[Studies on analgesics. (5). Electroencephalographic studies of the effect of aminoalkylacylaminothiophene on the central nervous system].
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Biomedical subjects
Publications and source records attributed to R Ishida.
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BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.
VP-16 and ICRF-193 are different types of antitumor topoisomerase II inhibitors, being cleavable and non-cleavable complex-stabilizing types, respectively. To examine the possibility of enhancing the efficacy of combination chemotherapy, we carried out simultaneous and sequencial treatment of cells with the two drugs. When KB cells were exposed continually to low concentrations (0.05 - 0.2 microM) of the drugs, the effects were synergistic. In contrast, when the cells were treated with high concentrations of ICRF-193 and VP-16 for 1 hour, the VP-16-induced cytotoxicity was prevented by ICRF-193 and the degree of prevention was increased by the pretreatment of cells with ICRF-193, while post-treatment with ICRF-193 had little effect on the cytotoxicity of VP-16. ICRF-193 at 1 microM was found to interact with about half molecules of topisomerase IIa and II beta in cells, as judged by increased amounts of a salt-stable complex. ICRF-193 inhibited in vitro VP-16-induced cleavable complex formation, but a much higher concentration was needed to reverse the cleavage already generated by VP-16. Thus, the antagonistic or synergistic effects of ICRF-193 and VP-16 depend on the concentration of the drug, as it may be critical as to how many molecules of cellular topoisomerase II interact with the drugs.