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排序方式: 共有179条查询结果,搜索用时 656 毫秒
11.
Chie Hashimoto Tetsuo Narumi Hiroyuki Otsuki Yuki Hirota Hiroshi Arai Kazuhisa Yoshimura Shigeyoshi Harada Nami Ohashi Wataru Nomura Tomoyuki Miura Tatsuhiko Igarashi Shuzo Matsushita Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2013,21(24):7884-7889
To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies. 相似文献
12.
Zsolt Radak Shuzo Kumagai Hideko Nakamoto Sataro Goto 《Journal of applied physiology》2007,102(4):1696-1701
Oxoguanine DNA glycosylase (OGG1) and uracil DNA glycosylase (UDG) are two of the most important repair enzymes that are involved in the base excision repair processes to eliminate oxidative damage from mammalian DNA, which accumulates with aging. Red and white skeletal muscle fibers have very different antioxidant enzyme activities and resistance to oxidative stress. In this paper, we demonstrate that the activity of OGG1 is significantly higher in the red type of skeletal muscle compared with white fibers from old rats. Exercise training resulted in increased OGG1 activity in the nuclei of red fibers and decreased activity in nuclei of white fibers and in the mitochondria of both red and white fibers. The activities of UDG were similar in both red and white muscle fibers. Exercise training appears to increase the activity of UDG in the nuclei and mitochondria. However, exercise training affects the activity of OGG1 in nuclei and mitochondria differently, suggesting different regulation of the enzymes. In contrast, UDG showed similar activities in nuclei and mitochondrial extracts of exercise-trained animals. These data provide evidence for differential regulation of UDG and OGG1 in maintaining fidelity of DNA in oxidatively stressed cells. 相似文献
13.
Effects of Chronic Administration of Interferon α A/D on Serotonergic Receptors in Rat Brain 总被引:7,自引:0,他引:7
The effects of chronic administration of interferon (IFN; recombinant human IFN -A/D) on serotonergic binding sites in rat brain were investigated. IFN was injected daily for 2 weeks at a dose of 100000 I.U./kg, (i.p.) in male Wistar rats. IFN did not alter either [3H]ketanserin binding to 5-HT2A receptors or [3H]paroxetine binding to 5-HT transporters. Scatchard analysis of [3H]8-hydroxy-dipropylaminotetraline (8-OH-DPAT) binding to 5-HT1A receptors demonstrated the presence of high- and low-affinity binding sites in both treatment and control groups. IFN significantly increased both Kd and Bmax measures of [3H]8-OH-DPAT binding at low-affinity binding sites, but not at the high-affinity sites. These results suggest that IFN affects the low-affinity 5-HT1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances. 相似文献
14.
Iwama T Hosokawa H Lin W Shimizu H Kawai K Yamagata S 《Bioscience, biotechnology, and biochemistry》2004,68(6):1357-1361
The oah2 gene homologous to the oah1 of Thermus thermophilus HB8 was cloned and sequenced. It comprised 1,236 bp encoding a protein of 412 amino acid residues and was overexpressed. The gene product, also having O-acetyl-L-homoserine sulfhydrylase (EC 4.2.99.10) activity, was purified to homogeneity and characterized comparatively with the oah1 product. The two proteins shared many characteristics. 相似文献
15.
Miyashita T Kawakami A Tamai M Izumi Y Mingguo H Tanaka F Abiru S Nakashima K Iwanaga N Aratake K Kamachi M Arima K Ida H Migita K Origuchi T Tagashira S Nishikaku F Eguchi K 《Biochemical and biophysical research communications》2003,312(2):397-404
Akt is known to be activated in the rheumatoid synovial tissues. We examined here functional role of Akt during tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis in rheumatoid synovial cells. Rheumatoid synovial cells in vitro were rapidly committed to apoptosis in response to TRAIL in mitochondria-dependent manner whereas Akt and extracellular signal-regulated kinase (ERK) were also phosphorylated. TRAIL-mediated apoptosis in synovial cells was significantly increased through inactivation of Akt by LY294002, however, that process was not so changed by adding ERK inhibitor, PD98059. Platelet-derived growth factor (PDGF) clearly phosphorylated both Akt and ERK in synovial cells, and PDGF pretreatment markedly suppressed TRAIL-mediated synovial cell apoptosis. The use of not PD98059 but LY294002 abrogated PDGF-mediated inhibitory effect toward TRAIL-induced apoptosis in synovial cells. The above protective effect of Akt was confirmed by the use of short interfering RNA (siRNA)-directed inhibition of Akt. Our data suggest that Akt is an endogenous inhibitor during TRAIL-mediated synovial cell apoptotic pathway, which may explain that synovial cells in situ of the rheumatoid synovial tissues are resistant toward apoptotic cell death in spite of death receptor expression. 相似文献
16.
Matsushita S 《Uirusu》2003,53(2):141-146
17.
Involvement of protein tyrosine phosphorylation in the effect of green tea polyphenols on Ehrlich ascites tumor cells in vitro 总被引:2,自引:0,他引:2
David Opare Kennedy Satomi Nishimura Tadayoshi Hasuma Yoshihisa Yano Shuzo Otani Isao Matsui-Yuasa 《Chemico-biological interactions》1998,110(3):645-172
Green tea extract and its polyphenolic components have been found to possess anticarcinogenic, antimutagenic, antihypertensive and antihepatotoxic effects, and several mechanisms have been proposed for these effects. In this study, the effects of five tea polyphenols, (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−) epicatechin-3-gallate (ECG), (−) epicatechin (EC) and (+)-catechin (C), were examined on the viability of Ehrlich ascites tumor cells in vitro and a possible relationship with tyrosine phosphorylation was determined. Proteins extracted from the cells treated with the tea polyphenols were separated by SDS-PAGE, and tyrosine-phosphorylated proteins were detected by immunoblotting with anti-phosphotyrosine antibody and the extent of phosphorylation determined. EGC (100 μM) caused a significant decrease in cell viability to 4.1±0.2% of the control value, and this correlated with a stimulation of protein tyrosine kinase (PTK) activity. EGCG (100 μM) also caused a slight decrease in cell viability (70% of the control value) but this and the other polyphenols, which had no effect on cell viability likewise, had no effect on tyrosine phosphorylation. Tyrosine phosphorylations of 42 and 45 kDa proteins were also observed for EGC. Further evaluation of the effect of EGC showed that the activity of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis in cells, decreased significantly as well. A significant correlation has therefore been observed between a cellular event, namely, a reduction in the viability of Ehrlich ascites tumor cells and an association with a tyrosine phosphorylation of 42 and 45 kDa proteins by the polyphenol EGC. 相似文献
18.
Takuya Kotani Tohru Takeuchi Takaaki Ishida Ryota Masutani Kentaro Isoda Kenichiro Hata Shuzo Yoshida Shigeki Makino Toshiaki Hanafusa 《PloS one》2015,10(10)
BackgroundActivated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.MethodsThe correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).ResultsThe median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).ConclusionsThe serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP. 相似文献
19.
20.
Nakayama EE Carpentier W Costagliola D Shioda T Iwamoto A Debre P Yoshimura K Autran B Matsushita S Theodorou I 《Immunogenetics》2007,59(6):511-515
Polymorphisms in human genes have been shown to affect the rate of disease progression to acquired immune deficiency syndrome
in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Recently, tripartite motif 5α (TRIM5α) was identified
as a factor that confers resistance to HIV-1 infection in Old World monkey cells. Subsequently, Sawyer et al. (Curr Biol 16:95–100,
2006) reported a single nucleotide polymorphism (H43Y) in the human TRIM5α gene and TRIM5α protein with 43Y was found to lose its ability to restrict HIV-1. In the present study, we reevaluated effects
of this allele on in vitro anti-HIV-1 activity as well as on HIV-1 disease progression in European and Asian cohorts of HIV-1-infected
individuals. Our epidemiological and molecular biological findings clearly indicate H43Y has a very minor effect on anti-HIV-1
activity of TRIM5α, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians. 相似文献