Biomedical subjects
Publications and source records attributed to D Schlessinger.
Amphotericin B was found to potentiate the antifungal effects of mycophenolic acid glucuronide, tetracycline, and actinomycin D by increasing the penetration of these antibiotics through the fungal cytoplasmic membrane. Because the fungi were over 100 times more susceptible than animal cells to these effects of amphotericin B, these observations might have clinical application.
A standard stringent strain of Escherichia coli makes little or no ribosomal ribonucleic acid (RNA) during starvation for an essential amino acid, whereas the isogenic relaxed strain makes both ribosomal and messenger RNA. A third class of strains was found which continues to make ribosomal RNA during starvation, but the RNA made is apparently unstable. There is little accumulation of RNA in the third class of strains, and few complete newly formed chains of (3)H-ribosomal RNA are observed in sedimentation analyses, even after long labeling times.
Mutants that require exogenous 3',5'-cyclic adenosine monophosphate (cAMP) for exponential growth were isolated from strains deficient in adenyl cyclase. Studies of one strain showed that cAMP is not incorporated into macromolecules; instead, it seems to have a regulatory function, i.e., in media lacking cAMP, cells form ribonucleic acid (RNA) and protein at linear rather than exponential rates. The exact lesion is not known; ribosomes, messenger RNA, and the beta and beta' subunits of RNA polymerase continue to be made in absence of added cAMP.
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Ribonuclease II action on polyuridylate is competitively inhibited by transfer ribonucleic acid and noncompetitively inhibited by sodium ions. At low substrate levels, adenosine-5'-triphosphate is also inhibitory.
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Native ribosomal RNA anid inttact pliage R17 RNA are insensitive to attack by ribonuclease V, an exonucleolytic activity associated with ribosome movement on the substrate RNA. However, ribosomal RNA becomes a substrate when it is heated under conditions that make it a template for protein synthesis, and R17 RNA is attacked if it is either heated or fragmnented. Accessibility of the 5' terminus of an RNA molecule is probably inzcreased by heating or fragmnentation and may determine its susceptibility to ribonuclease V.
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Unique among adenine nucleotides tested by filter binding assays, 3':5'-cyclic AMP binds to the G translocation factor. Binding is dependent on the presence of GTP, and is inhibited by GDP, by the analog 5'-beta,gamma-methylene GTP, and by the antibiotic fusidic acid. The cAMP seems to be released during the ribosome-dependent translocation of charged tRNA catalyzed by G factor. Bound cAMP inhibits GTPase and ribosome-associated degradation of messenger RNA, but does not inhibit protein synthesis. cAMP might thereby regulate the ratio of productive to degradative transits of ribosomes on messenger RNA, and this may account for some part of its profound effect on levels of specific bacterial messenger RNA species.
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