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Biomedical subjects

A Raina

Publications and source records attributed to A Raina.

At least 37 records · Page 2Linked to original sources
PubMed1982

Synthesis of Semliki-forest virus in polyamine-depleted baby-hamster kidney cells.

The role of polyamines in macromolecular synthesis has been studied using the synthesis of Semliki-Forest virus (SF virus) in normal and alpha-difluoromethylornithine-treated baby-hamster kidney (BHK21) cells as a model system. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, the rate-limiting enzymes in polyamine biosynthesis, decreased rapidly in mock- and SF-virus-infected cells, indicating that virus production in BHK21 cells was not dependent on polyamines formed after infection. A prolonged treatment of BHK21 cells with alpha-difluoro-methylornithine, a specific inhibitor of polyamine synthesis, resulted in a marked inhibition of the initial rate of virus production, which appeared 72 h after the beginning of the treatment. This inhibition was reversed by putrescine, spermidine and spermine, and at last partially by several other diamines and polyamine homologues. Polyamine-depletion also markedly reduced viral RNA polymerase activity in SF-virus infected cells. Addition of spermidine to the culture medium rapidly increased viral RNA polymerase activity in the inhibitor-treated cells but had no effect on the enzyme activity when added directly to the assay mixture. The results indicated that polyamines are needed for maximum initial rate of SF-virus replication and suggest that the inhibition of virus production in polyamine-depleted cells is at least partly due to malfunction of the protein-synthetic machinery of the host cell.

Animals↗
PubMed1982

Inhibition of the synthesis of polyamines and macromolecules by 5'-methylthioadenosine and 5'-alkylthiotubercidins in BHK21 cells.

5'-Methylthioadenosine and four 5'-alkylthiotubercidins were tested for their ability to inhibit polyamine synthesis in vitro and to decrease polyamine concentration and prevent growth of baby-hamster-kidney (BHK21) cells. 5'-Methylthioadenosine and 5'-methylthiotubercidin decreased the activity of spermidine synthase from brain to roughly the same extent, whereas brain spermine synthase was much more strongly inhibited by 5'-methylthioadenosine compared with 5'-methylthiotubercidin. These nucleoside derivatives also inhibited the growth of BHK21 cells and increased the concentration of putrescine. 5'-Methylthioadenosine decreased cellular spermine concentration, whereas 5'-methylthiotubercidin lowered the concentration of spermidine. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were enhanced in cells grown in the presence of 5'-methylthiotubercidin. The growth inhibition produced by these nucleoside derivatives was not reversed by exogenous spermidine or spermine. 5'-Ethylthiotubercidin, 5'-propylthiotubercidin and 5'-isopropylthiotubercidin did not appreciably inhibit spermidine or spermine synthase in vitro or decrease the cellular polyamine content, but effectively prevented the growth of BHK21 cells. All nucleoside derivatives at concentrations of 0.2-1 mm caused a rapid inhibition of protein synthesis. It is concluded that the growth inhibition produced by 5'-methylthioadenosine and 5'-alkylthiotubercidins was not primarily due to polyamine depletion but other target sites, for instance the cellular nucleotide pool, cell membranes etc. must be considered.

Adenosine↗
PubMed1982

Clinico-pathological study of testicular involvement in leprosy.

Twenty five patients of lepromatous leprosy were studied clinically and histopathologically for testicular involvement. Testicular pain or swelling was the commonest complaint (68%) followed by sterility (28%) and impotence (4%). Reduced testicular size associated with soft feel was observed in 76% patients. Gynaecomastia was present in 36% and altered sexual hair pattern in 24%. Eleven out of sixteen (69%) patients had oligo/azoospermia. Out of the twenty testicular biopsies 15 (75%) had definite histological evidence of leprous pathology, irrespective of testicular size, semen picture and clinical signs and symptoms. One out of three epididymal biopsies showed minimal changes. Histopathological changes varied markedly, it was not possible to categorize these into vascular, interstitial and obliterative phases.

Adolescent↗
PubMed1981

Inhibitors of polyamine biosynthesis. 9. Effects of S-adenosyl-L-methionine analogues on mammalian aminopropyltransferases in vitro and polyamine biosynthesis in transformed lymphocytes.

Seven analogues of S-adenosyl-L-methionine were studied as inhibitors or substrates for mammalian spermidine and spermine synthases. One of these, S-(5'-deoxy-5'-adenosyl)-(+/-)-1-methyl-3-(methylthio)propylamine (5), showed a unique spectrum of activities on the polyamine biosynthesis enzymes. It was an inhibitor of S-adenosyl-L-methionine decarboxylase from rat liver and spermine synthase from bovine brain and rat ventral prostate. This compound was a substrate for the spermidine synthases from bovine brain and rat ventral prostate but not a substrate for the spermine synthases from these same sources. At concentrations of 0.2 mM and higher, compound 5 blocked the increases in polyamine levels and in [3H]thymidine incorporation induced by concanavalin A in cultured mouse lymphocytes. At approximately a 0.5 mM concentration of 5, the cellular polyamine levels and the rate of thymidine incorporation were similar to those of the unstimulated lymphocytes. Lower concentrations of 5 (0.02-0.1 mM) produced a dose-dependent increase in thymidine incorporation. A dose-dependent decrease in the cellular polyamine levels was observed in the range of 0.05-0.5 mM of the inhibitor. These results suggest that the effects of 5 on transformed lymphocytes are complex and may not be solely due to the inhibition of polyamine biosynthesis by this compound.

Animals↗
PubMed1981

Roles of polyamines in the replication of animal viruses.

Several animal viruses are known to contain significant amounts of polyamines but so far the function of these viral components is poorly understood. In this study the role of polyamines in the replication of two different types of viruses, herpes simplex virus type 2 and Semliki Forest virus (SFV) has been investigated. Purified SFV was found to contain fairly small amounts of polyamines, sufficient to neutralize only about 3% of viral nucleic acid phosphate, i.e., 1/20 of that found in herpes simplex virus. The production of both viruses was, however, markedly inhibited in BHK21 cells depleted of polyamines by treatment with alpha-difluoromethylornithine, a specific inhibitor of polyamine synthesis. This inhibition was reversed by putrescine, spermidine and spermine, and at least partly reversed by several other diamines and polyamine homologs. The activity of viral RNA polymerase induced by SFV infection was markedly reduced in polyamine-depleted cells but increased rapidly after addition of spermidine to the culture medium. It appears that the inhibition of virus production in polyamine-depleted cells is due in part to malfunction of protein synthetic machinery of the host cell. The possibility that other steps in virus synthesis and assembly are affected by polyamine deficiency is currently being investigated.

DNA-Directed RNA Polymerases↗
PubMed1979

Polyamine synthesis in mammalian tissues. Isolation and characterization of spermine synthase from bovine brain.

Spermine synthase, a propylamine transferase, which catalyses the biosynthesis of spermine from S-methyladenosylhomocystemine and spermidine has been purified to an apparent homogeneity (about 6000-fold) from bovine brain using spermine-Sepharose affinity chromatography. The enzyme preparation was free from S-adenosylmethionine decarboxylase and spermidine synthase activities. The molecular Stokes radius of the enzyme was calculated to be 4.16 nm. The enzyme has an apparent molecular weight of approximately 88 000, composing of two subunits of equal size. The enzyme showed a broad pH optimum between 7.0 and 8.0 and an acidic isoelectric point at pH 5.10. The apparent Km values for S-methyladenosylhomocysteamine was 0.6 microM and about 60 microM for spermidine. The enzyme showed strict specificity to spermidine as the propylamine acceptor. Both the reaction products, spermine and 5'-methylthioadenosine inhibited the enzyme activity, methylthioadenosine being a powerful competitive inhibitor with respect to S-methyladenosylhomocysteamine (Ki value of about 0.3 microM). Putrescine also inhibited competitively with respect to spermidine (Ki value of about 1.7 mM). Spermine synthase had no requirements for metal or other cofactors.

Animals↗
PubMed1976

A sensitive isotopic assay method for S-adenosylhomocysteine hydrolase. Some properties of the enzyme from rat liver.

A rapid and sensitive isotopic method is presented for the assay of S-adenosylhomocysteine hydrolase (EC 3.3.1.1) activity, based on the formation of radioactive S-adenosylhomocysteine labelled in the adenosine portion. The radioactive product is separated either by low-voltage paper electrophoresis or by using phosphocellulose ion-exchange paper. Some kinetic properties of the enzyme from rat liver have shown to be clearly different from those reported earlier for this enzyme. The use of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent inhibitor of adenosine deaminase, makes it possible to measure the S-adenosylhomocysteine hydrolase activity in tissues with a high adenosine deaminase activity, e.g. in intestinal mucosa.

Adenosine↗
PubMed1975

Physiology of the natural polyamines putrescine, spermidine and spermine.

The biochemistry and biological function of the naturally occurring polyamines, putrescine, spermidine, and spermine, have been reviewed with special reference to animal organisms. These compounds are universally distributed in all living material. Their biosynthesis from ornithine and methionine is accurately controlled and may fluctuate according to the metabolic needs of the cell. Polyamines strongly and specifically interact with nucleic acids in vitro. It appears that under physiological conditions a substantial portion of cellular polyamines is noncovalently bound to nucleic acids and nucleic acid-containing structures such as ribosomes. Polyamines are able to stimulate protein and ribonucleic acid synthesis in vitro. In several systems characterized by rapid growth polyamines and ribonucleic acid accumulate in parrallel. Evidence that polyamines may have an essential role in protein and/or nucleic acid synthesis is substantiated by recent observations on polyamine-deficient bacterial mutants, although no specific function has been established with certainty as yet. Some clinical applications of polyamine research related to cancer are also discussed briefly.

Adrenocorticotropic Hormone↗