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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 703 records · Page 39Linked to original sources

Relationship between the antiviral effects of interferons and their abilities to depress cytochrome P-450.

Several hybrid human interferons have now been constructed by recombinant DNA techniques. Two of these hybrid interferons, IFN-alpha AD(Bgl) and IFN-alpha AD(Pvu) differ by only three amino acids, but IFN-alpha AD(Bgl) was fifteen times more potent than IFN-alpha AD(Pvu) in antiviral activity towards infection of mouse L-929 cells by vesicular stomatitis virus. Only the hybrid with the greater antiviral activity in the mouse depressed cytochrome P-450, aminopyrine N-demethylase and benzo[a]pyrene hydroxylase in the liver. These experiments demonstrate that minor changes in amino acid structure not only have a major effect on the antiviral properties of interferon but also influence the ability of interferon to depress cytochrome P-450 in the liver.

Aminopyrine N-Demethylase↗

Analysis of pulmonary surfactant apoproteins by isoelectric focusing.

Apoproteins of Mr 38 000, 32 000 and 26 000 are found in surfactant isolated from rat lungs. The surfactant isolated from monkey lungs, on the other hand, contains the 38 kDa apoprotein and not the 32 and 26 kDa apoproteins. These preparations of pulmonary surfactant contain, in addition, several serum proteins. We have used a combination of salt- and sucrose-density gradient centrifugations to isolate and further purify surfactant from the washings of rat lungs. Thus, a preparation of pulmonary surfactant was obtained which contained exclusively the 38, 32, 26 and 10-12 kDa apoproteins, and which was rich in phosphatidylcholine and phosphatidylglycerol. Using an immunoassay and an immunoblotting technique, it was established that the 38, 32 and 26 kDa apoproteins are not serum proteins. The surfactant apoproteins of rat and monkey were further subjected to the high-resolution of isoelectric focusing. Thus, rat surfactant apoproteins resolved into 11 bands in the pH range 4.64-5.53. A second-dimensional electrophoresis in a sodium dodecyl sulfate system led to the migration of the 11 bands, separated by first-dimensional isoelectric focusing, into three distinct groups with apparent molecular weights of 38 000, 32 000 and 26 000, respectively. Upon isoelectric focusing, the apoproteins from monkey lung surfactant also separated into several bands in the pH range 5.18-5.82. After electrophoresis in the second dimension as above, these bands migrated as a single group with an apparent molecular weight of 38 000. Neuraminidase treatment of rat surfactant apoproteins, and subsequent IEF, led to the disappearance of several low-pI variants with a concomitant increase in the amounts of higher-pI variants. Thus, the sialic acid content of surfactant apoproteins accounts for, in large part, the observed charge heterogeneity.

Animals↗

Deficient lung surfactant apoproteins in amniotic fluid with mature phospholipid profile from diabetic pregnancies.

An enzyme-linked immunoassay to quantitate lung surfactant apoproteins (15 to 250 ng/ml) in human amniotic fluid is described. The immunoassay was used to quantify lung surfactant in 72 samples of amniotic fluid, for which lecithin/sphingomyelin (L/S) ratios, lecithin and phosphatidylglycerol concentrations, and foam stability indices were also available. The results obtained with the immunoassay were in general agreement with those of the other methods. Measurement of the apoproteins, however, may be a better predictor of fetal lung immaturity and of respiratory distress syndrome than the L/S ratio and the concentration of lecithin. This conclusion is based on the data obtained in the analyses of samples of amniotic fluid from four diabetic and five nondiabetic pregnancies, the infants of which developed respiratory distress. In all cases, the apoprotein concentration was less than 2.1 micrograms/ml, which indicated fetal lung immaturity. In six of these cases (one diabetic and five nondiabetic pregnancies), lung immaturity was also predicted on the basis of other tests. However, in three other cases of diabetic pregnancy, the L/S ratio and lecithin concentration falsely indicated lung maturity. In addition to its being an effective predictor of fetal lung maturity in diabetic, as well as nondiabetic, pregnancies, the immunoassay is better suited for clinical use because of its high specificity, sensitivity, and ease of performance.

Amniotic Fluid↗

Epstein-Barr virus-induced lymphoma in a cardiac transplant recipient.

A monoclonal diffuse histiocytic lymphoma developed during the course of a serologically documented primary Epstein-Barr virus infection in a 22-year-old cardiac transplant recipient taking cyclosporine and prednisone. Throat washings revealed the virus at tumor presentation, and the tumor was shown to contain Epstein-Barr nuclear antigen-positive cells and the viral genome. Prolonged inversion of the T cell helper/suppressor ratio was demonstrated. A brief course of acyclovir appeared to halt viral shedding in the throat but had no apparent effect on the tumor.

Acyclovir↗

Studies on follicular patterns in buffalo-heifers.

Frequent palpation per rectum was used to delineate patterns of development and atresia of large follicles (> 0.80 cm) on the ovaries of pre-, peri- and postpubertal heifers. The average size of large follicles in prepubertal, peripubertal and postpubertal heifers were 1.25, 1.35 and 1.36 cm, respectively. In 65.39 per cent of the postpubertal heifers, midcycle follicles (> 0.80 cm) could be successfully palpated from day 9 to 13 of the estrous cycle. Moreover, the development and atresia of large follicles in heifers were found to be continuous processes. Follicles were exhibited on the ovaries regularly at intervals of 10-11 days.

Journal Article↗

Body size and pelvic area relationships at puberty and two-month-pregnancy in buffalo - heifers.

The relationships among body weight, height at hook bone, height at pin bone, hip width, rump length, pin width and pelvic area were estimated in puberal (n=50) and two-month pregnant (n=35) Murrah buffalo-heifers. In both types, significant correlations (P angle0.10) existed among all measurements studied. Averages for pelvic area at puberty and two-month pregnancy were 285.05 and 302.00 sq. cm, respectively. At the time of parturition, no buffalo heifer exhibited dystocia due to narrow pelvic opening.

Journal Article↗

Persistence and movement of phorate at high concentrations in soil.

The entrance of a large number of chemicals into the agricultural market has caused concern to both cultivators and scientists because of their effectiveness at the target site, possibility of underground water contamination, and other undesirable effects such as phytotoxicity and effects on nontarget species. The persistence and movement of phorate--a systemic granular insecticide--were studied at high concentrations (4 and 8 kg a.i./ha) in field soil in two seasons, i.e., winter and summer. Periodic sampling for total phorate residues (TPR) at various vertical depths showed that it leached more efficiently at the higher dose (i.e., 8 kg a.i./ha) in both seasons. The horizontal mobility was also higher at this dose. Irrespective of the treatments, TPR leaching was significantly greater in winter with the higher dose, whereas its movement in the horizontal plane was comparatively greater in summer with this dose. The TPR concentration peaks remained stationary at 7.5 cm depth at all the redistribution times until the pesticide was nearly dissipated under both treatments and in both seasons. TPR persistence was higher at the higher dose. Its persistence was comparatively greater in winter than in summer. The present findings show that there seems to be no threat of underground water contamination by this pesticide even at a rate as high as 8 kg a.i./ha.

Insecticides↗

Energy metabolism in Cotugnia digonopora and the effect of anthelmintics.

Incorporation of 32Pi into organic phosphate by mitochondria of Cotugnia digonopora was supported maximally by malate. Fumarate and succinate induced lower but significant production of ATP. Pyruvate, alpha-ketoglutarate and oxalacetate proved to be poor substrates and citrate and isocitrate had no effect. A net phosphorylation of approximately 2 mol of ADP was observed for each mol of CO2 liberated from malate or succinate. In contrast, with pyruvate, in spite of a high rate of decarboxylation, the production of ATP was extremely low. 2,4-Dinitrophenol inhibited phosphorylation. All anthelmintics examined interfered with the mitochondrial phosphorylation of ADP, with maximum inhibition by salicylanilide compounds. The anticestodal activity of the latter group of compounds, niclosamide for example, may, therefore, be attributed to their ability to inhibit mitochondrial phosphorylation.

Animals↗

Cotugnia digonopora: carbohydrate metabolism and effect of anthelmintics on immature worms.

Cotugnia digonopora consumes, in 24 hours, glucose equivalent to 38% of its body-weight and converts it into metabolites. The Krebs' cycle is insignificant in the breakdown of glucose because very little CO2 is formed. Ether-extractable acids account for most of the consumed sugar, confirming that metabolism is predominantly anaerobic. Glucose is assimilated as glycogen rather than as nucleic acids, lipids and proteins. Niclosamide, praziquantel and mebendazole strongly inhibit uptake of glucose by the parasite. A considerable increase in the production of lactic acid over that of ether-soluble and volatile acids under the influence of these drugs, suggests a change in the catabolism of sugar towards homolactate fermentation.

Animals↗

H2 blockers in chronic urticaria.

Two hundred unselected patients with chronic idiopathic urticaria were treated with adequate doses of conventional antihistamines given at frequent intervals; 98.5% were completely freed of disease while on therapy. In three cases, the lesions subsided but did not clear completely. The addition of 800 mg of cimetidine in divided doses cleared the lesions in two cases, and in the third case the dose of H1 blocker was increased, which resulted in complete clearance of wheals and symptoms. Addition of H2 blockers play a role, but only in a very small percentage of patients with chronic idiopathic urticaria who do not completely respond to adequate doses of H1 blockers.

Adolescent↗

Genetics of site specific colon cancer: a family study.

In a kindred of 46 individuals of an Indian Sikh family with no history of consanguinity, 8 suffered from site specific colon (caecum) cancer (not associated with polyposis). The clinical features in the affected kindred were indicative of a "cancer family syndrome". The study of the family depicted an autosomal dominant transmission pattern of site specific colon cancer, with probably 100% penetrance in the affected individuals. A low percentage of mitotic index (MI) was observed in the two probands who were available for the study. No structural or numerical chromosomal aberrations were observed in either case. It is probable that the gene responsible in this family could have begun by mutation at the germ cell level in the 1st generation and remained in a heterozygous condition in the affected individuals.

Adenocarcinoma, Mucinous↗

Inhibition of the synthesis of hepatic cytochrome P-450 by the interferon-inducing agent poly rI.rCi.

The levels of cytochrome P-450, cytochrome b5, aminopyrine N-demethylase, and benzo[a]pyrene hydroxylase were depressed in hepatic microsomes following treatment of mice with the interferon inducer poly rI.rC. The decrease in the hepatic mixed function oxidase system was accompanied by an increase in the incorporation of amino acids into total microsomal protein. Fractionation of solubilized microsomes using a Sephacryl S-200 gel filtration column demonstrated that the increase in amino acid incorporation tended to be associated with proteins with molecular weights under 67 000. The fractions which contained cytochrome P-450 were further separated using a DEAE cellulose column. The amount of labelled amino acids associated with the cytochrome P-450 fractions was uniformly depressed in preparations from poly rI.rC treated animals compared with saline-treated controls. These results suggest that poly rI.rC causes a depression in the rate of synthesis of the apoprotein of cytochrome P-450 while increasing the incorporation of amino acids into other hepatic proteins. The decrease in apocytochrome P-450 synthesis explains the marked loss of drug biotransformation which occurs following induction of interferon.

Amino Acids↗

An immunologic study of the secretory products of rat Clara cells.

Lungs of adult rats were lavaged with normal saline containing 0.25 mM phenylmethylsulfonyl fluoride. The surfactant pellet was removed by centrifugation and serum proteins in the lavage were removed by affinity chromatography using rabbit anti-rat whole serum antiserum. The residual proteins, thought to represent products of secretory cells, were used as the immunogen to inject rabbits. The resulting antiserum was absorbed with affinity columns of rat serum and rat liver extract. The gamma globulin fraction of the unbound antiserum was found to react with two proteins in the lavage by immunodiffusion and crossed immunoelectrophoresis. The antiserum specifically stained, by the immunoperoxidase method, a subpopulation of cells consistent in morphology with Clara cells lining the bronchioles and bronchi. The antigens were detectable, by immunohistochemistry, in rat fetus at 19 days of gestation, a progressive increase in the antigen content was noted with increasing gestational age and an adult pattern was noted at 2 weeks of age. In adult animals the intracellular content of the antigens appears to be about twofold greater than their content in the lavage fluid.

Animals↗

Structural and ontogenetic relationships of rat lung surfactant apoproteins.

Glycoproteins of molecular weights (MW) of 38,000, 32,000, and 26,000 are found in surfactant isolated from rat lungs. These proteins were further examined for their specificity to pulmonary surfactant, structural and metabolic interrelationships, and relation to the ontogenesis of pulmonary surfactant. With ultracentrifugations in salt and sucrose density gradients, a preparation of pulmonary surfactant was isolated from rat lung lavage fluid, which was rich in surfactant lipids (phosphatidylcholine and phosphatidylglycerol), and contained exclusively the 38,000-, 32,000-, 26,000-, and 10,000- to 12,000-dalton proteins. The 38,000-, 32,000-, and 26,000-dalton proteins are not serum proteins. Using an antiserum specific for the combined 38,000-, 32,000-, and 26,000-dalton proteins and the immunoperoxidase technique, the source of one or more of these three proteins was found to be alveolar epithelial type II cells, the cells involved in the synthesis and secretion of pulmonary surfactant. These proteins, when dissociated from lipids, show considerable self-association and form homopolymers. On isoelectric focusing, these proteins show considerable charge heterogeneity, which, in large part, is due to terminally linked sialic acid residues. Partial proteolysis of these proteins and subsequent analyses of the released polypeptides suggest the existence of large segments of homology between the 38,000-, and 32,000-dalton proteins. The relationship of the 38,000-, and 32,000-dalton proteins with the 26,000-, and 10,000- to 12,000-dalton proteins is not clear as yet. The results of protein analyses of purified tubular myelin and of lamellar bodies suggest that the 26,000-dalton protein may be derived extracellularly, possibly from other surfactant proteins by the action of enzymes present in the alveolar lining layer. We observed no reactivity of the antibody raised against the 38,000-, 32,000-, and 26,000-dalton proteins with the 10,000- to 12,000-dalton protein. The 38,000-, 32,000-, and 26,000-dalton proteins appear during fetal lung maturation at the same gestational time as the surfactant is known to appear, and their combined content increases thereafter in fetal lungs and in amniotic fluid. It appears that the less glycosylated (32,000-dalton protein) of the 38,000- and 32,000-dalton proteins appears first during fetal lung development.

Animals↗