SYNOVIAL MEMBRANE AND RELATED CONNECTIVE TISSUES

我们研究的长期目标是定义病因学， 各种类型淀粉样变性的发病机制和治疗。要完成 为了达到这些目标，我们计划探讨继发性淀粉样变性的发病机制。 通过研究炎症与血清淀粉样蛋白A组分的关系 (SAA)，通过生化和免疫组化鉴定各种类型的淀粉样蛋白 免疫细胞化学方法导致分离和更精确 这些组件的描述。细胞免疫功能的研究进展 将对淀粉样蛋白进行分析，并将继续努力定义和改变 药物干预下人类淀粉样蛋白的自然历史。在AA中 (继发性)淀粉样变性，我们假设SAA的产生是为了满足 在非特异性宿主防御中的关键作用，以及在宿主的过程中 恢复原状，通常从流通中清除。然而，在 慢性炎症，不溶的AA纤维从羧基堆积 SAA的末端蛋白分解(L)。建议进行研究以进一步阐明 参与合成和降解的细胞和细胞产物 萨阿。在AL(原发性)淀粉样变性中，我们将检验以下假设 这是免疫细胞异位症和扩展序列数据，以进一步检查 轻链参与，并开发出更好的分型抗血清。的作用 家族性淀粉样变性和不同类型老年性淀粉样变性中的前白蛋白 将会被进一步研究。方法学将包括组织培养、氨基 酸测序，用过氧化物酶标记的免疫细胞化学分析， 并使用电子显微镜和实验模型。患有各种疾病的患者 各种类型的淀粉样蛋白，尤其是那些有各种家族性淀粉样蛋白的 桑代克纪念实验室将跟踪观察这些症状。 淀粉样蛋白自然病史的持续研究和干预 秋水仙碱等药物将继续，以及对 淀粉样变性的心血管损害。由于淀粉样蛋白在ITS中普遍存在 在人类体内的分布，并越来越多地被认为是与 衰老以及许多炎症性和恶性的并发症 随着疾病的发展，定义其多重 病因学和设计现实的治疗方法。

The long term aim of our studies is the definition of the etiology, pathogenesis and treatment of various forms of amyloidosis. To accomplish these aims, we plan to approach the pathogenesis of secondary amyloidosis through studies of inflammation, in relation to serum amyloid A component (SAA), to identify various types of amyloid by biochemical and immunocytochemical methods leading to the isolation and more precise delineation of these components. Aspects of cellular immune function of amyloid will be analyzed and efforts will continue to define and alter the natural history of human amyloid by pharmacologic intervention. In AA (secondary) amyloidosis, we hypothesize that SAA is produced to fulfill an essential role in nonspecific host defense, and in the process of host restitution, is normally cleared from the circulation. However, during chronic inflammation, insoluble AA fibrils accumulate from carboxyl terminal proteolysis of SAA(L). Studies are proposed to elucidate further those cells and cell products involved in the synthesis and degradation of SAA. In AL (primary) amyloidosis, we shall examine the hypothesis that this is an immunocyte dyscrasia and extend sequence data to examine further the light chains involved, and develop better typing antisera. The role of prealbumin in familial amyloidosis and in various types of senile amyloid will be further examined. Methodologies will include tissue culture, amino acid sequencing, immunocytochemical analyses with peroxidase labels, electron microscopy and use experimental models. Patients with various forms of amyloid, especially those with a variety of familial amyloid syndromes will be followed in the Thorndike Memorial Laboratory. Continuing studies of the natural history of amyloid and intervention with agents such as colchicine will continue, as well as studies of the cardiovascular lesions of amyloidosis. Since amyloid is ubiquitous in its distribution in man, and is increasingly recognized as an accompaniment of aging as well as a complication of many inflammatory and malignant diseases, it has become increasingly important to define its multiple etiologies and devise realistic methods of therapy.