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  • Title: Intrahepatocellular localization of copper in Wilson's disease.
    Author: Yano M, Sakamoto N, Takikawa T, Hayashi H.
    Journal: Nagoya J Med Sci; 1993 Mar; 55(1-4):131-7. PubMed ID: 8247102.
    Abstract:
    It is well known that excess copper plays a role in the pathogenesis of Wilson's disease; however, the hepatic copper contents, determined either histochemically or biochemically, are not always correlated with the activity of Wilson's disease. To better understand copper-induced cytotoxicity, intrahepatocellular localization of copper was studied in five patients with Wilson's disease. The liver specimens were obtained by biopsy to confirm the clinical diagnosis of Wilson's disease before treatment. Neither hepatic copper content nor histochemical copper deposits were correlated with any of the biochemical indices studied. Energy-dispersion X-ray microanalysis was done on the nuclei, lysosomes and lysosome-free cytoplasm of hepatocytes. Lysosomes had the highest Cu X-ray intensity but no correlation was shown between the lysosomal copper content and biochemical indices. The nucleus/lysosome-free cytoplasm ratio of the copper content was correlated with the serum levels of aminotransferases. These results suggest that the copper increasing gradient from the lysosome-free cytoplasm to the nucleus is associated with hepatocyte necrosis, and probably causes irreversible nuclear damage.
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