Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemin allows maximal protein synthesis in intact rabbit reticulocytes and their cell-free lysate preparations by retarding the formation of a translational repressor (HCR) found in the postribosomal supernate. In order to evaluate the role of HCR in the pathogenesis of hypochromic anemias, HCR was isolated and partially purified from intact rabbit reticulocytes incubated in vitro with either 0.1 mM alpha,alpha-dipyridyl (an iron-chelating agent) or 0.1 M ethanol. Both of these agents inhibit reticulocyte protein synthesis. Hemin (50 muM) protects against the inhibition by both agents. A ferrous iron-transferrin mixture, however, protects only against alpha,alpha-dipyridyl. Both alpha,alpha-dipyridyl and ethanol inhibit heme synthesis before the time that protein synthesis is affected, while neither lowers either ATP or GSH levels. These results indicate that while both agents inhibit heme synthesis, alpha,alpha-dipyridyl does so by inducing iron deficiency while ethanol works at a non-iron-requiring step. When HCR was isolated from intact cells and assayed in the reticulocyte cell-free systems, plus and minus hemin, premature appearance of HCR was found in cells incubated in vitro with alpha,alpha-dipyridyl or ethanol. When hemin was present in the intact cell incubation, the appearance of HCR was retarded. The HCR from alpha,alpha-dipyridyl ethanol-treated cells was partially purified and eluted at the same location on a Sephadex G-200 column (molecular weight approximately 3 x 10(5)) as that from postribosomal supernates incubated minus hemin. In addition rabbits with phenylhydrazine-induced hemolytic anemia were given intravenous ethanol in vivo at a dose of 0.4 ml/kg. This concentration of alcohol resulted in an inhibition of the rate of heme synthesis and protein synthesis as well as an acceleration of HCR formation in reticulocytes. The HCR from these in vivo treated rabbits was isolated, partially purified, and assayed in an identical fashion as the in vitro experiments. These in vivo experiments further support the physiological and pathophysiological role of HCR in reticulocytes. On the basis of these results a model for a role of HCR in some of the hypochromic anemias is proposed. In iron deficiency or chronic disease (where iron is not available to the erythroblast for heme synthesis) HCR appears prematurely and inhibits protein synthesis. When heme synthesis is inhibited by ethanol but there is sufficient intracellular iron, HCR appears prematurely and inhibits protein synthesis, iron accumulates in the erythroblast, and the end result is sideroblastic anemia.
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PMID:A rabbit reticulocyte model for the role of hemin-controlled repressor in hypochromic anemias. 0 17

Sheep were treated with large amounts of copper (20 mg of CuSO4,5H2O/kg body wt. per day) for 9 weeks to examine the effect of copper excess on iron metabolism. In addition to confirming that massive haemolysis and accumulation of copper occurs in the liver, kidney and plasma after 7 weeks of exposure to excess copper, it was observed that excess copper produced an increased plasma iron concentration and transferrin saturation within 1 week. Further, iron preferentially accumulated in the spleen between 4 and 6 weeks of copper treatment, producing 3-fold increases in the iron content of both the ferritin and non-ferritin fractions. A 3-4 fold increase was also observed in the amount of ferritin that could be isolated from the spleen. The copper treatment had little or no effect on the concentration of iron in the liver and bone marrow. The following properties of erythrocytes were also unaffected by copper treatment: size, haemoglobin content and pyruvate kinase activity, although the erythrocyte concentration of copper increased after 6 weeks. Copper accumulated in the spleen between 6 and 9 weeks, probably owing to the phagocytosis of erythrocytes containing high concentrations of copper. The data suggest that copper excess influences iron metabolism, initially by causing a compensated haemolytic anaemia, and later by interfering with re-utilization of iron from ferritin in the reticuloendothelial cells of the spleen.
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PMID:The effect of copper excess on iron metabolism in sheep. 62 72

The mRNA level for ferrochelatase was assessed in the total cytoplasmic RNA isolated from mouse erythroleukaemic cells, line 707, in the course of induction of erythroid differentiation with hexamethylenebisacetamide and from spleen cells of mice in different stages of erythroid differentiation after phenylhydrazine administration. The level of this mRNA increased after five days of induction of erythroleukaemic cells about six times. An even more marked increase of the mRNA level for ferrochelatase (13.5X) was found in the total cytoplasmic RNA isolated from erythropoietic spleen cells of mice after induction of haemolytic anaemia by phenylhydrazine. Haem synthesis inhibitors (succinylacetone, isonicotinic acid hydrazide and penicillamine) caused a reduced gene expression for ferrochelatase in erythroleukaemic cells of mice induced with hexamethylenebisacetamide. Conversely addition of precursors of haem synthesis (5-aminolaevulinic acid or protoporphyrin IX) led to an increased mRNA synthesis for ferrochelatase. In addition to protoporphyrin synthesis the supply of another substrate, iron, is decisive for the gene expression ferrochelatase. Iron chelators (desferrioxamine or pyridoxal isonicotinoylhydrazone) reduced and iron donors (iron bound to transferrin or pyridoxal isonicotinoylhydrazone) enhanced mRNA synthesis for ferrochelatase. Added haemin reduces mRNA synthesis for ferrochelatase in fully induced erythroleukaemic cells but increases the gene expression ferrochelatase in the course of induction of erythroid differentiation because it acts as an inducing agent.
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PMID:[Ferrochelatase gene expression in erythroid cells]. 128 76

In various anaemias the values of 8 acute phase factors were determined simultaneously before and at the end of treatment: seromucoid, sialic acid, acid alpha 1-glycoprotein, alpha 1-antitrypsin, haptoglobin, ceruloplasmin, transferrin and fibrinogen. In iron-deficiency anaemia without coexistent inflammatory changes in organs the levels of 4 proteins--seromucoid, alpha 1-antitrypsin, ceruloplasmin and transferrin, were consistently raised. In iron-deficiency anemia with concomitant infection 4 proteins also were increased, but in place of alpha 1-antitrypsin the haptoglobin level was raised. In megaloblastic anaemia the ceruloplasmin level was increased, and in haemolytic anaemia one factor--sialic acid--was decreased. At the end of treatment the concentrations of certain proteins were changed depending on their specific role in various forms of anaemia and on various additional factors. In iron-deficiency anaemia without coexistent infection the concentration of seromucoid was decreased, and in this anaemia with coexistent infection alpha 1-antitrypsin, haptoglobin, and fibrinogen levels were raised, in haemolytic anaemia only fibrinogen was increased, and megaloblastic anaemia was associated with raised seromucoid level. The therapeutic result was good in all these anaemias with the exception of iron-deficiency anaemia associated with infection in which it was less propitious.
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PMID:[Acute phase factors in anemia]. 172 69

One of the most important factors for the proliferation and hemoglobin synthesis of erythroid cells is iron atom. This atom is tightly bound to serum transferrin (Tf) and is taken up by erythroblasts and reticulocytes through transferrin receptor (TfR). Both Tf and TfR are reutilizable and have roles for the efficient intracellular accumulation of iron. In addition to the reutilization (recycling), the expression of TfR is also regulated by cytoplasmic iron concentration; the increase of iron downregulate the synthesis of TfR at the translational level and vice versa. This mechanism was recently explained by the binding between "iron responsive element (IRE)" in the 5' end of TfR mRNA and IRE binding protein by a transacting manner. Johnstone et al, and we found that TfR was externalized from sheep reticulocyte and human erythroleukemia cell, K562, respectively. Furthermore, we confirmed that this shed TfR was detected in blood and concluded that the quantitation of TfR in serum is a useful index for evaluating the erythropoiesis. The serum TfR was increased in iron deficiency anemia, hemolytic anemia and polycythemia and was decreased in aplastic anemia. In renal anemia, it was increased after the administration of erythropoietin (Epo). By the in vitro liquid culture of peripheral blood stem cells using interleukin 3 and Epo, it was found that soluble TfR was derived from the erythroblasts during the maturation process.
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PMID:[Expression and extracellular release of transferrin receptors on erythropoiesis]. 189 Jul 32

A ferrokinetic study was performed in 79 patients, 25 with absolute polycythaemia, 19 with relative polycythaemia and 35 presenting anaemia of different aetiology. The incorporation of transferrin into the erythron (ITE) was estimated on each case. The mean ITE values found in absolute primary and secondary polycythaemia and in secondary polycythaemia were, respectively, 281 +/- 85, 181 +/- 99 and 74 +/- 19 mumol/L tb/d (i.e., micromoles per litre of total blood per day). The mean ITE in iron deficiency anaemia was 110 +/- 43 mumol/L tb/d, in haemolytic anaemia this was 274 +/- 151 mumol/L tb/d, and in patients with myelodysplastic syndromes such values was 116 +/- 49 mumol/L tb/d. Significant differences were found for each group of patients with respect to a normal control group. Such findings are in accordance with the pathophysiology of the different pathologies studied. The values found in haemolytic anaemia and myelodysplastic syndromes are similar to those reported by others. The results of this study stress the advantages of evaluating the erythropoietic activity of the bone marrow by means of the ITE.
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PMID:[Incorporation of transferrin into the erythron in anemic and polycythemic conditions]. 194 36

The possibility of a metabolic chronic liver disease must always be borne in mind since in certain cases treatment can prevent the lesions from getting worse. The clinical and biochemical context should suggest either (1) genetic haemochromatosis when faced with high serum iron and ferritin levels and elevated transferrin saturation or with a suggestive clinical context (melanoderma, diabetes, hypogonadism, arthropathy, myocardiopathy); or (2) Wilson's disease in young subjects, especially in the presence of neurological and ocular signs or of haemolytic anaemia; or (3) porphyria in case of cutaneous manifestations caused by exposure to sun light. Hence the importance of full clinical examination in patients with chronic liver disease.
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PMID:[Metabolic cirrhosis (hemochromatosis, Wilson's disease, erythropoietic protoporphyria)]. 206 17

Monoclonal antibody reagents were used to develop a sensitive enzyme-linked immunoassay for clinical measurement of circulating transferrin receptor. By using transferrin-bound receptor for the preparation of the immunologic reagents, we developed an assay that gives an identical dose-response curve with either free or transferrin-bound receptor. The mean concentration of circulating receptor in 82 normal male and female volunteers was 5.63 +/- 1.42 mg/L. The level was reduced significantly in patients with primary aplastic anemia and post-transplant aplasia (2.58 +/- 1.07 mg/L and 2.32 +/- 0.48 mg/L, respectively) and was sharply elevated in patients with hemolytic anemia and iron deficiency anemia (33.1 +/- 17 and 18.0 +/- 11.4 mg/L, respectively). Our assay values are approximately 20-fold higher than results published previously in a study that used an immunoradiometric assay. The disparity apparently relates to a difference in sensitivity of the latter assay for free and transferrin-bound receptor. Measurements of serum transferrin receptor provide a useful clinical index of either total or iron-deficiency erythropoiesis.
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PMID:The clinical measurement of serum transferrin receptor. 267 98

Erythropoietic activity is known to be closely associated with marrow iron uptake. A modification of the standard measure of plasma iron turnover has been developed in which erythron transferrin uptake (ETU) rather than iron uptake has been calculated. The ETU has the advantage of providing a parameter of erythroid marrow activity independent of change produced by plasma iron and transferrin saturation. Measurements in 80 patients with anemia were compared to the normal value of 60 +/- 12 mumol/L whole blood/d. The mean ETU for ten patients with severe aplastic anemia and for six patients with pure red-cell aplasia were 12 +/- 8 and 12 +/- 11 mumol/L whole blood/d, respectively. In ten transfusion-dependent patients with renal failure under dialysis therapy, the mean value was 35 +/- 11, while ten other dialyzed patients who were transfusion independent had a mean ETU of 73 +/- 21 mumol/L whole blood/d. Sixteen patients with hemolytic anemia had an average ETU of 400 +/- 130, while 28 patients with ineffective erythropoiesis had a mean value of 474 +/- 147 mumol/L whole blood/d. While patients with hypoproliferative anemia showed no relation between the severity of anemia and ETU, those with hyperproliferative erythroid marrow showed increasing values as the anemia became more severe. Sequential measurements in patients with aplastic anemia under treatment and in thalassemic patients under transfusion therapy showed the value of this measurement in monitoring the effects of treatment on erythroid marrow activity. It is concluded that the measurement of ETU provides a more direct ferrokinetic evaluation of erythroid activity in anemic states.
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PMID:Erythroid marrow function in anemic patients. 309 23

The effect of marrow transplantation on erythropoiesis was studied in three normal dogs (T0), three irradiated dogs receiving compatible marrow (T1), and three irradiated dogs (T2) who donated their marrow to a recipient animal and then at a later date underwent a marrow transplant from the initial marrow recipient. Plasma iron turnover was measured (a) under basal conditions, (b) after plasma iron was elevated by iron infusion, and (c) after hemolytic anemia had been produced by phenylhydrazine. Basal plasma iron turnover in T0, T1, and T2 animals averaged 1.3, 1.0, and 1.3 mg/dl whole blood/day. Turnover of the three groups increased to 7.1, 6.2, and 6.4 mg/dl whole blood/day after the induction of anemia by phenylhydrazine. These values were converted from the transferrin saturation present at the time of the measurement to the calculated turnover at 100% saturation, thereby expressing the maximum capacity of tissues to assimilate iron. After this correction, the calculated maximum uptake was shown to be increased over basal by 3.7, 4.0, and 3.8 times. To validate this approach, an additional comparison was made between baseline turnovers at elevated levels of plasma iron and anemic animals at similarly elevated plasma iron levels. The increment of the three groups was shown to be 3.7, 3.9, and 4.0 times basal. These studies illustrate the use of a refined method of ferrokinetic evaluation of erythropoiesis and indicate that the proliferative reserve in transplanted animals is unimpaired.
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PMID:Erythropoietic reserve in marrow-transplanted dogs. 351 Aug 95


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