CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide

Although deposition of amyloid beta-peptide (Abeta) as Abeta plaques involves activation of microglia-mediated inflammatory responses, activated microglia ultimately fail to clear Abeta plaques in the brains of either Alzheimer's disease (AD) patients or AD mouse models. Mounting evidence suggests that chronic microglia-mediated immune response during Abeta deposition etiologically contributes to AD pathogenesis by promoting Abeta plaque formation. However, the mechanisms that govern microglia response in the context of cerebral Abeta/beta-amyloid pathology are not well understood. We show that ligation of CD40 by CD40L modulates Abeta-induced innate immune responses in microglia, including decreased microglia phagocytosis of exogenous Abeta(1-42) and increased production of pro-inflammatory cytokines. CD40 ligation in the presence of Abeta(1-42) leads to adaptive activation of microglia, as evidenced by increased co-localization of MHC class II with Abeta. To assess their antigen-presenting cell (APC) function, cultured microglia were pulsed with Abeta(1-42) in the presence of CD40L and co-cultured with CD4(+) T cells. Under these conditions, microglia stimulate T cell-derived IFN-gamma and IL-2 production, suggesting that CD40 signaling promotes the APC phenotype. These data provide a mechanistic explanation for our previous work showing decreased microgliosis associated with diminished cerebral Abeta/beta-amyloid pathology when blocking CD40 signaling in transgenic Alzheimer's mice.     

Wnt signaling induces epithelial-mesenchymal transition with proliferation in ARPE-19 cells upon loss of contact inhibition

Proliferation and epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy. This study aims at clarifying the role of growth factors, such as epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor-β1 (TGF-β1), in controlling how RPE proliferates while undergoing EMT. When contact inhibition of post-confluent ARPE-19 cells was disrupted by EGTA, an increase of BrdU labeling was noted only in the presence of EGF and/or FGF-2, and was accompanied by EMT as evidenced by the loss of a normal RPE phenotype (altered cytolocalization of RPE65, N-cadherin, ZO-1, and Na,K-ATPase) and the gain of a mesenchymal phenotype (increased expression of vimentin, S100A4, and α-smooth muscle actin). EMT with proliferation by EGTA+EGF+FGF-2 was accompanied by activation of canonical Wnt signaling (judged by the TCF/LEF promoter activity, increased nuclear levels of and interaction between β-catenin and LEF1 proteins, and the replication by overexpression of β-catenin), abolished by concomitant addition of XAV939, a Wnt inhibitor, but not associated with suppression of Hippo signaling (negative expression of nuclear TAZ or YAP and cytoplasmic p-TAZ or p-YAP). The causative role of Wnt signaling on EMT with proliferation was confirmed by overexpression of stable S33Y β-catenin with EGTA treatment. In addition, contact inhibition disrupted by EGTA in the presence of TGF-β1 also led to EMT, but suppressed proliferation and Wnt signaling. The Wnt signaling triggered by EGF+FGF-2 was sufficient and synergized with TGF-β1 in activating the Smad/ZEB1/2 signaling responsible for EMT. These findings establish a framework for further dissecting how RPE might partake in a number of proliferative vitreoretinopathies characterized by EMT.     

Defining stem and progenitor cells within adipose tissue

Adipose tissue-derived stem cells (ADSC) are routinely isolated from the stromal vascular fraction (SVF) of homogenized adipose tissue. Freshly isolated ADSC display surface markers that differ from those of cultured ADSC, but both cell preparations are capable of multipotential differentiation. Recent studies have inferred that these progenitors may reside in a perivascular location where they appeared to coexpress CD34 and smooth muscle actin (alpha-SMA) but not CD31. However, these studies provided only limited histological evidence to support such assertions. In the present study, we employed immunohistochemistry and immunofluorescence to define more precisely the location of ADSC within human adipose tissue. Our results show that alpha-SMA and CD31 localized within smooth muscle and endothelial cells, respectively, in all blood vessels examined. CD34 localized to both the intima (endothelium) and adventitia neither of which expressed alpha-SMA. The niche marker Wnt5a was confined exclusively to the vascular wall within mural smooth muscle cells. Surprisingly, the widely accepted mesenchymal stem cell marker STRO-1 was expressed exclusively in the endothelium of capillaries and arterioles but not in the endothelium of arteries. The embryonic stem cell marker SSEA1 localized to a pericytic location in capillaries and in certain smooth muscle cells of arterioles. Cells expressing the embryonic stem cell markers telomerase and OCT4 were rare and observed only in capillaries. Based on these findings and evidence gathered from the existing literature, we propose that ADSC are vascular precursor (stem) cells at various stages of differentiation. In their native tissue, ADSC at early stages of differentiation can differentiate into tissue-specific cells such as adipocytes. Isolated, ADSC can be induced to differentiate into additional cell types such as osteoblasts and chondrocytes.     

高重力加速度及其模拟条件下脑电变化研究综述

高重力加速度及其模拟条件下脑电变化的相关研究在航空医学领域具有重要意义。本文综合介绍了飞行中＋Gz和离心机＋Gz作用、下体负压作用、不同程度缺氧、短暂意识丧失下的脑电变化特点及其相互之间的关系。国内外学者围绕＋Gz及其模拟条件下的脑电变化规律已取得一定研究成果,但在脑电的定量分析,以及利用脑电对＋Gz加速度引起的短暂意识丧失进行前驱预警等方面的研究尚待深入。本文为高重力加速度环境下的脑电变化特征研究提供重要参考依据,对探寻利用脑电预警高重力加速度引起的意识丧失具有现实意义。     

军事飞行人员腰椎峡部裂影像学诊断和医学鉴定的专家建议

笔者通过文献综述、前期研究经验以及医学鉴定专家组的经验,对腰椎峡部裂影像学检查技术、影像学诊断标准、分型、运动生物力学分析和飞行安全风险评估等方面进行全面深入的分析,针对飞行人员峡部裂患者的影像诊断和医学鉴定标准进行探讨和修订,并提出建议案,旨在对腰椎峡部裂进行更精准的医学鉴定和保证飞行安全.     

Reduced striatal tyrosine hydroxylase in incidental Lewy body disease

Incidental Lewy body disease (ILBD) is the term used when Lewy bodies are found in the nervous system of subjects without clinically documented parkinsonism or dementia. The prevalence of ILBD in the elderly population has been estimated at between 3.8 and 30%, depending on subject age and anatomical site of sampling. It has been speculated that ILBD represents the preclinical stage of Parkinson’s disease (PD) and/or dementia with Lewy bodies (DLB). Studies of ILBD could potentially identify early diagnostic signs of these disorders. At present, however, it is impossible to know whether ILBD is a precursor to PD or DLB or is just a benign finding of normal aging. We hypothesized that, if ILBD represents an early stage of PD or DLB, it should be associated with depletion of striatal dopaminergic markers. Eleven subjects with ILBD and 27 control subjects were studied. The ILBD subjects ranged in age from 74 to 96 years (mean 86.5) while the control subjects’ age ranged from 75 to 102 years (mean 86.7). Controls and subjects did not differ in terms of age, postmortem interval, gender distribution, medical history conditions, brain weight, neuritic plaque density or Braak neurofibrillary stage. Quantitative ELISA measurement of striatal tyrosine hydroxylase (TH), the principal enzyme for dopamine synthesis, showed a 49.8% (P = 0.01) reduction in ILBD cases, as compared with control cases. The finding suggests that ILBD is not a benign condition but is likely a precursor to PD and/or DLB.     

高性能载人离心机推拉效应模拟方法研究

目的开发利用高性能载人离心机的功能,进行推拉效应(PPE)模拟方法的研究。方法推拉动作(PPM)加速度曲线的参数设为:Gmin为-1Gz持续5s,Gmax范围为从+2.5Gz持续10s开始按0.25Gz的幅度递增,对编制的模拟PPM加速度曲线进行试运行后,以12名战斗机飞行员和6名志愿者为受试者,分别测定了在预先有和无-1Gz5s作用情况下受试者的基础+Gz耐力。结果 -1Gz的产生会附带产生+1Gx和+0.5Gy,能够为人体所耐受。预先暴露于-1Gz5s后所有受试者的基础+Gz耐力均显著下降,志愿者组平均下降(0.87±0.13)G(P0.01),飞行员组平均下降(0.95±0.25)G(P0.01)。1名志愿者和1名飞行员受试者在PPM暴露的"拉"阶段发生加速度导致的意识丧失(G-LOC)结论在高性能载人离心机上初步建立推拉效应模拟方法,为后续的推拉效应研究奠定基础。     

男性勃起功能障碍的基础研究进展

男性勃起功能障碍是指男性持续性或反复发作的难以达到和维持阴茎勃起来完成性交和满意的性活动的病理现象。阴茎的勃起依赖于一系列正常的神经和血管性反应,包括正常的性心理反应,正常的生理结构,正常的内分泌,神经和血管功能。任何一个环节的     

Venous grafting for the correction of penile curvature in Peyronie's disease

A number of procedures have been developed to correct penile deformity secondary to Peyronie's disease. In many cases, tunica-shortening procedures have had reasonable success. The most popular of these are tunical plication and Nesbit's wedge resection. However, these procedures shorten the penis and do not correct the hourglass deformity. Tunica-lengthening by using autologous or synthetic materials has been reported with varying success. However, notable shortcomings including graft contracture, recurrence, and impotence have been reported. This review describes our experience with tunica incision and venous grafting.