ELECTRON MICROSCOPY OF MYOPATHIES

肌病的电子显微镜检查

• 批准号: 3393463
• 负责人: ANDREW George ENGEL
• 金额: $ 23.6万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3393463
• 关键词: acetylcholine; autoantibody; autoimmune disorder; biopsy; bungarotoxins; complement pathway; dermatomyositis; disease /disorder classification; electron microscopy; electrophysiology; freeze etching; histochemistry /cytochemistry; human subject; immunochemistry; immunocytochemistry; inflammation; laboratory mouse; laboratory rat; membrane activity; membrane structure; monoclonal antibody; muscle disorder diagnosis; muscular dystrophy; myasthenia gravis; myofibrils; necrosis; neurochemistry; neuromuscular junction; neuromuscular transmission; nicotinic receptors

The present proposal seeks support for the continuation of an investigative program of human and experimentally induced muscle diseases. The diseases are approached through analysis of the light microscopic and ultrastructural reactions in the muscle fiber, neuromuscular junction, intramuscular nerves and blood vessels. Individual diseases are studied systematically by combined light microscopic histochemistry, immunocytochemistry, phase and electron microscopy, immunoelectron microscopy and freeze-fracture electron microscopy. Whenever possible, the observations are quantitated by morphometric methods and correlated with available physiologic and biochemical data. The two main themes for the renewal period pertain to defects of neuromuscular transmission and mechanisms of muscle fiber injury. In acquired myasthenia gravis/the relative contributions of the immunopathologic mechanisms which result in end-plate acetylcholine receptor (AChR) deficiency will be evaluated. In a congenital myasthenic syndrome attributed to impaired acetylcholine resynthesis or mobilization, an ultrastructural correlate will be sought for the stimulation induced failure of neuromuscular transmission. In three clinically and morphologically distinct myasthenic syndromes associated with congenital end-plate AChR deficiency, detailed analyses of end-plate ultrastructure, AChR distribution and cholinergic binding sites will be carried out. In the Lambert-Eaton myasthenic syndrome the hypothesis will be tested that presynaptic membrane active zones represent the target of pathogenic autoantibodies. In Duchenne dystrophy and other myopathies necrotic and prenecrotic muscle fibers will be studied to define the ultrastructural binding site of the complement membrane attack complex. The pathogenesis of inflammatory myopathies will be investigated by monoclonal antibody analysis of the mononuclear cells in muscle; subsets of these cells involved in muscle fiber destruction will be defined, and the ultrastructural aspects of this mechanism will be elucidated. In dermatomyositis the hypothesis will be tested that the pathologic features of the disease are mediated by a circulating autoantibody.

本提案寻求支持继续开展调查 人类和实验诱发的肌肉疾病的计划。 疾病 通过光学显微镜的分析来接近 肌纤维、神经肌肉接头的超微结构反应， 肌内神经和血管。 研究个体疾病 通过结合光学显微组织化学系统地， 免疫细胞化学、相差和电子显微镜、免疫电子 显微镜和冷冻断裂电子显微镜。 只要有可能， 观察结果通过形态测量方法进行定量并与 可用的生理和生化数据。 本次活动的两大主题 更新期与神经肌肉传递缺陷有关 肌纤维损伤的机制。 获得性重症肌无力/ 免疫病理学机制的相对贡献导致 将评估终板乙酰胆碱受体 (AChR) 缺陷。 在一个 乙酰胆碱受损导致的先天性肌无力综合征 再合成或动员，将寻求超微结构相关性 用于刺激引起的神经肌肉传递失败。 在 三种临床和形态学上不同的肌无力综合征 与先天性终板 AChR 缺陷相关，详细分析 终板超微结构、AChR 分布和胆碱能结合位点 将进行。 在兰伯特-伊顿肌无力综合征中 将检验突触前膜活性区代表的假设 致病性自身抗体的靶标。 在杜氏营养不良和其他 将研究坏死和坏死前肌纤维的肌病以确定 补体膜攻击的超微结构结合位点 复杂的。 将研究炎症性肌病的发病机制 通过肌肉中单核细胞的单克隆抗体分析；子集 将定义参与肌纤维破坏的这些细胞，以及 该机制的超微结构方面将得到阐明。 在 皮肌炎的假设将被检验，病理特征 该疾病的发生是由循环自身抗体介导的。