Growth and differentiation factors for B cells from human T cell clones.
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Biomedical subjects
Publications and source records attributed to M Okada.
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Oxidative in vitro metabolism of N,N-dibutylnitrosamine (DBN) by 9000g supernatant fraction (S9 fraction) prepared from rat liver and oxidation of DBN by chemical model systems (Udenfriend and Fenton) were investigated. The products retaining the N-nitroso group of DBN were analyzed by gas-liquid chromatography. Incubation of DBN with the S9 fraction gave hydroxy derivatives of DBN at the omega, omega-1, and omega-2 positions, while the chemical reaction of DBN in the Udenfriend and the Fenton model systems afforded compounds with an oxo group at the same positions. In all cases, omega-1 oxidation was predominant, followed by omega and then by omega-2 oxidations, while omega and omega-1 oxidations were the principal metabolic pathways of DBN in vivo in the rat. The differences in the oxidative transformation of DBN among in vitro enzymatic, non-enzymatic and in vivo systems are discussed.
Enzymatic alpha-hydroxylation is believed to be the initial step in the metabolic activation of mutagenic and carcinogenic nitrosamines. Oxidative in vitro metabolism of N,N-dibutylnitrosamine (DBN) by hepatic microsomal fractions prepared from rats treated with phenobarbital and polychlorinated biphenyl (PCB) was investigated. Following incubation of DBN with the microsomal fractions, N-butyl-N-(3-hydroxybutyl)nitrosamine was identified by gas-liquid chromatography as the principal metabolite with the N-nitroso moiety, and butyraldehyde and/or two isomeric butyl alcohols (n- and sec-) were also identified and determined by gas-liquid chromatography and high-pressure liquid chromatography. The latter compounds originate from the unstable alpha-hydroxylated intermediate, N-butyl-N-(1-hydroxybutyl)nitrosamine, by spontaneous decomposition. An increased production of butyraldehyde with a concomitant enhancement of the mutagenicity of DBN toward Salmonella typhimurium TA1535 was observed when microsomes prepared from phenobarbital- and PCB-treated rats were used. SKF 525-A not only inhibited the mutagenic activation of DBN by microsomes from rats treated with the inducers but also selectively inhibited the formation of butyraldehyde and butyl alcohols from DBN. These results indicate that among the four initial hydroxylations (alpha, omega-2, omega-1, and omega) of the butyl chain demonstrated in the metabolism of DBN, alpha-hydroxylation is primarily involved in the mutagenic activation.
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The correlation of prognosis with various clinical and pathologic factors was studied by use of multiple stepwise linear regression analysis among 77 patients undergoing resections for gastric cancer. Factors such as depth of penetration, invasion of the duodenum, macroscopic appearance, intramural and extramural growth pattern of the cancer, lymphatic or vascular invasion, and cancer cell-free dense submucosal fibrosis around the cancerous area were significant, and independent factors correlated with the prognosis, in that order. When these factors were taken into account, other factors such as sex and age of the patient, location, size, and histologic classification of the tumor, and folds' convergence were not significant.
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