By Gunter Weiss, Victor R. Gordeuk, Chaim Hershko
This ebook summarizes the most up-tp-date study at the anemia of continual affliction and identifies powerful diagnostic options for this universal medical condition-covering key subject matters on the topic of the layout and choice of healing strategies together with the remedy of the underlying illness, the biology of erythropoietin and the legislation of erythropoiesis, the disturbance of iron homeostasis, and the advanced nature of the systemic inflammatory reaction.
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Extra resources for Anemia of Chronic Disease (Basic and Clinical Oncology)
The association of HFE mutations with hereditary hemochromatosis (20) suggests that HFE, which is primarily 14 Pantopoulos expressed in gastric epithelial cells, circulating monocytes and tissue resident macrophages (77,78), performs an important regulatory function in systemic iron metabolism. As HFE can modulate cellular iron metabolism, it is conceivable that it may also control the iron status of precursor enterocytes and macrophages. This may be critical to program differentiating mucosal cells for dietary iron absorption upon maturation and to control iron release from macrophages by regulating the expression of genes involved in iron transport (43).
Iron also directly participates in a mechanism for oxygen sensing. Cells of higher eukaryotes respond to reduced oxygen availability by activation of the hypoxia inducible factor (HIF) that controls the transcription of a wide array of genes involved in erythropoiesis, angiogenesis, cell proliferation=survival, glycolysis, and iron metabolism. The expression of HIF is regulated at the level of protein stability. Under normoxic conditions, the oxygen-sensitive subunit HIF-1a is hydroxylated at P402 and P564 within two functionally independent degradation domains.
Similarly, a mutation resulting in a premature stop codon (K264X) accounts for the chardonnay (cdy) phenotype in zebrafish (60). Taken together, in these animal models, defects in DMT1 activity lead to iron deficiency and severe hypochromic microcytic anemia. Defective expression of hephaestin in hemizygous male sex-linked anemia (sla) mice is also associated with microcytic anemia due to inefficient iron delivery to the circulation (56). 12 Pantopoulos The important function of ceruloplasmin in body iron metabolism is evident by the severe iron overload associated with human aceruloplasminemia (61,62).