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)

The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.
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PMID:Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat. 141 29

In order to assess the effectiveness of cytapheresis as a possible alternative therapy for iron depletion, we performed a prospective study on eight unrelated patients with idiopathic hemochromatosis (HC). Isovolemic large-volume erythrocytapheresis (EA) (1000 ml apherisate) was carried out every four weeks until serum ferritin levels dropped below 300 micrograms/l (initial therapy). In all patients iron depletion was achieved after a mean of 8.5 months (8.9 EA with a total removal of 9.41 RBC). Serum ferritin levels decreased during initial therapy from 2596 +/- 399 to 168 +/- 83 ug/l. Serum iron level (240 +/- 35 to 125 +/- 48 ug/dl) and transferrin saturation (91 +/- 6 to 19 +/- 10%) declined accordingly. Clinical reexamination after initial therapy revealed improvement of clinical symptoms, normalization of hepatic iron, but liver histology remained unchanged. Reaccumulation of iron was prevented by maintenance EA therapy every five to six months (follow-up 18-36 months). Isovolemic large-volume EA is an effective, fast and safe method to remove excessive stored iron in patients with HC. Compared to phlebotomy, EA can selectively remove RBC, while saving plasma proteins, platelets, and clotting factors. Although, the need for special equipment and trained personnel as well as the relatively high costs are limiting factors of EA so far, it can be of crucial advance in some patients with HC.
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PMID:Repeated isovolemic large-volume erythrocytapheresis in the treatment of idiopathic hemochromatosis. 147 84

Serum ferritin was measured in 50 patients at diagnosis of diabetes mellitus (DM) and in 20 patients with established DM and poor metabolic control. Twenty-two patients had hyperferritinemia at diagnosis. Four patients had a recognised cause for their hyperferritinemia. In the remaining 18 patients ferritin levels decreased from a mean of 506 +/- 3.6 (SE) ug/l at diagnosis to 254 +/- 29.2 ug/l seven months later (p < 0.001). Metabolic control improved significantly over the same time. All 20 patients with established DM and poor metabolic control had normal ferritin levels. When compared with the newly diagnosed hyperferritinemic patients no difference was found in levels of glycosylated haemoglobin, but ferritin values differed significantly between the two groups (p < 0.001). These results indicate that transient hyperferritinemia is a feature of newly diagnosed DM but not of established DM with poor control. If used to screen diabetic patients for haemochromatosis, serum ferritin should be measured in established DM rather than at diagnosis.
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PMID:Serum ferritin in newly diagnosed and poorly controlled diabetes mellitus. 147 45

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

We report on a 74-year-old female patient with primary hemochromatosis complicated by hyperthyroidism. The serum ferritin level was reduced throughout a 217 day administration of deferoxamine (1 g/day). At the same time, the thyroid gland was changed from hyper- to hypo- functional proportionally.
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PMID:Change in the thyroid function by use of deferoxamine in a patient with hemochromatosis complicated by hyperthyroidism. 157 42

This paper addresses the question of whether abnormalities in ferritin expression in the iron storage disease hemochromatosis (HC) involve major deletions or alterations in regions containing the two ferritin H genes that lie near the disease locus on chromosome 6p. We present evidence from analyses of Southern blots that neither gene is deleted in hemochromatosis. We also describe a polymorphism in one of the genes that we have previously shown to be a processed pseudogene. This polymorphism does not correlate with the presence of HC. The PIC value for this polymorphism was calculated as 0.49.
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PMID:Polymorphism in a ferritin H gene from chromosome 6p. 167 57

The light and electronmicroscopic representation of non-haemiron in the bone-marrow provides the unique opportunity of extensively evaluating the iron metabolism. In the bone-marrow, macrophages represent the physiological place of iron storage. The iron in the cytoplasma is stored in them in the form of free ferritin molecules and lysomally as aggregated ferritin and/or haemosiderin in siderosomes. In an equal iron balance and unimpaired internal iron exchange only erythroblasts (sideroblasts) and erythrocytes (siderocytes) of the bone-marrow besides macrophages possess siderosomes. In addition to this physiological or orthotopic iron storage a heterotopic iron storage can be observed under pathological conditions, particularly with iron overloading of the organism, in the endothelial cells of sinusoids and plasma cells. In detail, the patterns of iron storage in the bone-marrow are described in the different stages of iron deficiency, disturbance of iron utilization in chronically inflammatory processes or tumour diseases, condition after intravenous iron administration, transfusion siderosis, hereditary haemochromatosis and sideroblastic anaemia.
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PMID:The diagnostic value of bone marrow iron. 170 12

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

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

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


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