プリン・ピリミジン代謝
Online ISSN : 2187-0101
Print ISSN : 0916-2836
22 巻 , 1 号
選択された号の論文の6件中1~6を表示しています
  • 上田 孝典
    1998 年 22 巻 1 号 p. 1-9
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
    The antitumor activities of ara-C in an experimental tumor system are identified in 1961. Its action mechanism was primarilyc onsidered to be the inhibition of ribonucleo-ti de diphosphate reductase, which was laterdi sproved. Then the inhibition of DNA poly-m erase was proposed to be the major site ofac tion, where ara-CTP showed competitive in hibition against dCTP. Meanwhile, the nu mber of nucleoside binding sites on cellme mbranes, the inactivation by cytidine dea-min ase, the activation by deoxycytidine kinase, a nd the dephosphorylation of ara-CTP weres hown to be factors that affect its activities. In 1980, Kufe reported a strong correlation between cytotoxicity and incorporation of ara-C into DNA, which was then established as the major mechanism of action. Recently, the cell death induced by ara-C was found to be due to apoptosis. Thus, the mediators which link the proper action mechanism of ara-C to the common pathway, apoptosis, such as protein kinase C, bcl 2 are now being extensively studied. Clinically, crucial parameters regarding pharmacodynamics are intracellular ara-CTP and ara-C incorporated into DNA. As the in vitro assay of ara-CTP showed promising results, establishment of assays for both parameters and its application to determine the indication and administrative dose of ara-C is being investigated.
  • 西田 〓太郎
    1998 年 22 巻 1 号 p. 11-17
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
    A study was conducted on simple methods for the prenatal diagnosis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency using amniotic cells. The amniotic cells were cultured in triplicate in 1 ml of MEM medium containing 10% fetal calf serum, antibiotics and "C-hypoxanthine at 37°C in a humidified atmosphere of 5% CO, and 95% air using sterile microplates with 24 flat-bottom wells. Following appropriate time of culture, the plates were washed with cold physiological saline, and the radioactivities of "C-hypoxanthine in the cells suspended in the trypsin solution were counted. Firstly, the influence of cell number and culture time on the uptake of "C-hypoxanthine in normal cells was studied. In the case of normal cells, it was shown that only 5,000 cells cultured for 12hours was sufficient to clarify the incorporation of "C-hypoxanthine. Next, batches of 10,000 amniotic cells from a normal subject and from two cases at risk for HPRT deficiency were cultured with "C-hypoxanthine and or "C-adenine for 24 hours. Marked uptakes of "C- hypoxanthine and "C- adenine were shown by cells from both thenormal subject and those from one patient. However, in the cells from the patient whose cell lysate did not show any HPRT activity, uptake of "Cadenine in the cells was evident while that of "C-hypoxanthine was not. Thus, this method seems to demonstrate simple and accurate diagnosis of HPRT deficiency in thefetus.
  • 今枝 正行, 木戸内 清, 鷲見 聡, 林 勝男, 大場 悟, 小林 正紀, 和田 義郎
    1998 年 22 巻 1 号 p. 19-25
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
    We analyzed urinary orotic acid concentrations in 165 healthy adults and 843 adult patients with various diseases, in order to establish the reference value for persons ages 20 years or older and evaluate the clinical significance. These were analyzed directly by high-performance liquid chromatography with column switching. When males and females were compared, orotic acid concentrations were higher in females (p<0.05). Orotic acid increased significantly in patients with hypertension, cerebral infarction and malignancy (p<0.01). The mechanism causing orotic aciduria in these patients is not clear at present, but should become clearer as further data are accumulated. The reference values for the patients in this study may be useful for diagnosing certain urea cycle disorders, such as late-onset type ornithine transcarbamylase deficiency accompanied by other disease.
  • 松本 美富士, 坂野 章吾, 難波 大夫, 速水 芳仁, 上田 龍三
    1998 年 22 巻 1 号 p. 27-32
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
    Nitric oxide (NO) is a potent mediator of physiological functions and pathogenic reactions in human disease. Recently, considable evidence supporting the pathogenic mechanism of NO in some arthritides has been demonstrated. We investigated the role of NO in the pathogenesis of acute gouty arthritis. Synovial fluids (SF) from gouty arthritis contained a high level of NO, compared to SF from osteoar thritis, rheumatoid arthritis (RA) and palindr omic rheumatism patients. Monocytes from normal peripheral blood did not produce NO, synthetic monosodium urate (MSU) crystals. However, activated macrophage(Mφ)in SF from active RA patients produced a high level of NO after stimulation with fresh serum-treated MSU crystals. These NO productions were augmented by the addition of inflammatory cytokines (interleukin-1 β or tumor necrosis factor α). Presenceof a specific antagonist of NO synthetase (NGmonomethyl-L-arginine) effectively inhibited the production of NO from Mφ. From these findings NO would be a potent mediator of acute gouty arthritis. after stimulation with fresh serum-treated
  • 1998 年 22 巻 1 号 p. 33-57
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
  • 1998 年 22 巻 1 号 p. 58-78
    発行日: 1998年
    公開日: 2012/11/27
    ジャーナル フリー
feedback
Top