PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
批准号:
3399863
负责人:
DAVID P RICHMAN
金额:
$10.82万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-07-01 至 1987-06-30
中文摘要
这项建议旨在利用我们最近在我们的
实验室确定抗乙酰胆碱抗体的机制
受体(AChR)诱导重症肌无力(MG)。这些观察,运行在
与目前的理论有些相反的是:L)单克隆抗体
阻断完整AChR功能的(MCAB)可导致严重急性
无组织学异常的肌无力;2)慢性
不能阻断AChR的抗AChR单抗在大鼠体内的应用
功能障碍导致MG的组织学异常
临床或肌电异常。我们建议确定
确定慢性综合征的确切性质是否
组织学异常是否具有致病意义
表示更严重的终板损伤的愈合阶段,类似于
实验性肌无力急性期(EAMG)。我们还建议
确定是否添加阻止AChR功能的MBAB,
MCAB在诱导AChR周转或组合方面更有效
需要许多出租车来制作完整的MG图片
组织学、临床和电生理异常。我们会
利用纯化的抗乙酰胆碱受体单抗和免疫球蛋白片段进行研究
临床无力、肌电功能、微小终板电位
AChR和AChR-mCAB复合体的振幅、肌肉含量、光和
电子显微镜改变,以及一些血清学和免疫学
参数。免疫学、生物化学、
电生理和病理技术应该提供
有关导致MG的事件顺序的信息。此信息
很可能提出了治疗或预防这种疾病的新方法。在……里面
此外,由于我们目前对MG的了解使其成为自身免疫的“模型”
疾病,这项研究中获得的信息可能适用于
其他不太了解的自身免疫性疾病。
英文摘要
This proposal is designed to use two recent observations made in our
laboratory to determine the mechanisms by which antibodies to acetylcholine
receptor (AChR) induce myasthenia gravis (MG). The observations, which run
somewhat counter to current theories, are: l) monoclonal antibodies
(mcabs) that block the function of intact AChR induce severe acute
myasthenia in the absence of histological abnormalities; 2) chronic
administration in rats of anti-AChR mcabs incapable of blocking AChR
function results in the histological abnormalities of MG in the absence of
clinical or electromyographic abnormality. We propose to determine the
precise nature of the chronic syndrome to establish whether the
histological abnormality has pathogenic significance or whether it
represents the healed stage of a more severe endplate injury similar to the
acute phase of experimental myasthenia (EAMG). We also propose to
determine whether the addition of either mcabs that block AChR function,
mcabs more efficient in inducing increased AChR turnover, or combinations
of many mcabs are required to produce the complete MG picture of
histological, clinical, and electrophysiological abnormalities. We will
make use of purified anti-AChR mcabs and Ig fragments and will study
clinical weakness, electromyographic function, miniature endplate potential
amplitudes, muscle content of AChR and AChR-mcab complexes, light and
electron microscopic changes, and a number of serological and immune
parameters. The combination of immunological, biochemical,
electrophysiological, and pathological techniques should provide
information on the sequence of events that leads to MG. This information
may well suggest new means of treating or preventing this disease. In
addition, since our present knowledge of MG makes it a "model" autoimmune
disease, the information gained in this study will likely be applicable to
other less well-understood autoimmune diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Development of Animal Models of Anti-MuSK Myasthenia
-
批准号:8048710
-
项目类别:
-
资助金额:$22.96万
-
财政年份:2010
-
负责人:DAVID P RICHMAN
-
依托单位:
Development of Animal Models of Anti-MuSK Myasthenia
-
批准号:8152160
-
项目类别:
-
资助金额:$18.81万
-
财政年份:2010
-
负责人:DAVID P RICHMAN
-
依托单位:
IX INTERNATIONAL CONFERENCE ON MYASTHENIA GRAVIS
-
批准号:2038867
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1997
-
负责人:DAVID P RICHMAN
-
依托单位:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
-
批准号:3100129
-
项目类别:
-
资助金额:$65.68万
-
财政年份:1987
-
负责人:DAVID P RICHMAN
-
依托单位:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
-
批准号:3100128
-
项目类别:
-
资助金额:$18.06万
-
财政年份:1987
-
负责人:DAVID P RICHMAN
-
依托单位:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
-
批准号:3100131
-
项目类别:
-
资助金额:$58.46万
-
财政年份:1987
-
负责人:DAVID P RICHMAN
-
依托单位:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
-
批准号:3100126
-
项目类别:
-
资助金额:$72.85万
-
财政年份:1987
-
负责人:DAVID P RICHMAN
-
依托单位:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
-
批准号:3100130
-
项目类别:
-
资助金额:$61.12万
-
财政年份:1987
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399864
-
项目类别:
-
资助金额:$10.72万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399867
-
项目类别:
-
资助金额:$16.08万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399865
-
项目类别:
-
资助金额:$11.25万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA
-
批准号:2263670
-
项目类别:
-
资助金额:$22.19万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399859
-
项目类别:
-
资助金额:$12.17万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399860
-
项目类别:
-
资助金额:$19.04万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA
-
批准号:2263669
-
项目类别:
-
资助金额:$21.16万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA
-
批准号:2263668
-
项目类别:
-
资助金额:$17.16万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399862
-
项目类别:
-
资助金额:$10.75万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
-
批准号:3399866
-
项目类别:
-
资助金额:$16.73万
-
财政年份:1984
-
负责人:DAVID P RICHMAN
-
依托单位:
ANTIIDIOTYPIC ANTIBODIES IN MYASTHENIA
-
批准号:2262830
-
项目类别:
-
资助金额:$22.26万
-
财政年份:1979
-
负责人:DAVID P RICHMAN
-
依托单位:
ANTI-IDIOTYPIC ANTIBODIES IN MYASTHENIA
-
批准号:3396281
-
项目类别:
-
资助金额:$17.15万
-
财政年份:1979
-
负责人:DAVID P RICHMAN
-
依托单位: