Hypozincemia was induced in rats by Salmonella typhimurium and live vaccine strain Francisella tularensis (LVS) infections. Hepatic synthesis of zinc-binding proteins (ZBP) was studied in order to elucidate the mechanisms involved in the redistribution of zinc from plasma to liver occurring during infectious illness. ZBP, labeled in vivo with 65Zn, were isolated and identified as metallothioneins based, in part, on their heat stability, dimorphism, and amino acid composition. Cysteine was the major amino acid found in both forms of metallothionein and constituted 28-31% of total residues. The apparent half-life of these proteins as measured by disappearance of 65Zn was determined to be 19 h in a relatively mild infection (LVS) and 38 h in a more severe S. typhimurium infection. Results provide evidence that metallothioneins not only have the previously postulated regulatory role in normal zinc homeostasis but are intimately involved in the zinc redistribution occurring during the acute stage of infectious illness.
Two patients with Fabry's disease were infused with normal plasma to provide active enzyme (ceramide trihexosidase) for hydrolysis of the plasma substrate, galactosylgalactosylglucosylceramide. Maximum ceramide trihexosidase activity occurred 6 hours after infusion of the plasma, attaining a level approximately 150 percent of that in normal plasma; enzymatic activity was detectable for 7 days. The amount of accumulated substrate in the plasma of these recipients decreased about 50 percent on day 10 after infusion. Thus, periodic replacement of ceramide trihexosidase activity in the plasma of patients with Fabry's disease might lead to consistently lower amounts of substrate in the plasma and a decrease in its rate of accumulation in tissues.
The systemic injection of rabbit leukocyte-derived factors into rats has been shown to depress plasma iron (1) and zinc (2) values, increase plasma copper concenz trations (3), enhance flux of amino acids to the liver (4, 5), and increase synthesis of acute-phase globulins (4). Kampschmidt et al. (6) intracisternally injected rabbit LEM into rats and observed a decrease in plasma iron concentration and an increase in blood neutrophils. Intracisternal injections of LEM into rabbits produced a marked fever at much lower doses than if given systemically, suggesting a primary site of action in the central nervous system (7). Depending upon the procedure of isolation, leukocytederived factors have been referred to as endogenous pyrogen , leukocyte pyrogen, or leukocytic endogenous mediator. Because of the multiplicity of activities associated with this crude preparation, the term "leukocyte endogenous mediator" (LEM) was assigned to these unpurified substances.Rabbit LEM was tested in rat 2B comparable with the majority of the work being done in this area, because Kampschmidt and Upchurch were unable to show a leukocytic pyrogen from rat polymorphonuclear leukocytes (8). LEM obtained from glycogen-induced peritoneal exudates in rabbits was injected into the lateral cerebral ventricle of rats in the present study to determine if alterations in plasma trace metal concentration, amino acid flux, and acute-phase
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