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1.
Y Aoyama K Ishida K Hori A Sakaguchi M Kudoh Y Yoshida 《Biochemical pharmacology》1992,44(9):1701-1705
AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM. 相似文献
2.
S Hayasaka M Takada T Shinohara S Imamura N Takifuji S Kudoh K Matsui Y Kusunoki N Masuda S Negoro 《Nihon Kyōbu Shikkan Gakkai zasshi》1991,29(7):802-807
Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%). 相似文献
3.
T Kuwahara T Kudoh H Nagase M Takamiya A Nakano T Ohtsuka H Yoshizaki M Arisawa 《European journal of pharmacology》1992,221(1):99-105
We found a novel nonpeptide CCKB receptor antagonist, tetronothiodin (Ro 09-1468), in the culture broth of Streptomyces sp. NR0489. The structure of the compound (C31O8H38S), which has a 19-membered ring with an alpha-acyltetronic acid and tetrahydrothiophene moiety, is completely different from that of any known CCK receptor antagonist. Tetronothiodin inhibited [125I]CCK-8 binding to rat brain CCKB receptors with an IC50 of 3.6 nM, whereas it showed only weak affinity for rat CCKA receptors (IC50 = 70 microM). As demonstrated autoradiographically, tetronothiodin concentration dependently inhibited [125I]CCK-8 binding to CCKB receptors in rat forebrain slices. The effects of tetronothiodin on cytosolic Ca2+ concentrations in GH3 cells, a rat anterior pituitary tumor cell line, were investigated with the fura-2 method. Tetronothiodin inhibited CCK-8-induced Ca2+ mobilization without affecting basal cytosolic Ca2+ concentrations. In conclusion, tetronothiodin is a new, potent and highly selective CCKB receptor antagonist. It is a useful tool for investigating the pharmacological and physiological roles of CCKB receptors. 相似文献
4.
Shiro Saito Makoto Hata Ryuichi Fukuyama Kosuke Sakai Jun Kudoh Hiroshi Tazaki Nobuyoshi Shimizu 《International journal of urology》1997,4(2):178-185
Background Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer.
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer. 相似文献
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer. 相似文献
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6.
Touraine et al reported some cases lacking HLA-class I antigens on the cell surface of their lymphocytes as "Bare lymphocyte syndrome" (BLS). Recently we experienced a case of BLS the clinical features of which are very similar to those of diffuse panbronchiolitis (DPB). Namely, she had chronic pansinusitis, diffuse nodular shadows on her chest X-ray film, obstructive impairment of pulmonary function tests and continuous increase of cold hemagglutinin titer. The pathogenesis of DPB is not confirmed. However, this case and other cases with sino-bronchial syndrome suggest that patients with DPB may have some immunodeficiencies. In addition the immunosuppressive action of erythromycin and its effectiveness on DPB were interesting. From these points of view, we discussed the relationship between this case and DPB, and the pathogenesis of DPB. 相似文献
7.
Abe S Takizawa H Sugawara I Kudoh S 《American journal of respiratory cell and molecular biology》2000,22(3):296-303
We devised a new in vitro cell exposure system to freshly generated diesel exhaust (DE), different from conventional in vitro culture systems, to examine the effects of DE on human epithelial cells. Using this system, we investigated the effects of DE on cytokine gene expressions in BET-1A human bronchial epithelial cells. DE significantly decreased [(3)H]thymidine incorporation into BET-1A cells. DE had a significant stimulatory effect on interleukin (IL)-8 release to a marked degree. IL-8 and transforming growth factor (TGF)-beta1 messenger RNA (mRNA) expression were induced by DE in a time-dependent manner. The gas obtained by filtration of DE alone did not show a sustained increase in IL-8 protein levels and showed no induction of IL-8 mRNA, suggesting that DE particles (DEPs) play an important role in the induction of IL-8 at both mRNA and protein levels. Antioxidants, pyrrolidine dithiocarbamate, and N-acetyl-L-cysteine significantly inhibited IL-8 mRNA and protein levels by BET-1A cells. These results indicate that freshly generated DEPs may be important in the induction of cytokines such as IL-8 and TGF-beta1 relevant to allergic airway inflammation. 相似文献
8.
Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis 总被引:10,自引:0,他引:10
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Yoshinobu Eishi Moritaka Suga Ikuo Ishige Daisuke Kobayashi Tetsuo Yamada Tamiko Takemura Touichiro Takizawa Morio Koike Shoji Kudoh Ulrich Costabel Josune Guzman Gianfranco Rizzato Marcello Gambacorta Ronald du Bois Andrew G. Nicholson Om P. Sharma Masayuki Ando 《Journal of clinical microbiology》2002,40(1):198-204
The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis. 相似文献
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