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991.
992.
993.
A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among these compounds, 4-?2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy?buty ric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activities for rat prostatic 5alpha-reductase (IC50 values of 9.6+/-1.0 and 13+/-1.5 nM, respectively), with the potency very close to that of finasteride. Compound 30, in which the moiety between the benzene ring and amide bond was replaced by quinolin-4-one ring, showed almost equipotent activity (IC50= 19+/-6.2nM) with the correspondent amide derivative 13. This result was consistent with the previous observation that the coplanarity of this moiety might contribute to the potent inhibitory activity. 相似文献
994.
G Tohda K Oida Y Okada S Kosaka E Okada S Takahashi H Ishii I Miyamori 《Canadian Metallurgical Quarterly》1998,18(12):1861-1869
Thrombomodulin (TM), a thrombin receptor protein found on the endothelial cell surface, contains 6 tandem epidermal growth factor (EGF)-like structures. Recombinant human TM peptide containing these 6 EGF-like domains (rTME1-6) exhibits mitogenic activity in Swiss 3T3 cells. We examined the localization of TM in atherosclerotic lesions and the effects of rTME1-6 on the growth of cultured rat vascular smooth muscle cells (SMCs). Immunohistochemical analysis demonstrated that TM antigen was localized on monocytes, macrophages, and vascular SMCs. In cultured vascular SMCs, rTME1-6 accelerated [3H]thymidine uptake into DNA in a dose-dependent manner up to 3.4 times the control level. This mitogenic activity was abolished by addition of polyclonal anti-human TM antibody. The rTME1-6-induced mitogenesis was enhanced by EGF. However, a neutralizing monoclonal antibody against the EGF receptor (monoclonal antibody 225) did not inhibit the mitogenic activity of rTME1-6. Calphostin C, a specific protein kinase C inhibitor, and lavendustin-A, an inhibitor of EGF receptor-specific protein tyrosine kinase, inhibited the mitogenic activities of both rTME1-6 and EGF. Finally, rTME1-6 treatment increased the level of phosphorylated mitogen-activated protein kinase in SMCs. Together, these results suggest that TM expression in atherosclerotic lesions may be associated with promotion of atherosclerosis through its mitogenic activity in vascular SMCs. 相似文献
995.
A Yokoyama T Muramatsu T Ohmori T Yokoyama K Okuyama H Takahashi Y Hasegawa S Higuchi K Maruyama K Shirakura H Ishii 《Canadian Metallurgical Quarterly》1998,19(8):1383-1387
Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers. 相似文献
996.
Freshly isolated adult rat ventricular cardiomyocytes have been used to characterize the action profile of the new thiazolidinedione antidiabetic drug MCC-555. Preincubation of cells with the compound (100 microM for 30 min or 10 microM for 2 h) did not modify basal 3-O-methylglucose transport, but produced a marked sensitizing effect (2- to 3-fold increase in insulin action at 3 x 10(-11) M insulin) and a further enhancement of maximum insulin action (1.8-fold). MCC-555 did not modulate autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). However, insulin action (10(-10) and 10(-7) M) on IRS-1-associated phosphatidylinositol (PI) 3-kinase activity was enhanced 2-fold in the presence of MCC-555. Association of the p85 adapter subunit of PI 3-kinase to IRS-1 was not modified by the drug. Immunoblotting experiments demonstrated expression of the peroxisomal proliferator-activated receptor-gamma in cardiomyocytes reaching about 30% of the abundance observed in adipocytes. The insulin-sensitizing effect of MCC-555 was lost after inhibition of protein synthesis by preincubation of the cells with cycloheximide (1 mM; 30 min). Cardiomyocytes from obese Zucker rats exhibited a completely blunted response of glucose transport at 3 x 10(-11) M insulin. MCC-555 ameliorates this insulin resistance, producing a 2-fold stimulation of glucose transport, with maximum insulin action being 1.6-fold higher than that in control cells. This drug effect was paralleled by a significant dephosphorylation of IRS-1 on Ser/Thr. In conclusion, MCC-555 rapidly sensitizes insulin-stimulated cardiac glucose uptake by enhancing insulin signaling resulting from increased intrinsic activity of PI 3-kinase. Acute activation of protein expression leading to a modulation of the Ser/Thr phosphorylation state of signaling proteins such as IRS-1 may be underlying this process. It is suggested that MCC-555 may provide a causal therapy of insulin resistance by targeted action on the defective site in the insulin signaling cascade. 相似文献
997.
998.
Ishii K. Nosaka H. Ida M. Kurishima K. Yamahata S. Enoki T. Shibata T. Sano E. 《Microwave Theory and Techniques》2003,51(11):2181-2187
We have designed and fabricated a low-power 4:1 multiplexer (MUX), 1:4 demultiplexer (DEMUX) and full-clock-rate 1:4 DEMUX with a clock and data recovery (CDR) circuit using undoped-emitter InP-InGaAs HBTs. Our HBTs exhibit an f/sub T/ of approximately 150 GHz and an f/sub max/ of approximately 200 GHz at a collector current density of 50 kA/spl mu/m/sup 2/. In the circuit design, we utilize emitter-coupled logic and current-mode logic series gate flip-flops and optimized the collector current density of each transistor to achieve low-power operation at required high bit rates. Error-free operation at bit rates of up to 50 Gbit/s were confirmed for the 4:1 MUX and 1:4 DEMUX, which dissipates 2.3 and 2.5 W, respectively. In addition, the full-clock-rate 1:4 DEMUX with the CDR achieved 40-Gbit/s error-free operation. 相似文献
999.
Characterization of degradation process of cyanobacterial hepatotoxins by a gram-negative aerobic bacterium 总被引:18,自引:0,他引:18
A bacterium termed 7CY, capable of decomposing cyanobacterial toxins, was isolated from surface water sample of Lake Suwa and degradation of microcystin-RR and nodularin-Har was investigated. The isolated 7CY was a gram-negative, aerobic bacillus, and a member of a genus Sphingomonas. The strain degraded microcystin-LY, -LW, and -LF completely as well as microcystin-LR within 4 days after their addition (6 microg/ml) whereas degradation of nodularin-Har did not occur at all during experiment. On the contrary, the strain was capable of degrading nodularin-Har in the presence of microcystin-RR and both toxins were completely decomposed within 6 days. The strain scarcely degraded nodularin-Har in the presence of microcystin-RR when glucose and ammonium chloride were added to the medium. The degradation of nodularin-Har did not occur in the medium from which bacterial cells had been removed after degradation of microcystin-RR. Furthermore, when microcystin-RR and nodularin-Har were added to the cytoplasm fraction of 7CY cells, microcystin-RR was rapidly degraded within 18 h, but nodularin-Har was not. The strain 7CY may require an enzyme(s) induced during the degradation of microcystin-RR in order to utilize nodularin-Har as nutrition. 相似文献
1000.
Norio Nakata Yusuke Saito Takanori Watanabe Akihiko Ishii 《Topics in Catalysis》2014,57(10-13):918-922
In the presence of dried methylaluminoxane as an activator, the hafnium(IV) dichloro pre-catalyst 4 incorporating with an [OSSO]-type ligand was found to promote precisely isospecific 1-hexene polymerizations of [mmmm] up to 95 % with fairly high activities (1,050–3,180 g mmol(4)?1 h?1) and relatively narrow polydispersities (M w/M n = 1.5–1.8). 相似文献