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Biomedical subjects

S Aoyagi

Publications and source records attributed to S Aoyagi.

At least 307 records · Page 17Linked to original sources

[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)].

The antimicrobial and antitumor activities, and the pulmonary toxicity of pepleomycin (NK631) were studied in comparison with bleomycin (BLM). NK631 showed a broad antimicrobial spectrum against gram positive and gram negative bacteria equally to BLM, and its activity was about twice higher than BLM. NK631 showed higher activity on cultured HeLa S3 cells and higher antitumor effect on the transplanted tumors of Ehrlich solid carcinoma in mice, AH66 and AH66F ascites hepatoma in rats, and lower antitumor effect on Ehrlich ascites carcinoma in mice than BLM. Similarly to BLM, NK631 did not show satisfactory activity on L1210 leukemia in mice. NK631 showed marked effect on chemically induced squamous cell carcinoma, spontaneous lymph sarcoma of a dog, human and dog gastric cancer heterotransplanted in nude mice equally to BLM. Furthermore NK631 exhibited remarkably higher antitumor activity on lymph node metastasis of AH66 ascites hepatoma of rats and chemically induced gastric carcinoma of rats than BLM. Pulmonary toxicity of NK631 was low as 1/3 in incidence and 1/4 in grade of the BLM in old mice system. This trend was confirmed by chemical analysis of hydroxyproline in lung.

Animals↗

Isolation and characterization of valine transfer RNA from Saccharomyces cerevisiae.

Two procedures for isolating valine tRNA from commercial bakers' yeast were investigated. The first involved: (a) counter double current distribution; (b) chromatography on benzoyl-DEAE-cellulose; (c) reverse phase chromatography on Chromosorb G saturated with trioctylpropylammonium bromide (Oakridge System 3). The material isolated lacked the 3'-terminal adenylic acid residue. The second procedure involved the first two steps above followed by: (a) enzymatic aminoacylation with a partially purified yeast extract; (b) derivatization with N-phenoxyacetoxysuccinimide; (c) chromatography on benzoyl-DEAE-cellulose; (d) reverse phase chromatography, System 3. The product was intact tRNA. It was a mixture of isoacceptors (59:41) differing by a modification (uracil leads to dihydrouracil) at position 48. It was free of denatured material; specific activity 1,825 pmol of valine/A260 unit of tRNA. Sequence analysis confirmed the recently corrected structure (Bonnet, J., Ebel, J. P., Dirheimer, G., Shershneva, L. P., Krutilina, A. I., Venkstern, T. V., and Bayev, A. A. (1974) Biochimie 56, 1211-1213). A preliminary study of the alkaline hydrolysis of the 7-methylguanosine residue that occurs at position 47 showed that at least two products are formed instead of only one as usually quoted in the literature. A rapid, ultramicro, chromatographic system for separating these products and measuring them quantitatively is described.

Guanosine↗

Bisulfite-induced C changed to U transitions in yeast valine tRNA.

The reaction of yeast tRNAVallab with NaHSO3 at 25 degrees and pH 5.8 has been studied. Six reactive residues have been located. C-17 in loop I is the most reactive (51% conversion) and C-73 in the first base pair of the acceptor stem the least reactive (8%). Three of the remaining reactive residues (C-39 in loop II, C-75 and C-76 near the acceptor stem) react to the same extent (36 to 38%) under the conditions of the experiment. C-37 in the anticodon reacted to a lesser extent (28%) than C-39 (36%), located just 2 residues away in the anticodon loop. No other changes were detected, but kinetic data suggest one or more additional residues may react very slowly. The C changed to U change in the anticodon (iac changed to iau) is a missense change (Val changed to Ile). Both mechanistic considerations and experimental data from the literature show that HSO3--induced deamination of cytosine residues occurs only at unstacked residues. We interpret the quantitative changes in tRNAVal to indicate that C-17 spends a large portion of its lifetime in an unstacked conformation. The stacking lifetimes of C-37, C-39, C-75, and C-76 seem to be similar but not identical. All other cytidine residues are much more tightly stacked. These results are consistent with the folded cloverleaf models that have been proposed from x-ray diffraction studies of yeast tRNAPhe. Residues C-46, C-49, C-57, and C-61, which are present in the single-stranded regions of the unfolded cloverleaf structure, do not react, suggesting that they are tightly stacked in solution under the conditions of this experiment. The data also suggest that anticodon-loop conformations other than the extremes with five bases stacked on either the 3' or 5' portion of the anticodon stem exist in solution and that the anticodon loop is flexible.

Base Sequence↗