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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 487 records · Page 27Linked to original sources
PubMed1979

Action of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine hydrochloride) in the germ tissue of mice: dominant lethal effects.

A study was carried out on the effects of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide (procarbazine, Natulan) in the dominant lethal test in the mouse. Male mice were dosed once and mated with fresh virgin females each week. The utilization of sperm, treated as spermatids or testicular sperm with 100-800 mg/kg, resulted in significant post- and pre-implantation death of embryos. Fertility was markedly reduced after the injection of 200 mg/kg of procarbazine and over. This is probably due to a cell killing effect, the most sensitive stages being differentiating spermatogonia, type A sermatogonia and resting primary spermatocytes. Total sterility was induced for several weeks with doses of 600 and 800 mg/kg. Up to 12 weeks after treatment the number of females with implants was still significantly lower than controls indicating a severe depletion of spermatogonial cells. The spectrum of effects correlates well with the drug's effect on nucleic acid and protein synthesis.

Animals↗
PubMed1979

Novel protein kinase, AUT-PK 85, isolated from adrenocortical carcinoma: purification and characterization.

We describe the purification to apparent homogeneity of a protein kinase (designated AUT-PK 85) from adrenocortical carcinoma 494, as evidenced by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme binds cyclic AMP (cAMP) and autophosphorylates but does not use histone, casein, or polysomes as substrates in the presence or absence of cAMP. Stoichiometry of phosphate incorporation was 0.71 mol/mol of enzyme. The enzyme was found to have a molecular weight of 85,000 based on gel filtration. The protein was composed of polypeptides having the same molecular weight 42,000, and thus it appears to consist of two subunits of equal size. The enzyme bound two cAMP molecules, indicating that each subunit binds one molecule of cAMP. The homogeneous enzyme did not inhibit the protein kinase activity of the free catalytic subunit of normal adrenal cAMP-dependent protein kinase under conditions such that recombination with the free regulatory subunit occurred. cAMP bound specifically to the enzyme with an apparent dissociation constant (cfKd) of 1.2 X 10(-8) M. Scatchard plot data indicated one type of binding sites for cAMP. The enzyme did not bind adenosine. This novel autophosphorylating, cAMP-binding, protein kinase may be a characteristic of certain adrenal neoplasms.

Adrenal Cortex Neoplasms↗
PubMed1979

A study of D-glucose uptake by small intestine of rats following in vivo vinblastine treatment.

The pharmacokinetics of tritiated vinblastine in rats has indicated a considerable excretion of the alkaloid through bile into the intestinal lumen. The present study was undertaken to find out whether the presence of the alkaloid in the lumen of small intestine alters the normal transport of nutrients across the small intestine. This was done by measuring the in vitro D-glucose uptake by slices of small intestine of rats pretreated with vinblastine. Vinblastine pretreatment was done by filling the lumen of in vivo segments of small intestine of rats with different concentrations of the alkaloid for 30 and 60 min before uptake was measured. A significant dose-dependent reduction in D-glucose uptake was observed.

Animals↗
PubMed1979

Stimulation of guanosine 3',5'-monophosphate-phosphodiesterase activity by adrenocorticotropic hormone-activated increase of guanosine 3',5'-monophosphate in isolated adrenocortical carcinoma cells.

The decline of the ACTH-stimulated cGMP to the basal level in isolated adrenocortical carcinoma cells was inhibited by cyclic phosphodiesterase inhibitors. Time-course experiments showed that the ACTH-induced level of cGMP preceded the activation of phosphodiesterase. Cells incubated with increasing concentrations of exogenous cGMP responded with a corresponding increase in the cGMP-phosphodiesterase activity. cAMP was 100-fold less effective than cGMP in the activation of cGMP-phosphodiesterase, indicating the nucleotide specificity of enzyme activation. The activation of cGMP-phosphodiesterase by ACTH-induced cGMP or exogenous cGMP was rapid. In contrast to these observations, there was no activation of cAMP-phosphodiesterase by exogenous cAMP or cGMP. These results indicate that one mechanism by which isolated adrenocortical carcinoma cells regulate the ACTH-induced increase in cGMP is the cyclic nucleotide control of the activity of its phosphodiesterase, thereby regulating cGMP degradation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1979

A study of the effect of vinca alkaloid 'vinblastine' on gastrointestinal motility in rats.

Vinblastine an alkaloid of the periwinkleplant (Vinca), produced marked alterations in the motility of gastrointestinal tract in rats. The alkaloid reduced the rate of gastric emptying and slowed the transit of test substance through the small intestine. The effect of the drug on gastric emptying appeared to be dose-dependent. The latency of drug action on gut motility was found to be 5--10 min, when injected through the jugular vein.

Animals↗
PubMed1978

Inhibition of Ca2+-activated cyclic nucleotide phosphodiesterase reaction by a heat-stable inhibitor protein from bovine brain.

An inhibitor protein of cyclic nucleotide phosphodiesterase is demonstrated in bovine brain extract and separated from modulator binding protein, a recently discovered inhibitory factor of phosphodiesterase. The new inhibitor protein is similar to the cyclic AMP phosphodiesterase inhibitor from bovine retina (Dumler, I. L., and Etingof, F. N. 1976) Biochim. Biophys, Acta 429, 474-484) in its heat stability: it retains full activity upon heating in a boiling water bath for 2 min. The new inhibitor protein counteracts the activation of the Ca2+-activatable cyclic nucleotide phosphodiesterase by the Ca2+-dependent modulator protein without affecting the basal activity of the enzyme. The inhibition of phosphodiesterase by the inhibitor can be reversed by high concentrations of modulator protein but is not influenced by a 20-fold increase in Ca2+ concentration. In contrast, a Ca2+-independent form of cyclic nucleotide phosphodiesterase is not inhibited by the inhibitor protein. These results suggest that the heat-stable inhibitor protein is specific against the action of the Ca2+-dependent modulator protein. Gel filtration analyses on Sephadex G-75 and G-100 columns have shown that the inhibitor protein and the modulator protein may associate in the presence of Ca2+. The molecular weights determined by the gel filtration for the free inhibitor protein and the complex of the inhibitor and modulator protein are about 70,000 and 85,000, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Leucocyte migration inhibition test in cases of ischaemic heart disease.

Cases of ischaemic heart disease have been studied for the cell-mediated immune response against human heart antigen by using the leucocyte migration inhibition test. In 30 cases of acute myocardial infarction, the leucocyte migration inhibition values started increasing from the first week reaching a peak in 3 to 4 weeks and then declining but still above control values 12 months after infarction. The leucocyte migration inhibition values were significantly higher than control values in another 10 patients with late complications of previous infarction and in those patients with acute myocardial infarction who were less than 40 years of age, who had extensive anterior infarction, or who had a past history of angina pectoris. The leucocyte migration inhibition values were negligible in all the 12 patients with stable angina pectoris, but were high in 2 of the 8 with unstable angina and in 3 of the 4 with the intermediate coronary syndrome. The leucocyte migration inhibition values were much higher in patients with complications, which may be the result of cardiac damage by a cell-mediated immune response.

Adult↗
PubMed1978

Purification of the heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase by affinity chromatography.

The recently discovered heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase (Sharma, R. K., Wirch, E. & Warg, J. H. (1978) J. Biol. Chem., in press) has been purified 238 214-fold from bovine brain extract using an affinity column of the modulator protein--Sepharose 4B conjugate. The purified sample appears to be homogeneous as judged by sodium dodecyl sulphate (SDS) gel electrophoresis. The protein band has a mobility corresponding to that of a polypeptide of molecular weight 68 000. Since the heat-stable inhibitor protein has a molecular weight of 70 000 under nondenaturing conditions, it suggests that it is a monomeric protein. The protein has no inhibitory activity toward the cAMP-dependent protein kinase or protein phosphatase. The purified sample has been tested for various enzyme activities which include ATPase, GTPase, cAMP phosphodiesterase, cGMP phosphodiesterase, 5'-nucleotidase, and protein kinase. None of these activities are exhibited by the purified sample.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗