[Morphological and cytofluorometric study of the giant cells of the trophoblast of the common vole]. The primary and secondary giant cells of trophoblast in placenta Microtus arvalis were studied. The giant polyploid nuclei are formed in result of series of successively proceeding endomitotic polyploidization of chromosomes. Two stages of endomitosis are described: endointerphase with the uniform net of thin chromatin threads and the stage when small round or rod-shaped paired chromosomes gather mostly under the nuclear membrane. Great number of round, oval, and complex-shaped nucleoli may be seen in nuclei during both stages of endomitosis, the number growing during polyploidization. The morphology of the chromosome-nucleolar apparatus involves peculiarities of the polyploidization mechanism in placenta Microtus arvalis trophoblast. Endomitosis occurs both in low and high-polyploid nuclei. Cytofluorometric determination of the DNA amount in nuclei polyploid nature. The degree of polyploidy of the trophoblast giant cells nuclei during terminal differentiation of placenta corresponds to 128c-512c, and some nuclei contain the DNA amount corresponding to 1024 and 2048 chromosomal sets. The cause of origin of the polyploid cells in trophoblast of rodents placenta is discussed.


[Dependence of heterochromatin differential staining on the time of its reduplication and the degree of condensation]. A comparison of the chromosomes banding pattern after G-and C-staining with the time of DNA reduplication and the degree of chromosome condensation, was carried out using Chinese hamster metaphase chromosomes. Chromosome condensation was studied under 5-bromodeoxyuridine and 5-bromodeoxycytidine treatment. All the chromosomal segments stained with C-technique are also stainable with G-technique, while only some G-positive segments are capable to be C-bands. C-bands are heterochromatic segments characterized by extremely late replication and great delay in condensation under the analog action, while G-bands are segments with earlier labelling and irregular decondensation. The data obtained suggest a close correlation between the capability of chromosomal region of G- and C- staining and the degree of its heterochromatinization.


[Highly permeable intercellular junctions in normal and transformed fibroblast cultures]. Intercellular junctions permeable to ions and fluorescein Na were studied with the aid of intracellular microelectrodes in the cultures of normal and transformed mouse-embryo and hamster-embryo fibroblast-like cells. Normal cells were effectively coupled by the highly permeable junctions. In cultures of 7 types of transformed cells, 3 types of coupling were detected: effective, decreased, and fully reduced couplings. The degree of uncoupling was not correlated with morphological patterns of malignization and tumorogeneity of transformed cultures. The decrease of permeability of intercellular junctions to ions and small molecules is concluded not to be necessary for malignization.


Use of corticosteroids to isolate IBR virus from cattle in Cyprus after respiratory disease and ataxia. An outbreak of ataxia, blindness, respiratory disease and kerato-conjunctivitis occurred in October 1972 in a beef feedlot in Cyprus.  Fifteen animals died and 10 that were severely ataxic were slaughtered; many animals became blind.  There was no opportunity to isolate virus when the disease was active but in March and October 1973 infectious bovine rhinotracheitis (IBR) virus was isolated from cattle after they had been treated corticosteroids to stimulate virus excretion.  It is probable that IBR virus caused the disease.  This is the first report of the isolation of IBR virus from cattle in Cyprus.


Another example of anti-IB.

Another example of anti-IB. Another example of anti-IB is reported.  The antibody would only react with cells having both B and I antigens and was transient.


[Changes in the glycogen content of the dog myocardium at various phases of the cardiac cycle with a normal coronary blood flow]. Alterations in content of glycogen in myocardium of isolated heart of dog were studied at different phases of heart cycle by means of a special apparatus for myocardial biopsy and prompt freezing. Significant alterations in content of glycogen were observed during heart contraction. The maximal decrease (by 30.7%) in content of glycogen was found in preparations, obtained immediately after the R peak of electrocardiogramm. During the later steps of refractory period an increase in content of glycogen was observed and at the point, positioned 0.25 sec apart from the R peak, content of glycogen exceeded by 91.7% the initial level.


Adoption and children with learning and behavior problems. One representative case study is used to illustrate the complex interaction of factors that can lead to tragic family dysfunction when an adopted child has learning and behavior problems. The presence of neurodevelopmental problems in an adopted child, special adoption issues and interparental and intraparental conflicts combine to place the child and his family at high risk. The child's neurodevelopmental difficulties are expressed primarily as subtle learning and behavior problems which make him a focus for parental conflict. In addition, the adoption issues of difference, impermanence, feelings of mutual obligation and fear of abandonment are generally poorly understood and form the basis for the development of unique interactional patterns of communication. Finally, in the families studied, it was often found that the adopting parents had serious personal and/or marital difficulties.


[67-Galliumscintigraphy as an auxiliary method for differentiation of mass lesions of the liver (author's transl)]. Liver scintigraphy with 67-Ga citrate and alphafetoprotein (afp) determinations in the serum were carried out in 84 patients with liver mass lesions in the preceding sulphur colloid scans. Among these patients 51 cases were histologically verfied and 33 patients were regarded as clinically-proven cases. Scanning was carried out 72 hours after the intravenous injection of 3 mC 67-Ga-citrate. Corresponding to the intensity of 67-Ga uptake within the former liver lesions 3 groups of 67-Ga scans were differentiated: Ga 0 (the lesion showed no Ga uptake), Ga plus (the Ga uptake within the lesion was equal to that of the surrounding liver tissue) and Ga plus plus (the Ga uptake within the former lesion exceeded the physiological Ga uptake in the normal liver tissue). The number of cases, results of Ga scintigraphy and afp examinations as well as histological, clinical and nuclear medical diagnosis were correlated. It was shown that Ga plus plus cases were strongly suspect of hepatoma, whereas in Ga 0 cases a diagnosis of hepatoma could be excluded. In patients with Ga plus further investigations have to be performed (repeated afp examinations, angiography of the coeliac artery), because cirrhotic regeneration nodules, metastases and necrotic hepatomata were all found within this group. According to our experience liver scanning with 67Ga represents a useful auxiliary examination in liver diagnosis. Ga citrate scintigraphy of the liver is indicated in all cases with mass lesions detected by the routine sulphur colloid scan and in all patients in whom there is clinical suspicion of hepatoma, inorder to differentiate the origin of the lesions. In 2 cases of hepatoma marked Ga uptake was observed at a time when the afp was still negative.


Bleomycin as carrier substance for 99m-Technetium in tumour diagnosis (author's transl). 99m-Tc-Bleomycin is a promising tool for scintigraphic imaging of some types of malignant tumours. The rapid decay of 99m-Tc, together with a high affinity of bleomycin for certain histologically-defined tumours recommends its use in humans. Moreover, by using high specific activities of bleomycin, no toxic effects are to be expected. At 00-C, the chelate of 99m-Tc and bleomycin is stable and its storage or transport are recommended at this temperature. Following the i.v. injection of rats with 99m-Tc-bleomycin, a high specific activity is found in the liver, spleen, lungs and skin. In view of its excretion by the kidneys an extremely high activity is found in the urogenital system. Scintigraphic imaging of lymph nodes in a case of Hodgkin's disease, of a embryonal carcinoma, of a thyroid carcinoma, of an astrocytoma and of a solid carcinoma was obtained in patients investigated by this method.


A study of complement components C3, C5, C6, C7, C8 and C9 in chronic membranoproliferative glomerulonephritis, systemic lupus erythematosus, poststreptococcal nephritis, idiopathic nephrotic syndrome and anaphylactoid purpura. In a comparative study the hemolytic activity of C3, C5, C6, C7, C8, C9 and the C3 proactivator (C3PA) were measured in sera of 22 patients with chronic membrano-proliferative glomerulonephritis (CMPGN), 15 patients with idiopathic nephrotic syndrome, 10 patients with systemic lupus erythematosus, 7 patients with anaphylactoid purpura and 10 patients with acute poststreptococcal nephritis. In CMPGN, C3, C5, C6, C7 and C8 were low in the majority of the patients, whereas C9 and C3PA were depressed only in 21% and 11% of the patients, respectively. By contrast, C3PA and C8 showed striking depressions in the idiopathic nephrotic syndrome. In lupus erythematosus, all the C factors, including C3PA were found to be low with the exception of C9, which was normal in 80% of the patients studied. C3, C5, C6 and C7 were found to be depressed in acute glomerulonephritis; C8 and C9 titers were normal. In all patients studied with anaphylactoid purpura, CH50 and C3 titers were elevated markedly.


[beta2-Microglobulin in healthy children and in children with renal diseases (author's transl)]. beta2 microglobulin is a plasma protein of low molecular weight (11800), which also appears in urine in small quantities and cerebrospinal fluid. Its serum concentration in healthy children is 0.12 plus or minus 0.04 mg/100 ml, its renal excretion is 0.07 plus or minus 0.05 mg/24 hrs. In glomerular nephropathy serum levels are augmented with diminished GFR, while in tubular nephropathy excretion in the urine is raised considerably. There is a close correlation between serum beta2 microglobulin and GFR.


[Method for determination of the bleomycin inactivating enzyme acitivity in tissues]. An enzyme that inactivates Bleomycin (BLM) can be extracted from tissue. The activity of this enzyme varies markedly in different tissues. In the present paper, a method is described by which the activity of the BLM-inactivating enzyme in different organs and tissues of mice can be determined. The highest activity is found in liver; lower enzyme concentrations occur in the testis, spleen, lung and brain. In skin this enzyme is almost completely missing.


[T and B lymphocytes in chronic lymphocytic leukemia and Hodgkin's disease.  Electron microscopic and immunologic studies]. The number of lymphocytes forming spontaneous rosettes with sheep erythrocytes, a property of thymus-dependent (T) cells, and the number of lymphocytes bearing surface immunoglobulins, a characteristic feature of bone marrow-dependent (B) cells, were determined in the peripheral blood of normals and of patients with chronic lymphocytic leukemia (CLL) and Hodgkin's disease.  As compared with normal individuals CLL patients had an increased percentage of lymphocytes with membrane-bound immunoglobulins, whereas the proportion of rosette-forming lymphocytes was reduced.  In Hodgkin's disease either normal, diminished, or increased B cell values were obtained; the percentage of T cells was decreased or within the lower range of normals.  Lymphocyte transformation by various mitogenic agents in vitro may be regarded as a model of lymphocyte reactivity during immunologic processes in vivo.  In order to study the functional capacity of lymphocytes in CLL and Hodgkin's disease in comparison with normal cells, purified peripheral blood lymphocytes from normals and patients with these diseases were incubated in vitro with phytohemagglutinin (PHA) and pokeweed mitogen (PWM) over 7 to 11 days.  DNA synthesis was determined by incorporation of 3-H-thymidine.  The cyto-architectural features of the cells before and during incubation with these phytomitogens were studied by electron microscopy.  Planimetric measurements were performed on micrographs of comparable cell sections (through nucleus and Golgi zone) for the determiniation of cell, nuclear, cytoplasmic, and mitochondrial area.  Furthermore, the number of mitochondria and of membrane-bounded acid phosphatase-positive lysosome-like organelles was determined in comparable sections of unstimulated and mitogen transformed lymphocytes.


In vivo uptake and metabolism of 3-h-5alpha-androstane-3alpha,17beta-diol and of 3-h-5alpha-androstane-3beta,17beta-diol by human prostatic hypertrophy. Tritiated 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) and 5alpha-androstane-3beta,17beta-diol (3beta-diol) respectively were administered to patients with benign prostatic hypertrophy (bph) undergoing prostatectomy. In prostate and skeletal muscle homogenates and in plasma the total radioactivity content as well as the formation of metabolites were measured. Histological examination of each ectomized prostate was performed to evaluate the cellular composition of the tissue. After 3alpha-diol injection, a higher uptake of radioactivity in the prostate was obtained than after 3beta-diol. Within 30 min the 3alpha-isomer was very efficiently converted to 5alpha-DHT, while most of the 3beta-isomer remained unchanged. There was, however, also after administration of the 3beta-diol a substantial biconversion to 5alpha-DHT as has been confirmed by recrystallization to constant specific radioactivity. Only after 3beta-diol epiandrosterone was detected in small but significant amounts. 3alpha-diol administration resulted in distinct concentrations of 3beta-diol, whereas the conversion of 3beta-diol to the 3alpha-isomer was insignificant. When comparing the histological composition of the prostatic tissue with the accumulation of radioactivity and the formation of metabolites only a weak correlation between glandular structure and radioactivity uptake after 3alpha-diol administration could be revealed.


Corneal clouding with increased acid mucopolysaccharide accumulation in Bowman's membrane. Two infants had bilateral congenital corneal clouding and abnormal acid mucopolysaccharide accumulation in a thickened Bowman's membrane. This unusual entity was not associated with acid mucopolysaccharide deposits in the skin and visceral tissues or with increased levels of acid mucopolysaccharide in the urine. The similarity and differences have been compared to the systemic mucopolysaccharidosis and macular corneal dystrophy.


Defective epithelial adhesion in anterior corneal dystrophies. Experimental and pathologic studies implicated the role of the epithelial basement membrane and its associated hemidesmosomes and anchoring fibrils in mediating tight adhesion between corneal epithelium and stroma. We evaluated the ultrastructural quality of basement membrane complexes in patients with Reis-Bücklers dystrophy, Cogan's microcystic dystrophy, and nontraumatic recurrent erosion who presented with clinically significant erosive symptoms. Despite the variable clinical and histopathologic appearances among these dystrophies, incompleteness of basement membrane complexes apparently was a common fault shared by these erosive disorders. Such basic incompetence at the basement membrane level can both provoke and sustain erosions, while the more individual pathologic manifestations of a given anterior dystrophy may be of less primary significance.


Variability of dermal elastin visualized ultrastructurally with iron hematoxylin. The Verhoeff iron hematoxylin-lead citrate (VIH-LC) method demonstrated vertical elastic fibers that were often composed only of microfibrillar component extending into the epidermal basement membrane in human skin. These fibers connected with a network of trabeculae composed of microfibrils and elastin fibrils in varying proportions. The large elastic fibers in the deep two thirds of the dermis consited mainly of compact bundles of small elstin fibrils in infants and of solid elastin cores with a fimbriated periphery in adults; Dermis of a 6-month-old fetus contained very few small elastic fibrils except around blood vessels. Skin of an elderly subject revealed exteme proliferation of unusual reticulated elastic fibers in various areas and disclosed abnormal nodules of elastin or collagen fibrils in finely particulate matter. Small elastin fibrils, abundant microfibrils, and intermixed individual collagen fibrils comprised an adventitial collar between sweat glands and fibroblasts. Elastin fibrils were absent from this collar in the fetus and increased with the subject's age. A permanganate-high iron diamine sequence appeared to impart density to the microfibrillar component of elastic fibers.


Fine structural and cytochemical identification of microperoxisomes in developing human erythrocytic cells. An alkaline diaminobenzidine (DAB) medium has been used to identify peroxidase activity in small granules (0.09 to 0.2 mu in diameter) present in all forms of maturing erythrocytic cells with the exception of erythrocytes. These granules, which were more frequent in proerythroblasts (from two to seven by thin section), were distinct from pleomorphic granules present in the close proximity to the Golgi apparatus. They were also distinct from ferritin molecules which were seen as aggregates in siderosomes of polychromatophilic erythroblasts. They often appeared in close association with the smooth membrane of the nuclear envelope. Optimal conditions for the visualization of these granules by incubation in alkaline DAB were obtained when the peroxidase activity of hemoglobin was reduced by addition of low concentrations of potassium cyanide. Lack of hydrogen peroxide in the incubation media completely inhibited the staining reaction of hemoglobin, while the positive reaction persisted in the granules. Aminotriazole in the incubation media prevented the staining of these organelles. These findings suggest that small granules seen in maturing erythroblasts contain catalase and that they correspond to microperoxisomes described in other tissues. The mechanism of their disappearance during reticulocyte maturation is unknown. The relationship between particulate catalase of erythroblasts and soluble erythrocytic catalase has not been elucidated.


Values, Myths, and Symbols.

Values, Myths, and Symbols. Defining "symbol" as that which draws together and unites experience and "myth" as a cluster of symbols set in dramatic form, the author discusses the lack of both symbols and myths in contemporary sociaty. This lack had led to a disintegration of commonly held values and, ultimately, to a great need for psychotherapy on the part of individuals seeking personal identity. The individual must define his or her own values according to personal myths. One basic function of psychotherapy is to help individuals in their attempt to recover values.


Blood histamine levels and eosinophil, basophil counts in urticaria. The blood histamine levels, basophil and eosinophil counts and the percentage of vacuolated eosinophils were observed in 30 controls and 15 patients of urticaria. There was a definite rise in eosinophil and basophil count during the acute stage of the disease which decreased in the quiescent or the symptom-free stage. The behavior of blood histamine level was similar. The mechanisms involved are discussed.


Kinetics of antibody response to Ehrlichia canis assayed by the indirect fluorescent antibody method. The kinetics of antibody production response to experimentally induced infection of dogs with Ehrlichia canis was determined by ion-exchange and molecularsieve chromatography and by indirect fluorescent antibody (IFA) test. The first IFA antibody at 7 days after inoculation resided in immunoglobulin M (IgM) and immunoglobulin A (IgA) classes. At approximately 21 days after inoculation, the antibody was in IgM, IgA, and immunoglobulin G (IgG) classes. Thereafter, antibody concentrations continued to increase in the IgG class; those in the other 2 immunoglobulin classes had a variable pattern. In 2 dogs which died 60 and 114 days after inoculation, a decrease of antibody concentration in the 3 immunoglobulin classes was evident at the time of death. In the carrier dog, however, which was killed 147 days after inoculation, antibody concentrations sustained increasing titers in the 3 immunoglobulin classes.


A new diagnostic unit for corneal ulcers. A self-contained microbiologic unit has been presented as an expedient to facilitate the diagnosis of corneal ulcers in an office or emergency room. In addition, rationale for its contents are indicated. Although the commonly isolated bacteria and fungi, as well as many of the rare forms, can be cultured on the intact media included in this unit, growth of strict anaerobes may not be supported without additional processing of the media.


Secretory immunoglobulin A in oral and respiratory passages in man. Secretory IgA (SIgA) is the predominant immunoglobulin in certain external secretions and may have an important role in immunological mucosal resistance. SIgA differs in chemical and immunological properties from serum IgA. The present study was undertaken to investigate the antigenic relationship between SIgA, free secretory component (FSC) and serum IgA and the localization of SIgA as well as other immunological classes in tissues of oral and respiratory passages by use of immunofluorescence technique. SIgA and FSC were highly purified from human colostrum and rabbit anti-SIgA and anti-SC antisera were prepared. On the basis of antigenic relationships between SIgA, FSC and serum IgA, it was emphasized that individual specific antisera for SC and IgA and/or SIgA should be used in immunochemical or immunohistological investigations for SIgA. The present study failed to detect SC determinants in palatine and lingual tonsils. However, it was evident that cells present in the pharyngeal tonsillar epithelium contain SC determinants. SC molecules may be synthesized in certain secretory cells of mucous membrane and glandular epithelium and the combining of SC with IgA could occur in the cytoplasm of epithelial cells, the intercellular spaces and/or in the lumens of glandular acini and ductules.


Antenatal diagnosis of genetic disease.

Antenatal diagnosis of genetic disease. During the past decade, a vast methodology has been developed for the study and antenatal diagnosis of genetic disorders. The cytogenetic antenatal diagnosis of chromosome abnormalities is possible through the application of new methods for chromosome visualization in cultured amniotic fluid cells. A variety of inborn errors of metabolism may be diagnosed prenatally by the study of amniotic fluid, amniotic fluid cells and cultivated fibroblasts from this biologic fluid. Additionally, morphologic malformations such as neural tube defects and fetal catastrophies may be diagnosed during gestation by the study of alpha fetoprotein and beta trace protein levels. In the past few years, the application of methods for the visualization of the intrauterine fetus has been made possible by the use of techniques such as sonography, contrast radiography and fetoscopy.


Effects of dihydrostreptomycin on ribosome function in vivo: lack of correlation between changes in ribosome patterns and growth. In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on ribosomes and compared them to the effects of this antibiotic on growth and protein synthesis. We have shown that no changes in ribosome distribution are observed until growth inhibition by dihydrostreptomycin is almost complete. Thus, intracellular dihydrostreptomycin can inhibit growth and net protein synthesis without apparently affecting the ribosome cycle. Since it is known that the antibiotic combines with free 30S subunits, the question is how such combination can bring about the observed inhibition of protein synthesis and growth. We suggest that specific interaction of intracellular antibiotic with proteins of the 30S subunits allows repeated use of the ribosome cycle by such affected particles, but with selective misreading of certain amino acid codons as terminator codons, so that they produce incomplete polypeptide chains. The cumulative effect of such a mechanism would lead to eventual cessation of protein synthesis and growth.


Pathology of the neuromuscular junction. Diagnosis of neuromuscular disease by the study of motor endplate structure in the light and electron microscopes is probably one of the most specialized examinations in the field of neuropathology. The classical means of staining endplates using gold, silver or methylene blue are described as well as more modern techniques suitable for light microscopy. Specific abnormalities in patterns of terminal innervation after methylene blue staining are noted. Techniques for localizing endplates suitable for electron microscopic study are given and some of the typical changes that occur in endplate structure in some neuromuscular diseases are indicated.


Ammonium and sulfate ion release of histamine from lung fragments. In vitro studies with guinea pig lung fragments incubated with 10- to 200-mM concentrations of ammonium ion demonstrated the release of substanial quantities of histamine. Of the anions tested with ammonium ion, sulfate was the most potent, while nitrate and acetate ions were of intermediate potency and chloride was less potent. An osmotic effect is unlikely since equal concentrations of sodium chloride failed to release histamine. Isoproterenol, known to decrease anaphylactic histamine release, and acetycholine, known to increase histamine release, had no effect on the ammonium sulfate-mediated release of histamine. N-6 2'-O-Dibutyryladenosine 3',5' monophosphate (dibutyryl c-AMP) was also ineffective. These studies suggest that the inhalation irritation associated with certain sulfate and other salts, may be a function of their ability to release histamine in the presence of amonium ion.


Granulopoietic activity in Felty's syndrome. The levels of urinary and serum granulopoietic factor have been determined in nine patients with Felty's syndrome and compared with similar levels in patients with rheumatoid arthritis without Felty's syndrome and patients with neutropenic disorders of other causes. These studies have shown that urinary and serum levels of colony stimulating activity (CSA) in patients with Felty's syndrome are low (mean urine CSA 10.0 and serum CSA 4.0) when compared to patients with neutropenic disorders without rheumatoid arthritis (mean urinary CSA 26.8 and serum CSA 9.4). These findings suggest that Felty's syndrome may be, in part, the result  of decreased production or activity of granulopoietic factors rather than due simply to increased granulocyte destruction.


Significance of plasma copper and caeruloplasmin concentrations in rheumatoid arthritis. To understand the role of copper in initiating protein alterations in rheumatoid arthritis (RA) as reported previously, concentrations of copper anc caeruloplasmin were determined in RA patients. The mean copper concentration of the RA population examined was 24.8 mumol/l (157.5 mug/100 ml), and the mean caeruloplasmin concentration in this RA population was 45.52 mg/100 ml. These values are not different from those reported by previous workers. However, when the RA population was divided into three groups according to sex and oestrogen therapy it was found that caeruloplasmin and copper concentrations in the group of female RA patients on oestrogens was significantly different from other groups (P less than 0.001). A highly significant (P less than 0.01) positive correlation was obtained between copper and caeruloplasmin concentrations (r = 0.91). Concentrations of copper and caeruloplasmin failed to explain the low sulphydryl content of plasma which was observed to be independent of these two parameters. Increased alpha2-globulin concentration, which was refractory to chrysotherapy but 'finger-printed' with a pure preparation of caeruloplasmin in electrophoresis, along with the absence of Kayser-Fleischer rings, supports the contention that copper is not present in a free ionic state in RA patients. This study shows that only a concurrent oestrogen therapy raises copper and caeruloplasmin concentration significantly in a female RA population. Past investigators appear to have overlooked this fact, and it could be that a disproportionate sex distribution (more female rheumatoid arthritics) could cause misleading results in RA studies. The role of oestrogens, copper, and caeruloplasmin in causing exacerbation of RA symptoms is discussed.


Esophageal carcinoma. The value of staging in long-term survival. A three-stage study of 177 patients in Puerto Rico who had esophageal carcinoma is presented. Those surviving five or more years over a twenty-one-year period were located. Next, the experience at the San Juan City Hospital from 1968 to 1973 was examined. The information obtained from those two groups led to the last stage, a prospective study in which treatment was based on objective staging of the extent of the disease. Only 27% of these patients are really potentially curable upon admission to the hospital, and they should have aggressive therapy. Adequate palliation can be obtained with radiotherapy and chemotherapy in the remainder. The findings that nearly half of the five-year survivors had metastases or tumor extension and that some patients survived for prolonged periods without treatment emphasize the need for individualized treatment and research in tumor immunology.


Heredopathia atactica polyneuritiformis (phytanic acid storage disease). A new case with special reference to dietary treatment. A 33-year-old man with Refsum disease exhibited clinical features of night blindness, dysequilibrium, hearing loss, itchy dry skin, symmetrical polyneuropathy, distal muscle weakness, pes cavus, and hammer toe. His total serum protein was increased, nerve conduction velocities were slow, and serum phytanic acid levels were high. Dietary restriction of phytol resulted in a decrease in serum phytanic acid without any visual and autitory changes; however, coordination, skin lesions, and nerve conduction velocities definitely improved.


[Pulsecytophotometric analysis of cervical cells of postmenopausal women (author's transl)]. 49 suspensions with cells of the cervix uteri exclusively taken from postmenopausal women were analysed with the pulsecytophotometer. 7 of these cases had an histologically verified invasive cancer of the cervix uteri. There were no false negative results, the percentage of false positive measurements was about 30%. This good result may arise from selecting the cell material analized exclusively from postmenopausal patients and the choice of mathematical model for histogram interpretation, which has been constructed analogously to the cycle of mitosis of cells. Comparing the different methods of preparation of the suspensions the standard procedure (RNase, pepsin, ultrasonic) before staining with ethidium bromide seems to be the best one.


Ocular pathology of infantile Niemann-Pick disease. Study of fetus of 23 weeks' gestation. A fetus of 23 weeks' gestation was aborted following the demonstration of sphingomyelinase deficiency (infantile form of Niemann-Pick disease) in cultured amniotic fluid cells that were obtained by amniocentesis. Histopathologic study of the eyes disclosed normal findings for the fetal age, except for fine lipid droplets in the inner plexiform layer of the retina. By electron microscopy, membranous cytoplasmic bodies (MCB) characteristic of lipid storage diseases were identified in many ocular tissues, including corneal epithelium and keratocytes, lens epithelial cells and fibroblasts of choroid and sclera, and in extraocular muscle. Selective accumulation of MCB in ganglion cells in the primitive macular region was not apparent. An extremely fine membranous component (30 to 40 Angstroms) was seen in some inclusions, suggesting a relatively pure phospholipid content.


Homologous retinal outer segment immunization in primates. A clinical and histopathological study. Immune intraocular inflammation was induced in primates with homologous retinal outer segments. Perivascular retinitis, uveitis, and edema of the optic nerve head were the prominent acute clinical features. Acute and chronic inflammation was seen in the central and peripheral retinal vessels and granulomatous infiltration was present in the choroid of the uvea. Selective degeneration of the outer segments of the photoreceptor cells of the retina with sparing of the inner segments and of the adjacent pigment epithelium was confirmed by light and electron microscopy. This study strongly suggests that photoreceptor outer segments are highly and specifically immunogenic. The inciting antigen has yet to be identified. Implication of rhodopsin will have to await further studies since it exists as the essential protein in the outer segment.


Correction of tricuspid atresia.

Correction of tricuspid atresia. Although Fontan and Baudet in 1971 described a physiological correction procedure for tricuspid atresia, very few successful operations have been reported. Two patients corrected 20 and 10 months ago at the Brompton Hospital are presented. These two patients exhibit many of the problems in the management of tricuspid atresia. The first patient aged 20 had undergone three previous palliative operations, a Blalock-Taussig shunt, a Glenn procedure, and an infundibular resection, and therefore presented a number of operative problems. In contrast the second patient, aged 8, whose condition had deteriorated considerably over the previous year, had had no previous surgical treatment. At operation he was found, in addition, to have a partial atrioventricular canal. Details of the operative procedures and the patients' postoperative course are described. The criteria for selection of patients for the Fontan operation are discussed as are the possible long-term hazards of homograft failure, atrial dysrhythmias, and hepatic dysfunction. The successful outcome of these two patients suggests that palliative surgery in infancy should allow for this form of correction in later life.


Monozygotic twins discordant for systemic lupus erythematosus. A pair of monozygotic twins discordant for systemic lupus erythematosus(SLE) were studied and no differences noted in their immune respose to tetanus toxoid, keyhole lympet hemocyanin, DNCB, delayed sensitivity, or antibody titers to viruses. Both were noted to have biologically false positive serology at an early age, but only one twon developed SLE. The clinically unaffected twin underwent castration at an early age, suggesting that ovarian hormones may play an important role in the development of SLE.


Adverse reactions to intravenous anaesthetics. One hundred consecutive reports of reactions to intravenous anaesthetics Althesin, thiopentone and Epontol are reviewed and analysed. Ten reactions are attributed to causes other than the anaesthetic drug, and four are believed to have been caused by the muscle relaxant employed. The remaining 86 reactions were grouped according to their clinical presentation: histaminoid reactions ( 19), histaminoid with bronchospasm (33), bronchospasm (12), cardiovascular collapse (uu), delayed histaminoid reactions (6), and clonic contractions (5). None of the first four reaction types was associated with only one anaesthetic. A knowledge of the sales of Althesin has allowed the incidence of reactions to be estimated as between one in 11,000 and one in 19,000.


Physiological studies in a large sibship with antitrypsin deficiency. A large sibship demonstrated the severe consequences of alpha-1 antitrypsin deficiency. Of II living sibs 6 were homozygous deficient (Pi type ZZ) and 5 heterozygous (Pi type MZ). The homozygous group showed severe obstructive ventilatory impairment by spirometry, marked abnormality of airway resistance and specific conductance with striking pulmonary hyperinflation. The heterozygous deficient group demonstrated a less severe obstructive defect by ventilation measurements with only marginal abnormality of airway resistance, specific conductance, and normal lung volumes. The evidence suggests that both the heterozygous and the homozygous states of alpha-1 antitrypsin deficiency are lung damaging.


[Precocious and acute infantile malnutrition. Effects on the increase of weight and height]. This paper describes the influence of early, severe and extended malnutrition on physical growth, weight and stature in a group of 33 children controlled in their development up to the age of 5 years. The program of treatment was mainly directed to promote the correction of nutritional deficiencies and to educate mothers in feeding practices. Those cases where it was not possible to obtain satisfactory collaboration from the family to the program offered, were excluded. The program that was carried out allowed to maintain, practically without relapses, a fast recovery of the weight and of the apparently good nutritional state of the children. It is also important to stress the absence of infectious diseases and gastrointestinal disturbances in spite of the fact that all patients returned to the same environment they belonged.


A comparison of different methods of detecting mucin in adenocarcinomas of the lung. The correct classification of carcinoma of the lung is not only of therapeutic and prognostic importance but is also considered to have epidemiological and aetiological significance. Histological tests for mucin are essential in the classification of lung tumours but there is little information available about the influence of the method of detection used on the results of classification. Five established staining techniques were tested using paraffin blocks from surgical specimens of 81 human lung tumours diagnosed as adenocarcinoma, i.e. tumours of WHO Type III. Mowry's alcian blue-periodic acid-Schiff (AB-PAS) technique gave the highest proportion of positives (93%) slightly fewer (90%) being obtained by the PAS technique alone. Both these methods were influenced by the presence of cytoplasmic hyaline globules, structures which cannot be regarded as mucin. The stain recommended by the World Health Organization was also influenced by the presence of hyaline globules, was less frequently positive than the PAS techniques and was considered to have no special advantages. The aldehyde fuchsin-alcian blue sequence was positive in only 83% of cases but provided some information about the type of mucin present. Southgate's mucicarmine also detected mucin in only 83% of cases. It was concluded that the apparent incidence of adenocarcinomas may be influenced by staining methods used. Some standardization of technique is desirable and the AB-PAS combination appears to be the most satisfactory.


Production of antibodies that bind biotin and inhibit biotin containing enzymes. Methods were developed for the coupling of biotin to bovine serum albumin and bovine gamma-globulin using a water-soluble carbodimide. The use of [14-C]biotin as a tracer allowed quantitation of the incorporation of biotin into the conjugates: 2.55 mol of biotin was incorporated per mol of gamma-globulin and 7-9 mol of biotin was incorporated per mol of serum albumin in different preparations. These conjugates were highly immunogenic in the rabbit and anti-bodies reactive with the biotinyl group itself could be detected by their ability to precipitate the heterologous biotinated carrier but not the unmodified heterologous carrier. There antisera rapidly inactivated transcarboxylase and pyruvate carboxylase and this inactivation could be blocked by pretreatment of the antisera with biotin or biocytin. Using enzyme inhibition to detect free antibody, the binding constant for biotin was found to be 5.0 x 10- minus 8 M and that for biocytin 3.5 x 10- minus 8 M.


Molecular conformation of bovine A1 basic protein, a coiling macromolecule in aqueous solution. Aqueous solutions of bovine A1 protein, the major component of the basic protein fraction of myelin, were studied by small angle X-ray diffraction. The experimentally determined molecular weight, 17,800, is within 3% of that corresponding to the amino acid sequence, 18, 395, and the radius of gyration was found to be 46.3 A. No equivalent scattering particle of uniform electron density could be found which was compatible with all parameters evaluated from the diffraction measurements. The possibility of a coiled shape was therefore investigated using a worm-like chain model. This yielded a contour length of 439 A and a persistence length of 15.7 A. The radius of gyration of this model chain, 47.1 A, is in quite reasonable accord with the experimental value. The latter, after correction for excluded volume effects and finite chain length, yields for the characteristic ratio, ro2/nplp-2, 5.4. This may be compared with the value, 6.1, obtained after applying a correction for finite chain length to the viscosity data given by Tanford et al. for 12 proteins in 6 M guanidine hydrochloride and 0.1 M beta-mercaptoethanol. These two experimental values fall in the expected order, since the 15% glycine content of the A1 protein is considerably higher than the average for other proteins, which is about 8%. The corresponding values predicted from conformational calculations by Miller et al. for random copolymers of the L-alanine-glycine type are 5.9 (18% glycine) and 7.0 (8% glycine). We conclude that the A1 protein exists predominately, if not exclusively, as a random coil in aqueous solution.


The inhibition of phospholipid synthesis in escherichia coli by phenethyl alcohol. The kinetics of lipid metabolism during phenethyl alcohol treatment of Escherichia coli were examined. Phenethyl alcohol at a non-bacteriostatic concentration reduces the accumulation of [32-P] phosphate into phospholipids and alters the phospholipid composition of the cell membrane. The changes in phospholipid composition are a result of the inhibitory effect of phenethyl alcohol on the rates of synthesis of the individual phospholipids. The inhibition in the rate of phosphatidylethanolamine synthesis by phenethyl alcohol was twice the inhibition in the rate of phosphatidyglycerol synthesis. The de novo rate of cardiolipin synthesis was only slightly inhibited. However, net cardiolipin accumulation increased during phenethyl alcohol treatment due to a more rapid turnover of phosphatidylglycerol to cardiolipin. Phenethyl alcohol also altered the fatty acid composition of the cell as a result of its inhibitory effect on the rate of individual fatty acid synthesis. However, the inhibition of phospholipid synthesis was not reversed by fatty acid supplementation of phenethyl alcohol treated cells. This result indicates that phenethyl alcohol does not inhibit phospholipid synthesis solely at the level of fatty acid synthesis.


Topological studies on the hydrolases bound to the intestinal brush border membrane. II. Interactions of free and bound aminopeptidase with a specific antibody. The position of the intestinal brush border aminopeptidase with respect to the lipid bilayer has been investigated with the aid of right side out vesicles prepared from the brush border and an immunological technique using an unlabelled or peroxidase-labelled antibody specific for aminopeptidase. The finding that the bound form of the enzyme was almost as readily inhibited and agglutinated as the free form during incubation with the antibody was consistent with the view that the majority of the aminopeptidase surface emerged from the bilayer. This finding was entirely corroborated by the observation that only a few antigenic determinants were not free to react with the antibody in bound aminopeptidase. This immunological technique may be applied to other membrane proteins provided that preparations of the pure proteins and of specific antibodies are available.


Regional and cellular localization of glycosyltransferases in rat small intestine. Changes in enzymes with differentiation of intestinal epithelial cells. Optimal assay conditions were determined for four glycosyltransferases in rat small intestinal mucosal homogenates and the regional distribution and cellular localization of these enzymes was studied. For each glycosyltransferase, similar levels of activity were found in duodenal, proximal jejunal and distal ileal segments; activities of the galactosyltransferases were lower in the distal jejunal-proximal ileal segment. Planar section studies indicated that the undifferentiated crypt cells had significantly higher levels of sialyltransferase activities in the jejunum and ileum than the mature villus cells. A similar crypt to villus gradient was found for a galactosyltransferase in the ileum. These data suggest that glycoprotein synthesis may be active in the undifferentiated crypt cells and that certain glycosyltransferases may serve as marker enzymes for cellular differentiation in the intestine.


Current-voltage studies on the thylakoid membrane in the presence of ionophores. The reversibility of the binding of ionophores to the thylakoid membrane is studied. While gramicidin binds practically irreversibly, valinomycin and nonactin bind reversibly, however, only a small fraction (about 1%) of the membrane-bound valinomycin or nonactin is active in ion transport. The current-voltage relationship is evaluated under these circumstances. We have found that it is practically linear. This together with the relationship between current and ion concentration agrees qualitatively with the results reported for bimolecular lipid membranes, which contain a large fraction of negatively charged lipids. For the ionophores, valinomycin and nonactin, the binding equilibria (K approximately equal to 10-4) and the turnover numbers (approximately equal to 3-10-4/s) are evaluated for their action on the thylakoid membrane. Possible reasons for the inactivity of the majority of membrane-bound ionophore molecules are discussed.


Immunoabsorption of membrane-specific antibodies for determination of exposed and hidden proteins in human erythrocyte membranes. Human erythrocyte membrane proteins solubilized with the non-ionic detergent Berol EMU-043 have been characterized by crossed immunoelectrophoresis with rabbit antibodies raised against the membrane material. Three out of sixteen membrane-specific immunoprecipitates disappeared when the antisera were first absorbed with intact erythrocytes. This finding indicates that three antigens are exposed on the outside of the erythrocyte membrane. One of these antigens showed acetylcholinesterase activity, and another was the major glycoprotein (glycophorin) as shown by crossed-line immunoelectrophoresis. No antigenic determinants of the latter protein were detected within the membrane or on its inner surface. In crossed immunoelectrophoresis with antisera after absorption with washed, non-sealed membranes only one precipitate remained. This precipitate corresponded to albumin. Accordingly, several proteins seem to have antigenic determinants exposed on the inside of the membrane.


Isolation and characterization of a basic encephalitogenic protein from the central nervous system of sheep. A basic protein has been purified from sheep brain. The purified protein sedimented in the analytical centrifuge at 56,000 r.p.m. as an homogenous product. This protein induced an allergic encephalitis when injected into guinea pigs. Some physiochemical properties of the protein were studied: the sedimentation coefficient was 1.52 and the molecular weight was 20,000 +/- 2,000, as estimated by electrophoresis in acrylamide gels containing SDS and urea; the specific extinction coefficient (see article) was 6.01 +/- 0.20. The aminoacid composition of the molecule was determined and its most prominent aspects are a high content of arginine and lysine, the presence of a single tryptophan, the total absence of cysteine and cystine and a blocked N-terminal residue. All these properties are very close to those of human and bovine encephalitogenic proteins.


Validity of plasma factor in schizophrenia as measured by tryptophan uptake. The uptake of L-tryptophan by chicken erythrocytes is stimulated by the presence of human plasma; however, there is no difference between the stimulation caused by plasmas of normal, chronic hospitalized nonschizophrenic, or chronic hospitalized schizophrenic subjects. Human plasma in general contains a complement-dependent antibody which reacts with an antigen present in the membrane of chicken erythrocytes resulting in hemolysis. Hemolysis can be maintained at a constant level by certain concentrations of Ca++ ion, the addition of which resulted in a gradual increase in tryptophan uptake. The calcium effect is probably due to the fact that the metal acts as a cofactor or modifier of component(s) of plasma causing higher uptake. The data indicate that hemolysis is not determining uptake of tryptophan by chicken erythrocytes.


Basophil counting with a new staining method using alcian blue. Difficulties in obtaining reproducible and accurate enumeration of circulating basophils with existing techniques have hampered investigation of this infrequent cell population. A new basophil staining method is described that employs alcian blue dye for staining of heparin within basophils at low pH and in the presence of lanthanum ions. Basophil recognition is facilitated by reducing nonspecific nuclear staining. This objective is achieved because of the differences in stability of alcian blue-heparin, alcian blue-nucleic acid, lanthanum-heparin, and lanthanum-mucliec acid complexes. Reduction of pH after staining also favors solubilization of leukocyte cytoplasmic proteins, providing greater contrast between stained and unstained cells by reducing light scattering of the unstained leukocytes . The alcian blue staining method is suitable both for chamber basophil counting and automated basophil counting using continuous-flow sampling and electro-optical detection. The new staining method was evaluated by comparing it with the chamber counting method using toluidine blue in a triple-blind study in which the results of basophil counting by the alcian blue chamber method, alcian blue automated instrument method, and the toluidine blue chamber method were analyzed for reproducibility and compared with an indirect basophil count obtained from a 1000-cell leukocyte differential and a total leukocyte count. Both alcian blue staining methods gave greater reporducibility that toluidine blue and were more accurate, as evidinced by a significantly higher correlation with the indirect basophil count. The improved reproducibility, accuracy, and convenience of this method over existing methods should facilitate the collection of more meaningful information about circulating basophil levels in health and disease.


A medical librarian's bag of tricks: coordinating books and media. The development of a coordinated program of print and nonprint materials in the Library of the College of Medicine and Dentistry of New Jersey is traced. Fundamental to creating a successful program is a good staff, freedom to grow, and strong administrative support. A positive and aggressive attitude on the part of librarians is an important ingredient in increasing utilization of media.


Plasma zinc legels in prostatic disease. Plasma zinc concentrations rise in men over the age of 55 years and fall in women of a similar age-group. They are higher in men with clinically diagnosed benign prostatic hyperplasia, but the level does not appear to be related to the size of the gland. Plasma zinc concentrations are not helpful in the diagnosis or management of carcinoma of the prostate, but may prove useful in excluding this diagnosis.


Serum ferritin assay and iron status in chronic renal failure and haemodialysis. Forty-four patients with chronic renal failure on haemodialysis for four months to eight years were studied. All recieved intravenous iron dextran 100 mg on alternate weeks. Serum ferritin concentrations correlated well with body iron stores estimated by grading the bone marrow stainable iron. Altogether 34 patients showed increased bone marrow iron stores and serum ferritin concentrations greater than controls; four patients showed absence of iron in the marrow, and three of these had subnormal serum ferritin concentrations. Serum ferritin assay represents the best method of repeatedly monitoring the exact amount of iron therapy needed by patients with chronic renal failure, particularly those on regular haemodialysis.


Specificity of human serum antibodies against endotoxin from N. gonorrhoeae. Sera from patients with gonorrhoea were used to study the specificity of human antibodies against determinant a of endotoxin from gonococcal strains 8551, V, and VII. The sera were tested by an indirect haemagglutination technique before and after absorption with endotoxin from the same strains. The sera were used untreated and treated with mercaptoethanol (ME). The untreated and ME-treated sera showed antibody activity against all the a determinants when examined unabsorbed. After absorption with any of the endotoxin preparations the sera usually demonstrated antibody activity against one or both of the other preparations. The pattern of reactivity thus observed differed from one serum to another. Treatment of sera with ME resulted in an altered pattern of reactivity of four of the five sera. The results indicate multispecificity of human antibodies against the a determinants.


Retrograde transport of horseradish peroxidase in the magnocellular neurosecretory system of the rat. Horseradish peroxidase (HRP) was injected into the pituitary in adult rats. After 2-3 days, the neurones of the supraoptic nuclei, the magnocellular parts of the paraventricular nuclei, and the various accessory neurosecretory hypothalamic nuclei showed accumulation of HRP. The HRP reaction product consisted of fine, discrete cytoplasmic granules, and in electron micrographys it was seen to be located in the lysosome-like dense bodies of 0.4-0.6 mum diameter which are normally present in the cytoplasm of the neurosecretory neuron.es. Very little reaction product was found in the neurosecretory axons. Reaction product was also found in the hypothalamic arcuate nuclei. This was the result of an endogenous peroxidase-like activity, since it occurred in control animals which had not received HRP. This endogenous reaction product is non-neuronal. Morphologically, it takes the form of distinctive clusters of coarse granules which are seen in electron micrographs to be characteristic angular bodies of 0.7-1.0 mum diameter located in the cytoplasm of astrocytes or their processes.


The smooth endoplasmic reticulum: structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport. The spatial arrangement of the smooth endoplasmic reticulum (SER) was studied in 0.5-2 mum thick sections of rat spinal and chick ciliary ganglia previously impregnated with heavy metal salts. Electron microscopy at low (10-5 V) or high (10-6 V) voltage showed the impregnated SER as a continuous system extending probably from the perikaryon to the axon terminal. Tubules of the SER, which were running in a parallel direction with the axon, were occasionally seen in close apposition with the axonal membrane. Moreover in the preterminal region, anastomosed tubules of the SER formed a subsurface 'primary network' and gave rise to a deeper 'secondary network' made of thinner tubules; synaptic vesicles bulging at the tip of thin tubules of the SER were frequently observed. To specify the role played by the SER in the fast axonal transport, chicken ciliary ganglia were slighty compressed and radioautographed 3 h after the intracerebral injection of [3-H]lysine. Quantitative analysis of the silver grain distribution indicated that labeled proteins, rapidly conveyed down the axon, piled up in regions containing an accumulation of SER profiles. On the basis of these results, it is concluded that: (1) the SER appears as a continuous intraaxonal pathway bridging the perikaryon and the axon terminal; (2) the SER conveys macromolecular components with the fast axonal transport; (3) the conveyed macromolecules, which are delivered to the axonal membrane and to the synaptic vesicles, are probably transferred by means of connections with the SER.


The effect of penicillin, dihydrostreptomycin and prednisolone treatment of experimental Candida krusei infections of the mammary glands of dairy cattle. The growth of Candida krusei in quarters treated intramammary with penicillin, dihydrostreptomycin and prednisolone was compared with growth in untreated quarters. No clinical mastitis occurred in any of the quarters of either group. The number of yeast organisms isolated from the quarter during and after the treatment period appeared similar in both groups. The number of leukocytes in all treated quarters increased during the antibiotic and steroid treatment period but the number of yeast isolated remained the same or decreased as compared to the control quarters.


Lactoglobulins (goat) in the immunofluorescence staining of parainfluenza virus type 2 in L-132 cells. Instillation of parainfluenza virus type 2 in the mammary gland of the goat resulted in the appearance of specific and high titered antibodies in the milk. The globulin fraction of the milk was separated and conjugated with fluorescein isothiocyanate. These conjugated antibodies could be successfully used in the specific staining of the homologous virus in infected L-132 cells. Therefore, milk from such immunized animals represents a rich and convenient source of specific antibodies for use in immunofluorescence and other serological tests.


Current concepts of chemotherapy combined with other modalities for head and neck cancer. This paper presents an overview of studies of therapy of head and neck squamous cell carcinoma in which chemotherapy was combined with other modalities. The rationale for using chemotherapy with surgery is discussed, but ststematic studies of this combination of modalities have not been reported. Systemic chemotherapy plus radiation therapy has been studied using hydrozyurea, t-fluorouracil (5-FU), and methotrexate (MTX). Uncontrolled studies with hydroxyurea report favorable results, but a well-controlled study gave negative results. Controlled studies with 5-FU have given favorable results in certain tumor stages and sites of origin. MTX plus radiation in a small series produced slightly better survival than radiation alone. Intra-arterial chemotherapy plus radiation therapy has been the subject of exploratory studies but no firm conclusions can be drawn from these studies. Chemotherapy plus immunotherapy has been explored and merits further study. Based on the studies reported to date one can suggest the need for large-scale randomized control studies of long-term chemotherapy combined with other modalities.


Simultaneous intermittent bleomycin and radiological treatment of laryngeal cancer. Bleomycin has been shown to have a significant effect on squamous cell carcinomas, particularly on highly differentiated types. Applying combined bleomycin and x-rays simultaneously in an intermittent schedule, a synergistic effect was obtained. It was possible to lower the dosage of each and still achieve remarkable therapeutic responses. At the same time the side effects were reduced. The total dosages have been bleomycin 180 mg and x-rays 4.200 r skin dose, tumor dose approximately 2.500 r. Eighty-two laryngeal cases received such treatment. Altogether a complete regression was achieved in 62 per cent. Glottic tumors showed complete regression in 85 per cent. In six out of 10 inoperable cases, the tumor became surgically accessible by laryngectomy. In successfully treated patients characteristic histological changes were found, consisting in unusually large amounts of fully keratinized cells.


Multiform ventricular ectopic rhythm. Evidence for multiple parasystolic activity. Six patients whose standare electrocardiograms showed multiform ventricular ectopic  rhythm were studied. All patients had advanced organic heart disease and a significant intraventricular conduction defect (left bundle branch block in five and right bundle branch block plus left anterior hemiblock in one). The ventricular arrhythmia was generally resistant to antiarrhythmic therapy. Five of the six patients died after 2 to 6 months form the period of observation from terminal heart failure. None died suddenly. The ventricular arrhythmia did not seem to be directly related to mortality in any patient. Critical analysis of several long rhythm strips in each case revealed that discharge from multiple ventricular parasytolic foci shared in the multiform ventricular activity. The concurrent discharge of a minimum of three parasytolic foci and a maximum of six foci was found in the same case with a total of 24 parasystolic foci in the six patients. There was a remarkable constancy of the QRS configuration of all parasytolic foci over periods of observation of up to  16 months. However, 22 out of 24 parasystolic rhythms showed significant variation in the apparent rhythm or the administration of drugs. Fourteen parasytolic foci showed evidence of exit block, some of which were exaples of a rapid parasystole with a high degree of exit block. The study suggests that multiform ventricular ectopic rhythm may, in part, be due to the concurrent discharge of multiple parasystolic foci.


Genetics of the GPT system. Family, mother/child and association studies. GPT types are presented for 150 Norwegian matings, with 454 children,  and 1703 Norwegian mother/child combinations. There were five exceptions to a simple codominant inheritance pattern, all believed to be due to a segregating Gpt-0-allele. Rare phenotypes were encountered in two of the families and in 11 of the mother/child combinations. Compiled family material and mother/child material are presented. No indication of association was found between GPT types and phenotypes within the ABO, Rh, MN, Hp, Gc, C3, PGM1, and ACP1 systems. There is a marked association between EBS-Ogna (epidermolysis bullosa simplex, type Ogna) affection and GPT phenotypes. This reflects the Gpt-EBS1 linkage phase. No evidence was found of association between GPT phenotypes and either nephrological diseases or PKU (phenylketonuria).


The effect of salicylate and chloroquine on prostaglandin-induced articular damage in the rabbit knee. Prostaglandins are found in increased concentrations in various arthritic joint fluids, and the E and F series have been shown to produce inflammation. Vane suggests that the effectiveness of aspirin is mediated by inhibition of synthesis or release of prostaglandins. In our studies PGE-1 intra-articularly produced the greatest amount of synovial and cartilage damage of the several PGs tested. Five knee intra-articular injections of 500 ng PGE-1 were given to 12 mature white New Zealand rabbits at 4 day intervals, with control solutions on the opposite sides. Four with intramuscular chloroquine at clinical levels and 4 controls. At 20 days histologic examination with H & E and safranin-O showed increased synovitis and abnormal cartilage in the controls and salicylate groups, normal cartilage in the chloroquine group. Whereas chloroquine's ability to stabilize cell membranes is protective in this experiment, salicylate's ability to prevent biosynthesis of prostaglandins is bypassed and therefore is not protective. Vane's hypothesis is supported by this study of PG induced experimental arthritis.


Kuru.

Kuru. Kuru is a progressive, invariably fatal cerebellar degeneration which occurs in a limited area of the New Guinea Highlands. The word kuru is derived from a term in the Fore language meaning to shake from fear, and it stems from the trembling which is a conspicuous symptom. Few neurologic diseases have attracted the attention of specialists in so many disciplines. No rare disease can have aroused more interest among the laity. Apart from an extensive scientific and anthropological literature, kuru has been the source of inspiration to journalists and travel writers, and it even occupies a prominent position in the plot of a popular novel. The facts concerning kuru are no less remarkable than the mythology that has grown up around it.


Present status of the Duffy blood group system. In 1950 a new blood group antibody was recognized in the serum of a multi-transfused hemophiliac patient. The reactive red-cell antigen was identified in 65% of random caucasians, and the systemic name Duffy was proposed. Two common antigens, Fy-a and Fy-b, were recognized and shown to be products of autosomal allelic genes, but the great majority of negro individuals were found to lack both antigens. In 1968 genetic studies showed Duffy to be linked to Un-1, which is an inherited structural variation of chromosome number 1. Duffy thus became the first autosomal blood group gene to be allocated to a specific chromosome. Recent studies have allowed recognition of three new antibodies (anti-Fy3, anti-Fy4, and anti-Fy5) in the Duffy system. The Rh blood group locus has also been assigned to chromosome 1, and there is evidence that the antigen defined by anti-Fy5 is a product of interaction between Duffy and Rh genes. The Duffy blood group appears to be one of importance in clinical blood transfusion practice, and possibly makes the greatest distinction of any of the red cell systems between different groups of the world population.


A study of the heights and weights of different groups of disturbed children. Mean centile heights and weights of 346 children referred to a child psychiatric clinic were recorded and compared with the psychiatric diagnoses of the children. Neurotic boys were found to have significantly greater mean centile heights than boys with (a) conduct disorders and (b) specific developmental disorders. No significant difference was found in the girls. The difference in boys' heights was not associated with any significant difference in social class, family size, or position in the family. No significant weight differences were found. The results are discussed, and it is concluded that the relationship between physical growth and psychiatric disorder in children merits further investigation.


A guide to differentiated developmental diagnosis with a case demonstrating its use. The great influx of children needing assessment has presented all diagnosticians with a large body of patients whose conflicts are relatively unfamiliar ones. These children do not fit into the expectable pattern of normal development, nor is an adult-oriented frame of reference of much help in understanding them. What seems needed is a schema in which the developmental deficiencies of these children are related to their present functioning. This paper introduces a guide covering five aspects of development. The guide gives descriptions of normal functioning at ages 0 to 1 1/2, 1 1/2 to 3, 3 to 6, and 6 to 10, and also shows the persistence of this functioning as it is reflected in the attitudes, feelings, and behavior of primary school children. A case illustration is presented that demonstrates the use of the guide.


Chromosomes of a cell line of Dipodomys panamintinus (kangaroo rat). A banding and autoradiographic study. The chromosomes of an established cell line of Dipodomys panamintinus have been characterised in terms of their C, G and Q banding patterns, and the distributions of silver grains in autoradiographs of chromosomes labelled in early or late S phase. No relationship could be established between C, G or Q banding regions of chromosomes and a particular S phase time of replication of the DNA in these banded regions. The implication of this result to the concept of heterochromatin is discussed.


Localization of rDNA and Giemsa-banded chromosome complement of white-handed gibbon, Hylobates lar. A karyotype based on banding pattern and chromosome length is presented for the white-handed gibbon, Hylobates lar. Little homology with the banding patterns of the chromosomes of the other Hominoidea can be seen, confirming the early evolutionary separation of Hylobatidae and the other apes. Hybridization in situ with ribosomal RNA shows that the secondary constriction of a submetacentric chromosome (15) is the only site of the nucleolar organizer, as in the Cercopithecoidea. The correlation of polymorphic variation in size of this secondary constriction with grain density suggests differences in the number of gene copies per chromosome.


Heterochromatic chromosomes and satellite DNAs of Drosophila nasutoides. Drosophila nasutoides is distinguished from other Drosophila species in that the metaphase karyotype shows a pair of very large V-shaped chromosomes. With Giemsa, a distinctive C-banding pattern is revealed along the arms of this large chromosome, indicating a largely heterochromatic nature. Furthermore, the banding patterns of the arms are symmetrical, indicating that it is an iso-chromosome. A comparison between the metaphase karyotype and polytene chromosomes suggests that the large V chromosome appears as the dot chromosome in polytene squash. One autosome has twice the arm length of typical Drosophila polytene chromosomes and arose either by centric fusion and a pericentric inversion, or by translocation connecting distal ends with a subsequent loss of one centromere. This chromosome appears to have a short arm which ectopically pairs with the proximal region of the long arm, representing a duplication of about ten bands. When the nuclear DNA is examined by neutral CsCl gradient, four satellites are observed. As much as sixty percent of the total DNA appears as satellites in the lysate of larval brains. No satellite was detectable in the lysate of salivary glands. These observations led us to suggest that the heterochromatic nature of the large V chromosome is due to the presence of all four satellites in this chromosome and that this  large chromosome appears as the dot because of the under-reduplication of the satellites during polytenization.


[Whipple's disease].

[Whipple's disease]. Whipple's disease is characterized morphologically by macrophages in the small intestine which store PAS-postive material, as well as coarsening and atrophy of the intestinal villi, with pseudocystic  cavitations. Without treatment it ends  fatally due to irreversible diarrhoea and cachexia. Until 1963, only 90 cases had been diagnosed, most of them at autopsy. Intestinal biopsy has facilitated the diagnosis in life. Treatment with antibiotics results in dramitic improvement and remission for many years. From this an at least partial bacterial cause of the disease has been deducted, but it has not been possible so far to identigy more precisely any causative bacteria. Two cases of Whple's disease with some special features are reported. Both occurred in women (previous reports were almost entirely of men). The severely ill patients were cured by tetracycline within a few weeks and have remained completely well at follow-up examinations. The morphological changes in the intestinal mucosa had partially regressed.


Rapid effects of single small doses of L-thyroxine and triiodo-L-thyronine on growth hormone, as studied in the rat by radioimmunoassy. The effects of thyroid hormone deprivation and restitution on growth hormone (GH) economy have been studied in the rat by means of a specific radioimmunoassay. The pituitary GH content and the plasma GH levels before and during stimulation with pentobarbital ("PB-test") were studied in male rats at different intervals after surgical thyroidectomy (T), and in T rats at different time intervals after the ip injection of 0.20, 1.75, and 5.0 mug thyroxine (T4) or 0.05, 0.10, 0.20 and 1.0 mug triiodothyronine (T3), all doses being referred to 100 g body wt. Pituitary GH content decreased very rapidly after T, a difference being shown at the end of the shortest time interval studied (24 h); 24 days after T, pituitary GH content was 0.3 percent or less of the pre-T level, the basal plasma GH was lower than in intact controls and an increase in plasma GH during PB-stimulation was no longer observed. When rats T for 30 days or longer were injected once with T4 or T3, pituitary GH content increased; basal plasma GH levels increased also and a positive response to PB was observed. An effect on pituitary GH content could be observed as soon as 2 h after the ip injection of 1.0 mug T3, or 6 h after 5.0 mug T4. The "latent period" was somewhat longer when lower doses of the hormones were used. Effects of a single 0.10 mug T3 dose could be detected within 12 h L-T3 appeared to be at least 9 times more potent in vivo tha T4, as assessed from the effect on pituitary GH. The mea-urement by RIA of changes in GH content of the rat pituitary may thus provide the most adequate parameter available at present (other than suppression of TRH-induced TSH release) for a biological effect in vivo of single doses of the thyroid hormones, a measurement clearly related to an important physiological role.


Observations on the T wave of the equine electrocardiogram. The paper describes changes observed in the T wave and T vectorcardiogram in horse after various periods of exercise. Using radiotelemetry and a bipole lead all horses showed negative T waves immediately after exercise. In some of them this was followed by a markedly positive T deflection. Possible reasons for these changes are briefly discussed.


Immunological comparison of basic encephalitogen and histone F2A1. The extent of immunological cross-reaction between basic encephalitogen and histone F2A1 on both the humoral antibody level and on the cellular level has been established. The extent of humoral cross-reaction was tested by direct complement fixation employing both anti-histone F2A1 and antisera to basic encephalitogen, by inhibition of complement fixation, by radioimmunoassay and by passive cutaneous anaphylaxis. The data obtained failed to reveal immunological cross-reaction at the cellular level was tested by the lymphocyte stimulation technique in rabbits and guinea pigs, by inhibition of lymphocyte stimulation and by delayed hypersensitivity skin reactions. A slight but significant cross-reaction between the two proteins on the cellular level was detected by inhibition of lymphocyte stimulation and by the delayed hypersensitivity test. It is concluded that the immunological studies provide limited evidence that the two proteins share antigenic determinants.


Absolute or relative values in csf electrophoresis? An evaluation of the gamma-globulins in multiple sclerosis and other neurological diseases. The frequencies of pathological results in 143 CSF samples of MS patients from the years 1964-1967, and 206 samples from 1968-1973 were compared after agar electrophoresis and cytological differentiation. As they were in good agreement, the two series were combined into one group of 349 MS patients for further comparison with three groups with other neurological diseases (inflammatory, neoplastic and vascular brain affections). Although the absolute gamma-globulin values (mg/l) are somewhat more frequently pathological than the relative values (rel%), they also correlate significantly with total protein and, therefore, do not offer a criterion with a diagnostic value of its own. From them - as from the total protein - a pathological CSF state cna be concluded, but no discrimination between MS and other diseases of the central nervous system is possible. The relative percent values for the gamma-globulins are much less correlated with total protein in all the 4 groups compared; consequently, they represent a more specific criterion for differential diagnosis.


Diabetic retinopathy and the fibrinolytic system. We found that patients with long-standing (greater than 10 years) diabetes who have not developed retinopathy had a significantly higher and almost normal fibrinolytic response to venous occlusion and also a higher spontaneous fibrinolytic activity than those who had developed retinopathy. In the latter, the low fibrinolytic activity of the blood was, however, not correlated to a low plasminogen activator activity of the vessel walls. Although generally lower than in controls, the activator activity of the vessel walls in the retinopathy group tended to be higher than in the rest, and in fact those with only minor vascular changes (microaneurysms) had a significantly higher activity than the other diabetics. The fibrinogen and alpha2-macroglobulin levels were higher in the retinopathy group. Thus multiple abnormalities of the fibrinolytic system were found to be related to diabetic microangiopathy.


Distribution of blood and serum protein group characteristics in patients with diabetes. In a sample of 1.033 diabetic patients characteristics of 10 group specific systems (ABO, MNS, Rh, P, K and Fy blood groups and Hp, Gc and Gm serum types) were tested in order to verify any association of hereditary group specific traits and diabetes. The patients were subgrouped for sex, seriousness of diabetes, age of manifestation and body type. The frequencies of the group specific traits were statistically compared with those of an appropriate control group using the chi2 test. Resulting from that investigation an increase of blood group 0 was found in diabetes below average in corpulence (basing upon the Rohrer index), and a confirmation was found for an already suspected association of diabetes and the Gm (a plus x plus) type.


Subepithelial collagen in intestinal malabsorption. Intestinal biopsies from 146 patients with adult coeliac disease and 13 patients with intestinal villous atrophy of different aetiology were assessed for the presence of subepithelial collagen and compared with a group of 20 control subjects. Subepithelial collagen was a common and non-specific finding observed in intestinal biopsies from patients suffering from adult coeliac disease (36%) and tropical sprue. In adult coeliac disease the described subepithelial changes usually regress following treatment, though marked subepithelial collagen deposition may indicate a poor prognosis. The study showed that the presence of marked subepithelial collagen in a flat jejunal biopsy does not define a separate clinical entity.


[Echinococcus multilocularis causing extensive biliary obstruction (author's transl)]. Infection of man by Echinococcus multilocularis occurs relatively seldom, most commonly localizing in the liver in the manner of a malignant tumour. A case of alveolar hydatid disease is reported presenting with extensive biliary obstruction, and a large cavitation in the liver due to necrosis. A review of epidemiology, clinical and roentgenological findings is given.


Familial inversion of chromosome No. 8: an affected child and a carrier fetus. An infant with multiple congenital anomalies was found to have a duplication-deficiency disorder involving chromosome No. 8. The abnormality was identified as an unbalanced recombinant inherited from the mother who was a carrier of a pericentric inversion of chromosome No. 8. The inversion was observed in several members of this family, including a fetus who was diagnosed by an amniocentesis. The inverted chromosome was demonstrated only with the use of a differential staining technique, in this case, by trypsin-Giemsa banding.


Mammalian chromosome identification in interspecific hybride cells using "Hoechst 33258". Treatment of fixed chromosome preparations of mouse-human hybrid cells with the benzimidazol derivative "Hoechst 33258" makes it possible to distinguish between mouse and human chromosomes. Treatment of live cells results in differential condensation of mouse and human centromeric regions. The effects of the dye on a mouse-human translocation and the species specific differences of staining and of condensation are in accordance with the assumption that the action of "H 33258" is specifically dependent on the base composition of the DNA.


Modulation of human neutrophil polymorphonuclear leucocyte migration by human plasma alpha-globulin inhibitors and synthetic esterase inhibitors. The exposure of isolated washed human neutrophils to purified human alpha1-antitrypsin resulted in a transient 2-fold enhancement of random migration and concomitant 70-90 per cent inhibition of chemotactic responsiveness to C5a or C3a, while treatment with alpha2-macroglobulin gave a less pronounced brief enhancement of random migration and prolonged 40-60 per cent suppression of chemotaxis. Peak effects occurred with concentrations of 1 mug/ml of alpha1-antitrypsin and 10 mug/ml of alpha2-macroglobulin. In contrast, the inhibitor of the activated first component of complement, at the highest concentration studied of 100/mug/ml, slightly enhanced chemotactic migration in response to C5a without influencing random migration. Preincubation of neutrophils with either L-1-tosylamide-2-phenylethyl-chloromethyl ketone (TPCK) or N-alpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK) at concentrations of 10-8-10-4M suppressed chemotaxis with concomitant inhibition of random migration by TPCK and enhancement of random migration by TLCK. All agents worked directly and irreversibly on the cells but caused only slight stimulation of the activity of the hexose monophosphate shunt of layers of adherent neutrophils. The results suggest that interaction of the plasma alpha-globulins or synthetic esterase inhibitors with surface receptors on neutrophils can influence both the random migration and responsiveness to chemotactic factors of these cells.


Multiple specificities of mammalian blood group substances comparatively studied with human isoagglutinins and fractionated anti-H lectins. Purified blood group-active substances derived from different pig, horse, baboon, Rhesus monkey and human tissues were quantitatively studied for their haemagglutination inhibiting potency with: (1) human IgM anti-A and anti-B; (2) human anti-Lea and anti-Leb; (3) Ulex europaeus extracts separated into lectin fractions with respective L-fucose-inhibitable ('anti-HF') and chitobiose-cellobiose-inhibitable ('anti-HC') combining sites. Irrespective of species origin, A and B blood group activity per milligram of purified material tended to be strikingly higher in substances low in, or devoid of, Lewis blood group activity. Most of the blood group substances displayed variable but about equally balanced amounts of Ulex anti-HF and anti-HC inhibiting activity. In contrast, pig submaxillary gland mucins displayed strikingly high levels of Ulex anti-HC inihibiting activity, even in the complete absence of Ulex anti-HF inhibiting activity. These serological findings are consistent with current biochemical concepts regarding the heterosaccharide microheterogeneity of blood group-active glycoproteins.


Immunosuppresive effect of a human hepatic glycoferroprotein, alpha2H globulin. A study on the transformation of normal human lymphocytes. A macroglycoferroprotein of hepatic orgin, alpah2H globulin, the serum level of which increases a few weeks or months before local recurrence of metastases, has been essayed for its immunosuppressive activity. The study was carried out using the lymphoblastic transformation test and was judged by tritiated thymidine incorporation and microscopic examination. PHA-induced blast transformation of 97 per cent of normal donor lymphocytes is inhibited by 100 mug/ml of alpha2H globulin. This inhibitory effect is proportional to the quantity of added alpha2H globulin. In is obvious with a concentration of 2-5 mug/ml, a frequently observed level in the serum of patient with tumours. Preincubation of lymphocytes with alpha2H globulin renders more effective the inhibitory action on PHA-induced transformation. A mechanism of competition between PHA and alpha2H globulin is suggested by preincubation and the inhibitory effect related to the doses. However, microscopic observation shows that alpha2H globulin acts on the earliest events occurring to the stimulated lymphocytes, by inhibiting cytoplasmic RNA and protein synthesis. The alpha2H globulin effect may not only have an immunosuppresive activity but it may have a more general effect, for example blocking or modifying cellular respiration.


Incomplete antibodies and immunoglobulin characterization in adult urodeles, Pleurodeles waltlii Michah. and Triturus alpestris Laur. Humoral immunoglobulin synthesis has been studied in two adult urodeles, Pleurodeles waltlii Michah. and Triturus alpestris Laur. following SRBC immunization. The specific antibody response is detected after a long period of immunization and is due exclusively to 'incomplete' antibodies which are unable to induce agglutination. The antibody titre is essentially dependent on the number of stimulations rather than on the dose or nature of the antigen (papainized or normal erythrocytes). Antibodies are detected in only 50 per cent of the immunized animals, 50 per cent never respond. This suggests that the latter group does not possess the genetic equipment (Ir genes) to recognize the antigenic determinants and to synthesize the corresponding antibodies. The sedimentation coefficient of the synthesized immunoglobulins was investigated by sucrose density gradient centrifugation and their characterization was carried out by starch and polyacrylamide gel electrophoresis. With this peculiar antigen even after a booster injection, only one class of immunoglobulin, an 18-2S IgM could be detected.


Immunological responses to Salmonella R antigens. The bacterial cell and the protein edestin as carriers for R oligosaccharide determinants. Responses in rabbits to heat-killed Salmonella minnesota R mutants (chemotypes Ra, Rc and Re) were heterogeneous with respect to the amounts and specific haemagglutinin activities (SHAA) of IgM and IgG antibodies produced to each mutant. Amounts of antibodies in IgM and IgG fractions of sera were determined by quantitative precipitation. For comparison, antibodies were also isolated using an R oligosaccharide-specific immunoadsorbent and quantitated spectrophotometrically. SHAA (haemagglutinating units/mg antibody) of IgG antibodies were similar for all three mutants. In contrast, the Ra mutant induced IgM antibodies with the highest SHAA, while the Re mutant induced IgM antibodies 10-fold lower in activity. The ratio of the amount of IgM/IgG produced was approximately 1/1 for both the Ra and the Rc mutants, while the ratio for the Re mutant was about 1/2. Salmonella R oligosaccharide-protein conjugates (chemotypes Rb2, Rc and Re) were prepared, and the responses to these antigens were compared with those to the heat-killed mutants. The conjugates were specific for the given chemotype, and they were strongly immunogenic when incorporated into Freund's complete adjuvant and administered intramuscularly. Haemagglutinin titres were relatively high, but amounts of antibodies were considerably reduced when the conjugates were administered intravenously without adjuvant. Rabbits immunized with the conjugates in the same manner as with heat-killed R mutants produced predominantly IgM responses in all three cases.


Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes. Granulocytes from the peripheral blood of normal subjects and a patient with hereditary myeloperoxidase deficiency were homogenized in 0.34 M sucrose. A granule-rich fraction, prepared by sedimentation at 27,000 x g for 20 min, contained components that killed C. parapsilosis in vitro. These were extractable with 0.01 M citric acid and were shown by micropreparative polyacrylamide electrophoresis to be multiple. The candidacidal activity of these neutrophil components was heat stable and they were somewhat more active at pH 5.0 than at pH 7.0. When rabbit or guinea pig heterophils were obtained from sterile peritoneal exudates and similarly fractionated, they also were found to contain components that killed C. parapsilosis in vitro. These were primarily associated with a group of lysosomal cationic proteins lacking direct counterpart in human neutrophils. Among the candidacidal components of the human neutrophil was a protein, more cationic than lysozyme, that exhibited naphthol-ASD acetate esterase activity.


Effect of trace metals on phagocytosis by alveolar macrophages. Experiments were performed to measure the effect of trace metals on a vital function of the alveolar macrophage (AM), phagocytosis. Since certain trace metals were found to reduce the viability of AMs, a technique was developed to permit examination of live cells only for phagocytosis. Evidence is presented that Ni(2+) selectively altered the phagocytic activity of AMs at concentrations lower than those which caused cell death. It is further shown that a level of VO(3) (-) that caused extensive lysis and death did not reduce phagocytosis in surviving cells. The effects of Cd(2+), Cr(3+), and Mn(2+) on AMs were also examined.


Possible role of protein(s) as antigenic determinant of the type-specific main antigen of Leptospira kremastos strain Kyoto. Acid hydrolysates of the type-specific main (TM) antigen isolated from Leptospira kremastos strain Kyoto showed a considerable inhibition of complement fixation reaction between TM antigen and anti-strain Kyoto serum. A fraction of 2 N HCl hydrolysate containing exclusively a large amount of neutral sugars showed no inhibition, whereas another fraction containing only a small amount of protein(s) showed a slight inhibition. The remaining fractions containing amino sugars, protein(s), and neutral sugars showed a slight inhibition, but the inhibition did not correlate with the amount of amino sugars. TM antigen, delipidized by hydrolysis with 1 N HCl for 4 min and then dialysis, showed a strong inhibition. The lipid fraction did not show any inhibition. The inhibitory effect of nondialyzable delipidized TM antigen was completely lost by treating the antigen with proteolytic enzymes, indicating that the antigenic determinant of L. kremastos strain Kyoto is intimately related with protein(s).


Systemic amyloidosis in mice inoculated with lyophilized Candida cells. Injection of lyophilized Candida albicans or C. parapsilosis cells induced amyloidosis in outbred CFW mice. The disease process was irreversible, and a significant number of animals died of systemic amyloidosis within 400 days after the last treatment. The techniques described may represent a model system for the study of systemic amyloidosis.


Chemical composition and immunological specificity of cell wall polysaccharide group antigens of streptococcal groups P and U. The group antigens of streptococcal groups P and U were extracted with formamide and purified on diethylaminoethyl-Sephadex A-25 and Sephadex G-200. The antigens were shown to be polysaccharides located in the cell walls of the organisms. In a precipitin test, the P and U group antigens did not cross-react with homologous sera of each other, nor with specific antiserum of the group antigen of group E streptococci. The polysaccharide comprising the group P antigen contained rhamnose, glucose, galactose, glucosamine, and galactosamine; the group U antigen was similar in composition but lacked galactosamine and contained more galactose.


Interaction of hepatitis B surface antigen (Australia antigen) with membrane vesicles of Pseudomonas aeruginosa. A lysogenic strain of Pseudomonas aeruginosa was cultured from the dialysis fluid of a patient on chronic hemodialysis treatment whose blood contained hepatitis B surface antigen (HB8Ag). When this bacterium was incubated for 4 to 7 days with serum containing HB8Ag or with purified HB8Ag, a loss of the HB8Ag-specific immunological reactivity was observed. Bacteriophages can be induced from the isolated P. aeruginosa with mitomycin C; the phages, after purification on CsCl gradients, also lyse P. aeruginosa strain 25102 (ATCC). Subsequent to gradient centrifugation of the lysate, a fraction was found with a density around 1.40 g/ml that inactivated HB8Ag after a 4-h incubation at 37 C as determined by counterelectrophoresis and hemagglutination inhibition. The activity was not found in appreciable amounts in other gradient fractions. The electron microscope shows that the active fraction contains envelope vesicles of 45 to 60 nm in diameter. In spite of their loss in HB8Ag activity, the HB8Ag particles (22nm) appeared morphologically intact. These findings suggest that an enzyme(s) is present in the vesicle fraction which inactivates antigenic determinants on HB8Ag particles. Thus, the presence of these bacteria in environments such as feces, dialysis tanks, and contaminated drinking water may prevent the detection of HB8Ag.


Effect of infection with Trichinella spiralis and BCG on thymic histology. The histology of mouse thymic tissue was examined following infection with Trichinella spiralis and/or BCG. ICR/CD-1 mice were orally infected with 200 T. spiralis 56 days preceding intravenous administration of 4x10-6 viable BCG. Following assessment of delayed hypersensitive foot pad reactions to BCG, the mice were bled and sacrificed. The thymus was removed from each animal, fixed in 10% neutral buffered formalin, embedded in paraffin and cut in 4 mum sections. Examination of serial sections indicated that T. spiralis and T. spiralis-BCG infections induced distinct anatomical changes within the thymic cortex and medulla, which may be related to previously described functional alterations of the immune system.


Human antibodies to bovine alpha-globulin. Antibodies to bovine gamma-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for IgE determination (RIST) when a sheep anti-IgE antiserum was used. Furthermore, falsely positive results can sometimes be caused by such antibodies in the determination of cow-dander- or cow's-milk-specific IgE by the radio-allergosorbent test (RAST). When a rabbit anti-IgE antiserum was used instead of the sheep anti-IgE, normal IgE levels and negative RAST results were obtained. The difference is explained by the higher degree of cross-reactivity between the anti-BGG antibodies and sheep alpha-globulin than between anti-BGG antibodies and rabbit alpha-globulin.


Functional anatomy of lymph nodes. I. The paracortical cords. Histological alterations in the paracortical zones of rabbit lymph nodes were produced by the intravenous injection of the acridine dye euchrysin. The paracortical parenchyma was reduced to narrow bands of lymphoid tissue which cuffed and outlined the venules against a distended and cell-filled sinus system. These perivenous lymphocyte cuffs, termed the paracortical cords, represented the basic anatomical unit of the thymus-dependent paracortical area. Both the paracortical cords and sinuses are cell traffic pathways, but during stages of antigen-induced lymphocyte trapping the cords retain more cells than do the sinuses. Proliferation of T cells and differentiation of B cells both occur within these cords in a microenvironment conductive to cellular cooperation.


Lymphoblastoid transformation and kinetics of appearance of viral nuclear antigen (EBNA) in cord-blood lymphocytes infected by Epstein-Barr Virus (EBV). Human cord-blood lymphocytes were infected with B95.8 Epstein-Barr virus (EBV) before and after separation into B- and T-cell populations. Lymphoblastoid cells exhibiting B-cell characteristics appeared after 2 to 3 days of culture in the total population and in the separated B-cell subpopulation but not in the T-cell subpopulation. EBV nuclear antigen (EBNA) was detected concurrently with the appearance of lymphoblastoid cells. The proportion of EBNA-positive cells corresponded to that of lymphoblastoid cells, and reached 50% after 4 days. EBNA was present only in cells with B-cell markers. These observations indicate that only B-cells are susceptible to EBV infection, that the transformation occurs within a few days and that EBNA is a valid early marker for susceptibility to EBV transformation.


Distinction between tumor-specific transplantation antigen and virion antigens in solubilized products from membranes of virus-induced leukemic cells. A membrane antigen from RBL-5 leukemic cells that was solubilized and partially purified is further characterized in this study. This soluble antigen is capable of immunizating syngeneic hosts to reject neoplastic cells and thus resembles TSTA. It also induces cytotoxic antibody in syngeneic hosts capable of specifically lysing RBL-5 cells in vitro. RBL-5, however, releases infectious virus (RLV); it was necessary therefore to rule out virus or structural virion antigens as the effective immunogen. Infectious virus was not detectable in our initial crude membrane (CM) material, nor in the papain-solubilized CS or the G-150 Sephadex-chromatographed fraction. Virus-neutralizing antibody was not detected, under stringent assay conditions, in the syngeneic anti-CM sera. Antigen preparations CM, CS and the chromatographeal fractions F1, F2 and F3 were assayed in a complement-fixation test against brood-reacting antisera capable of detecting virus envelope antigen and gs antigen and against syngeneic antisera. Although our antigen preparations were positive for virion antigens, CS and F2 contained an antigen that reacted only with syngeneic antiserum. These same fractions were those reactive as immunogens. On the basis of these data, it is postulated that a cellular membrane component, other than viral, functions as TSTA.


Transplantable murine tumors release mouse-tropic and xenotropic type-C viruses. Transplantable mouse tumors used in many areas of cancer research generally produce several host-range classes of infectious type-C virus. The release of virus from such tumors should be considered in the design and evaluation of experiments in which they are used.