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定量细胞化学在结缔组织疾病研究中的应用。

The application of quantitative cytochemistry to the study of diseases of the connective tissues.

作者信息

Henderson B

出版信息

Prog Histochem Cytochem. 1983;15(1):1-83. doi: 10.1016/s0079-6336(83)80001-1.

DOI:10.1016/s0079-6336(83)80001-1
PMID:6419282
Abstract

The connective tissues are a complex organisation of tissues, cells and intercellular materials spread throughout the body and are subject to a large number of diseases. Such complexity makes the study of the metabolism of the connective tissues in health and more particularly in disease states difficult if one uses conventional biochemical methodology. Fortunately the techniques of quantitative cytochemistry, as developed in recent years, have made it possible to study the metabolism of even such complex and refractory connective tissues as bone. Using properly validated assays of enzyme activity in unfixed sections from various tissues a number of the diseases of the connective tissues have been studied. For example the synovia from patients with rheumatoid arthritis and related conditions have been studied using these techniques and marked alterations in the metabolism of the synovial lining cell population of this tissue have been demonstrated. These alterations in metabolism are believed to be related to the destruction of cartilage and bone found in such diseases. Investigations of the metabolism of the chondrocytes of articular cartilage in a strain of mice which spontaneously develops osteoarthritis has revealed a lack of certain key enzymes of carbohydrate metabolism in precisely those areas where degradation of the matrix of articular cartilage begins suggesting a causal relationship between these events. These same techniques have been used to study the cellular kinetics and metabolism of the dermis and epidermis in the disfiguring disease, psoriasis. The metabolism of healing bone fractures, the diagnosis and treatment of the mucopolysaccharidoses and the metabolic effects of currently used anti-inflammatory and anti-rheumatic drugs have also been examined. Perhaps the most exciting aspect of these studies has been the development and use of the technique of the cytochemical bioassay (CBA) to study hormonally mediated diseases of the connective tissues. Such studies have recently shed new light on the molecular lesion in pseudohypoparathyroidism. Though still in their relative infancy the studies described in this review show the potential inherent in the use of quantitative cytochemistry for the study of diseases of the connective tissues.

摘要

结缔组织是遍布全身的组织、细胞和细胞间物质的复杂组合,易患多种疾病。如果使用传统的生化方法,这种复杂性使得研究健康状态下尤其是疾病状态下结缔组织的代谢变得困难。幸运的是,近年来发展起来的定量细胞化学技术使得研究甚至像骨骼这样复杂且难处理的结缔组织的代谢成为可能。通过对来自各种组织的未固定切片进行经过适当验证的酶活性测定,已经对多种结缔组织疾病进行了研究。例如,利用这些技术对类风湿性关节炎及相关病症患者的滑膜进行了研究,并证明了该组织滑膜衬里细胞群体的代谢有明显改变。这些代谢改变被认为与这类疾病中发现的软骨和骨骼破坏有关。对一种自发发生骨关节炎的小鼠品系的关节软骨软骨细胞代谢的研究表明,在关节软骨基质开始降解的精确区域恰恰缺乏某些碳水化合物代谢的关键酶,这表明这些事件之间存在因果关系。同样的技术已被用于研究毁容性疾病牛皮癣中真皮和表皮的细胞动力学及代谢。还研究了愈合骨折的代谢、粘多糖贮积症的诊断和治疗以及目前使用的抗炎和抗风湿药物的代谢作用。也许这些研究最令人兴奋的方面是细胞化学生物测定(CBA)技术的发展和应用,用于研究结缔组织的激素介导疾病。这类研究最近为假性甲状旁腺功能减退症的分子病变带来了新的认识。尽管仍处于相对初期阶段,但本综述中描述的研究显示了使用定量细胞化学研究结缔组织疾病所固有的潜力。

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Assessment of lysosomal function by quantitative histochemical and cytochemical methods.
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