NEUROMUSCULAR AND CENTRAL NERVOUS SYSTEM DISEASES AND THEIR EXPERIMENTAL MODELS

神经肌肉和中枢神经系统疾病及其实验模型

• 批准号: 3846204
• 负责人: M C DALAKAS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3846204
• 关键词: HIV infections; Primates; Retroviridae; autoimmune disorder; biopsy; brain; communicable diseases; dermatomyositis; disease /disorder model; drug adverse effect; gene expression; heart; histochemistry /cytochemistry; histocompatibility antigens; human immunodeficiency virus; human subject; human tissue; immunopathology diagnosis; laboratory rat; laminin; mitochondria; muscle; muscle disorder diagnosis; muscular dystrophy; myelinopathy; myofibrils; nervous system disorder diagnosis; neural cell adhesion molecules; neuromuscular disorder; poliomyelitis; polymyositis; sciatic nerve; simian immunodeficiency virus; tissue /cell culture; virus infection mechanism; virus receptors; zidovudine

The Section runs the Laboratory of Muscle Enzyme Histochemistry that processes up to 300 muscle and nerve biopsies per year for diagnostic studies. Examined muscle specimens are from patients with neuromuscular manifestations related to systemic autoimmune, viral, metabolic, endocrine or infectious diseases, and from patients with primary neuromuscular disorders, such as polymyositis, dermatomyositis, neurogenic muscular atrophies, muscular dystrophies, post-polio syndrome, polyneuropathies, mitochondrial encephalomyopathies and biochemical or genetic muscle diseases. The laboratory is also involved in the following immunologic, biochemical and virologic studies that examine the susceptibility of the muscle and nerve to immune or viral mediated injuries: (a) Study of the regeneration of human muscle in health and disease, and monitor 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 or HIV-infected lymphoid cells to infect human myotubes in culture and induce expression of MHC-antigens; (c) study the expression of the poliovirus receptor in human muscle and the ability of the poliovirus to infect and replicate in human myotubes; (d) study the toxicity of AZT to muscle mitochondria by applying various concentrations of AZT to human muscle in culture; and (e) use of animal models to study the pathogenesis of: (i) retrovirus-induced inflammatory myopathy by examining muscles from monkeys infected with simian immunodeficiency virus; (ii) AZT-induced mitochondrial myopathy by studying structural, metabolic and functional changes in the muscle, heart, and brain mitochondria in rats injected with AZT; and (iii) autoimmune demyelinating polyneuropathies by searching for myelinotoxic or axonotoxic autoantibodies in sciatic nerves of rats after intraneural injection of the patient's serum.

该科设有肌肉酶组织化学实验室， 每年处理多达300个肌肉和神经活检， 问题研究 检查的肌肉标本来自神经肌肉疾病患者， 与系统性自身免疫、病毒、代谢、 内分泌或感染性疾病，以及原发性 神经肌肉疾病，如多发性肌炎，皮肌炎， 神经源性肌肉萎缩症，肌肉萎缩症，脊髓灰质炎后综合征， 多发性神经病、线粒体脑肌病和生化或 遗传性肌肉疾病 该实验室还参与了 在免疫学、生物化学和病毒学研究之后， 肌肉和神经对免疫或病毒介导的 损伤：（a）研究健康人体肌肉再生， 疾病，并监测卫星细胞的成熟，通过检查 神经细胞粘附分子和层粘连蛋白的表达;（B）研究 肌肉和神经对逆转录病毒感染的易感性， HIV或HIV感染的淋巴细胞感染人肌管的能力 在培养物中并诱导MHC抗原的表达;（c）研究 脊髓灰质炎病毒受体在人体肌肉中的表达以及 （d）研究脊髓灰质炎病毒在人体肌管中的感染和复制; 应用不同浓度AZT对肌肉线粒体的毒性 （e）使用动物模型研究 发病机制：（i）逆转录病毒引起的炎性肌病， 检查感染猿免疫缺陷的猴子的肌肉 病毒;（ii）AZT诱导的线粒体肌病， 肌肉、心脏和大脑的代谢和功能变化 注射AZT大鼠的线粒体;和（iii）自身免疫 脱髓鞘性多发性神经病通过寻找髓鞘毒性或 坐骨神经损伤后大鼠坐骨神经中的轴毒性自身抗体 注射病人的血清