SYNOVIAL MEMBRANE AND RELATED CONNECTIVE TISSUES

我们研究的长期目标是确定病因， 各种形式的淀粉样变性的发病机制和治疗。 完成 因此，我们计划探讨继发性淀粉样变性的发病机制， 通过对炎症的研究， (SAA)，通过生化和免疫学方法鉴定各种类型的淀粉样蛋白， 免疫细胞化学方法导致的分离和更精确的 这些组件的描述。 细胞免疫功能的研究进展 淀粉样蛋白将被分析，并将继续努力定义和改变 人类淀粉样蛋白的自然史通过药物干预。 在AA （继发性）淀粉样变性，我们假设SAA的产生是为了实现一个 在非特异性宿主防御中起重要作用，在宿主 恢复原状，通常从流通中清除。 但在 慢性炎症，不溶性AA纤维从羧基积累 SAA（L）的末端蛋白水解。 建议进行研究以进一步阐明 这些细胞和细胞产物参与的合成和降解， SAA。 在AL（原发性）淀粉样变性中，我们将检验以下假设： 这是一个免疫细胞恶液质和扩展序列数据进一步研究 轻链参与，并开发更好的分型抗血清。 的作用 家族性淀粉样变性和各种类型老年淀粉样变性中的前白蛋白 将进一步审查。 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， 电子显微镜和使用实验模型。 例各种 淀粉样蛋白的形式，特别是那些有各种家族性淀粉样蛋白 将在桑代克纪念实验室进行随访。 淀粉样蛋白自然史的持续研究和 秋水仙碱等药物的研究将继续进行， 淀粉样变性的心血管病变。 由于淀粉样蛋白在其 在人身上的分布，并越来越多地被认为是伴随着 衰老以及许多炎症和恶性肿瘤的并发症 疾病，它已成为越来越重要的定义其多重 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.