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Studies of Diagnosis and Pathogenesis of Wilson’s Disease

  • Xiuling Leung
  • Rong Chen
  • Zhoulin Liu
  • Yinru Zhang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 363)

Abstract

We have studied the copper and metallothionein (MT) atin culture skin fibroblasts of patients and heterozygotes with Wilson’s disease (WD) and controls (5 cases each) after incubation in mediums containing various concentrations of copper (C1: 15.74 μmol/L, C2: 78.70 μmol/L, C3: 157.38 μmol/L, C4: 314.76 μmol/L).tiThe results are as follows:
  1. 1.

    In each of the three groups, the copper/protein ratio (Cu/P) in cytosols of vn1–5 passages is significantly higher than that of 6–10, 11–15, 16–20 passages. There are no significant differences among 6–10, 11–15 and 16–20 passages.

     
  2. 2.

    In standard medium, Cu/P in cytosols of three groups are not significantly different, but Cu/P of patients is significantly higher than that of the other two groups after incubation in C4 medium for 12 or 24 hours.

     
  3. 3.

    After incubation in C1, C2, C3 and C4 mediums respectively, the Cu/P in cytosols of the three groups only increased in C4 medium with time (within 72 hours). It is higher in the patient group than the other two groups.

     
  4. 4.

    In the three groups, cytosol copper distributed similarly in two peaks after Sephadex G-75 chromatography, which are on high molecular weight (HMW) proteins and MT fractions respectively. It remained the same after incubation in various concentrations of copper. The copper content found in MT fractions in WD patients is much higher than that of controls and heterozygotes. It is even higher after incubation in various concentrations of copper but no changes was found in controls and heterozygotes.

     
  5. 5.

    The MT contents were not significantly different in cytosols of the three groups when cultured in standard medium. However, they were all elevated in the three groups after incubation in C4 medium but not in C1, C2 and C3 mediums. WD patients showed higher MT contents than the other two groups.

     
The results of our experiments suggest that:
  1. 1.

    The copper content is stabled in 6–20 passages of cultured skin fibroblasts in the three groups. The skin culture fibroblasts are ideal for further studies of copper metabolism of WD.

     
  2. 2.

    The copper content measurement in cytosol of culture skin fibroblasts in C4 medium for 12 or 24 hours can be used in distinguishing WD patients from heterozygoates and normals. Yet the copper contents in cytosols of the WD patients differ from those of the heterozygotes and normals only when culture in C4 medium but not the standard ones.

     
  3. 3.

    The deposition of copper in cytosol of WD patient fibroblasts is highly related to MT.

     
  4. 4.

    The MT in WD patients may have an abnormal high inductivity by copper, which might also play an important role in the copper deposition in WD cells.

     

Keywords

Copper Content Skin Fibroblast Standard Medium Copper Deposition Wilson Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Xiuling Leung
    • 1
  • Rong Chen
    • 1
  • Zhoulin Liu
    • 1
  • Yinru Zhang
    • 1
  1. 1.Department of Neurology 1st Affiliated HospitalSun Yat-sen University of Medical SciencesGuangzhouPeople’s Republic of China

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