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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 667 records · Page 37Linked to original sources
PubMed1974

Pathogenesis of temperature-sensitive mutants of sindbis virus in the embryonated egg. I. Characterization and kinetics of viral multiplication.

Exploratory experiments were performed with temperature-sensitive (ts) mutants of Sindbis virus for studies on viral pathogenesis in the embryonated egg, a host which is immunologically underdeveloped. Parent and mutants were found to be virulent at the permissive temperature (33 C), but only the mutants were attenuated at the nonpermissive temperature (38.5 C). The degree of attenuation varied with the mutant and the route of inoculation. Chicks which survived infection by ts mutants at a nonpermissive temperature weighed the same as controls and showed no obvious abnormalities on gross examination. Whenever death of the embryo at the nonpermissive temperature occurred after inoculation with a mutant, it was apparently due to the selection of a population of temperature-insensitive virulent revertants. Kinetic studies showed that, after inoculation of the chorioallantoic membrane and incubation at the permissive temperature, a number of cycles of virus multiplication and dissemination apparently occurred rapidly. At the nonpermissive temperature, multiplication was undetectable. Certain pathophysiological signs were seen in the slower, less virulent infections by the mutants at the permissive temperature that were apparently masked or obscured in the more virulent, rapid infection by the parent. From these results and those reported in a subsequent paper, it appears that ts mutants of viruses possess potential as valuable tools for analyzing pathogenesis and immunity in the intact animal host that are complementary to more conventional approaches which employ normal (temperature-insensitive) viruses.

Animals↗
PubMed1974

Pathogenesis of temperature-sensitive mutants of sindbis virus in the embryonated egg. II. Control of the infectious process.

Viral infection in the embryonated egg was controlled through appropriate temperature shifts. Through such control of the infection, certain groups of key tissues were implicated in the pathogenic processes that lead to death of the embryo, whereas other tissues were eliminated as relatively unimportant. Temperature shift-down experiments suggested that some mutants could resume the infectious process after relatively long periods (ribonucleic acid-negative mutants, Sts-4 and Sts-17) at the nonpermissive temperature, whereas others (RNA-positive mutants, Sts-2 and Sts-10) could not resume infection, even after a relatively short period at the nonpermissive temperature.

Animals↗
PubMed1974

Effect of beta-propiolactone inactivation of polyoma virus on viral functions.

Polyoma virus was inactivated by treatment with beta-propiolactone. T-antigen production, polyoma-RNA synthesis, induction of host DNA synthesis (measured by incorporation of labeled thymidine into the cell culture), and in vitro transforming ability were inactivated to a similar degree by various beta-propiolactone concentrations (0.25% beta-propiolactone reduced these functions approximately 96%), whereas plaque-forming ability and the ability of the virus to replicate its DNA and to synthesize capsid antigen were inactivated by a given concentration of beta-propiolactone to a much greater degree (0.25% beta-propiolactone led to a reduction of plaque-forming ability of over 8 logs). The significance of these data and their relationship to previously published experiments are discussed.

Animals↗
PubMed1973

Fermentation of glucose, fructose, and xylose by Clostridium thermoaceticum: effect of metals on growth yield, enzymes, and the synthesis of acetate from CO 2 .

Clostridium thermoaceticum ferments xylose, fructose, and glucose with acetate as the only product. In fermentations with mixtures of the sugars, xylose is first fermented, then fructose, and last, glucose. Fructose inhibits the fermentation of glucose, and this inhibition appears to be due to a repression of the synthesis of an enzyme needed for glucose utilization. Addition of metals to the culture medium increases the cell yield drastically from about 7 to 18 g per liter, and Y(glucose) values between 40 and 50 are obtained. According to the postulated pathways of the fermentation of glucose and synthesis of acetate from CO(2) by C. thermoaceticum, 3 mol of ATP are available as energy for growth. Thus a Y(adenosine 5'-triphosphate) of 13 to 16 is obtained. Because the normal Y(ATP) value is 10.5, this could mean that an additional source of ATP is available by an unknown mechanism. The addition of metals also increases the nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase activity, the overall reaction ((14)CO(2) --> acetate), and the incorporation of the methyl group of 5-methyltetrahydrofolate into acetate. These reactions are catalyzed very efficiently by cells harvested in early growth, whereas cells obtained at the end of a fermentation have very low formate dehydrogenase activity and capacity to incorporate CO(2) into acetate. The following enzymes involved in the synthesis of acetate from CO(2) and in the metabolism of pyruvate are present in extracts of C. thermoaceticum: 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate reductase, phosphate acetyltransferase, and acetate kinase. These enzymes are not or are very little affected by the addition of metals to the growth medium. The amount of corrinoids in cells from early growth is low, whereas it is high in cells harvested late in growth. The opposite is found for the activity of delta-aminolevulinate dehydratase, which is high at the beginning of growth and low at the end.

Acetates↗
PubMed1973

Effects of polyadenylic acids on functions of murine RNA tumor viruses.

Single-stranded polyribonucleotides, which competitively inhibit murine RNA tumor virus reverse transcriptase in vitro, were tested as inhibitors of various virus functions in cell culture. The compounds had two concentration-dependent effects. At high concentrations (100 mug/ml), both poly(adenylic acid) [poly(A)] and poly(2'-O-methyladenylic acid) [poly(Am)] inhibited the uptake of radioactively labeled leukemia virus by Swiss mouse embryo cells, but neither had a similar effect on Sindbis virus adsorption. At low concentrations (10 mug/ml), poly(Am) did not inhibit the uptake of leukemia virus but did inhibit virus replication by 85%; in contrast, the replication of Sendai virus and Sindbis virus was not inhibited significantly at this concentration. Both compounds were effective only when added prior to or early during virus infection. Poly(Am) was a much more effective inhibitor than poly(A), probably due to the nuclease resistance of the former compound. Poly(Am) at 5 mug/ml also inhibited transformation of 3T3 cells by Moloney sarcoma virus. However, neither poly(A) nor poly(Am) at high concentrations inhibited the activation of endogenous leukemia virus by iododeoxyuridine in AKR mouse embryo cells. These results suggest that virus reverse transcriptase plays an essential role in both the replication of exogenous murine leukemia viruses and the transformation of cells by murine sarcoma viruses but probably has no role in the activation of endogenous leukemia virus.

Adenosine Monophosphate↗