Peters T J
J Clin Pathol. 1981 Jan;34(1):1-12. doi: 10.1136/jcp.34.1.1.
Classical approaches to the study of pathological tissue have relied mainly on morphological techniques. In an attempt to quantitate the abnormalities and to investigate the pathogenesis of tissue disorders at a subcellular level we have combined analytical subcellular fractionation by sucrose density gradient centrifugation with microanalysis of tissue enzymic activities. The methodological problems of performing these studies on milligram quantities of tissue are discussed. Details of the appropriate equipment are provided, and its application to the study of human liver specimens is described. As an example of this approach, biochemical and subcellular fractionation experiments on tissue from patients with both primary and secondary hepatic lysosomal storage diseases are discussed. Examination of the lysosomal changes reveals that increased enzyme activity is a common finding in these disorders but tissue damage occurs only when there is evidence of enhances lysosomal fragility with intracellular release of degradative enzymes. Other tissues which have proved amenable to study in this manner and in which profitable results in the investigation of their disorders have been obtained are listed.
研究病理性组织的经典方法主要依赖形态学技术。为了定量异常情况并在亚细胞水平研究组织疾病的发病机制，我们将蔗糖密度梯度离心分析亚细胞分级分离与组织酶活性微量分析相结合。讨论了对毫克级组织进行这些研究的方法学问题。提供了适用设备的详细信息，并描述了其在人类肝脏标本研究中的应用。作为这种方法的一个例子，讨论了对原发性和继发性肝溶酶体贮积病患者组织进行的生化和亚细胞分级分离实验。对溶酶体变化的检查表明，酶活性增加在这些疾病中是常见现象，但只有当有证据表明溶酶体脆性增强且降解酶细胞内释放时才会发生组织损伤。列出了已证明可用这种方式进行研究并在其疾病调查中取得有益结果的其他组织。
