Use of a Stable Copper Isotope (65Cu) in the Differential Diagnosis of Wilson's Disease

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14–26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32–77 days). 3. The incorporation of 65Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Low temperature regulation of antifreeze glycopeptide levels in Atlantic cod (Gadus morhua)

The influence of water temperature and photoperiod on the timing of the annual cycle of plasma antifreeze glycoproteins (AFGP) was examined in Atlantic cod. Long day lengths (18 h) or continuous light had no effect on the time of appearance or disappearance of AFGP from the plasma. Cold water (0 °C) advanced the time of AFGP appearance by as much as 100 days. Long day lengths had no effect on this early induction of AFGP production. AFGP was not detectable in the plasma of fish exposed to water temperatures greater than 1 °C. Although small amounts of AFGP did appear in the plasma of cod exposed to 1 °C, it immediately began to disappear while plasma levels in normal and 0 °C acclimated cod continued to rise. The biological half time of AFGP activity was very sensitive to temperature, ranging from 15.6 days at 5 °C to 99.4 days at 0 °C. The results of this study suggest that the appearance of AFGP in cod during the winter months is dependent on the cod's exposure to water temperatures at least as low as 1 °C. Although 1 °C appears to be capable of initiating production of AFGP, it is not low enough to allow normal protective levels to be built up in the plasma.