Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 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

A patient with characteristic features of iron deficiency was unexpectedly found to have circulating siderocytes. Bone marrow iron stain at this time showed absence of both hemosiderin and ringed sideroblasts; electron microscopy revealed absence of mitochondrial iron loading but presence of cytoplasmic ferritin in normoblasts. Replenishment of iron stores led to development of typical sideroblastic anemia. These observations suggest that increased percentage of siderocytes in otherwise typical iron deficiency anemia may signify the presence of a sideroblastic process masked by iron deficiency due to bleeding.
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PMID:Primary sideroblastic anemia masked by bleeding. 7 31

Microcytic anemia is defined as the presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low MCV (less than 83 micron 3). Iron deficiency is the most common cause of microcytic anemia. The absence of iron stores in the bone marrow remains the most definitive test for differentiating iron deficiency from the other microcytic states, ie, anemia of chronic disease, thalassemia, and sideroblastic anemia. However, measurement of serum ferritin, iron concentration, transferrin saturation and iron-binding capacity, and, more recently, serum transferrin receptors may obviate proceeding to bone marrow evaluation. The human body maintains iron homeostasis by recycling the majority of its stores. Disruptions in this balance are commonly seen during menstruation, pregnancy, and gastrointestinal bleeding. Although the iron-absorptive capacity is able to increase upon feedback regarding total body iron stores or erythropoietic activity, this physiologic response is minimal. Significant iron loss requires replacement with iron supplements. The vast majority of patients respond effectively to inexpensive and usually well-tolerated oral iron preparations. In the rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective. In either form of treatment, it is necessary to replete iron stores in addition to correcting the anemia.
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PMID:Microcytic anemia. Differential diagnosis and management of iron deficiency anemia. 157 56

A modified silver stain is described for the demonstration of ringed sideroblasts in bone marrow. It is more sensitive than Perls' reaction for that purpose, especially when iron stores of marrow are low or absent. Ringed sideroblasts may still be demonstrable by silver stain in cases of sideroblastic anemia without ringed sideroblasts, for which severe iron deficiency prevents detection of the abnormal sideroblasts by Perls' reaction. As iron has been reported to be present in mitochondria of ringed sideroblasts in the form of ferric phosphate, it is possible that the silver stain demonstrates the phosphate moiety and not the iron, thus explaining its greater sensitivity in iron deficiency as compared to Perls' reaction. Further study is necessary to confirm the staining mechanism, to elucidate the composition of iron deposits, and to explain the pathophysiology of sideroblastic anemia.
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PMID:Silver stain for ringed sideroblasts. A sensitive method that differs from Perls' reaction in mechanism and clinical application. 169 93

Disorders of iron metabolism affect the expression of hemoglobin H in hemoglobin H disease. Two cases of iron deficiency with reduced synthesis of hemoglobin H are described in the literature. We report two more cases, one with anemia of chronic disease and another with alcoholic sideroblastic anemia where the hemoglobin H was not detected at presentation and appeared after treatment of the underlying disorder. The pathogenesis of suppression of hemoglobin H is discussed.
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PMID:Suppression of hemoglobin H in disorders of iron metabolism. 310 19

An up to date review of our knowledge of human iron metabolism is given including problems of iron balance, internal transport, and intracellular mechanisms. Current knowledge of the iron proteins is summarized and this background is used in discussing the pathophysiology of iron deficiency and overload, together with the internal derangements such as sideroblastic anemia which form much of the clinical practice associated with disorders of iron metabolism. The therapeutic approach to these problems will be described.
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PMID:Iron deficiency and iron overload. 389 43

The records on 375 consecutive bone marrow aspirations were reviewed to establish the incidence and association of peripheral and bone marrow basophilia. Seventeen cases of peripheral basophilia were identified (4.5 percent incidence) and were associated with iron deficiency (five cases), lung carcinoma (four cases), anemia of undetermined cause (four cases), and chronic myelogenous leukemia, myelodysplasia, chronic renal failure, and acute myelogenous leukemia (one case each). There were six cases of marrow basophilia, including iron-deficiency anemia (two cases), sideroblastic anemia with myelodysplasia, mild dyspoiesis, anemia of chronic disease, and acute erythroleukemia. Marrow basophilia was significantly associated with myelodysplasia and sideroblastic anemia, but was not found in 37 patients with lymphoproliferative disorders. There were no instances of simultaneous marrow and peripheral basophilia. These data support the concept that marrow basophilia is a specific, although not sensitive, marker of disruption of the normal marrow maturation controls.
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PMID:Basophils in peripheral blood and bone marrow. A retrospective review. 670 76

The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase of platelet accumulation of about an order of magnitude. Our studies concern the role of red cell size. We have studied this effect using an annular perfusion chamber, according to Baumgartner, with human umbilical arteries and a steady-flow system. Normal human red blood cells (MCV 95 cu mu) increased platelet adherence sevenfold, as the hematocrit increases from 0 to 0.6. Small erythrocytes from goats (MCV 25 cu mu) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (MCV 70 cu mu) caused an intermediate increase in adherence. Red blood cells from newborns (MCV 110-130 cu mu) caused a larger increase in platelet adherence than normal red cells at hematocrit 0.4. These results were further confirmed with large red blood cells from two patients. Experiments with small red cells (MCV 70 cu mu) of patients with iron deficiency showed that platelet adherence was similar to normal red cells, provided the red cell diameter was normal. Small red blood cells of a patient with sideroblastic anemia caused decreased adherence. These data indicate that red cell size is of major importance for platelet adherence. Red cell diameter is more important than average volume. However, for size differences in the human range, the hematocrit remains the dominant parameter.
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PMID:Red blood cell size is important for adherence of blood platelets to artery subendothelium. 686 Jul 93

We encountered two patients who presented with hypochromic-microcytic anemia and were refractory to iron therapy. The symptoms were suggestive of anemia of chronic disease (ACD); however, there was no evidence of any such disease, either inflammatory or malignant. These patients were reminiscent of patients originally described as having primary defective iron reutilization. The hematologic picture consisted of hypochromic-microcytic anemia, low serum iron, low to normal iron binding capacity, high serum ferritin, and increased bone marrow iron in the absence of ringed sideroblasts. These patients had symptomatic anemia and received danazol (200 mg orally) three times per day to which they responded very well with an increase of approximately 3 g in the hemoglobin concentration over 1 year and amelioration of their symptoms. Danazol was well tolerated and did not cause any virilizing side effects. Doses were lowered in maintenance after 1 year to 200 mg once per week, and responses were sustained up to 36 months of follow-up duration. In the differential diagnosis of hypochromic-microcytic anemia, especially in postmenopausal women, one has to consider this type of treatable anemia when more common types such as iron deficiency, chronic inflammation, malignancy, sideroblastic anemia, or thalassemia have been ruled out.
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PMID:Treatment of primary defective iron-reutilization syndrome: revisited. 1098 70

Sideroblastic anemia is an anemic condition characterized by chronic hypochromic anemia and the presence of large iron deposits in erythroid cells. Seven dogs with sideroblastic anemia were evaluated retrospectively. Historical, clinical, and clinicopathologic findings were reviewed to determine whether the condition was idiopathic or associated with disease conditions or drug or toxin exposure. Associated diseases were identified in 6 affected dogs and included acute hepatitis, pancreatitis, acute hepatitis and pancreatitis, inflammatory disease, glomerulonephritis, and myelofibrosis. None of the dogs had a history of recent exposure to drugs or toxins. One dog had no evidence of associated disease. Regardless of the associated disease condition, sideroblastic anemia was characterized by moderate to severe nonregenerative and frequently hypochromic anemia with prominent dysplastic features in bone marrow that were most prominent in the erythroid series. Survival varied from days to years. Identification of large numbers of siderocytes or sideroblasts in blood or bone marrow is inconsistent with a diagnosis of iron deficiency and should prompt a search for inflammatory disease conditions, including hepatitis, pancreatitis, and glomerulonephritis.
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PMID:Sideroblastic anemia in 7 dogs (1996-2002). 1595 46


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