[Synthesis of potential biologically active benzotheno-oxazinones].
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Biomedical subjects
Publications and source records attributed to W Siede.
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Using the thermoconditional yeast mutant rev2ts that controls an apparently site-specific step of mutagenic DNA repair it was possible to measure the time course of REV2 dependent UV-induced reversion of the ochre allele his5-2 and recovery of survival for UV-treated stationary phase cells: due to the rev2ts coded protein being active at 23 degrees C, survival and mutation frequencies increased with duration of incubation under permissive conditions in growth medium before the temperature was shifted to 36 degrees C (restrictive temperature). This increase was abolished in the presence of the protein synthesis inhibitor, cycloheximide. Furthermore, the REV2 dependent recovery of survival could be blocked or nearly blocked by cycloheximide added at any time during repair. Therefore, REV2 dependent repair can be characterized as a process requiring concomitant protein synthesis. These findings give further support to the concept that in yeast, mutagenesis involves UV inducible components of DNA repair.
The time course of REV2 dependent recovery from prelethal UV damage and UV-induced locus-specific reversion of the his5-2 allele was determined in temperature-shift experiments by use of a thermoconditional allele of the rev2 gene (rad5-8, rev2ts). In UV-irradiated, exponentially growing rev2ts cells the REV2 dependent repair activity persists for up to 8 h at permissive temperature (23 degrees C), while the REV2 dependent mutagenic process is mostly completed within 2 h. The REV2 dependent process in exponentially growing cells is highly impaired by inhibition of protein synthesis. However, a REV2 dependent repair activity independent of de novo synthesis is detectable, even in the presence of up to 200 micrograms/ml cycloheximide, a response not found in stationary phase cells. Thus, the REV2 dependent process seems to be partially constitutive in exponentially growing cells. Additionally, exponentially growing rev2ts cells were considerably more UV-sensitive at restrictive temperature (36 degrees C) than were stationary phase cells.
Mutants of Saccharomyces cerevisiae with enhanced sensitivity to the DNA cross-linking agent nitrogen mustard (HN2) have been isolated and partially characterized with respect to their phenotypic and genetic properties. The screening technique, based on HN2-sensitivity as sole criterion, yields approxiamtely 1 sensitive isolate in 200 clones when applied to an intensively mutagenized population of a resistant parent strain. Mutants characterized so far are all due to recessive nuclear genes and represent at least seven complementation groups. They exhibit different degrees as well as different patterns of sensitivity towards monofunctional and bifunctional alkylating agents, and ultraviolet light.
The favorable effect of glucocorticoids on the development of the chronic active hepatitis is statistically proved on the basis of the amelioration of the survival rate in controlled studies. The so-called lupoid hepatitis is significantly better influenced than the HBs-Ag positive chronic hepatitis. By additional therapy with azathioprine it is possible to reduce the dose of glucocorticoids. Therefore it is better to combine glucocorticoids and azathioprine in some cases, especially in those with a high dosed glucocorticoid therapy. Further prospective studies are necessary to check more precisely the therapeutic effect of the different remedies. The effect of D-penicillamine is vague. A treatment with chloroquine is indicated in cases with contraindications again glucocorticoids and azathioprine.
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