Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.

The presence of abundant intraneuronal amyloid in the form of neurofibrillary tangles (NFT) in the brains of Guamanian parkinsonism-dementia patients and the absence of extraneuronal amyloid in the form of vascular amyloid deposits or senile plaques permit the purification of NFT without contamination with extraneuronal amyloid. Thus, we have isolated and determined the amino acid sequence of the polypeptide subunit of the amyloid fibrils of these NFT and describe their ultrastructure. The NFT, which consist of single and paired helical filaments, similar to those of Alzheimer disease, and occasionally triple helical filaments, are composed of multimeric aggregates of a polypeptide of 42 amino acids (A4 protein). The relative molecular mass of the subunit protein, 4.0-4.5 kDa, is the same as the molecular mass of the amyloid of NFT, of the amyloid plaque cores, and of vascular amyloid deposits in Alzheimer disease and Down syndrome; the sequence of 15 amino acid residues at the N-terminus of the amyloid fibrils in the NFT of Guamanian parkinsonism-dementia is identical to that of the amyloid of NFT, amyloid plaque cores, and cerebrovascular deposits in Alzheimer disease and Down syndrome. Furthermore, the heterogeneity, or variation in polypeptide length, of the N-terminus of the amyloid of Guamanian parkinsonism-dementia is the same as in Alzheimer disease and Down syndrome. Our observations indicate that the brain amyloids of these diseases have a common subunit protein, which would also indicate a common pathogenesis.     

高血压患者空腹血游离脂肪酸组成与腰臀比、胰岛素活性的关系

目的观察原发性高血压患者空腹血游离脂肪酸(freefattyacid,FFA)组成与向心性肥胖、胰岛素抗性、年龄、血清锌和饮食的关系及性别差异。方法采用社区人群整群抽样、病例对照方法,筛选出高血压患者109例,其中肥胖患者70例,非肥胖患者39例,并以饮食习惯相近的123例血压正常个体(其中肥胖个体66例,非肥胖者57人)为对照,用高效液相色谱直接衍生化法检测空腹血清各种FFA浓度,放免法测定胰岛素水平。结果(1)多元逐步线性回归和分层分析显示空腹血清FFA组成(包括n3PUFA水平、P/S比值、C20:5/C18:3、C22:6/C20:5及C20:4/C18:2比值)存在年龄和性别差异,即小于45岁年龄组高血压患者的FFA改变显著性大与超过46岁年龄组,男性高血压患者的FFA改变显著性大于女性。(2)分层、相关及回归分析显示空腹血清FFA组成与腰臀围比值、胰岛素敏感指数、血清锌水平、饮食习惯相关(均P<0.05)。(3)原发性高血压患者血清锌水平略低于非高血压个体(14.9±5.0vs非高血压组16.8±6.4)μmol/L,P=0.45。结论原发性高血压患者空腹血游离脂肪酸组成改变与向心性肥胖、胰岛素抵抗、锌缺乏、年龄和饮食有关,并存在性别差异。     

Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast/Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk ovarian cancer. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2 or MSH6, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancer as well as a 9-12% lifetime risk of ovarian cancer. Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome.     

To the point: medical education reviews--providing feedback

Formative feedback is an essential component of effective teaching and learning. Without it, the learner flounders. Furthermore, the Liaison Committee on Medical Education requires formative feedback within the clerkship and specifies that students must have the time and ability to remediate deficiencies before completing the clerkship. Few articles in the medical literature address how to give effective feedback. However, the themes within these articles are consistent. Formative feedback should be an interactive activity between the teacher and learner. Feedback must be approached with mutual respect and should be provided in a safe environment. Quality feedback is timely, specific to the situation, constructive, based on direct observation and nonjudgmental. With effective feedback, learners (and teachers) can discover what to improve, as well as which behaviors and skills to reinforce and augment. Learners appreciate and request specific feedback. In addition, learners tend to rate teachers who provide feedback more highly than they rate teachers who do not provide feedback. This article in the "To the Point" series will focus on the components of effective feedback and provide a practical and effective approach to giving feedback.     

微电极阵列细胞传感器芯片技术的研究进展

综述了目前国际上基于微电极阵列技术的细胞传感器芯片的研究状况。介绍了微电极阵列的工艺设计、界面模型以及在细胞电生理研究中的应用,同时分析了细胞胞外记录技术在实现组织-细胞以及细胞间信号传导过程的实时动态检测的特点和目前存在的问题。在此基础上,介绍了单细胞以及细胞传感器网络芯片技术的发展。最后,提出微电极阵列细胞传感器研究的发展方向。     

Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.     

血府逐瘀口服液对大鼠缺氧-再给氧损伤心脏微血管内皮细胞黏附分子表达的影响

目的 观察血府逐瘀口服液对心脏微血管内皮细胞缺氧／复氧损伤中黏附分子表达的影响。方法 通过心脏微血管内皮细胞体外培养技术，建立缺氧／复氧损伤模型，模拟心肌缺血再灌注损伤。用免疫细胞化学法和图像定量分析系统，观察心脏微血管内皮细胞的细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达变化。结果大鼠心脏微血管内皮细胞缺氧4h后ICAM-1和VCAM-1的蛋白表达较对照组升高，但无统计学意义（P〉0．05），再给氧6h、12h后ICAM-1和VCAM一1的表达较对照组明显增高（P〈0．01）。血府逐瘀口服液能显著降低ICAM-1和VCAM-1的蛋白表达，这种作用随着剂量的增加而增强。结论 血府逐瘀口服液可通过降低心脏微血管内皮细胞的ICAM-1和VCAM-1表达，减少白细胞浸润，从而减轻缺血再灌注损伤中的炎性反应对心功能造成损害。     

葡萄糖转运蛋白4囊泡运输及相关的临床疾病

葡萄糖转运蛋白4（Glut4）是骨骼肌、心肌以及脂肪细胞摄取葡萄糖的重要媒介,它在维持机体糖稳态中起关键作用。因此,对Glut4的囊泡运输及相关蛋白、分子信号转导通路以及相关临床疾病的研究意义重大。本文综述了微管、微丝、分子马达在胰岛素受体细胞Glut4囊泡运输中发挥的作用,及最近报道的一些与Glut4共定位蛋白的特殊作用。此外本文对胰岛素刺激Glut4转运的多条信号通路以及Glut4相关临床疾病也做了详细介绍。     

ERK在ALR抑制免疫过程中的变化及意义

目的观察肝再生增强因子(ALR)对外周血单核细胞增殖时ERK的影响,以探明ALR免疫抑制相关机理。方法梯度离心法分离健康人外周单核细胞,用ConA 5μg/ml刺激细胞增殖,选定最佳研究时间;观察不同剂量ALR抑制功能,选用最佳抑制剂量;利用Western blot检测ALR抑制细胞增殖时ERK的磷酸化改变。结果 ConA刺激细胞增殖最佳时间是60 h,ALR能抑制细胞增殖,并呈剂量依赖关系,30μg/ml ALR抑制效果最显著;ALR对单核细胞无直接增殖作用。ConA能引起ERK含量和磷酸化明显增加,ALR则抑制ConA对ERK的刺激,以抑制ERK2最明显。结论 ALR可能通ERK的含量和抑制ERK2的磷酸化抑制细胞增殖。