ELECTRON MICROSCOPY OF MYOPATHIES

肌病的电子显微镜检查

• 批准号: 3393461
• 负责人: ANDREW George ENGEL
• 金额: $ 22.4万
• 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/3393461
• 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; inflammation; membrane activity; membrane structure; monoclonal antibody; muscle disorder diagnosis; muscular dystrophy; myasthenia gravis; myofibrils; necrosis; neurochemistry; neuromuscular junction; neuromuscular transmission

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.

本建议寻求支持继续进行一项调查