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Biomedical subjects

T Negishi

Publications and source records attributed to T Negishi.

At least 163 records · Page 9Linked to original sources

[Effects of long-term administration of Tegafur on patients with relapsing advanced carcinoma (stage D) of the prostate].

Daily 600 mg of Tegafur, in addition to antiandrogen therapy, was administered to 20 patients with relapsing prostatic carcinoma at stage D. Thirteen of the patients died and 7 patients are still alive. These patients were evaluated according to the objective response criteria of NPCP . Three patients showed partial regression, 9 patients showed stable prognosis and 8 patients showed progression. The patients who died had a mean survival duration of 77 weeks, which is longer than in other reports on the treatment of relapsing prostatic carcinoma. No severe toxicity was observed in any of the patients. These findings suggest that Tegafur is effective for the treatment of relapsing prostatic carcinoma.

Aged↗

A sensitive assay for mutagenic activity of N-nitrosamines and its use for detection of modulators of the mutagenicity.

By carrying out the pre-incubation of bacteria with N-nitrosamines under acidic conditions, the mutagenicity of N-nitrosodimethylamine on Salmonella TA100 and E. coli WP2 try, hcr was detected with increased sensitivity, compared to usual assays in neutral buffers. Using this modified assay system, compounds have been screened for their modulating effects on N-nitrosamine-mediated mutagenesis and the following were found to be inhibitors: cysteine, cysteamine, bisulfite, n-propylamine, n-butylamine, n-hexylamine, n-octylamine, n-nonylamine, serotonine, tryptamine, epinephrine, norepinephrine and oleic acid. The mechanisms of inhibition are discussed.

Amines↗

The pH-dependent response of Salmonella typhimurium TA100 to mutagenic N-nitrosamines.

The mutagenicity of some N-nitrosodialkylamines, i.e. N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodi-n-butylamine, N-nitrosomorpholine and N-nitrosopyrrolidine, was assayed on Salmonella typhimurium TA100 by the pre-incubation method, and the effect of changing the pH of the pre-incubation mixture was examined. Markedly higher mutagenicities were observed when the pre-incubation of bacteria with nitrosamine and S9 mix was done at pH 5.2, compared with mutagenicities observable after the pre-incubations at conventional pH 7. Pre-incubations at pH 6.2 resulted in responses of intermediate strength. With phenobarbital-induced rat S9, the ratios of mutagenic potency found by the pH 5.2 pre-incubation to that found by the pH 7.2 preincubation were 15-30 for N-nitrosodimethylamine, 5-10 for N-nitrosodiethylamine, 10-20 for N-nitrosodi-n-butylamine, 2-3 for N-nitrosomorpholine and 4-6 for N-nitrosopyrrolidine. The mutagenic potency of each nitrosamine varied with the change of S9 source. The S9 sources examined were PCB-induced rat and mouse livers, and uninduced rat and mouse livers. No exceptions were observed for these S9 preparations regarding the higher mutagenicity at pH 5 than at pH 7. It is speculated that the higher mutagenicity observed by the pH 5 pre-incubation was due to the stability of the active intermediate, alpha-hydroxynitrosodialkylamines, in weakly acidic media.

Animals↗

Inhibitory effect of hemin on the mutagenic activities of carcinogens.

An inhibitory effect of hemin on mutagenicities of a range of carcinogens was found by adding hemin to the preincubation mixture of the Ames' test. Strong inhibitions were observed for benzo[alpha]pyrene, 3-methylcholanthrene, 7,10-dimethylbenz[alpha]anthracene, chrysene, 2-acetylaminofluorene, 2-nitrofluorene and aflatoxin B1. Generally, 50% inhibition was caused by an amount of hemin 1--2 equivalents to the mutagen. Excess of hemin caused complete inhibitions. Hemin did not affect the mutagenicities of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline-1-oxide, nitromin, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, N-nitrosodi-n-butyl-amine, quinoxaline-1,4-dioxide and carbadox. Biliverdin, bilirubin and chlorophyllin were also effective as inhibitors for the mutagenicity of benzo[alpha]pyrene.

Carcinogens↗