NEUROMUSCULAR AND CNS DISEASES AND THEIR EXPERIMENTAL MODELS

该科每年处理100多例肌肉和神经活组织检查 用于诊断和研究研究。接受检查的肌肉来自患者 与：与全身性、自身免疫性、 病毒性、代谢性、内分泌性或感染性疾病； 神经肌肉疾病，如多发性肌炎、皮肌炎、 包涵体肌炎，神经源性肌肉萎缩，肌肉 营养不良、脊髓灰质炎后综合征、多发性神经病、线粒体 脑肌病；生化和遗传性肌肉疾病患者 中枢性核心病或肥厚性心肌病等疾病； 以及来自实验动物的。该实验室还参与了 在免疫学、生化和病毒学研究之后 检查肌肉和神经对免疫或病毒的易感性 介导性损伤：(A)研究不同类型患者的基因缺陷 代谢性肌病、线粒体病或脊髓性肌萎缩； (B)研究患者免疫球蛋白的结合情况 人类糖脂和糖蛋白的副蛋白血症神经病和 将免疫反应与临床表现联系起来；(C)研究 脊髓灰质炎病毒受体在人体肌肉中的表达 以及脊髓灰质炎病毒的机制(细胞凋亡或坏死) 在体外感染、复制和杀死运动神经元或人类肌管； (D)研究细胞因子和淋巴因子的作用，重点是白介素1， IL2、TGFβ在人肌管上的表达，并检测各种免疫治疗方法 药物可抑制其毒性或免疫增强作用；(E)研究 促凋亡或抗凋亡分子的上调，如 Fas，FasL，Bcl一2，Bcl一xl，在体内外的人肌肉中；(F) AZT、FIAU等核苷类似物对小鼠的毒性研究 肌肉线粒体对线粒体的氧化磷酸化和 麻省理工学院。通过将这些制剂应用于培养中的人类肌肉来获得DNA； (G)用动物模型研究：(I)AZT诱导的机制 线粒体肌病和ddC诱导的神经毒性 肌肉和神经的结构、代谢和功能改变 注射AZT或ddC对健康大鼠线粒体的影响 L-卡尼汀在逆转或改善核苷诱导的小鼠脑损伤中的作用 实验动物或组织中的神经肌肉毒性 培养；(Iii)转化生长因子-b基因敲除小鼠的炎症反应；以及 (4)MDX小鼠体内T细胞受体和细胞因子的变化 携带抗肌营养不良蛋白基因的腺病毒载体。

The Section processes more than 100 muscle and nerve biopsies per year for diagnostic and research studies. Examined muscles are from patients with: neuromuscular manifestations related to systemic, autoimmune, viral, metabolic, endocrine or infectious diseases; primary neuromuscular disorders, such as polymyositis, dermatomyositis, inclusion body myositis, neurogenic muscular atrophies, muscular dystrophies, post-polio syndrome, polyneuropathies, mitochondrial encephalomyopathies; patients with biochemical and genetic muscle diseases, such as central core disease or hypertrophic cardiomyopathy; and from experimental animals. The laboratory is also involved in the following immunological, biochemical and virological studies that examine the usceptibility of the muscle and nerve to immune or viral mediated injuries: (a) study the genetic defect in patients with various metabolic myopathies, mitochondriopathies or spinal muscular atrophies; (b) study the binding of immunoglobulin from patients with paraproteinemic neuropathies to human glucolipids and glucoproteins and correlate the immunoreactivity with the clinical picture; (c) study the expression of the poliovirus receptor in human muscle in vivo and in vitro, and the mechanism (apoptosis or necrosis) by which the poliovirus infects, replicates and kills motor neurons or human myotubes in vitro; (d) study the effect of cytokines and lymphokines with emphasis on IL1, IL2, TGFbeta on human myotubes and examine if various immunotherapeutic agents can inhibit their toxic or immunopotentiating effect; (e) study the up-regulation of pre-apoptotic or anti-apoptotic molecules such as fas, fasL, Bcl-2, Bcl-XL, in human muscle in vitro and in vivo; (f) study the toxicity of nucleoside analogues, such as AZT and FIAU to muscle mitochondria to the mitochondrial oxidative phosphorylation and the mit. DNA by applying these agents to human muscle in culture; and (g) use animal models to study: (i) the mechanism of AZT-induced mitochondrial myopathy and ddC-induced neurotoxicity by examining the structural, metabolic and functional alterations in the muscle and nerve mitochondria of healthy rats injected with AZT or ddC; (ii) the effect of L-carnitine in reversing or improving the nucleoside-induced neuromuscular toxicity in the experimental animals or in tissue cultures; (iii) the inflammatory response in TGF-b knock-out mice; and (iv) the T cell receptor and cytokine profile in mdx mice treated with an adenovirus vector carrying the dystrophin gene.