Myron Pollycove

Iron metabolism in Wilson's disease: Kinetic studies with iron59

THE METAmLIsbi OF IRON in Wilson’s disease has not received much attention, although several reports over the past forty years or more have indicated that an important relationship exists. In 1922, Lowyl reported excess storage of iron in the liver, a finding reiterated in 1958 by Butt and his co-workers.2 Cartwright and co-workers3 and Walshe4 reported the occurrence of hemolysis in patients with Wilson’s disease. Wiseman; found evidence of a relationship between the absorption of copper and iron from the gastrointestinal tract. Goldberg and colleaguess had shown that an excess of copper produced hemolytic anemia in animals, and, perhaps more relevant to Wilson’s disease, Lahey and associates7 had found that copper-deficient animals may develop a severe anemia morphologically similar to anemia of iron deficiency. There is experimental evidence that ceruloplasmin and iron may act in a coupled oxidation sy~tem~.~ and that ceruloplasmin may be involved in oxidation of ferrous iron to ferric iron preparatory to formation of a ferric-transferrin complex.1° Decreased serum iron levels in one of our patients with Wilson’s disease, a finding similar to that reported by Tschabitscher and Schinko,” led to the studies reported here.

Decreased de novo DNA-Thymine Synthesis and Increased Thymidine-3H Incorporation into DNA by Human Bone Marrow Cultured with Aminopterin.

Summary When incubated with normal human bone marrow cells in the presence of 624 L-serine-3-14C and thymidine-3H, aminopterin decreases de novo synthesis of DNA-thymine-14C to 16%, while incorporation of thymidine-3H into DNA is increased to 140% of control values. These results are interpreted as evidence for increased utilization of preformed thymidine in DNA synthesis in the presence of aminopterin. The possible mechanisms for this increased incorporation of preformed thymidine into DNA in the presence of aminopterin are discussed.

Determination of Regional Blood Flow in Gastrointestinal Tract of Intact Animals

Summary A technic is described for estimating regional blood flow in the gastrointestinal tract. This method utilizes the short range of the beta particle in tissue to limit the blood volume monitored by a special Geiger-Muller tube placed in the intestinal lumen.

Detection of the carrier of Wilson's disease

SUMMARYWhole-body counting over a three- to four-week period following the intravenous administration of copper 67 in 11 normal volunteers, 2 neurological control patients, 7 control subjects with cirrhosis, and 10 homozygotes and 7 heterozygotes of Wilsons disease showed that whole-body retention of radio-copper was prolonged in the wilsonian subjects, both homozygous and heterozygous, and in cirrhotic patients with ascites or hepatocellular failure or both. If the latter can be excluded, prolonged whole-body retention of radiocopper serves to identify the presence of the abnormal gene or allele of Wilsons disease. Because of overlap, it is not possible to distinguish the heterozygote from the homozygote by whole-body counting alone. External probe counting over the liver and muscle, carried out in 5 control subjects, 8 homozygotes, and 5 heterozygotes, revealed abnormal hepatic uptake with little apparent release of radiocopper and usually evident uptake in muscle in the homozygotes and reasonably normal hepatic uptake with delayed release and no apparent muscle uptake in the heterozygotes, compared with the control subjects. It appears that external monitoring of hepatic and muscle radioactivity, in addition to whole-body turnover measurements after intravenous copper 67, permits more accurate determination of the genetic status of individuals in respect to Wilsons disease.