NEUROMUSCULAR AND CNS DISEASES AND THEIR EXPERIMENTAL MODELS

该部门处理了100多块肌肉和 每年用于诊断和研究的神经活组织检查。 检查的肌肉来自患有神经肌肉疾病的患者 与全身、自身免疫、病毒、代谢、 内分泌或感染性疾病；原发性神经肌肉疾病， 如多发性肌炎、皮肌炎、包涵体肌炎、 神经性肌萎缩、肌营养不良、脊髓灰质炎后 综合征、多发性神经病、线粒体脑肌病； 患有生化和遗传性肌肉疾病的患者，如 磷酸果糖激酶缺乏症、肥厚型心肌病；或 存储性肌病；以及来自实验动物的。实验室 还参与了下列免疫学、生化和 病毒学研究，检查肌肉和 神经对免疫或病毒介导的损伤：(A)研究遗传 各种代谢性肌病患者的缺陷(重点 关于磷酸果糖激酶缺乏症)、线粒体疾病和 遗传性空泡性肌病，重点是结蛋白储存； (B)研究患者免疫球蛋白的结合情况 人类糖脂和糖脂的副蛋白血症神经病 糖蛋白和免疫反应性与临床的相关性 图片；(C)研究脊髓灰质炎病毒受体在人类体内的表达 肌肉在体内和体外，脊髓灰质炎病毒感染和 在人肌管中复制及其机制(细胞凋亡或 脊髓灰质炎病毒杀死运动神经元)；(D)研究 细胞因子和淋巴因子的作用，重点是IL-1、IL-2、 转化生长因子β在人肌管上的表达及体外检测 免疫治疗药物可以抑制它们的毒性或 免疫增强作用；(E)研究上调 促凋亡或抗凋亡分子，如Fas，FasL，Bcl2， Bclxl、flip、人ILP在体内外人肌肉中的表达；(F) 研究表面分子及其参与的mRNA和配体 患者肌肉活检标本中的抗原提呈 患有自身免疫性疾病；g)检查基质的表达 金属蛋白酶的免疫细胞化学、酶谱和 自身免疫性神经病患者组织中的聚合酶链式反应 肌病；h)研究核苷类似物的毒性，例如 AZT和FIAU对肌肉线粒体、线粒体氧化的影响 磷酸化和MIT。通过将这些试剂应用于人类 文化中的肌肉。选择性、单纤维、mDNA检测 考虑耗尽；i)使用动物模型来研究：(I) AZT诱导线粒体肌病的机制及机制 DDC神经毒性的结构、代谢研究 以及肌肉和神经线粒体的功能改变 注射AZT或ddC的健康大鼠；(Ii)炎症 转化生长因子-β双基因敲除小鼠的反应及其作用 各种整合素；以及(Iii)T细胞受体和细胞因子谱 携带抗肌营养不良蛋白的腺病毒载体治疗mdx小鼠 吉恩。

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 phosphofructokinase deficiency, hypertrophic cardiomyopathy; or storage myopathies; and from experimental animals. The laboratory is also involved in the following immunological, biochemical and virological studies that examine the susceptibility of the muscle and nerve to immune or viral mediated injuries: (a) study the genetic defect in patients with various metabolic myopathies (with emphasis on phosphofructokinase deficiency), mitochondriopathies and hereditary vacuolar myopathies with emphasis on desmin-storage; (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, the ability of the poliovirus to infect and replicate in human myotubes and the mechanism (apoptosis or necrosis) by which the poliovirus kills motor neurons; (d) study the effect of cytokines and lymphokines with emphasis on IL1, IL2, TGFbeta on human myotubes and examine in vitro if various immunotherapeutic agents can inhibit their toxic or immunopotentiating effect; (e) study the up-regulation of pro-apoptotic or anti-apoptotic molecules such as fas, fasL, Bcl-2, Bcl-XL, FLIP, human ILP in human muscle in vitro and in vivo; (f) study surface molecules, their mRNA and ligands involved in antigen presentation in the muscle biopsy specimens from patients with autoimmune disorders; g) examine the expression of matrix metalloproteinases using immunocytochemistry, zymography and PCR in the tissues of patients with autoimmune neuropathies and myopathies; h) study the toxicity of nucleoside analogues, such as AZT and FIAU to muscle mitochondria, mitochondrial oxidative phosphorylation and mit. DNA by applying these agents to human muscle in culture. Examination of selective, single fiber, mDNA depletion is considered; i) 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 inflammatory response in TGF-beta double knock-out mice and the role of various integrins; and (iii) the T cell receptor and cytokine profile in mdx mice treated with an adenovirus vector carrying the dystrophin gene.