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21.
E Ohshima H Takami H Sato S Mohri H Obase I Miki A Ishii S Shirakura A Karasawa K Kubo 《Journal of medicinal chemistry》1992,35(18):3402-3413
A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation. 相似文献
22.
Kazuhiko Suzuki Hiroshi Tanaka Satoshi Kaneko Motoi Nishi Shin Teramoto Susumu Itoh Shosaku Abe 《The Journal of asthma》2003,40(3):243-250
The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking. 相似文献
23.
Kazuhiko Sonoyama Haruaki Ninomiya Osamu Igawa Yasuhiro Kaetsu Yoshiyuki Furuse Toshihiro Hamada Junichiro Miake Peili Li Yasutaka Yamamoto Kazuhide Ogino Akio Yoshida Shin-ichi Taniguchi Yasutaka Kurata Satoshi Matsuoka Toshio Narahashi Goshi Shiota Yoshihisa Nozawa Hiroaki Matsubara Masatsugu Horiuchi Yasuaki Shirayoshi Ichiro Hisatome 《Hypertension research》2006,29(11):923-934
We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells. 相似文献
24.
Histological, immunohistochemical, and electron microscopic evidence of an extracellular, or ghost Pick body has been found in the granular cell layer and, rarely, in the pyramidal cell layer of the hippocampus of an autopsy case of Pick's disease. The ghost Pick body appeared as a blurred, weak argyrophilic mass in the neuropil, and it was composed of accumulated fibrillary structures, 13 nm in diameter, intermingled with glial filament bundles. These ghost Pick bodies did not react with anti-tau and antiubiquitin antibodies, but did react weakly with antiglial fibrillary acidic protein antibody, whereas intracytoplasmic Pick bodies were strongly immunolabeled with anti-tau but only weakly with anti-ubiquitin anti-bodies. These results suggest that the Pick body is discharged into the neuropil after destruction of the mother neuron, loses its immunoreactivity to certain tau and ubiquitin antibodies during this process (thereby inducing a glial reaction) and remains in the neuropil as a ghost Pick body. 相似文献
25.
26.
Yumiko Motoi Masashi Takanashi Masako Itaya Kazuhiko Ikeda Yoshikuni Mizuno Hideo Mori 《Neuropathology》2004,24(1):60-65
In the present case, a patient in whom limb apraxia and asymmetrical parkinsonism developed suggesting corticobasal degeneration, is reported. Neuropathologic examination revealed numerous tufted astrocytes in the precentral cortex in addition to the characteristic pathologic findings of PSP. Therefore, on the basis of clinicopathologic features, atypical progressive supranuclear palsy was diagnosed. In addition, the brain tissue of the present patient was investigated with an antibody specific for four‐repeat tau (4R‐tau). In the precentral cortex, numerous tau‐positive tufted astrocytes, pretangles, and threads were positive for 4R‐tau. Using a confocal microscopy we demonstrated that tufted astrocytes positive for 4R‐tau were adjacent to astrocytes positive for GFAP. The present findings suggest that accumulation of four‐repeat tau in astrocytes is a degenerative process rather than a reactive process. 相似文献
27.
Jun-ichi Shikata MD Kazuhiko Ohtaki Kenjiro Amino Yoshitsugu Takeda 《Surgery today》1990,20(6):660-664
Two nationwide questionnaire surveys of intestinal obstruction in Japan were undertaken, covering two two-year periods, from
January, 1975 to December, 1976 and from January, 1985 to December, 1986, respectively. The findings of a comparative review
of these two surveys indicated that although the overall mortality of intestinal obstruction had not changed between 1975/76
and 1985/86, being 6.8 per cent and 6.5 per cent, respectively, simple adhesive obstruction had decreased from 3.2 per cent
in 1975/76 to 2.0 per cent in 1985/86. The main cause of adhesion was laparotomy and in cases of both simple adhesive obstruction
and strangulated adhesive obstruction, the rate of adhesion secondary to laparotomy of the upper gastrointestinal tract and
colon and rectum had increased between 1975/76 and 1985/86. Obstructions caused by neoplasms had increased from 8.2 per cent
in 1975/76 to 10.0 per cent in 1985/86, while those caused by adhesions had incresed further still, from 42.5 per cent in
1975/76 to 60.8 per cent in 1985/86. Among the latter group, nonoperatively treated cases had increased, which may be accounted
for by the fact that facilities which adopt non-operative treatment using intestinal decompression as the first choice for
simple adhesive obstruction cases have increased. In both surveys, the mortality of cases receiving nonoperative treatment
was lower than that of operative cases. 相似文献
28.
Masahiro Fujita Kazuhiko Ito Hiroshi Kawamoto Saburo Kashii Mihoko Norioka Sumie Monden Minoru Okuma 《European journal of haematology》1993,50(4):200-205
Abstract: A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 μmol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 × 105and 1 × 106cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10. 相似文献
29.
Yuichi Ando Kenji Kikuchi Naoya Ichikawa Kazuhiko Meigata Yuji Nomura Kenshi Watanabe Yoshifumi Beck Hisakazu Degawa Shinji Tomikawa Takeshi Nagao Hisanori Chida 《Surgery today》1997,27(4):353-356
We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction. 相似文献
30.