( SRIs ) is uncertain , and response predictors are unavailable ."}
{"id": "920", "text": "Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor ( GCII ) .", "annotated_text": "Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened <protein>limbic-hippocampal glucocorticoid type II receptor</protein> ( <protein>GCII</protein> ) ."}
{"id": "921", "text": "We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs .", "annotated_text": "We hypothesized that <protein>lymphocyte GCII</protein> is altered in adolescent MDD and could serve as a marker for response to SRIs ."}
{"id": "922", "text": "In an open-label study , adolescents ( n = 20 ) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell ( sites/cell ) values of 793 +/- 106 versus 2 , 563 +/- 499 ( +/- SEM ) for matched controls ( n = 18 ) ( t = 3.5 ; df = 36 ; p < .001 ) .", "annotated_text": "In an open-label study , adolescents ( n = 20 ) meeting DSM-III-R criteria for MDD showed baseline <protein>lymphocyte GCII sites</protein> per cell ( sites/cell ) values of 793 +/- 106 versus 2 , 563 +/- 499 ( +/- SEM ) for matched controls ( n = 18 ) ( t = 3.5 ; df = 36 ; p < .001 ) ."}
{"id": "923", "text": "GCII was bimodally distributed , with SRI responders differing from nonresponders ( t = 3.9 ; df = 14 ; p < .001 ) .", "annotated_text": "<protein>GCII</protein> was bimodally distributed , with SRI responders differing from nonresponders ( t = 3.9 ; df = 14 ; p < .001 ) ."}
{"id": "924", "text": "GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders .", "annotated_text": "<protein>GCII</protein> accurately classified 90 percent of sertraline responders and 80 percent of nonresponders ."}
{"id": "925", "text": "Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment ( t = 2.1 , df = 10 ; p < .05 ) .", "annotated_text": "Only SRI responders showed <protein>GCII</protein> sites/cell upregulated after 6 weeks of treatment ( t = 2.1 , df = 10 ; p < .05 ) ."}
{"id": "926", "text": "The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription .", "annotated_text": "The role of <protein>NFATp</protein> in <dna>cyclosporin A-sensitive tumor necrosis factor-alpha gene</dna> transcription ."}
{"id": "927", "text": "The tumor necrosis factor-alpha ( TNF alpha ) gene is an immediate early gene in activated T cells , in that it is rapidly induced without a requirement for protein synthesis .", "annotated_text": "The <dna>tumor necrosis factor-alpha ( TNF alpha ) gene</dna> is an immediate early gene in activated <cell_type>T cells</cell_type> , in that it is rapidly induced without a requirement for protein synthesis ."}
{"id": "928", "text": "Maximal induction of TNF alpha mRNA can be induced by treatment of T cells with calcium ionophores alone , via a calcineurin -dependent process that is blocked by cyclosporin A .", "annotated_text": "Maximal induction of <rna>TNF alpha mRNA</rna> can be induced by treatment of <cell_type>T cells</cell_type> with calcium ionophores alone , via a <protein>calcineurin</protein> -dependent process that is blocked by cyclosporin A ."}
{"id": "929", "text": "We have previously identified a promoter element , kappa 3 , that is required for calcium-stimulated , cyclosporin A-sensitive induction of the TNF alpha gene in activated T cells .", "annotated_text": "We have previously identified a <dna>promoter element</dna> , <dna>kappa 3</dna> , that is required for calcium-stimulated , cyclosporin A-sensitive induction of the <dna>TNF alpha gene</dna> in activated <cell_type>T cells</cell_type> ."}
{"id": "930", "text": "Here , we demonstrate that the kappa 3 binding factor contains NFATp , a cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene transcription .", "annotated_text": "Here , we demonstrate that the <protein>kappa 3 binding factor</protein> contains <protein>NFATp</protein> , a <protein>cyclosporin-sensitive DNA-binding protein</protein> required for <dna>interleukin-2 gene</dna> transcription ."}
{"id": "931", "text": "NFATp binds to two sites within the kappa 3 element , and occupancy of both sites is required for TNF alpha gene induction .", "annotated_text": "<protein>NFATp</protein> binds to two sites within the <dna>kappa 3 element</dna> , and occupancy of both sites is required for <protein>TNF</protein> alpha gene induction ."}
{"id": "932", "text": "Thus , although the kappa 3 element has little sequence similarity to other NFATp-binding sites , it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp .", "annotated_text": "Thus , although the <dna>kappa 3 element</dna> has little sequence similarity to other <dna>NFATp-binding sites</dna> , it appears to function as a <dna>cyclosporin-sensitive promoter element</dna> in <cell_type>T cells</cell_type> by virtue of its ability to bind <protein>NFATp</protein> ."}
{"id": "933", "text": "The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes , starting at the earliest stages of T cell activation .", "annotated_text": "The involvement of <protein>NFATp</protein> in transcriptional activation of both the <protein>interleukin-2</protein> and <dna>TNF alpha genes</dna> suggests that this factor plays an important role in the coordinate induction of multiple <dna>cytokine genes</dna> , starting at the earliest stages of T cell activation ."}
{"id": "934", "text": "Regulation and specificity of MNDA expression in monocytes , macrophages , and leukemia/B lymphoma cell lines .", "annotated_text": "Regulation and specificity of <protein>MNDA</protein> expression in <cell_type>monocytes</cell_type> , <cell_type>macrophages</cell_type> , and <cell_line>leukemia/B lymphoma cell lines</cell_line> ."}
{"id": "935", "text": "The expression of the human myeloid cell nuclear differentiation antigen ( MNDA ) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports .", "annotated_text": "The expression of the <protein>human myeloid cell nuclear differentiation antigen</protein> ( <protein>MNDA</protein> ) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports ."}
{"id": "936", "text": "The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia .", "annotated_text": "The specificity of <protein>MNDA</protein> expression for cells in the granulocyte-macrophage lineage was reexamined in <cell_line>cell lines</cell_line> established from patients with Philadelphia chromosome-positive chronic myeloid leukemia ."}
{"id": "937", "text": "Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro , while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA .", "annotated_text": "Cell lines that expressed <protein>MNDA</protein> exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro , while cell lines exhibiting properties of very early stage cells or <cell_type>multipotential cells</cell_type> did not express <protein>MNDA</protein> ."}
{"id": "938", "text": "Cells originating from cases of Burkitt 's lymphoma were negative .", "annotated_text": "Cells originating from cases of Burkitt 's lymphoma were negative ."}
{"id": "939", "text": "By contrast , three lymphoblastoid cell lines ( immortalized in vitro with Epstein-Barr virus ) were weakly positive and MNDA was up-regulated by interferon-alpha ( IFN-alpha ) treatment .", "annotated_text": "By contrast , three <cell_line>lymphoblastoid cell lines</cell_line> ( immortalized in vitro with Epstein-Barr virus ) were weakly positive and <protein>MNDA</protein> was up-regulated by <protein>interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) treatment ."}
{"id": "940", "text": "As we reported previously , MNDA mRNA level in adherent monocytes is elevated by IFN-alpha ; in this study , we further assessed MNDA expression in in vitro monocyte-derived macrophages .", "annotated_text": "As we reported previously , <rna>MNDA mRNA</rna> level in adherent <cell_type>monocytes</cell_type> is elevated by <protein>IFN-alpha</protein> ; in this study , we further assessed <protein>MNDA</protein> expression in in vitro monocyte-derived <cell_type>macrophages</cell_type> ."}
{"id": "941", "text": "Three additional agents ( endotoxin , phytohemagglutinin , and phorbol ester ) and other conditions that affect function , cytokine production , differentiation , and/or growth of monocytes were examined for their ability to alter MNDA expression .", "annotated_text": "Three additional agents ( endotoxin , <protein>phytohemagglutinin</protein> , and phorbol ester ) and other conditions that affect function , <protein>cytokine</protein> production , differentiation , and/or growth of <cell_type>monocytes</cell_type> were examined for their ability to alter <protein>MNDA</protein> expression ."}
{"id": "942", "text": "The results varied with the agent , cell type , and stage of differentiation .", "annotated_text": "The results varied with the agent , cell type , and stage of differentiation ."}
{"id": "943", "text": "Changes in MNDA expression occurred slowly ( hours to days ) , suggesting that MNDA could mediate changes realized over a long period .", "annotated_text": "Changes in <protein>MNDA</protein> expression occurred slowly ( hours to days ) , suggesting that <protein>MNDA</protein> could mediate changes realized over a long period ."}
{"id": "944", "text": "The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point .", "annotated_text": "The results also reveal a discordance in certain <cell_line>MNDA positive cells</cell_line> between steady-state levels or changes in levels of protein and <rna>mRNA</rna> indicating that the regulation of <protein>MNDA</protein> expression occurs at more than one point ."}
{"id": "945", "text": "Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes /macrophages .", "annotated_text": "Changes in <protein>MNDA</protein> expression are consistent with a role in opposing macrophage differentiation and activation of <cell_type>monocytes</cell_type> <cell_type>/macrophages</cell_type> ."}
{"id": "946", "text": "DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 ( EBNA-2 ) : evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2-positive cell lines .", "annotated_text": "DNA-binding studies of the <protein>Epstein-Barr virus nuclear antigen 2</protein> ( <protein>EBNA-2</protein> ) : evidence for complex formation by <protein>latent membrane protein gene promoter-binding proteins</protein> in <cell_line>EBNA-2-positive cell lines</cell_line> ."}
{"id": "947", "text": "The Epstein-Barr virus ( EBV ) nuclear antigen 2 ( EBNA-2 ) protein is essential for the immortalization of human primary B cells by EBV .", "annotated_text": "The <protein>Epstein-Barr virus ( EBV ) nuclear antigen 2</protein> ( <protein>EBNA-2</protein> ) protein is essential for the immortalization of <cell_type>human primary B cells</cell_type> by EBV ."}
{"id": "948", "text": "EBNA-2 trans-activates cellular and viral genes like CD23 , c-fgr , latent membrane protein 1 ( LMP1 ) and terminal protein 1 ( TP1 ) .", "annotated_text": "<protein>EBNA-2</protein> trans-activates <dna>cellular and viral genes</dna> like <dna>CD23</dna> , <dna>c-fgr</dna> , <protein>latent membrane protein 1</protein> ( <protein>LMP1</protein> ) and <protein>terminal protein 1</protein> ( <protein>TP1</protein> ) ."}
{"id": "949", "text": "Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A ( of EBV type 1 ) to the DNA .", "annotated_text": "Trans-activation of the <dna>TP1 promoter</dna> and of the <dna>BamHI C promoter</dna> has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of <protein>EBNA-2 type A</protein> ( of EBV type 1 ) to the DNA ."}
{"id": "950", "text": "EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines .", "annotated_text": "<protein>EBNA-2</protein> is able to trans-activate the expression of the <dna>LMP gene</dna> in several cell lines ."}
{"id": "951", "text": "Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation .", "annotated_text": "Various reports have delineated the <dna>cis-acting elements</dna> of the <dna>LMP promoter</dna> through which <protein>EBNA-2</protein> mediates trans-activation ."}
{"id": "952", "text": "To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions , we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes .", "annotated_text": "To determine whether <protein>EBNA-2</protein> also trans-activates the <dna>LMP promoter</dna> by protein-protein interactions , we performed a series of gel retardation assays and competition experiments with <dna>LMP promoter fragments</dna> of different sizes ."}
{"id": "953", "text": "We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site .", "annotated_text": "We determined that the <dna>protein-binding region</dna> on the <dna>LMP promoter</dna> was within a <dna>42 bp fragment</dna> encompassing nucleotides -135 to -176 relative to the <dna>LMP transcriptional start site</dna> ."}
{"id": "954", "text": "of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions .", "annotated_text": "of the DNA fragments investigated indicated interaction of <protein>EBNA-2</protein> with the DNA via protein-protein interactions ."}
{"id": "955", "text": "No significant differences between EBNA-2 -positive and EBNA-2 -negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter .", "annotated_text": "No significant differences between <protein>EBNA-2</protein> -positive and <protein>EBNA-2</protein> -negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of <protein>EBNA-2A</protein> to the <dna>TP1 promoter</dna> ."}
{"id": "956", "text": "However , analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter-binding proteins form a complex of higher M ( r ) in EBNA-2-positive cell extracts .", "annotated_text": "However , analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the <protein>LMP promoter-binding proteins</protein> form a complex of higher M ( r ) in <cell_type>EBNA-2-positive cell</cell_type> extracts ."}
{"id": "957", "text": "These complexes were destroyed by detergent .", "annotated_text": "These complexes were destroyed by detergent ."}
{"id": "958", "text": "We deduce from these results that EBNA-2-positive cells might indeed contain specific complexes bound to the LMP promoter which are , however , too labile to be detected in a standard gel retardation assay .", "annotated_text": "We deduce from these results that <cell_line>EBNA-2-positive cells</cell_line> might indeed contain <protein>specific complexes</protein> bound to the <dna>LMP promoter</dna> which are , however , too labile to be detected in a standard gel retardation assay ."}
{"id": "959", "text": "Simultaneous activation of Ig and Oct-2 synthesis and reduction of surface MHC class II expression by IL-6 .", "annotated_text": "Simultaneous activation of <protein>Ig</protein> and <protein>Oct-2</protein> synthesis and reduction of surface <protein>MHC class II</protein> expression by <protein>IL-6</protein> ."}
{"id": "960", "text": "Terminal differentiation of B cells to plasma cells in vivo is characterized by secretion of Ig and extinction of MHC class II expression on the cell surface .", "annotated_text": "Terminal differentiation of <cell_type>B cells</cell_type> to <cell_type>plasma cells</cell_type> in vivo is characterized by secretion of <protein>Ig</protein> and extinction of <protein>MHC class II</protein> expression on the cell surface ."}
{"id": "961", "text": "We show that IL-6 signaling leads to marked increases in the synthesis and secretion of Ig in clonal human B cell lines and newly isolated polyclonal B lymphocytes in vitro .", "annotated_text": "We show that <protein>IL-6</protein> signaling leads to marked increases in the synthesis and secretion of <protein>Ig</protein> in <cell_line>clonal human B cell lines</cell_line> and newly <cell_type>isolated polyclonal B lymphocytes</cell_type> in vitro ."}
{"id": "962", "text": "The IL-6-induced cells resemble plasma cells in ultrastructure and in reduced expression of surface MHC class II .", "annotated_text": "The <cell_line>IL-6-induced cells</cell_line> resemble <cell_type>plasma cells</cell_type> in ultrastructure and in reduced expression of <protein>surface MHC class II</protein> ."}
{"id": "963", "text": "Enhanced Ig synthesis is a result of coordinated transcriptional activation of Ig genes without promoter or isotype specificity , and differential accumulation of the mRNA encoding the secreted form of Ig heavy chain .", "annotated_text": "Enhanced <protein>Ig</protein> synthesis is a result of coordinated transcriptional activation of <dna>Ig genes</dna> without promoter or isotype specificity , and differential accumulation of the <rna>mRNA</rna> encoding the secreted form of <protein>Ig heavy chain</protein> ."}
{"id": "964", "text": "It is saturable and subject to negative control when IL-6 stimulation is prolonged .", "annotated_text": "It is saturable and subject to negative control when <protein>IL-6</protein> stimulation is prolonged ."}
{"id": "965", "text": "Coordinate with temporal changes in Ig synthesis , the DNA-binding activity and the synthesis of the B cell-enriched transcription factor Oct-2 are regulated .", "annotated_text": "Coordinate with temporal changes in <protein>Ig</protein> synthesis , the DNA-binding activity and the synthesis of the <protein>B cell-enriched transcription factor</protein> <protein>Oct-2</protein> are regulated ."}
{"id": "966", "text": "Thus , differentiation of B cells with IL-6 in vitro recapitulates the hallmarks of terminal B differentiation in vivo ; Oct-2 may have a role in this process .", "annotated_text": "Thus , differentiation of <cell_type>B cells</cell_type> with <protein>IL-6</protein> in vitro recapitulates the hallmarks of terminal B differentiation in vivo ; <protein>Oct-2</protein> may have a role in this process ."}
{"id": "967", "text": "T-cell functional regions of the human IL-3 proximal promoter .", "annotated_text": "<dna>T-cell functional regions</dna> of the <dna>human IL-3 proximal promoter</dna> ."}
{"id": "968", "text": "The human interleukin-3 ( IL-3 ) gene is expressed almost exclusively in activated T cells .", "annotated_text": "The <dna>human interleukin-3 ( IL-3 ) gene</dna> is expressed almost exclusively in activated <cell_type>T cells</cell_type> ."}
{"id": "969", "text": "Its expression is regulated at both the transcriptional and post-transcriptional level .", "annotated_text": "Its expression is regulated at both the transcriptional and post-transcriptional level ."}
{"id": "970", "text": "We have previously shown that treatment of Jurkat T cells with phytohemaglutinin ( PHA ) and the phorbol ester , PMA , activated transcription initiation from the IL-3 gene .", "annotated_text": "We have previously shown that treatment of <cell_line>Jurkat T cells</cell_line> with <protein>phytohemaglutinin</protein> ( <protein>PHA</protein> ) and the phorbol ester , PMA , activated transcription initiation from the <dna>IL-3 gene</dna> ."}
{"id": "971", "text": "To define the regions of the gene required for transcription activation , we generated a series of reporter constructs containing different regions of the IL-3 gene 5 ' and 3 ' flanking sequences .", "annotated_text": "To define the regions of the gene required for transcription activation , we generated a series of reporter constructs containing different regions of the <dna>IL-3 gene 5 ' and 3 ' flanking sequences</dna> ."}
{"id": "972", "text": "Both positive and negative regulatory elements were identified in the proximal 5 ' flanking region of the IL-3 gene .", "annotated_text": "Both <dna>positive and negative regulatory elements</dna> were identified in the <dna>proximal 5 ' flanking region</dna> of the <dna>IL-3 gene</dna> ."}
{"id": "973", "text": "The promoter region between -173 and -60 contained the strongest activating elements .", "annotated_text": "The <dna>promoter region</dna> between <dna>-173 and -60</dna> contained the strongest <dna>activating elements</dna> ."}
{"id": "974", "text": "The transcription factor AP-1 could bind to this positive activator region of the promoter .", "annotated_text": "The <protein>transcription factor</protein> <protein>AP-1</protein> could bind to this positive activator region of the promoter ."}
{"id": "975", "text": "We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA /PHA .", "annotated_text": "We also examined the function of the <dna>IL-3 CK-1/CK-2 elements</dna> that are present in many <dna>cytokine genes</dna> and found that they acted as a repressor of basal level expression when cloned upstream of a <dna>heterologous promoter</dna> but were also inducible by PMA <protein>/PHA</protein> ."}
{"id": "976", "text": "Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development .", "annotated_text": "Expression of the <dna>Runt domain-encoding PEBP2 alpha genes</dna> in <cell_type>T cells</cell_type> during thymic development ."}
{"id": "977", "text": "The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor , PEBP2 , which is implicated as a T-cell-specific transcriptional regulator .", "annotated_text": "The <dna>PEBP2 alpha A and PEBP2 alpha B genes</dna> encode the <protein>DNA-binding subunit</protein> of a <protein>murine transcription factor</protein> , <protein>PEBP2</protein> , which is implicated as a <protein>T-cell-specific transcriptional regulator</protein> ."}
{"id": "978", "text": "These two related genes share the evolutionarily conserved region encoding the Runt domain .", "annotated_text": "These two related genes share the evolutionarily conserved region encoding the <protein>Runt domain</protein> ."}
{"id": "979", "text": "PEBP2 alpha B is the murine counterpart of human AML1 , which is located at the breakpoints of the 8 ; 21 and 3 ; 21 chromosome translocations associated with acute myeloid leukemia .", "annotated_text": "<protein>PEBP2 alpha B</protein> is the <protein>murine counterpart</protein> of <protein>human AML1</protein> , which is located at the breakpoints of the <dna>8 ; 21 and 3 ; 21 chromosome translocations</dna> associated with acute myeloid leukemia ."}
{"id": "980", "text": "Northern ( RNA ) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus .", "annotated_text": "Northern ( RNA ) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus ."}
{"id": "981", "text": "Furthermore , transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns , as well as 4-week-old adult mice , by in situ hybridization .", "annotated_text": "Furthermore , transcripts of <protein>PEBP2 alpha A</protein> and <protein>mouse AML1/PEBP2 alpha B</protein> were detected in <cell_type>T lymphocytes</cell_type> in the thymuses from day 16 embryos and newborns , as well as 4-week-old adult mice , by in situ hybridization ."}
{"id": "982", "text": "The expression of the genes persisted in peripheral lymph nodes of adult mice .", "annotated_text": "The expression of the genes persisted in peripheral lymph nodes of adult mice ."}
{"id": "983", "text": "The transcripts were detected in all the CD4- CD8- , CD4+ CD8+ , CD4+ CD8- , and CD4- CD8+ cell populations .", "annotated_text": "The transcripts were detected in all the <cell_type>CD4- CD8- , CD4+ CD8+ , CD4+ CD8- , and CD4- CD8+ cell populations</cell_type> ."}
{"id": "984", "text": "The results indicated that both genes are expressed in T cells throughout their development , supporting the notion that PEBP2 is a T-cell-specific transcription factor .", "annotated_text": "The results indicated that both genes are expressed in <cell_type>T cells</cell_type> throughout their development , supporting the notion that <protein>PEBP2</protein> is a <protein>T-cell-specific transcription factor</protein> ."}
{"id": "985", "text": "Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice .", "annotated_text": "Transcripts of <protein>mouse AML1/PEBP2 alpha B</protein> were also detected in day 12 fetal hematopoietic liver and in the <cell_type>bone marrow cells</cell_type> of newborn mice ."}
{"id": "986", "text": "The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis .", "annotated_text": "The implication of mouse <protein>AML1/PEBP2 alpha B</protein> expression in <cell_type>hematopoietic cells</cell_type> other than those of <cell_type>T-cell lineage</cell_type> is discussed in relation to myeloid leukemogenesis ."}
{"id": "987", "text": "Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells .", "annotated_text": "Effects of glucocorticoids on transcription factor activation in <cell_type>human peripheral blood mononuclear cells</cell_type> ."}
{"id": "988", "text": "Glucocorticoids have an inhibitory effect on inflammatory and immune responses , and this may be through the modulation of transcription factor binding to DNA .", "annotated_text": "Glucocorticoids have an inhibitory effect on inflammatory and immune responses , and this may be through the modulation of <protein>transcription factor</protein> binding to DNA ."}
{"id": "989", "text": "The interaction of the transcription factors , activator protein-1 ( AP-1 ) , nuclear factor kappa B ( NF kappa B ) , and cAMP-responsive element binding protein ( CREB ) with DNA and glucocorticoid receptors ( GR ) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays .", "annotated_text": "The interaction of the <protein>transcription factors</protein> , <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) , <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) , and <protein>cAMP-responsive element binding protein</protein> ( <protein>CREB</protein> ) with DNA and <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) was analyzed in <cell_type>human peripheral blood mononuclear cells</cell_type> by gel mobility shift assays ."}
{"id": "990", "text": "TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased AP-1 and NF kappa B DNA binding by up to 200 % but decreased CREB binding ( 38 % ) over a 60-min time course .", "annotated_text": "TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased <protein>AP-1</protein> and NF kappa B DNA binding by up to 200 % but decreased <protein>CREB</protein> binding ( 38 % ) over a 60-min time course ."}
{"id": "991", "text": "Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50 % decrease in AP-1 , NF kappa B , and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment .", "annotated_text": "Dexamethasone produced a rapid and sustained increase in <dna>glucocorticoid response element</dna> binding and a concomitant 40-50 % decrease in AP-1 , NF kappa B , and CREB DNA binding that was blocked by combined dexamethasone and <protein>cytokine</protein> or PMA treatment ."}
{"id": "992", "text": "These latter effects were due to increases in the nuclear localization of GR , not to reduced amounts of the other transcription factors .", "annotated_text": "These latter effects were due to increases in the nuclear localization of <protein>GR</protein> , not to reduced amounts of the other <protein>transcription factors</protein> ."}
{"id": "993", "text": "This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling .", "annotated_text": "This suggests that in these cells <protein>GR</protein> within the nucleus interacts with <protein>cytokine-stimulated transcription factors</protein> by the process of cross coupling ."}
{"id": "994", "text": "This may be an important molecular site of steroid action .", "annotated_text": "This may be an important molecular site of steroid action ."}
{"id": "995", "text": "Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy .", "annotated_text": "Differential induction of the <protein>NF-AT complex</protein> during restimulation and the induction of T-cell anergy ."}
{"id": "996", "text": "Stimulation of human CD4+ T-cell clones through the T-cell receptor ( TcR ) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy .", "annotated_text": "Stimulation of <cell_line>human CD4+ T-cell clones</cell_line> through the <protein>T-cell receptor</protein> ( <protein>TcR</protein> ) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy ."}
{"id": "997", "text": "During the induction of anergy , T cells are phenotypically similar to cells responding to an immunogenic stimulus .", "annotated_text": "During the induction of anergy , <cell_type>T cells</cell_type> are phenotypically similar to cells responding to an immunogenic stimulus ."}
{"id": "998", "text": "The amount of TcR at the cell surface is downmodulated , whereas the CD2 and CD25 receptors are increased .", "annotated_text": "The amount of <protein>TcR</protein> at the cell surface is downmodulated , whereas the <protein>CD2 and CD25 receptors</protein> are increased ."}
{"id": "999", "text": "When restimulated , however , anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2 .", "annotated_text": "When restimulated , however , <cell_type>anergic T cells</cell_type> fail to up-regulate transcription of the <dna>IL-2 gene</dna> and in consequence do not produce <protein>IL-2</protein> ."}
{"id": "1000", "text": "In this study , we have compared the ability of various transcription factors to bind to their appropriate site on DNA .", "annotated_text": "In this study , we have compared the ability of various <protein>transcription factors</protein> to bind to their appropriate site on DNA ."}
{"id": "1001", "text": "Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation .", "annotated_text": "Factors were isolated from the nuclei of <cell_type>T cells</cell_type> that were in the induction phase of anergy or were undergoing activation ."}
{"id": "1002", "text": "The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes .", "annotated_text": "The pattern of binding activity in restimulated <cell_type>T cells</cell_type> is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the <protein>IL-2</protein> and the beta chain of the <dna>TcR genes</dna> ."}
{"id": "1003", "text": "The measured binding to a TCF-1 site is the same in the nuclei of resting , activated , and anergized cells .", "annotated_text": "The measured binding to a <dna>TCF-1 site</dna> is the same in the nuclei of <cell_type>resting , activated , and anergized cells</cell_type> ."}
{"id": "1004", "text": "The inducible factors NK-kappa B , beta E2 , CD28RC , and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells .", "annotated_text": "The <protein>inducible factors</protein> <protein>NK-kappa B</protein> , <protein>beta E2</protein> , <protein>CD28RC</protein> , and <protein>AP-1</protein> are not expressed in <cell_type>resting cells</cell_type> and are twofold lower in anergized as compared with activated cells ."}
{"id": "1005", "text": "In contrast , anergic T cells express approximately eightfold lower amounts of NF-AT , a member of the class of inducible factors that regulates IL-2 gene transcription .", "annotated_text": "In contrast , <cell_type>anergic T cells</cell_type> express approximately eightfold lower amounts of <protein>NF-AT</protein> , a member of the class of <protein>inducible factors</protein> that regulates <dna>IL-2 gene</dna> transcription ."}
{"id": "1006", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "1007", "text": "The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation .", "annotated_text": "The number of <protein>glucocorticoid receptors</protein> in <cell_type>peripheral human lymphocytes</cell_type> is elevated by a zinc containing trace element preparation ."}
{"id": "1008", "text": "A trace element preparation ( Beres Drops Plus , BDP ) elevates the number of glucocorticoid receptors ( gcR ) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients .", "annotated_text": "A trace element preparation ( Beres Drops Plus , BDP ) elevates the number of <protein>glucocorticoid receptors</protein> ( <protein>gcR</protein> ) in <cell_type>peripheral lymphocytes</cell_type> isolated both from healthy blood donors and rheumatoid arthritis patients ."}
{"id": "1009", "text": "This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin ( IL ) -6 .", "annotated_text": "This enhancement by BDP was found either for constitutive expression of <protein>gcRs</protein> or in experiments when the <cell_type>lymphocytes</cell_type> were stimulated by <protein>interleukin ( IL ) -6</protein> ."}
{"id": "1010", "text": "There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha ( TNF alpha ) -induced changes of gcRs .", "annotated_text": "There was no significant effect of BDP on <protein>IL-1</protein> and <protein>tumour necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) -induced changes of <protein>gcRs</protein> ."}
{"id": "1011", "text": "The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation , since the augmenting effect was abolished if BDP did not contain zinc .", "annotated_text": "The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation , since the augmenting effect was abolished if BDP did not contain zinc ."}
{"id": "1012", "text": "The DNA and steroid binding domains of the glucocorticoid receptor are not altered in mononuclear cells of treated CLL patients .", "annotated_text": "The DNA and <protein>steroid binding domains</protein> of the <protein>glucocorticoid receptor</protein> are not altered in <cell_type>mononuclear cells</cell_type> of treated CLL patients ."}
{"id": "1013", "text": "The aim of this study was to investigate whether mutations in the glucocorticoid receptor could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia ( CLL ) to combination chemotherapy .", "annotated_text": "The aim of this study was to investigate whether mutations in the <protein>glucocorticoid receptor</protein> could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia ( CLL ) to combination chemotherapy ."}
{"id": "1014", "text": "The receptor was tested immunocytochemically , in steroid binding assays , and by a mutation screening ( denaturing gradient gel electrophoresis ) of the receptor-cDNA .", "annotated_text": "The receptor was tested immunocytochemically , in steroid binding assays , and by a mutation screening ( denaturing gradient gel electrophoresis ) of the <protein>receptor-cDNA</protein> ."}
{"id": "1015", "text": "The receptor concentration , as measured by staining and steroid binding test , varied considerably but showed no clear correlation to clinical response .", "annotated_text": "The receptor concentration , as measured by staining and steroid binding test , varied considerably but showed no clear correlation to clinical response ."}
{"id": "1016", "text": "Using a highly sensitive mutation screening assay of the DNA- and the steroid-binding region , none of the treated patients revealed any mutation , suggesting that the glucocorticoid receptor in the CLL patients tested is not altered in these domains .", "annotated_text": "Using a highly sensitive mutation screening assay of the <protein>DNA- and the steroid-binding region</protein> , none of the treated patients revealed any mutation , suggesting that the <protein>glucocorticoid receptor</protein> in the CLL patients tested is not altered in these domains ."}
{"id": "1017", "text": "In one individual who had not been treated before analysis a silent mutation was found in one receptor allele .", "annotated_text": "In one individual who had not been treated before analysis a silent mutation was found in one receptor allele ."}
{"id": "1018", "text": "The results suggest that mechanisms other than altered ligand or DNA binding of the receptor may be responsible for the lack of response to chemotherapy .", "annotated_text": "The results suggest that mechanisms other than altered ligand or DNA binding of the receptor may be responsible for the lack of response to chemotherapy ."}
{"id": "1019", "text": "This conclusion is discussed in relation to the mechanism of corticoid resistance in mouse and human lymphoma cells in culture .", "annotated_text": "This conclusion is discussed in relation to the mechanism of corticoid resistance in <cell_line>mouse and human lymphoma cells</cell_line> in culture ."}
{"id": "1020", "text": "An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression .", "annotated_text": "An <dna>AP1 binding site</dna> upstream of the <dna>kappa immunoglobulin intron enhancer</dna> binds <protein>inducible factors</protein> and contributes to expression ."}
{"id": "1021", "text": "Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by trans-acting factors which interact with two distinct enhancer elements .", "annotated_text": "Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by <protein>trans-acting factors</protein> which interact with two distinct <dna>enhancer elements</dna> ."}
{"id": "1022", "text": "A new protein-DNA interaction has been identified upstream of the intron enhancer , within the matrix-associated region of the J-C intron .", "annotated_text": "A new protein-DNA interaction has been identified upstream of the <dna>intron enhancer</dna> , within the <dna>matrix-associated region</dna> of the <dna>J-C intron</dna> ."}
{"id": "1023", "text": "The binding activity is greatly inducible in pre-B cells by bacterial lipopolysaccharide and interleukin-1 but specific complexes are found at all stages of B cell development tested .", "annotated_text": "The binding activity is greatly inducible in <cell_type>pre-B cells</cell_type> by bacterial lipopolysaccharide and <protein>interleukin-1</protein> but specific complexes are found at all stages of B cell development tested ."}
{"id": "1024", "text": "The footprinted binding site is homologous to the consensus AP1 motif .", "annotated_text": "The <dna>footprinted binding site</dna> is homologous to the <dna>consensus AP1 motif</dna> ."}
{"id": "1025", "text": "The protein components of this complex are specifically competed by an AP1 consensus motif and were shown by supershift to include c-Jun and c-Fos , suggesting that this binding site is an AP1 motif and that the Jun and Fos families of transcription factors play a role in the regulation of the kappa light chain gene .", "annotated_text": "The protein components of this complex are specifically competed by an <dna>AP1 consensus motif</dna> and were shown by supershift to include <protein>c-Jun</protein> and <protein>c-Fos</protein> , suggesting that this <dna>binding site</dna> is an <dna>AP1 motif</dna> and that the <protein>Jun and Fos families</protein> of <protein>transcription factors</protein> play a role in the regulation of the <dna>kappa light chain gene</dna> ."}
{"id": "1026", "text": "Mutation of the AP1 motif in the context of the intron enhancer was shown to decrease enhancer-mediated activation of the promoter in both pre-B cells induced with LPS and constitutive expression in mature B cells .", "annotated_text": "Mutation of the <dna>AP1 motif</dna> in the context of the <dna>intron enhancer</dna> was shown to decrease enhancer-mediated activation of the promoter in both <cell_type>pre-B cells</cell_type> induced with LPS and constitutive expression in <cell_type>mature B cells</cell_type> ."}
{"id": "1027", "text": "Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T-cell lines .", "annotated_text": "Distinct <dna>DNase-I hypersensitive sites</dna> are associated with <protein>TAL-1</protein> transcription in <cell_line>erythroid and T-cell lines</cell_line> ."}
{"id": "1028", "text": "The tal-1 gene , frequently activated in human T-cell acute lymphoblastic leukemia ( T-ALL ) , is expressed in the erythroid , megakaryocytic , and mast cell lineages during normal hematopoiesis .", "annotated_text": "The <dna>tal-1 gene</dna> , frequently activated in human T-cell acute lymphoblastic leukemia ( T-ALL ) , is expressed in the <cell_type>erythroid , megakaryocytic , and mast cell lineages</cell_type> during normal hematopoiesis ."}
{"id": "1029", "text": "To gain further insight into the molecular mechanisms that control tal-1 expression , we investigated tal-1 chromatin structure in erythroid/megakaryocytic cell lines and in T-cell lines either with or without tal-1 rearrangements .", "annotated_text": "To gain further insight into the molecular mechanisms that control <dna>tal-1</dna> expression , we investigated <dna>tal-1</dna> chromatin structure in <cell_line>erythroid/megakaryocytic cell lines</cell_line> and in <cell_line>T-cell lines</cell_line> either with or without <dna>tal-1 rearrangements</dna> ."}
{"id": "1030", "text": "Tal-1 transcription was shown to be monoallelic in Jurkat , a T-cell line that expresses tal-1 in the absence of apparent genomic alteration of the locus .", "annotated_text": "Tal-1 transcription was shown to be monoallelic in <cell_line>Jurkat</cell_line> , a T-cell line that expresses <dna>tal-1</dna> in the absence of apparent genomic alteration of the locus ."}
{"id": "1031", "text": "Methylation studies indicated that the tal-15 ' GC-rich region behaves like a CpG island , hypomethylated in normal cells , and methylated de novo on transcriptionally inactive alleles in established cell lines .", "annotated_text": "Methylation studies indicated that the <dna>tal-15 ' GC-rich region</dna> behaves like a <dna>CpG island</dna> , hypomethylated in <cell_type>normal cells</cell_type> , and methylated de novo on <dna>transcriptionally inactive alleles</dna> in <cell_line>established cell lines</cell_line> ."}
{"id": "1032", "text": "Five major DNase-I hypersensitive sites ( HS ) were mapped in the tal-1 locus .", "annotated_text": "Five major <dna>DNase-I hypersensitive sites</dna> ( <dna>HS</dna> ) were mapped in the <dna>tal-1</dna> locus ."}
{"id": "1033", "text": "HS I , IV , and V were exclusively observed in the erythroid/megakaryocytic cell lines that express tal-1 from the promoters 1a and 1b .", "annotated_text": "<dna>HS I , IV , and V</dna> were exclusively observed in the <cell_line>erythroid/megakaryocytic cell lines</cell_line> that express <dna>tal-1</dna> from the <dna>promoters 1a and 1b</dna> ."}
{"id": "1034", "text": "HS II was weak in hematopoietic cell lines , absent in Hela , and greatly enhanced in Jurkat , suggesting that this region might be implicated in the cis-activation of tal-1 promoter 1b in this cell line .", "annotated_text": "<dna>HS II</dna> was weak in <cell_line>hematopoietic cell lines</cell_line> , absent in <cell_line>Hela</cell_line> , and greatly enhanced in <cell_line>Jurkat</cell_line> , suggesting that this region might be implicated in the cis-activation of <dna>tal-1 promoter 1b</dna> in this cell line ."}
{"id": "1035", "text": "HS III was weak in HEL and Jurkat , and greatly enhanced in DU528 , a T-cell line that bears a t ( 1 ; 14 ) and initiates tal-1 transcription within exon 4 .", "annotated_text": "<dna>HS III</dna> was weak in <cell_line>HEL</cell_line> and <cell_line>Jurkat</cell_line> , and greatly enhanced in <cell_line>DU528</cell_line> , a <cell_line>T-cell line</cell_line> that bears <dna>a t ( 1 ; 14 )</dna> and initiates <dna>tal-1</dna> transcription within <dna>exon 4</dna> ."}
{"id": "1036", "text": "These results suggest that distinct regulatory elements are associated with the use of the different tal-1 promoters .", "annotated_text": "These results suggest that distinct <dna>regulatory elements</dna> are associated with the use of the different <dna>tal-1 promoters</dna> ."}
{"id": "1037", "text": "Erythropoietin -dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT .", "annotated_text": "<protein>Erythropoietin</protein> -dependent induction of <protein>hemoglobin</protein> synthesis in a <cell_line>cytokine-dependent cell line</cell_line> <cell_line>M-TAT</cell_line> ."}
{"id": "1038", "text": "M-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages .", "annotated_text": "<cell_line>M-TAT</cell_line> is a <cell_line>cytokine-dependent cell line</cell_line> with the potential to differentiate along the <cell_type>erythroid and megakaryocytic lineages</cell_type> ."}
{"id": "1039", "text": "We cultured M-TAT cells long term ( > 1 year ) in the continuous presence of erythropoietin ( EPO ) , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , or stem cell factor ( SCF ) .", "annotated_text": "We cultured <cell_line>M-TAT cells</cell_line> long term ( > 1 year ) in the continuous presence of <protein>erythropoietin</protein> ( <protein>EPO</protein> ) , <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) , or <protein>stem cell factor</protein> ( <protein>SCF</protein> ) ."}
{"id": "1040", "text": "These long term cultures are referred to as M-TAT/EPO , M-TAT/GM-CSF , and M-TAT/SCF cells , respectively .", "annotated_text": "These long term cultures are referred to as <cell_line>M-TAT/EPO , M-TAT/GM-CSF , and M-TAT/SCF cells</cell_line> , respectively ."}
{"id": "1041", "text": "Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells .", "annotated_text": "<protein>Hemoglobin</protein> concentration and <protein>gamma-globin</protein> and <rna>erythroid delta-aminolevulinate synthase mRNA</rna> levels were significantly higher in <cell_line>M-TAT/EPO cells</cell_line> than in <cell_line>M-TAT/GM-CSF cells</cell_line> ."}
{"id": "1042", "text": "When the supplemented cytokine was switched from GM-CSF to EPO , hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly ( within 5 h ) , and the level of GATA-1 mRNA increased .", "annotated_text": "When the supplemented <protein>cytokine</protein> was switched from <protein>GM-CSF</protein> to <protein>EPO</protein> , <protein>hemoglobin</protein> synthesis in <cell_line>M-TAT/GM-CSF cells</cell_line> increased rapidly ( within 5 h ) , and the level of <rna>GATA-1 mRNA</rna> increased ."}
{"id": "1043", "text": "In contrast , the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin , even in the presence of EPO , indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF .", "annotated_text": "In contrast , the addition of <protein>GM-CSF</protein> to the <cell_line>M-TAT/EPO cell culture</cell_line> decreased the amount of hemoglobin , even in the presence of <protein>EPO</protein> , indicating that the <protein>EPO</protein> signal for erythroid differentiation is suppressed by <protein>GM-CSF</protein> ."}
{"id": "1044", "text": "Thus , erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF .", "annotated_text": "Thus , erythroid development of <cell_line>M-TAT cells</cell_line> is promoted by <protein>EPO</protein> and suppressed by <protein>GM-CSF</protein> ."}
{"id": "1045", "text": "These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation .", "annotated_text": "These results support the hypothesis that <protein>EPO</protein> actively influences the programming of gene expression required for <cell_type>erythroid progenitor cell</cell_type> differentiation ."}
{"id": "1046", "text": "The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells .", "annotated_text": "The role of <protein>cellular transcription factor E2F</protein> in the regulation of <rna>cdc2 mRNA</rna> expression and cell cycle control of human <cell_type>hematopoietic cells</cell_type> ."}
{"id": "1047", "text": "cdc2 mRNA transcripts were detected in immature bone marrow cells and became undetectable along with differentiation .", "annotated_text": "<rna>cdc2 mRNA transcripts</rna> were detected in <cell_type>immature bone marrow cells</cell_type> and became undetectable along with differentiation ."}
{"id": "1048", "text": "Peripheral blood resting cells did not express cdc2 mRNA , but it was induced in T-lymphocytes when the cells reentered the cell cycle in response to specific mitogens .", "annotated_text": "<cell_type>Peripheral blood resting cells</cell_type> did not express <rna>cdc2 mRNA</rna> , but it was induced in <cell_type>T-lymphocytes</cell_type> when the cells reentered the cell cycle in response to specific mitogens ."}
{"id": "1049", "text": "In contrast , cdc2 mRNA could not be induced in granulocytes and monocytes even after the culture with the appropriate stimulants .", "annotated_text": "In contrast , <rna>cdc2 mRNA</rna> could not be induced in <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> even after the culture with the appropriate stimulants ."}
{"id": "1050", "text": "In order to investigate the mechanism of the regulation of cdc2 mRNA expression in hematopoietic cells , we isolated the 5'-flanking sequence of the cdc2 gene and found the putative E2F binding site at the position of nucleotides -124 to -117 .", "annotated_text": "In order to investigate the mechanism of the regulation of <rna>cdc2 mRNA</rna> expression in <cell_type>hematopoietic cells</cell_type> , we isolated the <dna>5'-flanking sequence</dna> of the <dna>cdc2 gene</dna> and found the putative E2F <dna>binding site</dna> at the position of <dna>nucleotides -124 to -117</dna> ."}
{"id": "1051", "text": "The binding of E2F at this region was detected by a gel-retardation assay and DNaseI footprinting in phytohemagglutinin-stimulated T-lymphocytes , which was coincident with the expression of cdc2 mRNA .", "annotated_text": "The binding of <protein>E2F</protein> at this region was detected by a gel-retardation assay and <protein>DNaseI</protein> footprinting in <cell_line>phytohemagglutinin-stimulated T-lymphocytes</cell_line> , which was coincident with the expression of <rna>cdc2 mRNA</rna> ."}
{"id": "1052", "text": "E2F binding was not observed in both granulocytes and monocytes .", "annotated_text": "<protein>E2F</protein> binding was not observed in both <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> ."}
{"id": "1053", "text": "Transient chloramphenicol acetyltransferase assay revealed that the region containing E2F binding site had a strong promoter activity , and introduction of the mutation at the E2F binding site resulted in a significant loss of the activity .", "annotated_text": "Transient <protein>chloramphenicol acetyltransferase</protein> assay revealed that the region containing <dna>E2F binding site</dna> had a strong promoter activity , and introduction of the mutation at the <dna>E2F binding site</dna> resulted in a significant loss of the activity ."}
{"id": "1054", "text": "E2F-1 and DP-1 mRNAs were not detectable in granulocytes , monocytes and resting T-lymphocytes but were induced after the mitogenic stimulation of T-lymphocytes .", "annotated_text": "<rna>E2F-1 and DP-1 mRNAs</rna> were not detectable in <cell_type>granulocytes</cell_type> , <cell_type>monocytes</cell_type> and <cell_type>resting T-lymphocytes</cell_type> but were induced after the mitogenic stimulation of <cell_type>T-lymphocytes</cell_type> ."}
{"id": "1055", "text": "The induction of E2F activity preceded the appearance of cdc2 mRNA , which is consistent with the role of E2F in the regulation of cdc2 mRNA expression .", "annotated_text": "The induction of <protein>E2F</protein> activity preceded the appearance of <rna>cdc2 mRNA</rna> , which is consistent with the role of <protein>E2F</protein> in the regulation of <cell_type>cdc2 mRNA expression</cell_type> ."}
{"id": "1056", "text": "These results suggest that cdc2 mRNA expression is related to the cell cycling of normal human hematopoietic cells and that E2F plays some roles in the regulation of its expression .", "annotated_text": "These results suggest that <rna>cdc2 mRNA</rna> expression is related to the cell cycling of <cell_type>normal human hematopoietic cells</cell_type> and that <protein>E2F</protein> plays some roles in the regulation of its expression ."}
{"id": "1057", "text": "Association of alterations in NF-kappa B moieties with HIV type 1 proviral latency in certain monocytic cells .", "annotated_text": "Association of alterations in <protein>NF-kappa B moieties</protein> with HIV type 1 proviral latency in certain <cell_type>monocytic cells</cell_type> ."}
{"id": "1058", "text": "Human immunodeficiency virus type 1 ( HIV-1 ) replication is controlled by a complex array of virally encoded and cellular proteins .", "annotated_text": "Human immunodeficiency virus type 1 ( HIV-1 ) replication is controlled by a complex array of <protein>virally encoded and cellular proteins</protein> ."}
{"id": "1059", "text": "A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells , both in cell culture and in vivo .", "annotated_text": "A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells , both in cell culture and in vivo ."}
{"id": "1060", "text": "Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types .", "annotated_text": "Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types ."}
{"id": "1061", "text": "It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1 , in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state , is associated with alterations in nuclear factor-kappa B ( NF-kappa B ) moieties demonstrated in these cells by electrophoretic mobility shift assays ( EMSAs ) and in situ UV cross-linking studies .", "annotated_text": "It is now demonstrated that HIV-1 proviral latency in the <cell_line>monocytic cell line U1</cell_line> , in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state , is associated with alterations in nuclear <protein>factor-kappa B ( NF-kappa B ) moieties</protein> demonstrated in these cells by electrophoretic mobility shift assays ( EMSAs ) and in situ UV cross-linking studies ."}
{"id": "1062", "text": "A predominance of p50 NF-kappa B moieties and possibly p50 homodimers or closely related species , rather than the p50-p56 heterodimer of NF-kappa B that is the predominant NF-kappa B species in most T lymphocytic and monocytic cells , is demonstrated in the nuclei of U1 cells .", "annotated_text": "A predominance of <protein>p50 NF-kappa B moieties</protein> and possibly <protein>p50 homodimers</protein> or closely related species , rather than the <protein>p50-p56 heterodimer</protein> of <protein>NF-kappa B</protein> that is the predominant <protein>NF-kappa B</protein> species in most <cell_type>T lymphocytic and monocytic cells</cell_type> , is demonstrated in the nuclei of <cell_line>U1 cells</cell_line> ."}
{"id": "1063", "text": "This pattern of NF-kappa B-related moieties differs from the latently infected T lymphocytic cell line ACH-2 , and from the U937 monocytic line , the parental cell line of the U1 cellular clone .", "annotated_text": "This pattern of <protein>NF-kappa B-related moieties</protein> differs from the <cell_line>latently infected T lymphocytic cell line ACH-2</cell_line> , and from the <cell_line>U937 monocytic line</cell_line> , the <cell_line>parental cell line</cell_line> of the <cell_line>U1 cellular clone</cell_line> ."}
{"id": "1064", "text": "As such , these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types .", "annotated_text": "As such , these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types ."}
{"id": "1065", "text": "[ Regulation of transcription of the interleukin-2 gene in B-lymphocytes ]", "annotated_text": "[ Regulation of transcription of the <dna>interleukin-2 gene</dna> in <cell_type>B-lymphocytes</cell_type> ]"}
{"id": "1066", "text": "Since most B cell clones immortalized with EBV virus can be induced to produce interleukin-2 , a typical T cell cytokine , we studied the role of different elements of the IL-2 promoter in such clones by transfection .", "annotated_text": "Since most <cell_line>B cell clones</cell_line> immortalized with EBV virus can be induced to produce <protein>interleukin-2</protein> , a typical <protein>T cell cytokine</protein> , we studied the role of different elements of the <dna>IL-2 promoter</dna> in such clones by transfection ."}
{"id": "1067", "text": "It was found , in particular , that the element TCEd , which binds the transcription factor NF-kB , is very active in all three B clones tested .", "annotated_text": "It was found , in particular , that the element <dna>TCEd</dna> , which binds the <protein>transcription factor</protein> <protein>NF-kB</protein> , is very active in all three <cell_line>B clones</cell_line> tested ."}
{"id": "1068", "text": "This element has no activity in T cells of the Jurkat line .", "annotated_text": "This element has no activity in <cell_type>T cells</cell_type> of the <cell_line>Jurkat line</cell_line> ."}
{"id": "1069", "text": "The NFATd element , which binds the transcription factor NFAT-1 and is very active in T cells , is only weakly active in one B clone and not at all in another .", "annotated_text": "The <dna>NFATd element</dna> , which binds the <protein>transcription factor</protein> <protein>NFAT-1</protein> and is very active in <cell_type>T cells</cell_type> , is only weakly active in one <cell_line>B clone</cell_line> and not at all in another ."}
{"id": "1070", "text": "Different elements thus contribute to IL-2 promoter activity in different cells .", "annotated_text": "Different elements thus contribute to <dna>IL-2 promoter</dna> activity in different cells ."}
{"id": "1071", "text": "Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus .", "annotated_text": "Regulation of <protein>I kappa B alpha</protein> and <protein>p105</protein> in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> persistently infected with human immunodeficiency virus ."}
{"id": "1072", "text": "The mechanisms regulating human immunodeficiency virus ( HIV ) persistence in human monocytes /macrophages are partially understood .", "annotated_text": "The mechanisms regulating human immunodeficiency virus ( HIV ) persistence in human <cell_type>monocytes</cell_type> <cell_type>/macrophages</cell_type> are partially understood ."}
{"id": "1073", "text": "Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation .", "annotated_text": "Persistent HIV infection of <cell_line>U937 monocytic cells</cell_line> results in <protein>NF-kappa B</protein> activation ."}
{"id": "1074", "text": "Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown .", "annotated_text": "Whether virus-induced <protein>NF-kappa B</protein> activation is a mechanism that favors continuous viral replication in <cell_type>macrophages</cell_type> remains unknown ."}
{"id": "1075", "text": "To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV-infected monocytes and macrophages , we have focused on the regulation of the I kappa B molecules .", "annotated_text": "To further delineate the molecular mechanisms involved in the activation of <protein>NF-kappa B</protein> in HIV-infected <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> , we have focused on the regulation of the I kappa B molecules ."}
{"id": "1076", "text": "First , we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages .", "annotated_text": "First , we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in <cell_type>macrophages</cell_type> ."}
{"id": "1077", "text": "In HIV-infected cells , I kappa B alpha protein levels are decreased secondary to enhanced protein degradation .", "annotated_text": "In HIV-infected cells , <protein>I kappa B alpha</protein> protein levels are decreased secondary to enhanced protein degradation ."}
{"id": "1078", "text": "This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription , i.e. , increased RNA and transcriptional activity of its promoter-enhancer .", "annotated_text": "This parallels the increased <protein>I kappa B alpha</protein> synthesis secondary to increased <protein>I kappa B alpha</protein> gene transcription , i.e. , increased RNA and transcriptional activity of its promoter-enhancer ."}
{"id": "1079", "text": "Another protein with I kappa B function , p105 , is also modified in HIV-infected cells : p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105 .", "annotated_text": "Another protein with I kappa B function , <protein>p105</protein> , is also modified in HIV-infected cells : <protein>p105</protein> and <protein>p50</protein> steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of <protein>p105</protein> ."}
{"id": "1080", "text": "Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif .", "annotated_text": "Transcriptional activity of <protein>p105</protein> is also increased in <cell_type>infected cells</cell_type> and is also mediated by <protein>NF-kappa B</protein> through a specific <dna>kappa B motif</dna> ."}
{"id": "1081", "text": "These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV , p105 and p50 , and MAD3 , with the end result of persistent NF-kappa B activation and viral persistence .", "annotated_text": "These results demonstrate the existence of a triple autoregulatory loop in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> involving HIV , <protein>p105</protein> and <protein>p50</protein> , and <protein>MAD3</protein> , with the end result of persistent NF-kappa B activation and viral persistence ."}
{"id": "1082", "text": "Furthermore , persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules .", "annotated_text": "Furthermore , persistent HIV infection of <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> provides a useful model with which to study concomitant modifications of different <protein>I kappa B molecules</protein> ."}
{"id": "1083", "text": "Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor .", "annotated_text": "Glucocorticoid-induced apoptosis of <cell_type>human leukemic cells</cell_type> is caused by the repressive function of the <protein>glucocorticoid receptor</protein> ."}
{"id": "1084", "text": "Induction of apoptosis in lymphocytes , which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia , depends on the glucocorticoid receptor .", "annotated_text": "Induction of apoptosis in <cell_type>lymphocytes</cell_type> , which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia , depends on the <protein>glucocorticoid receptor</protein> ."}
{"id": "1085", "text": "However , the events leading from the activated receptor to cell lysis are not understood .", "annotated_text": "However , the events leading from the activated receptor to cell lysis are not understood ."}
{"id": "1086", "text": "A prevailing hypothesis postulates induction of so-called ' lysis genes ' by the activated receptor .", "annotated_text": "A prevailing hypothesis postulates induction of so-called ' <dna>lysis genes</dna> ' by the <protein>activated receptor</protein> ."}
{"id": "1087", "text": "In this study , we show that an activation-deficient glucocorticoid receptor mutant is as effective as the wild-type receptor in repression of AP-1 activity , inhibition of interleukin-2 production , inhibition of c-myc expression and induction of apoptosis .", "annotated_text": "In this study , we show that an <protein>activation-deficient glucocorticoid receptor mutant</protein> is as effective as the <protein>wild-type receptor</protein> in repression of <protein>AP-1</protein> activity , inhibition of <protein>interleukin-2</protein> production , inhibition of <dna>c-myc</dna> expression and induction of apoptosis ."}
{"id": "1088", "text": "Furthermore , we show that retinoic acid can also induce apoptosis in these cells through the retinoic acid receptor , whose repressive functions but not target site specificity , are similar to those of the glucocorticoid receptor .", "annotated_text": "Furthermore , we show that retinoic acid can also induce apoptosis in these cells through the <protein>retinoic acid receptor</protein> , whose repressive functions but not target site specificity , are similar to those of the <protein>glucocorticoid receptor</protein> ."}
{"id": "1089", "text": "Therefore , the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other transcription factors required for cell survival .", "annotated_text": "Therefore , the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other <protein>transcription factors</protein> required for cell survival ."}
{"id": "1090", "text": "HIV type 1 protease activation of NF-kappa B within T lymphoid cells .", "annotated_text": "HIV type 1 <protein>protease</protein> activation of <protein>NF-kappa B</protein> within <cell_type>T lymphoid cells</cell_type> ."}
{"id": "1091", "text": "NF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes , including IL-2 and the IL-2 receptor , and viral genes transcribed from the HIV-1 LTR .", "annotated_text": "<protein>NF-kappa B</protein> is a <protein>nuclear protein</protein> of the <protein>rel oncogene family</protein> capable of enhancing transcription of <dna>several cellular genes</dna> , including <protein>IL-2</protein> and the <protein>IL-2 receptor</protein> , and <dna>viral genes</dna> transcribed from the <dna>HIV-1 LTR</dna> ."}
{"id": "1092", "text": "It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro .", "annotated_text": "It has been reported that <protein>HIV-1 protease</protein> may cleave the <protein>NF-kappa B</protein> precursor to its active form in vitro ."}
{"id": "1093", "text": "In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells .", "annotated_text": "In this study the effects of HIV protease on <protein>NF-kappa B</protein> precursor activation were examined in Jurkat <cell_type>T cells</cell_type> by introducing a <dna>protease expression vector</dna> into the cells ."}
{"id": "1094", "text": "Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease .", "annotated_text": "Increased <protein>NF-kappa B</protein> activity was observed and this increased activity was blocked by a specific inhibitor of the <protein>viral protease</protein> ."}
{"id": "1095", "text": "Viral transcription , as measured using LTR -CAT assays , was only slightly enhanced in the HIV-protease expressing cells , while secretion of IL-2 and expression of the IL-2 receptor were not affected .", "annotated_text": "Viral transcription , as measured using <dna>LTR</dna> <protein>-CAT</protein> assays , was only slightly enhanced in the <cell_type>HIV-protease expressing cells</cell_type> , while secretion of <protein>IL-2</protein> and expression of the <protein>IL-2</protein> receptor were not affected ."}
{"id": "1096", "text": "The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function .", "annotated_text": "The limited activation of <protein>NF-kappa B</protein> by <protein>HIV protease</protein> appears unlikely to have a significant effect on virus expression or T cell function ."}
{"id": "1097", "text": "Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated , transduced interferon gene : targeted expression to human immunodeficiency virus type 1-infected cells .", "annotated_text": "Inhibition of human immunodeficiency virus type 1 replication by a <dna>Tat-activated , transduced interferon gene</dna> : targeted expression to <cell_type>human immunodeficiency virus type 1-infected cells</cell_type> ."}
{"id": "1098", "text": "We have examined the feasibility of using interferon ( IFN ) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 ( HIV-1 ) therapy in this study .", "annotated_text": "We have examined the feasibility of using <protein>interferon</protein> ( <protein>IFN</protein> ) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 ( HIV-1 ) therapy in this study ."}
{"id": "1099", "text": "To limit expression of a transduced HIV-1 long terminal repeat ( LTR ) -IFNA2 ( the new approved nomenclature for IFN genes is used throughout this article ) hybrid gene to the HIV-1-infected cells , HIV-1 LTR was modified .", "annotated_text": "To limit expression of a transduced <dna>HIV-1 long terminal repeat ( LTR ) -IFNA2</dna> ( the new approved nomenclature for <dna>IFN genes</dna> is used throughout this article ) <dna>hybrid gene</dna> to the <cell_line>HIV-1-infected cells</cell_line> , <dna>HIV-1 LTR</dna> was modified ."}
{"id": "1100", "text": "Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat -mediated transactivation in T-cell lines , as well as in a monocyte line , U937 .", "annotated_text": "Deletion of the <dna>NF-kappa B elements</dna> of the <dna>HIV-1 LTR</dna> significantly inhibited <protein>Tat</protein> -mediated transactivation in <cell_line>T-cell lines</cell_line> , as well as in a <cell_line>monocyte line</cell_line> , <cell_line>U937</cell_line> ."}
{"id": "1101", "text": "Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 ( ISG15 ) , containing the IFN-stimulated response element , partially restored Tat -mediated activation of LTR in T cells as well as in monocytes .", "annotated_text": "Replacement of the <dna>NF-kappa B elements</dna> in the <dna>HIV-1 LTR</dna> by a <dna>DNA fragment</dna> derived from the <dna>5'-flanking region</dna> of <dna>IFN-stimulated gene 15</dna> ( <dna>ISG15</dna> ) , containing the <dna>IFN-stimulated response element</dna> , partially restored <protein>Tat</protein> -mediated activation of <dna>LTR</dna> in <cell_type>T cells</cell_type> as well as in <cell_type>monocytes</cell_type> ."}
{"id": "1102", "text": "Insertion of this chimeric promoter ( ISG15 LTR ) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells , while this promoter was not responsive to tumor necrosis factor alpha -mediated activation .", "annotated_text": "Insertion of this <dna>chimeric promoter</dna> ( <dna>ISG15 LTR</dna> ) upstream of the <dna>human IFNA2 gene</dna> directed high levels of <protein>IFN</protein> synthesis in <cell_line>Tat-expressing cells</cell_line> , while this promoter was not responsive to <protein>tumor necrosis factor alpha</protein> -mediated activation ."}
{"id": "1103", "text": "ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells .", "annotated_text": "<dna>ISG15-LTR-IFN hybrid gene</dna> inserted into the <dna>retrovirus vector</dna> was transduced into <cell_line>Jurkat</cell_line> and <cell_line>U937 cells</cell_line> ."}
{"id": "1104", "text": "Selected transfected clones produced low levels of IFN A ( IFNA ) constitutively , and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained .", "annotated_text": "Selected <cell_line>transfected clones</cell_line> produced low levels of <protein>IFN A</protein> ( <protein>IFNA</protein> ) constitutively , and their abilities to express <protein>interleukin-2</protein> and <protein>interleukin-2 receptor</protein> upon stimulation with <protein>phytohemagglutinin</protein> and phorbol myristate acetate were retained ."}
{"id": "1105", "text": "Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days .", "annotated_text": "Enhancement of <protein>IFNA</protein> synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days ."}
{"id": "1106", "text": "Virus isolated from IFNA-producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene .", "annotated_text": "Virus isolated from <cell_line>IFNA-producing cells</cell_line> was able to replicate in the <cell_line>U937 cells</cell_line> but did not replicate efficiently in <cell_line>U937 cells</cell_line> transduced with the <dna>IFNA gene</dna> ."}
{"id": "1107", "text": "These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication .", "annotated_text": "These results suggest that targeting <protein>IFN</protein> synthesis to <cell_line>HIV-1-infected cells</cell_line> is an attainable goal and that autocrine <protein>IFN</protein> synthesis results in a long-lasting and permanent suppression of HIV-1 replication ."}
{"id": "1108", "text": "Chromosomal localization of two KOX zinc finger genes on chromosome bands 7q21-q22 .", "annotated_text": "Chromosomal localization of two <dna>KOX zinc finger genes</dna> on <dna>chromosome bands</dna> <dna>7q21-q22</dna> ."}
{"id": "1109", "text": "Human cDNAs encoding Kruppel-type zinc finger domains , designated KOX 1-32 , have been cloned from human T lymphocyte cell line libraries .", "annotated_text": "<dna>Human cDNAs</dna> encoding <protein>Kruppel-type zinc finger domains</protein> , designated <dna>KOX 1-32</dna> , have been cloned from <dna>human T lymphocyte cell line libraries</dna> ."}
{"id": "1110", "text": "We report here the regional localizations by in situ hybridization of KOX 18 and KOX 25 on chromosome bands 7q21q22 .", "annotated_text": "We report here the regional localizations by in situ hybridization of <dna>KOX 18</dna> and <dna>KOX 25</dna> on <dna>chromosome bands 7q21q22</dna> ."}
{"id": "1111", "text": "Pulse-field gel electrophoresis ( PFGE ) analysis showed that these genes are physically located within a DNA fragment of 250 kb .", "annotated_text": "Pulse-field gel electrophoresis ( PFGE ) analysis showed that these genes are physically located within a <dna>DNA fragment</dna> of <dna>250 kb</dna> ."}
{"id": "1112", "text": "The genes KOX 4 and KOX 9 , mapped on chromosome 8q24 , were found to be located within a DNA fragment of 450 kb .", "annotated_text": "The genes <dna>KOX 4</dna> and <dna>KOX 9</dna> , mapped on <dna>chromosome 8q24</dna> , were found to be located within a <dna>DNA fragment</dna> of 450 kb ."}
{"id": "1113", "text": "From the present and previous data , eighteen different KOX genes have been located at least two by two within nine DNA fragments of 200 to 580 kb .", "annotated_text": "From the present and previous data , eighteen different <dna>KOX genes</dna> have been located at least two by two within nine <dna>DNA fragments</dna> of 200 to 580 kb ."}
{"id": "1114", "text": "Influence of age on the production of Fos and Jun by influenza virus-exposed T cells .", "annotated_text": "Influence of age on the production of <protein>Fos</protein> and <protein>Jun</protein> by <cell_type>influenza virus-exposed T cells</cell_type> ."}
{"id": "1115", "text": "This study investigated age-related T cell responses after in vitro exposure to influenza A virus .", "annotated_text": "This study investigated age-related T cell responses after in vitro exposure to influenza A virus ."}
{"id": "1116", "text": "Mononuclear leukocytes from young or elderly persons were sham-exposed or exposed to influenza virus for 1 , 24 , and 72 h .", "annotated_text": "<cell_type>Mononuclear leukocytes</cell_type> from young or elderly persons were sham-exposed or exposed to influenza virus for 1 , 24 , and 72 h ."}
{"id": "1117", "text": "Immunofluorescent staining and flow cytometric analysis were then used to detect T cells producing the transcriptional regulating proteins Fos and Jun .", "annotated_text": "Immunofluorescent staining and flow cytometric analysis were then used to detect <cell_type>T cells</cell_type> producing the <protein>transcriptional regulating proteins</protein> <protein>Fos</protein> and <protein>Jun</protein> ."}
{"id": "1118", "text": "Fewer virus-exposed cells from elderly donors stained for Fos and Jun at each data point compared with cells from young donors .", "annotated_text": "Fewer virus-exposed cells from elderly donors stained for <protein>Fos</protein> and <protein>Jun</protein> at each data point compared with cells from young donors ."}
{"id": "1119", "text": "Flow cytometric analysis also showed that at 72 h of virus exposure fewer T cells from the elderly produced interferon-gamma ( IFN-gamma ) , suggesting a link between the magnitude of the Fos and Jun and IFN-gamma responses .", "annotated_text": "Flow cytometric analysis also showed that at 72 h of virus exposure fewer <cell_type>T cells</cell_type> from the elderly produced <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) , suggesting a link between the magnitude of the <protein>Fos</protein> and <protein>Jun</protein> and <protein>IFN-gamma</protein> responses ."}
{"id": "1120", "text": "Thus , failure of virus-exposed T cells to produce Fos and Jun could contribute to the increase in illness due to influenza virus in the elderly .", "annotated_text": "Thus , failure of <cell_type>virus-exposed T cells</cell_type> to produce <protein>Fos</protein> and <protein>Jun</protein> could contribute to the increase in illness due to influenza virus in the elderly ."}
{"id": "1121", "text": "The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors .", "annotated_text": "The regulation of HIV by retinoic acid correlates with cellular expression of the <protein>retinoic acid receptors</protein> ."}
{"id": "1122", "text": "OBJECTIVES : To analyze the effect of retinoic acids ( RA ) on HIV-1 expression and correlate this effect with expression levels of RA receptors ( RARs ) in T-lymphoid and monocytoid cell lines .", "annotated_text": "OBJECTIVES : To analyze the effect of retinoic acids ( RA ) on HIV-1 expression and correlate this effect with expression levels of <protein>RA receptors</protein> ( <protein>RARs</protein> ) in <cell_line>T-lymphoid and monocytoid cell lines</cell_line> ."}
{"id": "1123", "text": "DESIGN AND METHODS : The effect of all-trans and 9-cis RA on HIV-1 production in T-lymphoid ( H9 , CEM ) and monocytoid ( U937 , THP-1 ) cell lines was measured during acute and chronic infection .", "annotated_text": "DESIGN AND METHODS : The effect of all-trans and 9-cis RA on HIV-1 production in <cell_line>T-lymphoid</cell_line> ( <cell_line>H9 , CEM</cell_line> ) and <cell_line>monocytoid ( U937 , THP-1 ) cell lines</cell_line> was measured during acute and chronic infection ."}
{"id": "1124", "text": "The expression levels of human RAR alpha ( hRAR alpha , receptor for all-trans RA ) and the human retinoid-X receptor alpha ( hRXR alpha receptor for 9-cis RA ) were determined by Northern blot analysis .", "annotated_text": "The expression levels of <protein>human RAR alpha</protein> ( <protein>hRAR alpha , receptor</protein> for all-trans RA ) and the <protein>human retinoid-X receptor alpha</protein> ( <protein>hRXR alpha receptor</protein> for 9-cis RA ) were determined by Northern blot analysis ."}
{"id": "1125", "text": "RESULTS : Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells , in the presence and absence of the co-stimulatory agent phorbol myristate acetate ( PMA ) .", "annotated_text": "RESULTS : Both all-trans and 9-cis RA inhibited virus replication in <cell_line>HIV-1 IIIB-infected monocytoid cells</cell_line> , in the presence and absence of the co-stimulatory agent phorbol myristate acetate ( PMA ) ."}
{"id": "1126", "text": "The retinoids had weak or no stimulatory effects on HIV production by T-cell lines .", "annotated_text": "The retinoids had weak or no stimulatory effects on HIV production by <cell_line>T-cell lines</cell_line> ."}
{"id": "1127", "text": "HIV production by PMA-stimulated T-cell lines was inhibited by these retinoids .", "annotated_text": "HIV production by <cell_line>PMA-stimulated T-cell lines</cell_line> was inhibited by these retinoids ."}
{"id": "1128", "text": "The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone .", "annotated_text": "The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone ."}
{"id": "1129", "text": "Human RAR alpha was expressed in H9 , U937 and THP-1 cells , but almost undetectable in CEM cells .", "annotated_text": "<protein>Human RAR alpha</protein> was expressed in <cell_line>H9</cell_line> , <cell_line>U937</cell_line> and <cell_line>THP-1 cells</cell_line> , but almost undetectable in <cell_line>CEM cells</cell_line> ."}
{"id": "1130", "text": "Human RXR alpha was significantly expressed in U937 and THP-1 cells , weakly expressed in H9 cells and not detectable in CEM cells .", "annotated_text": "<protein>Human RXR alpha</protein> was significantly expressed in <cell_line>U937 and THP-1 cells</cell_line> , weakly expressed in <cell_line>H9 cells</cell_line> and not detectable in <cell_line>CEM cells</cell_line> ."}
{"id": "1131", "text": "After stimulation by PMA , RXR alpha expression increased in H9 and U937 cells but not in CEM cells .", "annotated_text": "After stimulation by PMA , <protein>RXR alpha</protein> expression increased in <cell_line>H9</cell_line> and <cell_line>U937 cells</cell_line> but not in <cell_line>CEM cells</cell_line> ."}
{"id": "1132", "text": "Human RAR alpha expression was unchanged in H9 and CEM cells , and elevated in U937 cells , after PMA stimulation .", "annotated_text": "Human RAR alpha expression was unchanged in <cell_line>H9</cell_line> and <cell_line>CEM cells</cell_line> , and elevated in <cell_line>U937 cells</cell_line> , after PMA stimulation ."}
{"id": "1133", "text": "CONCLUSION : The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs .", "annotated_text": "CONCLUSION : The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of <protein>RARs</protein> ."}
{"id": "1134", "text": "Endogenous or exogenously administered RA may have a significant role in HIV regulation .", "annotated_text": "Endogenous or exogenously administered RA may have a significant role in HIV regulation ."}
{"id": "1135", "text": "Functions of glutathione and glutathione disulfide in immunology and immunopathology .", "annotated_text": "Functions of glutathione and glutathione disulfide in immunology and immunopathology ."}
{"id": "1136", "text": "Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione ( GSH ) and glutathione disulfide ( GSSG ) levels and potentiates immunological functions of lymphocytes in vitro .", "annotated_text": "Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione ( GSH ) and glutathione disulfide ( GSSG ) levels and potentiates immunological functions of <cell_type>lymphocytes</cell_type> in vitro ."}
{"id": "1137", "text": "At low GSSG levels , T cells can not optimally activate the immunologically important transcription factor NF kappa B , whereas high GSSG levels inhibit the DNA binding activity of NF kappa B .", "annotated_text": "At low GSSG levels , <cell_type>T cells</cell_type> can not optimally activate the immunologically important <protein>transcription factor</protein> <protein>NF kappa B</protein> , whereas high GSSG levels inhibit the DNA binding activity of <protein>NF kappa B</protein> ."}
{"id": "1138", "text": "The effects of GSSG are antagonized by reduced thioredoxin ( TRX ) .", "annotated_text": "The effects of GSSG are antagonized by reduced <protein>thioredoxin</protein> ( <protein>TRX</protein> ) ."}
{"id": "1139", "text": "As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide , they are likely targets for GSSG action .", "annotated_text": "As the <protein>protein tyrosine kinase</protein> activities <protein>p56lck</protein> and <protein>p59fyn</protein> are activated in intact cells by hydrogen peroxide , they are likely targets for GSSG action ."}
{"id": "1140", "text": "These redox-regulated enzymes trigger signal cascades for NF kappa B activation and transduce signals from the T cell antigen receptor , from CD4 and CD8 molecules , and from the IL-2 receptor beta-chain .", "annotated_text": "These <protein>redox-regulated enzymes</protein> trigger signal cascades for <protein>NF kappa B</protein> activation and transduce signals from the <protein>T cell antigen receptor</protein> , from <protein>CD4</protein> and <protein>CD8 molecules</protein> , and from the <protein>IL-2 receptor beta-chain</protein> ."}
{"id": "1141", "text": "The effector phase of cytotoxic T cell responses and IL-2 -dependent functions are inhibited even by a partial depletion of the intracellular GSH pool .", "annotated_text": "The effector phase of <cell_type>cytotoxic T cell</cell_type> responses and <protein>IL-2</protein> -dependent functions are inhibited even by a partial depletion of the intracellular GSH pool ."}
{"id": "1142", "text": "As signal transduction is facilitated by prooxidant conditions , we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency .", "annotated_text": "As signal transduction is facilitated by prooxidant conditions , we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency ."}
{"id": "1143", "text": "As HIV-infected patients and SIV-infected rhesus macaques have , on the average , significantly decreased plasma cyst ( e ) ine and intracellular GSH levels , we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well .", "annotated_text": "As HIV-infected patients and SIV-infected rhesus macaques have , on the average , significantly decreased plasma cyst ( e ) ine and intracellular GSH levels , we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well ."}
{"id": "1144", "text": "T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity : a preliminary report .", "annotated_text": "<cell_type>T cells</cell_type> from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity : a preliminary report ."}
{"id": "1145", "text": "Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma ( RCC ) may be related to alterations in signal transduction pathways .", "annotated_text": "Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma ( RCC ) may be related to alterations in signal transduction pathways ."}
{"id": "1146", "text": "We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity .", "annotated_text": "We report that <cell_type>T cells</cell_type> from RCC patients have two alterations in kappa B motif-specific DNA-binding activity ."}
{"id": "1147", "text": "The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts , which was observed in the electrophoretic mobility shift assay .", "annotated_text": "The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts , which was observed in the electrophoretic mobility shift assay ."}
{"id": "1148", "text": "The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro .", "annotated_text": "The magnitude of kappa B activity in <cell_type>unstimulated patient T cells</cell_type> was similar to that observed in <cell_type>T cells</cell_type> from normal individuals that had been activated in vitro ."}
{"id": "1149", "text": "On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins , the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 ( p50 ) subunit .", "annotated_text": "On the basis of Western blotting experiments using <protein>antibodies</protein> to <protein>kappa B/Rel family proteins</protein> , the kappa B-binding activity constitutively expressed in <cell_type>T cells</cell_type> from RCC patients is composed mostly of the <protein>NF-kappa B1 ( p50 ) subunit</protein> ."}
{"id": "1150", "text": "The second abnormality in kappa B-binding activity in T cells from these patients is that RelA , a member of the Rel homology family which is part of the normal NF-kappa B complex , was not induced in the nucleus following activation .", "annotated_text": "The second abnormality in kappa B-binding activity in <cell_type>T cells</cell_type> from these patients is that <protein>RelA</protein> , a member of the <protein>Rel homology family</protein> which is part of the normal <protein>NF-kappa B complex</protein> , was not induced in the nucleus following activation ."}
{"id": "1151", "text": "Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells .", "annotated_text": "Western blotting analysis did not detect any <protein>RelA</protein> in nuclear extracts either before or after stimulation of <cell_type>T cells</cell_type> ."}
{"id": "1152", "text": "The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli .", "annotated_text": "The altered kappa B-binding activity in <cell_type>T cells</cell_type> from RCC patients may impair their capacity to respond normally to various stimuli ."}
{"id": "1153", "text": "Hemoglobin switching in humans is accompanied by changes in the ratio of the transcription factors , GATA-1 and SP1 .", "annotated_text": "<protein>Hemoglobin</protein> switching in humans is accompanied by changes in the ratio of the <protein>transcription factors</protein> , <protein>GATA-1</protein> and <protein>SP1</protein> ."}
{"id": "1154", "text": "BACKGROUND : Understanding the mechanism of developmental regulation of hemoglobin switching has scientific as well as clinical relevance because of the influence of fetal hemoglobin ( HbF ) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia .", "annotated_text": "BACKGROUND : Understanding the mechanism of developmental regulation of <protein>hemoglobin</protein> switching has scientific as well as clinical relevance because of the influence of fetal <protein>hemoglobin</protein> ( <protein>HbF</protein> ) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia ."}
{"id": "1155", "text": "We have previously found that the normal developmental patterns of globin gene expression are recapitulated in an experimental system of primary cultures that support differentiation of erythroid progenitors .", "annotated_text": "We have previously found that the normal developmental patterns of <dna>globin gene</dna> expression are recapitulated in an experimental system of <cell_line>primary cultures</cell_line> that support differentiation of <cell_type>erythroid progenitors</cell_type> ."}
{"id": "1156", "text": "We further found that high activities of the transcriptional activators , GATA-1 and SP1 , are associated with normal adult erythroid differentiation .", "annotated_text": "We further found that high activities of the <protein>transcriptional activators</protein> , <protein>GATA-1</protein> and <protein>SP1</protein> , are associated with normal adult erythroid differentiation ."}
{"id": "1157", "text": "MATERIALS AND METHODS : In the present work , we have studied , the activities of GATA-1 and SP1 during differentiation of cultured erythroid progenitors derived from cord blood and from fetal livers , as well as from beta zero-thalassemia patients .", "annotated_text": "MATERIALS AND METHODS : In the present work , we have studied , the activities of <protein>GATA-1</protein> and <protein>SP1</protein> during differentiation of cultured <cell_type>erythroid progenitors</cell_type> derived from cord blood and from fetal livers , as well as from beta zero-thalassemia patients ."}
{"id": "1158", "text": "RESULTS : The results showed high GATA-1 binding activity and very low SP1 activity in the fetal liver cultures .", "annotated_text": "RESULTS : The results showed high <protein>GATA-1</protein> binding activity and very low <protein>SP1</protein> activity in the <cell_line>fetal liver cultures</cell_line> ."}
{"id": "1159", "text": "This pattern was in contrast to cultures derived from normal adult peripheral blood , in which both GATA-1 and SP1 activities were high .", "annotated_text": "This pattern was in contrast to cultures derived from normal adult peripheral blood , in which both <protein>GATA-1</protein> and <protein>SP1</protein> activities were high ."}
{"id": "1160", "text": "Cord blood cultures showed an additive combination of `` adult '' and `` fetal '' patterns .", "annotated_text": "Cord blood cultures showed an additive combination of `` adult '' and `` fetal '' patterns ."}
{"id": "1161", "text": "The progenitors derived from a beta zero-thalassemia patient with high HbF production showed `` fetal '' pattern .", "annotated_text": "The progenitors derived from a beta zero-thalassemia patient with high <protein>HbF</protein> production showed `` fetal '' pattern ."}
{"id": "1162", "text": "On the other hand , in cultures of 2 beta zero-thalassemia patients without high HbF , `` adult '' pattern was observed .", "annotated_text": "On the other hand , in cultures of 2 beta zero-thalassemia patients without high <protein>HbF</protein> , `` adult '' pattern was observed ."}
{"id": "1163", "text": "CONCLUSIONS : In the present work , we show that human fetal and adult erythroid progenitors are distinct in their transcription factors , and that the commitment to fetal or adult program occurs at a very early differentiation stage .", "annotated_text": "CONCLUSIONS : In the present work , we show that <cell_type>human fetal and adult erythroid progenitors</cell_type> are distinct in their <protein>transcription factors</protein> , and that the commitment to fetal or adult program occurs at a very early differentiation stage ."}
{"id": "1164", "text": "Our studies also demonstrate that under anemic stress , recruitment of fetal progenitors may occur in adulthood .", "annotated_text": "Our studies also demonstrate that under anemic stress , recruitment of <cell_type>fetal progenitors</cell_type> may occur in adulthood ."}
{"id": "1165", "text": "Transcription-independent turnover of I kappa B alpha during monocyte adherence : implications for a translational component regulating I kappa B alpha/MAD-3 mRNA levels .", "annotated_text": "Transcription-independent turnover of <protein>I kappa B alpha</protein> during monocyte adherence : implications for a translational component regulating <rna>I kappa B alpha/MAD-3 mRNA</rna> levels ."}
{"id": "1166", "text": "We identified I kappa B alpha/MAD-3 as an immediate-early gene in human monocytes that is expressed in response to a variety of signals , including adhesion , lipopolysaccharide , and phorbol myristate acetate .", "annotated_text": "We identified <protein>I kappa B alpha/MAD-3</protein> as an <dna>immediate-early gene</dna> in <cell_type>human monocytes</cell_type> that is expressed in response to a variety of signals , including adhesion , lipopolysaccharide , and phorbol myristate acetate ."}
{"id": "1167", "text": "Within 5 min of monocyte adhesion , the level of the I kappa B alpha protein is markedly diminished but is rapidly replaced in a cycloheximide-sensitive manner within 20 min .", "annotated_text": "Within 5 min of monocyte adhesion , the level of the <protein>I kappa B alpha protein</protein> is markedly diminished but is rapidly replaced in a cycloheximide-sensitive manner within 20 min ."}
{"id": "1168", "text": "Accompanying the rapid turnover of the I kappa B alpha protein is simultaneous translocation of NF-kappa B-related transcription factors to nuclei of adhered monocytes .", "annotated_text": "Accompanying the rapid turnover of the <protein>I kappa B alpha protein</protein> is simultaneous translocation of <protein>NF-kappa B-related transcription factors</protein> to nuclei of adhered monocytes ."}
{"id": "1169", "text": "The demonstration that NF-kappa B can regulate I kappa B alpha/MAD-3 gene transcription in other cell types suggested that the rapid increase in steady-state I kappa B alpha/MAD-3 mRNA levels we observed within 30 min of monocyte adherence would result from NF-kappa B -dependent transcriptional stimulation of the I kappa B alpha/MAD-3 gene .", "annotated_text": "The demonstration that <protein>NF-kappa B</protein> can regulate <dna>I kappa B alpha/MAD-3 gene</dna> transcription in other cell types suggested that the rapid increase in steady-state <rna>I kappa B alpha/MAD-3 mRNA</rna> levels we observed within 30 min of monocyte adherence would result from <protein>NF-kappa B</protein> -dependent transcriptional stimulation of the <dna>I kappa B alpha/MAD-3 gene</dna> ."}
{"id": "1170", "text": "Nuclear run-on analyses indicated that , instead , while several immediate-early cytokine genes , such as the interleukin 1 beta ( IL-1 beta ) gene , were transcriptionally activated during monocyte adhesion , the rate of I kappa B alpha/MAD-3 gene transcription remained constant .", "annotated_text": "Nuclear run-on analyses indicated that , instead , while several <dna>immediate-early cytokine genes</dna> , such as the <dna>interleukin 1 beta ( IL-1 beta ) gene</dna> , were transcriptionally activated during monocyte adhesion , the rate of <dna>I kappa B alpha/MAD-3 gene</dna> transcription remained constant ."}
{"id": "1171", "text": "The adherence-dependent increase in I kappa B alpha/MAD-3 mRNA levels was also not a consequence of mRNA stabilization events .", "annotated_text": "The adherence-dependent increase in <rna>I kappa B alpha/MAD-3 mRNA</rna> levels was also not a consequence of <rna>mRNA</rna> stabilization events ."}
{"id": "1172", "text": "Interestingly , while increases in both IL-1 beta and I kappa B alpha/MAD-3 mRNA levels were detected in nuclei of adherent monocytes , cytoplasmic levels of IL-1 beta mRNA increased during adherence whereas those of I kappa B alpha/MAD-3 mRNA did not .", "annotated_text": "Interestingly , while increases in both IL-1 beta and I kappa B alpha/MAD-3 mRNA levels were detected in nuclei of <cell_type>adherent monocytes</cell_type> , cytoplasmic levels of <rna>IL-1 beta mRNA</rna> increased during adherence whereas those of <rna>I kappa B alpha/MAD-3 mRNA</rna> did not ."}
{"id": "1173", "text": "Taken together , our data suggest that two interactive mechanisms regulate monocytic I kappa B alpha/MAD-3 mRNA levels .", "annotated_text": "Taken together , our data suggest that two interactive mechanisms regulate <rna>monocytic I kappa B alpha/MAD-3 mRNA</rna> levels ."}
{"id": "1174", "text": "We propose that adherent monocytes regulate nuclear processing ( or decay ) of I kappa B alpha/MAD-3 mRNA , thereby increasing mRNA levels without stimulating I kappa B alpha/MAD-3 gene transcription .", "annotated_text": "We propose that <cell_type>adherent monocytes</cell_type> regulate nuclear processing ( or decay ) of <rna>I kappa B alpha/MAD-3 mRNA</rna> , thereby increasing mRNA levels without stimulating <dna>I kappa B alpha/MAD-3 gene</dna> transcription ."}
{"id": "1175", "text": "Moreover , since inhibition of protein synthesis leads to accumulation of I kappa B alpha/MAD-3 mRNA without stimulating I kappa B alpha/MAD-3 gene transcription , we suggest that low cytoplasmic levels of I kappa B alpha/MAD-3 mRNA are maintained by a translation-dependent degradation mechanism .", "annotated_text": "Moreover , since inhibition of protein synthesis leads to accumulation of <rna>I kappa B alpha/MAD-3 mRNA</rna> without stimulating <dna>I kappa B alpha/MAD-3 gene</dna> transcription , we suggest that low cytoplasmic levels of <rna>I kappa B alpha/MAD-3 mRNA</rna> are maintained by a translation-dependent degradation mechanism ."}
{"id": "1176", "text": "Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor function via the basic helix-loop-helix and PAS domains .", "annotated_text": "Distinct roles of the molecular <protein>chaperone hsp90</protein> in modulating dioxin receptor function via the basic <protein>helix-loop-helix</protein> and <protein>PAS domains</protein> ."}
{"id": "1177", "text": "The intracellular dioxin receptor mediates signal transduction by dioxin and functions as a ligand-activated transcription factor .", "annotated_text": "The <protein>intracellular dioxin receptor</protein> mediates signal transduction by dioxin and functions as a <protein>ligand-activated transcription factor</protein> ."}
{"id": "1178", "text": "It contains a basic helix-loop-helix ( bHLH ) motif contiguous with a Per-Arnt-Sim ( PAS ) homology region .", "annotated_text": "It contains a <protein>basic helix-loop-helix ( bHLH ) motif</protein> contiguous with a <protein>Per-Arnt-Sim ( PAS ) homology region</protein> ."}
{"id": "1179", "text": "In extracts from nonstimulated cells the receptor is recovered in an inducible cytoplasmic form associated with the 90-kDa heat shock protein ( hsp90 ) , a molecular chaperone .", "annotated_text": "In extracts from nonstimulated cells the receptor is recovered in an inducible cytoplasmic form associated with the <protein>90-kDa heat shock protein</protein> ( <protein>hsp90</protein> ) , a <protein>molecular chaperone</protein> ."}
{"id": "1180", "text": "We have reconstituted ligand-dependent activation of the receptor to a DNA-binding form by using the dioxin receptor and its bHLH-PAS partner factor Arnt expressed by in vitro translation in reticulocyte lysate .", "annotated_text": "We have reconstituted ligand-dependent activation of the receptor to a <protein>DNA-binding form</protein> by using the <protein>dioxin receptor</protein> and its <protein>bHLH-PAS partner factor</protein> <protein>Arnt</protein> expressed by in vitro translation in reticulocyte lysate ."}
{"id": "1181", "text": "Deletion of the PAS domain of the receptor resulted in constitutive dimerization with Arnt .", "annotated_text": "Deletion of the <protein>PAS domain</protein> of the receptor resulted in constitutive dimerization with <protein>Arnt</protein> ."}
{"id": "1182", "text": "In contrast , this receptor mutant showed low levels of xenobiotic response element-binding activity , indicating that the PAS domain may be important for DNA-binding affinity and/or specificity of the receptor .", "annotated_text": "In contrast , this receptor mutant showed low levels of xenobiotic response element-binding activity , indicating that the <protein>PAS domain</protein> may be important for DNA-binding affinity and/or specificity of the receptor ."}
{"id": "1183", "text": "It was not possible to reconstitute dioxin receptor function with proteins expressed in wheat germ lysate .", "annotated_text": "It was not possible to reconstitute <protein>dioxin receptor</protein> function with proteins expressed in wheat germ lysate ."}
{"id": "1184", "text": "In line with these observations , reticulocyte lysate but not wheat germ lysate promoted the association of de novo synthesized dioxin receptor with hsp90 .", "annotated_text": "In line with these observations , reticulocyte lysate but not wheat germ lysate promoted the association of de novo synthesized <protein>dioxin receptor</protein> with <protein>hsp90</protein> ."}
{"id": "1185", "text": "At least two distinct domains of the receptor mediated interaction with hsp90 : the ligand-binding domain located within the PAS region and , surprisingly , the bHLH domain .", "annotated_text": "At least two distinct domains of the receptor mediated interaction with <protein>hsp90</protein> : the <protein>ligand-binding domain</protein> located within the <protein>PAS region</protein> and , surprisingly , the <protein>bHLH domain</protein> ."}
{"id": "1186", "text": "Whereas ligand-binding activity correlated with association with hsp90 , bHLH- hsp90 interaction appeared to be important for DNA-binding activity but not for dimerization of the receptor .", "annotated_text": "Whereas ligand-binding activity correlated with association with <protein>hsp90</protein> , bHLH- <protein>hsp90</protein> interaction appeared to be important for DNA-binding activity but not for dimerization of the receptor ."}
{"id": "1187", "text": "Several distinct roles for hsp90 in modulating dioxin receptor function are therefore likely : correct folding of the ligand-binding domain , interference with Arnt heterodimerization , and folding of a DNA-binding conformation of the bHLH domain .", "annotated_text": "Several distinct roles for <protein>hsp90</protein> in modulating <protein>dioxin receptor</protein> function are therefore likely : correct folding of the ligand-binding domain , interference with <protein>Arnt</protein> heterodimerization , and folding of a DNA-binding conformation of the <protein>bHLH domain</protein> ."}
{"id": "1188", "text": "Thus , the dioxin receptor system provides a complex and interesting model of the regulation of transcription factors by hsp90 .", "annotated_text": "Thus , the <protein>dioxin receptor</protein> system provides a complex and interesting model of the regulation of <protein>transcription factors</protein> by <protein>hsp90</protein> ."}
{"id": "1189", "text": "Induction of transcription factors in human T lymphocytes by aspirin-like drugs .", "annotated_text": "Induction of <protein>transcription factors</protein> in <cell_type>human T lymphocytes</cell_type> by aspirin-like drugs ."}
{"id": "1190", "text": "Aspirin-like drugs ( ALD ) induce calcium mobilization , an essential component of T cell activation , but do not induce the biosynthesis of IL-2 .", "annotated_text": "Aspirin-like drugs ( ALD ) induce calcium mobilization , an essential component of T cell activation , but do not induce the biosynthesis of <protein>IL-2</protein> ."}
{"id": "1191", "text": "To understand the extent to which ALD may mimic mitogenic stimulation , we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells .", "annotated_text": "To understand the extent to which ALD may mimic mitogenic stimulation , we studied cytoplasmic and nuclear signaling steps in <cell_line>ALD-treated T cells</cell_line> ."}
{"id": "1192", "text": "We found that ALD induce a transient activation of protein kinase ( PKC ) but have no effect ( in comparison to anti-CD3 antibodies ) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation .", "annotated_text": "We found that ALD induce a transient activation of <protein>protein kinase</protein> ( <protein>PKC</protein> ) but have no effect ( in comparison to <protein>anti-CD3 antibodies</protein> ) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation ."}
{"id": "1193", "text": "ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin , a tyrosine-protein kinase -specific inhibitor .", "annotated_text": "ALD-induced calcium mobilization and <protein>PKC</protein> activation are independent of <protein>tyrosine protein kinase</protein> activity as shown by the lack of effect of herbimycin , a <protein>tyrosine-protein kinase</protein> -specific inhibitor ."}
{"id": "1194", "text": "Although we detected no IL-2 mRNA in ALD-treated cells , the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region : NFAT , NF kappa B , and AP-1 .", "annotated_text": "Although we detected no <rna>IL-2 mRNA</rna> in <cell_line>ALD-treated cells</cell_line> , the nuclei of these cells contain proteins capable of binding to three <dna>regulatory sequences</dna> in the <dna>IL-2 promoter region</dna> : <protein>NFAT</protein> , <protein>NF kappa B</protein> , and <protein>AP-1</protein> ."}
{"id": "1195", "text": "These binding activities are expressed only in activated T cells .", "annotated_text": "These binding activities are expressed only in <cell_type>activated T cells</cell_type> ."}
{"id": "1196", "text": "The expression of AP-1 depended on calcium mobilization and PKC activation .", "annotated_text": "The expression of <protein>AP-1</protein> depended on calcium mobilization and <protein>PKC</protein> activation ."}
{"id": "1197", "text": "These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling , although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD .", "annotated_text": "These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling , although some events induced by stimulation with <protein>anti-CD3 antibodies</protein> are not induced by ALD ."}
{"id": "1198", "text": "The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors .", "annotated_text": "The signal is transmitted to the nucleus and induces DNA-binding activity by several <protein>transcription factors</protein> ."}
{"id": "1199", "text": "However , the ALD stimulus is not capable of causing complete T cell activation .", "annotated_text": "However , the ALD stimulus is not capable of causing complete T cell activation ."}
{"id": "1200", "text": "Protein kinase C is not a downstream effector of p21ras in activated T cells .", "annotated_text": "<protein>Protein kinase C</protein> is not a downstream effector of <dna>p21ras</dna> in <cell_type>activated T cells</cell_type> ."}
{"id": "1201", "text": "The aim of this present study was to investigate the role of protein kinase C ( PKC ) , downstream of p21ras , in activating interleukin-2 ( IL-2 ) gene expression .", "annotated_text": "The aim of this present study was to investigate the role of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) , downstream of <dna>p21ras</dna> , in activating <dna>interleukin-2 ( IL-2 ) gene</dna> expression ."}
{"id": "1202", "text": "It has been reported that PKC is an effector of p21ras in T cells .", "annotated_text": "It has been reported that <protein>PKC</protein> is an <protein>effector</protein> of <dna>p21ras</dna> in <cell_type>T cells</cell_type> ."}
{"id": "1203", "text": "Data is presented , using the potent and selective PKC inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant , which clearly shows that PKC is not downstream of p21ras in the induction of NF-AT and AP-1 transcriptional activity and in the expression of IL-2 in human Jurkat T cells .", "annotated_text": "Data is presented , using the potent and selective <protein>PKC</protein> inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant , which clearly shows that <protein>PKC</protein> is not downstream of <dna>p21ras</dna> in the induction of <protein>NF-AT</protein> and <protein>AP-1</protein> transcriptional activity and in the expression of <protein>IL-2</protein> in <cell_line>human Jurkat T cells</cell_line> ."}
{"id": "1204", "text": "Reporter gene experiments demonstrated that NF-kappa B transcriptional activity is not affected by expression of activated p21ras .", "annotated_text": "Reporter gene experiments demonstrated that <protein>NF-kappa B</protein> transcriptional activity is not affected by expression of activated <dna>p21ras</dna> ."}
{"id": "1205", "text": "The signaling pathways involving PKC activation , calcium mobilization and ras activation combine to provide the necessary components for production of IL-2 during T cell activation .", "annotated_text": "The signaling pathways involving <protein>PKC</protein> activation , calcium mobilization and <protein>ras</protein> activation combine to provide the necessary components for production of <protein>IL-2</protein> during T cell activation ."}
{"id": "1206", "text": "The C-terminus of the B cell activator Oct-2 functions as an activation domain in yeast .", "annotated_text": "The <protein>C-terminus</protein> of the <protein>B cell activator</protein> <protein>Oct-2</protein> functions as an <protein>activation domain</protein> in yeast ."}
{"id": "1207", "text": "Oct-1 and Oct-2 are human transcriptional activators that bind to the same DNA element but activate distinct sets of genes .", "annotated_text": "<protein>Oct-1</protein> and <protein>Oct-2</protein> are human <protein>transcriptional activators</protein> that bind to the same DNA element but activate distinct sets of genes ."}
{"id": "1208", "text": "We expressed these factors in S. cerevisiae and observed greater than 5-fold stimulation of a lacZ reporter gene only with Oct-2 .", "annotated_text": "We expressed these factors in S. cerevisiae and observed greater than 5-fold stimulation of a <dna>lacZ reporter gene</dna> only with <protein>Oct-2</protein> ."}
{"id": "1209", "text": "Transfer of the Oct-2 C-terminal domain onto either Oct-1 ( Oct1.2 ) or a nonactivating DNA-binding domain from GAL4 created activators capable of greater than 15 and 10-fold stimulation of activity , respectively .", "annotated_text": "Transfer of the <protein>Oct-2 C-terminal domain</protein> onto either <protein>Oct-1</protein> ( <protein>Oct1.2</protein> ) or a <protein>nonactivating DNA-binding domain</protein> from <protein>GAL4</protein> created activators capable of greater than 15 and 10-fold stimulation of activity , respectively ."}
{"id": "1210", "text": "Thus , the C-terminus of Oct-2 is sufficient to confer activation potential to nonactive DNA-binding fragments in yeast .", "annotated_text": "Thus , the <protein>C-terminus</protein> of <protein>Oct-2</protein> is sufficient to confer activation potential to nonactive <dna>DNA-binding fragments</dna> in yeast ."}
{"id": "1211", "text": "Glucocorticoid-induced apoptosis of lymphoid cells .", "annotated_text": "Glucocorticoid-induced apoptosis of <cell_type>lymphoid cells</cell_type> ."}
{"id": "1212", "text": "The induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis .", "annotated_text": "The induction of cell death in <cell_type>lymphoid cells</cell_type> by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis ."}
{"id": "1213", "text": "Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids .", "annotated_text": "Although the exact mechanism by which apoptosis occurs in <cell_type>lymphocytes</cell_type> is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids ."}
{"id": "1214", "text": "The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied , as well as the involvement of several oncogenes in glucocorticoid-induced cell lysis .", "annotated_text": "The role of <dna>chromatin</dna> degradation and <protein>endonucleases</protein> in the apoptotic process has been closely studied , as well as the involvement of several <dna>oncogenes</dna> in glucocorticoid-induced cell lysis ."}
{"id": "1215", "text": "In addition , the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention .", "annotated_text": "In addition , the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention ."}
{"id": "1216", "text": "Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes .", "annotated_text": "<protein>Interleukin-2</protein> induces tyrosine phosphorylation and nuclear translocation of <protein>stat3</protein> in <cell_type>human T lymphocytes</cell_type> ."}
{"id": "1217", "text": "An early biochemical event associated with T cell activation through the interleukin-2 receptor ( IL-2R ) is tyrosine phosphorylation of several intracellular substrates .", "annotated_text": "An early biochemical event associated with T cell activation through the <protein>interleukin-2 receptor</protein> ( <protein>IL-2R</protein> ) is tyrosine phosphorylation of several intracellular substrates ."}
{"id": "1218", "text": "The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown .", "annotated_text": "The exact mechanism by which <protein>IL-2</protein> regulates transcription of different genes is presently unknown ."}
{"id": "1219", "text": "Here , we report that stimulation through the IL-2R induced tyrosine phosphorylation and subsequent nuclear translocation of stat3 , a newly identified member of the signal transducers and activators of transcription ( STAT ) family of proteins .", "annotated_text": "Here , we report that stimulation through the <protein>IL-2R</protein> induced tyrosine phosphorylation and subsequent nuclear translocation of <protein>stat3</protein> , a newly identified member of the <protein>signal transducers and activators of transcription ( STAT ) family</protein> of proteins ."}
{"id": "1220", "text": "In contrast , stat1 proteins were not tyrosine phosphorylated after IL-2 ligation , whereas tyrosine-phosphorylated stat1 proteins ( 91 and 84 kDa proteins ) were translocated to the nucleus following interferon-gamma treatment of HeLa cells .", "annotated_text": "In contrast , stat1 proteins were not tyrosine phosphorylated after <protein>IL-2</protein> ligation , whereas <protein>tyrosine-phosphorylated stat1 proteins</protein> ( <protein>91 and 84 kDa proteins</protein> ) were translocated to the nucleus following <protein>interferon-gamma</protein> treatment of <cell_line>HeLa cells</cell_line> ."}
{"id": "1221", "text": "Apart from stat3 , another cytoplasmic protein was tyrosine phosphorylated and subsequently translocated to the nucleus in response to IL-2 .", "annotated_text": "Apart from <protein>stat3</protein> , another <protein>cytoplasmic protein</protein> was tyrosine phosphorylated and subsequently translocated to the nucleus in response to <protein>IL-2</protein> ."}
{"id": "1222", "text": "This protein had an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera .", "annotated_text": "This protein had an apparent molecular mass of 84 kDa and was not recognized by <protein>stat3</protein> or <protein>stat1 mAb</protein> or antisera ."}
{"id": "1223", "text": "Since IL-2 induced nuclear translocation of the 84 kDa protein and stat3 followed identical kinetics , p84 is a candidate for a new , yet undefined , member of the STAT family .", "annotated_text": "Since <protein>IL-2</protein> induced nuclear translocation of the <protein>84 kDa protein</protein> and <protein>stat3</protein> followed identical kinetics , <protein>p84</protein> is a candidate for a new , yet undefined , member of the STAT family ."}
{"id": "1224", "text": "Taken together , we report that IL-2 induces tyrosine phosphorylation and subsequent nuclear translocation of stat3 and an as yet undefined 84-kDa protein in antigen-specific human T cell lines .", "annotated_text": "Taken together , we report that <protein>IL-2</protein> induces tyrosine phosphorylation and subsequent nuclear translocation of <protein>stat3</protein> and an as yet undefined <protein>84-kDa protein</protein> in <cell_line>antigen-specific human T cell lines</cell_line> ."}
{"id": "1225", "text": "Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA ( p65 ) -mediated induction of the c-rel gene .", "annotated_text": "Human T-cell leukemia virus type I <protein>Tax</protein> activation of <protein>NF-kappa B/Rel</protein> involves phosphorylation and degradation of <protein>I kappa B alpha</protein> and <protein>RelA</protein> ( <protein>p65</protein> ) -mediated induction of the <dna>c-rel gene</dna> ."}
{"id": "1226", "text": "The tax gene product of human T-cell leukemia virus type I ( HTLV-I ) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth .", "annotated_text": "The tax gene product of human T-cell leukemia virus type I ( HTLV-I ) is a potent <protein>transcriptional activator</protein> that both stimulates viral gene expression and activates an array of <dna>cellular genes</dna> involved in <cell_type>T-cell</cell_type> growth ."}
{"id": "1227", "text": "Tax acts indirectly by inducing or modifying the action of various host transcription factors , including members of the NF-kappa B/Rel family of enhancer-binding proteins .", "annotated_text": "Tax acts indirectly by inducing or modifying the action of various host <protein>transcription factors</protein> , including members of the <protein>NF-kappa B/Rel family</protein> of <protein>enhancer-binding proteins</protein> ."}
{"id": "1228", "text": "In resting T cells , many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins , including I kappa B alpha .", "annotated_text": "In <cell_type>resting T cells</cell_type> , many of these <protein>NF-kappa B/Rel factors</protein> are sequestered in the cytoplasm by various <protein>ankyrin-rich inhibitory proteins</protein> , including <protein>I kappa B alpha</protein> ."}
{"id": "1229", "text": "HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes ; however , the biochemical mechanism ( s ) underlying this response remains poorly understood .", "annotated_text": "<protein>HTLV-I Tax</protein> expression leads to the constitutive nuclear expression of biologically active <protein>NF-kappa B</protein> and <protein>c-Rel complexes</protein> ; however , the biochemical mechanism ( s ) underlying this response remains poorly understood ."}
{"id": "1230", "text": "In this study , we demonstrate that Tax -stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha .", "annotated_text": "In this study , we demonstrate that <protein>Tax</protein> -stimulated nuclear expression of <protein>NF-kappa B</protein> in both <cell_line>HTLV-I-infected and Tax-transfected human T cells</cell_line> is associated with the phosphorylation and rapid proteolytic degradation of <protein>I kappa B alpha</protein> ."}
{"id": "1231", "text": "In contrast to prior in vitro studies , at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation , thereby promoting the nuclear translocation of the active NF-kappa B complex .", "annotated_text": "In contrast to prior in vitro studies , at least a fraction of the phosphorylated form of <protein>I kappa B alpha</protein> remains physically associated with the <protein>NF-kappa B complex</protein> in vivo but is subject to rapid degradation , thereby promoting the nuclear translocation of the active <protein>NF-kappa B complex</protein> ."}
{"id": "1232", "text": "We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA ( p65 ) subunit of NF-kappa B , which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element .", "annotated_text": "We further demonstrate that <protein>Tax</protein> induction of nuclear <protein>c-Rel</protein> expression is activated by the <protein>RelA</protein> ( <protein>p65</protein> ) subunit of <protein>NF-kappa B</protein> , which activates transcription of the <dna>c-rel gene</dna> through an intrinsic <dna>kappa B enhancer element</dna> ."}
{"id": "1233", "text": "In normal cells , the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production , indicating the presence of an autoregulatory loop .", "annotated_text": "In normal cells , the subsequent accumulation of <protein>nuclear c-Rel</protein> acts to inhibit its own continued production , indicating the presence of an autoregulatory loop ."}
{"id": "1234", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "1235", "text": "Activation of NF-kappa B in vivo is regulated by multiple phosphorylations .", "annotated_text": "Activation of <protein>NF-kappa B</protein> in vivo is regulated by multiple phosphorylations ."}
{"id": "1236", "text": "The activation of nuclear factor kappa B ( NF-kappa B ) in intact cells is mechanistically not well understood .", "annotated_text": "The activation of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) in intact cells is mechanistically not well understood ."}
{"id": "1237", "text": "Therefore we investigated the modifications imposed on NF-kappa B/I kappa B components following stimulation and show that the final step of NF-kappa B induction in vivo involves phosphorylation of several members of the NF-kappa B/I kappa B protein families .", "annotated_text": "Therefore we investigated the modifications imposed on <protein>NF-kappa B/I kappa B components</protein> following stimulation and show that the final step of <protein>NF-kappa B</protein> induction in vivo involves phosphorylation of several members of the <protein>NF-kappa B/I kappa B protein families</protein> ."}
{"id": "1238", "text": "In HeLa cells as well as in B cells , TNF-alpha rapidly induced nuclear translocation primarily of p50-p65 , but not of c-rel .", "annotated_text": "In <cell_line>HeLa cells</cell_line> as well as in <cell_type>B cells</cell_type> , TNF-alpha rapidly induced nuclear translocation primarily of <protein>p50-p65</protein> , but not of <protein>c-rel</protein> ."}
{"id": "1239", "text": "Both NF-kappa B precursors and I kappa B alpha became strongly phosphorylated with the same kinetics .", "annotated_text": "Both <protein>NF-kappa B</protein> precursors and <protein>I kappa B alpha</protein> became strongly phosphorylated with the same kinetics ."}
{"id": "1240", "text": "In addition to the inducible phosphorylation after stimulation , B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha .", "annotated_text": "In addition to the inducible phosphorylation after stimulation , <cell_type>B lymphocytes</cell_type> containing constitutive nuclear <protein>NF-kappa B</protein> revealed constitutively phosphorylated <protein>p65</protein> and <protein>I kappa B alpha</protein> ."}
{"id": "1241", "text": "Phosphorylation was accompanied by induced processing of the precursors p100 and p105 and by degradation of I kappa B alpha .", "annotated_text": "Phosphorylation was accompanied by induced processing of the precursors <protein>p100</protein> and <protein>p105</protein> and by degradation of <protein>I kappa B alpha</protein> ."}
{"id": "1242", "text": "As an in vitro model we show that phosphorylation of p105 impedes its ability to interact with NF-kappa B , as has been shown before for I kappa B alpha .", "annotated_text": "As an in vitro model we show that phosphorylation of <protein>p105</protein> impedes its ability to interact with <protein>NF-kappa B</protein> , as has been shown before for <protein>I kappa B alpha</protein> ."}
{"id": "1243", "text": "Surprisingly , even p65 , but not c-rel , was phosphorylated after induction in vivo , suggesting that TNF-alpha selectively activates only specific NF-kappa B heteromers and that modifications regulate not only I kappa B molecules but also NF-kappa B molecules .", "annotated_text": "Surprisingly , even <protein>p65</protein> , but not <protein>c-rel</protein> , was phosphorylated after induction in vivo , suggesting that <protein>TNF-alpha</protein> selectively activates only specific <protein>NF-kappa B</protein> heteromers and that modifications regulate not only <protein>I kappa B molecules</protein> but also <protein>NF-kappa B</protein> molecules ."}
{"id": "1244", "text": "In fact , cellular NF-kappa B activity was phosphorylation-dependent and the DNA binding activity of p65-containing NF-kappa B was enhanced by phosphorylation in vitro .", "annotated_text": "In fact , cellular <protein>NF-kappa B</protein> activity was phosphorylation-dependent and the DNA binding activity of <protein>p65-containing NF-kappa B</protein> was enhanced by phosphorylation in vitro ."}
{"id": "1245", "text": "Furthermore , we found that the induction by hydrogen peroxide of NF-kappa B translocation to the nucleus , which is assumed to be triggered by reactive oxygen intermediates , also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by TNF-alpha .", "annotated_text": "Furthermore , we found that the induction by hydrogen peroxide of <protein>NF-kappa B</protein> translocation to the nucleus , which is assumed to be triggered by reactive oxygen intermediates , also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by <protein>TNF-alpha</protein> ."}
{"id": "1246", "text": "Thus , phosphorylation appears to be a general mechanism for activation of NF-kappa B in vivo .", "annotated_text": "Thus , phosphorylation appears to be a general mechanism for activation of <protein>NF-kappa B</protein> in vivo ."}
{"id": "1247", "text": "Treatment of HL60 cells with various combinations of retinoids and 1 alpha , 25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis .", "annotated_text": "Treatment of <cell_line>HL60 cells</cell_line> with various combinations of retinoids and 1 alpha , 25 dihydroxyvitamin D3 results in differentiation towards <cell_type>neutrophils</cell_type> or <cell_type>monocytes</cell_type> or a failure to differentiate and apoptosis ."}
{"id": "1248", "text": "It is well documented that treatment of serum-grown HL60 cells with 10 ( -7 ) M all-trans retinoic acid ( all-trans RA ) induces neutrophil differentiation , whereas treatment with 10 ( -7 ) M 1 alpha , 25 dihydroxyvitamin D3 ( D3 ) induces differentiation towards monocytes .", "annotated_text": "It is well documented that treatment of <cell_line>serum-grown HL60 cells</cell_line> with 10 ( -7 ) M all-trans retinoic acid ( all-trans RA ) induces <cell_type>neutrophil</cell_type> differentiation , whereas treatment with 10 ( -7 ) M 1 alpha , 25 dihydroxyvitamin D3 ( D3 ) induces differentiation towards <cell_type>monocytes</cell_type> ."}
{"id": "1249", "text": "In recent investigations , using serum-free grown HL60 cells , we observed that all-trans RA , at 10 ( -7 ) M , did not induce neutrophil differentiation and that all-trans RA , at 10 ( -8 ) M , reduced the D3 concentration required for monocyte differentiation to 5 x 10 ( -9 ) M .", "annotated_text": "In recent investigations , using <cell_line>serum-free grown HL60 cells</cell_line> , we observed that all-trans RA , at 10 ( -7 ) M , did not induce neutrophil differentiation and that all-trans RA , at 10 ( -8 ) M , reduced the D3 concentration required for <cell_type>monocyte</cell_type> differentiation to 5 x 10 ( -9 ) M ."}
{"id": "1250", "text": "In this study , co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of HL60 cells have been analysed in detail .", "annotated_text": "In this study , co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of <cell_line>HL60 cells</cell_line> have been analysed in detail ."}
{"id": "1251", "text": "Treatment of serum-free grown HL60 cells with 5 x 10 ( -7 ) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation ( up to 25 % mature cells ) .", "annotated_text": "Treatment of <cell_line>serum-free grown HL60 cells</cell_line> with 5 x 10 ( -7 ) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation ( up to 25 % mature cells ) ."}
{"id": "1252", "text": "As shown for all-trans RA , 9-cis RA cooperated with D3 to promote monocyte differentiation .", "annotated_text": "As shown for all-trans RA , 9-cis RA cooperated with D3 to promote monocyte differentiation ."}
{"id": "1253", "text": "Culture of HL60 cells in 5 x 10 ( -7 ) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10 ( -15 ) -10 ( -12 ) D3 , a failure to differentiate and apoptosis at 10 ( -11 ) -10 ( -10 ) M D3 , followed by co-operativity between 9-cis RA and 5 x 10 ( -9 ) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation .", "annotated_text": "Culture of <cell_line>HL60 cells</cell_line> in 5 x 10 ( -7 ) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10 ( -15 ) -10 ( -12 ) D3 , a failure to differentiate and apoptosis at 10 ( -11 ) -10 ( -10 ) M D3 , followed by co-operativity between 9-cis RA and 5 x 10 ( -9 ) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation ."}
{"id": "1254", "text": "Similar results were obtained when HL60 cells were treated with 5 x 10 ( -7 ) all-trans RA together with a wide range of concentrations of D3 .", "annotated_text": "Similar results were obtained when <cell_line>HL60 cells</cell_line> were treated with 5 x 10 ( -7 ) all-trans RA together with a wide range of concentrations of D3 ."}
{"id": "1255", "text": "Cross titration analyses of the effects of 9-cis RA and D3 on HL60 cell differentiation were undertaken to determine the boundaries of the concentrations of each agent , alone and in combination , that give rise to optimal neutrophil and monocyte differentiation of HL60 cells .", "annotated_text": "Cross titration analyses of the effects of 9-cis RA and D3 on <cell_line>HL60 cell</cell_line> differentiation were undertaken to determine the boundaries of the concentrations of each agent , alone and in combination , that give rise to optimal neutrophil and monocyte differentiation of <cell_line>HL60 cells</cell_line> ."}
{"id": "1256", "text": "The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy .", "annotated_text": "The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy ."}
{"id": "1257", "text": "Isolation of differentially expressed sequence tags from steroid-responsive cells using mRNA differential display .", "annotated_text": "Isolation of differentially expressed sequence tags from <cell_type>steroid-responsive cells</cell_type> using <rna>mRNA</rna> differential display ."}
{"id": "1258", "text": "Transcriptional control of steroid-regulated gene networks by nuclear receptor proteins results in the coordinate expression of a limited number of target genes .", "annotated_text": "Transcriptional control of <dna>steroid-regulated gene networks</dna> by <protein>nuclear receptor proteins</protein> results in the coordinate expression of a limited number of <dna>target genes</dna> ."}
{"id": "1259", "text": "Although much is known about the structure and function of steroid receptors , relatively few cell-specific steroid-regulated genes have been isolated and characterized .", "annotated_text": "Although much is known about the structure and function of steroid receptors , relatively few cell-specific steroid-regulated genes have been isolated and characterized ."}
{"id": "1260", "text": "In this paper we describe results using mRNA differential display reverse transcriptase PCR ( DDPCR ) to identify and isolate short cDNA sequence tags from thymocyte and prostate cells under various hormone conditions .", "annotated_text": "In this paper we describe results using <rna>mRNA</rna> differential display <protein>reverse transcriptase</protein> PCR ( DDPCR ) to identify and isolate short cDNA sequence tags from <cell_type>thymocyte</cell_type> and <cell_type>prostate cells</cell_type> under various hormone conditions ."}
{"id": "1261", "text": "Using this technique we have isolated several differentially expressed sequence tags ( DESTs ) from the mouse thymocyte cell line WEHI 7.2 .", "annotated_text": "Using this technique we have isolated several <dna>differentially expressed sequence tags</dna> ( <dna>DESTs</dna> ) from the <cell_line>mouse thymocyte cell line</cell_line> <cell_line>WEHI 7.2</cell_line> ."}
{"id": "1262", "text": "Two of these DESTs , GIG10 and GIG18 , are rapidly induced by dexamethasone within 2 h of treatment .", "annotated_text": "Two of these <dna>DESTs</dna> , <dna>GIG10</dna> and <dna>GIG18</dna> , are rapidly induced by dexamethasone within 2 h of treatment ."}
{"id": "1263", "text": "GIG10 is a novel sequence and GIG18 is the mouse homologue of a human expressed sequence tag isolated from activated B lymphocytes .", "annotated_text": "<dna>GIG10</dna> is a novel sequence and <dna>GIG18</dna> is the mouse homologue of a <dna>human expressed sequence tag</dna> isolated from <cell_type>activated B lymphocytes</cell_type> ."}
{"id": "1264", "text": "We also used DDPCR to isolate DESTs from androgen-modulated rat ventral prostate tissue , one of which we characterized and found to correspond to the 3 ' end of prostatic spermine binding protein mRNA , a known androgen-regulated gene .", "annotated_text": "We also used DDPCR to isolate <dna>DESTs</dna> from androgen-modulated rat ventral prostate tissue , one of which we characterized and found to correspond to the <rna>3 ' end</rna> of <rna>prostatic spermine binding protein mRNA</rna> , a known <dna>androgen-regulated gene</dna> ."}
{"id": "1265", "text": "Modifications of the original DDPCR protocol , which we found can potentially decrease the frequency of isolating false-positive DESTs , are described and the merits of DDPCR , relative to other differential cDNA cloning strategies , are discussed .", "annotated_text": "Modifications of the original DDPCR protocol , which we found can potentially decrease the frequency of isolating false-positive <dna>DESTs</dna> , are described and the merits of DDPCR , relative to other differential cDNA cloning strategies , are discussed ."}
{"id": "1266", "text": "Activation of human thymocytes after infection by EBV .", "annotated_text": "Activation of <cell_type>human thymocytes</cell_type> after infection by EBV ."}
{"id": "1267", "text": "The discovery of EBV in certain T cell malignancies and the expression of the EBV receptor , CR2/CD21 , on a population of immature thymocytes , T lymphoblastoid cell lines , and childhood acute T lymphoblastic leukemia cells suggested that EBV-receptor interactions on T cells may be of importance .", "annotated_text": "The discovery of EBV in certain T cell malignancies and the expression of the <protein>EBV receptor</protein> , <protein>CR2/CD21</protein> , on a population of <cell_type>immature thymocytes</cell_type> , <cell_line>T lymphoblastoid cell lines</cell_line> , and <cell_type>childhood acute T lymphoblastic leukemia cells</cell_type> suggested that EBV-receptor interactions on <cell_type>T cells</cell_type> may be of importance ."}
{"id": "1268", "text": "We have shown that , within the thymus , a population of large , immature cells expresses CD21 .", "annotated_text": "We have shown that , within the thymus , a population of <cell_type>large , immature cells</cell_type> expresses <protein>CD21</protein> ."}
{"id": "1269", "text": "EBV altered the activation responses of immature thymocytes in vitro .", "annotated_text": "EBV altered the activation responses of <cell_type>immature thymocytes</cell_type> in vitro ."}
{"id": "1270", "text": "Triggering through CD2 is mitogenic for mature , but not immature , T cells .", "annotated_text": "Triggering through <protein>CD2</protein> is mitogenic for mature , but not immature , <cell_type>T cells</cell_type> ."}
{"id": "1271", "text": "However , during infection by EBV , ligation of CD2 caused thymocytes to proliferate in the absence of exogenous cytokines .", "annotated_text": "However , during infection by EBV , ligation of <protein>CD2</protein> caused <cell_type>thymocytes</cell_type> to proliferate in the absence of <protein>exogenous cytokines</protein> ."}
{"id": "1272", "text": "This function was a result of the interaction of EBV with its receptor , CD21 , but was caused by infection rather than surface signaling , because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect of B95-8 .", "annotated_text": "This function was a result of the interaction of EBV with its receptor , <protein>CD21</protein> , but was caused by infection rather than surface signaling , because neither <protein>specific mAb</protein> nor the P3HR-1 strain of virus mimicked the effect of B95-8 ."}
{"id": "1273", "text": "Immature thymocytes were infected by EBV , as determined by the internalization of the viral genome and its transcriptional activity .", "annotated_text": "Immature <cell_type>thymocytes</cell_type> were infected by EBV , as determined by the internalization of the <dna>viral genome</dna> and its transcriptional activity ."}
{"id": "1274", "text": "Consistent with the activity of B95-8 , EBNA-2 transcripts were identified within infected thymocyte populations .", "annotated_text": "Consistent with the activity of <protein>B95-8</protein> , <rna>EBNA-2 transcripts</rna> were identified within <cell_line>infected thymocyte populations</cell_line> ."}
{"id": "1275", "text": "In addition , components of the viral replicative pathway were expressed during infection of thymocytes .", "annotated_text": "In addition , components of the viral replicative pathway were expressed during infection of <cell_type>thymocytes</cell_type> ."}
{"id": "1276", "text": "These components included transcription of BZLF-1 , an early gene that characterizes EBV-infected B cells after disruption of latency .", "annotated_text": "These components included transcription of <dna>BZLF-1</dna> , an <dna>early gene</dna> that characterizes <cell_type>EBV-infected B cells</cell_type> after disruption of latency ."}
{"id": "1277", "text": "A second transcript was identified as encoding the recently characterized RAZ , which also is associated with replicative infection .", "annotated_text": "A second transcript was identified as encoding the recently characterized <protein>RAZ</protein> , which also is associated with replicative infection ."}
{"id": "1278", "text": "The consequences of EBV infection of T cells at an early stage of differentiation may lead to failure of normal T cell repertoire development , autoimmunity , or malignancy .", "annotated_text": "The consequences of EBV infection of <cell_type>T cells</cell_type> at an early stage of differentiation may lead to failure of normal T cell repertoire development , autoimmunity , or malignancy ."}
{"id": "1279", "text": "Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function .", "annotated_text": "Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function ."}
{"id": "1280", "text": "Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis .", "annotated_text": "Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis ."}
{"id": "1281", "text": "Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids .", "annotated_text": "Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids ."}
{"id": "1282", "text": "In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids , 14 normal healthy subjects were treated with two doses of either budesonide ( BUD ) or fluticasone propionate ( FP ) for 2 weeks .", "annotated_text": "In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids , 14 normal healthy subjects were treated with two doses of either budesonide ( BUD ) or fluticasone propionate ( FP ) for 2 weeks ."}
{"id": "1283", "text": "Before treatment , at regular intervals during the treatment , 1 week and finally 6 weeks after termination of treatment , the effects on glucocorticoid receptor ( GR ) and methallothionein ( MTIIa ) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay .", "annotated_text": "Before treatment , at regular intervals during the treatment , 1 week and finally 6 weeks after termination of treatment , the effects on glucocorticoid receptor ( GR ) and methallothionein ( MTIIa ) mRNA expression levels were examined in <cell_type>peripheral lymphocytes</cell_type> using a solution hybridization assay ."}
{"id": "1284", "text": "Serum cortisol , osteocalcin and urinary cortisol levels were also determined .", "annotated_text": "Serum cortisol , osteocalcin and urinary cortisol levels were also determined ."}
{"id": "1285", "text": "An insulin tolerance test ( ITT ) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response .", "annotated_text": "An insulin tolerance test ( ITT ) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response ."}
{"id": "1286", "text": "In peripheral lymphocytes , GR mRNA levels were significantly down-regulated .", "annotated_text": "In <cell_type>peripheral lymphocytes</cell_type> , <rna>GR mRNA</rna> levels were significantly down-regulated ."}
{"id": "1287", "text": "MTIIa mRNA levels increased significantly .", "annotated_text": "<rna>MTIIa mRNA</rna> levels increased significantly ."}
{"id": "1288", "text": "Serum osteocalcin decreased significantly during treatment with both BUD and FP .", "annotated_text": "Serum <protein>osteocalcin</protein> decreased significantly during treatment with both BUD and FP ."}
{"id": "1289", "text": "Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment .", "annotated_text": "Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment ."}
{"id": "1290", "text": "In conclusion , intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function , but also have an effect on specific gene expression in peripheral lymphocytes .", "annotated_text": "In conclusion , intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function , but also have an effect on specific gene expression in <cell_type>peripheral lymphocytes</cell_type> ."}
{"id": "1291", "text": "These effects are receptor-dependent , reversible , and according to serum and urinary cortisol levels and ITT , leave the hypothalamic-pituitary-adrenal function intact .", "annotated_text": "These effects are receptor-dependent , reversible , and according to serum and urinary cortisol levels and ITT , leave the hypothalamic-pituitary-adrenal function intact ."}
{"id": "1292", "text": "Finally , these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids .", "annotated_text": "Finally , these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids ."}
{"id": "1293", "text": "Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex : role of tumor necrosis factor alpha .", "annotated_text": "Biphasic control of <protein>nuclear factor-kappa B</protein> activation by the <protein>T cell receptor complex</protein> : role of <protein>tumor necrosis factor alpha</protein> ."}
{"id": "1294", "text": "The regulation of nuclear factor ( NF ) -kappa B activation by the T cell receptor ( TcR ) /CD3 complex in primary human T cells has been studied at various times after activation .", "annotated_text": "The regulation of <protein>nuclear factor ( NF ) -kappa B</protein> activation by the <protein>T cell receptor ( TcR ) /CD3 complex</protein> in primary human <cell_type>T cells</cell_type> has been studied at various times after activation ."}
{"id": "1295", "text": "Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor ( IL-2R ) alpha chain promoter on resting T cells .", "annotated_text": "Only <protein>p50 NF-kappa B protein</protein> bound the <dna>kappa B element</dna> of <dna>interleukin-2 receptor ( IL-2R ) alpha chain promoter</dna> on resting <cell_type>T cells</cell_type> ."}
{"id": "1296", "text": "However , immediately after TcR/CD3 cross-linking ( after approximately 1 h ; immediate ) binding of p50.p65 heterodimers was observed .", "annotated_text": "However , immediately after <protein>TcR/CD3</protein> cross-linking ( after approximately 1 h ; immediate ) binding of <protein>p50.p65 heterodimers</protein> was observed ."}
{"id": "1297", "text": "p50.c-rel heterodimers were also detected bound to this sequence at early time points ( 7-16 h ; early ) , and both remained active at later time points ( 40 h ; late ) after activation .", "annotated_text": "<protein>p50.c-rel heterodimers</protein> were also detected bound to this sequence at early time points ( 7-16 h ; early ) , and both remained active at later time points ( 40 h ; late ) after activation ."}
{"id": "1298", "text": "This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel , at immediate and early time points .", "annotated_text": "This regulation takes place mainly at the level of nuclear translocation of <protein>p65</protein> and <protein>c-rel</protein> , at immediate and early time points ."}
{"id": "1299", "text": "Activation also induced c-rel and p105/p50 mRNA synthesis , but not p65 mRNA whose expression was constitutive .", "annotated_text": "Activation also induced c-rel and p105/p50 mRNA synthesis , but not <rna>p65 mRNA</rna> whose expression was constitutive ."}
{"id": "1300", "text": "Interestingly , all those early and late events , but not the immediate ones , were inhibited by a neutralizing anti-tumor necrosis factor alpha ( TNF-alpha ) monoclonal antibody .", "annotated_text": "Interestingly , all those early and late events , but not the immediate ones , were inhibited by a neutralizing <protein>anti-tumor necrosis factor alpha ( TNF-alpha ) monoclonal antibody</protein> ."}
{"id": "1301", "text": "Similarly , cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers , at early and late times .", "annotated_text": "Similarly , cycloheximide prevented the <protein>p65</protein> and <protein>c-rel</protein> translocation and consequent formation of active binding heterodimers , at early and late times ."}
{"id": "1302", "text": "Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of TNF-alpha prevented all inhibition .", "annotated_text": "Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of <protein>TNF-alpha</protein> prevented all inhibition ."}
{"id": "1303", "text": "These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic : TcR/CD3 triggers its immediate translocation , which is transient if no TNF-alpha is present .", "annotated_text": "These results indicate that the regulation of <protein>NF-kappa B</protein> activation during T cell activation by <protein>TcR/CD3</protein> signals is biphasic : <protein>TcR/CD3</protein> triggers its immediate translocation , which is transient if no <protein>TNF-alpha</protein> is present ."}
{"id": "1304", "text": "TNF-alpha , therefore , emerges as the main factor responsible for a second phase of NF-kappa B regulation , controlling both translocation of p65 and c-rel , and new mRNA synthesis for c-rel and p105/p50 .", "annotated_text": "<protein>TNF-alpha</protein> , therefore , emerges as the main factor responsible for a second phase of <protein>NF-kappa B</protein> regulation , controlling both translocation of <protein>p65</protein> and <protein>c-rel</protein> , and new <rna>mRNA</rna> synthesis for <protein>c-rel</protein> and <protein>p105/p50</protein> ."}
{"id": "1305", "text": "The transcription factor Sp1 is required for induction of the murine GM-CSF promoter in T cells .", "annotated_text": "The <protein>transcription factor Sp1</protein> is required for induction of the <dna>murine GM-CSF promoter</dna> in <cell_type>T cells</cell_type> ."}
{"id": "1306", "text": "The cis-acting region , GM-kappa B/GC-box ( positions -95 and -73 ) , within the murine GM-CSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate ( PMA ) and calcium ionophore ( A23187 ) in T cells .", "annotated_text": "The <dna>cis-acting region</dna> , <dna>GM-kappa B/GC-box</dna> ( <dna>positions -95</dna> and <dna>-73</dna> ) , within the <dna>murine GM-CSF gene promoter</dna> is required for maximal induction by stimulation with phorbol-12-myristate acetate ( PMA ) and calcium ionophore ( A23187 ) in <cell_type>T cells</cell_type> ."}
{"id": "1307", "text": "GM-kappa B defines a binding site for NF-kappa B , and GC-box defines a binding site for three ( A1 , A2 , B ) constitutive proteins .", "annotated_text": "<protein>GM-kappa B</protein> defines a binding site for <protein>NF-kappa B</protein> , and <dna>GC-box</dna> defines a binding site for three ( <protein>A1</protein> , <protein>A2</protein> , <protein>B</protein> ) <protein>constitutive proteins</protein> ."}
{"id": "1308", "text": "We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/GC-box region , suggesting that the GC-motif can function independently of the GM-kappa B motif .", "annotated_text": "We report here that three copies of the <dna>GC-box</dna> can functionally compensate for the <dna>GM-kappa B/GC-box region</dna> , suggesting that the GC-motif can function independently of the <dna>GM-kappa B motif</dna> ."}
{"id": "1309", "text": "The major GC-box binding activity A1 was purified and identified as the transcription factor Sp1 .", "annotated_text": "The major <dna>GC-box</dna> binding activity <protein>A1</protein> was purified and identified as the <protein>transcription factor Sp1</protein> ."}
{"id": "1310", "text": "We show that depletion of Sp1 ( A1 ) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates .", "annotated_text": "We show that depletion of <protein>Sp1</protein> ( <protein>A1</protein> ) from nuclear extracts specifically decreases in vitro transcription activity on <protein>GM-CSF</protein> templates ."}
{"id": "1311", "text": "Since the human GM-CSF promoter has a base difference within the GC-box , we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene .", "annotated_text": "Since the <dna>human GM-CSF promoter</dna> has a base difference within the <dna>GC-box</dna> , we speculate that this may explain why the human promoter is weak and that an <dna>upstream enhancer</dna> is required for the induction of the <dna>human GM-CSF gene</dna> ."}
{"id": "1312", "text": "A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein .", "annotated_text": "A factor that regulates the <dna>class II major histocompatibility complex gene</dna> <dna>DPA</dna> is a member of a subfamily of <protein>zinc finger proteins</protein> that includes a <protein>Drosophila developmental control protein</protein> ."}
{"id": "1313", "text": "A novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described .", "annotated_text": "A novel <dna>DNA sequence element</dna> termed the <dna>J element</dna> involved in the regulated expression of <dna>class II major histocompatibility complex genes</dna> was recently described ."}
{"id": "1314", "text": "To study this element and its role in class II gene regulation further , a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene .", "annotated_text": "To study this element and its role in <dna>class II gene</dna> regulation further , a <dna>cDNA library</dna> was screened with oligonucleotide probes containing both the <dna>S element</dna> and the nearby <dna>J element</dna> of the <dna>human DPA gene</dna> ."}
{"id": "1315", "text": "Several DNA clones were obtained by this procedure , one of which , clone 18 , is reported and characterized here .", "annotated_text": "Several <dna>DNA clones</dna> were obtained by this procedure , one of which , <dna>clone 18</dna> , is reported and characterized here ."}
{"id": "1316", "text": "It encodes a protein predicted to contain 688 amino acid residues , including 11 zinc finger motifs of the C2H2 type in the C-terminal region , that are Kruppel-like in the conservation of the H/C link sequence connecting them .", "annotated_text": "It encodes a protein predicted to contain 688 amino acid residues , including 11 <protein>zinc finger motifs</protein> of the <protein>C2H2 type</protein> in the <protein>C-terminal region</protein> , that are Kruppel-like in the conservation of the <protein>H/C link sequence</protein> connecting them ."}
{"id": "1317", "text": "The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human , mouse , and Drosophila sequences , defining a subfamily of Kruppel-like zinc finger proteins termed TAB ( tramtrack [ ttk ] -associated box ) here .", "annotated_text": "The <protein>160 N-terminal amino acids</protein> in the <protein>nonfinger region</protein> of <protein>clone 18</protein> are highly homologous with similar regions of several other <dna>human , mouse , and Drosophila sequences</dna> , defining a subfamily of Kruppel-like <protein>zinc finger proteins</protein> termed <protein>TAB</protein> ( <protein>tramtrack [ ttk ] -associated box</protein> ) here ."}
{"id": "1318", "text": "One of the Drosophila sequences , ttk , is a developmental control gene , while a second does not contain a zinc finger region but encodes a structure important in oocyte development .", "annotated_text": "One of the <dna>Drosophila sequences</dna> , <dna>ttk</dna> , is a <dna>developmental control gene</dna> , while a second does not contain a <protein>zinc finger region</protein> but encodes a structure important in oocyte development ."}
{"id": "1319", "text": "An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers .", "annotated_text": "An <protein>acidic activation domain</protein> is located between the <protein>N-terminal conserved region</protein> of <protein>clone 18</protein> and its <protein>zinc fingers</protein> ."}
{"id": "1320", "text": "This protein appears to require both the S and J elements , which are separated by 10 bp for optimal binding .", "annotated_text": "This protein appears to require both the <dna>S and J elements</dna> , which are separated by 10 bp for optimal binding ."}
{"id": "1321", "text": "Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter , indicating its functional importance in the expression of this class II gene .", "annotated_text": "Antisense cDNA to <protein>clone 18</protein> inhibited the expression of a reporter construct containing the <dna>DPA promoter</dna> , indicating its functional importance in the expression of this <dna>class II gene</dna> ."}
{"id": "1322", "text": "Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway .", "annotated_text": "Separation of oxidant-initiated and redox-regulated steps in the <protein>NF-kappa B</protein> signal transduction pathway ."}
{"id": "1323", "text": "Studies presented here show that overall NF-kappa B signal transduction begins with a parallel series of stimuli-specific pathways through which cytokines ( tumor necrosis factor alpha ) , oxidants ( hydrogen peroxide and mitomycin C ) , and phorbol ester ( phorbol 12-myristate 13-acetate ) individually initiate signaling .", "annotated_text": "Studies presented here show that overall <protein>NF-kappa B</protein> signal transduction begins with a parallel series of stimuli-specific pathways through which <protein>cytokines</protein> ( <protein>tumor necrosis factor alpha</protein> ) , oxidants ( hydrogen peroxide and mitomycin C ) , and phorbol ester ( phorbol 12-myristate 13-acetate ) individually initiate signaling ."}
{"id": "1324", "text": "These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation .", "annotated_text": "These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal <protein>NF-kappa B</protein> activation ."}
{"id": "1325", "text": "We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa B activation in only one of two human T-cell lines ( Wurzburg but not Jurkat ) , whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily stimulate in both lines .", "annotated_text": "We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger <protein>NF-kappa B</protein> activation in only one of two <cell_line>human T-cell lines</cell_line> ( <cell_line>Wurzburg</cell_line> but not <cell_line>Jurkat</cell_line> ) , whereas <protein>tumor necrosis factor alpha</protein> and phorbol 12-myristate 13-acetate readily stimulate in both lines ."}
{"id": "1326", "text": "We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway .", "annotated_text": "We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway ."}
{"id": "1327", "text": "We include a redox-regulatory mechanism ( s ) in this common pathway to account for the previously demonstrated redox regulation of NF-kappa B activation in Jurkat cells ( in which oxidants do n't activate NF-kappa B ) ; we put tyrosine phosphorylation in the common pathway by showing that kinase activity ( inhibitable by herbimycin A and tyrphostin 47 ) is required for NF-kappa B activation by all stimuli tested in both cell lines .", "annotated_text": "We include a redox-regulatory mechanism ( s ) in this common pathway to account for the previously demonstrated redox regulation of <protein>NF-kappa B</protein> activation in <cell_line>Jurkat cells</cell_line> ( in which oxidants do n't activate <protein>NF-kappa B</protein> ) ; we put tyrosine phosphorylation in the common pathway by showing that kinase activity ( inhibitable by herbimycin A and tyrphostin 47 ) is required for <protein>NF-kappa B</protein> activation by all stimuli tested in both cell lines ."}
{"id": "1328", "text": "Since internal sites of oxidant production have been shown to play a key role in the cytokine -stimulated activation of NF-kappa B , and since tyrosine kinase and phosphatase activities are known to be altered by oxidants , these findings suggest that intracellular redox status controls NF-kappa B activation by regulating tyrosine phosphorylation event ( s ) within the common step of the NF-kappa B signal transduction pathway .", "annotated_text": "Since internal sites of oxidant production have been shown to play a key role in the <protein>cytokine</protein> -stimulated activation of <protein>NF-kappa B</protein> , and since tyrosine kinase and phosphatase activities are known to be altered by oxidants , these findings suggest that intracellular redox status controls <protein>NF-kappa B</protein> activation by regulating tyrosine phosphorylation event ( s ) within the common step of the <protein>NF-kappa B</protein> signal transduction pathway ."}
{"id": "1329", "text": "Deleted chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection : study of three candidate genes .", "annotated_text": "Deleted <dna>chromosome 20</dna> from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection : study of three candidate genes ."}
{"id": "1330", "text": "Alagille syndrome ( AGS ) is a well-defined genetic entity assigned to the short arm of Chromosome ( Chr ) 20 by a series of observations of AGS patients associated with microdeletions in this region .", "annotated_text": "Alagille syndrome ( AGS ) is a well-defined genetic entity assigned to the <dna>short arm</dna> of <dna>Chromosome ( Chr ) 20</dna> by a series of observations of AGS patients associated with microdeletions in this region ."}
{"id": "1331", "text": "By fusing lymphoblastoid cells of an AGS patient that exhibited a microdeletion in the short arm of Chr 20 encompassing bands p11.23 to p12.3 with rodent thermosensitive mutant cells ( CHOtsH1-1 ) deficient in-leucyl-tRNA synthetase , we isolated a somatic cell hybrid segregating the deleted human Chr 20 .", "annotated_text": "By fusing <cell_type>lymphoblastoid cells</cell_type> of an AGS patient that exhibited a microdeletion in the <dna>short arm of Chr 20</dna> encompassing bands <dna>p11.23 to p12.3</dna> with <cell_line>rodent thermosensitive mutant cells</cell_line> ( <cell_line>CHOtsH1-1</cell_line> ) deficient <protein>in-leucyl-tRNA synthetase</protein> , we isolated a <cell_line>somatic cell hybrid</cell_line> segregating the deleted human <dna>Chr 20</dna> ."}
{"id": "1332", "text": "This hybrid clone , designated NR2 , was characterized by several methods , including PCR , with eight pairs of oligonucleotides mapped to Chr 20 : D20S5 , D20S41 , D20S42 , D20S56 , D20S57 , D20S58 , adenosine deaminase ( ADA ) , and Prion protein ( PRIP ) ; Restriction Fragment Length Polymorphism ( RFLP ) analyses with four genomic anonymous probes ( D20S5 , cD3H12 , D20S17 , D20S18 ) ; and fluorescent in situ hybridization ( FISH ) with total human DNA and D20Z1 , a sequence specific to the human Chr 20 centromere , as probes .", "annotated_text": "This hybrid clone , designated <cell_line>NR2</cell_line> , was characterized by several methods , including PCR , with eight pairs of oligonucleotides mapped to <dna>Chr 20</dna> : <dna>D20S5</dna> , <dna>D20S41</dna> , <dna>D20S42</dna> , <dna>D20S56</dna> , <dna>D20S57</dna> , <dna>D20S58</dna> , <dna>adenosine deaminase</dna> ( <protein>ADA</protein> ) , and <dna>Prion protein</dna> ( <protein>PRIP</protein> ) ; Restriction Fragment Length Polymorphism ( <dna>RFLP</dna> ) analyses with four <dna>genomic anonymous probes</dna> ( <dna>D20S5</dna> , <dna>cD3H12</dna> , <dna>D20S17</dna> , <dna>D20S18</dna> ) ; and fluorescent in situ hybridization ( FISH ) with <dna>total human DNA</dna> and <dna>D20Z1</dna> , a sequence specific to the <dna>human Chr 20 centromere</dna> , as probes ."}
{"id": "1333", "text": "The NR2 hybrid allowed us to exclude three candidate genes for AGS : hepatic nuclear factor 3 beta ( HNF3 beta ) , paired box 1 ( PAX1 ) , and cystatin C ( CST3 ) as shown by their localization outside of the deletion .", "annotated_text": "The <cell_line>NR2 hybrid</cell_line> allowed us to exclude three <dna>candidate genes</dna> for AGS : <dna>hepatic nuclear factor 3 beta</dna> ( <dna>HNF3 beta</dna> ) , <dna>paired box 1</dna> ( <dna>PAX1</dna> ) , and <dna>cystatin C</dna> ( <dna>CST3</dna> ) as shown by their localization outside of the deletion ."}
{"id": "1334", "text": "The NR2 hybrid is a powerful tool for the mapping of new probes of this region , as well as for obtaining new informative probes specific for the deletion by subtractive cloning of the region .", "annotated_text": "The <cell_line>NR2 hybrid</cell_line> is a powerful tool for the mapping of new probes of this region , as well as for obtaining new informative probes specific for the deletion by subtractive cloning of the region ."}
{"id": "1335", "text": "Such markers will be useful for linkage analysis and screening of cDNA libraries .", "annotated_text": "Such markers will be useful for linkage analysis and screening of <dna>cDNA libraries</dna> ."}
{"id": "1336", "text": "Positive and negative regulation of the composite octamer motif of the interleukin 2 enhancer by AP-1 , Oct-2 , and retinoic acid receptor .", "annotated_text": "Positive and negative regulation of the <dna>composite octamer motif</dna> of the <dna>interleukin 2 enhancer</dna> by <protein>AP-1</protein> , <protein>Oct-2</protein> , and <protein>retinoic acid receptor</protein> ."}
{"id": "1337", "text": "The differentiating agent retinoic acid ( RA ) has been previously reported to interfere with 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) /Ca ( 2+ ) -induced signals for the regulation of the -96 to -66-bp octamer motif found in the enhancer for the interleukin ( IL ) -2 gene , which encodes a major T lymphocyte growth factor .", "annotated_text": "The differentiating agent retinoic acid ( RA ) has been previously reported to interfere with 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) /Ca ( 2+ ) -induced signals for the regulation of the <dna>-96 to -66-bp octamer motif</dna> found in the enhancer for the <dna>interleukin ( IL ) -2 gene</dna> , which encodes a major <protein>T lymphocyte growth factor</protein> ."}
{"id": "1338", "text": "The IL-2 octamer motif is a composite cis-element which binds Oct-1 and Oct-2 as well as a TPA/Ca ( 2+ ) -inducible nuclear factor , previously termed octamer-associated protein ( OAP40 ) .", "annotated_text": "The <dna>IL-2 octamer motif</dna> is a composite <dna>cis-element</dna> which binds <protein>Oct-1</protein> and <protein>Oct-2</protein> as well as a <protein>TPA/Ca ( 2+ ) -inducible nuclear factor</protein> , previously termed <protein>octamer-associated protein</protein> ( <protein>OAP40</protein> ) ."}
{"id": "1339", "text": "We show here that Oct-2 , despite the presence of an active transcriptional activation domain , requires TPA/Ca ( 2+ ) -induced signals to strongly transactivate the IL-2 octamer motif in Jurkat T cells .", "annotated_text": "We show here that <protein>Oct-2</protein> , despite the presence of an active transcriptional activation domain , requires TPA/Ca ( 2+ ) -induced signals to strongly transactivate the <dna>IL-2 octamer motif</dna> in Jurkat T cells ."}
{"id": "1340", "text": "This Oct-2 -dependent transactivation is inhibited by RA .", "annotated_text": "This <protein>Oct-2</protein> -dependent transactivation is inhibited by RA ."}
{"id": "1341", "text": "The presence of an intact COOH-terminal domain of Oct-2 contributes to both TPA/Ca ( 2+ ) -induced transactivation and the RA-mediated repression .", "annotated_text": "The presence of an <protein>intact COOH-terminal domain</protein> of <protein>Oct-2</protein> contributes to both TPA/Ca ( 2+ ) -induced transactivation and the RA-mediated repression ."}
{"id": "1342", "text": "We also show that both Fos and Jun components of the AP-1 factors participate in the OAP40 complex .", "annotated_text": "We also show that both <protein>Fos</protein> and <protein>Jun</protein> components of the <protein>AP-1</protein> factors participate in the <protein>OAP40 complex</protein> ."}
{"id": "1343", "text": "Furthermore , transfected c-jun , jun-B , jun-D , c-fos , or Fos-B expression vectors partially substitute for TPA and Ca2+ and cooperate with Oct-2 for the transactivation of the combined OAP/octamer cis-element .", "annotated_text": "Furthermore , transfected <dna>c-jun , jun-B , jun-D , c-fos , or Fos-B expression vectors</dna> partially substitute for TPA and Ca2+ and cooperate with <protein>Oct-2</protein> for the transactivation of the combined <dna>OAP/octamer cis-element</dna> ."}
{"id": "1344", "text": "Mutations of the genuine octamer-binding site abrogate both the binding of Oct-1 and Oct-2 and the TPA/Ca ( 2+ ) -induced transactivation of the OAP/octamer motif .", "annotated_text": "Mutations of the <dna>genuine octamer-binding site</dna> abrogate both the binding of <protein>Oct-1</protein> and <protein>Oct-2</protein> and the TPA/Ca ( 2+ ) -induced transactivation of the <dna>OAP/octamer motif</dna> ."}
{"id": "1345", "text": "OAP confers to Oct-2 responsivity to both TPA/Ca2+ and RA , since specific mutations of the AP-1/OAP-binding site significantly reduce the transactivation by Oct-2 in response to TPA and Ca2+ and abolish the inhibition by RA .", "annotated_text": "<protein>OAP</protein> confers to <protein>Oct-2</protein> responsivity to both TPA/Ca2+ and RA , since specific mutations of the <dna>AP-1/OAP-binding site</dna> significantly reduce the transactivation by <protein>Oct-2</protein> in response to TPA and Ca2+ and abolish the inhibition by RA ."}
{"id": "1346", "text": "Furthermore , retinoic acid receptor ( RAR ) alpha is able to inhibit in vitro the formation of the complex between the nuclear AP-1 /OAP and its specific binding site , resulting in the interference with Oct-2 -dependent cis-regulatory function of this AP-1 element .", "annotated_text": "Furthermore , <protein>retinoic acid receptor</protein> ( <protein>RAR</protein> ) alpha is able to inhibit in vitro the formation of the complex between the nuclear <protein>AP-1</protein> <protein>/OAP</protein> and its specific binding site , resulting in the interference with <protein>Oct-2</protein> -dependent cis-regulatory function of this <protein>AP-1</protein> element ."}
{"id": "1347", "text": "Therefore , we propose that the TPA/calcium-activated AP-1 /OAP element is the main target of positive or negative regulatory signals influencing the IL-2 octamer motif , through synergism with Oct-2 and antagonism by RAR .", "annotated_text": "Therefore , we propose that the TPA/calcium-activated <protein>AP-1</protein> <protein>/OAP</protein> element is the main target of positive or negative regulatory signals influencing the <dna>IL-2 octamer motif</dna> , through synergism with <protein>Oct-2</protein> and antagonism by <protein>RAR</protein> ."}
{"id": "1348", "text": "Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency .", "annotated_text": "Missense mutation in <dna>exon 7</dna> of the <dna>common gamma chain gene</dna> causes a moderate form of X-linked combined immunodeficiency ."}
{"id": "1349", "text": "Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease ( XCID ) suggested that XCID and X-linked severe combined immunodeficiency ( XSCID ) might arise from different genetic defects .", "annotated_text": "Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease ( XCID ) suggested that XCID and X-linked severe combined immunodeficiency ( XSCID ) might arise from different genetic defects ."}
{"id": "1350", "text": "The recent discovery of mutations in the common gamma chain ( gamma c ) gene , a constituent of several cytokine receptors , in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID .", "annotated_text": "The recent discovery of mutations in the <dna>common gamma chain ( gamma c ) gene</dna> , a constituent of several <protein>cytokine receptors</protein> , in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID ."}
{"id": "1351", "text": "The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic , short tandem repeats ( CAG ) , in the androgen receptor gene , which also contains a methylation-sensitive HpaII site .", "annotated_text": "The status of <dna>X chromosome</dna> inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic , short tandem repeats ( CAG ) , in the <dna>androgen receptor gene</dna> , which also contains a <dna>methylation-sensitive HpaII site</dna> ."}
{"id": "1352", "text": "As in XSCID , X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes .", "annotated_text": "As in XSCID , X-chromosome inactivation in obligate carriers of XCID was nonrandom in <cell_type>T and B lymphocytes</cell_type> ."}
{"id": "1353", "text": "In addition , X chromosome inactivation in PMNs was variable .", "annotated_text": "In addition , <dna>X chromosome</dna> inactivation in PMNs was variable ."}
{"id": "1354", "text": "Findings from this analysis prompted sequencing of the gamma c gene in this pedigree .", "annotated_text": "Findings from this analysis prompted sequencing of the <dna>gamma c gene</dna> in this pedigree ."}
{"id": "1355", "text": "A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother .", "annotated_text": "A missense mutation in the region coding for the cytoplasmic portion of the <dna>gamma c gene</dna> was found in three affected males but not in a normal brother ."}
{"id": "1356", "text": "Therefore , this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID .", "annotated_text": "Therefore , this point mutation in the <dna>gamma c gene</dna> leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID ."}
{"id": "1357", "text": "Posttranscriptional regulation of macrophage tissue factor expression by antioxidants .", "annotated_text": "Posttranscriptional regulation of macrophage <protein>tissue factor</protein> expression by antioxidants ."}
{"id": "1358", "text": "Tissue factor ( TF ) expression by cells of monocyte/macrophage lineage represents an important mechanism underlying the initiation of fibrin deposition at sites of extravascular inflammation .", "annotated_text": "<protein>Tissue factor</protein> ( <protein>TF</protein> ) expression by cells of <cell_type>monocyte/macrophage lineage</cell_type> represents an important mechanism underlying the initiation of <protein>fibrin</protein> deposition at sites of extravascular inflammation ."}
{"id": "1359", "text": "Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various transcription factors , including nuclear factor kappa B and AP-1 .", "annotated_text": "Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various <protein>transcription factors</protein> , including <protein>nuclear factor kappa B</protein> and <protein>AP-1</protein> ."}
{"id": "1360", "text": "The effect of antioxidant treatment on lipopolysaccharide ( LPS ) -induced TF expression was examined in murine peritoneal macrophages and human monocytes .", "annotated_text": "The effect of antioxidant treatment on lipopolysaccharide ( LPS ) -induced <protein>TF</protein> expression was examined in <cell_type>murine peritoneal macrophages</cell_type> and <cell_type>human monocytes</cell_type> ."}
{"id": "1361", "text": "Both pyrrolidine dithiocarbamate , an oxidant scavenger , and N-acetyl-cysteine , a precursor of the endogenous antioxidant glutathione , inhibited stimulation of macrophage procoagulant activity by LPS .", "annotated_text": "Both pyrrolidine dithiocarbamate , an oxidant scavenger , and N-acetyl-cysteine , a precursor of the endogenous antioxidant glutathione , inhibited stimulation of macrophage procoagulant activity by LPS ."}
{"id": "1362", "text": "Northern blot analysis showed that neither of these agents reduced LPS-stimulated TF mRNA accumulation , thereby suggesting a posttranscriptional mechanism for the effect .", "annotated_text": "Northern blot analysis showed that neither of these agents reduced LPS-stimulated <protein>TF</protein> mRNA accumulation , thereby suggesting a posttranscriptional mechanism for the effect ."}
{"id": "1363", "text": "Immunofluorescence studies of human monocytes using polyclonal anti-TF antibody showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of TF antigen that occurs in response to LPS .", "annotated_text": "Immunofluorescence studies of <cell_type>human monocytes</cell_type> using polyclonal <protein>anti-TF antibody</protein> showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of <protein>TF antigen</protein> that occurs in response to LPS ."}
{"id": "1364", "text": "Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the 47-kD mature glycoprotein in LPS-treated cells , a finding consistent with the results of the immunofluorescence studies .", "annotated_text": "Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the <protein>47-kD mature glycoprotein</protein> in <cell_line>LPS-treated cells</cell_line> , a finding consistent with the results of the immunofluorescence studies ."}
{"id": "1365", "text": "Furthermore , these conditions did not result in an accumulation of the less mature forms of TF .", "annotated_text": "Furthermore , these conditions did not result in an accumulation of the less mature forms of <protein>TF</protein> ."}
{"id": "1366", "text": "When considered together , these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly translated protein .", "annotated_text": "When considered together , these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly <protein>translated protein</protein> ."}
{"id": "1367", "text": "The effect of antioxidants on tumor necrosis factor appeared to be species specific , with no effect on LPS-induced tumor necrosis factor in murine cells , but with inhibition in human monocytes .", "annotated_text": "The effect of antioxidants on <protein>tumor necrosis factor</protein> appeared to be species specific , with no effect on LPS-induced tumor necrosis factor in murine cells , but with inhibition in <cell_type>human monocytes</cell_type> ."}
{"id": "1368", "text": "The posttranscriptional effect of antioxidants on TF expression data suggests a novel mechanism whereby these agents might modulate monocyte /macrophage activation .", "annotated_text": "The posttranscriptional effect of antioxidants on <protein>TF</protein> expression data suggests a novel mechanism whereby these agents might modulate <cell_type>monocyte</cell_type> <cell_type>/macrophage</cell_type> activation ."}
{"id": "1369", "text": "Characterization of the CD48 gene demonstrates a positive element that is specific to Epstein-Barr virus-immortalized B-cell lines and contains an essential NF-kappa B site .", "annotated_text": "Characterization of the <dna>CD48 gene</dna> demonstrates a positive element that is specific to <cell_type>Epstein-Barr virus-immortalized B-cell lines</cell_type> and contains an essential <dna>NF-kappa B site</dna> ."}
{"id": "1370", "text": "Epstein-Barr virus ( EBV ) infection of mature , resting B cells drives them to become lymphoblasts expressing high levels of cell surface molecules , such as CD48 , characteristically expressed on normal activated B cells .", "annotated_text": "Epstein-Barr virus ( EBV ) infection of mature , <cell_type>resting B cells</cell_type> drives them to become lymphoblasts expressing high levels of cell surface molecules , such as <protein>CD48</protein> , characteristically expressed on <cell_type>normal activated B cells</cell_type> ."}
{"id": "1371", "text": "Here , we report on the identification of an enhancer element in the CD48 gene which reproducibly confers strong transcriptional activity only in EBV-positive B-lymphoblastoid cell lines .", "annotated_text": "Here , we report on the identification of an <dna>enhancer element</dna> in the <dna>CD48 gene</dna> which reproducibly confers strong transcriptional activity only in <cell_line>EBV-positive B-lymphoblastoid cell lines</cell_line> ."}
{"id": "1372", "text": "The element is not activated upon infection of established EBV-negative B-cell lines , indicating that EBV fails to drive these cells to a fully lymphoblastoid phenotype .", "annotated_text": "The element is not activated upon infection of established <cell_line>EBV-negative B-cell lines</cell_line> , indicating that EBV fails to drive these cells to a fully <cell_type>lymphoblastoid phenotype</cell_type> ."}
{"id": "1373", "text": "An NF-kappa B binding site is an essential component of the element but alone is not sufficient to account for the activity or the specificity of the element .", "annotated_text": "An <protein>NF-kappa B</protein> binding site is an essential component of the element but alone is not sufficient to account for the activity or the specificity of the element ."}
{"id": "1374", "text": "We have detected a specific nuclear protein complex that binds to the element and show that NF-kappa B1 ( p50 ) is a part of this complex .", "annotated_text": "We have detected a specific <protein>nuclear protein complex</protein> that binds to the element and show that <protein>NF-kappa B1</protein> ( <protein>p50</protein> ) is a part of this complex ."}
{"id": "1375", "text": "The EBV-encoded latent membrane protein 1 is capable of transactivating the isolated CD48 NF-kappa B site but not the intact element , suggesting that the latent membrane protein 1 -driven activation of NF-kappa B/Rel must interact with other regulatory pathways to control expression of cellular genes as EBV drives resting B cells into the cell cycle .", "annotated_text": "The <protein>EBV-encoded latent membrane protein 1</protein> is capable of transactivating the isolated <protein>CD48</protein> <dna>NF-kappa B site</dna> but not the <dna>intact element</dna> , suggesting that the <protein>latent membrane protein 1</protein> -driven activation of <protein>NF-kappa B/Rel</protein> must interact with other regulatory pathways to control expression of cellular genes as EBV drives <cell_type>resting B cells</cell_type> into the cell cycle ."}
{"id": "1376", "text": "Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T cells via a protein kinase C -independent mechanism .", "annotated_text": "Thapsigargin induces <protein>IL-2 receptor alpha-chain</protein> in <cell_type>human peripheral</cell_type> and <cell_line>Jurkat T cells</cell_line> via a <protein>protein kinase C</protein> -independent mechanism ."}
{"id": "1377", "text": "Thapsigargin ( TG ) , an inhibitor of Ca ( 2+ ) -ATPase , depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels .", "annotated_text": "Thapsigargin ( TG ) , an inhibitor of <protein>Ca ( 2+ ) -ATPase</protein> , depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels ."}
{"id": "1378", "text": "TG plus phorbol myristate acetate ( PMA ) but not TG alone induced IL-2 in Jurkat T cells , suggesting that TG had no effect on protein kinase C ( PKC ) .", "annotated_text": "TG plus phorbol myristate acetate ( PMA ) but not TG alone induced <protein>IL-2</protein> in <cell_line>Jurkat T cells</cell_line> , suggesting that TG had no effect on <protein>protein kinase C</protein> ( <protein>PKC</protein> ) ."}
{"id": "1379", "text": "However , TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA in Jurkat T cells in a dose-dependent manner .", "annotated_text": "However , TG induced increases in <protein>IL-2R alpha protein</protein> as well as <rna>IL-2R alpha mRNA</rna> in <cell_line>Jurkat T cells</cell_line> in a dose-dependent manner ."}
{"id": "1380", "text": "A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells .", "annotated_text": "A similar increase in <protein>IL-2R alpha</protein> by TG was also observed in <cell_type>human peripheral T cells</cell_type> ."}
{"id": "1381", "text": "Further , like PMA , TG markedly induced NF kappa B in Jurkat T cells .", "annotated_text": "Further , like PMA , TG markedly induced <protein>NF kappa B</protein> in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "1382", "text": "However , TG and PMA exhibited a synergistic action on IL-2R alpha expression , suggesting that TG and PMA induce IL-2R alpha through distinct pathways .", "annotated_text": "However , TG and PMA exhibited a synergistic action on <protein>IL-2R alpha</protein> expression , suggesting that TG and PMA induce <protein>IL-2R alpha</protein> through distinct pathways ."}
{"id": "1383", "text": "PMA -but not TG-induced IL-2R alpha is inhibited by the PKC inhibitor H7 , whereas TG -but not PMA-induced IL-2R alpha was inhibited by cholera toxin , forskolin and 1 , 9-dideoxy forskolin .", "annotated_text": "<protein>PMA -but not TG-induced IL-2R alpha</protein> is inhibited by the <protein>PKC</protein> inhibitor H7 , whereas <protein>TG -but not PMA-induced IL-2R alpha</protein> was inhibited by cholera toxin , forskolin and 1 , 9-dideoxy forskolin ."}
{"id": "1384", "text": "In toto , these results suggest that TG induces IL-2R alpha in human T cells through a PKC -independent pathway .", "annotated_text": "In toto , these results suggest that TG induces <protein>IL-2R alpha</protein> in <cell_type>human T cells</cell_type> through a <protein>PKC</protein> -independent pathway ."}
{"id": "1385", "text": "Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system .", "annotated_text": "Physiological concentration of estradiol inhibits <cell_type>polymorphonuclear leukocyte</cell_type> chemotaxis via a receptor mediated system ."}
{"id": "1386", "text": "Estrogen exhibits a variety of actions , including immuno-modulatory effects , in vivo and in vitro .", "annotated_text": "Estrogen exhibits a variety of actions , including immuno-modulatory effects , in vivo and in vitro ."}
{"id": "1387", "text": "The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood .", "annotated_text": "The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood ."}
{"id": "1388", "text": "We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes ( PMNs ) , which are important in the immune response .", "annotated_text": "We investigated the possible mechanisms of estradiol acting via the <cell_type>polymorphonuclear leukocytes</cell_type> ( <cell_type>PMNs</cell_type> ) , which are important in the immune response ."}
{"id": "1389", "text": "The agent , 17 beta-estradiol , but not 17 alpha-estradiol , significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner ( control vs estrogen 10 ( -10 ) - ( -6 ) M , P < 0.05 ) .", "annotated_text": "The agent , 17 beta-estradiol , but not 17 alpha-estradiol , significantly reduced <cell_type>PMNs</cell_type> chemotaxis to FMLP in a dose-dependent manner ( control vs estrogen 10 ( -10 ) - ( -6 ) M , P < 0.05 ) ."}
{"id": "1390", "text": "Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs ( 10 ( -10 ) mol ) .", "annotated_text": "Physiological concentrations of estradiol significantly reduced the chemotaxis of <cell_type>PMNs</cell_type> ( 10 ( -10 ) mol ) ."}
{"id": "1391", "text": "Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists , eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of PMNs , restoring it to the control level .", "annotated_text": "Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists , eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of <cell_type>PMNs</cell_type> , restoring it to the control level ."}
{"id": "1392", "text": "These observations suggest that 17 beta-estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism .", "annotated_text": "These observations suggest that 17 beta-estradiol suppressed the chemotaxis of <cell_type>PMNs</cell_type> by a receptor-dependent mechanism ."}
{"id": "1393", "text": "In addition , the level of estradiol in human plasma , which PMNs were drawn , showed a close , inverse correlation with the PMNs chemotaxis to FMLP ( r = -0.821 p < 0.001 ) .", "annotated_text": "In addition , the level of estradiol in <cell_type>human plasma</cell_type> , which <cell_type>PMNs</cell_type> were drawn , showed a close , inverse correlation with the <cell_type>PMNs</cell_type> chemotaxis to FMLP ( r = -0.821 p < 0.001 ) ."}
{"id": "1394", "text": "Estrogen may modify the activity of neutrophils during the normal menstrual cycle , not only during pregnancy , and influence inflammation .", "annotated_text": "Estrogen may modify the activity of <cell_type>neutrophils</cell_type> during the normal menstrual cycle , not only during pregnancy , and influence inflammation ."}
{"id": "1395", "text": "Identification of the TCL1 gene involved in T-cell malignancies .", "annotated_text": "Identification of the <dna>TCL1 gene</dna> involved in <cell_type>T-cell</cell_type> malignancies ."}
{"id": "1396", "text": "The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal translocations and inversions with one of the T-cell receptor loci in human T-cell leukemias and lymphomas .", "annotated_text": "The <dna>TCL1 locus</dna> on <dna>chromosome 14q32.1</dna> is frequently involved in chromosomal translocations and inversions with one of the <dna>T-cell receptor loci</dna> in human T-cell leukemias and lymphomas ."}
{"id": "1397", "text": "The chromosome 14 region translocated or rearranged involves approximately 350 kb of DNA at chromosome band 14q32.1 .", "annotated_text": "The <dna>chromosome 14 region</dna> translocated or rearranged involves approximately 350 kb of DNA at chromosome band 14q32.1 ."}
{"id": "1398", "text": "Within this region we have identified a gene coding for a 1.3-kb transcript , expressed only in restricted subsets of cells within the lymphoid lineage and expressed at high levels in leukemic cells carrying a t ( 14 ; 14 ) ( q11 ; q32 ) chromosome translocation or a inv ( 14 ) ( q11 ; q32 ) chromosome inversion .", "annotated_text": "Within this region we have identified a gene coding for a <rna>1.3-kb transcript</rna> , expressed only in restricted subsets of cells within the <cell_type>lymphoid lineage</cell_type> and expressed at high levels in <cell_type>leukemic cells</cell_type> carrying a t ( 14 ; 14 ) ( q11 ; q32 ) chromosome translocation or a inv ( 14 ) ( q11 ; q32 ) chromosome inversion ."}
{"id": "1399", "text": "The cognate cDNA sequence reveals an open reading frame of 342 nt encoding a protein of 14 kDa .", "annotated_text": "The <dna>cognate cDNA sequence</dna> reveals an <dna>open reading frame</dna> of 342 nt encoding a <protein>protein of 14 kDa</protein> ."}
{"id": "1400", "text": "The TCL1 gene sequence , which , to our knowledge , shows no sequence homology with other human genes , is preferentially expressed early in T- and B-lymphocyte differentiation .", "annotated_text": "The <dna>TCL1 gene</dna> sequence , which , to our knowledge , shows no sequence homology with other <dna>human genes</dna> , is preferentially expressed early in <cell_type>T- and B-lymphocyte</cell_type> differentiation ."}
{"id": "1401", "text": "Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 ( macrophage colony-stimulating factor ) receptor promoter and binds PEBP2/CBF ( AML1 ) .", "annotated_text": "Identification of a region which directs the monocytic activity of the <dna>colony-stimulating factor 1 ( macrophage colony-stimulating factor ) receptor promoter</dna> and binds <protein>PEBP2/CBF</protein> ( <protein>AML1</protein> ) ."}
{"id": "1402", "text": "The receptor for the macrophage colony-stimulating factor ( or colony-stimulating factor 1 [ CSF-1 ] ) is expressed from different promoters in monocytic cells and placental trophoblasts .", "annotated_text": "The receptor for the <protein>macrophage colony-stimulating factor</protein> ( or <protein>colony-stimulating factor 1</protein> [ <protein>CSF-1</protein> ] ) is expressed from different promoters in <cell_type>monocytic cells</cell_type> and <cell_type>placental trophoblasts</cell_type> ."}
{"id": "1403", "text": "We have demonstrated that the monocyte-specific expression of the CSF-1 receptor is regulated at the level of transcription by a tissue-specific promoter whose activity is stimulated by the monocyte/B-cell-specific transcription factor PU.1 ( D.-E.Zhang , C.J.Hetherington , H.-M.Chen , and D.G.Tenen , Mol.Cell. Biol.14 : 373-381 , 1994 ) .", "annotated_text": "We have demonstrated that the monocyte-specific expression of the <protein>CSF-1 receptor</protein> is regulated at the level of transcription by a <dna>tissue-specific promoter</dna> whose activity is stimulated by the <protein>monocyte/B-cell-specific transcription factor</protein> <protein>PU.1</protein> ( D.-E.Zhang , C.J.Hetherington , H.-M.Chen , and D.G.Tenen , Mol.Cell. Biol.14 : 373-381 , 1994 ) ."}
{"id": "1404", "text": "Here we report that the tissue specificity of this promoter is also mediated by sequences in a region II ( bp -88 to - 59 ) , which lies 10 bp upstream from the PU.1-binding site .", "annotated_text": "Here we report that the tissue specificity of this <dna>promoter</dna> is also mediated by sequences in a <dna>region II</dna> ( bp -88 to - 59 ) , which lies <dna>10 bp upstream</dna> from the <dna>PU.1-binding site</dna> ."}
{"id": "1405", "text": "When analyzed by DNase footprinting , region II was protected preferentially in monocytic cells .", "annotated_text": "When analyzed by <protein>DNase</protein> footprinting , <dna>region II</dna> was protected preferentially in <cell_type>monocytic cells</cell_type> ."}
{"id": "1406", "text": "Electrophoretic mobility shift assays confirmed that region II interacts specifically with nuclear proteins from monocytic cells .", "annotated_text": "Electrophoretic mobility shift assays confirmed that <dna>region II</dna> interacts specifically with <protein>nuclear proteins</protein> from <cell_type>monocytic cells</cell_type> ."}
{"id": "1407", "text": "Two gel shift complexes ( Mono A and Mono B ) were formed with separate sequence elements within this region .", "annotated_text": "Two <protein>gel shift complexes</protein> ( <protein>Mono A</protein> and <protein>Mono B</protein> ) were formed with separate sequence elements within this region ."}
{"id": "1408", "text": "Competition and supershift experiments indicate that Mono B contains a member of the polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family , which includes the AML1 gene product , while Mono A is a distinct complex preferentially expressed in monocytic cells .", "annotated_text": "Competition and supershift experiments indicate that <protein>Mono B</protein> contains a member of the <protein>polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family ,</protein> which includes the AML1 gene product , while <protein>Mono A</protein> is a distinct complex preferentially expressed in <cell_type>monocytic cells</cell_type> ."}
{"id": "1409", "text": "Promoter constructs with mutations in these sequence elements were no longer expressed specifically in monocytes .", "annotated_text": "<dna>Promoter constructs</dna> with mutations in these sequence elements were no longer expressed specifically in <cell_type>monocytes</cell_type> ."}
{"id": "1410", "text": "Furthermore , multimerized region II sequence elements enhanced the activity of a heterologous thymidine kinase promoter in monocytic cells but not other cell types tested .", "annotated_text": "Furthermore , <dna>multimerized region II sequence elements</dna> enhanced the activity of a heterologous thymidine kinase promoter in <cell_type>monocytic cells</cell_type> but not other cell types tested ."}
{"id": "1411", "text": "These results indicate that the monocyte/B-cell-specific transcription factor PU.1 and the Mono A and Mono B protein complexes act in concert to regulate monocyte-specific transcription of the CSF-1 receptor .", "annotated_text": "These results indicate that the <protein>monocyte/B-cell-specific transcription factor</protein> <protein>PU.1</protein> and the <protein>Mono A and Mono B protein complexes</protein> act in concert to regulate monocyte-specific transcription of the <protein>CSF-1 receptor</protein> ."}
{"id": "1412", "text": "Pyrrolidine dithiocarbamate , a potent inhibitor of nuclear factor kappa B ( NF-kappa B ) activation , prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes .", "annotated_text": "Pyrrolidine dithiocarbamate , a potent inhibitor of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) activation , prevents apoptosis in human <cell_line>promyelocytic leukemia HL-60 cells</cell_line> and <cell_type>thymocytes</cell_type> ."}
{"id": "1413", "text": "We examined the effect of pyrrolidine dithiocarbamate ( PDTC ) , which potently blocks the activation of nuclear factor kappa B ( NF-kappa B ) , on the induction of apoptosis by a variety of agents .", "annotated_text": "We examined the effect of pyrrolidine dithiocarbamate ( PDTC ) , which potently blocks the activation of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) , on the induction of apoptosis by a variety of agents ."}
{"id": "1414", "text": "Treatment of a human promyelocytic leukemia cell line , HL-60 , with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr .", "annotated_text": "Treatment of a <cell_line>human promyelocytic leukemia cell line</cell_line> , <cell_line>HL-60</cell_line> , with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced <protein>NF-kappa B</protein> activation within 1 hr and subsequently caused apoptosis within 3-4 hr ."}
{"id": "1415", "text": "The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr .", "annotated_text": "The simultaneous addition of 50-500 microM PDTC with these agents blocked <protein>NF-kappa B</protein> activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr ."}
{"id": "1416", "text": "However , PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates .", "annotated_text": "However , PDTC failed to inhibit the <protein>endonuclease</protein> activity contained in the whole cell lysates ."}
{"id": "1417", "text": "The inhibitory effect of PDTC was also observed in etoposide -and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM .", "annotated_text": "The inhibitory effect of PDTC was also observed in etoposide -and dexamethasone-induced apoptosis in <cell_type>human thymocytes</cell_type> at a concentration of 1-10 microM ."}
{"id": "1418", "text": "Since PDTC has both antioxidant and metal-ion chelating activities , we tested the effects of N-acetyl-L-cysteine ( NAC ) ( antioxidant ) or o-phenanthroline ( OP ) ( metal-ion chelator ) on the induction of apoptosis .", "annotated_text": "Since PDTC has both antioxidant and metal-ion chelating activities , we tested the effects of N-acetyl-L-cysteine ( NAC ) ( antioxidant ) or o-phenanthroline ( OP ) ( metal-ion chelator ) on the induction of apoptosis ."}
{"id": "1419", "text": "Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr , but not 10-60 mM NAC , suppressed subsequent occurrence of apoptosis induced by etoposide .", "annotated_text": "Pretreatment of HL-60 cells or <cell_type>thymocytes</cell_type> with 100-500 microM OP for 2 hr , but not 10-60 mM NAC , suppressed subsequent occurrence of apoptosis induced by etoposide ."}
{"id": "1420", "text": "These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells .", "annotated_text": "These results suggest that the activation of <protein>NF-kappa B</protein> plays an important role in the apoptotic process of <cell_type>human hematopoietic cells</cell_type> ."}
{"id": "1421", "text": "Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation .", "annotated_text": "Overexpression of <protein>protein kinase C-zeta</protein> stimulates <cell_type>leukemic cell</cell_type> differentiation ."}
{"id": "1422", "text": "A function for protein kinase C-zeta ( PKC-zeta ) , a member of the phorbol ester nonresponsive atypical protein kinase C subfamily , in modulating differentiation was examined in the leukemic U937 cell .", "annotated_text": "A function for <protein>protein kinase C-zeta</protein> ( <protein>PKC-zeta</protein> ) , a member of the phorbol ester nonresponsive atypical <protein>protein kinase C subfamily</protein> , in modulating differentiation was examined in the <cell_line>leukemic U937 cell</cell_line> ."}
{"id": "1423", "text": "Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time , lower saturation density at confluency , and an increase in adherence to plastic as compared to control cells .", "annotated_text": "Transfected <cell_line>U937 cells</cell_line> stably overexpressing <protein>PKC-zeta</protein> displayed a longer doubling time , lower saturation density at confluency , and an increase in adherence to plastic as compared to <cell_line>control cells</cell_line> ."}
{"id": "1424", "text": "PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology , surface antigen expression , and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters .", "annotated_text": "<cell_line>PKC-zeta cells</cell_line> expressed a more differentiated phenotype as assessed by changes in morphology , surface antigen expression , and <protein>lysosomal enzyme</protein> activities and were distinct from <cell_line>parental U937 cells</cell_line> stimulated to differentiate by exposure to phorbol esters ."}
{"id": "1425", "text": "In contrast to parental U937 cells , PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity .", "annotated_text": "In contrast to parental <cell_line>U937 cells</cell_line> , <cell_line>PKC-zeta cells</cell_line> constitutively expressed <rna>mRNA transcripts</rna> for <dna>c-jun</dna> and a low mobility <protein>AP-1</protein> binding activity ."}
{"id": "1426", "text": "Thus , PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment .", "annotated_text": "Thus , <protein>PKC-zeta</protein> overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other <protein>PKC subfamilies</protein> induced by phorbol ester treatment ."}
{"id": "1427", "text": "Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell .", "annotated_text": "Increased expression of the <dna>c-jun</dna> protooncogene and an increase in <protein>AP-1</protein> binding activity in <cell_line>PKC-zeta cells</cell_line> provides a potential mechanism for explaining the altered differentiation status of this cell ."}
{"id": "1428", "text": "A family of serine proteases expressed exclusively in myelo- monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells .", "annotated_text": "A family of <protein>serine proteases</protein> expressed exclusively in myelo- <cell_type>monocytic cells</cell_type> specifically processes the <protein>nuclear factor-kappa B subunit p65</protein> in vitro and may impair human immunodeficiency virus replication in these cells ."}
{"id": "1429", "text": "Two groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 ( HIV-1 ) replication .", "annotated_text": "Two groups of <cell_line>U937 promonocytic cells</cell_line> were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 ( HIV-1 ) replication ."}
{"id": "1430", "text": "`` Plus '' clones replicated the virus efficiently , whereas `` minus '' clones did not .", "annotated_text": "<cell_line>`` Plus '' clones</cell_line> replicated the virus efficiently , whereas <cell_line>`` minus '' clones</cell_line> did not ."}
{"id": "1431", "text": "We examined these clones for differences in nuclear factor ( NF ) -kappa B activity which might account for the observed phenomenon .", "annotated_text": "We examined these clones for differences in <protein>nuclear factor ( NF ) -kappa B</protein> activity which might account for the observed phenomenon ."}
{"id": "1432", "text": "Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools , whereas minus clones produced an apparently novel , faster-migrating complex , as judged by electrophoretic mobility shift assays .", "annotated_text": "Stimulation of <cell_line>plus clones</cell_line> liberated the classical <protein>p50-p65 complex</protein> from cytoplasmic pools , whereas <cell_line>minus clones</cell_line> produced an apparently novel , <protein>faster-migrating complex</protein> , as judged by electrophoretic mobility shift assays ."}
{"id": "1433", "text": "It is surprising that the faster-migrating complex was composed also of p50 and p65 .", "annotated_text": "It is surprising that the <protein>faster-migrating complex</protein> was composed also of <protein>p50</protein> and <protein>p65</protein> ."}
{"id": "1434", "text": "However , the p65 subunit was COOH-terminally truncated , as shown by immunoprecipitation .", "annotated_text": "However , the <protein>p65 subunit</protein> was COOH-terminally truncated , as shown by immunoprecipitation ."}
{"id": "1435", "text": "The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases , such as elastase , cathepsin G , and proteinase 3 .", "annotated_text": "The truncation resulted from limited proteolysis of <protein>p65</protein> during cellular extraction which released particular <protein>lysosomal serine proteases</protein> , such as <protein>elastase</protein> , <protein>cathepsin G</protein> , and <protein>proteinase 3</protein> ."}
{"id": "1436", "text": "These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones , but not in the plus clones , as demonstrated in the case of cathepsin G .", "annotated_text": "These specific proteases are coordinately expressed and were present exclusively in the <cell_line>minus U937 clones</cell_line> , but not in the <cell_line>plus clones</cell_line> , as demonstrated in the case of <protein>cathepsin G</protein> ."}
{"id": "1437", "text": "In addition , these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes , in each case correlating with the truncated from of p65 .", "annotated_text": "In addition , these proteases were detected in certain subclones of <cell_line>THP-1</cell_line> and <cell_line>HL-60 cells</cell_line> and in primary <cell_type>monocytes</cell_type> , in each case correlating with the truncated from of <protein>p65</protein> ."}
{"id": "1438", "text": "We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G .", "annotated_text": "We demonstrate in vitro cleavage of <protein>p65</protein> by purified <protein>elastase</protein> and <protein>cathepsin G</protein> ."}
{"id": "1439", "text": "It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo-monocytic cells .", "annotated_text": "It is possible that particular <protein>serine proteases</protein> may have inhibiting effects on the replication of HIV-1 in <cell_line>myelo-monocytic cells</cell_line> ."}
{"id": "1440", "text": "The data also demonstrate that special precautions must be taken when making extracts from myelo-monocytic cells .", "annotated_text": "The data also demonstrate that special precautions must be taken when making extracts from <cell_line>myelo-monocytic cells</cell_line> ."}
{"id": "1441", "text": "A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma [ see comments ]", "annotated_text": "A <dna>germline TaqI restriction fragment length polymorphism</dna> in the <dna>progesterone receptor gene</dna> in ovarian carcinoma [ see comments ]"}
{"id": "1442", "text": "Clinical outcome in ovarian carcinoma is predicted by progesterone receptor status , indicating an endocrine aspect to this disease .", "annotated_text": "Clinical outcome in ovarian carcinoma is predicted by <protein>progesterone receptor</protein> status , indicating an endocrine aspect to this disease ."}
{"id": "1443", "text": "Peripheral leucocyte genomic DNAs were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland , as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany .", "annotated_text": "<dna>Peripheral leucocyte genomic DNAs</dna> were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland , as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany ."}
{"id": "1444", "text": "Southern analysis using a human progesterone receptor ( hPR ) cDNA probe identified a germline TaqI restriction fragment length polymorphism ( RFLP ) defined by two alleles : T1 , represented by a 2.7 kb fragment ; and T2 , represented by a 1.9 kb fragment and characterised by an additional TaqI restriction site with respect to T1 .", "annotated_text": "Southern analysis using a <dna>human progesterone receptor ( hPR ) cDNA probe</dna> identified a <dna>germline TaqI restriction fragment length polymorphism</dna> ( <dna>RFLP</dna> ) defined by two alleles : <dna>T1</dna> , represented by a <dna>2.7 kb fragment</dna> ; and <dna>T2</dna> , represented by a <dna>1.9 kb fragment</dna> and characterised by an additional <dna>TaqI restriction site</dna> with respect to <dna>T1</dna> ."}
{"id": "1445", "text": "An over-representation of T2 in ovarian cancer patients compared with controls in the pooled Irish/German population ( P < 0.025 ) was observed .", "annotated_text": "An over-representation of <dna>T2</dna> in ovarian cancer patients compared with controls in the pooled Irish/German population ( P < 0.025 ) was observed ."}
{"id": "1446", "text": "A difference ( P < 0.02 ) in the distribution of the RFLP genotypes between Irish and German control populations was also observed .", "annotated_text": "A difference ( P < 0.02 ) in the distribution of the <dna>RFLP</dna> genotypes between Irish and German control populations was also observed ."}
{"id": "1447", "text": "The allele distributions could not be shown to differ significantly from Hardy-Weinberg distribution in any subgroup .", "annotated_text": "The allele distributions could not be shown to differ significantly from Hardy-Weinberg distribution in any subgroup ."}
{"id": "1448", "text": "Using hPR cDNA region-specific probes , the extra TaqI restriction site was mapped to intron G of the hPR gene .", "annotated_text": "Using <dna>hPR cDNA region-specific probes</dna> , the extra TaqI restriction site was mapped to <dna>intron G</dna> of the <dna>hPR gene</dna> ."}
{"id": "1449", "text": "OBF-1 , a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins .", "annotated_text": "<protein>OBF-1</protein> , a <protein>novel B cell-specific coactivator</protein> that stimulates <dna>immunoglobulin promoter</dna> activity through association with <protein>octamer-binding proteins</protein> ."}
{"id": "1450", "text": "Recent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2 , other B cell components are required for lymphoid-restricted , octamer site-mediated immunoglobulin gene promoter activity .", "annotated_text": "Recent biochemical and genetic studies indicate that in addition to the <protein>octamer-binding proteins</protein> <protein>Oct-1</protein> and <protein>Oct-2</protein> , other <protein>B cell components</protein> are required for lymphoid-restricted , octamer site-mediated <dna>immunoglobulin gene promoter</dna> activity ."}
{"id": "1451", "text": "Using a genetic screen in yeast , we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 ( OBF-1 ) , a novel protein that specifically associates with Oct-1 and Oct-2 .", "annotated_text": "Using a genetic screen in yeast , we have isolated <dna>B cell-derived cDNAs</dna> encoding <protein>Oct-binding factor 1</protein> ( <protein>OBF-1</protein> ) , a novel protein that specifically associates with <protein>Oct-1</protein> and <protein>Oct-2</protein> ."}
{"id": "1452", "text": "Biochemical studies demonstrate that OBF-1 has no intrinsic DNA-binding activity and recognizes the POU domains of Oct-1 and Oct-2 , but not those of Oct-4 and Oct-6 .", "annotated_text": "Biochemical studies demonstrate that <protein>OBF-1</protein> has no intrinsic DNA-binding activity and recognizes the <protein>POU domains</protein> of <protein>Oct-1</protein> and <protein>Oct-2</protein> , but not those of <protein>Oct-4</protein> and <protein>Oct-6</protein> ."}
{"id": "1453", "text": "The OBF-1 mRNA is expressed in a highly cell-specific manner , being most abundant in B cells and essentially absent in most of the other cells or tissues tested .", "annotated_text": "The <rna>OBF-1 mRNA</rna> is expressed in a highly cell-specific manner , being most abundant in <cell_type>B cells</cell_type> and essentially absent in most of the other cells or tissues tested ."}
{"id": "1454", "text": "Furthermore , expression of OBF-1 in HeLa cells selectively stimulates the activity of a natural immunoglobulin promoter in an octamer site -dependent manner .", "annotated_text": "Furthermore , expression of <protein>OBF-1</protein> in <cell_line>HeLa cells</cell_line> selectively stimulates the activity of a natural <dna>immunoglobulin promoter</dna> in an <dna>octamer site</dna> -dependent manner ."}
{"id": "1455", "text": "Thus , OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein .", "annotated_text": "Thus , <protein>OBF-1</protein> has all the properties expected for a <protein>B cell-specific transcriptional coactivator protein</protein> ."}
{"id": "1456", "text": "Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply .", "annotated_text": "Modulation of <protein>transcription factor NF kappa B</protein> activity by intracellular glutathione levels and by variations of the extracellular cysteine supply ."}
{"id": "1457", "text": "HIV-infected individuals and SIV-infected rhesus macaques have , on the average , decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels .", "annotated_text": "HIV-infected individuals and SIV-infected rhesus macaques have , on the average , decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels ."}
{"id": "1458", "text": "We now show that a depletion of intracellular glutathione in a human T cell line ( Molt-4 ) inhibits the activation and nuclear translocation of the transcription factor NF kappa B , whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of NF kappa B .", "annotated_text": "We now show that a depletion of intracellular glutathione in a <cell_line>human T cell line</cell_line> ( <cell_line>Molt-4</cell_line> ) inhibits the activation and nuclear translocation of the <protein>transcription factor NF kappa B</protein> , whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of <protein>NF kappa B</protein> ."}
{"id": "1459", "text": "Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and GSSG can be shown to inhibit the DNA-binding activity directly in cell-free systems , our studies suggest that GSSG is a physiologically relevant inhibitor in intact cells also .", "annotated_text": "Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and <protein>GSSG</protein> can be shown to inhibit the DNA-binding activity directly in cell-free systems , our studies suggest that <protein>GSSG</protein> is a physiologically relevant inhibitor in <cell_type>intact cells</cell_type> also ."}
{"id": "1460", "text": "NF kappa B controls many immunologically important genes , so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine .", "annotated_text": "<protein>NF kappa B</protein> controls many <dna>immunologically important genes</dna> , so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine ."}
{"id": "1461", "text": "Two distinct signalling pathways are involved in the control of the biphasic junB transcription induced by interleukin-6 in the B cell hybridoma 7TD1 .", "annotated_text": "Two distinct signalling pathways are involved in the control of the biphasic <dna>junB</dna> transcription induced by <protein>interleukin-6</protein> in the <cell_line>B cell hybridoma 7TD1</cell_line> ."}
{"id": "1462", "text": "We have measured the level of junB mRNA in the B hybridoma cell line 7TD1 , under interleukin-6 ( IL-6 ) stimulation .", "annotated_text": "We have measured the level of <rna>junB mRNA</rna> in the <cell_line>B hybridoma cell line 7TD1</cell_line> , under <protein>interleukin-6</protein> ( <protein>IL-6</protein> ) stimulation ."}
{"id": "1463", "text": "IL-6 increases junB mRNA in a biphasic fashion .", "annotated_text": "<protein>IL-6</protein> increases <rna>junB mRNA</rna> in a biphasic fashion ."}
{"id": "1464", "text": "The first early-induced peak was transient and likely corresponds to the well documented typical junB mRNA , stimulated in response to numerous growth factors , including IL-6 .", "annotated_text": "The first early-induced peak was transient and likely corresponds to the well documented typical <rna>junB mRNA</rna> , stimulated in response to numerous <protein>growth factors</protein> , including <protein>IL-6</protein> ."}
{"id": "1465", "text": "At variance , the second peak which has never been reported previously , lasted several hours .", "annotated_text": "At variance , the second peak which has never been reported previously , lasted several hours ."}
{"id": "1466", "text": "As a consequence of its effect on junB mRNA , IL-6 stimulated , in a biphasic fashion , the nuclear accumulation of the JunB protein .", "annotated_text": "As a consequence of its effect on <rna>junB mRNA</rna> , <protein>IL-6</protein> stimulated , in a biphasic fashion , the nuclear accumulation of the <protein>JunB protein</protein> ."}
{"id": "1467", "text": "In this study , we demonstrated that IL-6 regulation occurred exclusively at the transcriptional level and that the bimodal increase of junB mRNA and JunB protein can be accounted for by a biphasic stimulation of junB transcription .", "annotated_text": "In this study , we demonstrated that <protein>IL-6</protein> regulation occurred exclusively at the transcriptional level and that the bimodal increase of <rna>junB mRNA</rna> and <protein>JunB protein</protein> can be accounted for by a biphasic stimulation of <dna>junB</dna> transcription ."}
{"id": "1468", "text": "Furthermore , our data point to two major differences between the mechanism of control of the early and the late IL-6 -induced junB transcription waves .", "annotated_text": "Furthermore , our data point to two major differences between the mechanism of control of the early and the late <protein>IL-6</protein> -induced <dna>junB</dna> transcription waves ."}
{"id": "1469", "text": "First , cycloheximide strongly potentiated the transcription of the second wave , whereas it failed to affect the early-induced burst .", "annotated_text": "First , cycloheximide strongly potentiated the transcription of the second wave , whereas it failed to affect the early-induced burst ."}
{"id": "1470", "text": "Second , tyrphostin , a tyrosine kinase inhibitor , impaired the expression of the first but not the second junB mRNA peak .", "annotated_text": "Second , tyrphostin , a tyrosine kinase inhibitor , impaired the expression of the first but not the second <rna>junB mRNA</rna> peak ."}
{"id": "1471", "text": "Conversely , genistein , another tyrosine kinase inhibitor , totally abolished the expression of the second peak of junB mRNA whereas it did not affect the expression of the first peak .", "annotated_text": "Conversely , genistein , another tyrosine kinase inhibitor , totally abolished the expression of the second peak of <rna>junB mRNA</rna> whereas it did not affect the expression of the first peak ."}
{"id": "1472", "text": "Altogether these data indicate that , in 7TD1 cells , IL-6 controls junB transcription in a biphasic fashion by means of two separate transduction pathways .", "annotated_text": "Altogether these data indicate that , in <cell_line>7TD1 cells</cell_line> , <protein>IL-6</protein> controls <dna>junB</dna> transcription in a biphasic fashion by means of two separate transduction pathways ."}
{"id": "1473", "text": "A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles .", "annotated_text": "A newly established <cell_line>megakaryoblastic/erythroid cell line</cell_line> that differentiates to <cell_type>red cells</cell_type> in the presence of <protein>erythropoietin</protein> and produces <cell_type>platelet-like particles</cell_type> ."}
{"id": "1474", "text": "In August , 1992 , we established a leukemic cell line ( NS-Meg ) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia .", "annotated_text": "In August , 1992 , we established a <cell_line>leukemic cell line</cell_line> ( <cell_line>NS-Meg</cell_line> ) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia ."}
{"id": "1475", "text": "The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff ( PAS ) staining and for surface CD4 , CD7 , CD13 , CD34 , CD41a , and glycophorin A antigens .", "annotated_text": "The <cell_line>NS-Meg cells</cell_line> were positive for <protein>alpha-naphthyl acetate esterase</protein> and periodic acid-Schiff ( PAS ) staining and for surface <protein>CD4</protein> , <protein>CD7</protein> , <protein>CD13</protein> , <protein>CD34</protein> , <protein>CD41a</protein> , and <protein>glycophorin A antigens</protein> ."}
{"id": "1476", "text": "Ultrastructurally , the cells had alpha-granules , demarcation membranes , and platelet peroxidase activity .", "annotated_text": "Ultrastructurally , the cells had alpha-granules , demarcation membranes , and <protein>platelet peroxidase</protein> activity ."}
{"id": "1477", "text": "The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules , mitochondria and dense bodies , strongly suggesting platelet production .", "annotated_text": "The <cell_line>NS-Meg cells</cell_line> spontaneously produced <cell_type>platelet-like particles</cell_type> which contained alpha-granules , mitochondria and dense bodies , strongly suggesting platelet production ."}
{"id": "1478", "text": "Erythropoietin ( Epo ) , granulocyte/macrophage colony stimulating factor ( GM-CSF ) , and interleukin 3 ( IL-3 ) promoted the growth of NS-Meg cells .", "annotated_text": "<protein>Erythropoietin</protein> ( <protein>Epo</protein> ) , <protein>granulocyte/macrophage colony stimulating factor</protein> ( <protein>GM-CSF</protein> ) , and <protein>interleukin 3</protein> ( <protein>IL-3</protein> ) promoted the growth of <cell_line>NS-Meg cells</cell_line> ."}
{"id": "1479", "text": "Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens .", "annotated_text": "Phorbol-12-myristate-13-acetate increased the expression of both <protein>CD41a</protein> and CD61 antigens ."}
{"id": "1480", "text": "Ten-day exposure to Epo induced mature erythroblasts and red cells .", "annotated_text": "Ten-day exposure to <protein>Epo</protein> induced <cell_type>mature erythroblasts</cell_type> and <cell_type>red cells</cell_type> ."}
{"id": "1481", "text": "These benzidine-positive cells were positive for hemoglobin F staining .", "annotated_text": "These <cell_line>benzidine-positive cells</cell_line> were positive for <protein>hemoglobin</protein> F staining ."}
{"id": "1482", "text": "Untreated NS-Meg cells expressed mRNA for the Epo receptor ( EpoR ) , for GATA-1 , and for alpha 1 , alpha 2 and gamma globin genes .", "annotated_text": "Untreated <cell_line>NS-Meg cells</cell_line> expressed <rna>mRNA</rna> for the <protein>Epo receptor</protein> ( <protein>EpoR</protein> ) , for <protein>GATA-1</protein> , and for <dna>alpha 1 , alpha 2 and gamma globin genes</dna> ."}
{"id": "1483", "text": "These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages .", "annotated_text": "These results indicate that <cell_line>NS-Meg cells</cell_line> undergo terminal differentiation of both <cell_type>megakaryocytic and erythroid lineages</cell_type> ."}
{"id": "1484", "text": "This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation .", "annotated_text": "This <cell_line>cell line</cell_line> should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation ."}
{"id": "1485", "text": "Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28 .", "annotated_text": "Differential regulation of <dna>proto-oncogenes</dna> <dna>c-jun</dna> and <dna>c-fos</dna> in <cell_type>T lymphocytes</cell_type> activated through <protein>CD28</protein> ."}
{"id": "1486", "text": "The T cell surface molecule CD28 binds to ligands on accessory cells and APCs , playing an important costimulatory role in the response of T cells to Ags .", "annotated_text": "The <protein>T cell surface molecule</protein> <protein>CD28</protein> binds to ligands on <cell_type>accessory cells</cell_type> and <cell_type>APCs</cell_type> , playing an important costimulatory role in the response of <cell_type>T cells</cell_type> to <protein>Ags</protein> ."}
{"id": "1487", "text": "Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete .", "annotated_text": "Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete ."}
{"id": "1488", "text": "In addition to activation of phospholipase C gamma 1 , ligation of this receptor also seems to activate a calcium-independent , CD28 -specific pathway .", "annotated_text": "In addition to activation of <protein>phospholipase C gamma 1</protein> , ligation of this receptor also seems to activate a calcium-independent , <protein>CD28</protein> -specific pathway ."}
{"id": "1489", "text": "In this paper , we report that cross-linking of CD28 ( but not CD2 , CD5 , LFA-1 , or CD7 ) leads to an elevation of c-jun mRNA , with only minimal activation of c-fos expression .", "annotated_text": "In this paper , we report that cross-linking of <protein>CD28</protein> ( but not <protein>CD2</protein> , <protein>CD5</protein> , <protein>LFA-1</protein> , or <protein>CD7</protein> ) leads to an elevation of <rna>c-jun mRNA</rna> , with only minimal activation of <dna>c-fos</dna> expression ."}
{"id": "1490", "text": "CD28 -dependent induction of c-jun expression requires protein tyrosine kinase activity , but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium .", "annotated_text": "<protein>CD28</protein> -dependent induction of <dna>c-jun</dna> expression requires <protein>protein tyrosine kinase</protein> activity , but does not depend on activation of a <protein>phorbol ester-responsive protein kinase C</protein> or elevation of cytosolic calcium ."}
{"id": "1491", "text": "Furthermore , CD28 -dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability .", "annotated_text": "Furthermore , <protein>CD28</protein> -dependent elevation of <rna>c-jun mRNA</rna> does not appear to be mediated at the level of mRNA stability ."}
{"id": "1492", "text": "A mechanism is suggested whereby expression of c-jun and junB , in the absence of members of the fos family , can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus .", "annotated_text": "A mechanism is suggested whereby expression of <dna>c-jun</dna> and <dna>junB</dna> , in the absence of members of the <dna>fos family</dna> , can prevent inappropriate activation of <cell_type>T cells</cell_type> caused by ligation of <protein>CD28</protein> in the absence of a specific antigenic stimulus ."}
{"id": "1493", "text": "Enhanced responsiveness to nuclear factor kappa B contributes to the unique phenotype of simian immunodeficiency virus variant SIVsmmPBj14 .", "annotated_text": "Enhanced responsiveness to <protein>nuclear factor kappa B</protein> contributes to the unique phenotype of simian immunodeficiency virus variant SIVsmmPBj14 ."}
{"id": "1494", "text": "Infection with a variant of simian immunodeficiency virus , SIVsmmPBj14 , leads to severe acute disease in macaques .", "annotated_text": "Infection with a variant of simian immunodeficiency virus , SIVsmmPBj14 , leads to severe acute disease in macaques ."}
{"id": "1495", "text": "This study was designed to investigate the functional significance of previously described mutations in the viral long terminal repeat ( LTR ) and to elucidate their contribution to the unique phenotype of SIVsmmPBj14 .", "annotated_text": "This study was designed to investigate the functional significance of previously described mutations in the <dna>viral long terminal repeat</dna> ( <dna>LTR</dna> ) and to elucidate their contribution to the unique phenotype of SIVsmmPBj14 ."}
{"id": "1496", "text": "LTR -directed transcription was measured by using luciferase reporter constructs that were transiently transfected into cultured cells .", "annotated_text": "<dna>LTR</dna> -directed transcription was measured by using <dna>luciferase reporter constructs</dna> that were transiently transfected into <cell_line>cultured cells</cell_line> ."}
{"id": "1497", "text": "In a wide range of cell types , the basal transcriptional activity of the LTR from SIVsmmPBj14 was found to be 2- to 4.5-fold higher than that of an LTR from a non-acutely pathogenic strain .", "annotated_text": "In a wide range of cell types , the basal transcriptional activity of the <dna>LTR</dna> from SIVsmmPBj14 was found to be 2- to 4.5-fold higher than that of an <dna>LTR</dna> from a non-acutely pathogenic strain ."}
{"id": "1498", "text": "These LTRs differ by five point mutations and a 22-bp duplication in SIVsmmPBj14 , which includes a nuclear factor kappa B ( NF kappa B ) site .", "annotated_text": "These <dna>LTRs</dna> differ by five point mutations and a <dna>22-bp duplication</dna> in SIVsmmPBj14 , which includes a <dna>nuclear factor kappa B ( NF kappa B ) site</dna> ."}
{"id": "1499", "text": "Transcriptional differences between these LTRs were further enhanced by two- to threefold upon treatment of cells with phorbol ester or tumor necrosis factor alpha or by cotransfection with plasmids expressing NF kappa B subunits .", "annotated_text": "Transcriptional differences between these <dna>LTRs</dna> were further enhanced by two- to threefold upon treatment of cells with phorbol ester or <protein>tumor necrosis factor alpha</protein> or by cotransfection with <dna>plasmids</dna> expressing <protein>NF kappa B</protein> subunits ."}
{"id": "1500", "text": "Mutagenesis studies , and the use of a reporter construct containing an enhancerless promoter , indicate that these transcriptional effects are due principally to the 22-bp sequence duplication and the NF kappa B site contained within it .", "annotated_text": "Mutagenesis studies , and the use of a reporter construct containing an enhancerless promoter , indicate that these transcriptional effects are due principally to the <dna>22-bp sequence duplication</dna> and the <dna>NF kappa B site</dna> contained within it ."}
{"id": "1501", "text": "Finally , infectious virus stocks that were isogenic except for the LTR were generated .", "annotated_text": "Finally , infectious virus stocks that were isogenic except for the <dna>LTR</dna> were generated ."}
{"id": "1502", "text": "The LTR from SIVsmmPBj14 was found to confer an increase in the kinetics of virus replication in cultured cells .", "annotated_text": "The <dna>LTR</dna> from SIVsmmPBj14 was found to confer an increase in the kinetics of virus replication in <cell_line>cultured cells</cell_line> ."}
{"id": "1503", "text": "Inclusion of this LTR in recombinant SIVs also resulted in a two- to threefold rise in the extent of cellular proliferation that was induced in quiescent simian peripheral blood mononuclear cells .", "annotated_text": "Inclusion of this <dna>LTR</dna> in recombinant SIVs also resulted in a two- to threefold rise in the extent of cellular proliferation that was induced in <cell_line>quiescent simian peripheral blood mononuclear cells</cell_line> ."}
{"id": "1504", "text": "These studies are consistent with the hypothesis that LTR mutations assist SIVsmmPBj14 in responding efficiently to cellular stimulation and allow it to replicate to high titers during the acute phase of viral infection .", "annotated_text": "These studies are consistent with the hypothesis that <dna>LTR</dna> mutations assist SIVsmmPBj14 in responding efficiently to cellular stimulation and allow it to replicate to high titers during the acute phase of viral infection ."}
{"id": "1505", "text": "Constitutive nuclear NF-kappa B in cells of the monocyte lineage .", "annotated_text": "Constitutive <protein>nuclear NF-kappa B</protein> in cells of the monocyte lineage ."}
{"id": "1506", "text": "In monocytes , the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes , of cell-surface receptors and in the expression of human immunodeficiency virus .", "annotated_text": "In <cell_type>monocytes</cell_type> , the <protein>nuclear factor NF-kappa B</protein> has been invoked as an important <protein>transcription factor</protein> in the expression of <dna>cytokine genes</dna> , of <protein>cell-surface receptors</protein> and in the expression of human immunodeficiency virus ."}
{"id": "1507", "text": "In such cells , DNA binding activity of NF-kappa B can be detected without intentional stimulation .", "annotated_text": "In such cells , DNA binding activity of <protein>NF-kappa B</protein> can be detected without intentional stimulation ."}
{"id": "1508", "text": "In our studies , cells of the human monocytic line Mono Mac 6 , cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide ( LPS ) , also exhibit such 'constitutive ' NF-kappa B , as demonstrated by mobility-shift analysis of nuclear extracts .", "annotated_text": "In our studies , cells of the <cell_line>human monocytic line</cell_line> <cell_line>Mono Mac 6</cell_line> , cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide ( LPS ) , also exhibit such 'constitutive ' <protein>NF-kappa B</protein> , as demonstrated by mobility-shift analysis of nuclear extracts ."}
{"id": "1509", "text": "This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted .", "annotated_text": "This <protein>nuclear NF-kappa B</protein> was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted ."}
{"id": "1510", "text": "Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B .", "annotated_text": "Protein-DNA complexes of constitutive <protein>NF-kappa B</protein> are similar in mobility to the <protein>LPS-induced NF-kappa B</protein> and both are recognized by an antibody specific to the <protein>p50 subunit</protein> of <protein>NF-kappa B</protein> ."}
{"id": "1511", "text": "By contrast , treatment of cells with pyrrolidine dithiocarbamate ( PDTC ) will only block LPS-induced NF-kappa B , but not the constitutive binding protein .", "annotated_text": "By contrast , treatment of cells with pyrrolidine dithiocarbamate ( PDTC ) will only block <protein>LPS-induced NF-kappa B</protein> , but not the <protein>constitutive binding protein</protein> ."}
{"id": "1512", "text": "Using LPS-free and serum-free conditions , constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage ( HL60 , U937 , THP-1 , Mono Mac 1 and Mono Mac 6 ) , but not in Molt 4 T cells or K562 stem cells .", "annotated_text": "Using LPS-free and serum-free conditions , constitutive <protein>NF-kappa B</protein> can be detected in different <cell_line>cell lines</cell_line> of the <cell_type>monocytic lineage</cell_type> ( <cell_line>HL60</cell_line> , <cell_line>U937</cell_line> , <cell_line>THP-1</cell_line> , <cell_line>Mono Mac 1</cell_line> and <cell_line>Mono Mac 6</cell_line> ) , but not in <cell_line>Molt 4 T cells</cell_line> or <cell_line>K562 stem cells</cell_line> ."}
{"id": "1513", "text": "When ordered according to stage of maturation , the amount of constitutive NF-kappa B was not increased in more mature cell lines .", "annotated_text": "When ordered according to stage of maturation , the amount of constitutive <protein>NF-kappa B</protein> was not increased in more <cell_line>mature cell lines</cell_line> ."}
{"id": "1514", "text": "Furthermore , when inducing differentiation in Mono Mac 6 cells , with vitamin D3 , no change in constitutive or inducible NF-kappa B can be detected .", "annotated_text": "Furthermore , when inducing differentiation in <cell_line>Mono Mac 6 cells</cell_line> , with vitamin D3 , no change in constitutive or inducible <protein>NF-kappa B</protein> can be detected ."}
{"id": "1515", "text": "Analysis of primary cells revealed substantial constitutive NF-kappa B -binding activity in blood monocytes , pleural macrophages and alveolar macrophages .", "annotated_text": "Analysis of primary cells revealed substantial constitutive <protein>NF-kappa B</protein> -binding activity in <cell_type>blood monocytes</cell_type> , <cell_type>pleural macrophages</cell_type> and <cell_type>alveolar macrophages</cell_type> ."}
{"id": "1516", "text": "The constitutive NF-kappa B appears to be functionally active , since a low level of tumour necrosis factor ( TNF ) transcript is detectable in monocytes , and this level can be increased by blocking transcript degradation using cycloheximide .", "annotated_text": "The constitutive <protein>NF-kappa B</protein> appears to be functionally active , since a low level of <rna>tumour necrosis factor ( TNF ) transcript</rna> is detectable in <cell_type>monocytes</cell_type> , and this level can be increased by blocking transcript degradation using cycloheximide ."}
{"id": "1517", "text": "The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages .", "annotated_text": "The level of constitutive <protein>NF-kappa B</protein> in these cells is variable and is frequently found to be lower in the more <cell_type>mature macrophages</cell_type> ."}
{"id": "1518", "text": "Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF , interleukin 6 , interleukin 10 , granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor , since neutralizing antibodies did not reduce constitutive DNA-binding activity .", "annotated_text": "Constitutive <protein>NF-kappa B</protein> was not maintained by autocrine action of <protein>cytokines</protein> <protein>TNF</protein> , <protein>interleukin 6</protein> , <protein>interleukin</protein> 10 , <protein>granulocyte-macrophage colony-stimulating factor</protein> or <protein>macrophage colony-stimulating factor</protein> , since neutralizing antibodies did not reduce constitutive DNA-binding activity ."}
{"id": "1519", "text": "Furthermore , blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B .", "annotated_text": "Furthermore , blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive <protein>NF-kappa B</protein> ."}
{"id": "1520", "text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 400 WORDS )"}
{"id": "1521", "text": "Steel factor affects SCL expression during normal erythroid differentiation .", "annotated_text": "<protein>Steel factor</protein> affects <protein>SCL</protein> expression during normal erythroid differentiation ."}
{"id": "1522", "text": "Steel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL , also known as Tcl-5 or Tal-1 , is a transcription factor involved in erythropoiesis .", "annotated_text": "<protein>Steel factor</protein> is one of the <protein>growth factors</protein> that controls the proliferation and differentiation of <cell_type>hematopoietic cells</cell_type> and <protein>SCL</protein> , also known as <protein>Tcl-5</protein> or <protein>Tal-1</protein> , is a <protein>transcription factor</protein> involved in erythropoiesis ."}
{"id": "1523", "text": "In this report , we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid ( BFU-E ) and the effects of Steel factor on SCL expression in proliferating erythroid cells .", "annotated_text": "In this report , we studied the role of SCL in the proliferation of <cell_type>human peripheral blood burst-forming unit-erythroid</cell_type> ( <cell_type>BFU-E</cell_type> ) and the effects of <protein>Steel factor</protein> on <protein>SCL</protein> expression in <cell_type>proliferating erythroid cells</cell_type> ."}
{"id": "1524", "text": "BFU-E-derived colonies increase progressively in size , as determined by cell number , from day 7 to day 14 of culture , with the greatest increase in colony size ( 10-fold expansion ) occurring between day 7 and day 10 .", "annotated_text": "<cell_line>BFU-E-derived colonies</cell_line> increase progressively in size , as determined by cell number , from day 7 to day 14 of culture , with the greatest increase in colony size ( 10-fold expansion ) occurring between day 7 and day 10 ."}
{"id": "1525", "text": "SCL protein levels in BFU-E-derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture , suggesting an association of SCL with erythroid proliferation .", "annotated_text": "<protein>SCL protein</protein> levels in <cell_line>BFU-E-derived cells</cell_line> were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture , suggesting an association of <protein>SCL</protein> with erythroid proliferation ."}
{"id": "1526", "text": "In contrast , SCL mRNA levels did not decrease significantly between day 7 and day 14 cells , suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed .", "annotated_text": "In contrast , <rna>SCL mRNA</rna> levels did not decrease significantly between day 7 and day 14 cells , suggesting that posttranscriptional mechanisms are largely responsible for the decrease in <protein>SCL protein</protein> observed ."}
{"id": "1527", "text": "The role of SCL in Steel factor -induced erythroid proliferation was then examined .", "annotated_text": "The role of <protein>SCL</protein> in <protein>Steel factor</protein> -induced erythroid proliferation was then examined ."}
{"id": "1528", "text": "In BFU-E-derived colonies cultured with Steel factor , colony size was significantly increased compared to control .", "annotated_text": "In <cell_line>BFU-E-derived colonies</cell_line> cultured with <protein>Steel factor</protein> , colony size was significantly increased compared to control ."}
{"id": "1529", "text": "In day 7 and day 10 erythroid precursors cultured with Steel factor , SCL protein was increased significantly compared to control .", "annotated_text": "In day 7 and day 10 <cell_type>erythroid precursors</cell_type> cultured with <protein>Steel factor</protein> , <protein>SCL protein</protein> was increased significantly compared to control ."}
{"id": "1530", "text": "The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation .", "annotated_text": "The increase in <protein>SCL</protein> protein levels in early <cell_type>erythroid precursors</cell_type> stimulated with <protein>Steel factor</protein> suggests one mechanism through which <protein>Steel factor</protein> may enhance normal erythroid proliferation ."}
{"id": "1531", "text": "SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation , suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel .", "annotated_text": "<rna>SCL mRNA</rna> levels assessed by Northern blot in day 7 cells did not increase significantly in response to <protein>Steel factor</protein> stimulation , suggesting that posttranscriptional mechanisms may also be important in the increase in <protein>SCL protein</protein> observed in response to <protein>Steel</protein> ."}
{"id": "1532", "text": "C/EBP beta regulation of the tumor necrosis factor alpha gene .", "annotated_text": "<protein>C/EBP beta</protein> regulation of the <dna>tumor necrosis factor alpha gene</dna> ."}
{"id": "1533", "text": "Activated macrophages contribute to chronic inflammation by the secretion of cytokines and proteinases .", "annotated_text": "<cell_type>Activated macrophages</cell_type> contribute to chronic inflammation by the secretion of <protein>cytokines</protein> and <protein>proteinases</protein> ."}
{"id": "1534", "text": "Tumor necrosis factor alpha ( TNF alpha ) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion .", "annotated_text": "<protein>Tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion ."}
{"id": "1535", "text": "The mechanism ( s ) responsible for the cell type-specific regulation of TNF alpha is not known .", "annotated_text": "The mechanism ( s ) responsible for the cell type-specific regulation of <protein>TNF alpha</protein> is not known ."}
{"id": "1536", "text": "We present data to show that the expression of TNF alpha is regulated by the transcription factor C/EBP beta ( NF-IL6 ) .", "annotated_text": "We present data to show that the expression of <protein>TNF alpha</protein> is regulated by the <protein>transcription factor</protein> <protein>C/EBP beta</protein> ( <protein>NF-IL6</protein> ) ."}
{"id": "1537", "text": "C/EBP beta activated the TNF alpha gene promoter in cotransfection assays and bound to it at a site which failed to bind the closely related protein C/EBP alpha .", "annotated_text": "<protein>C/EBP beta</protein> activated the <dna>TNF alpha gene promoter</dna> in cotransfection assays and bound to it at a site which failed to bind the closely related protein <protein>C/EBP alpha</protein> ."}
{"id": "1538", "text": "Finally , a dominant-negative version of C/EBP beta blocked TNF alpha promoter activation in myeloid cells .", "annotated_text": "Finally , a dominant-negative version of <protein>C/EBP beta</protein> blocked <dna>TNF alpha promoter</dna> activation in <cell_type>myeloid cells</cell_type> ."}
{"id": "1539", "text": "Our results implicate C/EBP beta as an important regulator of TNF alpha by myelomonocytic cells .", "annotated_text": "Our results implicate <protein>C/EBP beta</protein> as an important regulator of <protein>TNF alpha</protein> by <cell_type>myelomonocytic cells</cell_type> ."}
{"id": "1540", "text": "Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells .", "annotated_text": "<protein>Calcium/calmodulin-dependent protein kinase II</protein> downregulates both calcineurin and protein kinase C-mediated pathways for <dna>cytokine gene</dna> transcription in <cell_type>human T cells</cell_type> ."}
{"id": "1541", "text": "Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ( [ Ca2+ ] i ) and activation of protein kinase C ( PKC ) .", "annotated_text": "Engagement of the <protein>T cell receptor</protein> for antigen activates <protein>phospholipase C</protein> resulting in an increase in intracellular free calcium concentration ( [ Ca2+ ] i ) and activation of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) ."}
{"id": "1542", "text": "Increased [ Ca2+ ] i activates Ca2+/calmodulin-dependent kinases including the multifunctional Ca2+/calmodulin-dependent protein kinase II ( CaM-K II ) , as well as calcineurin , a type 2B protein phosphatase .", "annotated_text": "Increased [ Ca2+ ] i activates <protein>Ca2+/calmodulin-dependent kinases</protein> including the multifunctional <protein>Ca2+/calmodulin-dependent protein kinase II</protein> ( <protein>CaM-K II</protein> ) , as well as <protein>calcineurin</protein> , a <protein>type 2B protein phosphatase</protein> ."}
{"id": "1543", "text": "Recent studies have identified calcineurin as a key enzyme for interleukin ( IL ) -2 and IL-4 promoter activation .", "annotated_text": "Recent studies have identified <protein>calcineurin</protein> as a key enzyme for interleukin ( IL ) -2 and IL-4 promoter activation ."}
{"id": "1544", "text": "However , the role of CaM-K II remains unknown .", "annotated_text": "However , the role of <protein>CaM-K II</protein> remains unknown ."}
{"id": "1545", "text": "We have used mutants of these kinases and phosphatases ( gamma B*CaM-K and delta CaM-AI , respectively ) to explore their relative role in cytokine gene transcription and their interactions with PKC -dependent signaling systems .", "annotated_text": "We have used mutants of these <protein>kinases</protein> and <protein>phosphatases</protein> ( <protein>gamma B*CaM-K</protein> and <protein>delta CaM-AI</protein> , respectively ) to explore their relative role in <dna>cytokine gene</dna> transcription and their interactions with <protein>PKC</protein> -dependent signaling systems ."}
{"id": "1546", "text": "gamma B*CaM-K and delta CaM-AI , known to exhibit constitutive Ca ( 2+ ) -independent activity , were cotransfected ( alone or in combination ) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene .", "annotated_text": "<protein>gamma B*CaM-K</protein> and <protein>delta CaM-AI</protein> , known to exhibit constitutive Ca ( 2+ ) -independent activity , were cotransfected ( alone or in combination ) in <cell_line>Jurkat T cells</cell_line> with a plasmid containing the intact <dna>IL-2 promoter</dna> driving the expression of the <dna>chloramphenicol acetyltransferase reporter gene</dna> ."}
{"id": "1547", "text": "Cotransfection of gamma B*CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate ( PMA ) .", "annotated_text": "Cotransfection of <protein>gamma B*CaM-K</protein> with the <dna>IL-2 promoter construct</dna> downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate ( PMA ) ."}
{"id": "1548", "text": "The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways .", "annotated_text": "The inhibitory effect of <protein>CaM-K II</protein> on <dna>IL-2 promoter</dna> was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways ."}
{"id": "1549", "text": "Under the same conditions , delta CaM-AI superinduced IL-2 promoter activity ( approximately twofold increase ) .", "annotated_text": "Under the same conditions , <protein>delta CaM-AI</protein> superinduced <dna>IL-2 promoter</dna> activity ( approximately twofold increase ) ."}
{"id": "1550", "text": "When both mutants were used in combination , gamma B*CaM-K inhibited the induction of the IL-2 promoter by delta CaM-AI .", "annotated_text": "When both mutants were used in combination , <protein>gamma B*CaM-K</protein> inhibited the induction of the <dna>IL-2 promoter</dna> by <protein>delta CaM-AI</protein> ."}
{"id": "1551", "text": "Similar results were obtained when a construct containing the IL-4 promoter also was used .", "annotated_text": "Similar results were obtained when a construct containing the <dna>IL-4 promoter</dna> also was used ."}
{"id": "1552", "text": "gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA .", "annotated_text": "<protein>gamma B*CaM-K</protein> also downregulated the activation of <protein>AP-1</protein> in response to transfection with a constitutively active mutant of <protein>PKC</protein> or stimulation with PMA ."}
{"id": "1553", "text": "These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells , and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC- dependent signaling systems .", "annotated_text": "These results suggest that <protein>CaM-K II</protein> may exert negative influences on <dna>cytokine gene</dna> transcription in <cell_type>human T cells</cell_type> , and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC- dependent signaling systems ."}
{"id": "1554", "text": "Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines .", "annotated_text": "Induction of <protein>ICAM-1</protein> and <protein>LFA-3</protein> by <protein>Tax1</protein> of human T-cell leukemia virus type 1 and mechanism of down-regulation of <protein>ICAM-1</protein> or <protein>LFA-1</protein> in <cell_line>adult-T-cell-leukemia cell lines</cell_line> ."}
{"id": "1555", "text": "The present study was undertaken to determine the role of HTLV-I TaxI in the up-regulation of ICAM-I and LFA-3 in human T cells transformed with HTLV-I and the mechanism of down-regulation of ICAM-I and LFA-I in ATL-derived cell lines .", "annotated_text": "The present study was undertaken to determine the role of <protein>HTLV-I TaxI</protein> in the up-regulation of <protein>ICAM-I</protein> and <protein>LFA-3</protein> in <cell_type>human T cells</cell_type> transformed with HTLV-I and the mechanism of down-regulation of <protein>ICAM-I</protein> and <protein>LFA-I</protein> in <cell_line>ATL-derived cell lines</cell_line> ."}
{"id": "1556", "text": "Induction of TaxI in a human T-cell line Jurkat carrying the TaxI gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM-I .", "annotated_text": "Induction of <protein>TaxI</protein> in a <cell_line>human T-cell line Jurkat</cell_line> carrying the <dna>TaxI gene</dna> under the <dna>metallothionein promoter</dna> led to increases in <rna>mRNA</rna> and surface expression of <protein>ICAM-I</protein> ."}
{"id": "1557", "text": "The response of LFA-3 to TaxI induction was , on the other hand , relatively slow and weak , and might be indirect .", "annotated_text": "The response of <protein>LFA-3</protein> to <protein>TaxI</protein> induction was , on the other hand , relatively slow and weak , and might be indirect ."}
{"id": "1558", "text": "Transactivation of the ICAM-I promoter by TaxI was further shown by co-transfection of a CAT reporter construct with the ICAM-I promoter and a plasmid expressing TaxI .", "annotated_text": "Transactivation of the <dna>ICAM-I promoter</dna> by <protein>TaxI</protein> was further shown by co-transfection of a <dna>CAT reporter construct</dna> with the <dna>ICAM-I promoter</dna> and a <dna>plasmid</dna> expressing <protein>TaxI</protein> ."}
{"id": "1559", "text": "The mechanism of down-regulation of ICAM-I or LFA-I in 4 ATL cell lines was next examined .", "annotated_text": "The mechanism of down-regulation of <protein>ICAM-I</protein> or <protein>LFA-I</protein> in <cell_line>4 ATL cell lines</cell_line> was next examined ."}
{"id": "1560", "text": "ICAM-I mRNA was quite low in MT-I , but no genomic changes were found .", "annotated_text": "<rna>ICAM-I mRNA</rna> was quite low in <cell_line>MT-I</cell_line> , but no genomic changes were found ."}
{"id": "1561", "text": "The CAT reporter with the ICAM-I promoter was inactive in MT-I .", "annotated_text": "The <dna>CAT reporter</dna> with the <dna>ICAM-I promoter</dna> was inactive in <cell_line>MT-I</cell_line> ."}
{"id": "1562", "text": "Finally , combined treatment of MT-I with 5-azacytidine and IFN-gamma induced re-expression of ICAM-I .", "annotated_text": "Finally , combined treatment of <cell_line>MT-I</cell_line> with 5-azacytidine and <protein>IFN-gamma</protein> induced re-expression of <protein>ICAM-I</protein> ."}
{"id": "1563", "text": "Collectively , ( a ) transcriptional factor ( s ) necessary for expression of ICAM-I gene may be repressed in MT-I through DNA methylation .", "annotated_text": "Collectively , ( a ) <protein>transcriptional factor</protein> ( s ) necessary for expression of <dna>ICAM-I gene</dna> may be repressed in <cell_line>MT-I</cell_line> through DNA methylation ."}
{"id": "1564", "text": "Three other ATL cell lines ( TL-OmI , H582 , HuT102 ) were found to have little mRNA for the LFA-I beta chain ( CD18 ) .", "annotated_text": "Three other <cell_line>ATL cell lines</cell_line> ( <cell_line>TL-OmI</cell_line> , <cell_line>H582</cell_line> , <cell_line>HuT102</cell_line> ) were found to have little <rna>mRNA</rna> for the <protein>LFA-I beta chain</protein> ( <protein>CD18</protein> ) ."}
{"id": "1565", "text": "H582 and HuT102 were also negative for the LFA-I alpha chain ( CDIIa ) mRNA .", "annotated_text": "<cell_line>H582</cell_line> and <cell_line>HuT102</cell_line> were also negative for the <rna>LFA-I alpha chain ( CDIIa ) mRNA</rna> ."}
{"id": "1566", "text": "No genomic changes were found , and a CAT reporter gene with the CD18 promoter was inactive in the 3 of them , again suggesting lack of ( a ) transcriptional factor ( s ) necessary for CD18 expression .", "annotated_text": "No genomic changes were found , and a <dna>CAT reporter gene</dna> with the <dna>CD18 promoter</dna> was inactive in the 3 of them , again suggesting lack of ( a ) <protein>transcriptional factor</protein> ( s ) necessary for <protein>CD18</protein> expression ."}
{"id": "1567", "text": "Infection with Theileria annulata induces expression of matrix metalloproteinase 9 and transcription factor AP-1 in bovine leucocytes .", "annotated_text": "Infection with Theileria annulata induces expression of <protein>matrix metalloproteinase 9</protein> and <protein>transcription factor</protein> <protein>AP-1</protein> in <cell_type>bovine leucocytes</cell_type> ."}
{"id": "1568", "text": "Theileria annulata infects bovine leucocytes and results in their reversible transformation such that they become immortalised and metastatic .", "annotated_text": "Theileria annulata infects <cell_type>bovine leucocytes</cell_type> and results in their reversible transformation such that they become immortalised and metastatic ."}
{"id": "1569", "text": "The present study describes parasite-induced changes in host cell gene expression which have a direct bearing on this transformation process .", "annotated_text": "The present study describes parasite-induced changes in <dna>host cell gene</dna> expression which have a direct bearing on this transformation process ."}
{"id": "1570", "text": "T. annulata-infected leucocytes produce a number of novel metalloproteinase activities .", "annotated_text": "<cell_type>T. annulata-infected leucocytes</cell_type> produce a number of novel <protein>metalloproteinase</protein> activities ."}
{"id": "1571", "text": "One of these , previously called B1 , is a 97-kDa protein which is secreted in large amounts and has been purified from protein-free , conditioned medium .", "annotated_text": "One of these , previously called <protein>B1</protein> , is a <protein>97-kDa protein</protein> which is secreted in large amounts and has been purified from protein-free , conditioned medium ."}
{"id": "1572", "text": "An antiserum to this enzyme was used to isolate a cDNA clone .", "annotated_text": "An antiserum to this enzyme was used to isolate a <dna>cDNA clone</dna> ."}
{"id": "1573", "text": "The predicted protein sequence of B1 is 81 % identical to human matrix metalloproteinase 9 ( MMP9 ) , demonstrating that it is the bovine homologue of this enzyme .", "annotated_text": "The predicted protein sequence of <protein>B1</protein> is 81 % identical to human <protein>matrix metalloproteinase 9</protein> ( <protein>MMP9</protein> ) , demonstrating that it is the bovine homologue of this enzyme ."}
{"id": "1574", "text": "RNAase protection assays demonstrated that the MMP9 activity , unique to infected cells , is due to increased MMP9 mRNA levels .", "annotated_text": "<protein>RNAase</protein> protection assays demonstrated that the <protein>MMP9</protein> activity , unique to <cell_type>infected cells</cell_type> , is due to increased <protein>MMP9</protein> mRNA levels ."}
{"id": "1575", "text": "We also assayed the levels of transcription factor AP-1 and demonstrated that it was constitutively present in increased amounts in Theileria-infected cells .", "annotated_text": "We also assayed the levels of <protein>transcription factor</protein> <protein>AP-1</protein> and demonstrated that it was constitutively present in increased amounts in <cell_type>Theileria-infected cells</cell_type> ."}
{"id": "1576", "text": "In addition we assayed the level of mRNA encoding c-Fos , a common component of AP-1 and observed that it was indeed up-regulated in infected cells .", "annotated_text": "In addition we assayed the level of <rna>mRNA</rna> encoding <protein>c-Fos</protein> , a common component of <protein>AP-1</protein> and observed that it was indeed up-regulated in <cell_type>infected cells</cell_type> ."}
{"id": "1577", "text": "Since AP-1 is implicated in the control of the cell cycle , and MMP9 can confer metastatic properties , these results are of considerable significance with respect to the transformed phenotype induced by Theileria infection .", "annotated_text": "Since <protein>AP-1</protein> is implicated in the control of the cell cycle , and <protein>MMP9</protein> can confer metastatic properties , these results are of considerable significance with respect to the transformed phenotype induced by Theileria infection ."}
{"id": "1578", "text": "B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2 .", "annotated_text": "<cell_type>B-cell</cell_type> proliferation and induction of early <protein>G1-regulating proteins</protein> by Epstein-Barr virus mutants conditional for <protein>EBNA2</protein> ."}
{"id": "1579", "text": "Infection of primary B-lymphocytes by Epstein-Barr virus ( EBV ) leads to growth transformation of these B-cells in vitro .", "annotated_text": "Infection of <cell_type>primary B-lymphocytes</cell_type> by Epstein-Barr virus ( EBV ) leads to growth transformation of these <cell_type>B-cells</cell_type> in vitro ."}
{"id": "1580", "text": "EBV nuclear antigen 2 ( EBNA2 ) , one of the first genes expressed after EBV infection of B-cells , is a transcriptional activator of viral and cellular genes and is essential for the transforming potential of the virus .", "annotated_text": "EBV nuclear antigen 2 ( <protein>EBNA2</protein> ) , one of the first genes expressed after EBV infection of <cell_type>B-cells</cell_type> , is a transcriptional activator of <dna>viral and cellular genes</dna> and is essential for the transforming potential of the virus ."}
{"id": "1581", "text": "We generated conditional EBV mutants by expressing EBNA2 as chimeric fusion protein with the hormone binding domain of the estrogen receptor on the genetic background of the virus .", "annotated_text": "We generated conditional EBV mutants by expressing <protein>EBNA2</protein> as <protein>chimeric fusion protein</protein> with the hormone binding domain of the <protein>estrogen receptor</protein> on the genetic background of the virus ."}
{"id": "1582", "text": "Growth transformation of primary normal B-cells by mutant virus resulted in estrogen-dependent lymphoblastoid cell lines expressing the chimeric EBNA2 protein .", "annotated_text": "Growth transformation of <cell_type>primary normal B-cells</cell_type> by mutant virus resulted in <cell_line>estrogen-dependent lymphoblastoid cell lines</cell_line> expressing the chimeric <protein>EBNA2 protein</protein> ."}
{"id": "1583", "text": "In the absence of estrogen about half of the cells enter a quiescent non-proliferative state whereas the others die by apoptosis .", "annotated_text": "In the absence of estrogen about half of the cells enter a quiescent non-proliferative state whereas the others die by apoptosis ."}
{"id": "1584", "text": "EBNA2 is thus required not only for initiation but also for maintenance of transformation .", "annotated_text": "<protein>EBNA2</protein> is thus required not only for initiation but also for maintenance of transformation ."}
{"id": "1585", "text": "Growth arrest occurred at G1 and G2 stages of the cell cycle , indicating that functional EBNA2 is required at different restriction points of the cell cycle .", "annotated_text": "Growth arrest occurred at G1 and G2 stages of the cell cycle , indicating that functional <protein>EBNA2</protein> is required at different restriction points of the cell cycle ."}
{"id": "1586", "text": "Growth arrest is reversible for G1/G0 cells as indicated by the sequential accumulation and modification of cell cycle regulating proteins .", "annotated_text": "Growth arrest is reversible for <cell_type>G1/G0 cells</cell_type> as indicated by the sequential accumulation and modification of <protein>cell cycle regulating proteins</protein> ."}
{"id": "1587", "text": "EBV induces the same cell cycle regulating proteins as polyclonal stimuli in primary B-cells .", "annotated_text": "EBV induces the same cell cycle regulating proteins as polyclonal stimuli in primary <cell_type>B-cells</cell_type> ."}
{"id": "1588", "text": "These data suggest that EBV is using a common pathway for B-cell activation bypassing the requirement for antigen , T-cell signals and growth factors .", "annotated_text": "These data suggest that EBV is using a common pathway for B-cell activation bypassing the requirement for antigen , T-cell signals and <protein>growth factors</protein> ."}
{"id": "1589", "text": "IL-1 receptor and TCR signals synergize to activate NF-kappa B -mediated gene transcription .", "annotated_text": "<protein>IL-1 receptor</protein> and <protein>TCR</protein> signals synergize to activate <protein>NF-kappa B</protein> -mediated gene transcription ."}
{"id": "1590", "text": "Previous studies have demonstrated that IL-1 receptor ( IL-1R ) - and TCR -initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes .", "annotated_text": "Previous studies have demonstrated that <protein>IL-1 receptor</protein> ( <protein>IL-1R</protein> ) - and <protein>TCR</protein> -initiated signals can interact synergistically to increase the rate of transcription of several <dna>lymphokine and lymphokine receptor genes</dna> during the competence phase of the activation program in <cell_type>T helper lymphocytes</cell_type> ."}
{"id": "1591", "text": "In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B .", "annotated_text": "In this report we describe how signals initiated through the <protein>type I IL-1R</protein> interact with signals from the antigen receptor to synergistically augment the transactivating properties of <protein>NF-kappa B</protein> ."}
{"id": "1592", "text": "The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester , 12-O-tetradecanoylphorbol-13-acetate , but not with calcium ionophores ; and are staurosporine sensitive but cyclosporine resistant .", "annotated_text": "The synergistic <protein>antigen receptor</protein> initiated signals are mediated through <protein>protein kinase C</protein> because they can be mimicked by the phorbol ester , 12-O-tetradecanoylphorbol-13-acetate , but not with calcium ionophores ; and are staurosporine sensitive but cyclosporine resistant ."}
{"id": "1593", "text": "Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals .", "annotated_text": "Gel shift analyses demonstrate that <protein>NF-kappa B</protein> nuclear translocation is stimulated primarily by <protein>IL-1</protein> rather than by <protein>antigen receptor</protein> signals ."}
{"id": "1594", "text": "Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha ( MAD3 ) - NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation .", "annotated_text": "Western blot and phosphorylation analyses demonstrate that the synergistic effect on <protein>NF-kappa B</protein> functional activity is independent of <protein>I kappa B alpha</protein> ( <protein>MAD3</protein> ) - <protein>NF-kappa B</protein> dissociation in the cytosol and is not associated with <protein>I kappa B</protein> nuclear translocation ."}
{"id": "1595", "text": "The IL-1 -induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis .", "annotated_text": "The <protein>IL-1</protein> -induced <protein>NF-kappa B</protein> DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis ."}
{"id": "1596", "text": "These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein ( s ) responsible for terminating NF-kappa B -DNA interaction in the nucleus .", "annotated_text": "These results suggest that <protein>IL-1</protein> induces both <protein>NF-kappa B</protein> nuclear translocation and the synthesis of a protein ( s ) responsible for terminating <protein>NF-kappa B</protein> -DNA interaction in the nucleus ."}
{"id": "1597", "text": "Antigen receptor signals prolong NF-kappa B -DNA interaction , probably by functionally antagonizing the IL-1 -induced synthesis of a protein ( s ) responsible for the transient NF-kappa B -DNA interaction and consequently synergistically enhance IL-1 -induced NF-kappa B -dependent gene transcription .", "annotated_text": "Antigen receptor signals prolong <protein>NF-kappa B</protein> -DNA interaction , probably by functionally antagonizing the <protein>IL-1</protein> -induced synthesis of a protein ( s ) responsible for the transient <protein>NF-kappa B</protein> -DNA interaction and consequently synergistically enhance <protein>IL-1</protein> -induced <protein>NF-kappa B</protein> -dependent gene transcription ."}
{"id": "1598", "text": "Identification of the promoter region of chicken anemia virus ( CAV ) containing a novel enhancer-like element .", "annotated_text": "Identification of the <dna>promoter region</dna> of chicken anemia virus ( CAV ) containing a novel <dna>enhancer-like element</dna> ."}
{"id": "1599", "text": "The single promoter region in the cloned genome [ Noteborn et al. , J. Virol. 65 ( 1991 ) 3131-3139 ] of chicken anemia virus ( CAV ) in chicken T-cells was analysed via CAT assays .", "annotated_text": "The single <dna>promoter region</dna> in the cloned genome [ Noteborn et al. , J. Virol. 65 ( 1991 ) 3131-3139 ] of chicken anemia virus ( CAV ) in <cell_type>chicken T-cells</cell_type> was analysed via <protein>CAT</protein> assays ."}
{"id": "1600", "text": "A unique region containing four or five near-perfect direct repeats ( DR ) of 21 bp with one 12-bp insert was proven to be the main transcription-activation element , with enhancer-like characteristics .", "annotated_text": "A unique region containing four or five near-perfect direct repeats ( DR ) of 21 bp with one <dna>12-bp insert</dna> was proven to be the main <dna>transcription-activation element</dna> , with enhancer-like characteristics ."}
{"id": "1601", "text": "PCR studies revealed that CAV isolates from across the world all contained this promoter sequence .", "annotated_text": "PCR studies revealed that CAV isolates from across the world all contained this <dna>promoter sequence</dna> ."}
{"id": "1602", "text": "Electrophoretic mobility-shift assays ( EMSA ) showed that individual DR units , as well as the 12-bp insert , can bind to nuclear factors of chicken T-cells .", "annotated_text": "Electrophoretic mobility-shift assays ( EMSA ) showed that <dna>individual DR units</dna> , as well as the <dna>12-bp insert</dna> , can bind to <protein>nuclear factors</protein> of <cell_type>chicken T-cells</cell_type> ."}
{"id": "1603", "text": "Competition assays revealed that the DR units bound to factors other than the 12-bp insert .", "annotated_text": "Competition assays revealed that the <dna>DR units</dna> bound to factors other than the <dna>12-bp insert</dna> ."}
{"id": "1604", "text": "A synthetic oligodeoxyribonucleotide containing an SP1-box ( 5'-GGGCGG ) could compete with factors binding to the 12-bp insert .", "annotated_text": "A synthetic oligodeoxyribonucleotide containing an <dna>SP1-box</dna> ( 5'-GGGCGG ) could compete with factors binding to the <dna>12-bp insert</dna> ."}
{"id": "1605", "text": "Purified human SP1 was shown to have very strong affinity for the 12-bp insert .", "annotated_text": "Purified <protein>human SP1</protein> was shown to have very strong affinity for the <dna>12-bp insert</dna> ."}
{"id": "1606", "text": "Functional Myc-Max heterodimer is required for activation-induced apoptosis in T cell hybridomas .", "annotated_text": "Functional <protein>Myc-Max heterodimer</protein> is required for activation-induced apoptosis in <cell_line>T cell hybridomas</cell_line> ."}
{"id": "1607", "text": "T cell hybridomas respond to activation signals by undergoing apoptotic cell death , and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo .", "annotated_text": "<cell_line>T cell hybridomas</cell_line> respond to activation signals by undergoing apoptotic cell death , and this is likely to represent comparable events related to tolerance induction in <cell_type>immature and mature T cells</cell_type> in vivo ."}
{"id": "1608", "text": "Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis .", "annotated_text": "Previous studies using antisense oligonucleotides implicated the <protein>c-Myc protein</protein> in the phenomenon of activation-induced apoptosis ."}
{"id": "1609", "text": "This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner , Max , which we show here inhibits activation-induced apoptosis .", "annotated_text": "This role for <protein>c-Myc</protein> in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner , <protein>Max</protein> , which we show here inhibits activation-induced apoptosis ."}
{"id": "1610", "text": "Further , coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis .", "annotated_text": "Further , coexpression of a <protein>reciprocally mutant Myc protein</protein> capable of forming functional <protein>heterodimers</protein> with the mutant <protein>Max</protein> can compensate for the dominant negative activity and restore activation-induced apoptosis ."}
{"id": "1611", "text": "These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max , and therefore , by regulating gene transcription .", "annotated_text": "These results imply that <protein>Myc</protein> promotes activation-induced apoptosis by obligatory heterodimerization with <protein>Max</protein> , and therefore , by regulating gene transcription ."}
{"id": "1612", "text": "Epstein-Barr virus SM protein .", "annotated_text": "<protein>Epstein-Barr virus SM protein</protein> ."}
{"id": "1613", "text": "The protein products of the Epstein-Barr virus ( EBV ) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells .", "annotated_text": "The protein products of the Epstein-Barr virus ( EBV ) BMLF1 open reading frame have been characterized in the early productive cycle in <cell_line>B95-8</cell_line> and <cell_line>Akata cells</cell_line> ."}
{"id": "1614", "text": "The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein .", "annotated_text": "The <protein>SM protein</protein> derived from the spliced RNA joining <protein>BSLF2</protein> to <protein>BMLF1</protein> is much the most abundant protein ."}
{"id": "1615", "text": "SM is a phosphoprotein in EBV -infected cells and can be phosphorylated in vitro with casein kinase II ( CKII ) .", "annotated_text": "<protein>SM</protein> is a <protein>phosphoprotein</protein> in EBV <cell_type>-infected cells</cell_type> and can be phosphorylated in vitro with <protein>casein kinase II</protein> ( <protein>CKII</protein> ) ."}
{"id": "1616", "text": "Computer analysis of the SM protein sequence showed a C terminal section of SM to be related to genome positional homologues of four other herpesviruses and revealed consensus CKII sites near the N termini of the EBV SM protein , the herpes simplex virus ( HSV ) ICP27 protein and the herpesvirus saimiri ( HVS ) open reading frame 57 protein .", "annotated_text": "Computer analysis of the <protein>SM protein</protein> sequence showed a <protein>C terminal section</protein> of <protein>SM</protein> to be related to <protein>genome positional homologues</protein> of four other herpesviruses and revealed <protein>consensus CKII sites</protein> near the <protein>N termini</protein> of the <protein>EBV SM protein</protein> , the <protein>herpes simplex virus ( HSV ) ICP27 protein</protein> and the <protein>herpesvirus saimiri ( HVS ) open reading frame 57 protein</protein> ."}
{"id": "1617", "text": "Site-directed mutagenesis of the consensus CKII site in EBV SM greatly reduced the in vitro phosphorylation of SM by CKII .", "annotated_text": "Site-directed mutagenesis of the <dna>consensus CKII site</dna> in EBV SM greatly reduced the in vitro phosphorylation of <protein>SM</protein> by <protein>CKII</protein> ."}
{"id": "1618", "text": "The mechanism of transactivation by BMLF1 proteins has been controversial but SM was shown to transactivate gene expression from a CAT reporter construct by increasing the amount of cytoplasmic CAT mRNA .", "annotated_text": "The mechanism of transactivation by <protein>BMLF1 proteins</protein> has been controversial but <protein>SM</protein> was shown to transactivate gene expression from a <dna>CAT reporter construct</dna> by increasing the amount of <rna>cytoplasmic CAT mRNA</rna> ."}
{"id": "1619", "text": "Mutagenesis of the CKII site in SM made no difference to the transactivation in this transient transfection assay .", "annotated_text": "Mutagenesis of the <protein>CKII</protein> site in <protein>SM</protein> made no difference to the transactivation in this transient transfection assay ."}
{"id": "1620", "text": "Inducible binding to the c-fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein .", "annotated_text": "Inducible binding to the c-fos serum response element during T cell activation is regulated by a <protein>phosphotyrosine-containing protein</protein> ."}
{"id": "1621", "text": "The proto-oncogene c-fos is an immediate-early gene , and one of the first genes transcribed after stimulation of most cells with a variety of ligands .", "annotated_text": "The <dna>proto-oncogene c-fos</dna> is an <dna>immediate-early gene</dna> , and one of the first genes transcribed after stimulation of most cells with a variety of ligands ."}
{"id": "1622", "text": "Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype .", "annotated_text": "Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype ."}
{"id": "1623", "text": "The serum response element ( SRE ) in the c-fos regulatory region participates in induction of transcription by various growth factors and by phorbol esters and subsequent squelching of transcription .", "annotated_text": "The <dna>serum response element</dna> ( <dna>SRE</dna> ) in the <dna>c-fos regulatory region</dna> participates in induction of transcription by various <protein>growth factors</protein> and by phorbol esters and subsequent squelching of transcription ."}
{"id": "1624", "text": "We show that an inducible protein complex ( Band A ) binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T , and becomes nondetectable by 60 min .", "annotated_text": "We show that an inducible <protein>protein complex</protein> ( <protein>Band A</protein> ) binds to <dna>SRE DNA</dna> within 10 min after mitogenic stimulation of <cell_line>human PBL-T</cell_line> , and becomes nondetectable by 60 min ."}
{"id": "1625", "text": "Band A contains the serum response factor plus additional factor ( s ) .", "annotated_text": "<protein>Band A</protein> contains the <protein>serum response factor</protein> plus additional factor ( s ) ."}
{"id": "1626", "text": "A protein that is phosphorylated on a tyrosine residue in resting PBL-T suppresses binding of a component of Band A to the SRE motif .", "annotated_text": "A protein that is phosphorylated on a tyrosine residue in <cell_line>resting PBL-T</cell_line> suppresses binding of a component of <protein>Band A</protein> to the <dna>SRE motif</dna> ."}
{"id": "1627", "text": "Upon stimulation of the cells , this protein no longer prevents binding of DNA by Band A , and suppression of binding is restored within 30 min .", "annotated_text": "Upon stimulation of the cells , this protein no longer prevents binding of DNA by <protein>Band A</protein> , and suppression of binding is restored within 30 min ."}
{"id": "1628", "text": "The phosphorylated tyrosine residue itself is important for the protein-protein interaction .", "annotated_text": "The phosphorylated tyrosine residue itself is important for the protein-protein interaction ."}
{"id": "1629", "text": "In vivo modification of major histocompatibility complex class II DRA promoter occupancy mediated by the AIR-1 trans-activator .", "annotated_text": "In vivo modification of <dna>major histocompatibility complex class II DRA promoter</dna> occupancy mediated by the <protein>AIR-1 trans-activator</protein> ."}
{"id": "1630", "text": "RJ 2.2.5 is a human B cell mutant derived from the Burkitt lymphoma Raji cell which is defective in the AIR-1 locus function .", "annotated_text": "<cell_line>RJ 2.2.5</cell_line> is a <cell_line>human B cell mutant</cell_line> derived from the <cell_line>Burkitt lymphoma Raji cell</cell_line> which is defective in the AIR-1 locus function ."}
{"id": "1631", "text": "This locus encodes a transcriptional trans-activator required for the constitutive expression of major histocompatibility complex ( MHC ) class II genes .", "annotated_text": "This locus encodes a transcriptional trans-activator required for the constitutive expression of <dna>major histocompatibility complex ( MHC ) class II genes</dna> ."}
{"id": "1632", "text": "Here we show , by in vivo DNase I footprinting , that the AIR-1 locus defect correlates with changes in the DRA promoter occupancy .", "annotated_text": "Here we show , by in vivo <protein>DNase I</protein> footprinting , that the <dna>AIR-1 locus defect</dna> correlates with changes in the <dna>DRA promoter</dna> occupancy ."}
{"id": "1633", "text": "Interestingly , reexpression of human MHC class II genes in RJ 2.2.5 x mouse spleen cell hybrids is associated with partial reversion of DRA promoter occupancy to the Raji pattern .", "annotated_text": "Interestingly , reexpression of <dna>human MHC class II genes</dna> in <cell_line>RJ 2.2.5 x mouse spleen cell hybrids</cell_line> is associated with partial reversion of <dna>DRA promoter</dna> occupancy to the Raji pattern ."}
{"id": "1634", "text": "DRA promoter occupancy in other class II-negative B cell lines , derived from patients with bare lymphocyte syndrome , is drastically different from the one observed in RJ 2.2.5 and Raji cells .", "annotated_text": "<dna>DRA promoter</dna> occupancy in other <cell_line>class II-negative B cell lines</cell_line> , derived from patients with bare lymphocyte syndrome , is drastically different from the one observed in <cell_line>RJ 2.2.5</cell_line> and <cell_line>Raji cells</cell_line> ."}
{"id": "1635", "text": "Moreover , the use of the DNase I as an in vivo footprinting agent reveals that the patients ' cell lines do not display a completely `` bare promoter `` as previously reported using dimethyl sulfate as the footprinting agent .", "annotated_text": "Moreover , the use of the <protein>DNase I</protein> as an in vivo footprinting agent reveals that the <cell_line>patients ' cell lines</cell_line> do not display a completely `` <dna>bare promoter</dna> `` as previously reported using dimethyl sulfate as the footprinting agent ."}
{"id": "1636", "text": "Thus , the use of DNase I allowed us , for the first time , to correlate the AIR-1 locus defect with class II promoter occupancy alterations and distinguish these alterations from the ones observed in phenotypically similar but genetically distinct MHC class II-negative cells .", "annotated_text": "Thus , the use of <protein>DNase I</protein> allowed us , for the first time , to correlate the <dna>AIR-1 locus defect</dna> with <dna>class II promoter</dna> occupancy alterations and distinguish these alterations from the ones observed in phenotypically similar but genetically distinct <cell_line>MHC class II-negative cells</cell_line> ."}
{"id": "1637", "text": "Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression : potential role of physical interactions between Elf-1 , HMG-I ( Y ) , and NF-kappa B family proteins .", "annotated_text": "Regulation of cell-type-specific <protein>interleukin-2 receptor alpha-chain</protein> gene expression : potential role of physical interactions between <protein>Elf-1</protein> , <protein>HMG-I ( Y )</protein> , and <protein>NF-kappa B family proteins</protein> ."}
{"id": "1638", "text": "The interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene is rapidly and potently induced in T cells in response to mitogenic stimuli .", "annotated_text": "The <dna>interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene</dna> is rapidly and potently induced in <cell_type>T cells</cell_type> in response to mitogenic stimuli ."}
{"id": "1639", "text": "Previously , an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified .", "annotated_text": "Previously , an <dna>inducible enhancer</dna> between <dna>nucleotides -299 and -228</dna> that contains <dna>NF-kappa B and CArG motifs</dna> was identified ."}
{"id": "1640", "text": "We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I ( Y ) .", "annotated_text": "We now report the characterization of a second <dna>essential positive regulatory element</dna> located between <dna>nucleotides -137 and -64</dna> that binds <protein>Elf-1</protein> and <protein>HMG-I ( Y )</protein> ."}
{"id": "1641", "text": "This element had maximal activity in lymphoid cells , paralleling the cell type specificity of Elf-1 expression .", "annotated_text": "This element had maximal activity in <cell_type>lymphoid cells</cell_type> , paralleling the cell type specificity of <protein>Elf-1</protein> expression ."}
{"id": "1642", "text": "Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I ( Y ) binding site was mutated .", "annotated_text": "Transcription from the <dna>IL-2R alpha promoter</dna> was inhibited when either the <dna>Elf-1 or the HMG-I ( Y ) binding site</dna> was mutated ."}
{"id": "1643", "text": "Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells .", "annotated_text": "Coexpression of both proteins activated transcription of the <dna>-137 to -64 element</dna> in <cell_line>COS-7 cells</cell_line> ."}
{"id": "1644", "text": "Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro , suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements .", "annotated_text": "<protein>Elf-1</protein> physically associated with <protein>HMG-I</protein> and with <protein>NF-kappa B</protein> <protein>p50</protein> and <protein>c-Rel</protein> in vitro , suggesting that protein-protein interactions might functionally coordinate the actions of the <dna>upstream and downstream positive regulatory elements</dna> ."}
{"id": "1645", "text": "This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins .", "annotated_text": "This is the first report of a physical interaction between an Ets family member and <protein>NF-kappa B family proteins</protein> ."}
{"id": "1646", "text": "These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins .", "annotated_text": "These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible <protein>IL-2R alpha</protein> gene expression and also have implications for other genes regulated by <protein>Elf-1</protein> and <protein>NF-kappa B family proteins</protein> ."}
{"id": "1647", "text": "Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937 .", "annotated_text": "Isolation of <dna>cDNA clones</dna> for 42 different <protein>Kruppel-related zinc finger proteins</protein> expressed in the <cell_line>human monoblast cell line U-937</cell_line> ."}
{"id": "1648", "text": "To study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development , a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937 .", "annotated_text": "To study the complexity and structural characteristics of <protein>zinc finger proteins</protein> expressed during human hematopoiesis and to isolate novel regulators of blood cell development , a degenerate oligonucleotide probe specific for a <protein>consensus zinc finger peptide domain</protein> was used to isolate 63 <dna>cDNA clones</dna> for <dna>Kruppel-related zinc finger genes</dna> from the <cell_line>human monoblast cell line U-937</cell_line> ."}
{"id": "1649", "text": "By extensive nucleotide sequence and Northern blot analysis , these cDNA clones were found to originate from approximately 42 different genes ( HZF 1-42 ) of which only 8 have previously been described .", "annotated_text": "By extensive nucleotide sequence and Northern blot analysis , these <dna>cDNA clones</dna> were found to originate from approximately 42 different genes ( <dna>HZF 1-42</dna> ) of which only 8 have previously been described ."}
{"id": "1650", "text": "Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells .", "annotated_text": "Northern blot analysis showed that a majority of these genes were expressed at comparable levels in <cell_line>U-937</cell_line> and <cell_line>HeLa cells</cell_line> ."}
{"id": "1651", "text": "The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues .", "annotated_text": "The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the <dna>Kruppel-related zinc finger genes</dna> are likely to be expressed in most human tissues ."}
{"id": "1652", "text": "In contrast , some of the genes displayed a restricted expression pattern , indicating that they represent potential regulators of monocyte differentiation or proliferation .", "annotated_text": "In contrast , some of the genes displayed a restricted expression pattern , indicating that they represent potential regulators of monocyte differentiation or proliferation ."}
{"id": "1653", "text": "Detailed structural analysis of the first 12 cDNAs ( HZF 1-10 ) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins .", "annotated_text": "Detailed structural analysis of the first 12 <dna>cDNAs</dna> ( <dna>HZF 1-10</dna> ) and a partial characterization of <dna>HZF 11-42</dna> revealed that a common feature of <protein>human Kruppel-related zinc finger proteins</protein> is the presence of tandem arrays of <protein>zinc fingers</protein> ranging in number from 3 to over 20 that are preferentially located in the <protein>carboxy-terminal regions</protein> of the proteins ."}
{"id": "1654", "text": "In addition , several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified .", "annotated_text": "In addition , several novel <dna>KRAB-containing zinc finger genes</dna> and a novel <dna>conserved sequence element</dna> were identified ."}
{"id": "1655", "text": "CAG repeat length variation in sperm from a patient with Kennedy 's disease .", "annotated_text": "CAG repeat length variation in <cell_type>sperm</cell_type> from a patient with Kennedy 's disease ."}
{"id": "1656", "text": "Using a modified sperm typing protocol , the mutation frequency of the CAG repeat region at the androgen receptor locus has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy ( SBMA ) .", "annotated_text": "Using a modified <cell_type>sperm</cell_type> typing protocol , the mutation frequency of the <dna>CAG repeat region</dna> at the <dna>androgen receptor locus</dna> has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy ( SBMA ) ."}
{"id": "1657", "text": "Among 258 X chromosome-containing sperm , 19 % had a repeat number equal to the donor 's somatic DNA ( 47 repeats ) , 66 % were expansions and 15 % were contractions .", "annotated_text": "Among 258 <cell_type>X chromosome-containing sperm</cell_type> , 19 % had a repeat number equal to the <dna>donor 's somatic DNA</dna> ( 47 repeats ) , 66 % were expansions and 15 % were contractions ."}
{"id": "1658", "text": "The average expansion was 2.7 repeats .", "annotated_text": "The average expansion was 2.7 repeats ."}
{"id": "1659", "text": "More than half of the expansions involved one or two repeats ; the largest was 11 repeats .", "annotated_text": "More than half of the expansions involved one or two repeats ; the largest was 11 repeats ."}
{"id": "1660", "text": "68 % of the contractions were also one or two repeats but six ( 16 % ) were very large ( 12-25 repeats ) .", "annotated_text": "68 % of the contractions were also one or two repeats but six ( 16 % ) were very large ( 12-25 repeats ) ."}
{"id": "1661", "text": "One contraction generated an allele in an intermediate size range ( 33-39 repeats ) .", "annotated_text": "One contraction generated an allele in an intermediate size range ( 33-39 repeats ) ."}
{"id": "1662", "text": "Such alleles have not been observed among more than 900 normal and SBMA X-chromosomes that have been examined .", "annotated_text": "Such alleles have not been observed among more than 900 normal and <dna>SBMA X-chromosomes</dna> that have been examined ."}
{"id": "1663", "text": "Comparison of the SBMA sperm typing results with mutation frequency data on normal alleles supports the hypothesis that trinucleotide repeat expansions may have a different molecular origin than contractions .", "annotated_text": "Comparison of the SBMA <cell_type>sperm</cell_type> typing results with mutation frequency data on normal alleles supports the hypothesis that <dna>trinucleotide repeat</dna> expansions may have a different molecular origin than contractions ."}
{"id": "1664", "text": "Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity : evidence for a NAD ( P ) H : quinone reductase -dependent mechanism .", "annotated_text": "Aspirin-like drugs can protect <cell_type>human T lymphocytes</cell_type> against benzoquinone cytotoxicity : evidence for a <protein>NAD ( P ) H : quinone reductase</protein> -dependent mechanism ."}
{"id": "1665", "text": "Benzene toxicity towards lymphocytes is thought to be mediated by metabolites of benzene including benzoquinone ( BQ ) .", "annotated_text": "Benzene toxicity towards <cell_type>lymphocytes</cell_type> is thought to be mediated by metabolites of benzene including benzoquinone ( BQ ) ."}
{"id": "1666", "text": "NAD ( P ) H : quinone reductase ( QR ) is known to protect against BQ toxicity .", "annotated_text": "<protein>NAD ( P ) H : quinone reductase</protein> ( <protein>QR</protein> ) is known to protect against BQ toxicity ."}
{"id": "1667", "text": "The expression of the QR gene is regulated by the transcription factor AP-1 .", "annotated_text": "The expression of the <dna>QR gene</dna> is regulated by the <protein>transcription factor</protein> <protein>AP-1</protein> ."}
{"id": "1668", "text": "We had previously found that aspirin-like drugs ( ALD ) induce AP-1 in human T lymphocytes .", "annotated_text": "We had previously found that aspirin-like drugs ( ALD ) induce <protein>AP-1</protein> in <cell_type>human T lymphocytes</cell_type> ."}
{"id": "1669", "text": "It was therefore hypothesized that ALD would protect lymphocytes against BQ toxicity by inducing QR .", "annotated_text": "It was therefore hypothesized that ALD would protect <cell_type>lymphocytes</cell_type> against BQ toxicity by inducing <protein>QR</protein> ."}
{"id": "1670", "text": "Molt-4 cells ( M4 ) , a human T lymphocyte cell line , were incubated with different concentrations of two ALD , flurbiprofen and sodium diclofenac , and then exposed to BQ .", "annotated_text": "<cell_line>Molt-4 cells</cell_line> ( <cell_line>M4</cell_line> ) , a <cell_line>human T lymphocyte cell line</cell_line> , were incubated with different concentrations of two ALD , flurbiprofen and sodium diclofenac , and then exposed to BQ ."}
{"id": "1671", "text": "Toxicity was measured by viability ( trypan blue exclusion ) .", "annotated_text": "Toxicity was measured by viability ( trypan blue exclusion ) ."}
{"id": "1672", "text": "Both drugs protected the cells against BQ cytotoxicity in a dose-dependent manner , e.g. , sodium diclofenac at 15 microM reduced the fraction of BQ-treated dead cells by 70 % .", "annotated_text": "Both drugs protected the cells against BQ cytotoxicity in a dose-dependent manner , e.g. , sodium diclofenac at 15 microM reduced the fraction of BQ-treated dead cells by 70 % ."}
{"id": "1673", "text": "ALDs induced QR activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity .", "annotated_text": "ALDs induced <protein>QR</protein> activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity ."}
{"id": "1674", "text": "The protective effect of ALD was significantly reduced by dicoumarol , a QR -specific inhibitor .", "annotated_text": "The protective effect of ALD was significantly reduced by dicoumarol , a <protein>QR</protein> -specific inhibitor ."}
{"id": "1675", "text": "Since human T cells and T cell lines do not metabolize arachidonic acid , our data suggest that ALD can protect human T lymphocytes against a metabolite of benzene by induction of QR activity .", "annotated_text": "Since <cell_type>human T cells</cell_type> and <cell_type>T cell lines</cell_type> do not metabolize arachidonic acid , our data suggest that ALD can protect <cell_type>human T lymphocytes</cell_type> against a metabolite of benzene by induction of <protein>QR</protein> activity ."}
{"id": "1676", "text": "Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4 .", "annotated_text": "Correlation of differentiation-inducing activity of retinoids on <cell_line>human leukemia cell lines</cell_line> <cell_line>HL-60</cell_line> and <cell_line>NB4</cell_line> ."}
{"id": "1677", "text": "Retinoids , including all-trans-retinoic acid , its isomers , and fifty synthetic retinoids ( retinobenzoic acids ) , were tested for differentiation-inducing activity on human leukemia cell lines HL-60 and NB4 .", "annotated_text": "Retinoids , including all-trans-retinoic acid , its isomers , and fifty synthetic retinoids ( retinobenzoic acids ) , were tested for differentiation-inducing activity on <cell_line>human leukemia cell lines</cell_line> <cell_line>HL-60</cell_line> and <cell_line>NB4</cell_line> ."}
{"id": "1678", "text": "A good linear correlation , with an r value of 0.91 , between the ED50 values for the differentiation-inducing activity towards HL-60 cells and that towards NB4 cells was found .", "annotated_text": "A good linear correlation , with an r value of 0.91 , between the ED50 values for the differentiation-inducing activity towards <cell_line>HL-60 cells</cell_line> and that towards <cell_line>NB4 cells</cell_line> was found ."}
{"id": "1679", "text": "Platelet-activating factor ( PAF ) positively auto-regulates the expression of human PAF receptor transcript 1 ( leukocyte-type ) through NF-kappa B .", "annotated_text": "<protein>Platelet-activating factor</protein> ( <protein>PAF</protein> ) positively auto-regulates the expression of <protein>human PAF receptor transcript 1</protein> ( leukocyte-type ) through <protein>NF-kappa B</protein> ."}
{"id": "1680", "text": "The human platelet-activating factor receptor ( PAFR ) gene is transcribed by two distinct promoters ( promoter 1 and promoter 2 ) to generate two transcripts ( designated as PAFR transcript 1 and PAFR transcript 2 ) , though their open reading frames are identical .", "annotated_text": "The <dna>human platelet-activating factor receptor ( PAFR ) gene</dna> is transcribed by two distinct <dna>promoters</dna> ( <dna>promoter 1</dna> and <dna>promoter 2</dna> ) to generate two transcripts ( designated as <rna>PAFR transcript 1</rna> and <rna>PAFR transcript 2</rna> ) , though their open reading frames are identical ."}
{"id": "1681", "text": "By primer extension analysis to discriminate two transcripts , we found that the levels of PAFR transcript 1 ( leukocyte-type ) , but not PAFR transcript 2 ( tissue-type ) , are upregulated by PAF as well as by 12-O-tetradecanoylphorbol-13-acetate ( TPA ) in the human stomach cancer cell line ( JR-St cells ) which expresses both functional PAFR transcript 1 and PAFR transcript 2 endogenously .", "annotated_text": "By primer extension analysis to discriminate two transcripts , we found that the levels of <rna>PAFR transcript 1</rna> ( leukocyte-type ) , but not <rna>PAFR transcript 2</rna> ( tissue-type ) , are upregulated by <protein>PAF</protein> as well as by 12-O-tetradecanoylphorbol-13-acetate ( TPA ) in the <cell_line>human stomach cancer cell line</cell_line> ( <cell_line>JR-St cells</cell_line> ) which expresses both functional <rna>PAFR transcript 1</rna> and <rna>PAFR transcript 2</rna> endogenously ."}
{"id": "1682", "text": "Functional analysis of the promoter 1 with a transient expression assay using chloramphenicol acetyltransferase ( CAT ) gene as a reporter showed that both PAF and TPA activated the promoter 1 but not the deleted promoter lacking the three consensus binding sites for NF-kappa B located from -571 bp to -459 bp .", "annotated_text": "Functional analysis of the <dna>promoter 1</dna> with a transient expression assay using <dna>chloramphenicol acetyltransferase ( CAT ) gene</dna> as a reporter showed that both <protein>PAF</protein> and TPA activated the <dna>promoter 1</dna> but not the deleted promoter lacking the three <dna>consensus binding sites</dna> for <protein>NF-kappa B</protein> located from -571 bp to -459 bp ."}
{"id": "1683", "text": "These findings suggest a molecular mechanism of positive regulation of PAFR gene expression by PAF through NF-kappa B , possibly by a phosphorylation reaction involving protein kinase C by PAF .", "annotated_text": "These findings suggest a molecular mechanism of positive regulation of <protein>PAFR</protein> gene expression by <protein>PAF</protein> through <protein>NF-kappa B</protein> , possibly by a phosphorylation reaction involving <protein>protein kinase C</protein> by <protein>PAF</protein> ."}
{"id": "1684", "text": "One gene , two transcripts : isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjogrens ' syndrome .", "annotated_text": "One gene , two <rna>transcripts</rna> : isolation of an alternative transcript encoding for the <protein>autoantigen La/SS-B</protein> from a <dna>cDNA library</dna> of a patient with primary Sjogrens ' syndrome ."}
{"id": "1685", "text": "A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjogrens ' syndrome .", "annotated_text": "A <dna>cDNA library</dna> was prepared from peripheral blood <cell_type>lymphocytes</cell_type> of an autoimmune patient with primary Sjogrens ' syndrome ."}
{"id": "1686", "text": "The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B .", "annotated_text": "The <dna>cDNA library</dna> was screened with the patients own autoimmune serum being monospecific for the <protein>nuclear autoantigen La/SS-B</protein> ."}
{"id": "1687", "text": "Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1 .", "annotated_text": "Thereby an alternative type of <rna>La mRNA</rna> was identified that differed from the known <rna>La mRNA</rna> due to an exchange of the <dna>exon 1</dna> ."}
{"id": "1688", "text": "Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron .", "annotated_text": "Sequencing of the genomic region between the <dna>exons 1 and 2</dna> showed that the <dna>alternative 5'-end</dna> is a part of the <dna>intron</dna> ."}
{"id": "1689", "text": "In addition , the presence of an alternative promoter site , which exists within the intron downstream of the exon 1 , became evident .", "annotated_text": "In addition , the presence of an <dna>alternative promoter site</dna> , which exists within the <dna>intron</dna> downstream of the <dna>exon 1</dna> , became evident ."}
{"id": "1690", "text": "In consequence , the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism .", "annotated_text": "In consequence , the <rna>alternative La mRNA</rna> is the result of a promoter switching combined with an alternative splicing mechanism ."}
{"id": "1691", "text": "In the intron , further transcription factor binding sites , including a NF-kappa B element , were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions .", "annotated_text": "In the intron , further <protein>transcription factor</protein> binding sites , including a <dna>NF-kappa B element</dna> , were identified leading to the suggestion that the expression of the gene encoding for the <protein>nuclear autoantigen La/SS-B</protein> alters in dependence on disease conditions ."}
{"id": "1692", "text": "Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B .", "annotated_text": "Cross-linking <protein>CD40</protein> on <cell_type>B cells</cell_type> rapidly activates <protein>nuclear factor-kappa B</protein> ."}
{"id": "1693", "text": "The B cell-associated surface molecule CD40 functions to regulate B cell responses .", "annotated_text": "The <protein>B cell-associated surface molecule CD40</protein> functions to regulate B cell responses ."}
{"id": "1694", "text": "Cross-linking CD40 on B cells can lead to homotypic cell adhesion , IL-6 production , and , in combination with cytokines , to Ig isotype switching .", "annotated_text": "Cross-linking <protein>CD40</protein> on <cell_type>B cells</cell_type> can lead to homotypic cell adhesion , <protein>IL-6</protein> production , and , in combination with <protein>cytokines</protein> , to Ig isotype switching ."}
{"id": "1695", "text": "Tyrosine kinase activity is increased shortly after engagement of this receptor .", "annotated_text": "Tyrosine kinase activity is increased shortly after engagement of this receptor ."}
{"id": "1696", "text": "Little is known about how the very early events induced by CD40 cross-linking link to cellular responses .", "annotated_text": "Little is known about how the very early events induced by <protein>CD40</protein> cross-linking link to cellular responses ."}
{"id": "1697", "text": "In this study , we demonstrate that nuclear factor ( NF ) -kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines .", "annotated_text": "In this study , we demonstrate that <protein>nuclear factor ( NF ) -kappa B</protein> and <protein>NF-kappa B-like transcription factors</protein> are activated after cross-linking <protein>CD40</protein> on resting <cell_type>human tonsillar B cells</cell_type> and on <cell_line>B cell lines</cell_line> ."}
{"id": "1698", "text": "The activation is rapid and is mediated through a tyrosine kinase-dependent pathway .", "annotated_text": "The activation is rapid and is mediated through a tyrosine kinase-dependent pathway ."}
{"id": "1699", "text": "The complexes detected in electrophoretic mobility shift assays contain p50 , p65 ( RelA ) , c-Rel , and most likely other components .", "annotated_text": "The complexes detected in electrophoretic mobility shift assays contain <protein>p50</protein> , <protein>p65</protein> ( <protein>RelA</protein> ) , <protein>c-Rel</protein> , and most likely other components ."}
{"id": "1700", "text": "By using transient transfection assays , we found that cross-linking CD40 supports NF-kappa B -dependent gene expression .", "annotated_text": "By using transient transfection assays , we found that cross-linking <protein>CD40</protein> supports <protein>NF-kappa B</protein> -dependent gene expression ."}
{"id": "1701", "text": "Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites .", "annotated_text": "Our results define the <protein>NF-kappa B</protein> system as an intermediate event in <protein>CD40</protein> signaling and suggest that the <protein>CD40</protein> pathway can influence the expression of <dna>B cell-associated genes</dna> with <dna>NF-kappa B consensus sites</dna> ."}
{"id": "1702", "text": "Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers .", "annotated_text": "Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in <cell_type>human monocytic cells</cell_type> by preventing activation of <protein>c-Rel/p65 heterodimers</protein> ."}
{"id": "1703", "text": "Tissue factor ( TF ) is expressed rapidly by human monocytes exposed to bacterial endotoxin ( lipopolysaccharide , or LPS ) .", "annotated_text": "<protein>Tissue factor</protein> ( <protein>TF</protein> ) is expressed rapidly by <cell_type>human monocytes</cell_type> exposed to <protein>bacterial endotoxin</protein> ( lipopolysaccharide , or LPS ) ."}
{"id": "1704", "text": "Transcriptional regulation is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site in the TF promoter .", "annotated_text": "Transcriptional regulation is mediated by binding of <protein>c-Rel/p65 heterodimers</protein> to a <dna>kappa B-like site</dna> in the <dna>TF promoter</dna> ."}
{"id": "1705", "text": "Nuclear translocation of cytosolic c-Rel/p65 heterodimers and other members of the NF-kappa B/Rel family requires dissociation and proteolytic degradation of the inhibitor protein , I kappa B alpha .", "annotated_text": "Nuclear translocation of <protein>cytosolic c-Rel/p65 heterodimers</protein> and other members of the <protein>NF-kappa B/Rel family</protein> requires dissociation and proteolytic degradation of the <protein>inhibitor protein</protein> , <protein>I kappa B alpha</protein> ."}
{"id": "1706", "text": "The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone ( TPCK ) and N alpha-tosyl-L-lysine chloromethyl ketone ( TLCK ) block activation of NF-kappa B/Rel proteins by preventing degradation of I kappa B alpha .", "annotated_text": "The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone ( TPCK ) and N alpha-tosyl-L-lysine chloromethyl ketone ( TLCK ) block activation of <protein>NF-kappa B/Rel proteins</protein> by preventing degradation of <protein>I kappa B alpha</protein> ."}
{"id": "1707", "text": "To determine if TPCK and TLCK inhibited LPS induction of TF expression , freshly isolated human monocytes and monocytic THP-1 cells were pretreated with these inhibitors for 30 min before LPS stimulation .", "annotated_text": "To determine if TPCK and TLCK inhibited LPS induction of <protein>TF</protein> expression , freshly isolated <cell_type>human monocytes</cell_type> and <cell_line>monocytic THP-1 cells</cell_line> were pretreated with these inhibitors for 30 min before LPS stimulation ."}
{"id": "1708", "text": "Both TPCK and TLCK inhibited LPS induction of TF protein , TF mRNA and TF promoter activity in a dose-dependent manner .", "annotated_text": "Both TPCK and TLCK inhibited LPS induction of <protein>TF protein</protein> , <rna>TF mRNA</rna> and <protein>TF</protein> promoter activity in a dose-dependent manner ."}
{"id": "1709", "text": "These inhibitors specifically prevented degradation of I kappa B alpha and nuclear translocation of c-Rel/p65 heterodimers .", "annotated_text": "These inhibitors specifically prevented degradation of <protein>I kappa B alpha</protein> and nuclear translocation of <protein>c-Rel/p65 heterodimers</protein> ."}
{"id": "1710", "text": "In contrast , TPCK and TLCK did not block induction of an immediate-early gene encoding the transcription factor , Egr-1 .", "annotated_text": "In contrast , TPCK and TLCK did not block induction of an <dna>immediate-early gene</dna> encoding the <protein>transcription factor</protein> , <protein>Egr-1</protein> ."}
{"id": "1711", "text": "Taken together , these data indicated that inhibiting nuclear translocation of c-Rel/p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells .", "annotated_text": "Taken together , these data indicated that inhibiting nuclear translocation of <protein>c-Rel/p65 heterodimers</protein> prevented LPS induction of <protein>TF</protein> gene transcription in <cell_type>monocytic cells</cell_type> ."}
{"id": "1712", "text": "1 , 25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism .", "annotated_text": "<protein>1 , 25-Dihydroxyvitamin D3 receptors</protein> in <cell_type>peripheral blood mononuclear cells</cell_type> from patients with primary and secondary hyperparathyroidism ."}
{"id": "1713", "text": "A decreased number of calcitriol ( 1 , 25 ( OH ) 2D3 ) receptors has been observed in parathyroid glands of uremic animals .", "annotated_text": "A decreased number of <protein>calcitriol ( 1 , 25 ( OH ) 2D3 ) receptors</protein> has been observed in parathyroid glands of uremic animals ."}
{"id": "1714", "text": "In humans , studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism .", "annotated_text": "In humans , studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism ."}
{"id": "1715", "text": "Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells ( PBMC ) , we have investigated the specific uptake of 3H-labelled 1 , 25 ( OH ) 2D3 in PBMC of 12 women with primary hyperparathyroidism ( PHP ) , 8 women with hyperparathyroidism secondary to chronic renal failure ( SH ) , 9 women with renal transplant ( RT ) , and 23 healthy women .", "annotated_text": "Since specific receptors for calcitriol have been described in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) , we have investigated the specific uptake of 3H-labelled 1 , 25 ( OH ) 2D3 in <cell_type>PBMC</cell_type> of 12 women with primary hyperparathyroidism ( PHP ) , 8 women with hyperparathyroidism secondary to chronic renal failure ( SH ) , 9 women with renal transplant ( RT ) , and 23 healthy women ."}
{"id": "1716", "text": "The median dissociation constant ( Kd ) was similar in all three groups of patients and in healthy women ( mean +/- S.D. ( range ) : PHP , 1.2 +/- 1.0 ( 0.2-4 ) x 10 ( -10 ) M ; SH , 0.6 +/- 0.4 ( 0.2-1.2 ) x 10 ( -10 ) M ; RT , 1.1 +/- 0.5 ( 0.4-1.9 ) x 10 ( -10 ) M ; controls , 1.0 +/- 0.6 ( 0.3-2.6 ) x 10 ( -10 ) M ) . However , the maximal binding capacity ( Nmax ) was significantly enhanced in PHP ( 3.9 +/- 1.9 ( 1.3-7.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0006 ) and decreased in SH ( 0.8 +/- 0.5 ( 0.2-1.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0001 ) , whereas no changes were seen in RT ( 2.3 +/- 0.7 ( 1.2-3.3 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ) .", "annotated_text": "The median dissociation constant ( Kd ) was similar in all three groups of patients and in healthy women ( mean +/- S.D. ( range ) : PHP , 1.2 +/- 1.0 ( 0.2-4 ) x 10 ( -10 ) M ; SH , 0.6 +/- 0.4 ( 0.2-1.2 ) x 10 ( -10 ) M ; RT , 1.1 +/- 0.5 ( 0.4-1.9 ) x 10 ( -10 ) M ; controls , 1.0 +/- 0.6 ( 0.3-2.6 ) x 10 ( -10 ) M ) . However , the maximal binding capacity ( Nmax ) was significantly enhanced in PHP ( 3.9 +/- 1.9 ( 1.3-7.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0006 ) and decreased in SH ( 0.8 +/- 0.5 ( 0.2-1.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0001 ) , whereas no changes were seen in RT ( 2.3 +/- 0.7 ( 1.2-3.3 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ) ."}
{"id": "1717", "text": "In three patients with PHP who were subjected to parathyroidectomy , the calcitriol number came down to normal .", "annotated_text": "In three patients with PHP who were subjected to parathyroidectomy , the calcitriol number came down to normal ."}
{"id": "1718", "text": "Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia .", "annotated_text": "Changes of <protein>calcitriol receptors</protein> in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia ."}
{"id": "1719", "text": "The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation .", "annotated_text": "The severe phenotype of females with <dna>tiny ring X chromosomes</dna> is associated with inability of these <dna>chromosomes</dna> to undergo X inactivation ."}
{"id": "1720", "text": "Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45 , X/46 , X , r ( X ) karyotype .", "annotated_text": "Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45 , X/46 , X , r ( X ) karyotype ."}
{"id": "1721", "text": "Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed .", "annotated_text": "Studies of these females show that the <dna>XIST locus</dna> on their <dna>tiny ring X chromosomes</dna> is either not present or not expressed ."}
{"id": "1722", "text": "As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia , nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active .", "annotated_text": "As <dna>XIST</dna> transcription is well correlated with inactivation of the <dna>X chromosome</dna> in <cell_type>female somatic cells</cell_type> and <cell_type>spermatogonia</cell_type> , nonexpression of the locus even when it is present suggests that these <dna>chromosomes</dna> are transcriptionally active ."}
{"id": "1723", "text": "We examined the transcriptional activity of ring X chromosomes lacking XIST expression ( XISTE- ) , from three females with severe phenotypes .", "annotated_text": "We examined the transcriptional activity of ring <dna>X chromosomes</dna> lacking <dna>XIST</dna> expression ( XISTE- ) , from three females with severe phenotypes ."}
{"id": "1724", "text": "The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active .", "annotated_text": "The two tiny ring <dna>X chromosomes</dna> studied with an <protein>antibody</protein> specific for the acetylated isoforms of <protein>histone H4</protein> marking <dna>transcribed chromatin domains</dna> were labeled at a level consistent with their being active ."}
{"id": "1725", "text": "We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes .", "annotated_text": "We also examined tow of the <dna>XISTE- ring chromosomes</dna> to determine whether <dna>genes</dna> that are normally silent on an <dna>inactive X</dna> are expressed from these <dna>chromosomes</dna> ."}
{"id": "1726", "text": "Analyses of hybrid cells show that TIMP , ZXDA , and ZXDB loci on the proximal short arm , and AR and PHKA1 loci on the long arm , are well expressed from the tiny ring X chromosome lacking XIST DNA .", "annotated_text": "Analyses of <cell_line>hybrid cells</cell_line> show that <dna>TIMP</dna> , <dna>ZXDA</dna> , and <dna>ZXDB loci</dna> on the <dna>proximal short arm</dna> , and <dna>AR</dna> and <dna>PHKA1 loci</dna> on the long arm , are well expressed from the <dna>tiny ring X chromosome</dna> lacking <dna>XIST DNA</dna> ."}
{"id": "1727", "text": "Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele .", "annotated_text": "Studies of the <dna>ring chromosome</dna> that has <dna>XIST DNA</dna> but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele ."}
{"id": "1728", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "1729", "text": "Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells .", "annotated_text": "Inhibition of activation of <protein>transcription factor AP-1</protein> by <protein>CD28</protein> signalling in <cell_type>human T-cells</cell_type> ."}
{"id": "1730", "text": "Co-stimulation of T-lymphocytes by T-cell receptor ( TcR ) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 ( IL-2 ) production .", "annotated_text": "Co-stimulation of <cell_type>T-lymphocytes</cell_type> by <protein>T-cell receptor</protein> ( <protein>TcR</protein> ) occupancy and activation of the <protein>CD28 surface molecule</protein> results in enhanced proliferation and <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) production ."}
{"id": "1731", "text": "The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter , called CD28-responsive element .", "annotated_text": "The increase in <protein>IL-2</protein> gene expression triggered by <protein>CD28</protein> involves a <dna>kappa B-like sequence</dna> in the <dna>5'-regulatory region</dna> of the <dna>IL-2 promoter</dna> , called <dna>CD28-responsive element</dna> ."}
{"id": "1732", "text": "Stimulation of T-cells by agonistic anti-CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate ( PMA ) - or TcR -derived signals induces the enhanced activation of the transcription factor NF-kappa B .", "annotated_text": "Stimulation of <cell_type>T-cells</cell_type> by agonistic <protein>anti-CD28 antibodies</protein> in conjunction with phorbol 12-myristate 13-acetate ( PMA ) - or <protein>TcR</protein> -derived signals induces the enhanced activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> ."}
{"id": "1733", "text": "Here we report that CD28 engagement , however , exerts opposite effects on the transcription factor AP-1 .", "annotated_text": "Here we report that <protein>CD28</protein> engagement , however , exerts opposite effects on the <protein>transcription factor AP-1</protein> ."}
{"id": "1734", "text": "Whereas anti-CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B , PMA-induced activation of AP-1 was significantly suppressed .", "annotated_text": "Whereas <protein>anti-CD28</protein> together with PMA increased the DNA binding and trans-activation activity of <protein>NF-kappa B</protein> , PMA-induced activation of <protein>AP-1</protein> was significantly suppressed ."}
{"id": "1735", "text": "The inhibitory effect exerted by anti-CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays .", "annotated_text": "The inhibitory effect exerted by <protein>anti-CD28</protein> was observed at the level of DNA binding as well as in functional reporter-gene assays ."}
{"id": "1736", "text": "These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation .", "annotated_text": "These results suggest that the two <protein>transcription factors</protein> are independently regulated and may perform different functions during T-cell activation ."}
{"id": "1737", "text": "HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization .", "annotated_text": "<protein>HIV-1 Nef</protein> leads to inhibition or activation of <cell_type>T cells</cell_type> depending on its intracellular localization ."}
{"id": "1738", "text": "Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys .", "annotated_text": "<protein>Nef</protein> of primate lentiviruses is required for viremia and progression to AIDS in monkeys ."}
{"id": "1739", "text": "Negative , positive , and no effects of Nef have also been reported on viral replication in cells .", "annotated_text": "Negative , positive , and no effects of <protein>Nef</protein> have also been reported on viral replication in cells ."}
{"id": "1740", "text": "To reconcile these observations , we expressed a hybrid CD8-Nef protein in Jurkat cells .", "annotated_text": "To reconcile these observations , we expressed a <protein>hybrid CD8-Nef protein</protein> in <cell_line>Jurkat cells</cell_line> ."}
{"id": "1741", "text": "Two opposite phenotypes were found , which depended on the intracellular localization of Nef .", "annotated_text": "Two opposite phenotypes were found , which depended on the intracellular localization of <protein>Nef</protein> ."}
{"id": "1742", "text": "Expressed in the cytoplasm or on the cell surface , the chimera inhibited or activated early signaling events from the T cell antigen receptor .", "annotated_text": "Expressed in the cytoplasm or on the cell surface , the <protein>chimera</protein> inhibited or activated early signaling events from the <protein>T cell antigen receptor</protein> ."}
{"id": "1743", "text": "Activated Jurkat cells died by apoptosis , and only cells with mutated nef genes expressing truncated Nefs survived , which rendered Nef nonfunctional .", "annotated_text": "Activated <cell_line>Jurkat cells</cell_line> died by apoptosis , and only cells with mutated <dna>nef genes</dna> expressing truncated <protein>Nefs</protein> survived , which rendered <protein>Nef</protein> nonfunctional ."}
{"id": "1744", "text": "These mutations paralleled those in other viral strains passaged in vitro .", "annotated_text": "These mutations paralleled those in other viral strains passaged in vitro ."}
{"id": "1745", "text": "Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation , but they also explain effects of Nef in HIV infection and progression to AIDS .", "annotated_text": "Not only do these positional effects of <protein>Nef</protein> reconcile diverse phenotypes of <protein>Nef</protein> and suggest a role for its N-terminal myristylation , but they also explain effects of <protein>Nef</protein> in HIV infection and progression to AIDS ."}
{"id": "1746", "text": "An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter .", "annotated_text": "An intricate arrangement of binding sites for the <protein>Ets family</protein> of <protein>transcription factors</protein> regulates activity of the <dna>alpha 4 integrin gene promoter</dna> ."}
{"id": "1747", "text": "alpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle .", "annotated_text": "<protein>alpha 4 integrins</protein> mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle ."}
{"id": "1748", "text": "Here we examine molecular mechanisms controlling the pattern of alpha 4 expression .", "annotated_text": "Here we examine molecular mechanisms controlling the pattern of <protein>alpha 4</protein> expression ."}
{"id": "1749", "text": "The activity of constructs containing 5 ' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not .", "annotated_text": "The activity of constructs containing <dna>5 ' deletion mutants</dna> of the <dna>alpha 4 gene promoter</dna> was compared in transfection assays into <cell_line>cell lines</cell_line> that express <protein>alpha 4</protein> and <cell_line>cell lines</cell_line> that do not ."}
{"id": "1750", "text": "The sequence between position -42 and -76 base pairs ( bp ) was required for efficient transcription in cells that express alpha 4 , but it showed no activity in HeLa cells , which do not express alpha 4 .", "annotated_text": "The sequence between position <dna>-42 and -76 base pairs</dna> ( bp ) was required for efficient transcription in cells that express <protein>alpha 4</protein> , but it showed no activity in <cell_line>HeLa cells</cell_line> , which do not express <protein>alpha 4</protein> ."}
{"id": "1751", "text": "Three binding sites for the Ets family of transcription factors are found in this region : two adjacent sites at positions -50 and -54 bp and a more 5 ' site at position -67 bp .", "annotated_text": "Three <dna>binding sites</dna> for the <protein>Ets family</protein> of <protein>transcription factors</protein> are found in this region : two adjacent sites at positions <dna>-50 and -54 bp</dna> and a more <dna>5 ' site</dna> at position <dna>-67 bp</dna> ."}
{"id": "1752", "text": "Using a series of constructs containing deletions and mutations in this region , we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha ( GABP alpha ) /GABP beta and for a low level of transcriptional activation .", "annotated_text": "Using a series of constructs containing deletions and mutations in this region , we found that the <dna>3'-most site</dna> alone was sufficient for binding <protein>GA-binding protein alpha</protein> ( <protein>GABP alpha ) /GABP beta</protein> and for a low level of transcriptional activation ."}
{"id": "1753", "text": "When all three sites were present , a second complex `` a '' was detected , which contains an unknown member of the Ets family .", "annotated_text": "When all three sites were present , a second complex `` a '' was detected , which contains an unknown member of the <protein>Ets family</protein> ."}
{"id": "1754", "text": "Formation of complex a was cell-type specific and correlated with a high level of transcription .", "annotated_text": "Formation of complex a was cell-type specific and correlated with a high level of transcription ."}
{"id": "1755", "text": "Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta , but it eliminated a .", "annotated_text": "Deletion of the <dna>5'-most Ets site</dna> had no effect on binding to <protein>GABP alpha/GABP beta</protein> , but it eliminated a ."}
{"id": "1756", "text": "Concomitant with this loss of a , a new Ets-1-containing complex `` c `` appeared .", "annotated_text": "Concomitant with this loss of a , a <protein>new Ets-1-containing complex</protein> `` <protein>c</protein> `` appeared ."}
{"id": "1757", "text": "Complex c substituted efficiently for complex a in transcriptional activation .", "annotated_text": "Complex c substituted efficiently for complex a in transcriptional activation ."}
{"id": "1758", "text": "We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein , they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter .", "annotated_text": "We conclude that although neither of the two <dna>5'-most Ets sites</dna> alone binds <protein>nuclear protein</protein> , they appear to act as modulators which control the pattern of <protein>Ets proteins</protein> that bind the <dna>alpha 4 gene promoter</dna> ."}
{"id": "1759", "text": "This arrangement of Ets sites , coupled with the tissue- and developmental-specific expression of Ets members , likely play a key role in defining the pattern of alpha 4 integrin .", "annotated_text": "This arrangement of <dna>Ets sites</dna> , coupled with the tissue- and developmental-specific expression of <protein>Ets members</protein> , likely play a key role in defining the pattern of <protein>alpha 4 integrin</protein> ."}
{"id": "1760", "text": "Mechanism of antiandrogen action : conformational changes of the receptor .", "annotated_text": "Mechanism of antiandrogen action : conformational changes of the receptor ."}
{"id": "1761", "text": "Androgen receptor mRNA was translated in vitro , and androgen- and antiandrogen-bound receptor complexes were studied using limited proteolytic digestion by trypsin .", "annotated_text": "<rna>Androgen receptor mRNA</rna> was translated in vitro , and <protein>androgen- and antiandrogen-bound receptor complexes</protein> were studied using limited proteolytic digestion by <protein>trypsin</protein> ."}
{"id": "1762", "text": "Partial proteolysis of androgen-bound receptor protein resulted in a 29-kDa proteolysis-resisting fragment , whereas antiandrogen binding stabilised a 35-kDa fragment .", "annotated_text": "Partial proteolysis of <protein>androgen-bound receptor protein</protein> resulted in a <protein>29-kDa proteolysis-resisting fragment</protein> , whereas antiandrogen binding stabilised a <protein>35-kDa fragment</protein> ."}
{"id": "1763", "text": "Both fragments contain the entire ligand binding domain , and the 35-kDa fragment extended into the hinge region of the receptor .", "annotated_text": "Both fragments contain the entire <protein>ligand binding domain</protein> , and the <protein>35-kDa fragment</protein> extended into the <protein>hinge region</protein> of the receptor ."}
{"id": "1764", "text": "Several antiandrogens show agonistic properties for a mutated androgen receptor ( LNCaP cell variant ) ; trypsin digestion of antiandrogen-bound mutated receptor also resulted in a 29-kDa fragment .", "annotated_text": "Several antiandrogens show agonistic properties for a <protein>mutated androgen receptor</protein> ( <cell_line>LNCaP cell variant</cell_line> ) ; <protein>trypsin</protein> digestion of <protein>antiandrogen-bound mutated receptor</protein> also resulted in a <protein>29-kDa fragment</protein> ."}
{"id": "1765", "text": "Our results point to an important difference between antiandrogens and antagonists of other steroid hormone receptors .", "annotated_text": "Our results point to an important difference between antiandrogens and antagonists of other <protein>steroid hormone receptors</protein> ."}
{"id": "1766", "text": "Antiandrogens result in protection of both the hinge region and C-terminus of the androgen receptor agonist proteolytic attack , whereas other studies showed that antiestrogens and antiprogestagens expose the C-terminal end of the ligand binding domain of their respective receptors to protease .", "annotated_text": "Antiandrogens result in protection of both the <protein>hinge region</protein> and <protein>C-terminus</protein> of the <protein>androgen receptor</protein> agonist proteolytic attack , whereas other studies showed that antiestrogens and antiprogestagens expose the <protein>C-terminal end</protein> of the <protein>ligand binding domain</protein> of their respective receptors to <protein>protease</protein> ."}
{"id": "1767", "text": "Differences in conformation of the hinge region distinguish androgen-bound from antiandrogen-bound receptor complexes , which represents an important feature of antiandrogen action .", "annotated_text": "Differences in conformation of the <protein>hinge region</protein> distinguish <protein>androgen-bound</protein> from <protein>antiandrogen-bound receptor complexes</protein> , which represents an important feature of antiandrogen action ."}
{"id": "1768", "text": "Activation of nuclear factor kappa B in human neuroblastoma cell lines .", "annotated_text": "Activation of <protein>nuclear factor kappa B</protein> in <cell_line>human neuroblastoma cell lines</cell_line> ."}
{"id": "1769", "text": "The nuclear factor kappa B ( NF-kappa B ) is a eukaryotic transcription factor .", "annotated_text": "The <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) is a eukaryotic <protein>transcription factor</protein> ."}
{"id": "1770", "text": "In B cells and macrophages it is constitutively present in cell nuclei , whereas in many other cell types , NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha ( TNF alpha ) , phorbol ester , and other polyclonal signals .", "annotated_text": "In <cell_type>B cells</cell_type> and <cell_type>macrophages</cell_type> it is constitutively present in cell nuclei , whereas in many other cell types , <protein>NF-kappa B</protein> translocates from cytosol to nucleus as a result of transduction by <protein>tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) , phorbol ester , and other polyclonal signals ."}
{"id": "1771", "text": "Using neuroblastoma cell lines as models , we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment .", "annotated_text": "Using <cell_line>neuroblastoma cell lines</cell_line> as models , we have shown that in <cell_type>neural cells</cell_type> <protein>NF-kappa B</protein> was present in the cytosol and translocated into nuclei as a result of <protein>TNF alpha</protein> treatment ."}
{"id": "1772", "text": "The TNF alpha -activated NF-kappa B was transcriptionally functional .", "annotated_text": "The <protein>TNF alpha</protein> -activated <protein>NF-kappa B</protein> was transcriptionally functional ."}
{"id": "1773", "text": "NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation .", "annotated_text": "<protein>NF-kappa B</protein> activation by <protein>TNF alpha</protein> was not correlated with cell differentiation or proliferation ."}
{"id": "1774", "text": "However , reagents such as nerve growth factor ( NGF ) and the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) , which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line , activated NF-kappa B , but only in that particular cell line .", "annotated_text": "However , reagents such as <protein>nerve growth factor</protein> ( <protein>NGF</protein> ) and the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) , which induce phenotypical differentiation of the <cell_line>SH-SY5Y neuroblastoma cell line</cell_line> , activated <protein>NF-kappa B</protein> , but only in that particular <cell_line>cell line</cell_line> ."}
{"id": "1775", "text": "In a NGF-responsive rat pheochromocytoma cell line , PC12 , PMA activated NF-kappa B , whereas NGF did not .", "annotated_text": "In a <cell_line>NGF-responsive rat pheochromocytoma cell line</cell_line> , <cell_line>PC12</cell_line> , PMA activated <protein>NF-kappa B</protein> , whereas <protein>NGF</protein> did not ."}
{"id": "1776", "text": "In other neuroblastoma cell lines , such as SK-N-Be ( 2 ) , the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation .", "annotated_text": "In other <cell_line>neuroblastoma cell lines</cell_line> , such as <cell_line>SK-N-Be ( 2 )</cell_line> , the lack of PMA induction of differentiation was correlated with the lack of <protein>NF-kappa B</protein> activation ."}
{"id": "1777", "text": "We found , moreover , that in SK-N-Be ( 2 ) cells protein kinase C ( PKC ) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression .", "annotated_text": "We found , moreover , that in <cell_line>SK-N-Be ( 2 ) cells</cell_line> <protein>protein kinase C</protein> ( <protein>PKC</protein> ) enzymatic activity was much lower compared with that in a <cell_line>control cell line</cell_line> and that the low <protein>PKC</protein> enzymatic activity was due to low <protein>PKC</protein> protein expression ."}
{"id": "1778", "text": "NF-kappa B was not activated by retinoic acid , which induced morphological differentiation of all the neuroblastoma cell lines used in the present study .", "annotated_text": "<protein>NF-kappa B</protein> was not activated by retinoic acid , which induced morphological differentiation of all the <cell_line>neuroblastoma cell lines</cell_line> used in the present study ."}
{"id": "1779", "text": "Thus , NF-kappa B activation was not required for neuroblastoma cell differentiation .", "annotated_text": "Thus , <protein>NF-kappa B</protein> activation was not required for <cell_type>neuroblastoma</cell_type> cell differentiation ."}
{"id": "1780", "text": "Furthermore , the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation .", "annotated_text": "Furthermore , the results obtained with <protein>TNF alpha</protein> proved that <protein>NF-kappa B</protein> activation was not sufficient for induction of <cell_type>neuroblastoma</cell_type> differentiation ."}
{"id": "1781", "text": "ERP , a new member of the ets transcription factor/oncoprotein family : cloning , characterization , and differential expression during B-lymphocyte development .", "annotated_text": "<protein>ERP</protein> , a new member of the <protein>ets transcription factor/oncoprotein family</protein> : cloning , characterization , and differential expression during B-lymphocyte development ."}
{"id": "1782", "text": "The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and , if aberrantly expressed , can cause cellular transformation .", "annotated_text": "The <dna>ets gene family</dna> encodes a group of proteins which function as <protein>transcription factors</protein> under physiological conditions and , if aberrantly expressed , can cause cellular transformation ."}
{"id": "1783", "text": "We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain ( IgH ) enhancer , pi and microB , which exhibit striking similarity to binding sites for ets-related proteins .", "annotated_text": "We have recently identified two regulatory elements in the <dna>murine immunoglobulin heavy-chain ( IgH ) enhancer</dna> , <dna>pi</dna> and <dna>microB</dna> , which exhibit striking similarity to <dna>binding sites</dna> for <dna>ets-related proteins</dna> ."}
{"id": "1784", "text": "To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site , we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family .", "annotated_text": "To identify <protein>ets-related transcriptional regulators</protein> expressed in <cell_type>pre-B lymphocytes</cell_type> that may interact with either the <dna>pi</dna> or the <dna>microB site</dna> , we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the <dna>ets family</dna> ."}
{"id": "1785", "text": "We have cloned the gene for a new ets-related transcription factor , ERP ( ets-related protein ) , from the murine pre-B cell line BASC 6C2 and from mouse lung tissue .", "annotated_text": "We have cloned the gene for a new <protein>ets-related transcription factor</protein> , <protein>ERP</protein> ( <protein>ets-related protein</protein> ) , from the <cell_line>murine pre-B cell line</cell_line> <cell_line>BASC 6C2</cell_line> and from mouse lung tissue ."}
{"id": "1786", "text": "The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family .", "annotated_text": "The <protein>ERP</protein> protein contains a region of high homology with the ETS DNA-binding domain common to all members of the <protein>ets transcription factor/oncoprotein family</protein> ."}
{"id": "1787", "text": "Three additional smaller regions show homology to the ELK-1 and SAP-1 genes , a subgroup of the ets gene family that interacts with the serum response factor .", "annotated_text": "Three additional smaller regions show homology to the ELK-1 and <protein>SAP-1</protein> genes , a subgroup of the <dna>ets gene family</dna> that interacts with the <protein>serum response factor</protein> ."}
{"id": "1788", "text": "Full-length ERP expresses only negligible DNA-binding activity by itself .", "annotated_text": "Full-length <protein>ERP</protein> expresses only negligible DNA-binding activity by itself ."}
{"id": "1789", "text": "Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site , the IgH enhancer pi site , and the lck promoter ets site , suggesting a carboxy-terminal negative regulatory domain .", "annotated_text": "Removal of the <protein>carboxy terminus</protein> enables <protein>ERP</protein> to interact with a variety of <dna>ets-binding sites</dna> including the <dna>E74 site</dna> , the <dna>IgH enhancer pi site</dna> , and the <dna>lck promoter ets site</dna> , suggesting a <protein>carboxy-terminal negative regulatory domain</protein> ."}
{"id": "1790", "text": "At least three ERP-related transcripts are expressed in a variety of tissues .", "annotated_text": "At least three <protein>ERP-related transcripts</protein> are expressed in a variety of tissues ."}
{"id": "1791", "text": "However , within the B-cell lineage , ERP is highly expressed primarily at early stages of B-lymphocyte development , and expression declines drastically upon B-cell maturation , correlating with the enhancer activity of the IgH pi site .", "annotated_text": "However , within the <cell_type>B-cell lineage</cell_type> , <protein>ERP</protein> is highly expressed primarily at early stages of <cell_type>B-lymphocyte</cell_type> development , and expression declines drastically upon B-cell maturation , correlating with the enhancer activity of the <dna>IgH pi site</dna> ."}
{"id": "1792", "text": "These data suggest that ERP might play a role in B-cell development and in IgH gene regulation .", "annotated_text": "These data suggest that <protein>ERP</protein> might play a role in <cell_type>B-cell</cell_type> development and in <dna>IgH gene</dna> regulation ."}
{"id": "1793", "text": "Gene for a tissue-specific transcriptional activator ( EBF or Olf-1 ) , expressed in early B lymphocytes , adipocytes , and olfactory neurons , is located on human chromosome 5 , band q34 , and proximal mouse chromosome 11 .", "annotated_text": "Gene for a <protein>tissue-specific transcriptional activator</protein> ( <protein>EBF</protein> or <protein>Olf-1</protein> ) , expressed in <cell_type>early B lymphocytes</cell_type> , <cell_type>adipocytes</cell_type> , and <cell_type>olfactory neurons</cell_type> , is located on <dna>human chromosome 5</dna> , <dna>band q34</dna> , and <dna>proximal mouse chromosome 11</dna> ."}
{"id": "1794", "text": "Murine B lymphocytes , adipocytes , and olfactory neurons contain a DNA-binding protein that participates in the regulation of genes encoding tissue-specific components of signal transduction .", "annotated_text": "<cell_type>Murine B lymphocytes</cell_type> , <cell_type>adipocytes</cell_type> , and <cell_type>olfactory neurons</cell_type> contain a <protein>DNA-binding protein</protein> that participates in the regulation of <dna>genes</dna> encoding tissue-specific components of signal transduction ."}
{"id": "1795", "text": "Purification and cloning of this protein , termed early B-cell factor ( EBF ) , from murine B lymphocytes and independent cloning of a protein , termed Olf-1 , from olfactory neuronal cells revealed virtual complete amino acid sequence identity between these proteins .", "annotated_text": "Purification and cloning of this protein , termed early <protein>B-cell factor</protein> ( <protein>EBF</protein> ) , from <cell_type>murine B lymphocytes</cell_type> and independent cloning of a protein , termed <protein>Olf-1</protein> , from <cell_type>olfactory neuronal cells</cell_type> revealed virtual complete amino acid sequence identity between these proteins ."}
{"id": "1796", "text": "As a first step towards identifying a human genetic disorder or mouse mutation for which EBF could be a candidate gene , we have chromosomally mapped the corresponding locus in both species .", "annotated_text": "As a first step towards identifying a human genetic disorder or mouse mutation for which <protein>EBF</protein> could be a candidate gene , we have chromosomally mapped the corresponding locus in both species ."}
{"id": "1797", "text": "By Southern hybridization analyses of somatic cell hybrid panels with murine cDNA probe , fluorescence chromosomal in situ hybridization ( FISH ) of human genomic clones , and analysis of recombinant inbred mouse strains , we have found single sites for EBF homologous sequences on human Chromosome ( Chr ) 5 , band q34 , and on proximal mouse Chr 11 , in an evolutionarily conserved region .", "annotated_text": "By Southern hybridization analyses of somatic cell hybrid panels with <dna>murine cDNA probe</dna> , fluorescence chromosomal in situ hybridization ( FISH ) of <dna>human genomic clones</dna> , and analysis of <cell_line>recombinant inbred mouse strains</cell_line> , we have found single sites for <dna>EBF homologous sequences</dna> on human Chromosome ( Chr ) 5 , <dna>band q34</dna> , and on <dna>proximal mouse Chr 11</dna> , in an <dna>evolutionarily conserved region</dna> ."}
{"id": "1798", "text": "Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B /AP-1 in T cells .", "annotated_text": "<protein>Calcineurin</protein> activates transcription from the <dna>GM-CSF promoter</dna> in synergy with either <protein>protein kinase C</protein> or <protein>NF-kappa B</protein> <protein>/AP-1</protein> in <cell_type>T cells</cell_type> ."}
{"id": "1799", "text": "Two cis-acting elements GM-kappa B/GC-box and CLE0 , of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate ( PMA ) and Ca2+ ionophore ( A23187 ) .", "annotated_text": "Two <dna>cis-acting elements</dna> <dna>GM-kappa B/GC-box</dna> and <dna>CLE0</dna> , of the <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene</dna> are required for maximal induction in <cell_line>Jurkat T cells</cell_line> by costimulation with phorbol-12-myristate acetate ( PMA ) and Ca2+ ionophore ( A23187 ) ."}
{"id": "1800", "text": "The GM-kappa B sequence is recognized by NF-kappa B , which is mainly induced by PMA .", "annotated_text": "The <dna>GM-kappa B sequence</dna> is recognized by <protein>NF-kappa B</protein> , which is mainly induced by PMA ."}
{"id": "1801", "text": "The CLE0 sequence interacts with factors , related to a PMA-induced AP-1 and a PMA/A23187-induced NF-AT .", "annotated_text": "The <dna>CLE0 sequence</dna> interacts with factors , related to a <protein>PMA-induced AP-1</protein> and a <protein>PMA/A23187-induced NF-AT</protein> ."}
{"id": "1802", "text": "We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene .", "annotated_text": "We examined whether signal transducing components in <cell_type>T cells</cell_type> can activate transcription of the <dna>GM-CSF gene</dna> ."}
{"id": "1803", "text": "Cotransfection of NF-kappa B ( p50/p65 ) - or AP-1 ( c-Jun/c-Fos ) - expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter .", "annotated_text": "Cotransfection of <dna>NF-kappa B ( p50/p65 ) - or AP-1 ( c-Jun/c-Fos ) - expression vectors</dna> into <cell_line>Jurkat cells</cell_line> with a <dna>luciferase reporter</dna> containing the <dna>GM-CSF promoter</dna> did not stimulate transcription from the <dna>GM-CSF promoter</dna> ."}
{"id": "1804", "text": "In contrast , cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 ( AP-1/NF-AT ) .", "annotated_text": "In contrast , cotransfection with a combination of <protein>NF-kappa B</protein> and <protein>AP-1</protein> significantly augmented transcription from the <dna>GM-CSF promoter</dna> containing the <dna>GM-kappa B/GC-box</dna> and the <dna>CLE0</dna> ( <protein>AP-1/NF-AT</protein> ) ."}
{"id": "1805", "text": "Expression of a constitutively active calcineurin ( CN ) , a Ca2+/calmodulin-dependent protein phosphatase , potentiated by two fold the transcriptional activation by NF-kappa B /AP-1 .", "annotated_text": "Expression of a constitutively active <protein>calcineurin</protein> ( <protein>CN</protein> ) , a <protein>Ca2+/calmodulin-dependent protein phosphatase</protein> , potentiated by two fold the transcriptional activation by <protein>NF-kappa B</protein> <protein>/AP-1</protein> ."}
{"id": "1806", "text": "Both constitutively active forms of CN and protein kinase C ( PKC ) synergistically activated transcription from the GM-CSF promoter .", "annotated_text": "Both constitutively active forms of <protein>CN</protein> and <protein>protein kinase C</protein> ( <protein>PKC</protein> ) synergistically activated transcription from the <dna>GM-CSF promoter</dna> ."}
{"id": "1807", "text": "These results suggest that cooperation among NF-kappa B- , AP-1- and NF-AT-binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+- signaling pathways downstream of T cell activation .", "annotated_text": "These results suggest that cooperation among <dna>NF-kappa B- , AP-1- and NF-AT-binding sequences</dna> is required for induction of the <dna>GM-CSF gene</dna> through PKC- and Ca2+- signaling pathways downstream of T cell activation ."}
{"id": "1808", "text": "Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma .", "annotated_text": "<dna>Nonpituitary human prolactin gene</dna> transcription is independent of <protein>Pit-1</protein> and differentially controlled in <cell_type>lymphocytes</cell_type> and in endometrial stroma ."}
{"id": "1809", "text": "Expression of the human PRL ( hPRL ) gene in extrapituitary sites such as the uterus ( decidualized endometrial stroma and myometrium ) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases ( kb ) upstream of the pituitary-specific start site .", "annotated_text": "Expression of the <dna>human PRL ( hPRL ) gene</dna> in extrapituitary sites such as the uterus ( decidualized endometrial stroma and myometrium ) and cells of the <cell_type>hematopoietic lineage</cell_type> is directed by an <dna>alternative promoter</dna> which is located approximately <dna>6 kilobases ( kb ) upstream</dna> of the <dna>pituitary-specific start site</dna> ."}
{"id": "1810", "text": "In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression , we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid ( dPRL ) promoter .", "annotated_text": "In order to delineate the tissue-specific mechanisms governing the control of nonpituitary <dna>PRL gene</dna> expression , we have cloned and sequenced <dna>3 kb 5'-flanking DNA</dna> of the upstream <dna>decidual/lymphoid ( dPRL ) promoter</dna> ."}
{"id": "1811", "text": "Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor ( PR ) binding .", "annotated_text": "Based on sequence homology we identified two <dna>binding motifs</dna> for <protein>Pit-1</protein> and seven <dna>half-sites</dna> for <protein>glucocorticoid receptor/progesterone receptor</protein> ( <protein>PR</protein> ) binding ."}
{"id": "1812", "text": "We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators , since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression , and progesterone induces decidual transformation of the endometrial stroma , a differentiation process during which the decidual PRL gene is activated .", "annotated_text": "We focused our studies on the role of <protein>Pit-1</protein> and of <protein>PR</protein> as potential <protein>transcriptional regulators</protein> , since the <protein>POU domain protein</protein> <protein>Pit-1</protein> is essential in the control of pituitary <protein>PRL</protein> expression , and progesterone induces decidual transformation of the endometrial stroma , a differentiation process during which the decidual <dna>PRL gene</dna> is activated ."}
{"id": "1813", "text": "We demonstrate in a variety of cell types , including lymphocytes and endometrial stroma , that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA .", "annotated_text": "We demonstrate in a variety of cell types , including <cell_type>lymphocytes</cell_type> and endometrial stroma , that <protein>Pit-1</protein> is not involved in the regulation of <dna>dPRL promoter/reporter gene constructs</dna> carrying <dna>3 kb 5'-flanking DNA</dna> ."}
{"id": "1814", "text": "Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter .", "annotated_text": "Our experiments also show that activated <protein>PR</protein> does not confer direct transcriptional control on the <dna>dPRL promoter</dna> ."}
{"id": "1815", "text": "When we compared the activity of the transfected dPRL promoter in PRL-secreting and nonsecreting lymphoid cells , we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene .", "annotated_text": "When we compared the activity of the transfected <dna>dPRL promoter</dna> in <cell_type>PRL-secreting and nonsecreting lymphoid cells</cell_type> , we found that the <dna>3 kb 5'-flanking region</dna> of the <dna>dPRL promoter</dna> did not contain elements restricting expression to only those <cell_type>lymphocytes</cell_type> that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous <dna>PRL gene</dna> ."}
{"id": "1816", "text": "This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL , but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells .", "annotated_text": "This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the <dna>dPRL promoter</dna> in decidualized <cell_type>endometrial stromal cells</cell_type> actively secreting <protein>PRL</protein> , but did not allow transcription in undifferentiated <cell_type>non-PRL-secreting endometrial stromal cells</cell_type> ."}
{"id": "1817", "text": "Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP , in the absence of progesterone , suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression .", "annotated_text": "Activation of the <dna>dPRL promoter</dna> construct in these undifferentiated cells could however be induced by the addition of cAMP , in the absence of progesterone , suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual <dna>PRL gene</dna> expression ."}
{"id": "1818", "text": "Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells .", "annotated_text": "Signals and <protein>nuclear factors</protein> that regulate the expression of <dna>interleukin-4 and interleukin-5 genes</dna> in <cell_type>helper T cells</cell_type> ."}
{"id": "1819", "text": "Mouse thymoma line EL-4 cells produce cytokines such as interleukin ( IL ) -2 , IL-3 , IL-4 , IL-10 , and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate ( PMA ) .", "annotated_text": "<cell_line>Mouse thymoma line EL-4 cells</cell_line> produce <protein>cytokines</protein> such as <protein>interleukin ( IL ) -2</protein> , <protein>IL-3</protein> , <protein>IL-4</protein> , <protein>IL-10</protein> , and <protein>granulocyte-macrophage colony-stimulating factor</protein> in response to phorbol 12-myristate 13-acetate ( PMA ) ."}
{"id": "1820", "text": "EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone ; however , cAMP greatly augments PMA-dependent IL-5 production .", "annotated_text": "<cell_line>EL-4 cells</cell_line> also produce low levels of <protein>IL-5</protein> when stimulated by PMA alone ; however , cAMP greatly augments PMA-dependent <protein>IL-5</protein> production ."}
{"id": "1821", "text": "A transient transfection assay revealed that two signals , PMA and cAMP , are required for optimal activation of the IL-5 promoter .", "annotated_text": "A transient transfection assay revealed that two signals , PMA and cAMP , are required for optimal activation of the <dna>IL-5 promoter</dna> ."}
{"id": "1822", "text": "In contrast , cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene , as well as the transfected IL-2 promoter .", "annotated_text": "In contrast , cAMP almost completely inhibited the PMA-dependent activation of the <dna>endogenous IL-2 gene</dna> , as well as the transfected <dna>IL-2 promoter</dna> ."}
{"id": "1823", "text": "These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene .", "annotated_text": "These results indicate that the <dna>IL-5 gene</dna> is positively regulated by cAMP in a manner opposite to that for the <dna>IL-2 gene</dna> ."}
{"id": "1824", "text": "One of the nuclear factors ( NFs ) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell .", "annotated_text": "One of the <protein>nuclear factors</protein> ( <protein>NFs</protein> ) that regulates the response of the <dna>IL-5 promoter</dna> to cAMP and PMA has properties similar to <protein>NF</protein> for <cell_type>activated t cell</cell_type> ."}
{"id": "1825", "text": "The P sequence of the IL-4 gene , defined as a responsive element for PMA and calcium ionophore ( A23187 ) , shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites .", "annotated_text": "The <dna>P sequence</dna> of the <dna>IL-4 gene</dna> , defined as a <dna>responsive element</dna> for PMA and calcium ionophore ( A23187 ) , shares sequence similarity with the <dna>NF kappa B and the NF-activated T cell binding sites</dna> ."}
{"id": "1826", "text": "We attempted to determine whether NF ( P ) , a nuclear factor specific for the P sequence , is related to NF-kappa B and nuclear factor for activated T cell ( NF-AT ) .", "annotated_text": "We attempted to determine whether <protein>NF ( P )</protein> , a nuclear factor specific for the <dna>P sequence</dna> , is related to <protein>NF-kappa B</protein> and <protein>nuclear factor for activated T cell</protein> ( <protein>NF-AT</protein> ) ."}
{"id": "1827", "text": "In electromobility shift assays both NF-kappa B ( P65 or P65/P50 heterodimer ) and NF-AT bound to the P sequence .", "annotated_text": "In electromobility shift assays both <protein>NF-kappa B</protein> ( <protein>P65</protein> or <protein>P65/P50 heterodimer</protein> ) and <protein>NF-AT</protein> bound to the <dna>P sequence</dna> ."}
{"id": "1828", "text": "However , sequence specificity of NF-AT was more similar to that of NF ( P ) , and only a small amount of P65 was detected in NF ( P ) .", "annotated_text": "However , sequence specificity of <protein>NF-AT</protein> was more similar to that of <protein>NF ( P )</protein> , and only a small amount of <protein>P65</protein> was detected in <protein>NF ( P )</protein> ."}
{"id": "1829", "text": "These results indicate that a component or components of NF-AT have the potential to reconstitute NF ( P ) , whereas NF-kappa B alone does not account for NF ( P ) in Jurkat crude extract .", "annotated_text": "These results indicate that a component or components of <protein>NF-AT</protein> have the potential to reconstitute <protein>NF ( P )</protein> , whereas <protein>NF-kappa B</protein> alone does not account for <protein>NF ( P )</protein> in Jurkat crude extract ."}
{"id": "1830", "text": "Taken together , these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes .", "annotated_text": "Taken together , these results suggest that <protein>NF-AT-like factors</protein> are involved in the regulation of <dna>IL-4 and IL-5 genes</dna> ."}
{"id": "1831", "text": "Solution structure of a POU-specific homeodomain : 3D-NMR studies of human B-cell transcription factor Oct-2 .", "annotated_text": "Solution structure of a <protein>POU-specific homeodomain</protein> : 3D-NMR studies of human <protein>B-cell transcription factor</protein> <protein>Oct-2</protein> ."}
{"id": "1832", "text": "The POU DNA-binding motif defines a conserved family of eukaryotic transcription factors involved in regulation of gene expression .", "annotated_text": "The <protein>POU DNA-binding motif</protein> defines a conserved family of <protein>eukaryotic transcription factors</protein> involved in regulation of gene expression ."}
{"id": "1833", "text": "This bipartite motif consists of an N-terminal POU-specific domain ( POUs ) , a flexible linker , and a C-terminal POU-specific homeodomain ( POUHD ) .", "annotated_text": "This <protein>bipartite motif</protein> consists of an <protein>N-terminal POU-specific domain</protein> ( <protein>POUs</protein> ) , a <protein>flexible linker</protein> , and a <protein>C-terminal POU-specific homeodomain</protein> ( <protein>POUHD</protein> ) ."}
{"id": "1834", "text": "Here we describe the solution structure of a POU-specific homeodomain .", "annotated_text": "Here we describe the solution structure of a <protein>POU-specific homeodomain</protein> ."}
{"id": "1835", "text": "An NMR model is obtained from Oct-2 , a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes .", "annotated_text": "An NMR model is obtained from <protein>Oct-2</protein> , a <protein>human B-cell specific transcription factor</protein> which participates in the regulation of <dna>immunoglobulin genes</dna> ."}
{"id": "1836", "text": "A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance ( 3D-NMR ) spectroscopy .", "annotated_text": "A fragment of <protein>Oct-2</protein> containing <protein>POUHD</protein> and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance ( 3D-NMR ) spectroscopy ."}
{"id": "1837", "text": "Complete 1H and 15N resonance assignment of the POUHD moiety is presented .", "annotated_text": "Complete 1H and 15N resonance assignment of the <protein>POUHD moiety</protein> is presented ."}
{"id": "1838", "text": "The POUHD solution structure , as calculated by distance geometry and simulated annealing ( DG/SA ) , is similar to that of canonical homeodomains .", "annotated_text": "The <protein>POUHD</protein> solution structure , as calculated by distance geometry and simulated annealing ( DG/SA ) , is similar to that of <protein>canonical homeodomains</protein> ."}
{"id": "1839", "text": "A salient difference between solution and crystal structures is observed in the C-terminal segment of alpha-helix 3 ( the HTH recognition helix ) , which is not well ordered in solution .", "annotated_text": "A salient difference between solution and crystal structures is observed in the <protein>C-terminal segment</protein> of <protein>alpha-helix 3</protein> ( the <protein>HTH recognition helix</protein> ) , which is not well ordered in solution ."}
{"id": "1840", "text": "Because this segment presumably folds upon specific DNA binding , its flexibility in solution may reduce the intrinsic DNA affinity of POUHD in the absence of POUs .", "annotated_text": "Because this segment presumably folds upon specific DNA binding , its flexibility in solution may reduce the intrinsic DNA affinity of <protein>POUHD</protein> in the absence of <protein>POUs</protein> ."}
{"id": "1841", "text": "NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line .", "annotated_text": "NF-kappa B-dependent and -independent pathways of HIV activation in a <cell_line>chronically infected T cell line</cell_line> ."}
{"id": "1842", "text": "J delta K cells were isolated as a chronically infected survivor cell line , following infection of Jurkat CD4+ T cells with dl-NF , a mutated strain of human immunodeficiency virus type 1 ( HIV-1 ) containing a deletion of the long terminal repeat ( LTR ) NF-kappa B sites .", "annotated_text": "<cell_line>J delta K cells</cell_line> were isolated as a <cell_line>chronically infected survivor cell line</cell_line> , following infection of <cell_line>Jurkat CD4+ T cells</cell_line> with dl-NF , a mutated strain of human immunodeficiency virus type 1 ( HIV-1 ) containing a deletion of the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) <protein>NF-kappa B</protein> sites ."}
{"id": "1843", "text": "J delta K cells exhibited very low levels of constitutive HIV production .", "annotated_text": "<cell_line>J delta K cells</cell_line> exhibited very low levels of constitutive HIV production ."}
{"id": "1844", "text": "HIV-1 expression was activated from J delta K cells by treatment with phorbol myristate acetate ( PMA ) , sodium butyrate ( NaB ) , or hexamethylene bisacetamide ( HMBA ) , but not tumor necrosis factor alpha ( TNF-alpha ) , confirming the role of NF-kappa B in mediating TNF-alpha induction of HIV transcription .", "annotated_text": "HIV-1 expression was activated from <cell_line>J delta K cells</cell_line> by treatment with phorbol myristate acetate ( PMA ) , sodium butyrate ( NaB ) , or hexamethylene bisacetamide ( HMBA ) , but not <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) , confirming the role of <protein>NF-kappa B</protein> in mediating <protein>TNF-alpha</protein> induction of HIV transcription ."}
{"id": "1845", "text": "The strong induction of HIV expression by NaB or HMBA in J delta K cells clearly demonstrates the existence of NF-kappa B -independent mechanisms of HIV activation in chronically infected cells .", "annotated_text": "The strong induction of HIV expression by NaB or HMBA in <cell_line>J delta K cells</cell_line> clearly demonstrates the existence of <protein>NF-kappa B</protein> -independent mechanisms of HIV activation in <cell_type>chronically infected cells</cell_type> ."}
{"id": "1846", "text": "J delta K cells may provide a useful model for characterizing NF-kappa B -independent transcriptional activation of the HIV LTR .", "annotated_text": "<cell_line>J delta K cells</cell_line> may provide a useful model for characterizing <protein>NF-kappa B</protein> -independent transcriptional activation of the <dna>HIV LTR</dna> ."}
{"id": "1847", "text": "JNK is involved in signal integration during costimulation of T lymphocytes .", "annotated_text": "<protein>JNK</protein> is involved in signal integration during costimulation of <cell_type>T lymphocytes</cell_type> ."}
{"id": "1848", "text": "T lymphocyte activation and interleukin-2 ( IL-2 ) production require at least two signals , generated by phorbol ester ( TPA ) and Ca2+ ionophore or costimulation of the T cell receptor ( TCR ) and the CD28 auxiliary receptor .", "annotated_text": "<cell_type>T lymphocyte</cell_type> activation and <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) production require at least two signals , generated by phorbol ester ( TPA ) and Ca2+ ionophore or costimulation of the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) and the <protein>CD28 auxiliary receptor</protein> ."}
{"id": "1849", "text": "We investigated how these stimuli affect mitogen activated protein ( MAP ) kinases .", "annotated_text": "We investigated how these stimuli affect <protein>mitogen activated protein ( MAP ) kinases</protein> ."}
{"id": "1850", "text": "Full activation of the MAP kinases that phosphorylate the Jun activation domain , JNK1 and JNK2 , required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28 .", "annotated_text": "Full activation of the <protein>MAP kinases</protein> that phosphorylate the <protein>Jun activation domain</protein> , <protein>JNK1</protein> and <protein>JNK2</protein> , required costimulation of <cell_type>T cells</cell_type> with either TPA and Ca2+ ionophore or antibodies to <protein>TCR</protein> and <protein>CD28</protein> ."}
{"id": "1851", "text": "Alone , each stimulus resulted in little or no activation .", "annotated_text": "Alone , each stimulus resulted in little or no activation ."}
{"id": "1852", "text": "Similar to its effect on IL-2 induction , cyclosporin A ( CsA ) inhibited the synergistic activation of JNK , and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation .", "annotated_text": "Similar to its effect on <protein>IL-2</protein> induction , cyclosporin A ( CsA ) inhibited the synergistic activation of <protein>JNK</protein> , and a competitive inhibitor of <protein>Jun</protein> phosphorylation by <protein>JNK</protein> inhibited <dna>IL-2 promoter</dna> activation ."}
{"id": "1853", "text": "By contrast , the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+ , CD28 , or CsA .", "annotated_text": "By contrast , the <protein>MAP kinases</protein> <protein>ERK1</protein> and <protein>ERK2</protein> were fully activated by TPA or <protein>TCR</protein> stimulation and were not affected by Ca2+ , CD28 , or CsA ."}
{"id": "1854", "text": "Hence , integration of signals that lead to T cell activation occurs at the level of JNK activation .", "annotated_text": "Hence , integration of signals that lead to T cell activation occurs at the level of <protein>JNK</protein> activation ."}
{"id": "1855", "text": "Inhibition of rat splenocyte proliferation with methylprednisolone : in vivo effect of liposomal formulation .", "annotated_text": "Inhibition of <cell_type>rat splenocyte</cell_type> proliferation with methylprednisolone : in vivo effect of liposomal formulation ."}
{"id": "1856", "text": "The effect of a liposomal formulation of methylprednisolone ( MPL ) on the inhibition of lymphocyte proliferation in spleen cells was investigated following IV dosing in rats .", "annotated_text": "The effect of a liposomal formulation of methylprednisolone ( MPL ) on the inhibition of lymphocyte proliferation in <cell_type>spleen cells</cell_type> was investigated following IV dosing in rats ."}
{"id": "1857", "text": "Liposomes do not alter the suppressive action of MPL when placed in lymphocyte culture .", "annotated_text": "Liposomes do not alter the suppressive action of MPL when placed in <cell_line>lymphocyte culture</cell_line> ."}
{"id": "1858", "text": "Rat splenocytes were found to have greater sensitivity to MPL ( EC50 = 7.9 nM ) than do human peripheral blood lymphocytes ( EC50 = 28 nM ) .", "annotated_text": "<cell_type>Rat splenocytes</cell_type> were found to have greater sensitivity to MPL ( EC50 = 7.9 nM ) than do <cell_type>human peripheral blood lymphocytes</cell_type> ( EC50 = 28 nM ) ."}
{"id": "1859", "text": "In vivo studies in rats utilized 2 mg/kg IV bolus doses of liposomal MPL compared to drug in solution .", "annotated_text": "In vivo studies in rats utilized 2 mg/kg IV bolus doses of liposomal MPL compared to drug in solution ."}
{"id": "1860", "text": "Animals were sacrificed at various times post-dosing until 120 h , spleen was excised and , after incubation of lymphocytes with PHA , splenocyte blastogenic responses were assessed by measuring cellular incorporation of 3H-thymidine .", "annotated_text": "Animals were sacrificed at various times post-dosing until 120 h , spleen was excised and , after incubation of <cell_type>lymphocytes</cell_type> with <protein>PHA</protein> , splenocyte blastogenic responses were assessed by measuring cellular incorporation of 3H-thymidine ."}
{"id": "1861", "text": "The suppressive effect of liposomal MPL in comparison with free drug was significantly prolonged ( > 120 h vs < 18 h ) .", "annotated_text": "The suppressive effect of liposomal MPL in comparison with free drug was significantly prolonged ( > 120 h vs < 18 h ) ."}
{"id": "1862", "text": "Inhibition effects versus time were described by a pharmacodynamic model using MPL concentrations in plasma as an input function .", "annotated_text": "Inhibition effects versus time were described by a pharmacodynamic model using MPL concentrations in <cell_type>plasma</cell_type> as an input function ."}
{"id": "1863", "text": "A nonlinear relationship was found between suppression of splenocyte proliferation and the concentration of bound glucocorticoid receptors in spleen .", "annotated_text": "A nonlinear relationship was found between suppression of <cell_type>splenocyte</cell_type> proliferation and the concentration of bound <protein>glucocorticoid receptors</protein> in spleen ."}
{"id": "1864", "text": "Only partial receptor occupancy accompanied complete lymphocyte suppression .", "annotated_text": "Only partial receptor occupancy accompanied complete lymphocyte suppression ."}
{"id": "1865", "text": "The suppression of endogenous corticosterone in plasma for both treatments was similar with values from L-MPL rats returning to baseline after 24 h .", "annotated_text": "The suppression of endogenous corticosterone in <cell_type>plasma</cell_type> for both treatments was similar with values from L-MPL rats returning to baseline after 24 h ."}
{"id": "1866", "text": "These results demonstrate enhanced efficacy of local immunosuppression by targeting spleen with liposomal MPL .", "annotated_text": "These results demonstrate enhanced efficacy of local immunosuppression by targeting spleen with liposomal MPL ."}
{"id": "1867", "text": "Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits .", "annotated_text": "Function of <dna>NF-kappa B/Rel binding sites</dna> in the <dna>major histocompatibility complex class II invariant chain promoter</dna> is dependent on cell-specific binding of different <protein>NF-kappa B/Rel subunits</protein> ."}
{"id": "1868", "text": "The promoter of the human major histocompatibility complex class II-associated invariant-chain gene ( Ii ) contains two NF-kappa B/Rel binding sites located at -109 to -118 ( Ii kappa B-1 ) and -163 to -172 ( Ii kappa B-2 ) from the transcription start site .", "annotated_text": "The <dna>promoter</dna> of the human major <dna>histocompatibility complex class II-associated invariant-chain gene</dna> ( <dna>Ii</dna> ) contains two <dna>NF-kappa B/Rel binding sites</dna> located at <dna>-109 to -118</dna> ( <dna>Ii kappa B-1</dna> ) and <dna>-163 to -172</dna> ( <dna>Ii kappa B-2</dna> ) from the transcription start site ."}
{"id": "1869", "text": "We report here that the differential function of each of these NF-kappa B/Rel sites in several distinct cell types depends on cell-specific binding of NF-kappa B/Rel transcription factors .", "annotated_text": "We report here that the differential function of each of these <dna>NF-kappa B/Rel sites</dna> in several distinct cell types depends on cell-specific binding of <protein>NF-kappa B/Rel transcription factors</protein> ."}
{"id": "1870", "text": "Ii kappa B-1 is a positive regulatory element in B-cell lines and in the Ii-expressing T-cell line , H9 , but acts as a negative regulatory element in myelomonocytic and glia cell lines .", "annotated_text": "<dna>Ii kappa B-1</dna> is a <dna>positive regulatory element</dna> in <cell_line>B-cell lines</cell_line> and in the <cell_line>Ii-expressing T-cell line</cell_line> , <cell_line>H9</cell_line> , but acts as a <dna>negative regulatory element</dna> in <cell_line>myelomonocytic and glia cell lines</cell_line> ."}
{"id": "1871", "text": "In vivo protein-DNA contacts are detectable at Ii kappa B-1 in cell lines in which this site is functional as either a positive or negative regulator .", "annotated_text": "In vivo protein-DNA contacts are detectable at <dna>Ii kappa B-1</dna> in <cell_line>cell lines</cell_line> in which this site is functional as either a <dna>positive or negative regulator</dna> ."}
{"id": "1872", "text": "Electrophoretic mobility supershift assays determine that members of the NF-kappa B/Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50 , p52 , p65 , and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation .", "annotated_text": "Electrophoretic mobility supershift assays determine that members of the <protein>NF-kappa B/Rel family</protein> of <protein>transcription factors</protein> can bind to this site in vitro and that <protein>DNA-binding complexes</protein> that contain <protein>p50</protein> , <protein>p52</protein> , <protein>p65</protein> , and <protein>cRel</protein> correlate with positive regulation whereas the presence of <protein>p50</protein> correlates with negative regulation ."}
{"id": "1873", "text": "Ii kappa B-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells , myelomonocytic , and glial cell lines .", "annotated_text": "<dna>Ii kappa B-2</dna> is a site of positive regulation in <cell_line>B-cell lines</cell_line> and a site of negative regulation in <cell_line>H9 T cells</cell_line> , <cell_line>myelomonocytic , and glial cell lines</cell_line> ."}
{"id": "1874", "text": "In vivo occupancy of this site is observed only in the H9 T-cell line .", "annotated_text": "In vivo occupancy of this site is observed only in the <cell_line>H9 T-cell line</cell_line> ."}
{"id": "1875", "text": "Again , in vitro supershift studies indicate that the presence of p50 , p52 , p65 , and cRel correlates with positive function whereas the presence of only p50 and p52 correlates with negative function .", "annotated_text": "Again , in vitro supershift studies indicate that the presence of <protein>p50</protein> , <protein>p52</protein> , <protein>p65</protein> , and <protein>cRel</protein> correlates with positive function whereas the presence of only <protein>p50</protein> and <protein>p52</protein> correlates with negative function ."}
{"id": "1876", "text": "This differential binding of specific NF-kappa B/Rel subunits is likely to mediate the disparate functions of these two NF-kappa B/Rel binding sites .", "annotated_text": "This differential binding of specific <protein>NF-kappa B/Rel subunits</protein> is likely to mediate the disparate functions of these two <dna>NF-kappa B/Rel binding sites</dna> ."}
{"id": "1877", "text": "Epstein-Barr virus ( EBV ) replicative gene expression in tumour cells of AIDS-related non-Hodgkin 's lymphoma in relation to CD4 cell number and antibody titres to EBV .", "annotated_text": "Epstein-Barr virus ( EBV ) replicative gene expression in <cell_type>tumour cells</cell_type> of AIDS-related non-Hodgkin 's lymphoma in relation to <protein>CD4</protein> cell number and antibody titres to EBV ."}
{"id": "1878", "text": "OBJECTIVE : To determine whether activation of Epstein-Barr virus ( EBV ) replication in tumour cells of AIDS-related non-Hodgkin 's lymphoma ( ARNHL ) is correlated with CD4+ cell counts and influences antibody response to EBV [ anti-Z Epstein-Barr replicative activator ( ZEBRA ) , anti-early antigen ( EA ) , anti-viral capsid antigen ( VCA ) ] .", "annotated_text": "OBJECTIVE : To determine whether activation of Epstein-Barr virus ( EBV ) replication in <cell_type>tumour cells</cell_type> of AIDS-related non-Hodgkin 's lymphoma ( ARNHL ) is correlated with <protein>CD4+</protein> cell counts and influences antibody response to EBV [ <protein>anti-Z Epstein-Barr replicative activator</protein> ( <protein>ZEBRA</protein> ) , <protein>anti-early antigen</protein> ( <protein>EA</protein> ) , <protein>anti-viral capsid antigen</protein> ( <protein>VCA</protein> ) ] ."}
{"id": "1879", "text": "DESIGN : Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology ( including anti- ZEBRA activity ) in sera from the same patients .", "annotated_text": "DESIGN : Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with <protein>CD4+</protein> cell counts and results of EBV serology ( including anti- <protein>ZEBRA</protein> activity ) in sera from the same patients ."}
{"id": "1880", "text": "METHODS : Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [ Epstein-Barr early region ( EBER ) RNA-positive ] .", "annotated_text": "METHODS : Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [ Epstein-Barr early region ( EBER ) RNA-positive ] ."}
{"id": "1881", "text": "Immunohistochemistry was performed with anti-ZEBRA , anti-EA-restricted , anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples .", "annotated_text": "Immunohistochemistry was performed with <protein>anti-ZEBRA</protein> , <protein>anti-EA-restricted , anti-VCA antibodies</protein> and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples ."}
{"id": "1882", "text": "Results were statistically correlated with those of CD4+ cell counts ( 17 out of 17 ) and with anti-EBV antibody titres ( 13 out of 17 ) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens .", "annotated_text": "Results were statistically correlated with those of <protein>CD4+</protein> cell counts ( 17 out of 17 ) and with anti-EBV antibody titres ( 13 out of 17 ) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using <protein>recombinant ZEBRA protein</protein> and synthetic peptides as <protein>antigens</protein> ."}
{"id": "1883", "text": "RESULTS : BZLF1 ( ZEBRA ) or early gene products ( EA-R and EA-D/BHLF1/NotI ) were detected in a small proportion ( < 0.01-5 % ) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization .", "annotated_text": "RESULTS : <protein>BZLF1</protein> ( <protein>ZEBRA</protein> ) or <protein>early gene products</protein> ( <protein>EA-R</protein> and <protein>EA-D/BHLF1/NotI</protein> ) were detected in a small proportion ( < 0.01-5 % ) of <cell_type>tumour cells</cell_type> in eight of these 17 cases by immunohistochemistry and in situ hybridization ."}
{"id": "1884", "text": "Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts ( P > 0.05 ) or anti-EBV antibody titres ( P > 0.05 ) .", "annotated_text": "Demonstration of replicative gene expression did not correlate with either low <protein>CD4+</protein> cell counts ( P > 0.05 ) or anti-EBV antibody titres ( P > 0.05 ) ."}
{"id": "1885", "text": "Anti- ZEBRA activity was not significantly increased in patients affected with ARNHL , the cells of which expressed replicative gene products ( P > 0.05 ) .", "annotated_text": "Anti- <protein>ZEBRA</protein> activity was not significantly increased in patients affected with ARNHL , the cells of which expressed replicative gene products ( P > 0.05 ) ."}
{"id": "1886", "text": "CONCLUSION : The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL .", "annotated_text": "CONCLUSION : The degree of immunodeficiency does not clearly enhance replicative gene expression in <cell_type>tumour cells</cell_type> of ARNHL ."}
{"id": "1887", "text": "EBV serology , including anti- ZEBRA activity , is not a reliable tool for predicting the occurrence of such proliferations .", "annotated_text": "EBV serology , including anti- <protein>ZEBRA</protein> activity , is not a reliable tool for predicting the occurrence of such proliferations ."}
{"id": "1888", "text": "Effects of prostaglandin E2 on Th0-type human T cell clones : modulation of functions of nuclear proteins involved in cytokine production .", "annotated_text": "Effects of <protein>prostaglandin E2</protein> on <cell_line>Th0-type human T cell clones</cell_line> : modulation of functions of <protein>nuclear proteins</protein> involved in <protein>cytokine</protein> production ."}
{"id": "1889", "text": "The effects of prostaglandin E2 ( PGE2 ) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated .", "annotated_text": "The effects of <protein>prostaglandin E2</protein> ( <protein>PGE2</protein> ) on <protein>cytokine</protein> production and proliferation of the <cell_line>CD4+ human helper T cell clone SP-B21</cell_line> were investigated ."}
{"id": "1890", "text": "In cells stimulated with anti-CD3 mAb , PGE2 inhibited cell proliferation and the production of all the cytokines examined .", "annotated_text": "In cells stimulated with <protein>anti-CD3 mAb</protein> , <protein>PGE2</protein> inhibited cell proliferation and the production of all the <protein>cytokines</protein> examined ."}
{"id": "1891", "text": "Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5 , but not that of other cytokines .", "annotated_text": "Addition of <protein>rIL-2</protein> fully restored the proliferative response and partially restored the production of <protein>IL-4</protein> and <protein>IL-5</protein> , but not that of other <protein>cytokines</protein> ."}
{"id": "1892", "text": "In contrast , in cells stimulated with phorbol myristate acetate ( PMA ) /A23187 , PGE2 enhanced the production of IL-4 and IL-5 , and only partially inhibited the production of other cytokines .", "annotated_text": "In contrast , in cells stimulated with phorbol myristate acetate ( PMA ) /A23187 , <protein>PGE2</protein> enhanced the production of <protein>IL-4</protein> and <protein>IL-5</protein> , and only partially inhibited the production of other <protein>cytokines</protein> ."}
{"id": "1893", "text": "Therefore , the effects of PGE2 vary depending on the mode of T cell activation , and the IL-4 and IL-5 are regulated differently from other cytokines .", "annotated_text": "Therefore , the effects of <protein>PGE2</protein> vary depending on the mode of T cell activation , and the <protein>IL-4</protein> and <protein>IL-5</protein> are regulated differently from other <protein>cytokines</protein> ."}
{"id": "1894", "text": "In a mobility shift assay , only the NF-kappa B ( p50/p50 ) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells .", "annotated_text": "In a mobility shift assay , only the <protein>NF-kappa B ( p50/p50 ) homodimer</protein> was observed in a complex formed with the <dna>kappa B sequence</dna> in unstimulated SP-B21 cells ."}
{"id": "1895", "text": "When cells were stimulated with anti-CD3 mAb or PMA/A23187 , a complex formation of NF-kappa B ( p50 /p65 ) heterodimer with the kappa B sequence was induced .", "annotated_text": "When cells were stimulated with <protein>anti-CD3 mAb</protein> or PMA/A23187 , a complex formation of <protein>NF-kappa B</protein> ( <protein>p50</protein> <protein>/p65</protein> ) heterodimer with the <dna>kappa B sequence</dna> was induced ."}
{"id": "1896", "text": "Interestingly , PGE2 or di-butyryl ( Bt2 ) cAMP abolished the binding of NF-kappa B ( p50/p65 ) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187 .", "annotated_text": "Interestingly , <protein>PGE2</protein> or di-butyryl ( Bt2 ) cAMP abolished the binding of <protein>NF-kappa B ( p50/p65 ) heterodimer</protein> to the <dna>kappa B sequence</dna> in cells stimulated with <protein>anti-CD3 mAb</protein> but not with PMA/A23187 ."}
{"id": "1897", "text": "Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C .", "annotated_text": "Our results suggest that the target of <protein>PGE2</protein> action is a component in the signal transduction pathway leading to the activation of <protein>protein kinase C</protein> ."}
{"id": "1898", "text": "However , the inhibition of the T cell activation signals by PGE2 is selective .", "annotated_text": "However , the inhibition of the T cell activation signals by <protein>PGE2</protein> is selective ."}
{"id": "1899", "text": "PGE2 enhanced the complex formation with NF-AT , AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation .", "annotated_text": "<protein>PGE2</protein> enhanced the complex formation with <dna>NF-AT , AP-1 and CLE0 sequences</dna> when the cells were activated by either <protein>anti-CD3 mAb</protein> or PMA/A23187 stimulation ."}
{"id": "1900", "text": "It seems therefore that PGE2 , by elevating cAMP levels , interferes with the activation pathway for NF-kappa B but not for NF-AT , AP-1 or CLE0 binding protein .", "annotated_text": "It seems therefore that <protein>PGE2</protein> , by elevating cAMP levels , interferes with the activation pathway for <protein>NF-kappa B</protein> but not for <protein>NF-AT</protein> , <protein>AP-1</protein> or <protein>CLE0 binding protein</protein> ."}
{"id": "1901", "text": "Characterization of NF ( P ) , the nuclear factor that interacts with the regulatory P sequence ( 5'-CGAAAATTTCC-3 ' ) of the human interleukin-4 gene : relationship to NF-kappa B and NF-AT .", "annotated_text": "Characterization of <protein>NF ( P )</protein> , the <protein>nuclear factor</protein> that interacts with the regulatory <dna>P sequence</dna> ( 5'-CGAAAATTTCC-3 ' ) of the <dna>human interleukin-4 gene</dna> : relationship to <protein>NF-kappa B</protein> and <protein>NF-AT</protein> ."}
{"id": "1902", "text": "The P sequence of the human interleukin-4 ( IL-4 ) gene , which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore ( A23187 ) in Jurkat T cells , shares sequence similarity with the NF-kappa B and the NF-AT binding sites .", "annotated_text": "The <dna>P sequence</dna> of the <dna>human interleukin-4 ( IL-4 ) gene</dna> , which was defined as a <dna>responsive element</dna> for phorbol 12-myristate 13-acetate and calcium ionophore ( A23187 ) in <cell_line>Jurkat T cells</cell_line> , shares sequence similarity with the <dna>NF-kappa B and the NF-AT binding sites</dna> ."}
{"id": "1903", "text": "We examined whether NF ( P ) , a nuclear factor specific for the P sequence , is related to NF-kappa B and NF-AT .", "annotated_text": "We examined whether <protein>NF ( P )</protein> , a <protein>nuclear factor</protein> specific for the <dna>P sequence</dna> , is related to <protein>NF-kappa B</protein> and <protein>NF-AT</protein> ."}
{"id": "1904", "text": "NF-kappa B ( P65 or P65/P50 heterodimer ) bound to the P sequence in electrophoretic mobility shift assays ( EMSA ) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells .", "annotated_text": "<protein>NF-kappa B</protein> ( <protein>P65</protein> or <protein>P65/P50 heterodimer</protein> ) bound to the <dna>P sequence</dna> in electrophoretic mobility shift assays ( EMSA ) and activated transcription through the <dna>P sequence</dna> when <dna>expression plasmids</dna> were cotransfected with <dna>P sequence-driven reporter plasmids</dna> in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "1905", "text": "In EMSAs , NF ( P ) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence .", "annotated_text": "In EMSAs , <protein>NF ( P )</protein> binding was inhibited by the <dna>unlabeled NF-AT binding site</dna> but not by the <dna>unlabeled AP1 binding site</dna> and <protein>purified NF-AT</protein> contained an activity that bound to the <dna>P sequence</dna> ."}
{"id": "1906", "text": "Both mobility shift and sequence specificity of NF-AT were similar to those of NF ( P ) and only a small amount of P65 was detected in NF ( P ) in crude nuclear extracts .", "annotated_text": "Both mobility shift and sequence specificity of <protein>NF-AT</protein> were similar to those of <protein>NF ( P )</protein> and only a small amount of <protein>P65</protein> was detected in <protein>NF ( P )</protein> in crude nuclear extracts ."}
{"id": "1907", "text": "These results indicate that the component ( s ) of NF-AT has the potential to reconstitute NF ( P ) whereas NF-kappa B alone can not account for NF ( P ) in crude extracts .", "annotated_text": "These results indicate that the component ( s ) of <protein>NF-AT</protein> has the potential to reconstitute <protein>NF ( P )</protein> whereas <protein>NF-kappa B</protein> alone can not account for <protein>NF ( P )</protein> in crude extracts ."}
{"id": "1908", "text": "Unlike NF-AT , NF ( P ) does not contain AP1 as its DNA binding component .", "annotated_text": "Unlike <protein>NF-AT</protein> , <protein>NF ( P )</protein> does not contain <protein>AP1</protein> as its <protein>DNA binding component</protein> ."}
{"id": "1909", "text": "Activation of early growth response 1 gene transcription and pp90rsk during induction of monocytic differentiation .", "annotated_text": "Activation of <dna>early growth response 1 gene</dna> transcription and <protein>pp90rsk</protein> during induction of monocytic differentiation ."}
{"id": "1910", "text": "The present work has studied mechanisms responsible for induction of early growth response 1 ( EGR-1 ) gene expression during monocytic differentiation of U-937 myeloid leukemia cells .", "annotated_text": "The present work has studied mechanisms responsible for induction of <dna>early growth response 1 ( EGR-1 ) gene</dna> expression during monocytic differentiation of <cell_line>U-937 myeloid leukemia cells</cell_line> ."}
{"id": "1911", "text": "Differentiation of U-937 cells with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , an activator of the serine/threonine protein kinase C , was associated with transcriptional activation of EGR-1 promoter-reporter constructs .", "annotated_text": "Differentiation of <cell_line>U-937 cells</cell_line> with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , an activator of the <protein>serine/threonine protein kinase C</protein> , was associated with transcriptional activation of <dna>EGR-1 promoter-reporter constructs</dna> ."}
{"id": "1912", "text": "The EGR-1 promoter contains six CC ( A/T ) 6GG ( CArG ) motifs .", "annotated_text": "The <dna>EGR-1 promoter</dna> contains six CC ( A/T ) 6GG ( CArG ) motifs ."}
{"id": "1913", "text": "The two 5'-most distal CArG sequences conferred TPA inducibility .", "annotated_text": "The two <dna>5'-most distal CArG sequences</dna> conferred TPA inducibility ."}
{"id": "1914", "text": "In contrast , there was little effect of TPA on EGR-1 transcription in a TPA-resistant U-937 cell variant , designated TUR .", "annotated_text": "In contrast , there was little effect of TPA on <dna>EGR-1</dna> transcription in a <cell_line>TPA-resistant U-937 cell variant</cell_line> , designated <cell_line>TUR</cell_line> ."}
{"id": "1915", "text": "Treatment of both U-937 and TUR cells with okadaic acid , an inhibitor of serine/threonine protein phosphatases 1 and 2A , was associated with induction of monocytic differentiation and EGR-1 transcription through the 5'-most CArG element .", "annotated_text": "Treatment of both <cell_line>U-937</cell_line> and <cell_line>TUR cells</cell_line> with okadaic acid , an inhibitor of <protein>serine/threonine protein phosphatases 1 and 2A</protein> , was associated with induction of monocytic differentiation and <dna>EGR-1</dna> transcription through the <dna>5'-most CArG element</dna> ."}
{"id": "1916", "text": "Since these findings supported the involvement of serine/threonine protein phosphorylation in the regulation of EGR-1 expression , we studied activation of the 40S ribosomal protein S6 serine/threonine kinases , pp70S6K and pp90rsk .", "annotated_text": "Since these findings supported the involvement of serine/threonine protein phosphorylation in the regulation of <dna>EGR-1</dna> expression , we studied activation of the <protein>40S ribosomal protein S6 serine/threonine kinases</protein> , <protein>pp70S6K</protein> and <protein>pp90rsk</protein> ."}
{"id": "1917", "text": "Although both kinases participate in regulating cell growth , there was no detectable activation of pp70S6K during TPA- or okadaic acid-induced monocytic differentiation .", "annotated_text": "Although both kinases participate in regulating cell growth , there was no detectable activation of <protein>pp70S6K</protein> during TPA- or okadaic acid-induced monocytic differentiation ."}
{"id": "1918", "text": "Moreover , rapamycin , an inhibitor of pp70S6K activation , had no effect on induction of EGR-1 expression .", "annotated_text": "Moreover , rapamycin , an inhibitor of <protein>pp70S6K</protein> activation , had no effect on induction of <dna>EGR-1</dna> expression ."}
{"id": "1919", "text": "In contrast , analysis of pp90rsk activity by phosphorylation of a peptide derived from S6 protein demonstrated stimulation of this kinase in TPA-treated U-937 , and not TUR , cells .", "annotated_text": "In contrast , analysis of <protein>pp90rsk</protein> activity by phosphorylation of a peptide derived from <protein>S6 protein</protein> demonstrated stimulation of this <protein>kinase</protein> in <cell_line>TPA-treated U-937 , and not TUR , cells</cell_line> ."}
{"id": "1920", "text": "Okadaic acid treatment of both cell types was associated with activation of pp90rsk .", "annotated_text": "Okadaic acid treatment of both cell types was associated with activation of <protein>pp90rsk</protein> ."}
{"id": "1921", "text": "Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals .", "annotated_text": "Antioxidants inhibit <cell_type>monocyte</cell_type> adhesion by suppressing <protein>nuclear factor-kappa B</protein> mobilization and induction of <protein>vascular cell adhesion molecule-1</protein> in <cell_type>endothelial cells</cell_type> stimulated to generate radicals ."}
{"id": "1922", "text": "Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha ( TNF ) is due to induction of surface receptors , such as vascular cell adhesion molecule-1 ( VCAM-1 ) .", "annotated_text": "Cell adhesion to <cell_type>endothelial cells</cell_type> <protein>stimulated by tumor necrosis factor-alpha</protein> ( <protein>TNF</protein> ) is due to induction of <protein>surface receptors</protein> , such as <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) ."}
{"id": "1923", "text": "The antioxidant pyrrolidine dithiocarbamate ( PDTC ) specifically inhibits activation of nuclear factor-kappa B ( NF-kappa B ) .", "annotated_text": "The antioxidant pyrrolidine dithiocarbamate ( PDTC ) specifically inhibits activation of <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) ."}
{"id": "1924", "text": "Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 ( ICAM-1 ) promoters , we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM-1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein endothelial cells ( HUVECs ) .", "annotated_text": "Since <dna>kappa B motifs</dna> are present in <dna>VCAM-1 and intercellular adhesion molecule-1 ( ICAM-1 ) promoters</dna> , we used PDTC to study the regulatory mechanisms of <protein>VCAM-1</protein> and <protein>ICAM-1</protein> induction and subsequent <cell_type>monocyte</cell_type> adhesion in <cell_line>TNF-treated human umbilical vein endothelial cells</cell_line> ( <cell_line>HUVECs</cell_line> ) ."}
{"id": "1925", "text": "PDTC or N-acetylcysteine dose dependently reduced TNF-induced VCAM-1 but not ICAM-1 surface protein ( also in human umbilical arterial endothelial cells ) and mRNA expression ( by 70 % at 100 mumol/L PDTC ) in HUVECs as assessed by flow cytometry and polymerase chain reaction .", "annotated_text": "PDTC or N-acetylcysteine dose dependently reduced <protein>TNF-induced VCAM-1</protein> but not <protein>ICAM-1 surface protein</protein> ( also in <cell_type>human umbilical arterial endothelial cells</cell_type> ) and mRNA expression ( by 70 % at 100 mumol/L PDTC ) in <cell_line>HUVECs</cell_line> as assessed by flow cytometry and polymerase chain reaction ."}
{"id": "1926", "text": "Gel-shift analysis in HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF , suggesting that only VCAM-1 induction was controlled by NF-kappa B .", "annotated_text": "Gel-shift analysis in <cell_line>HUVECs</cell_line> demonstrated that PDTC prevented <protein>NF-kappa B</protein> mobilization by <protein>TNF</protein> , suggesting that only <protein>VCAM-1</protein> induction was controlled by <protein>NF-kappa B</protein> ."}