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Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
33.
S. Xing X. Zhang J. H. Liu X. Huang P. Zhou 《Clinical and experimental immunology》2019,195(1):121-131
Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c+ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT. 相似文献
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颗粒松质骨压紧植骨全髋关节置换术治疗创伤性髋关节炎的疗效 总被引:2,自引:0,他引:2
目的探讨颗粒松质骨压紧植骨全髋关节置换术(THA)治疗髋臼骨折继发创伤性髋关节炎的疗效。方法1998年12月-2005年5月,对15例髋臼骨折继发创伤性髋关节炎患者行颗粒松质骨压紧植骨THA,所有患者髋臼假体均采用骨水泥固定,颗粒骨均取自体骨,术后24h后开始被动活动,3个月后开始全负重锻炼。临床随访采用Harris髋关节评分(HSS)系统评分,对任何原因引起髋臼假体翻修均视为临床失败。根据Conn等影像学评价法观察颗粒骨长人情况,根据DeLee的三区法测量臼杯、骨水泥与移植骨间的界面宽度,臼杯的移位程度则依据其相对于泪点间线的距离而定。结果14例患者获得平均4.3年(1.0-7.5年)随访,HHS评分由术前平均42分(10-62分)提高到随访结束时平均84分(58-98分)。1例髋部有轻度疼痛,无患者行翻修手术。大部分髋部恢复了其正常的旋转中心,仅有2例高出对侧0.8 mm。大多数患者影像学表现稳定,2例在Ⅰ区和Ⅲ区出现进行性增宽的透亮带,1例在Ⅲ区出现非进行性增宽的透亮带。1例臼杯假体在术后7年出现明显移位(6 mm),但并没有行翻修手术。结论颗粒骨压紧植骨技术作为一种生物学髋臼重建方法,其联合THA治疗髋臼骨折后继发创伤性关节炎伴髋臼缺损的疗效令人满意,能够恢复髋关节的正常解剖和功能活动。 相似文献
37.
目的了解广东高校贫困生心理健康状况并提出相应建议。方法用康奈尔医学指数(CMI)及社会支持评定量表,对广东省5所高校500名学生进行了问卷调查,并采用SPSS11.0进行相关统计和分析。结果贫困大学生的心理健康状况在某些方面存在不足,在性别、地域来源等有差异。结论高校应重视贫困大学生的心理健康状况,加强情感引导,尤其不能忽视对女贫困大学生的关注和帮助。 相似文献
38.
J Phua E S C Koay D Zhang L K Tai X L Boo K C Lim T K Lim 《The European respiratory journal》2006,28(4):695-702
Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections. 相似文献
39.
目的:探讨下颈椎的屈曲程度与后路经寰枢关节螺钉固定术的可能性。方法:回顾已施行经寰枢关节螺钉固定术病例的术前颈椎过屈位X线像,测量C2~C7间的角度,复习手术经过,分析可完成螺钉固定的颈椎曲度及其它相关因素。结果:在已完成后路经寰枢关节螺钉固定术的75例患者中有58例屈颈侧位X线像显示下颈椎呈后凸状态,后凸角平均为17.25°;另17例屈颈侧位片见下颈椎呈前凸状态,但这些病例都是体形瘦长者。结论:后路经寰枢关节螺钉固定术仅适合于下颈椎可以很好屈曲及体形瘦长的病例。 相似文献
40.
目的探讨氦氖激光血液照射辅助治疗控制癌痛的疗效。方法对52例中晚期癌症重度痛患者在使用口服吗啡治疗基础上加用低能量氦氖激光血液照射治疗1周后,对疼痛缓解程度及平均缓解时间进行对照观察。结果加用激光照射组的镇痛疗效优于单用吗啡组,P<0.05,有效率分别为92%和84%,P>0.05,显效率分别为67%和46%,u=2.07,P<0.05,均数缓解时间分别为(8±3)h和(8±4)h,t=0.78,P>0.05,差异无显著性意义。结论氦氖激光血液照射治疗有一定协同镇痛作用。 相似文献