Relationship between E - cadherin and diabetic nephropathy

Objective To identify novel biomarker for diabetic nephropathy (DN) by urinary proteomic methods, and to detect the expression of E-cadherin in urine and renal tissue of patients with DN. Methods Urine samples were collected from 12 cases of type 1 diabetic nephropathy patients (T1DN), 12 cases of type 2 diabetic nephropathy patients (T2DN), 12 cases of nephritic syndrome patients (NS), and 12 cases of healthy Controls. Comparative proteomic approach of two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were employed to identify DN-related biomarker in urine samples. The differential expression of the identified biomarker in urine samples and renal biopsy specimens were detected by Western blotting and immunohistochemistry method. Results E-cadherin was identified by 2DE/MS, which was significantly up-regulated in T1DN and T2DN groups (all P＜ 0.01). Western blotting confirmed the expression of E-cadherin was significantly higher in T1DN and T2DN groups than in NS and Control groups (all P＜0.01). Immunohistochemical stain showed E-cadherin was mainly expressed in the membrane and cytoplasm of renal tubular epithelial cell, and its expression was markedly decreased in DN kidneys compared with healthy Controls (P＜0.05). Conclusions E-cadherin is identified as a novel DN-related biomarker, which is specifically increased in urine of DN patients.     

宾州忧虑问卷在中国大学生人群中的初步修订

目的:考察宾州忧虑问卷在中国非临床样本中的因素结构,并检验宾州忧虑问卷的总分和各素分的性别差异。方法:于2005-11选择北京大学2002～2005级的本科生677人为量表结构分析和一致性信度检验的测试样本。第一次施测8周后选择2004级本科生40人作为重测样本。调查问卷包括宾州忧虑问卷(16个项目,各项目均采取5点程度评估);Padua问卷(包括60个项目,各项目均采取5点程度评估,包含4个因素,因素Ⅰ:思维失控与怀疑感。因素Ⅱ:污染。因素Ⅲ:检查。因素Ⅳ:受驱使与行为失控感);状态特质焦虑问卷(状态焦虑量表和特质焦虑量表两个分量表共40个描述题组成,用来测量个体作为人格特质的焦虑倾向);贝克抑郁问卷(评价抑郁的严重程度,4级评分,总分范围为0～39分)。采用集体测试采集数据。结果:发放问卷677份,全部收回且合格,均进入结果分析。①探索性因素分析获得宾州忧虑问卷的2个因素:一般焦虑和焦虑缺失。②宾州忧虑问卷信度检验:总分的α系数为0.89,一般焦虑和焦虑缺失的α系数分别为0.91,0.69,重测信度分别为0.72,0.55。③宾州忧虑问卷的总分及一般焦虑和焦虑缺失因素的得分与状态特质焦虑问卷总分,贝克抑郁量表总分,Padua强迫问卷的因素1(思维失控与怀疑感)得分有较高的相关,说明有良好的汇聚效度。④男女被试在宾州忧虑问卷总分及一般焦虑和焦虑缺失因素得分差异无显著性意义。结论:宾州忧虑问卷在中国大学生人群中具备合格的信度和汇聚效度,需进一步研究其区分效度。     

Movement disorders in women: A review

The field of women's health developed based on the recognition that there are important sex‐based differences regarding several aspects of medical illnesses. We performed a literature review to obtain information about differences between women and men for neurological movement disorders. We identified important differences in prevalence, genetics, clinical expression, course, and treatment responses. In addition, we found that female life events, including menstruation, pregnancy, breast feeding, menopause, and medications prescribed to women (such as oral contraceptives and hormone‐replacement therapy), have significant implications for women with movement disorders. Understanding this biological sex‐specific information can help improve the quality and individualization of care for women with movement disorders and may provide insights into neurobiological mechanisms. © 2013 International Parkinson and Movement Disorder Society     

Evidence that the LRRK2 ROC domain Parkinson's disease‐associated mutants A1442P and R1441C exhibit increased intracellular degradation

Mutations in the leucine‐rich repeat kinase 2 (lrrk2) gene are the leading genetic cause of Parkinson's disease (PD). In characterizing the novel ROC domain mutant A1442P, we compared its steady‐state protein levels, propensity to aggregate, and toxicity with the pathogenic R1441C mutant and wild‐type (WT) LRRK2. Mutant (R1441C and A1442P) and WT LRRK2 fused to green fluorescent protein (GFP) and FLAG were transiently expressed in HEK293 cells using plasmid constructs. Western analysis and fluorescence microscopy consistently demonstrated lower mutant LRRK2 protein levels compared with WT. A time‐course expression study using flow cytometry showed that WT LRRK2 expression increased initially but then plateaued by 72 hr. Conversely, R1441C and A1442P mutant expression attained 85% and 74% of WT levels at 24 hr but fell to 68% and 55% of WT levels by 72 hr, respectively. We found that proteasome inhibition markedly increased mutant LRRK2 to levels approaching those of WT. Taken together, our findings reveal increased intracellular degradation for both mutants. Furthermore, the impact of mutant and WT LRRK2 expression on HEK293 cell viability was assessed under normative and oxidative (hydrogen peroxide) conditions and found not to differ. Expression of WT and mutant LRRK2 protein gave rise to intracellular aggregates of similar appearance and cellular localization. In summary, we provide evidence that the novel A1442P mutant and the previously investigated R1441C pathogenic mutant exhibit increased intracellular degradation, a property reportedly demonstrated for the pathogenic LRRK2 kinase domain mutant I2020T. © 2013 Wiley Periodicals, Inc.