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Biomedical subjects

R S Bhatt

Publications and source records attributed to R S Bhatt.

22 records · Page 2Linked to original sources
PubMed1983

Cloning and sequence analysis of cDNA for the precursor of human growth hormone-releasing factor, somatocrinin.

Molecular cloning has established the primary structures of two precursors of the human pancreas growth hormone-releasing factor (hpGRF-44), somatocrinin. Both polypeptides contain the sequence of hpGRF-44 flanked by basic processing sites. Furthermore, the precursors include a putative signal sequence and a carboxyl-terminal amidation signal for hpGRF-44. The two forms of mRNA code for pre-pro-GRF-107 and pre-pro-GRF-108. Pre-pro-GRF-108 differs from pre-pro-GRF-107 by the insertion of a serine in the carboxyl-terminal portion of the precursor. In vitro translation of tumor poly(A)+ RNA followed by immunoprecipitation with GRF-specific antiserum and gel electrophoresis showed the molecular weight of preprosomatocrinin to be approximately 13,000, which is in good agreement with the molecular weight deduced from the sequences of the cDNA clones.

Amino Acid Sequence↗
PubMed1981

Interaction of 5-ethynyl-2'-deoxyuridylate with thymidylate synthetase.

The interaction of 5-ethynyl-2'-deoxyuridylate (5-ethynyl-dUMP; 1) with thymidylate (dTMP) synthetase has been investigated. The compound was an inhibitor of the enzyme, competitive with 2'-deoxyuridylate (dUMP) when the reaction was initiated by addition of enzyme (Ki = 2.7 X 10(-6) M). However, upon preincubation of 1 with dTMP synthetase, the inhibition pattern became noncompetitive. The time course of the enzyme reaction in the presence of 1 was nonlinear, indicating an increase in binding with time. Irreversible inactivation of the enzyme did not occur. The compound did not appear to become altered structurally as a result of interaction with the enzyme. A ternary complex was formed among dTMP synthetase, compound 1, and 5,10-methylenetetrahydrofolate, which was stable enough to survive Sephadex G-25 filtration but dissociated upon denaturation of the enzyme.

Binding, Competitive↗
PubMed1980

Comparison of adriamycin- and ouabain-induced cytotoxicity and inhibition of 86rubidium transport in wild-type and ouabain-resistant C3H/10T1/2 mouse fibroblasts.

Ouabain (OUA) inhibited 86Rb uptake (50% inhibitory concentration = 0.8 X 10(-4) M) over concentration ranges close to those at which it caused a reversible cytotoxicity (50% lethal dose = 2.5 X 10(-4) M) in growing wild-type C3H/10T1/2 cells. On the other hand, Adriamycin (ADM) inhibited 86Rb uptake (50% inhibitory concentration = 2 X 10(-3) M) but at concentrations 10(4)-fold higher than those causing irreversible cytotoxicity in growing wild-type cells (50% lethal dose = 3 X 10(-8) M). While OUA inhibited 86Rb uptake more in wild-type cells than in a OUA-resistant mutant, ADM inhibited 86Rb uptake to the same extent in confluent wild-type and OUA-resistant cells. Further, three OUA-resistant mutants were not cross-resistant to ADM- or daunomycin (DM)-induced cytotoxicity during log phase or to ADM-induced cytotoxicity at confluence. In addition, ADM, DM, or 5-iminodaunomycin did not displace the cardiac glycosides digoxin or digitoxin from their respective antibody complexes. The order of potency of anthracycline derivatives in inhibiting 86Rb uptake in confluent wild-type cells was the same as their order of inhibiting the growth of wild-type cells and in detaching confluent wild-type cells (DM > ADM > 5-iminodaunomycin) but did not correlate with their cardiotoxic potentials (ADM > DM > 5-iminodaunomycin). Therefore, in this model system, ADM cytotoxicity is mediated differently from OUA cytotoxicity. Further, we find no biological evidence consistent withADM binding to the OUA site on the cell surface (Na+-K+) adenosine triphosphatase and therefore no evidence in this model system that ADM cardiotoxicity could be a digitalis-type toxicity per se.

Animals↗