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

Transferrin binding to human placental sites was inhibited by the acute-phase proteins alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-MG), whereas haptoglobin, C-reactive protein and ferritin displayed no such effect. In equilibrium saturation binding assays, the effective acute-phase proteins decreased the apparent affinity of the binding sites for transferrin, but the transferrin binding-site density Bmax. was not significantly changed. For instance, the addition of 30 microM alpha 1-AT increased the KD of transferrin from 8.46 +/- 1.51 nM to 21.6 +/- 3.04 nM; the Bmax. values were 1.17 +/- 0.18 pmol/mg of protein and 1.04 +/- 0.25 pmol/mg of protein respectively. In kinetic studies, alpha 1-AT decreased the association rate constant k+1 of the 125I-transferrin-binding-site complex from 2.18(+/- 0.21) x 10(7) M-1.min-1 to 3.99(+/- 0.18) x 10(6) M-1.min-1. In contrast, the dissociation rate constant k-1 was not changed (0.0948 +/- 0.002 min-1, 0.089 +/- 0.0017 min-1). On isoelectric focusing, no alteration in transferrin protein pattern or shift in isoelectric point was detected in the presence of alpha 1-AT. Inhibition of transferrin binding by the acute-phase proteins alpha 1-AT and alpha 2-MG is competitive. Interestingly, inhibition is already present at physiological concentrations. However, full inhibition is only achieved at concentrations above the normal range, which are attained in acute-phase reactions.
 ...
PMID:The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor. 767 93

During the period 1986-93 22 patients were diagnosed as having primary hemochromatosis. Only 11 of them had elevated aminotransferases. Transferrin saturation was higher > 63% in 17 (77%) and serum-ferritin was higher in all the patients. (257 mumol/l to 6,500 mumol/l). A percutaneous liver biopsy was performed in 20 patients, all of whom showed a characteristic grading from 2 + to 4+ using Perls' stain. Two males had cirrhosis with simultaneous hepatocellular carcinoma, and another two had cirrhosis. One patient had diabetes mellitus type I. We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes. If transferrin saturation is higher than 50% in females and 60% in males, serum ferritin should be determined. A percutaneous liver biopsy should be performed if both values are higher than normal. Screening of siblings is important because of the autosomal recessive pattern of inheritance.
 ...
PMID:[Clinical experience with early hemochromatosis]. 807 82

Iron studies were compared in 434 patients from 80 hemochromatosis families classified as putative homozygotes, heterozygotes, and normal by HLA typing. There were 28 of 255 (11%) heterozygotes with an elevated serum ferritin and 22 of 255 (8.6%) with an elevated transferrin saturation. Serum ferritin (140 +/- 10.2 micrograms/liter; mean +/- standard error) was greater in heterozygotes than in normal subjects (87 +/- 8.5 micrograms/liter; P < .05, Mann Whitney test). Transferrin saturation was greater in heterozygotes (38% +/- 0.88%) than in normal patients (29% +/- 1.1%; P < .0001). Mean hepatic iron concentration was 54 +/- 6 mumol/g (n = 17), and the hepatic iron index was < 2 in these patients. Most heterozygotes for hemochromatosis have a normal serum ferritin and transferrin saturation. Heterozygotes with minor elevations in serum ferritin or transferrin saturation do not have significant iron overload as assessed by hepatic iron concentration.
 ...
PMID:Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes. 814 Nov 20

The value of s-Transferrin Receptor (s-TfR) measurements in recognizing simultaneous iron deficiency in anaemia of chronic disease was examined in 35 anaemic patients with active rheumatoid arthritis. Based on a quantification of stainable bone marrow (marrow iron grade 0-4) and serum ferritin concentrations (levels < 60 micrograms l-1) compatible with iron deficiency) the anaemia was found to be aggravated by iron deficiency in 19/35 or 54% of the patients. There was no significant difference between the mean s-TfR concentrations in patients with adequate iron in comparison to patients with iron depletion [2.9 (1.6) mg l-1 v. 2.7 (1.4) mg l-1; t = 0.273; p = 0.786; Student's t-test]. Mean s-TfR levels in both patients with adequate iron and depleted iron stores were within the normal range, but tended to be higher than in normal individuals [mean (SD): 1.54 (0.43) mg l-1]. In patients with no stainable marrow iron (MIG 0; N = 15) a significant inverse correlation was found between s-TfR concentrations and s-ferritin levels (r = 0.57; p < 0.05). 5/15 patients with MIG = 0 exhibited significantly raised concentrations of s-TfR values > 3.05 mg l-1 (the highest normal value of the normal range). Increases of s-TfR levels were consistently moderate, and never exceeded a level of 7 mg l-1, which is markedly lower than concentrations measured in patients with iron deficiency anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum transferrin receptor levels in anaemic patients with rheumatoid arthritis. 817 Dec 75

We have investigated the effects of the pro-inflammatory cytokines interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on the iron metabolism of the human monocytic cell line U937. Cells were treated with each cytokine for up to 24 h, and then iron uptake from diferric transferrin was determined. The intracellular distribution of this iron, the expression of the transferrin receptor and levels of mRNA for the two ferritin subunits were also studied. IL-1 beta, TNF alpha and IFN gamma all decreased transferrin-iron uptake into cells, and all three cytokines had effects on the proportion of iron associated with ferritin. With TNF alpha there was a marked enhancement of the fraction incorporated into ferritin. Transferrin-receptor expression was diminished by TNF alpha and IL-1 beta, but not IFN gamma, suggesting different effector mechanisms. Both TNF alpha and IFN gamma increased the amount of cellular mRNA for ferritin H-chain, but not the L-chain; IL-1 beta affected mRNA for neither ferritin. These data demonstrate that cytokines, which can be present at high concentrations in inflammation, have the capacity to affect macrophage iron uptake, transferrin receptor expression, intracellular iron handling and the relative abundance of ferritin-subunit mRNA, and may therefore be important mediators in the observed perturbations of iron metabolism in inflammatory diseases.
 ...
PMID:Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA. 825 Aug 40

Transferrin receptors on proliferating and malignant cells are well documented. Iron is an essential micronutrient for cell growth that plays an important role in energy metabolism and DNA synthesis. Malignant cells requiring more iron modulate a transferrin receptor. Iron-bound transferrin interacts with this receptor, facilitating the transport of iron across the cell membrane. Transferrin is a glycoprotein and is the chief iron transport protein in mammalian blood. The more aggressive the tumor, the higher the transferrin receptor levels and the greater the proliferative index. We have found by cytochemical and ultrastructural studies that ferritin, an iron storage protein, is increased in breast cancer tissue. Anaplastic tumors have higher tissue ferritin levels. Tissue ferritin concentration may be an indirect method of measuring transferrin receptors and thus might be an index of proliferation and a prognostic indicator. Transferrin may be used as a carrier to target toxic therapy selectively to tumor tissue. A platinum transferrin complex (MPTC-63) has been developed and shown to be cytostatic in tissue culture, animal, and human studies. It also sensitizes tissue to agents that produce free radicals, such as adriamycin, and thus is synergistic with other drugs and radiation. Other transferrin complexes and conjugates of gallium, indium, and daunorubicin have also shown growth inhibition in tissue culture and animals. Human studies are in progress. By studying iron metabolism in breast cancer, we may be able to selectively inhibit tumor growth without toxic effects, and with other tumor biologic data be better able to select the stage I patient for adjuvant therapy.
 ...
PMID:Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study. 827 55

Iron and iron-binding proteins play a critical role in the physiology of many human systems, including the immune system. Intense interval exercise in trained men (mean [SD] age = 31.5 [4.5] yr; VO2max = 64.3 [3.8] ml.kg-1.min-1) is associated with significant modulation of iron status parameters. The concentration of red blood cells, hemoglobin, and transferrin all increased significantly immediately post-test (P < 0.01), increases which can largely be attributed to hemoconcentration. Serum iron was elevated by approximately 25% both immediately and 1 h post-test (P < 0.08). Maximum post-test serum iron values (either immediately or 1 h post-test) were significantly elevated with respect to rest (P < 0.01). Transferrin concentration was also significantly elevated at 24 h post-test (P < 0.05). Transferrin saturation was not significantly altered by this protocol (P > 0.10). Despite a trend toward elevation at 24 h post-test, ferritin concentration was not significantly different from the resting value at any sampling point. Intense interval exercise appears to be associated with significant modulation of iron status, the biological importance of which remains to be determined.
 ...
PMID:The effect of intense interval exercise on iron status parameters in trained men. 835 Jun 98

To determine the etiology of hypoferremia in recently sedentary hunter-gatherers, a community located in the Kalahari Desert of Botswana was studied. Iron profiles of 106 Basarwa (Bushmen, San) volunteers were examined. Hematocrits were measured in the field. The remaining blood was processed for transportation to a research medical laboratory for further studies. Subnormal serum iron values were present, depending on the subpopulation, in 50-52% of the volunteers. Transferrin saturation was subnormal in 35-49% of those tested. The absence of subnormal serum ferritin levels indicates that dietary iron deficiency is not the cause of the hypoferremia. Instead, serum ferritin was greater than 50 micrograms/l (a level indicative of anemia of chronic disease/inflammation) in 92% of the hypoferremic adult Basarwa. We suggest that by depriving microbes of needed iron, the frequency of the anemia of infections and chronic disease in this population might be a response to, and defense against, a chronically high pathogen load in a community that has not yet incorporated sanitation practices appropriate for sedentary aggregations.
 ...
PMID:Etiology of hypoferremia in a recently sedentary Kalahari village. 848 Aug 65

Transferrin, the transferrin receptor, and ferritin are integral to the body's management of iron, an element required for life but highly toxic when present in excess. The transferrin receptor and ferritin are regulated posttranscriptionally by iron: the transferrin receptor by mRNA stability and ferritin by mRNA translation. Results described here indicate that transferrin, like ferritin, is regulated by iron at the level of translation. Chimeric genes introduced into the mouse genome were composed of the human transferrin 5' regulatory region fused to the chloramphenicol acetyl transferase (CAT) reporter gene. Iron administration to transgenic mice resulted in a significant decrease of transferrin-directed CAT enzyme activity and CAT protein in liver, but no significant decrease in human transferrin-CAT mRNA levels. Binding of specific RNA iron regulatory elements by proteins in cytoplasmic extracts have been shown to regulate ferritin and transferrin receptor synthesis. Similar results have been obtained with transferrin mRNA. A decreased binding of human transferrin 5'-untranslated region RNA by factors in cytoplasmic extracts of livers from mice receiving iron was found when compared to extracts from control mice. A human transferrin RNA-protein complex migrated electrophoretically with the same mobility as a ferritin iron responsive element RNA-iron responsive element binding protein complex. The ferritin iron responsive element RNA also competed with the human transferrin 5'-untranslated region RNA-protein complexes formed and vice versa. Therefore, iron modulation of human transferrin may share a factor common or similar to that observed in ferritin and transferrin receptor iron modulation.
 ...
PMID:Posttranscriptional regulation of chimeric human transferrin genes by iron. 849 18

Recombinant human erythropoietin (rHuEpo) seems to be more efficient when given subcutaneously (SC) instead of intravenously (IV) for therapy of anaemia in haemodialysis patients. This was a cross-over study designed to assess the efficiency of rHuEpo when given SC rather than IV in a 1 year follow-up. Sixteen patients received IV rHuEpo for 6 months, then SC rHuEpo for 6 months. They were four males and 12 females with a mean age of 56 years (range 15-82). Haemoglobin concentration ([Hb]) was kept at 10 g/dl and transferrin saturation (TS) at more than 25%. Mean [Hb] was 9.7 +/- 1.0 g/dl with IV rHuEpo and 9.9 +/- 0.9 g/dl with SC rHuEpo (NS). Transferrin saturation was 27% before rHuEpo, 31% with IV rHuEpo and 34% with SC rHuEpo (NS vs IV rHuEpo). Serum ferritin was 691 +/- 113 ng/ml before rHuEpo, 652 +/- 94 ng/ml with IV rHuEpo and 997 +/- 132 ng/ml with SC rHuEpo (P < 0.05 vs IV rHuEpo). Intact parathyroid hormone was 354 +/- 83 pg/ml before rHuEpo, 201 +/- 63 pg/ml with IV rHuEpo and 122 +/- 33 pg/ml with SC rHuEpo (NS vs IV rHuEpo). Doses of IV rHuEpo were 156 +/- 24 U/kg/week and SC rHuEpo 74 +/- 13 U/kg/week (i.e. a saving of 53%; P < 0.001). We conclude that subcutaneous administration of rHuEpo is twice as efficient as IV rHuEpo in patients with good functional iron reserve.
 ...
PMID:Subcutaneous versus intravenous administration of erythropoietin improves its efficiency for the treatment of anaemia in haemodialysis patients. 852 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>