Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increase in serum ferritin, which occurs in 40 to 70% of chronic alcoholics, remains poorly understood. We tested the hypothesis which links hyperferritinemia in chronic alcoholism not only to ferritin release from damaged liver cells, but also to increased ferritin secretion. Fifty-eight chronic alcoholic patients hospitalized for alcohol withdrawal were subdivided into three groups according to liver damage. Their serum levels of ferritin and ferritin bound to concanavalin A (ferritin Con A, which represents glycosylated, i.e., secreted ferritin) were measured serially on days 1, 7, and 11 of withdrawal and compared with a control group. The results were: (1) Total serum ferritin increased in alcoholics. Both free and Con A ferritins increased in equal proportions, the ferritin Con A to total ferritin ratio remaining unchanged. The increase was dependent on liver disease, as both free and Con A ferritins increased significantly with the severity of liver illness. Serum ferritin levels were related to iron status: it correlated with hepatic iron concentration (obtained in 19 patients); however, high ferritin values were not related to the degree of iron overload, which remained low. Finally, there was no correlation between serum ferritin and the average of alcohol consumption. (2) Both free and Con A ferritin decreased by about 40% during alcohol withdrawal. In conclusion, we have demonstrated that (1) total serum ferritin is increased in chronic alcoholism and (2) that this ferritin increase is due in part to an increase in ferritin Con A, proof of the induction of ferritin secretion by alcohol in humans.
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PMID:Increase in glycosylated and nonglycosylated serum ferritin in chronic alcoholism and their evolution during alcohol withdrawal. 168 73

To clarify the pathogenesis of hepatic iron toxicity, we investigated the effect of chronic dietary iron overload on the expression of several genes in rat liver. After 10 wk of iron treatment, when only minor histological features of liver damage were appreciable, the level of pro-alpha 2(I)-collagen mRNA was already higher than in control liver and increased further at 30 wk of treatment. Also, the relative amount of L ferritin subunit mRNA was enhanced early by iron load and was even more elevated at the latest time point considered, whereas neither H ferritin subunit nor transferrin mRNA levels were affected by iron treatment. In contrast, after chronic iron treatment, no variations were found in the steady-state level of mRNAs transcribed from liver-specific and preferentially expressed genes (albumin, alpha-fetoprotein, apolipoprotein A-1), growth-related genes (c-myc, c-Ha-ras and c-fos) and stress-induced genes (heat shock protein 70). These results suggest that chronic dietary iron overload in rats can specifically activate target genes in the liver (i.e., L ferritin and procollagen) in the absence of either histological signs of severe liver damage or alterations in differentiated liver functions.
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PMID:Liver gene expression during chronic dietary iron overload in rats. 169 54

174 serum ferritin assays in 121 patients with various haemolytic disorders have been performed. The mean serum ferritin levels were significantly increased in all these disorders in contrast to healthy controls. The highest serum ferritin levels were found in pyruvate kinase (PK) deficiency, moderate increase was observed in hereditary sphaerocytosis (HS) and in autoimmune haemolytic anaemia (AIHA) with massive haemolysis and in glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Mild elevation of serum ferritin levels was depicted in paroxysmal nocturnal haemoglobinuria (PNH), in beta thalassaemia minor and in other types of haemoglobinopathies. The range of values was associated with a degree of haemolysis and its relation to duration of the disease was not apparent in most cases. Highly significant differences between serum ferritin levels in splenectomized and non-splenectomized patients with HS and between serum ferritin levels in patients with AIHA with massive haemolysis or in remission were found. As compared to normal controls, significant increase of serum ferritin levels was observed even in patients with AIHA in remission or in splenectomized patients with HS. In two patients with PK deficiency the levels exceeding 2,000 micrograms/l indicated manifest iron overload. A reliability of serum ferritin assay as an index of iron stores in haemolytic disorders has been discussed.
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PMID:Serum ferritin in patients with various haemolytic disorders. 169 23

Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.
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PMID:Current concepts in rational therapy for haemochromatosis. 171 64

The ability of lymphocytes to utilise iron from different sources has been investigated. Iron uptake from transferrin by proliferating lymphocytes gradually increased as saturation of the protein with iron was increased up to 100%, but rose sharply when addition of further iron resulted in the presence of non-transferrin bound iron. Increasing the saturation of transferrin with iron caused an increased rate of proliferation up to about 100% saturation but when the level of iron present exceeded the binding capacity of the protein, proliferation decreased and at high levels of iron it was reduced below that seen in the absence of transferrin. Comparison of the degree of iron uptake from transferrin and from iron chelators showed that the hydrophilic chelator ferric nitrilotriacetate (FeNTA) donated larger amounts of iron to cells than did transferrin or the lipophilic chelator ferric-pyridoxal isonicotinoyl hydrazone (FePIH), but did not promote proliferation, and when present in high amounts caused inhibition. In contrast, FePIH supported proliferation as efficiently as transferrin. In cells cultured with FeNTA, iron was found predominantly in an insoluble form while in the cells cultured with Fe-transferrin or FePIH the largest proportion of iron was found in the non-ferritin high molecular weight fraction, which probably represents iron in enzymes and other metabolically-important proteins. In no case did iron associated with ferritin exceed 15% of the total uptake, and the cells showed no marked increase in synthesis of ferritin in response to any of the forms of iron. These results indicate that different forms of iron are handled in different ways by lymphocytes, and that iron delivered from hydrophilic chelates may be toxic and not readily available for metabolic use. Lymphocytes appear to be poorly equipped to sequester excess iron in ferritin, and this may account for abnormalities in the immune system reported in patients with iron overload.
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PMID:Uptake and intracellular handling of iron from transferrin and iron chelates by mitogen stimulated mouse lymphocytes. 173 57

To assess the clinical value of human leukocyte antigen typing in the diagnosis and management of hereditary hemochromatosis, 105 siblings of 35 proband cases of hemochromatosis were retrospectively analyzed to study whether the exclusion of human leukocyte antigen typing would have adversely affected management. All siblings and probands had already been tested for human leukocyte antigen-A and human leukocyte antigen-B typing, serum ferritin and transferrin saturation. The median age of siblings was 55 yr (range = 11 to 82). Siblings were categorized according to putative genotype (homozygote, heterozygote and normal) using human leukocyte antigen typing. Phenotypic expression of hemochromatosis was considered to be iron overload as indicated by an elevated ferritin (male = greater than 350 micrograms/L, female = greater than 200 micrograms/L) and/or transferrin saturation (greater than 55%). Six of 37 homozygotes had a normal ferritin and transferrin saturation, with five of these patients under 32 yr old. No putative heterozygotes with both an abnormal ferritin and transferrin saturation were seen, although 12 of 48 (25%) heterozygotes had either an elevated ferritin or transferrin saturation. Twenty of 20 normal siblings had a normal ferritin and transferrin saturation. To assess the cost of screening with and without human leukocyte antigen typing, a cost model simulation was used that compared the costs of both methods in a hypothetical family (proband, homozygote, heterozygote and normal sibling).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human leukocyte antigen typing of siblings in hereditary hemochromatosis: a cost approach. 173 29

Human serum has been shown to be bactericidal for most strains of Yersinia enterocolitica. Systemic Y enterocolitica infections have been reported in iron-overloaded hemodialysis patients treated with deferoxamine. Both iron and deferoxamine are known to enhance the growth of Y enterocolitica. We inoculated sera from 12 hemodialysis patients whose serum ferritin levels ranged from 26 to 6,855 micrograms/mL (ng/mL), as well as three controls, with Yersinia organisms. After latencies of 0 to 24 hours, inoculated sera were then plated on blood agar. Bactericidal activity was demonstrated in all sera and the degree of activity did not correlate with ferritin levels. Bactericidal activity was also demonstrated in sera from three deferoxamine treated patients. We conclude that in vitro, sera of end-stage renal failure patients, with and without iron overload, are as bactericidal as control sera for Y enterocolitica and that deferoxamine therapy does not interfere with that bactericidal activity.
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PMID:Serum bactericidal activity for Yersinia enterocolitica in hemodialysis patients: effects of iron overload and deferoxamine. 173 96

To further evaluate a possible abnormality in the reticuloendothelial cells in hemochromatosis, the binding of a monoclonal anti-human liver ferritin antibody to monocytes was studied in 19 patients with hemochromatosis, 8 patients with secondary iron overload, 1 patient with hyperferritinemia without iron overload, and 15 normal volunteers. Binding of the antibody to the monocytes was analyzed using a fluorescence-activated cell sorter (FACS). Binding of the anti-ferritin antibody to monocytes was demonstrated in 34.7 +/- 4.5% (mean +/- standard error) of the monocytes in untreated hemochromatosis patients (mean serum ferritin = 2294 +/- 415 micrograms/L), 6.75 +/- 2.03% in treated hemochromatosis patients (mean serum ferritin = 263 +/- 85 micrograms/L), 12.3 +/- 2.7% of the monocytes in the secondary iron overload patients (mean serum ferritin = 2476 +/- 867 micrograms/L), 4.1% in the patient with hyperferritinemia (serum ferritin = 1192) and 4.1 +/- 0.5% of the monocytes in the normal volunteers (mean serum ferritin = 55.2 +/- 11.9 micrograms/L). % binding of anti-ferritin antibody was significantly greater in hemochromatosis patients compared to patients with secondary iron overload (p less than 0.05) despite a comparable degree of iron overload in the secondary iron overload group. The addition of exogenous human ferritin to samples from treated hemochromatosis patients and normal volunteers did not significantly increase the % of monocytes binding anti-ferritin antibody. These results suggest that monocytes from iron-loaded hemochromatosis patients express increased surface ferritin which may represent release of ferritin and a metabolic defect characteristic of hemochromatosis.
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PMID:Monocyte membrane ferritin in hemochromatosis. 174 18

The clinical features and therapy of chronic iron overload are reviewed. Chronic iron overload is classified as primary or secondary hemochromatosis. In primary hemochromatosis a genetic defect in iron metabolism results in increased absorption of iron from the gastrointestinal tract. The excess iron in secondary hemochromatosis may be derived from increased gastrointestinal absorption due to ineffective erythropoiesis or from medicinal, dietary, or transfusional sources. Phlebotomy is the treatment of choice in patients with primary hemochromatosis. Iron chelation therapy is indicated in patients who are not candidates for phlebotomy. Deferoxamine mesylate, the only commercially available iron chelator, is usually administered subcutaneously or intravenously over 10-12 hours/day. Serum ferritin concentrations are measured every three to six months to monitor the effectiveness of therapy. The adverse effects of deferoxamine include local skin reactions, ototoxicity, cataracts, growth impairment, and increased susceptibility to infectious organisms. Patient compliance may be compromised by the routes of administration and cost of deferoxamine. Early detection and prompt treatment are necessary to prevent organ damage. Phlebotomy and iron chelation therapy are effective in the treatment of chronic iron overload.
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PMID:Treatment of chronic iron overload. 174 62

Iron overload was produced in Wistar rats by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe(3+)-NTA) for one to six months. Pancreatic tissues from these iron-overloaded rats and untreated controls were examined for insulin (for B cells), glucagon (for A cells), transferrin receptor (TfR), transferrin (Tf) and ferritin (Ft) using immunohistochemical methods, and for iron by histochemical Berlin blue staining. In the islets of iron-overloaded rats, increased Ft staining appeared prior to deposition of Berlin blue-stainable iron, and the staining intensity of Ft and iron was stronger in B cells than in A cells. In the islets of untreated control rats, the staining intensity of TfR was stronger in B cells than in A cells. TfR staining of the islets was weaker in iron-overloaded rats than in the controls. These findings suggest that 1) iron uptake by islet cells in vivo is regulated and mediated by TfR, 2) intracytoplasmic Ft transforms into stainable iron in iron-overloaded rats, and 3) predominance of TfR expression in B cells may result in selective deposition of iron and predispose B cells to damage and diabetes mellitus in iron-overloaded rats.
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PMID:Transferrin receptors and selective iron deposition in pancreatic B cells of iron-overloaded rats. 177 64


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