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排序方式: 共有187条查询结果,搜索用时 18 毫秒
1.
Increased glomerular and extracellular malondialdehyde levels in patients and rats with focal segmental glomerulosclerosis 总被引:1,自引:0,他引:1
Kuo HT Kuo MC Chiu YW Chang JM Guh JY Chen HC 《European journal of clinical investigation》2005,35(4):245-250
BACKGROUND: Evidence suggests an increase in oxidative stress in patients with chronic kidney disease, as glomerulosclerosis is the prerequisite for chronic kidney disease; whether the oxidative stress already exists early on is not known. MATERIALS AND METHODS: In this study we measured the plasma and urinary levels of malondialdehyde (MDA), the end product of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and rats with primary focal segmental glomerulosclerosis (FSGS), and compared our findings with those of minimal change disease (MCD) and normal controls (NC). RESULTS: Our results showed that plasma MDA level was significantly increased in patients with FSGS compared with both patients with MCD and normal controls. The urinary MDA level was also significantly increased and was significantly correlated with plasma MDA level in patients with FSGS. The immunostaining for glomerular MDA and SOD was significantly higher in the patients with FSGS than in either the patients with MCD or NC, and was also significantly higher in rats with puromycin aminonucleoside (PAN)-induced FSGS than in rats with MCD. Glomerular MDA level was significantly correlated with the degree of glomerulosclerosis in the patients with FSGS. CONCLUSIONS: Our data suggest that oxidative stress occurs early on before the onset of renal failure, and may play an important role in the pathogenesis of glomerulosclerosis. 相似文献
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Huang YT Pan SL Guh JH Chang YL Lee FY Kuo SC Teng CM 《Molecular cancer therapeutics》2005,4(10):1628-1635
Although the indazole compound, YC-1, is reported to exert anticancer activities in several cancer cell types, its target and mechanism of action have not been well explored. The objectives of this study were to ascertain whether YC-1 directly induces apoptosis in prostate cancer cells and to explore the mechanism(s) whereby YC-1 causes cell death. Hormone-refractory metastatic human prostate cancer PC-3 cells were selected for this study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay indicated that YC-1 suppresses growth of PC-3 cells in a concentration-dependent and time-dependent manner. Apoptosis was determined using 4',6-diamidino-2-phenylindole staining, and cell cycle progression was examined by FACScan flow cytometry. YC-1 treatment showed chromatin condensation and increased the percentage of PC-3 cells in the hypodiploid sub-G0-G1 phase, indicative of apoptosis. Additionally, exposure to YC-1 was found to induce activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. Translocation and activation of nuclear factor-kappaB (NF-kappaB) were determined by immunofluorescent staining and ELISA, respectively. The results showed that YC-1 abolished constitutive nuclear translocation and activation of NF-kappaB/p65. Furthermore, inhibition of inhibitor of kappaBalpha (IkappaBalpha) phosphorylation and accumulation of IkappaBalpha were observed. The antitumor effects of YC-1 were evaluated by measuring the growth of tumor xenografts in YC-1-treated severe combined immunodeficient mice. The volumes of PC-3 tumors produced in severe combined immunodeficient mice were observed to decline significantly after treatment with YC-1 compared with vehicle controls. We concluded that the antitumor effects of YC-1 in PC-3 cells include the induction of apoptosis and the suppression of NF-kappaB activation. Given these unique actions, further investigations of the effects of YC-1 against hormone-refractory prostate cancer are warranted. 相似文献
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Katherine Fleming-Dutra Chukwuma Mbaeyi Ruth Link-Gelles Nicole Alexander Alice Guh Elizabeth Forbes Bernard Beall Jonas M. Winchell Maria da Gloria Carvalho Fabiana Pimenta Maja Kodani Cindy Vanner Hilary Stevens Diane Brady Mardea Caulcrick-Grimes Utpala Bandy Matthew R. Moore 《Emerging infectious diseases》2012,18(11):1889-1893
During a pneumococcal disease outbreak in a pediatric psychiatric unit in a hospital in Rhode Island, USA, 6 (30%) of 20 patients and staff were colonized with Streptococcus pneumoniae serotype 15A, which is not included in pneumococcal vaccines. The outbreak subsided after implementation of antimicrobial drug prophylaxis and enhanced infection control measures. 相似文献
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TGF-beta is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize TGF-beta to ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) is a member of the TGF-beta superfamily and is highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK-49F cells (rat fibroblasts). We showed that TGF-beta1 induces an increase in fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed the TGF-beta1-induced increase in fibronectin concomitant with a significant decrease in type I TGF-beta receptors (TGF-beta RI). Moreover, BMP-2 significantly shortened the half-life of TGF-beta RI. These results are related to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2-mediated degradation of TGF-beta RI. This was confirmed because BMP-2 time course dependently enhanced the ubiquitination level of TGF-beta RI. In addition, Smads would seem to be involved in the interaction of BMP-2 and TGF-beta. We demonstrated that BMP-2 significantly reversed the TGF-beta1-induced increase in pSmad2/3 and reversed the TGF-beta1-induced decrease in inhibitory Smad7. Most importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in TGF-beta RI. We evaluated the clinical efficacy of BMP-2 using unilateral ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral ureteral obstruction kidneys, interstitial fibrosis was prominent. However, treatment with BMP-2 dramatically reduced Masson's trichrome staining (collagen) in the interstitial and tubular areas of the kidneys concomitantly with a reduction in TGF-beta RI. These results suggest that BMP-2 acts as a novel fibrosis antagonizing cytokine partly by down-regulating TGF-beta RI and Smads. 相似文献
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Bansback N Marra C Tsuchiya A Anis A Guh D Hammond T Brazier J 《Arthritis and rheumatism》2007,57(6):963-971
OBJECTIVE: To estimate the relationship between preference-based measures, EuroQol (EQ-5D) and SF-6D, and the Health Assessment Questionnaire (HAQ) disability index (DI) in patients with rheumatoid arthritis (RA), and to characterize components that are predictors of health utility. METHODS: Patients with RA participating in 2 studies in the UK (n = 151) and Canada (n = 319) completed the HAQ, EQ-5D, and Short Form 36 (SF-36). The SF-36, a generic measure of quality of life, was converted into the preference-based SF-6D. From these results we developed models of the relationship between the HAQ and SF-6D and EQ-5D using various regression analyses. RESULTS: The optimal model developed for the EQ-5D entered levels for each item as independent variables (model 5). A root mean square error (RMSE) of 0.18 suggested relatively good predictive ability. For the SF-6D, RMSEs were lower (0.09), suggesting better predictions than for the EQ-5D, but models with more explanatory variables did not improve results (model 2 or 4 optimal). The models were able to predict actual SF-6D and EQ-5D across the range of the HAQ DI. CONCLUSION: Our approach enabled calculations of quality-adjusted life years from existing trials where only the HAQ was measured. All aspects of the HAQ may not be reflected in the preference-based measures, and this method is suboptimal to direct measurement of health state utility in clinical trials. Given this limitation, our approach provides an alternative for researchers who need health-state utility values, but had not included a preference-based measure in their clinical study because of resource constraints or a desire to limit patient burden. 相似文献
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Chi-Chih Hung Jinn-Yuh Guh Mei-Chuan Kuo Yung-Hsiung Lai Hung-Chun Chen 《Nephrology, dialysis, transplantation》2006,21(2):547-548
Sir, Aminoglycoside-induced renal tubular dysfunction could be dividedinto Fanconi-like syndrome (FS) and Bartter-like syndrome (BS)[1]. The risk factors and mechanisms of tubular dysfunctionare little known. Here, we report a case of gentamicin-inducedFS, BS and distal renal tubular acidosis (RTA) and propose thepossible involvement of mitochondria. Case. A 66-year-old Chinese male was admitted because ofpneumonia. 相似文献
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