Localization by immunofluorescence and by light- and electron-microscopic immunoperoxidase techniques of Tamm-Horsfall glycoprotein in adult hamster kidney. 1. Tamm-Horsfall glycoprotein was isolated from hamster urine and antiserum against it was produced in rabbits. Immunoglobulin G was isolated from the antiserum. 2. Indirect methods of immunofluorescence staining were applied to kidney sections previously fixed by both perfusion and immersion methods. Tamm-Horsfall glycoprotein was identified associated with only the cells of the ascending limb of the loop of Henle and the distal convoluted tubule. Maculae densae were free of the glycoprotein. 3. Indirect immunoperoxidase procedures with light microscopy were applied to kidney sections. The results extended those found by immunofluorescence by showing that the glycoprotein is largely associated with the plasma membrane of the cells. Macula densa cells were shown to be free of the glycoprotein, although the luminal surface of the remaining cells in the transverse section of the nephron at that region was shown to contain it. 4. A variety of immuno-electron-microscopic techniques were applied to sections previously fixed in a number of ways. Providing periodate/lysine/paraformaldehyde was used as the fixative, the glycoprotein was often seen to be present not only on the luminal surface of the cells of the thick ascending limb of the loop of Henle and of the distal convoluted tubule, but also on the basal plasma membrane, including the infoldings. 5. It is generally accepted that the hyperosmolarity in the medulla of the kidney results from passage of Cl(-) ions with their accompanying Na(+) ions across the single cell layer of the lumen of the thick ascending limb of the loop of Henle, a region of the nephron with relatively high impermeability to water. We suggest that Tamm-Horsfall glycoprotein operates as a barrier to decrease the passage of water molecules by trapping the latter at the membrane of the cells. Our hypothesis requires the glycoprotein on the basal plasma membrane also.


The temperature-dependence of adenylate cyclase from baker's yeast. The Michaelis constant of membrane-bound adenylate cyclase increased from 1.1 to 1.8 mM between 7 and 38 degrees C (delta H = 13 kJ/mol). Over this temperature range, the maximum velocity increased 10-fold, and the Arrhenius plot was nearly linear, with an average delta H* of 51 kJ/mol. The temperature-dependence of the reaction rate at 2 mM-ATP was examined in more detail: for Lubrol-dispersed enzyme, Arrhenius plots were nearly linear with average delta H* values of 45 and 68 kJ/mol, respectively, for untreated and gel-filtered enzymes; for membrane-bound enzyme, delta H changed from 40 kJ/mol above about 21 degrees C to 62 kJ/mol below 21 degrees C, but this behaviour does not necessarily indicate an abrupt, lipid-induced, transition in the reaction mechanism.


The catalytically active form of histidinol dehydrogenase from Salmonella typhimurium. The active-enzyme-sedimentation procedure was used to identify the catalytically competent form of histidinol dehydrogenase (EC 1.1.1.23) isolated from Salmonella typhimurium. At pH 9.4 the active species has a sedimentation coefficient S20,W of 5.4S, indicating that the dimer with a mol.wt. of approx. 83 000 is the enzymically active form.


The sensitivity of Mycoplasma mycoides var. capri cells to gamma-radiation after growth in a medium containing the thymine analogue 5-vinyluracil. Cells of the bacterium Mycoplasma mycoides var. capri grown in a medium containing the potential radiation-sensitive thymine analogue 5-vinyluracil show a 3-fold increase in sensitivity towards irradiation of a dose of 15 krads of gamma-rays.


Effects in vitro of alloxan on the glucose metabolism of mouse pancreatic B-cells. To facilitate detailed studies of the B-cytotoxic action of alloxan we developed a model using isolated pancreatic islets of normal mice. An essential feature of this model is the low temperature employed during exposure to alloxan, which minimizes the degradation of the drug. The islets were incubated with alloxan for 30min at 4 degrees C and subsequently various aspects of their metabolism were studied. The O(2) consumption was measured by the Cartesian-diver technique. Islets exposed to 2mm-alloxan and control islets had the same endogenous respiration, whereas the O(2) uptake of the alloxan-treated islets was inhibited and that of the control islets stimulated when they were incubated with 28mm-glucose as an exogenous substrate. The islet glucose oxidation was estimated by measurement of the formation of (14)CO(2) from [U-(14)C]glucose at 37 degrees C. Compared with the controls, alloxan-treated islets showed a decrease in the glucose-oxidation rate in a dose-dependent manner. Pretreatment of the islets with 28mm-glucose for 30min at 37 degrees C completely protected against this effect, whereas preincubations at glucose concentrations below 16.7mm failed to exert any protective effect. The glucose utilization was estimated as the formation of (3)H(2)O from [5-(3)H]glucose. Alloxan (2mm) failed to affect islet glucoseutilization rate in the presence of either 2.8 or 28mm-glucose. In contrast, islets exposed to 5 or 10mm-alloxan exhibited lowered glucose utilization. It is concluded that in vitro alloxan has an acute inhibitory effect on the islet glucose metabolism, and that this action can be prevented by previous exposure to a high glucose concentration. The results are consistent with the idea that the B-cytotoxicity of alloxan reflects an interaction with intracellular sites involved in the oxidative metabolism of the B-cell.


Identification of a clinical subset of systemic lupus erythematosus by antibodies to the SM antigen. The clinical and renal histologic attributes of 135 systemic lupus erythematosus (SLE) patients with DNA and/or Sm antibodies were compared to determine if the presence of the Sm antibodies served as a marker for a specific subset of SLE. Although Raynaud's phenomenon was more frequent in patients with Sm antibodies (P less than 0.005), serious central nervous system disease was over three times as common in patients with DNA antibodies (P less than 0.005). Only one of 23 patients with Sm antibodies had diffuse proliferative glomerulonephritis on renal biopsy, whereas 6 of 14 patients with only DNA antibodies had this histologic finding (P = 0.01). The Sm antibody system may therefore identify a subset of SLE patients with milder central nervous system and renal disease.


Accelerated appearance of neoplasms in female NZB/NZW mice treated with high-dose cyclophosphamide. Prolonged immunosuppressive therapy with cyclophosphamide increases the prevalence of neoplasms in NZB/NZW mice, an animal model of systemic lupus erythematosus. The current study was designed to compare the oncogenic properties of high dose cyclophosphamide with a low dose therapeutic regimen. Female NZB/NZW mice received life-long therapy with "high dose" cyclophosphamide, 16 mg/kg/day, or "low-dose" cyclophosphamide, 5.7 mg/kg/day; control mice received saline. High dose therapy clearly accelerated appearance of neoplasms. Seventeen of 19 mice treated with high-dose cyclophosphamide developed neoplasms at the mean age of 61 weeks. Fifty-seven percent of these tumors were mammary carcinomas. Neoplasms appeared in all mice treated with low dose; mean longevity in this treatment group was 80 weeks (compared to high dose treated mice, P less than 0.001). Carcinomas, pulmonary adenomas, and lymphomas were the most common tumors in mice receiving low dose therapy. Positive tests for ANA were suppressed in high dose treated mice. AntiDNA antibody levels and glomerulonephritis were decreased significantly in both groups of cyclophosphamide-treated mice compared to controls. It was concluded that the high daily dose of immunosuppressive drug was related to early oncogenesis in autoimmune NZB/NZW mice.


Effect of p-hydroxyphenyl-propionic ester of tranexamic acid hydrochloride (Cetraxate) on peptic ulcer. Multi-center clinical study. The therapeutic effects of a new antiulcer drug, a p-hydroxyphenyl-propionic ester of tranexamic acid (cetraxate, CET) hydrochloride, were investigated in 234 patients with gastric ulcer by double blind controlled study using trans-3,7-dimethyl-2,6-octadienyl-5,9,13-trimethyltetradeca-4,8,12-trienoate (gefarnate) as the standard drug in 18 medical institutions. The cure rates confirmed by endoscopic examination in CET-treated patients were 28, 61 and 73% each after 4, 8 and 12 weeks of medication, while those in gefarnate-treated patients were 23, 47 and 55%, respectively, with statistical significance after 8 and 12 weeks. Global utility rate based on the judgement by the physician in charge also supported the results with cure rate. Stratified analysis again confirmed the superiority of CET hydrochloride against gefarnate in the hospitalized patients in terms of both cure rate and global utility rate. However, there was no significant difference between the two drugs as to the effects in the out-patients. Among the symptoms, there was also a significant difference between the improvement rate of epigastralgia with the two drugs in favour of CET hydrochloride. No serious side effects were reported throughout the study.


Lymphocytes and monocytes in the aortic intima--An electron-microscopic study in the rat. In an electron-microscopic survey of the aorta in the adult rat, white blood cells were found adhering to the intima; these were invariably lymphocytes or monocytes. Similar cells were also found beneath the endothelium. Counts were not made, but published data indicate that mononuclear cells lying over or within the rat aortic intima are approximately 1 for every 9 endothelial cells. This infiltration by blood-borne cells is interpreted as a pathologic event, possibly in response to a chemical message (antigen?) originating from the underlying media.


["In vitro" and "in vivo" antibacterial activity of a new synthetic antibiotic cinoxacin]. The Authors have conducted the experimental studies tending to valuate the antibacterial activity in vitro and in vivo of cinoxacin versus that demonstrated by nalidixic acid. The obtained results demonstrate the cinoxacin presents a similar antibacterial activity to that of nalidixic acid.


Nefopam in postoperative pain.

Nefopam in postoperative pain. Three comparable groups of surgical patients were given nefopam 0.2 mg kg-1 or 0.4 mg kg-1 or morphine 0.15 mg kg-1 for pain relief after operation. Nefopam 0.4 mg kg-1 was equi-analgesic with morphine 0.15 mg kg-1 and produced no obvious cardiovascular or respiratory side-effects.


Cardiovascular response to the i.v. administration of morphine in critically ill patients undergoing IPPV. The haemodynamic changes following the administration of morphine 0.15 and 0.30 mg kg-1 i.v. were studied in 11 patients, free from known cardiac disease. All patients were acutely ill and their lungs were being ventilated mechanically. In those patients receiving 0.15 mg kg-1, the only haemodynamic change was a slight and transitory decrease in the systolic arterial pressure. In contrast, several changes were observed in patients receiving 0.30 mg kg-1: an immediate and prolonged decrease in the cardiac index was noted along with transient decreases in heart rate, stroke volume index, arterial pressure and left stroke work index. These results suggest that the haemodynamic cost of morphine 10 mg is negligible but could be significant when 20 mg has been administered and must be weighed against its beneficial effects in the critically ill patient.


Decreased plasma protein binding of phenytoin in patients on valproic acid. 1 Plasma protein binding of phenytoin and of valproic acid were measured in ten epileptic patients on this drug combination. Ten other epileptics not on valproic acid served as controls. All patients had normal kidney function. 2 The measured free fraction of phenytoin among the patients on valproic acid ranged from 12.5 to 23.2% and after recalculation to a plasma albumin level of 45 g/l from 12.5 to 20.0 (median 15.4%). This differed significantly (P = 0.002, Mann- Whitney U-test) from the control patients where the normalized values ranged from 9.9 to 13.9% with a median value of 11.8%. 3 The measured free fractions of phenytoin and of valproic acid showed a significant correlation which, however, was due to the quantitative relation between the degree of binding of both these drugs and the concentration of plasma albumin. There was no discernable relation in this material between the free concentration of valproic acid and the free fraction of phenytoin. 4 It is concluded that patients on combined treatment with phenytoin and valproic acid have an unpredictably raised free fraction of phenytoin. This drug interaction therefore can complicate the important plasma level monitoring of phenytoin in epileptic patients unless the free concentration of this drug can be analysed or estimated.


Modification of phenytoin clearance by valproic acid in normal subjects. 1 The effect of valproic acid on the distribution and elimination kinetics of intravenously administered phenytoin has been investigated in eight normal volunteers. 2 In each of the subjects studied the volume of distribution of phenytoin increased significantly during treatment with sodium valproate (1200 mg daily for 7 days). 3 Phenytoin clearance was markedly increased in presence of valproic acid as compared to control values (0.52 +/- 0.17 v 0.38 +/- 0.11 ml min-1 kg-1 respectively, P less than 0.02). 4 It is suggested that the increase of the volume of distribution and of the serum clearance are secondary to displacement of phenytoin from plasma protein binding sites by valproic acid.


Comparison of propranolol and metoprolol in the management of hyperthyroidism. 1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.


Contact allergic sensitivity to chrysanthemum and the photosensitivity dermatitis and actinic reticuloid syndrome. Of sixty-nine examples of the photosensitivity dermatitis and actinic reticuloid syndrome, nine were found to be allergically sensitive to chrysanthemum oleoresin extract. Although this extract showed evidence in vitro of a phototoxic action we were unable with in vivo studies to explain the connection between the contact allergic sensitivity and the photosensitivity. The fractions responsible for the in vitro phototoxicity appear to be different from those involved in the in vivo contact allergic sensitivity. This study provides further support for the view that in the photosensitivity dermatitis and actinic reticuloid syndrome contact allergic sensitivity is of importance.


The events leading to the death of patients with pemphigus and pemphigoid. This paper is based upon a study of all available records of patients certified as having died in hospital from pemphigus and pemphigoid in England and Wales from 1962 to 1969. The results differ from most published series in that many of the 210 patients died still with extensive skin lesions and with biochemical abnormalities, such as low serum albumin, sodium and chloride, which were secondary to this. Side-effects of treatment, such as diabetes, peptic ulceration, and infections, were also important but the commonest immediate causes of death were respiratory tract infections and pulmonary embolism.


IgA linear dermatosis of childhood (chronic bullous disease of childhood). Of twenty-seven cases of subepidermal blistering disease of children twelve corresponded clinically, histologically and immunologically to dermatitis herpetiforms of adults, six to bullous pemphigoid, and eight to chronic bullous disease of childhood (CBDC), i.e. IgA linear dermatosis. This latter disease seems to be a distinct entity, different from both dermatitis herpetiformis and bullous pemphigoid, and is characterized immunopathologically by linear IgA deposits at the basement membrane zone. These cases usually do not show intestinal involvement and respond well to combined treatment with sulphones and corticosteroids, whereas sulphones or sulphapyridine alone are, even in very high doses, not sufficient for full control of the disease. CBDC or IgA linear dermatosis of childhood may be regarded as a counterpart of IgA linear dermatosis of adults.


p-(Bromoacetamido)phenyl uridyl pyrophosphate: an active-site-directed irreversible inhibitor for uridine diphosphate galactose 4-epimerase. The synthesis of p-(bromoacetamido)phenyl uridyl pyrophosphate (BUP) is described. This compound is an active-site-directed irreversible inhibitor of Escherichia coli UDP-galactose 4-epimerase. The inactivation follows pseudo-first-order kinetics at pH 8.5 in nonnucleophilic buffers, and a saturation effect is seen in the pseudo-first-order rate constant as the concentration of BUP is increased. The half-saturation parameter for BUP in the inactivation is 0.21 +/- 0.02 mM, which compares favorably with the inhibition constant of 0.3 +/- 0.05 mM for BUP acting as a competitive reversible inhibitor of the enzyme. The inactivation rate is slow, however, with a minimum half-time of 12 h at pH 8.5 and 27 degrees C. Both specific alkylation and nonspecific alkylation by BUP occur, but nonspecific alkylation is faster than the inactivation and the rate of inactivation correlates well with the rate of covalent incorporation of one molecule of [14C]BUP at the active site.


Partial purification and characterization of a protein lysine methyltransferase from plasmodia of Physarum polycephalum. Plasmodia of Physarum polycephalum have an active protein lysine methyltransferase (S-adenosylmethionine:protein-lysine methyltransferase, EC 2.1.1.43). This enzyme has been purified 40-fold with a 13% yield, and it catalyzes the transfer of methyl groups from S-adenosyl-L-methionine to the epsilon-amino group of lysine residues with formation of N epsilon-mono-, N epsilon-di-, and N epsilon-trimethyllysines in a molar ratio of 4:1:1 based on [14C]methyl incorporation into the methylated lysines. The ratio remains unchanged at all stages of the partial purification, as well as after fractionation by sucrose density gradient centrifugation and gel electrophoresis. The rate of protein methylation is time dependent, enzyme concentration dependent, and requires the presence of a sulfhydryl reducing agent for optimal activity. The enzyme has optimal activity at pH 8 and is inhibited by S-adenosyl-L-homocysteine and EDTA. Lysine-rich and arginine-rich histones serve as the most effective exogenous protein acceptors; P. polycephalum actomyosin is inactive, and chick skeletal myofibrillar proteins are 25% as effective as exogenous mixed histones as substrates. Lysine, polylysine, ribonuclease A, cytochrome c, and bovine serum albumin are not methylated.


Collagen synthesis by bovine aortic endothelial cells in culture. Endothelial cells isolated from bovine aorta synthesize and secrete type III procollagen in culture. The procollagen, which represents the major collagenous protein in culture medium, was specifically precipitated by antibodies to bovine type III procollagen and was purified by diethyl-aminoethylcellulose chromatography. Unequivocal identification of the pepsin-treated collagen was made by direct comparison with type III collagen isolated by pepsin digestion of bovine skin, utilizing peptide cleavage patterns generated by vertebrate collagenase, CNBr, and mast cell protease. The type III collagen was hydroxylated to a high degree, having a hydroxyproline/proline ratio of 1.5:1.0. Pulse-chase studies indicated that the procollagen was not processed to procollagen intermediates or to collagen. Pepsin treatment of cell layers, followed by salt fractionation at acidic and neutral pH, produced several components which were sensitive to bacterial collagenase and which comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with alpha A, alpha B, and type IV collagen chains purified from human placenta by similar techniques. Bovine aortic endothelial cells also secreted fibronectin and a bacterial collagenase-insensitive glycoprotein which, after reduction, had a molecular weight of 135,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (using procollagen molecular weight standards) and which was not precipitable by antibodies to cold-insoluble globulin or to alpha 2-macroglobulin. Collagen biosynthesis by these cells provides an interesting model system for studying the polarity of protein secretion and the attachment of cells to an extracellular matrix. The presence of type III collagen in the subendothelium and the specific interaction of this protein with fibronectin and platelets suggest the involvement of this collagen in thrombus formation following endothelial cell injury.


Protein synthesis kinetics with ribosomes from temperature-sensitive mutants of Escherichia coli. The kinetics of MS2 ribonucleic acid (RNA) directed protein synthesis have been investigated at seven temperatures between 30 and 47 degrees C by using ribosomes isolated from a wild type strain and seven temperature-sensitive mutants of Escherichia coli. The amount of MS2 coat protein formed at each temperature was determined by gel electrophoresis of the products formed with control ribosomes. With ribosomes from each of the mutant strains, the activation energy required to drive protein synthesis below the maximum temperature (up to 40 degrees C) was increased relative to the control (wild type) activity. Preincubation of the ribosomes at 44 degrees C revealed the kinetics of thermal inactivation, with ribosomes from each of the mutants having a half-life for inactivation less than that of the control ribosomes. A good correlation was observed between the relative activity of the different ribosomes at 44 degrees C and their relative rate of thermal inactivation. Mixing assays allowed the identification of a temperature-sensitive ribosomal subunit for each of the mutants. Defects in one or more of three specific steps in protein synthesis (messenger RNA binding, transfer RNA binding, transfer RNA binding, and subunit reassociation) were identified for the ribosomes from each mutant. The relationship between temperature sensitivity and protein synthesis in these strains is discussed.


Structure and enzymatic functions of thioredoxin refolded by complementation of two tryptic peptide fragments. The physicochemical and catalytic properties of thioredoxin-T' are described. This complemented protein structure consists of a 1:1 complex between the inactive fragments thioredoxin-T-(1--73) and thioredoxin T-(74--108). These are generated by selective trypsin cleavage at Arg-73 in lysine-modified and denatured Escherichia coli thioredoxin. Thioredoxin-T' was a slowly formed but stable complex with an apparent KD below 10(-8) M. The tryptophan fluorescence spectrum and the CD spectrum were very similar to those of native thioredoxin; some conformational differences were detected by gel chromatography and radioimmunoassay. Thioredoxin-T'-S2 was a substrate for NADPH and thioredoxin reductase and had 1--2% of the activity of native thioredoxin. This low relative activity was the result of a major increase in the Km value. Thioredoxin-(SH)2 was a hydrogen donor for E. coli ribonucleotide reductase with about 3% relative activity. These results for thioredoxin-T' are correlated with the known three-dimensional structure of thioredoxin. The microenvironment around Arg-73 that is close to the active disulfide appears to be of critical importance for the interactions of thioredoxin with thioredoxin reductase and ribonucleotide reductase.


Effect of an induced conformational change on the physical properties of two chemotactic receptor molecules. The physical properties and conformational dynamics of the Salmonella typhimurium ribose and galactose receptors have been examined. Studies involving circular dichroism, fluorescence, absorption spectroscopy, and sedimentation analysis show that the two receptor proteins have different morphologies and exhibit diverse responses to sugar binding. The ribose receptor lacks both tryptophan and disulfide residues, and the galactose receptor lacks disulfides and has only a single tryptophan residue. By virtue of these fortuitous properties, the conformational changes induced in these proteins by sugar binding can be dissected by utilizing a variety of physical probes. A ligand-induced conformational change in the ribose receptor is shown by circular dichroism and fluorescence spectroscopy, which reveal spectral changes assignable to tyrosine, phenylalanine, and methionine residues. A conformational change in the galactose receptor has been demonstrated by fluorescence spectroscopy involving the distant reporter group method, which shows changes assignable to tryptophan and methionine sites and which is corroborated by sedimentation analysis. It is clear that there are extensive conformational changes in the two receptor proteins and that the different physical methods provide complementary information on the nature of these changes.


Selective repression of transcription by base sequence specific synthetic polymers. We report the effect of novel synthetic polymers on deoxyribonucleic acid (DNA) directed ribonucleic acid (RNA) synthesis in vitro. Polymers contained base-selective monomers, including a GC-specific phenazine derivative and an AT-specific triphenylmethane dye. Radical chain polymerization was carried out in aqueous solution by using monomers bound to a template DNA, which was obtained from either lambda or T7 bacteriophage. Polymers were isolated and reannealed with DNA samples, including competitive mixtures of T7 and lambda DNAs. We measured transcription from DNA-polymer complexes by using Escherichia coli RNA polymerase and determined not only the reduction in total transcription levels but also the relative inhibition of lambda- or T7-specific transcription by using a hybridization assay. The results show that micromolar concentrations of individual dyes are sufficient to cause substantial inhibition of transcription when the dyes are incorporated into polymers. More significantly, a number of the polymers inhibited more strongly transcription from the DNA which had served as template for polymer synthesis than from the DNA present as competitor in the annealing process. We conclude that template synthesis of DNA-binding polymers can lead to preferential inhibition of function of the original template. The apparent relative affinity of polymer for competing DNAs can be altered by at least an order of magnitude depending on which DNA was used as the synthesis template. The results offer a new approach to improving the specificity of DNA-binding drugs.


Circular dichroism study of the solution conformation of luteinizing hormone releasing hormone. A systematic investigation has been made into the circular dichroic behavior of luteinizing hormone releasing hormone and its peptide fragments and deletion analogues. The results are interpreted to mean that the hormone exists in solution as an ensemble of conformers with different sensitivities to temperature and solvent composition. The far-ultraviolet circular dichroic spectra exhibited by the hormone under different experimental conditions can be simulated satisfactorily by the weighted addition of the spectra of its aliphatic- and aromatic-containing halves. However, the structure of the hormone is not simply the sum of its halves, since some conformational feature of the intact molecule perturbs the near-ultraviolet circular dichroism of its aromatic residues.


Isolation and characterization of twenty-three ribosomal proteins from large subunits of yeast. The proteins of large ribosomal subunits from Saccharomyces cerevisiae were separated into 25 fractions by chromatography on columns of carboxymethylcellulose (CMC). Twenty-three proteins were then purified from the 12 CMC fractions by filtration through Sephadex G-75, Sephadex G-100, and Sephacryl S-200, and/or by phosphocellulose column chromatography. The isolated proteins are YP 1, YP 2, YP 9, YP 11, YP 13', YP 16, YP 18, YP 26, YP 39, YP 41, YP 42, YP 42', YP 44, YP 45, YP 47', YP 52a, YP 53, YP 55, YP 59, YP 62, YP 68, YP A1, and YP A2. The molecular weight and amino acid composition of these proteins are presented.


The Escherichia coli phosphoenolpyruvate-dependent phosphotransferase system: observation of heterogeneity in the amino acid composition of HPr. Resonances of the aromatic protons of tyrosine have been observed in the proton nuclear magnetic resonance (1H NMR) spectrum of purified HPr from Escherichia coli. Analysis of the NMR spectrum of native HPr suggests that the tyrosine is located in a single position in the secondary structure and that this position is on the interior of the molecule inaccessible to solvent. Previous reports suggested that E. coli HPr contained no tyrosine [Anderson, B., Weigel, N., Kundig, W., & Roseman, S. (1971) J. Biol. Chem. 246, 7023--7033]. In contrast, we find, by amino acid analysis and ultraviolet and NMR spectroscopy, that E. coli HPr does contain tyrosine but at a subintegral level of 0.5 +/- 0.1 mol of tyrosine per mol of HPr.


N-(5-Phosphoribosyl)anthranilate isomerase-indoleglycerol-phosphate synthase. 2. Fast-reaction studies show that a fluorescent substrate analogue binds independently to two different sites. The mechanism of binding of reduced 1-(2-carboxyphenylamino)-1-deoxyribulose 5-phosphate (rCdRP) to two different binding sites on the bifunctional enzyme is determined by kinetic studies, using temperature-jump and stopped-flow equipment with fluorescence detection. Two rapid binding processes and a comparatively slow isomerization process are observed over a wide range of enzyme and rCdRP concentrations. Kinetic measurements with low concentrations of rCdRP show that the isomerization is coupled only to the more rapid of the two binding reactions that involves the active site of indoleglycerol-phosphate synthase. The slower of the two binding reactions represents rCdRP binding in one step to the active site of (phosphoribosyl)anthranilate isomerase. The simplest mechanism explaining quantitatively the dependence of the relaxation times on concentration consists of rCdRP binding to two sites on the enzyme that are intrinsically different and independent, even to the extent that a ligand-induced isomerization of one site is not transmitted to the other site. Simulation studies show that the concentration dependences of the amplitudes of the three relaxation processes are also consistent with the mechanism. The results are discussed in terms of two autonomous domains of folding of the polypeptide chain.


Electrophoretic variation of aconitase and phosphoglucomutase detected in Microtus californicus. Four electrophoretic variants of cytoplasmic aconitase (citrate (isocitrate) hydro-lyase, EC 4.2.1.3) were detected in a population of Microtus californicus when samples were screened by starch gel electrophoresis using Tris/citrate buffers at pH 7.0 and pH 8.7. Variation at what is presumed to be the phosphoglucomutase-3 locus (alpha-D-glucose-1,6-diphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1) was also detected with liver samples but was not detected in kidney samples or red blood cells lysates. This nongenetic variation is due to oxidation of free sulfhydryl groups.


Reactivity of anti nucleoside antibodies with metaphase chromosomes. It is shown that the binding of anti-nucleoside antibodies to fixed human metaphase chromosomes can be revealed using the immunoperoxidase procedure while under the same conditions no antibody binding is revealed using the immunofluorescence procedure.


Mechanical cardiopulmonary support and artificial hearts. The literature pertaining to the field of mechanical support of the circulation has been selective reviewed. The principal restraints to its further progress have been highlighted, and the efforts of the writer and his coworkers in certain of these sensitive areas has been commented on. The future of the materials problem, a major one, lies in study at the molecular level.


Hb A1c: a review on its structure, biosynthesis, clinical significance and methods of assay. Normal red blood cells contain, in addition to the major hemoglobin (Hb A) some minor fractions as Hb A2 and glycosylated hemoglobins: Hb A1a, Hb A1b, Hb A1c. The study of the glycosylated hemoglobins has been greatly stimulated by the observation that their proportion was increased in diabetes mellitus. This paper sums up the more recent knowledge on the structure of the minor fractions, and mainly on Hb A1c. Biosynthesis of these hemoglobins is also considered. Since the glycosylated hemoglobins has raised a great interest, different techniques were designed for its assay: chemical, chromatographic and immunological techniques and isoelectric focusing. In this paper, these different methods are reviewed and compared.


[Immunoluminescent detection of antibodies to testicular antigens in experimental autoimmune orchitis]. Antibodies interacting with spermatid structures in the testis sections and with acrosome and caudal regions of spermatozoa in the smears of sperm were determined in the sera of guinea pigs and mice with experimental autoimmune orchitis by the indirect immunofluorescent method. The antibodies were found in mice from the 14th to the 30th day and in guinea pigs from the 14th to the 60th day after immunization. Circulation time and the level of the fluorescent antibodies were significantly decreased in immunized female guinea pigs and mice. Fluorescent antibodies did not show cytotoxic effect and belonged to the IgG fraction. The fluorescent antibodies of guinea pigs did not react with the mouse testicular antigens in cross reaction. The analogous results were seen in the cross reaction of the mouse antibodies with the guinea pig antigens.


[Specifically reactive cells in experimental allergic pertussis encephalomyelitis]. Dynamics of emergence of specific reactive cell (SRC) with respect to the brain antigen in the draining regional lymph nodes and peripheral blood was studied in experimental whooping cough allergic encephalomyelitis (EAE) in guinea pigs. The greatest number of SRC in the regional lymph nodes, that markedly decreased by the 9th day of sensitization, was revealed in the middle of the EAE incubation period (the 6-7th day), whereas the peripheral blood showed the highest SRC number during this period. The SRC number rose in the regional lymph nodes and dropped in the peripheral blood at the height of EAE progress (the 20th day). It is concluded that SRC found may be attributed to T lymphocyte population.


[Cellular regulation of human lymphocyte mitogenic factor release in vitro]. Production of the mitogenic facotr by human lymphocytes stimulated with phytohemagglutinin (PHA) was investigated. Anti-PHA antibodies were used for studying the culture medium mitogenic activity. The mitogenic factor production markedly increased after lymphocyte irradiation. When macrophages were eliminated, using iron powder, mitogenic factor generation was also increased. It was demonstrated that lymphocyte irradiation and macrophage elimination stimulated the mitogenic factor production throgh different mechanisms.


[Localization of neurospecific protein-antigens on the surface membrane of neurons and glia of grape shails]. The existence of cross (common) proteins-antigens on the membrane of nervous and glial cells of Helix pomatia in vitro was proved by Coons' method of immunofluorescence. The presence of the neurospecific protein S-100 on the membrane of these cells and antigenous heterogeneity of the membranes of the neuronal cell population were established. The antigen concentration was shown to vary on the somatic and axonal membranes. The distribution pattern of specific luminescence indicates potential qualitative and/or quantitative differences in the content of neurospecific proteins in various portions of the neuronal membrane.


[Role of the thymus in regulation of the macrophage migration inhibitory factor production in mice of different genotypes]. The influence of the thymus on the production of the macrophage migration inhibitory factor (MIF) was studied in C57BL and CBA mice thymectomized at 4--6 weeks of age. On the 1--21st day after the operation they were immunized intraperitoneally with complete Freund's adjuvant. MIF production stimulated by tuberculin was determined on the maximum of the immune response. MIF production was abolished in mice of both lines already during the first days. To elucidate a relationship between MIF production and the presence of the thymus the former was investigated in the thymectomized "nude" mice. The mice showed no MIF production. It was found as well that thymectomy can interrupt the immune response in early stages of its development and completely eliminates MIF production the first days after immunization. Moreover, thymectomy in adult mice also changes spontaneous migration of macrophages both in immunized and non-immunized mice. These changes were more pronounced in C57BL mice.


[Reconstruction of the tubular epithelium of allotransplanted kidneys of man in late periods following transplantation]. The structure of allotransplanted kidneys (AK) from human cadavers that remained in the recipient's body for a long time (4 months-6 years) has been studied. AK that preserved good function up to the patient's death not consequent on the transplant insufficiency showed a weak immunocellular connective tissue, with the epithelium of proximal canaliculi being cytologically reconstructed. The reconstruction lay in formation of numerous polykaryocytes having a hypertrophied brush-like outline. This phenomenon ("proximal polykaryocytosis") is assessed as a manifestation of regeneratory potencies of the epithelium of AK proximal tubules in late periods after transplantation. Chronic moderate hypoxia of AK was conducive to reconstruction of the epithelium of the nephron proximal part. Inadequate function of AK was related to the development of chronic rejection resistant to the treatment, and AK demonstrated an intensive immunocellular reaction and developed gross sclerosis that produced atrophy of most AK tubular.


Inherited glucosephosphate isomerase deficiency. A review of known variants and some aspects of the pathomechanism of the deficiency. Since the first report of GPI deficiency in 1967 many patients from all over the world have been described. The patients suffer from a typical nonspherocytic hemolytic anemia with hemolytic crises during acute infections. The disease is inherited as an autosomal recessive, half of the patients are homozygotic, the others are double heterozygotes. The biochemical properties of the deficient enzymes vary widely. Thus, many well characterized enzymes have been designated as different variants. The modification of physicochemical properties surpasses kinetic aberrations. All defective variants are more or less unstable. The activity diminishes progressively, leading to a rise in G6P concentration and in red cells after aging in vitro to a dramatic impairment of glycolysis and concomittant hemolysis. The cause of the metabolic block is the diminished GPI activity itself and not an inhibition of hexokinase by the high G6P.


Report to the Veterans' Administration Department of Medicine and Surgery on service-connected traumatic limb amputations and subsequent mortality from cardiovascular disease and other causes of death. Men drafted into the Army, hospitalized during 1944 to 1945 for service-connected trauma to the extremities, and consequently separated for disability were followed for mortality from January 1946 to April 1977. Three groups were established consisting of those whose injury resulted in (a) limb amputation, (b) disfiguration without loss of body part, (c) loss of part of hand or part of foot. Group (a) had a mortality, standardized for age and calendar time, 1.4 times that of Group (b), matched on age and length of service at admission, and 1.3 times that of Group (c), similar on age and length of service to Group (a). The excess mortality of limb amputees was statistically significant (P less than .05) for ischemic heart disease, other diseases of the cardiovascular system, suicide by poisoning, alcholic cirrhosis, and cute pancreatitis. Possibly (P less than .1) there was also an increased risk of diabetes and cancer of the buccal cavity and pharynx.


Renal transplantation with multiple arteries. Out of a total of 184 transplant operations there were 27 kidneys with 2 or more renal arteries. Five of these were in 23 related transplants. Ischaemic times were increased compared with those of kidneys with single arteries, but the incidence and duration of acute tubular necrosis and also the length of time spent in hospital were similar in both groups. Excessive bleeding and other complications were no more common than following single arterial anastomosis. Kidneys with multiple arteries can be used safely if careful interrupted suturing is performed, the kidneys are perfused before and kept cool during the procedure and polar arteries are not tied.


Comparison of buprenorphine and pethidine given intravenously on demand to relieve postoperative pain. In a double-blind study of on-demand intravenous analgesia buprenorphine was found to be about 600 times as potent as pethidine. The incidence of side effects was similar with both drugs. The quality of analgesia, subjectively assessed, was good with both drugs using this method of administration. Provided that its low potential for abuse is substantiated, buprenorphine appears to be a powerful analgesic that may successfully be given intravenously on demand.


Immunological effect of co-trimoxazole on platelets. Diminished survival of transfused platelets occurred in two patients given co-trimoxazole, and a third patient taking this drug developed thrombocytopenia. By means of an indirect immunofluorescence assay antibodies against donor platelets coated with co-trimoxazole were found in the sera in all cases. These antibodies were directed against the trimethoprim component of co-trimoxazole and not against sulphamethoxazole. Co-trimoxazole is a potent antimicrobial agent and is advocated for treatment and prophylaxis in leukaemia. Hence its adverse effect on platelets is of great importance.


Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients. A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression.


Bacterial contamination of expressed breast milk. In a study of breast milk collected into sterile bottles rinsed in 1% hypochlorite solution the hypochlorite solution adherent to the sides of the bottles apparently caused a large reduction in bacterial contamination of the milk after storage at 4 degrees C for up to four hours. Heating expressed breast milk at 62.5 degrees C for five minutes destroyed over 90% of the Escherichia coli, Staphylococcus aureus, and group B beta-haemolytic streptococci inoculated into the milk samples. Rinsing collecting bottles with hypochlorite solution may be valuable in collecting milk with a low bacterial content for human-milk banks. Furthermore, the currently accepted pasteurisation time of 30 minutes may be excessive.


Dendritic bundles: survey of anatomical experiments and physiological theories. Dendritic bundles have been found throughout the mammalian brain. Unquestionably, these bundles must serve one or more important, fundamental roles in the brain's functioning. However, no physiological experiments to determine their function have been performed on these well-established anatomical units. We survey the numerous anatomical reports of bundling. In addition, we discuss several physiological possibilities for the functional significance of bundles.


Separate hypoglycaemic thresholds for gastric acid and pepsin secretion following insulin or posterior hypothalamic stimulation. The level of hypoglycaemia required to elicit gastric secretion of acid and pepsin was studied in urethane-anaesthetized rats. Hypoglycaemia was induced by intravenous injection of insulin or by electrical stimulation of the posterior hypothalamus. In each case the blood glucose values below which gastric secretion was stimulated were significantly higher for pepsin than for acid secretion. This consistently resulted in the onset of pepsin secretion in advance of the onset of acid secretion. These observations suggest that the production of the different components of the gastric juice was under the influence of either separate hypothalamic glucoreceptors, or a single set of glucoreceptors able to respond selectively to different blood glucose levels.


Obesity may be due to a malfunctioning of brown fat. Recent basic research on the functioning of brown fat, a heat-producing tissue, has been fitted together with research on obesity to provide an exciting and challenging new approach to the study of the cause of obesity and could serve as a starting point for the development of new modes of treatment. Recent studies on brown adipose tissue have shown that a defect in this tissue is one probable cause of obesity.


Platelet transfusions.

Platelet transfusions. Platelets play a pivotal role in hemostasis by forming the initial hemostatic plug and augmenting the formation of the more permanent fibrin thrombus. Thrombocytopenia may lead to bleeding, which can be treated with therapeutic platelet transfusions or prevented with prophylactic transfusions. While many advances have been made in platelet transfusion technology, problems remain. These include the short storage life of liquid-stored platelets and the frequent development of alloantibodies (the refractory state) in patients receiving a number of transfusions. Significant progress, however, is being made in both areas.


Immunofluorescence assay for antinuclear factor: a nonspecific test in hospitalized medical patients. Serum from 149 randomly selected hospitalized medical patients was tested for the presence of antinuclear factor (ANF) by the conventional immunofluorescence technique. Patients with positive and negative results were then compared as to clinical history, particularly previous drug exposure, physical findings, and levels of C-reactive protein and immune complexes in the serum. The frequency of ANF positivity was found to be very high (23%). Although the presence of ANF was significantly correlated (P less than 0.02) with a higher age, it was not significantly related to any other clinical or laboratory feature assessed. It was concluded that ANF testing cannot serve as a blind diagnostic screening tool for connective tissue diseases because of its nonspecificity.


Antihypertensive efficacy of propranolol given twice daily. The therapeutic efficacy of propranolol in four and two daily doses was compared in 63 treated hypertensive patients in a multicentre trial. After 3 months of a stable diastolic blood pressure while receiving propranolol four times a day the patients were switched to a twice-a-day regimen, the drug being given at 8 am and 8 pm, with the same total daily dose, for 3 more months. Blood pressures and heart rates were measured at 8 am, 12 noon, 4 pm and 8 pm at 4-week intervals. There were no significant changes in mean blood pressure after the change to the twice-a-day regimen, although some patients reported new side effects. Compliance appeared to be unaffected.


Depression and loss: a theme in Robert Burton's "Anatomy of melancholy" (1621). Robert Burton's Anatomy of Melancholy (1621) can hardly be thought of as a modern study in psychiatry, but it contains more elements of modern theory than have been recognized. Attempts to recommend the book to modern readers have missed the point that Burton, more clearly than other seventeenth century writers on melancholy, sees traumatic loss of attachment figures, status symbols and personal health as predisposing to mood disorders. In this he strongly anticipates such work as that of John Bowlby in Attachment and Loss (1969), 1973). Burton's theory is divided between the humoural physiological theory descending from Galen and the observation that loss is a frequent precursor of melancholy. He cannot reconcile the two, writing a book only poised on the verge of modernity. The Anatomy of Melancholy nevertheless very fully discusses etiological "hunches" which have found verification in recent studies of traumatic loss.


Venography in axillary-subclavian vein thrombosis. Nineteen patients with 20 axillary-subclavian vein thromboses were examined by venography. In 70% the axillary and subclavian veins were involved in continuity. The innominate vein was seldom involved, although demonstration of this was difficult. In 50% of the patients the thrombosis was a secondary phenomenon associated with either breast carcinoma, central venous pressure lines, heroin addiction, or cervical rib.


The localization of oxytocin, vasopressin, somatostatin and luteinizing hormone releasing hormone in the rat neurohypophysis. The hypothalamic hormones arginine-vasopressin (AVP), oxytocin (OXT), somatostatin (SOM), and luteinizing hormone-releasing hormone (LHRH) were localized in the rat neurohypophysis by the use of semithin serial sections and the unlabeled antibody enzyme method. Clusters of AVP fibres are present within the central region of the neural lobe, clusters of OXT fibres mainly in the peripheral part. The AVP fibres enter bilaterally into the neural lobe. The results call into question previous reports on the presence of AVP on receptors in the pars intermedia cells, since incubation with anti-AVP resulted in similar staining in the pars intermedia of the Wistar and homozygous Brattleboro rat, a mutant strain deficient in AVP. The same intermediate lobe cells are stained after incubation of serial sections with anti-AVP and anti-alpha-melanocyte-stimulating hormone (alpha-MSH). This staining of anti-AVP could be removed by solid phase absorption to alpha-MSH and is thus most probably due to cross reaction with alpha-MSH. SOM fibres appear to be present in the peripheral parts of the proximal neurohypophysial stalk and mainly lateral in its more distal parts. In the neural lobe they rapidly decrease in number, although some fibres continue into the distal part of the neural lobe, running bilaterally and situated adjacent to the pars intermedia. The SOM staining within magnocellular elements, which has been reported in the literature, can most probably be explained by cross reaction of anti-SOM with neurophysins. LHRH fibres are very scarce in the neurohypophysial stalk and absent in the neural lobe.


Developmental correlation between hypothalamic somatostatin and hypophysial growth hormone. The objective of the present study was to determine, by means of immunocytochemistry, the age in fetal development at which GH is first detectable in the pituitary gland and somatostatin in the median eminence, and to correlate temporally the development of these two hormones throughout the remainder of pregnancy. Mice were studied at 15-19 days of gestation with the peroxidase-antiperoxidase (PAP) technique of Sternberger. Somatotropes in the pars distalis were initially detected at 16 days of gestation and by 17 days they were a prominent component of the parenchymal cell population of the hypophysis. These cells were ovoid and distributed unformly throughout the pars distalis; many were located adjacent to sinusoidal capillaries. Their number and staining intensity increased by 19 days. Somatostatin was not consistently observed in the median eminence until 19 days of gestation. Reaction product indicative of the presence of somatostatin in presumptive nerve endings was located on the ventral surface of the median eminence and in the external lamina of the infundibulum in proximity to the superficial portal capillaries. Results of the present in investigation support the concept that the potential for neuroendocrine control of GH secretion exists in the mouse by the end of fetal development. Several hypotheses concerning the temporal relationship between the appearance of somatostatin in the hypothalamus and of GH in the anterior pituitary gland are discussed.


Localization of somatostatin-, substance P- and calcitonin-like immunoreactivity in the neural ganglion of Ciona intestinalis L. (Ascidiaceae). Indirect immunofluorescence studies using antisera to synthetic somatostatin, human calcitonin and substance P indicate, in the neural complex of the sea-squirt, Ciona intestinalis L., that these polypeptides are present in large perikarya situated at the periphery of the cerebral ganglion as well as in some smaller perikarya in the medulla. In the medullary and transitional zone, there are nerve fibres that cross-react positively with anti-calcitonin and anti-substance P.


Calcitonin-like cells in the pharynx of the ascidian Styela clava. A small group of granulated endocrine cells have been described in the endostylar region of the pharynx in Styela. These cells are argyrophilic and exhibit calcitonin-like immunofluorescence. Tests with antisera to other peptides all proved negative. Cells from animals exposed to elevated calcium levels showed a degree od degranulation. The possibility that these cells may represent ancestral ultimobranchial "C" cells is discussed.


Recovery of S. cerevisiae a cells from G1 arrest by alpha factor pheromone requires endopeptidase action. Radioactive alpha factor is degraded to discrete biologically inactive fragments by the target a cells of S. cerevisiae, but not by alpha cells which make the pheromone. The pattern of cleavage products and sequence analysis of one fragment indicated that the first scission occurred between leucine 6 and lysine 7. The protease inhibitors tosyl-L-argininyl-methyl ester (TAME), tosyl-L-lysyl-chloromethylketone (TLCK) and N-acetyl-L-leucyl-L-leucyl-L-argininal (leupeptin) markedly prolonged the period of G1 arrest in a cells exposed to alpha factor, while other standard protease inhibitors had little or no effect. The presence of TAME and leupeptin, or TLCK, reduced the rate of degradation of radioactively labeled alpha factor by a cells. Intact yeast cells have apparent esterase and amidase activities that are blocked by the same spectrum of inhibitors that potentiate alpha factor action. Purified alpha factor is a competitive inhibitor of these hydrolytic activities. The activities are present in yeast mutants which have greatly reduced levels of the three major vacuole-associated proteases (A, B and C) or which carry an ochre mutation in the major neutral protease (B). These observations indicate that the inactivation of alpha factor is due to endoproteolytic cleavage, the destruction of the pheromone is required to overcome its effects on growth and that degradation of the molecule may involve surface bound endopeptidase(s).


Isolation and characterization of stable hybrid mRNA molecules transcribed from ribosomal protein promoters in E. coli. The promoters from the str and spc operons of ribosomal proteins from E. coli were inserted into the Hind II cleavage site of mini-Col E1 (pVH51) plasmid. For both promoters, strains with the hybrid plasmid accumulated a small RNA species not present in strains carrying the vector. These RNAs were analyzed by RNA sequencing techniques and compared to DNA sequences. In both cases, synthesis of the new RNA species is initiated by the cloned r protein promoter at the site predicted by previous in vitro experiments. The RNAs extend across the Hind II site used for cloning and terminate specifically in the vector sequences. The termination site was localized to six consecutive thymine nucleotides preceded by a sequence with dyad symmetry. We found that the RNA from the str promoter was 205 (+/- 3) nucleotides long and that from the spc promoter was 177 (+/- 3) nucleotides long. These "hybrid mRNAs" are much more stable than ordinary mRNA. The str hybrid mRNA has a half-life of about 8 min, and the spc hybrid mRNA has a half-life of about 18 min at 37 degrees C. These hybrid mRNAs provide an in vivo system with which to examine directly the discrete transcription products from ribosomal protein promoters, and to study promoter function and mRNA metabolism in vivo.


Desmin and vimentin coexist at the periphery of the myofibril Z disc. Two-dimensional gel electrophoresis has revealed that vimentin, the predominant subunit of intermediate filaments in cells of mesenchymal origin, is a component of isolated skeletal myofibrils. It thus coexists in mature muscle fibers with desmin, the major subunit of muscle intermediate filaments. Antisera to desmin and vimentin, shown to be specific for their respective antigens by two-dimensional immunoautoradiography, have been used in immunofluorescence to demonstrate that vimentin has the same distribution as desmin in skeletal muscle. Both desmin and vimentin surround each myofibril Z disc and form honeycomb-like networks within each Z plane of the muscle fiber. This distribution is complementary to that of alpha-actinin within a given Z plane. Desmin and vimentin may thus be involved in maintaining the lateral registration of sarcomeres by transversely linking adjacent myofibrils at their Z discs. This linkage would support and integrate the fiber as a whole, and provide a molecular basis for the cross-striated appearance of skeletal muscle.


DNA sequence of the gene for the outer membrane lipoprotein of E. coli: an extremely AT-rich promoter. The outer membrane lipoprotein is the most abundant protein in an E. coli cell. Its structural gene (Ipp) was cloned into a lambda phage vector and the nucleotide sequence of a DNA fragment of 814 bp encompassing the Ipp gene was determined. The promoter region of the gene was found to have the following features. First, a segment of 261 bp preceding the transcription initiation site (-1 to -261) has a very high AT content of 70%, in contrast to 53% for the mRNA region of 322 bp, 44% for a segment of 127 bp after the transcription termination site and 49% for the average AT content of the E. coli chromosome. Second, in particular, of the first 45 bp upstream from the transcription initiation site (-1 to -45), 36 bases (80%) are A or T. Third, there is a heptanucleotide sequence homologous to the "Pribnow box," eight bases apart from the transcription initiation site. Fourth, a sequence homologous to the "RNA polymerase recognition site" exists on both strands between positions -27 and -39. Finally, there is a long dyad symmetry centered at the transcription initiation site.


Normal tRNAs promote ribosomal frameshifting. The addition of Ser AGC AGU tRNA to an E. coli cell-free protein synthesizing system which contains the endogenous tRNA levels results in up to 100% of the ribosomes translating the MS2 coat gene shifting into the -1 reading frame. An analogous phenomenon is seen at a much lower level without the tRNA addition, where a shift into the +1 frame can also be detected. Thus translation with the endogenous tRNA levels yields proteins which have the amino terminus of the coat protein but which are substantially larger than the coat protein and comprise about 5% of the coat translation. Since the lysis gene overlaps the 3' end of the coat gene in the +1 frame, we conclude that the reading frame shift into the +1 frame yields a hybrid protein. Also, we present evidence that ribosomes translating the synthetase gene shift into the -1 frame near the distal end of the gene. This frameshifting is promoted by thrACU ACC tRNA. Specific competitor tRNAs for both Thr and Ser tRNA-promoted frameshifting have been characterized. The generality of this new mechanism for producing additional proteins is unclear, but it investigation should increase understanding of the coding mechanism and its origin.


DNA sequence analysis of the transposon Tn3: three genes and three sites involved in transposition of Tn3. The complete nucleotide sequence of the transposon Tn3 and of 20 mutations which affect its transposition are reported. The mutations, generated in vitro by random insertion of synthetic restriction sites, proved to contain small duplications or deletions immediately adjacent to the new restriction site. By determining the phenotype and DNA sequence of these mutations we were able to generate an overlapping phenotypic and nucleotide map. This 4957 bp transposon encodes three polypeptides which account for all but 350 bp of its total coding capacity. These proteins are the transposase, a high molecular weight polypeptide (1015 amino acids) encoded by the tnpA gene; the Tn3-specific repressor, a low molecular weight polypeptide (185 amino acids) encoded by the tnpR gene; and the 286 amino acid beta-lactamase. The 38 bp inverted repeats flanking Tn3 appear to be absolutely required in cis for Tn3 to transpose. Genetic data suggest that Tn3 contains a third site (Gill et al., 1978), designated IRS (internal resolution site), whose absence results in the insertion of two complete copies of Tn3 as direct repeats into the recipient DNA. We suggest that these direct repeats of complete copies of Tn3 are intermediates in transposition, and that the IRS site is required for recombination and subsequent segregation of the direct repeats to leave a single copy of Tn3 (Gill et al.,  1978). A 23 nucleotide sequence within the amino terminus of the transposase which shares strong sequence homology with the inverted repeat may be the internal resolution site.


Transcription of cloned tRNA genes and the nuclear partitioning of a tRNA precursor. The transcription of transfer RNA genes (tDNAs) and processing of the transcripts have been studied by injecting cloned tDNAs into Xenopus oocyte nuclei. Three main conclusions can be drawn. First, eucaryotic nuclear tRNA genes, but neither procaryotic nor mitochondrial tRNA genes, are expressed in injected oocytes. While both nematode and yeast tDNAS direct the synthesis of authentic tRNAs, neither E. coli tDNA nor human mitochondrial tDNAs support the synthesis of defined tRNAs when injected into oocytes. Second, competition experiments with co-injected 5S genes and inhibition experiments with alpha-amanitin show that injected tDNAs are transcribed by RNA polymerase III. Third, oocytes injected with a nematode tDNA synthesize a tRNA precursor which is processed post-transcriptionally by removal of a 5' leader sequence. This precursor is found exclusively in the nucleus and is processed in the nucleus before the mature tRNA enters the cytoplasm.


Isolation of cloned DNA sequences containing ribosomal protein genes from Saccharomyces cerevisiae. Yeast mRNA enriched for ribosomal protein mRNA was obtained by isolating poly(A)+ small mRNA from small polysomes. A comparison of cell-free translation of this small mRNA and total mRNA, and electrophoresis of the products on two-dimensional gels which resolve most yeast ribosomal proteins, demonstrated that a 5-10 fold enrichment for ribosomal protein mRNA was obtained. One hundred different recombinant DNA molecules possibly containing ribosomal protein genes were selected by differential colony hybridization of this enriched mRNA and unfractionated mRNA to a bank of yeast pMB9 hybrid plasmids. After screening twenty-five of these candidates, five different clones were found which contain yeast ribosomal protein gene sequences. The yeast mRNAs complementary to these five plasmids code for 35S-methionine-labeled polypeptides which co-migrate on two-dimensional gels with yeast ribosomal proteins. Consistent with previous studies on ribosomal protein mRNAs, the amounts of mRNA complementary to three of these cloned genes are controlled by the RNA2 locus. Although two of the five clones contain more than one yeast gene, none contain more than one identifiable ribosomal protein gene. Thus there is no evidence for "tight" linkage of yeast ribosomal protein genes. Two of the cloned ribosomal protein genes are single-copy genes, whereas two other cloned sequences contain two different copies of the same ribosomal protein gene. The fifth plasmid contains sequences which are repeated in the yeast genome, but it is not known whether any or all of the ribosomal protein gene on this clone contains repetitive DNA.


The Radiation Therapy Oncology Group: a progress report. The Radiation Therapy Oncology Group (RTOG), founded in 1971, comprises 35 university hospitals which are participating in 21 active protocols, four registries and eight pilot studies, including Phase I/II studies. Case accession has grown to over 1000 in 1977 with 19,801 patients being entered in the RTOG initial registration. Goals of the RTOG include: advancing knowledge of the role of radiation therapy in disease management; improving control of primary and regional disease; reducing morbidity and complications from treatment; and collaborating with other oncology disciplines to obtain data on multimodality therapy.


Evaluation of a fixed alternating treatment in patients with advanced breast cancer. A total of 128 patients were randomly assigned to two induction treatment programs: Adriamycin and L-PAM versus Cytoxan, 5-Fluorouracil, and Prednisone in an effort to assess their primary capacity for objective response. The two regimens appeared quite comparable in this respect. The 100 patients who had achieved clinical benefit following initial treatment were subsequently randomly allocated to reveive either a fixed alternate treatment program involving the two drug regimens or were continued on the treatment program responsible for their initial improvement. Although those patients who received the fixed alternate treatment shcedule had a somewhat longer progression-free interval compared to the two single-treatment programs (median duration of 16 months versus 12 months, respectively), the three treatment programs including the fixed alternate treatment schedules had comparable median survivals of 21-24 months with little difference noted in survival curves at any point thus far in the analysis. There were no differences noted in survival for the fixed alternating treatment group of patients, with respect to which induction regimen had been utilized to achieve initial response. The toxicity for these treatment programs was tolerable and compatible with outpatient administration. Myelosuppression occurred in the vast majority of patients on either regimen but in both regimens was relatively platelet sparing.


Importance of controlling the regional draining lymph nodes in breast cancer. A major issue in the treatment of breast cancer deals with local control of disease and the necessity for removing microscopically involved lymph nodes. Many radiation oncologists are looking to the parasternal lymphatics as possible renewed justification for postoperative radiation. It is concluded that prospectively designed studies are needed to assay the importance of the internal mammary nodes and their adequate control. Lymphoscintigraphy may offer a method of evaluating these nodes without radical surgery.


Analysis of adjuvant therapy in large bowel cancer. Since 1958 there has been intense efforts in adjuvant systemic therapy for colorectal cancer. Peri-operative chemotherapy with HN2, TSPA + FUDR produced no clear-cut prolongation of disease-free survival. Short-term (two courses) and long-term (18 months) therapy with 5-FU by the Veterans Administration surgical Adjuvant Group is reported to give marginal increases (7--9%) in survival at 5 years. These findings are confirmed by the COG study of prolonged 5-FU which shows prolongation of disease-free survival of borderline statistical significance for Dukes' C colon (P = 0.051) + rectum (P = 0.016). Short-term benefit to 18 months was conferred by prolonged 5-FU in the VASAG + COG studies, for patients who have had a palliative resection. Combination chemotherapy might be more active, but no results are available from the controlled trials utilizing 5-FU + MeCCNU or immunotherapy. Preoperative irradiation in the VASAG studies resulted in downstaging in terms of operative findings of lymph node involvement and was of survival benefit in those patients have an AP resection for cure or palliation of rectal cancer (P less than 0.02). More intensive preoperative radiation programs are ongoing, as well as postoperative radiation with and without chemotherapy. Further progress awaits the discovery of truly active chemotherapy programs, as well as better techniques of radiation enhancement.


Evaluation of combined therapy in carcinoma of the bladder. A number of studies are considered in order to evaluate the benefits of combined treatment for patients with Stage B2C transitional carcinoma of the bladder. It is found that for a variety of reasons, such treatment is not shown to be beneficial; the conclusion is that routine combined preoperative therapy is investigative but cannot be recommended as a community standard.


Evaluation of intensified chemotherapy in children with advanced rhabdomyosarcoma (clinical groups III and IV). The Intergroup Rhabdomyosarcoma Study (IRS) Committee of the Cancer and Leukemia Group B Children's Cancer Study Group, Southwest Oncology Group. Twenty-seven previously untreated children with gross residual (20) or metastatic (seven) rhabdomyosarcoma were treated with pulse-VAC (vincristine weekly for 12 doses plus dactinomycin and cyclophosphamide simultaneously given daily for 5 days) and radiotherapy. Toxicity during the 12-week induction period included 23 of 27 (85%) with an absolute neutrophil count (ANC) under 500/mm3; 16/27 (59%) were given intravenous (I.V.) antibodies. Three patients developed Gram-negative sepsis and two of them died. In the first 12 weeks, eight children had a complete response (CR) and another 10 a good partial response (PR), a total of 18 of 27 favorable responses (67%). At 12 weeks, 20 patients received either intermittent pulse-VAC (Regimen H) or a pulse of adriamycin plus vincristine and cyclophosphamide alternating with pulse-VAC (Regimen I) every 4--6 weeks. After this first "maintenance," only seven patients (35%) developed an ANC under 500/mm3 and only three (15%) were given I.V. antibiotics. Severe toxicity disappeared with drug dose reduction in subsequent courses. The overall CR rate was 59% with a PR rate of 15%, a total of 74% favorable responses. This rate is not significantly better than that obtained by previous IRS chemotherapy and radiotherapy schedules for patients with gross residual and metastatic rhabdomyosarcoma. Future studies in these patients will concentrate on diminishing myelosuppression while shortening the rest period between pulses, in order to deliver more drug per unit time.


Measurement of cardiac output by carbon dioxide rebreathing. Twenty patients were studied on a bicycle ergometer at rest and at varying workloads to compare methods of measuring cardiac output. In nine patients, a comparison of carbon dioxide rebreathing and dye dilution techniques for measuring cardiac output were made. In eleven patients, comparisons between carbon dioxide rebreathing, dye dilution, and direct oxygen Fick techniques were made. The cardiac output measured by carbon dioxide rebreathing was reproducible and compared well with both the dye dilution and direct oxygen Fick. The correlation coefficient for the relationship between carbon dioxide rebreathing and direct oxygen Fick cardiac outputs was 0.80 and between carbon dioxide rebreathing and dye dilution cardiac outputs was 0.75. The relationship between dye dilution and direct oxygen Fick cardiac output was 0.71. The carbon dioxide rebreathing technique is a safe, non-invasive and reproducible method to measure cardiac output. The results compare well with the cardiac output measured by either the direct oxygen Fick or dye dilution technique.


Games, goods and gods: an analysis of Iroquoian gambling. This study questions the traditional, historical view of the Indian as a compulsive gambler. Eleven northern Iroquoian gambling games were examined in both their secular and sacred environments. The analysis demonstrated that social gambling served to establish economic parity within, and between, the ritualistic gambling associated with many ceremonies was quasi-religious in nature and necessary to ensure that the desired outcome of the rite was realized.


Response to bronchial provocation and exercise in children with cystic fibrosis. Ten of fifteen cystic fibrosis children with positive skin prick tests to common antigens gave an immediate bronchial reaction to the antigen inhaled, five of them also gave a late reaction; however only one gave a history of asthma. The antigen most commonly eliciting a positive skin reaction in cystic fibrosis patients is Aspergillus fumigatus. In six children tested to this antigen the bronchial response varied, two were negative, one gave an immediate reaction and three gave a dual (immediate and late) reaction. None of the children showed the characteristic pattern of response to exercise seen in asthmatic patients, an initial rise in Peak Expiratory Flow Rate followed by a fall of greater than 14% below the resting level. Two patients showed an abnormal rise in Peak Expiratory Flow Rate during exercise, a pattern described previously in cystic fibrosis. The results suggest that bronchial allergy, immediate or late does completely explain susceptibility to asthma, and that other factors including perhaps the type of bronchial reactivity shown by bronchoconstriction after exercise may be required. However the majority of the children tested had bronchial allergy and anti-allergy therapy such as inhaled sodium cromoglycate may have a place in the management of selected patients with cystic fibrosis.


Homogeneous enzymoimmunoassay for anticonvulsant drugs: effects of hapten-enzyme bridge length. The effects of the enzyme-hapten chemical bridge on the quality of the enzymatic tracer in homogeneous enzymoimmunoassay were studied, using as a model the conjugates of glucose-6-phosphate dehydrogenase with different phenobarbital and diphenylhydantoin carboxyalkyl derivatives. For both series of conjugates the maximal immunoinhibition level was found to depend critically on the bridge length, best results being obtained with carboxymethyl derivatives. A tendency to immuno re-activation with increasing degrees of hapten substitution in the enzyme structure, particularly evident for phenobarbital-carboxyethyl and carboxypropyl conjugates, was also observed. Effects of steric hindrance on the antibody interaction, in the case of short bridges, and ineffectiveness of antibody interaction towards the active enzyme site, in the case of long bridges, have been hypothesized to contribute in defining a critical bridge size for immuno inhibition processes. Instead the tendency to immunoactivation has been tentatively interpreted in terms of occurrence of "conformational" antibody interactions involving hapten residues in enzyme regions other than the catalytic site.


Evidence for thyroid antigen-reactive T lymphocytes infiltrating the thyroid gland in Graves' disease. We have investigated the relative distribution and some in vitro functions of thyroid-infiltrating immunocompetent cells obtained at fine-needle aspiration biopsy in twelve patients with Graves' disease and thirteen patients with Hashimoto's thyroiditis. In both disorders the predominant (57--59%) thyroid-infiltrating cell was a small lymphocyte. Significant numbers of plasma cells (10%) were seen only in Hashimoto's thyroiditis. Mononuclear phagocytes (monocytes plus macrophages) were present in similar numbers (12--18%) in both disorders. In both Graves' and Hashimoto's disease there was a relative reduction of (thymus-dependent) lymphocytes in the thyroid gland as compared to the blood. Blood and thyroid-infiltrating T lymphocytes were tested for in vitro cell-mediated immunity (CMI) to thyroid antigen in the leucocyte migration inhibition test (LMT). CMI was readily demonstrated in the blood of most patients with Graves' and Hashimoto's disease. When the thyroid-infiltrating lymphocytes were tested for CMI in the LMT, only the infiltrating cells from patients with Graves' disease displayed CMI, whereas the thyroid-infiltrating lymphocytes in Hashimoto's disease were negative. Fractionation of the immunocompetent cells demonstrated that the thyroid antigen-induced LMT response of blood and thyroid-infiltrating lymphocytes in Graves' disease is a T lymphocyte-dependent phenomenon.


Failure of naloxone to alter growth hormone and prolactin levels in acromegalic and in hyperprolactinaemic patients. We examined the effects of high-dose intravenous naloxone administration in four acromegalic patients (mean serum growth hormone level 72 ng/ml) and in seven hyperprolactinaemic women (mean serum prolactin level 59 ng/ml), in order to assess whether this opiate antagonist would be effective in lowering growth hormone and prolactin levels. No effect was observed. This lack of effect suggests that an opioid pathway is not involved in the maintenance of elevated growth hormone or prolactin secretion in these patients. However, conclusions regarding the possible role of endogenous opioids in regulation of pituitary function in normal individuals cannot be drawn from this study.


Testicular endocrine function in paraplegic men. The responses of FSH and LH to the injection of LHRH were studied in fifteen paraplegic men and ten normal controls. The basal FSH levels in the paraplegic men were elevated in eight cases, basal LH being raised in nine cases. The responses of FSH were exaggerated in fourteen patients, and LH responses were exaggerated in nine patients. Only one patient was normal in respect of both hormones. Subnormal plasma testosterone was found in three patients. This depressed testicular function could not be explained as being due to spread of urinary tract infection and a direct neurological effect is the probable explanation.


Uncultured cells in amniotic fluid from normal and abnormal foetuses. Direct smears of uncultured amniotic fluid cells were analysed in 41 pregnancies between 17 and 22 weeks of gestation. These included 27 normal pregnancies where a healthy child was born at term, six anencephalic and five spina bifida pregnancies, and three other abnormal pregnancies. In normal amniotic fluid, epithelioid cells predominated but small numbers of histiocyte-like cells, typical macrophages and elongated cells were also present. The proportion of macrophages and elongated cells was significantly increased in all anencephalic cases. Two of the spina bifida cases also showed abnormal cellular proportions. Haemosiderin and lipid material was demonstrated in some of the cellular proportions. Haemosiderin and lipid material was demonstrated in some of the macrophages. Tissue smears and histological preparations suggest that these cells may originate from both the amnion and the fibrovascular membrane covering the neural lesion. This direct method of observation of amniotic fluid cells, not involving culture techniques, could provide a rapid means of prenatal diagnosis of anencephaly, and may help in the diagnosis of spina bifida.


Metabolic requirements for fetal growth. Table 1 outlines a metabolic balance sheet for the sheep fetus. It is clear that maternal substrate concentrations as well as placental function are important in assuring the provision of adequate substrate to meet fetal metabolic and growth requirements. It is intriguing that the fetus appears to use substrates not usually regarded as important in extrauterine diets (lactate) and to use substrates for catabolic purposes normally thought to be primarily anabolic substrates (amino acids). This information emphasizes the hazards of extrapolating metabolic and nutritional patterns seen in extrauterine life in reaching conclusions concerning the fetus. It likewise emphasizes the importance of ongoing studies in maternal and fetal nutrition and metabolism.


Infection in the surgical patient: an imbalance in the normal equilibrium. Infection in the surgical patient, like infection elsewhere in the body, is a manifestation of a disturbed host-bacteria equilibrium in favor of the bacteria. It results when bacteria indigenous to that patient achieve dominance over the factors of host resistance. This is reflected by a quantitative increase in the bacterial presence. To be able rationally to prevent and manage such infection requires understanding of how each prophylactic or therapeutic maneuver will work to reestablish the normal equilibrium in the specific situation in which the surgeon finds his patient.


Clinical pharmacokinetics of isoniazid.

Clinical pharmacokinetics of isoniazid. The pharmacokinetics of isoniazid in man are described. Pronounced interindividual variation in circulating isoniazid concentration and clearance which occur after dosing with the drug are associated with hereditary differences in the acetylator status. The variations in rate of isoniazid inactivation and elimination in different (rapid and slow) acetylator phenotypes are primarily due to differences in the rate of acetylation of isoniazid by a genetically controlled polymorphic N-acetyltransferase in liver and small intestine. An appreciable 'first-pass' effect is observed following oral isoniazid administration, particularly in the rapid acetylator phenotype. Liver disease can cause a significant prolongation in the clearance of isoniazid; in the acutely ill patient, the prolongation correlates most closely with serum bilirubin elevation, although the degree of prolongation is less important than the intrinsic genetic difference between acetylator phenotypes. The effect of renal impairment on isoniazid excretion is relatively unimportant, even in slow acetylators. Methods for monitoring blood and urine concentrations of isoniazid and for acetylator phenotype determination which are convenient for the patient and clinician are available. Implications of phenotype differences in acetylator status for the optimal management of tuberculosis with isoniazid are considered. Attempts to devise new isoniazid formulations for this purpose are being evaluated.


Natural host defense mechanisms.

Natural host defense mechanisms. Severe injury, whether the result of a major accident, a large burn, or a complicated surgical operation, often results in sepsis. Under such conditions both specific and nonspecific host defense systems are affected. The individual facets of major concern are chemotaxis, phagocytosis, intracellular killing, complement depletion, and depression of humoral and cellular mediated immunity. The most profound changes occur in cell-mediated immunity. Within a few hours o injury, the number of circulating T cells becomes depleted, concomitantly thoracic duct lymphocytes are markedly reduced. This change is not only quantitative but functional. The clinical impact of these deficient host defense mechanisms lies in the fact that low virulent organisms may become a lethal threat to the injured patient. Currently, investigators are attempting to reverse thse deficiencies through the use of immunotherapy.


Plasma 25-hydroxy-vitamin D in normal subjects and patients with terminal renal failure, on maintenance haemodialysis and after transplantation. 1. Plasma 25-hydroxy-vitamin D concentration was measured in 40 normal subjects, 19 patients with terminal renal failure, 137 patients who had been on dialysis up to 11 years and in 17 renal transplant patients. 2. The mean plasma concentration of 25-hydroxy-vitamin D was below normal in patients with terminal renal failure and in patients who had been on maintenance haemodialysis for less than 1 year. The mean concentration in patients who had been on dialysis for more than 1 year and in renal transplant patients was normal. 3. The seasonal variation of plasma 25-hydroxy-vitamin D concentration found in the 58 patients on maintenance haemodialysis for more than 2 years is similar to that reported in normal subjects.


Long term retention of sealants applied by inexperienced operators in Minneapolis. A clinical trial of 4047 single applications of Nuva Seal placed on the occlusal surfaces of primary molars, permanent first and second molars and premolars by 250 dental students showed that the sealants were not well retained. The sealant was fully retained on 86% of all permanent posterior teeth at 3 months, on 76% at 6 months, 58% at 12 months, 52% at 24 months and 41% at 36 months. At 4 years, complete sealant coverage was shown by 14% of primary molars, 25% of permanent molars and 68% of premolars. Permanent mandibular molars and premolars were superior to permanent maxillary molars and premolars in fully retaining sealants. Following sealant failure, i.e. providing partial coverage or missing, permanent maxillary molars and premolars were more prone to occlusal caries than permanent mandibular molars and premolars. At 4 years, caries was diagnosed in 40% of applications to permanent molars and in 9% of applications to premolars. Twelve instances of caries under apparently intact sealants were seen.


Computer-aided determination of haemodynamic properties of human heart from cine left ventriculography. The silhouettes of the left ventricle seen on a cine ventriculogram were used as the graphic input to a pattern analysis programme. The programme measured the coordinates of points around silhouette. It selected the longest chord within the perimeter and determined its length, the area within the perimeter, and the volume of the resulting ellipsoid of revolution. The output from the programme was a global clinical report which included scaled reproductions of the silhouettes, maximum and minimum ventricular volumes, the stroke volume, and the ejection fraction. Local analysis consists in comparison of the contraction profile for the specific patient with the mean pattern obtained from a control group of 24 patients with no myocardial pathology. The graphical and numerical results help in following the progress of disease, in choosing candidates for coronary artery bypass, and in evaluating the results of medical or surgical treatment.


Radiology of basilar skull fractures.

Radiology of basilar skull fractures. Injury to the basal portion of the anterior, middle, and posterior fossae of the skull are rather easily overlooked unless the radiologist carefully searches for indirect or direct signs of such injury. Representative injuries of each area are reviewed and radiological signs are illustrated. Combination fractures transversing several areas are also considered and illustrated.


Clobetasone butyrate and hydrocortisone butyrate in the treatment of eczema: a double-blind comparison. Forty patients with symmetrical eczematous lesions on their extremities were treated in a double-blind fashion with 0.05% clobetasone butyrate and 0.1% hydrocortisone butyrate in cream bases. After 2 weeks of treatment, a preference for clobetasone butyrate was observed in 7 cases, for hydrocortisone butyrate in 9 cases and in 24 cases both sides responded equally. The lesions on both sides improved steadily throughout the study in all cases. When completing the trial after 2-weeks' treatment, the clobetasone butyrate-treated lesions had healed in 8 cases and the hydrocortisone butyrate-treated lesions in 10 cases. No local side-effects were observed.


Neoplastic obstruction of the small and large intestine. Obstructive symptoms due to small bowel tumors are the most common indication of primary malignant disease in the small intestine. Primary obstructing tumors of the small bowel are treated best by resection and primary anastomosis. Malignant lesions of the duodenum sometimes will require pancreaticoduodenectomy and those of the distal ileum, right hemicolectomy. Obstruction due to localized metastatic disease can be treated by resection and primary anastomosis but, more frequently, one or more side-to-side enteroenterostomies will be needed, especially in abdominal carcinomatosis. The complication of LBO due to colorectal cancer is an ominous sign. The less favorable prognosis is a result of the higher operative mortality, advanced stage of disease and lower resectability rate. Obstructing neoplasms of the right side of the colon are treated best by immediate resection and primary anastomosis. Left-sided colon obstruction due to malignancy traditionally is treated by preliminary diversion followed later by definitive resection. Insufficient data are available to evaluate any benefit on operative mortality and long-term survival with a more aggressive approach involving decompression and resection of the obstructing carcinoma at the initial operation. It is doubtful that any marked improvement in current mortality and survival figures will result from wide deviations of the current principles of operative managment. Early diagnosis of the cancer before obstruction occurs remains the primary means of improving survival rates. This involves not only primary means of improving survival rates. This involves not only patient education regarding presenting symptoms, but improvement of physician recognition and response to these complaints so that the appropriate tests are ordered and treatment is initiated.


Epithelial polyps of the large bowel: a pathological and colonoscopic study. Ninety patients who had epithelial polyps or carcinoma of the large bowel and underwent at least 2 colonscopic examinations were studied. The cases were divided into three groups: patients who ;ad only one polyp; those in whom more than one epithelial polyp were found and those who had adenocarcinoma of the large bowel and underwent follow-up colonoscopic examinations. The distribution of the polpys was plotted as to type and distribution in the colon. There seemed to be a trend for the polyp found in follow-up examinations to be located proximal to the splenic flexure. In this regard it was noted that the subsequently found polyps in group II were smaller than those removed on the initial colonoscopic examination. No relationship could be found between any histologic type of epithelial polyp and the presence of carcinoma.


Reiter's disease: modern concepts.

Reiter's disease: modern concepts. Reiter's disease (RD) is a reactive arthritis syndrome in which arthritis, conjunctivitis, dermatitis, and urethritis are the main features. It may be an acute and self-limited disease or it may cause severe debilitation. It generally follows an infectious episode, such as Shigella dysentery or nonspecific urethritis. Recent evidence has shown that patients in whom RD develops have a genetic disposition since the presence of HLA-B27 correlates highly with RD. Therapy of RD involves supportive care.


North American blastomycosis: a review.

North American blastomycosis: a review. North American blastomycosis, first reported in 1894, and once thought to be a geographically localized disease, has now been reported worldwide. The greatest number of cases occur in the Mississippi, Missouri, and Ohio River basins. The organism enters the body via the lungs with subsequent dissemination to other organs, including the skin, eyes, bones, and genitourinary system. Patients most often present with cutaneous or pulmonary complaints. Demonstration of characteristic fungal morphology in microscopic smears or in histologic specimens is highly suggestive of Blastomyces dermatitidis. However, proof of the diagnosis is obtained only by mycologic culture. Some progress has been made using other laboratory methods to produce a rapid diagnosis. This paper reviews in detail the varied clinical presentations of blastomycosis, the laboratory diagnosis, and current treatment.


Management of eczematous dermatitis with amcinonide or betamethasone valerate. A double-blind comparative study. A new topical corticosteroid formulation, 0.1 percent amcinonide cream, was compared with 0.1 percent betamethasone valerate cream in a double-blind, parallel study of the management of eczematous dermatitis. Both treatment groups showed statistically significant improvement in most symptoms and in overall disease status after one and two weeks of treatment. The amcinonide group had greater improvement in individual symptoms and significantly greater overall improvement than did the betamethasone valerate group. Side effects were few and minor in both groups. The amcinonide cream was found to be both safe and effective for the management of eczematous dermatitis.


[Studies on staphylococcal enterotoxin B. III. Purification with absorbents]. The biological and immunological activities of Staphylococcal enterotoxin B are stable in pH 2.0 approximately 11.0, and also resistant to proteolytic enzyme (trypsin, pepsin) digestion for 3 approximate 4 hours. Therefore, the toxin could be purified with trypsin digest and then absorbed on kaolin and Kieselgel, followed by eluting the different pH buffer solutions. Further purifications was chromatographied on CM-Sephadex column.


[Reaction of HCl secretion, total proteolytic activity and pepsin after a selective proximal vagotomy in duodenal ulcer patients]. The gastric secretion of hydrochloric acid, total proteolytic activity, and especially pepsin were studied before and 6 months after selective proximal vagotomy in 15 patients suffering from recurrent duodenal ulcer, and compared with that of ten sound volunteers. The patients with duodenal ulcer showed a significantly increased secretion of acid and proteolytic enzymes. After vagotomy, the basal acid output was reduced by 70%, the secretion of the total proteolytic activity by 54%, and that of pepsin by 45%. The concentration of the total proteolytic activity and of pepsin in the gastric juice was increased after vagotomy. Although the total basal proteolytic activity after vagotomy was still increased by 15% as compared with that in the volunteers, due to the drastically reduced basal acid output the actual intragastric basal proteolytic activity was expected to be reduced after vagotomy.


Morphogenesis of the synapton during yeast meiosis. The formation of the synapton (synaptonemal complex) was followed by an electron microscopic examination of large samples of Saccharomyces cerevisiae cells at various stages of meiosis. Three temperature-sensitive mutants were used, cdc4, cdc5 and cdc7, which undergo a slow but normal meiosis at 25 degrees C. At the restrictive temperature of 34 degrees C, cdc4 and cdc5 arrest at an advanced enough stage of meiosis to allow the study of synapton morphogenesis. Based on the frequencies of nuclear structures, we describe the formation of the central region and central elements of the synapton in the dense body, which may be part of the nucleolus. This process occurs during early meiotic stages, concomittantly with recombination commitment and premeiotic DNA replication. Mature synaptons usually appear after premeiotic S, at the pachytene stage, and later disappear. A possible intermediate stage in this disappearance is found in arrested cdc5 cells, which contain paired lateral elements without central elements. Following the frequencies of spindle plaque configurations, we conclude that the plaques in meiosis duplicate once at the beginning of the main DNA replication, as is also observed prior to mitosis. In contrast to mitotic cells, however, meiotic plaques remain duplicated for a long period, until the synaptons disappear, and only then separate from each other to form a spindle. During late stages of the first meiotic division, the outer plates of the spindle plaques thicken, to duplicate later and give the second division spindles. The characteristically thick outer plate may have a role in the formations of the ascopore wall.


Localization of satellite DNAs in the chromosomes of the guinea pig. The in situ hybridization method has been used to investigate the localization of each of the three satellite DNAs present in the genome of the guinea pig. Purified fractions of the satellite DNAs were utilized as templates for synthesis of 3H-labeled complementary RNA (cRNA) by E. coli RNA polymerase, then each cRNA was hybridized to metaphase spreads of embryonic guinea pig cells. The cRNAs of all three satellite DNAs hybridized predominantly to the centromeric region of the chromosomes. The cRNAs of satellite DNAs II and III hybridized to all chromosomes except the Y chromosome. The cRNA of satellite DNA I did not hybridize to the Y chromosome nor to two pairs of small acrocentric chromosomes. Satellite II cRNA hybridized to the telomeric region of chromosomes 3 and 4.