Alkylation of DNA with a mitomycin derivative, 7-N-(p-hydroxyphenyl)-mitomycin C. Reductive alkylation nd preferential binding to adenine.
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Biomedical subjects
Publications and source records attributed to Y Hashimoto.
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Adenosine triphosphate (ATP) and sodium nitroprusside (SNP) are administered to patients to induce and control hypotension during anesthesia. SNP is authorized for clinical use in USA and UK, and ATP is clinically used in other countries such as Japan. We investigated how these two drugs act on the cardiovascular systems of 20 dogs whose hearts had been denervated by a procedure we had devised. ATP (10 dogs) or SNP (10 dogs) was administered to reduce mean arterial pressure by 30% to 70% of control. Before, during and after induced hypotension, we measured major cardiovascular parameters. Hypotension induced by ATP was accompanied by significant decreases in mean pulmonary arterial pressure (p less than 0.001), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.001), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), total body oxygen consumption (p less than 0.05), and heart rate (p less than 0.001); all these variables returned normal within 30 min after ATP was stopped. Cardiac output did not change. During hypotension produced by SNP similar decreases were observed in mean pulmonary arterial pressure (p less than 0.01), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.01), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), and oxygen content difference between arterial and mixed venous blood (p less than 0.05), while heart rate (p less than 0.001) and cardiac output (p less than 0.05) were increased. Recoveries of heart rate and left ventricular end-diastolic pressure were not shown within 60 min after SNP had been stopped. Both ATP and SNP should act on the pacemaker tissue of the heart.
Pepsin digests of human post-burn wound tissues grafted with autologous fresh skin showed a significantly lower ratio, 0.37 +/- 0.04 (mean +/- S.D.), of type III to type I collagen determined by interrupted gel electrophoresis than the ratio, 0.55 +/- 0.13, measured in ungrafted wound tissues (p less than 0.001). In wounds grafted with frozen skin there was no significant difference from ungrafted wounds, but a significantly higher ratio, 0.46 +/- 0.08, than that in wounds grafted with fresh skin (p less than 0.001). These results were consistent with the histological features of the wound tissues.
The presence of tumor-specific or tumor-associated antigens in primary urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in ACI/N rats was examined by means of mixed lymphocyte-tumor cell culture. Bladder tumors (papilloma with cancer foci or cancer) induced by BBN treatment for 18 weeks or more (BT), epithelial cells from papillary hyperplasia induced by 6-week BBN treatment (PH), and normal bladder epithelial cells (NBE) were isolated from the bladder and used as stimulator cells after mitomycin C treatment. BT, PH and NBE all strongly stimulated the blastogenesis of the autologous lymphocytes on culture in medium containing fetal calf serum (FCS), but the spleen cells also stimulated the autologous lymphocytes in this medium. Although the magnitudes of blastogenesis were lower than those in FCS medium, on culture in medium containing rat serum, BT, PH and NBE, but not spleen cells, stimulated the blastogenesis of the autologous lymphocytes. The response with BT was significantly higher than the response with NBE, but there was no statistically significant difference between the response with BT and the response with PH. These results suggest that FCS medium, but not medium with rat serum, evokes the blastogenic response of lymphocytes cultured with autologous spleen cells, and that blastogenic responses with autologous bladder cancer can be produced by stimulation with some sort of tissue antigen present in normal or pre-neoplastic urinary bladder epithelial cells.
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To obtain permanent preparations for morphologic examination of hemopoietic cells cultured in methylcellulose medium, a new method designated as "the membrane filtration technique" has been devised. Permanent preparations of erythroid colonies, bursts and leukemic colonies, which have been grown mainly in methylcellulose medium, are illustrated in this paper. The stages of differentiation of cells within these colonies can be easily recognized by means of Wright-Giemsa staining.
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The carcinogenicities of 2-methoxy-4-aminoazobenzene and 3-methoxy-4-aminoazobenzene (2-MeO-AAB and 3-MeO-AAB) and their N-hydroxy derivatives (N-OH-2-MeO-AAB and N-OH-3-MeO-AAB) were tested in (C3H X C57BL/6) F1 mice. Topical sc injections, twice weekly for 8 weeks, of 4 or 8 mumol of N-OH-3-MeO-AAB dissolved in 0.1 ml of olive oil containing 10% dimethyl sulfoxide induced fibrosarcomas at the site of application. Similar treatment with 3-MeO-AAB or 2-MeO-AAB as well as N-OH-2-MeO-AAB failed to induce sarcomas. Oral administration of 0.09% 3-MeO-AAB in the diet for 13 months induced hepatic tumors in female mice but not in males. 2-MeO-AAB did not induce tumors in male or female mice. The relationship between carcinogenicity, mutagenicity, the ability to induce unscheduled DNA synthesis, and the metabolism of these azo dyes is discussed.
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