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Biomedical subjects

J S Roth

Publications and source records attributed to J S Roth.

64 records · Page 4Linked to original sources
PubMed1966

The reaction of ribonuclease inhibitor with modified ribonucleases.

1. The effect of chemical modification of ribonuclease on its reaction with ribonuclease inhibitor has been studied. 2. Removal of free amino groups from the enzyme with nitrous acid or by acetylation did not affect the reaction. Some changes altered the stoicheiometry of the reaction and ribonuclease S was found to be inhibited linearly by increasing amounts of ribonuclease inhibitor, in contrast with ribonuclease A, which is inhibited in a non-linear way. One derivative of ribonuclease containing dimethylaminonaphthalenesulphonyl groups actually reacted with ribonuclease inhibitor to a greater extent (and linearly) than did the unaltered enzyme. 3. The positively charged histidine at the active site and the active enzyme did not appear to be necessary for the reaction since 1-carboxymethylhistidine-119-ribonuclease reacted with ribonuclease inhibitor to almost the same extent as the native enzyme. In general, any significant change in the conformation of ribonuclease was accompanied by a loss in its ability to combine with inhibitor. The presence of 8m-urea also prevented reaction of ribonuclease with inhibitor. 4. Some characteristics of the reaction of ribonuclease inhibitor, ribonuclease and deaminated ribonuclease with RNA and deaminated RNA were investigated.

Chemical Phenomena↗
PubMed1966

Studies on the function of intracellular ribonucleases. IV. Some observations on the properties of ribosomes and polysomes from rat liver and hepatomas.

Polysome and ribosome preparations from normal rat liver and from a series of transplantable rat hepatomas of different growth rates were compared. All the hepatomas had a significantly higher percentage of RNA in a polysome preparation than did the normal liver, and the polysome preparations from the tumors, with the exception of the Dunning hepatoma which has a high lipid content, gave a greater yield of RNA and protein per gram of wet tissue than the liver did. Heavier polysomes were considerably less prevalent in the tumors than in the liver, and the tumors contained a larger proportion of monomer and dimer ribosomes than the liver did. Evidence is presented that the increased monomer and dimer ribosome population of the hepatomas studied is not an artifact of preparation, but represents the true intracellular distribution. Ribosomes from normal liver and Morris 5123-D hepatoma were readily dissociated by 20 min' treatment with 1.0 mM EDTA, but ribosomes from the Dunning, Novikoff ascites, and McCoy MDAB hepatomas were little affected by such treatment. With higher concentrations of EDTA, the ribosomes from the Novikoff ascites and McCoy MDAB hepatomas broke down and did not form specific subunits as did ribosomes from liver and the Morris 5123-D hepatoma but rather gave rise to a variety of small degradation products. This behavior is ascribed to a higher RNase content of the Novikoff and McCoy MDAB hepatomas. Dunning hepatoma ribosomes were resistant to 4 mM EDTA.

Animals↗
PubMed1966

Studies on the function of intracellular ribonucleases. V. Ribonuclease activity in ribosomes and polysomes prepared from rat liver and hepatomas.

The RNase activity and properties of ribosome and polysome preparations from normal rat liver and some hepatomas have been examined. Polysome and ribosome preparations from the Novikoff, McCoy MDAB, and Dunning hepatomas had considerably higher specific RNase activity than corresponding preparations from normal rat liver, Novikoff ascites, or Morris 5123 hepatomas. The optimum pH of the RNase was approximately 8.5 for all samples tested, and the samples showed no evidence of latent RNase activity when treated with 3 M sodium chloride, EDTA, urea, or p-chloromercuribenzenesulfonic acid. The RNase activity appeared to be associated principally with breakdown products and/or subunits smaller than 80S. In the presence of Mg(++) ions, subunits could reaggregate to form monomer ribosomes indistinguishable from the natural products, but some of the reassociated ribosomes could contain RNase activity which had been bound to the smaller particles. Similar results were obtained with spermine. In the hepatomas, evidence was obtained for the preexistence of considerable amounts of the smaller, RNase-containing subunits in the cell. When a small amount of crystalline bovine pancreatic RNase was added to partly dissociated ribosomes, the RNase was found only in association with the smaller subunits, and little or no enzyme was taken up by ribosomes or polysomes. The results have led to the conclusion that RNase is not a normal constituent of the ribosome or polysome, but that RNase may become associated with these particulates if dissociation and reassociation take place. Some implications of these findings for the stability of messenger RNA and for the mechanism of its breakdown are discussed.

Animals↗
PubMedDate not supplied

The disposition and metabolism of 2',3'-dideoxycytidine, an in vitro inhibitor of human T-lymphotrophic virus type III infectivity, in mice and monkeys.

The pharmacokinetics and metabolism of the anti-human T-lymphotrophic virus type III/lymphadenopathy-associated virus agent 2',3-dideoxycytidine have been examined in BDF1 mice and rhesus monkeys, with ancillary enzyme studies carried out on tissue derived from both the latter species and also from human subjects. For the pharmacokinetic studies, 2',3-dideoxycytidine and its catabolic product 2',3-dideoxyuridine have been separated and measured in plasma, urine, and cerebrospinal fluid by a reverse HPLC method. For metabolic studies, tritium-labeled drug (labeled in the 5- and 6-positions of the pyrimidine ring) has been employed, utilizing an ion exchange HPLC analytical method suitable for the separation of the parent nucleoside from its mono-, di-, and triphosphates in cell extracts and in tissue homogenates. The drug is rapidly cleared from plasma in a biphasic manner (terminal t 1/2 in BDF1 mice and rhesus monkeys of 67 min and 109 min, respectively) following an iv bolus dose of 325 mg/m2. This two-compartment open model is predictive of plasma concentrations during long term ip infusions in mice. Dideoxycytidine is predominantly excreted in the urine as unchanged parent compound, although a minor urinary metabolite (2,3-dideoxyuridine) is detected in the monkey but not in the mouse. Oral absorption of 2',3'-dideoxycytidine is rapid, with plasma levels approaching those seen after iv administration within 45 min in the mouse. Entry to the central nervous system is also rapid, but the cerebrospinal fluid to plasma AUC ratio after iv administration is only 0.026-0.040 in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗