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11.
K Tamazawa H Arima T Kojima Y Isomura M Okada S Fujita T Furuya T Takenaka O Inagaki M Terai 《Journal of medicinal chemistry》1986,29(12):2504-2511
Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism. 相似文献
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Yuki Izawa Masanori Yoshizumi Keisuke Ishizawa Yoshiko Fujita Shuji Kondo Shoji Kagami Kazuyoshi Kawazoe Koichiro Tsuchiya Shuhei Tomita Toshiaki Tamaki 《Hypertension research》2007,30(11):1107-1117
Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling. 相似文献
14.
M Yamashita K Inoue A Yamashita Y Fujita 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》1990,81(4):554-560
Intravesical instillation of anti-cancer drugs for superficial urinary bladder cancer is generally carried out with the aim of prophylaxis against recurrence and chemotherapy against tumor. But since sensitivity of tumor cells to each anti-cancer drug differs individually, the anti-cancer drug to be used should also be decided individually. We selected a new sensitivity test, ATP-sensitivity-assay, which measures intracellular adenosine triphosphate (ATP) volume by Luciferin-Luciferase reaction, for the decision of the anti-cancer drug. In this paper, we evaluated the direct anti-tumor activity of the drugs that were decided by ATP-sensitivity-assay of intravesical chemotherapy. Six drugs, that are Doxorubicin (ADM), Mitomycin C (MMC), Pirarubicin (THP-ADM), Cytarabine (Ara-C), Bleomycin (BLM) and Cisplatin (CDDP) were tested in this research and size of tumors of six patients reduced to 34-93% after 6 times' installation. A woman got cystitis induced by ADM after 3 times' instillation but instillation was completed. ATP-sensitivity-assay is useful for deciding the anti-cancer drugs for intravesical chemotherapy and prophylaxis for superficial bladder cancer. 相似文献
15.
M Shinonaga J Hayashi S Shinada S Nakazawa Y Fujita M Ueno S Equchi 《Kyobu geka. The Japanese journal of thoracic surgery》1990,43(4):276-279
We have used recombinant human erythropoietin (rEPO) in order to prevent patients from developing anemia following preoperative autologous blood preservation. Thereby, we have been able to reduce intraoperative homologous blood transfusion during cardiac operations. In June and July, 1989, six middle-aged selective patients received rEPO (200 IU/kg) intravenously every other day starting from fifteen days before the day of their operations. One unit (200 ml) of autologous blood was drawn and preserved every few days. However, no significant differences were observed in red cell counts, hematocrit, hemoglobin and serum protein levels between before and after preservation. Not only preoperative autologous blood preservation with provision of rEPO, but also using the intraoperative autotransfusion system enabled us to perform cardiac operations on 5 out of 6 patients without any homologous blood transfusion. None of the six patients exhibited any undesirable effects due to rEPO administration. Their postoperative courses were excellent. 相似文献
16.
Roberto Civitelli M.D. Eturo Ogata Louis V. Avioli Gary Stein Samuel Edelstein John A. Eisman Yasuho Nishii Hajime Orimo Jane Lian Takuo Fujita Yasufumi Hayashi Shigeaki Kato Tadashi Kobayashi Hirotoshi Morii Rikushi Morita Toshitaka Nakamura Yoshiki Seino Masataka Shiraki Tatsuo Suda Naoyuki Takahashi Hideaki Takahashi Tastuhiko Tanisawa Akifumi Tokita 《Calcified tissue international》1995,57(6):409-414
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K Fujita H Matsushima A Munakata T Kunitake 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》1992,83(12):1999-2004
Multifactorial analysis on 395 patients revealed important factors which prolong the pyuria after transurethral prostatectomy. They were the age of the patient, anemia and leukocytosis before surgery. These are factors which relate with the defense mechanism of the patient. Local factors, such as the duration of indwelling urethral catheter, the size of the prostate or prostatic bed and preoperative infection, were not so important for prolonging the pyuria after transurethral prostatectomy. The time of the resection and weight of the prostate had an intimate relation each other, and the former was the more important factor. The use of antimicrobials probably controlled these local risk factors, thus making them unimportant in the prolongation of the pyuria after transurethral prostatectomy. 相似文献