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排序方式: 共有229条查询结果,搜索用时 15 毫秒
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KD Forsyth 《Journal of paediatrics and child health》2003,39(3):240-240
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J A Vanneste P B Augustijn F C Stam 《Journal of neurology, neurosurgery, and psychiatry》1988,51(1):131-135
Two half-sisters aged 14 and 18 years are described with a rigid spine syndrome as the cardinal clinical feature of an autosomal dominant neuromuscular disorder. Ten years previously, a diagnosis of multicore disease had been made from the clinical signs and muscle biopsy findings. Long term follow-up revealed a non-specific muscular dystrophy with axial predominance and a rigid spine in the younger girl; the older sister presented at the age of 18 with a rigid spine as the only myopathic sign. Computed tomography of the muscles showed severe involvement of the paraspinal musculature, in contrast with either less or no involvement of the other muscles. 相似文献
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Yoshino M Kuhlmann MK Kotanko P Greenwood RN Pisoni RL Port FK Jager KJ Homel P Augustijn H de Charro FT Collart F Erek E Finne P Garcia-Garcia G Grönhagen-Riska C Ioannidis GA Ivis F Leivestad T Løkkegaard H Lopot F Jin DC Kramar R Nakao T Nandakumar M Ramirez S van der Sande FM Schön S Simpson K Walker RG Zaluska W Levin NW 《Journal of the American Society of Nephrology : JASN》2006,17(12):3510-3519
Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences. 相似文献
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Bong Jik Kim Dong‐Kyu Kim Jin Hee Han Jayoung Oh Ah Reum Kim Chung Lee Nayoung KD Kim Hye‐Rim Park Min Young Kim Sejoon Lee Seungmin Lee Doo Yi Oh Woong‐Yang Park Sungjin Park Byung Yoon Choi 《Human mutation》2019,40(5):525-531
Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G>C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G>C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage. 相似文献
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Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young 《World journal of gastroenterology : WJG》2018,24(2):195-210
AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep~(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep~(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. 相似文献