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SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA

SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA
恶性高热中的骨骼肌损伤
批准号:
3271905
负责人:
THOMAS E NELSON
金额:
$7.7万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-08-01 至 1993-11-30

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中文摘要
翻译
恶性高热(MH)是一种人类遗传性疾病,多种疾病 容易出现危及生命的代谢亢进的动物物种 由某些麻醉剂引发的综合征。 的 该项目中描述的实验旨在回答问题 关于人类 MH 的病因学和病理生理学。 研究将 涉及 3 个不同的物种(人、狗、猪),每个物种都有一个基因 MH 倾向。 犬和猪 MH 的比较研究 遗传模型将在不同层次的组织中进行, 即纯化的蛋白质亚细胞细胞器膜、完整的骨骼 肌肉组织和完整的动物。 平行膜和肌肉 将对获得的组织进行组织水平的研究 来自人类 MH 诊断性肌肉活检标本。 预计 动物和人类数据的比较将为以下方面提供更好的基础: 了解人类的 MH。 病因学研究集中在一个假设上: MH 是持续肌质 Ca2 的结果,继发于 麻醉药对肌浆网 Ca2+ 调节的作用 (SR)膜系统。 机电 (E-C) 耦合的各个部位 将用完整的骨骼肌进行药理学研究 在碎片化的 SR 膜囊泡和纯化的蛋白质中进行生化分析。 预计结果将确定 E-C 耦合途径的位置 MH 肌肉可能会出现缺陷,并且如果相同的缺陷部位 所研究的 3 个物种共有。 这些结果可能有助于我们 了解其他肌肉疾病的机制。 临床上 咬肌强直综合征通常是 MH 发作的症状,是一种 与麻醉相关的严重且未解决的问题。 实验 旨在研究完整的动物、活检的骨骼肌和分离的 SR 膜将尝试解决咬肌的独特性 与该临床综合征相关的药理学和生理学。 在 除了扩展我们对 MH 的知识和理解之外 综合症,这些研究也将有助于我们了解 不同浓度挥发性麻醉药的作用机制 生物组织。
英文摘要
Malignant Hyperthermia (MH) is a genetic disease in man and various animal species predisposing to a life-threatening hypermetabolic syndrome that is triggered by certain anesthetic agents. The experiments described in this project are designed to answer questions regarding the etiology and pathophysiology of MH in man. Studies will involve 3 different species (man, dog, pig) each with a genetic predisposition to MH. Comparative studies in the canine and porcine MH genetic models will be performed at varying levels of organization, i.e., purified protein subcellular organelle membrane, intact skeletal muscle tissue and the intact animal. Parallel membrane and muscle tissue levels of investigations will be performed on tissue obtained from human MH diagnostic muscle biopsy specimens. It is expected that comparison of animal and human data will provide a better basis for understanding MH in man. Etiologic studies focus on a hypothesis that MH is a consequence of sustained myoplasmic Ca2+, secondary to the action of anesthetics on Ca2+ regulation by the sarcoplasmic reticulum (SR) membrane system. Various sites of electromechanical (E-C) coupling will be investigated pharmacologically with intact skeletal muscle and biochemically in fragmented SR membrane vesicles and purified protein. The results are expected to determine where in the E-C coupling pathway a defect may occur in MH muscle and if the same defective site(s) is common to the 3 species studied. Such results may contribute to our understanding of mechanisms for other muscle diseases. The clinical syndrome of masseter muscle rigidity, often a symptom of MH onset, is a serious and unresolved problem associated with anesthesia. Experiments designed to study intact animals, biopsied skeletal muscle and isolated SR membranes will attempt to address the uniqueness of masseter muscle pharmacology and physiology in relation to this clinical syndrome. In addition to expanding our knowledge and understanding of the MH syndrome, these studies will also contribute to our understanding of the mechanism of action of volatile anesthetics at different levels of biological organization.
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SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA
  • 批准号:
    2608752
  • 项目类别:
  • 资助金额:
    $23.75万
  • 财政年份:
    1992
  • 负责人:
    THOMAS E NELSON
  • 依托单位:
SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA
  • 批准号:
    3271903
  • 项目类别:
  • 资助金额:
    $10.87万
  • 财政年份:
    1992
  • 负责人:
    THOMAS E NELSON
  • 依托单位:
SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA
  • 批准号:
    2021772
  • 项目类别:
  • 资助金额:
    $25.98万
  • 财政年份:
    1992
  • 负责人:
    THOMAS E NELSON
  • 依托单位:
SKELETAL MUSCLE LESION IN MALIGNANT HYPERTHERMIA
  • 批准号:
    2174165
  • 项目类别:
  • 资助金额:
    $20.86万
  • 财政年份:
    1992
  • 负责人:
    THOMAS E NELSON
  • 依托单位:
海外基金