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41.
Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival 总被引:14,自引:0,他引:14
Imadome K Shimizu N Arai A Miura O Watanabe K Nakamura H Nonoyama S Yamamoto K Fujiwara S 《The Journal of infectious diseases》2005,192(8):1340-1348
We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus. 相似文献
42.
Addya S Shiroto K Turoczi T Zhan L Kaga S Fukuda S Surrey S Duan LJ Fong GH Yamamoto F Maulik N 《Journal of molecular and cellular cardiology》2005,38(2):345-351
This study attempts to address an important clinical issue by identifying potential candidates of VEGF signaling through Flt-1 receptor that trigger angiogenic signal under ischemic stress. To determine the significance of VEGF-Flt-1 (VEGFR1) signaling in ischemic preconditioned (PC) myocardium, we used heterozygous Flt-1 knockout (KO) mice to dissect the pathway and identify candidate genes involved in VEGF signaling. DNA microarrays were employed to detect, characterize and distinguish altered myocardial gene expression by comparing between wild type (WT) CD-1 and heterozygous Flt-1 KO mice when exposed to ischemia (30 min) and reperfusion (2 h). Moreover, KO mice demonstrated reduced beneficial effects of PC when compared to the WT with PC. In the KO and WT mice, the % recovery of the left ventricular developed pressure and the maximum first derivative of the developed pressure after ischemia/reperfusion without PC were similar. However, when animals were subjected to PC, the left ventricular functional recovery throughout the reperfusion period was significantly lower in KO mice than in WT mice. These results indicate for the first time that in the heterozygous Flt-1 KO mice, PC is not as effective as that found in WT. This observation may be due to downregulation of several important genes such as growth-regulated oncogene 1 (Gro1), heat shock proteins (HSP), I kappa B kinase beta (IKK beta), colony-stimulating factor-1 (CSF-1) and annexin A7, suggesting the importance of VEGF-Flt-1 receptor signaling during PC. 相似文献
43.
Yoshiji H Kuriyama S Noguchi R Yoshii J Ikenaka Y Yanase K Namisaki T Kitade M Yamazaki M Masaki T Fukui H 《Journal of hepatology》2005,42(5):687-693
BACKGROUND/AIMS: Chemoprevention should be a promising approach to improve the prognosis of the patients with hepatocellular carcinoma (HCC). Angiogenesis is now recognized as a crucial step not only in tumor growth, but also in early carcinogenesis. The aim of this study was to elucidate the combination effect of the clinically used vitamin K(2) (VK) and the angiotensin-converting enzyme inhibitor, perindopril (PE), on hepatocarcinogenesis, especially in conjunction with angiogenesis. METHODS: In a diethylnitrosamine-induced rat hepatocarcinogenesis model, the effects of VK and PE on the development of liver enzyme-altered preneoplastic lesions and angiogenesis were examined. RESULTS: Treatment with both VK and PE markedly inhibited the development of preneoplastic lesions in association with suppression of neovascularization in the liver. The combination treatment with VK and PE exerted a more potent inhibitory effect as compared with the single agent treatments. The in vitro study demonstrated that VK and PE inhibited the endothelial cell (EC) tubular formation. VK also suppressed the EC proliferation in a dose-dependent manner. CONCLUSIONS: The combination of VK and PE exerted a chemopreventive effect against rat liver carcinogenesis via suppression of angiogenesis. Since both agents are widely used in the clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against HCC in the future. 相似文献
44.
45.
Masao Omata Shuhei Nishiguchi Yoshiyuki Ueno Hitoshi Mochizuki Namiki Izumi Fusao Ikeda Hidenori Toyoda Osamu Yokosuka Kazushige Nirei Takuya Genda Takeji Umemura Tetsuo Takehara Naoya Sakamoto Yoichi Nishigaki Kunio Nakane Nobuo Toda Tatsuya Ide Mikio Yanase Keisuke Hino Bing Gao Kimberly L. Garrison Hadas Dvory‐Sobol Akinobu Ishizaki Masa Omote Diana Brainard Steven Knox William T. Symonds John G. McHutchison Hiroshi Yatsuhashi Masashi Mizokami 《Journal of viral hepatitis》2014,21(11):762-768
Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis. 相似文献
46.
The mechanisms involved in the antiatherosclerotic effects of androgens are unclear. Although lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells plays critical roles in atherosclerosis, the effects of androgens on endothelial LOX-1 expression has not been examined. Therefore, to investigate the effects of dihydrotestosterone (DHT) on LOX-1 expression in rabbit aortic endothelial cells and cultured human aortic endothelial cells (HAEC), pellets containing DHT or placebo were s.c. implanted into 26 male New Zealand white rabbits at the time of castration or sham operation. The rabbits were then fed a high-cholesterol diet (HCD) for 2 wk. Microscopic examination of the aortic arch revealed that DHT significantly reduced HCD-induced LOX-1 expression in endothelial cells compared with placebo. In cultured HAEC, DHT at concentrations above 10(-9) to 10(-7) mol/liter inhibited TNFα-induced LOX-1 mRNA and protein expression. Deletion and mutation analysis of human LOX-1 promoter-luciferase constructs transfected into HAEC with an androgen receptor (AR) expression plasmid revealed that the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE; nucleotides -60/-53) contributed to the inhibitory effects of DHT on TNFα-induced LOX-1 expression. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that TNFα- and TPA-dependent enrichment of p65 and phosphorylated c-Jun in the TRE chromatin region was inhibited by DHT-AR. Consistent with these results, DHT also suppressed TPA-induced expression of LOX-1. In conclusion, DHT exerts antiatherosclerotic effects by suppressing endothelial LOX-1 expression. This effect is partly mediated by the suppression of nuclear factor-κB- and activator protein 1-dependent activation of the LOX-1 promoter. 相似文献
47.
Ma CS Avery DT Chan A Batten M Bustamante J Boisson-Dupuis S Arkwright PD Kreins AY Averbuch D Engelhard D Magdorf K Kilic SS Minegishi Y Nonoyama S French MA Choo S Smart JM Peake J Wong M Gray P Cook MC Fulcher DA Casanova JL Deenick EK Tangye SG 《Blood》2012,119(17):3997-4008
T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4(+) T cells to the Tfh lineage, because IL-12 induces naive human CD4(+) T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5, which typify Tfh cells. We have now examined CD4(+) T cells from patients deficient in IL-12Rβ1, TYK2, STAT1, and STAT3 to further explore the pathways involved in human Tfh cell differentiation. Although STAT1 was dispensable, mutations in IL12RB1, TYK2, or STAT3 compromised IL-12-induced expression of IL-21 by human CD4(+) T cells. Defective expression of IL-21 by STAT3-deficient CD4(+) T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4(+)CXCR5(+) T cells. These results highlight the nonredundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients. 相似文献
48.
Shigeaki Sawada Yutaka Shimada Shinichi Sekine Kazuto Shibuya Isaku Yoshioka Koshi Matsui Tomoyuki Okumura Toru Yoshida Takuya Nagata Hideyuki Uotani Kazuhiro Tsukada 《International surgery》2013,98(4):372-378
Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of 18F-FDG PET are not specific for malignancy because 18F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for 18F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on 18F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on 18F-FDG PET. 相似文献
49.
Yoshio Iwashima Masanobu Yanase Takeshi Horio Osamu Seguchi Yoshihiro Murata Tomoyuki Fujita Koichi Toda Yuhei Kawano Takeshi Nakatani 《Artificial organs》2013,37(7):606-614
Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m2 was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2‐year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS. 相似文献