Department of Pathology, The New York Hospital-Cornell Medical Center, New York.
J Exp Med. 1959 Oct 31;110(5):801-10. doi: 10.1084/jem.110.5.801.
Goldfish kept in water containing ionized copper and a detergent added with the aim of decreasing coagulation of the mucus on the gills, took in and retained this metal in their brains, livers, and kidneys, in concentrations comparable to those that occur naturally in Wilson's disease, as chemical assays disclosed. Histochemical studies made it clear that much copper had accumulated within the large neurons, principally in those of the telencephalon and anterior horn region of the spinal cord and in the tubular epithelial cells of the kidneys, the nuclei of the parenchymal cells of the liver, the sarcoplasm of the skeletal muscle, and in the epithelial covering of the gills. The intraneuronal deposition of copper was regularly associated after a time with conspicuous cytologic changes, notably contraction and hyperchromaticity of the nerve cells with tortuosity and fragmentation of the axis cylinders and lysis and loss of neurons. The accumulation of metal in the renal epithelium was frequently accompanied by necrosis and was regularly associated with hyperplasia and calcification of the epithelial cells of the larger renal tubules in all goldfish kept for prolonged periods in copper-rich water. The deposition of copper in the liver was not accompanied by consistent cytologic changes. The similarity of the cytologic alterations induced in the central nervous systems by copper and those that occur naturally in hepatolenticular degeneration in human beings provides evidence that copper itself plays an important role in the pathologic alterations of the brain in Wilson's disease.
金鱼饲养在含有铜离子和清洁剂的水中，目的是减少鳃黏液的凝结。化学分析显示，这些金鱼的大脑、肝脏和肾脏中会吸收并保留这种金属，其浓度与威尔逊病中自然发生的浓度相当。组织化学研究清楚地表明，大量的铜在大神经元内积累，主要是在端脑和脊髓前角区域的神经元以及肾脏的管状上皮细胞、肝脏实质细胞的核、骨骼肌的肌浆和鳃的上皮覆盖物中。随着时间的推移，铜在神经元内的沉积通常与明显的细胞学变化相关，特别是神经细胞的收缩和嗜碱性增加，轴突扭曲和碎片化，以及神经元的溶解和丧失。金属在肾上皮中的积累经常伴随着坏死，并且在所有长时间饲养在富含铜的水中的金鱼中，经常伴随着较大的肾小管上皮细胞的增生和钙化。铜在肝脏中的沉积并不伴随着一致的细胞学变化。铜在中枢神经系统中引起的细胞学改变与人类肝豆状核变性中自然发生的改变相似，这为铜本身在威尔逊病中大脑的病理改变中发挥重要作用提供了证据。
