An elevated serum iron is commonly found in patients with infectious hepatitis (1-4) and evidence has been presented (5, 6) that acute hepatocellular necrosis, regardless of its etiology, is invariably accompanied by a rise in serum iron. A close time relationship between elevation of the serum iron and actual disintegration of liver cells has been found (6), and the hyperferremia has been attributed to a release of storage iron from the dying liver cells. As the iron is largely stored in the liver as ferritin, it was of interest to investigate whether ferritin is released into the peripheral blood of patients with acute hepatocellular disease, while it could not be demonstrated in the blood of normal individuals (7).Mazur, Shorr, and Baez (8-10) have reported the presence of VDM, which is said to be identical with ferritin, in the peripheral blood in several conditions including hepatic cirrhosis, congestive heart failure and shock. The concentrations of this vasoactive material were so minute that their detection required the use of the mesoappendix bioassay. We were, in this study, concerned with a possible relationship between serum iron rise and the release of ferritin iron from the necrotic liver cells. METHODSCrystalline ferritin-apoferritin was prepared from human liver tissue (autopsy material) according to the method of Granick (7). The crude ferritin was recrystallized five times with CdSO4, reprecipitated at 50 per cent saturation with (NH4),SO4, and dialyzed against tap water for 24 hours. At that time the preparation was usually free of NH4 ions.The antiserum was prepared according to the procedure of Mazur and Shorr (8). Rabbits were injected intravenously with aluminum precipitated human ferritin over a period of four weeks. Each animal received a total of 4.4 mg. of antigen nitrogen, and thereafter booster injections of 0.15 mg. of antigen nitrogen. The antisera were chilled, sharply centrifuged and pooled. The antiferritin titer of the antiserum was determined by adding known amounts of ferritin dissolved in human serum to one cc. of the 1: 10 diluted antiserum. The mixture was incubated for one hour at 370 C. and stored for three days at 40 C. The tubes were then centrifuged, the precipitate washed with chilled saline, and the iron and nitrogen in the precipitate were measured. The supernatant was tested for excess of antigen or antibody.The iron content of ferritin was measured by Scott's method (11). Other iron methods employed were the methods of Wong (12), of Barkan and Walker (13) and a modification of the latter as described below.The ferritin determination in the blood of patients was carried out in the following manner: The blood was collected in iron free tubes and the serum was sharply centrifuged to remove all red cells. Four cc. of this serum was added to 0.3 of antiserum, to 0.3 of 1: 3 diluted antiserum, and to 0.3 cc. of normal rabbit serum, respectively.After one hour of incubation at 370 C. and three days' storage at 4°C., the tubes were centrifuged. When ferritin was present...
(1) Protein deprivation in rats resulted in a rapid depression of iron incorporation. The depression reached its maximum within 6 days. Realimentation with protein was followed within 3 days by a return of iron incorporation to normal values. (2) Red cell mass declined during protein starvation in a linear fashion, indicating a removal of senescent red cells after a life span of 70 days. The increasing severity of the anemia of protein starvation is the cumulative result of this removal in the absence of any significant replacement. (3) Daily injections of 1.3 units of erythropoietin prevented a decrease in red cell mass over an observation period of 28 days of protein starvation. (4) Diminished erythropoietin formation or retardation of protein synthesis in erythroid precursors due to lowered substrate concentration are considered as possible causes of erythropoietic depression.
(1) Rats on a normal and non-protein diet were hypertransfused to suppress their endogenous erythropoietin formation. Injection of erythropoietin elicited nearly identical increases in radioiron incorporation in the two dietary groups. (2) Normal and protein-starved rats were exposed to lowered atmospheric pressure. At each level of hypoxia the erythropoietin titer in the plasma of protein-starved rats were significantly lower than those in normal diet groups. (3) Re-proteinization resulted in significant increases in erythropoietin level. (4) It is concluded that protein deficiency does not affect cytoplasmic protein synthesis in erythroid precursors directly, and the depression of erythropoiesis is attributed to a diminished formation of erythropoietin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.