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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between food iron absorption, iron stores, and plasma iron level was studied. On a low iron diet subjects with idiopathic hemochromatosis (IH) during reaccumulation of iron after phlebotomies showed a fall in plasma iron. Fortification of the diet with 22--135 mg of iron/day for 3 days caused little or no change in the plasma iron in subjects with normal iron stores, whereas in subjects with iron deficiency a significant rise in plasma iron occurred with the addition of 45 mg of iron/day. In subjects with IH with normal iron stores, plasma iron increased with the addition of 22.5 mg/day. These studies indicate that iron absorption is an important determinant of the elevated plasma iron in IH and that the plasma iron tolerance test combined with the serum ferritin may be used to detect excessive absorption of iron.
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PMID:Influence of food iron absorption on the plasma iron level in idiopathic hemochromatosis. 9 52

(1) Brief introduction to iron metabolism and the biochemistry of ferritin. (2) Early studies of circulating ferritin. (3) Methods for measuring serum ferritin concentrations -- immunoradiometric, radioimmuno- and enzyme-linked immuno assays based on liver or spleen ferritin -- an evaluation of these techniques. (4) Serum ferritin concentrations in normal subjects -- definition of normality -- relationship between storage iron and serum ferritin concentrations -- changes during development from birth to old age -- iron deficiency -- variability of serum ferritin concentration -- evaluation of use of ferritin assay for assessment of storage iron levels. (5) Serum ferritin concentrations in disease -- hemochromatosis -- secondary iron overload -- liver damage -- infection and chronic disease -- cancer. (6) Assay of serum ferritin with antibodies to ferritins other than liver or spleen -- ferritinemia and cancer. (7) Properties of serum ferritin -- molecular weight -- iron content -- isoelectric focusing patterns -- carbohydrate content -- immunological properties. (8) Physiology of circulating ferritin -- release of ferritin from tissues -- origin of circulating ferritin -- clearance from the plasma -- iron and protein turnover. (9) Summary -- factors influencing serum ferritin concentrations and clinical use of ferritin estimations.
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PMID:Serum ferritin. 37 39

The relationship between serum ferritin and duodenal ferritin was examined in normal subjects and in patients with iron deficiency, secondary iron overload, or idiopathic hemochromatosis (IHC). A positive correlation between serum ferritin and duodenal ferritin concentrations was found in all groups. In the iron-overload conditions, duodenal ferritin concentration was lower at all levels of serum ferritin in comparison with normal and iron-deficient subjects. Patients with secondary iron overload did not differ from those with IHC, which indicates that any decrease in duodenal ferritin concentration was secondary to the excess body iron stores. Purified duodenal ferritin from normal subjects and patients with iron-overload conditions showed the same two distinct isoferritins by isoelectric focusing. After the oral administration of iron, two additional isoferritins were detected. These resembled the major isoferritins of liver.
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PMID:Duodenal ferritin content and structure: relationship with body iron stores in man. 66 70

Five genetic traits in man and laboratory animals have major effects on iron transport. The heterogeneous condition, hemochromatosis, in some families appears to segregate as a Mendelian trait, and is associated with defective control of intestinal iron absorption. In the very rare human autosomal recessive trait, atransferrinemia, there is an almost total lack of transferrin and gross maldistribution of iron through the body. In mice, sex-linked anemia (an X-linked recessive trait) causes iron deficiency through defective iron absorption, at the "exit" step; a similar defect probably exists in placental iron transfer. In microcytic anemia of mice, an autosomal recessive trait, iron absorption is also impaired because of a defect of iron entry into cells, which is probably generalized. Belgrade rat anemia, less understood at present, also may involve a major disorder of iron metabolism. Study of these mutations has provided new knowledge of iron metabolism and its genetic control Their phenotypic interaction with nutritional factors, especially the form and quantity of iron in the diet, may provide new insights for the study of nutrition.
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PMID:Genetic defects of iron transport. 78 24

Iron deficiency is one of the most serious nutritional problems confronting the United States and the world today. An understanding of the mechanisms operative in the control of uptake and utilization of iron is essential to develop suitable prophylactic and therapeutic strategies. Iron excess can also be a serious health hazard. Studies on Bantu siderosis, hemochromatosis and other overload pathologies also provide insight into the intake and storage of this metal. Several models for iron transport across the mucosal membrane are developed. The most satisfactory seems to involve chelation of the iron to provide solubility diffusion passively across the gut membrane, and equilibrium binding to various storage sites within the tissue. Both ferric and ferrous forms are available. The solution chemistry of iron governs its biological behavior. Low-molecular-weight compounds present in normal dietary foodstuffs, as well as those prepared synthetically, can enhance the uptake of oral iron. Suitable application of complexes of iron with fructose, nitrilotriacetate, citrate and other molecules should be efficacious in the treatment of iron deficiency anemia. Potential dangers of food fortification with iron are acknowledged, and application of immunoassay techniques for measuring circulating ferritin suggest it as a rapid and inexpensive monitor for overload.
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PMID:Tired blood and rusty livers. 125 66

To gain insights at the molecular level into the expression of iron-regulated genes [transferrin (Tf), transferrin receptor (TfR), and ferritin H and L subunits] in human intestinal areas relevant to iron absorption, the steady-state levels of specific messenger RNAs (mRNAs) were analyzed in gastric and duodenal samples obtained from 6 normal subjects, or 10 patients with anemia, 14 patients with untreated iron overload, and 8 patients with various gastrointestinal disorders. No Tf mRNA was detected in human gastroduodenal tissue, confirming earlier findings in the rat. In normal subjects, although higher levels of ferritin H- and L-subunit mRNAs were consistently found in duodenal than in gastric samples, no differences in the content of TfR transcripts were detected. However, a dramatic increase in TfR mRNA levels was specifically found in duodenal samples from subjects with mild iron deficiency but severe anemia. This response of the TfR gene is presumably secondary to decreased cellular iron content due to its accelerated transfer into the bloodstream, as also indicated by the low levels of ferritin subunit mRNAs found in the same tissue samples, and is not linked to faster growth rate of mucosal cells because no changes in duodenal expression of histone, a growth-related gene, were detected. In patients with secondary iron overload, a down-regulation of duodenal TfR gene expression and a concomitant increase in ferritin mRNA content were documented. On the contrary, a lack of TfR gene down-regulation and an abnormally low accumulation of ferritin H- and L-subunit mRNAs were detected in the duodenums of subjects with idiopathic hemochromatosis. Whether these molecular abnormalities in idiopathic hemochromatosis are relevant to the metabolic defect(s) of the disease is presently unknown.
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PMID:Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum. 153 99

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated from the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.
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PMID:Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation. 250 4

The currently accepted concept of iron absorption proposes first the entry of iron into the intestinal mucosal cell through the brush border membrane. It is a relatively slow process. In the cell, the iron may be transferred to plasma or become sequestered by ferritin. The latter becomes unavailable for transfer to plasma and is exfoliated and excreted. In iron deficiency and idiopathic hemochromatosis, the rate of iron uptake into the intestinal mucosal cell is increased and entry into ferritin is decreased, whereas the rate of transfer to plasma remains constant. The reverse occurs in case of secondary iron overload. It is currently accepted that a transferrin, whose levels increase in iron deficiency, enters the intestinal lumen from the liver via bile, where it may sequester iron and bring it into the cells by the process of endocytosis. Iron presented as inorganic ferric or ferrous salts may also be absorbed, though the more soluble ferrous salts are adsorbed much more rapidly. Heme iron is absorbed very effectively, though it is not subject to regulation by the individual's iron status to the same extent as is inorganic iron absorption. Brush border membranes apparently contain saturable iron receptors for inorganic iron, but whether or not the absorption process requires energy is an open question. Absorption of iron may also be affected by its availability; different food components affect iron absorbability to a different extent.
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PMID:Biochemistry of nonheme iron in man. II. Absorption of iron. 266 38

Fluorescently labeled antibodies were used to identify transferrin receptors and mucosal transferrin in human gastrointestinal biopsy sections. Transferrin receptors were evident in the villous epithelium and the crypt areas of duodenum, ileum, and colon, predominantly in the basal-lateral area. In 7 subjects with low iron stores, the intensity of duodenal villous staining for receptor, on a scale of 0-4, was 2.1 +/- 0.3 (mean +/- SD). This value was significantly higher than the value in 13 subjects with normal iron stores (1.1 +/- 0.4). In 5 patients with hereditary hemochromatosis, duodenal transferrin receptor staining was not significantly different from that in the subjects with normal iron stores. Transferrin staining was found in the apical cytoplasm of epithelial cells in the duodenum, ileum, and colon, but observer assessment was not sufficiently reproducible to make a quantitative analysis. Our results suggest that iron deficiency is accompanied by an increase in transferrin receptors in duodenal absorptive cells, and the genetic lesion in hemochromatosis does not involve an increase in transferrin receptors in the intestinal mucosa compared with subjects with normal iron stores.
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PMID:Transferrin receptors in the human gastrointestinal tract. Relationship to body iron stores. 301 5

There is increasing evidence that both iron overload and iron deficiency are associated with significant abnormalities of immune function. In diseases associated with iron overload there is increased susceptibility to both infection and neoplasia. The precise mechanisms are still being unravelled but iron overload has been shown to impair antigen-specific immune responses and to reduce the number of functional helper precursor cells. Similarly, iron in vitro in concentrations reported to be present in the serum of patients with iron overload impairs the generation of cytotoxic T-cells, enhances suppressor T-cell activity and reduces the proliferative capacity of helper T-cells. The predominant tumor seen in iron overload is primary hepatocellular carcinoma; however other aetiological factors appear to be involved in addition to iron overload, especially hepatic cirrhosis. Nevertheless, primary liver cancer occurs much more frequently in hemochromatosis than in other forms of cirrhosis. Iron deficiency is associated with an altered response to infection but the relationship is again a complex one. The cellular mechanisms involved have yet to be clearly defined, although impaired T and B cell function have been demonstrated.
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PMID:Iron status and cellular immune competence. 328 53


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