NEUROMUSCULAR AND CNS DISEASES AND THEIR EXPERIMENTAL MODELS

该科设有肌肉酶组织化学实验室， 每年处理多达200个肌肉和神经活检， 调查研究。 检查的肌肉来自以下患者：神经肌肉 与全身性、自身免疫性、病毒性、代谢性、 内分泌或感染性疾病;原发性神经肌肉疾病，如 如多发性肌炎、皮肌炎、神经源性肌肉萎缩、肌肉萎缩、 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;以及生化和遗传肌肉 疾病，如中央核心疾病或肥厚性心肌病。 该实验室还参与了以下免疫学， 生物化学和病毒学研究， 肌肉和神经免疫或病毒介导的损伤：（a）研究 人体肌肉在健康和疾病的再生和成熟， 通过检测神经细胞粘附的表达， 分子和层粘连蛋白;（B）研究肌肉和神经的易感性 逆转录病毒感染以及HIV和HTLV-I或HIV 和HTLV-I感染的淋巴样细胞感染培养中的人肌管 并诱导新的表面抗原的表达; c）研究 脊髓灰质炎病毒受体在人体肌肉中的体内和体外， 脊髓灰质炎病毒感染人肌管并在其中复制的能力， 脊髓灰质炎病毒诱导细胞凋亡的机制;（d） 研究细胞因子和淋巴因子对人肌管的作用， 在体外检查潜在的治疗剂如IVIg是否可以 抑制其毒性或免疫增强作用;（e）检查 ICAM-1在体内和体外通过促进 细胞毒性T细胞与肌管的粘附;（f）研究 AZT对肌肉线粒体、线粒体氧化磷酸化和 （g）通过将AZT应用于培养的人类肌肉来研究线粒体DNA; 左旋卡尼汀逆转线粒体异常的作用 （h）使用动物模型， 研究：（i）逆转录病毒引起的炎性肌病的发病机制 通过检查感染了猿猴病毒的猴子的肌肉， 免疫缺陷病毒;（ii）AZT诱导线粒体的机制 通过检查结构、代谢和功能 注射AZT的健康大鼠肌肉线粒体的改变; (iii)左旋卡尼汀逆转或改善AZT诱导的 肌病的大鼠;和（iv）的机制，双脱氧胞苷 在健康大鼠中引起神经毒性。

The Section runs the Laboratory of Muscle Enzyme Histochemistry that processes up to 200 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, neurogenic muscular atrophies, muscular dystrophies, post-polio syndrome, polyneuropathies, mitochondrial encephalomyopathies; and patients with biochemical and genetic muscle diseases, such as central core disease or hypertrophic cardiomyopathy. 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 regeneration of human muscle in health and disease and the maturation of satellite cells by examining the expression of neural cell adhesion molecules and laminins; (b) study the susceptibility of muscle and nerve to infection with retroviruses and the ability of HIV and HTLV-I or HIV and HTLV-I-infected lymphoid cells to infect human myotubes in culture and induce expression of new surface antigens; 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 of apoptotic cell death induced by the poliovirus; (d) study the effect of cytokines and lymphokines on human myotubes and examine in vitro if potentially therapeutic agents such as IVIg can inhibit their toxic or immunopotentiating effect; (e) examine the role of ICAM-I in enhancing myocytotoxicity in vivo and in vitro by promoting the adhesion of cytotoxic T cells to myotubes; (f) study the toxicity of AZT to muscle mitochondria, mitochondrial oxidative phosphorylation and mitochondrial DNA by applying AZT to human muscle in culture; (g) study the effect of L-carnitine in reversing the mitochondrial abnormalities induced by AZT on human myotubes in vitro; and (h) use animal models to study: (i) the pathogenesis of retrovirus-induced inflammatory myopathy by examining muscles from monkeys infected with the simian immunodeficiency virus; (ii) the mechanism of AZT-induced mitochondrial myopathy by examining the structural, metabolic and functional alterations in the muscle mitochondria of healthy rats injected with AZT; (iii) the effect of L-carnitine in reversing or improving the AZT-induced myopathy in the rats; and (iv) the mechanism by which dideoxycytidine induces neuro~toxicity in healthy rats.