Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic development was examined in erythroid precursor cells, which were isolated from the spleens of mice infected with the anemia-inducing strain of Friend virus (FVA cells). FVA cells undergo differentiation in vitro from the proerythroblast stage through the reticulocyte stage over a 48-hour period in the presence of erythropoietin. Concomitant with marked decreases in cellular size and energy demand, metabolic capacities of both glycolysis and oxygen consumption diminish after 48 hours in culture by 7- and 18-fold, respectively. Because the oxidative capacity decreases more than glycolytic ability does, the metabolic machinery increasingly shifts toward anaerobic metabolism. During the 48-hour period of differentiation, the 2,3-diphosphoglyceric acid (DPG) content per cell and 2,3-DPG mutase activity per cell increased eightfold and threefold, respectively. Freshly harvested FVA cells have adenosine triphosphate (ATP) levels of 7.23 +/- 2.52 mumol/10(10) cells or 3.76 +/- 1.31 mumol/mL cell water which are 12- or 2.3-fold higher, respectively, than the ATP levels of mature red blood cells. In the course of FVA cell differentiation, ATP content per cell decreases by fourfold, but ATP concentration in cell water remains unchanged because of a corresponding decrease in cellular size and water content during differentiation. These studies show that in the face of dramatic decreases in cell size and cellular energy demand, terminally differentiating erythroid cells maintain a constant ATP level by undergoing an involution of their glycolytic machinery as well as by losing their aerobic metabolic capacity.
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PMID:Metabolic adaptation during erythropoietin-mediated terminal differentiation of mouse erythroid cells. 182 79

The ability of vitamin E (alpha-tocopherol) to stimulate erythroid progenitor cells was investigated in an attempt to identify ways to ameliorate zidovudine (azidothymidine, AZT)-induced anemia. In vitro, alpha-tocopherol acid succinate (ATS), upon incubation with murine bone marrow cells at concentrations of up to 4 micrograms/ml, caused a dose-dependent increase in erythroid colony-forming unit (CFU-E)-derived colonies. This increase was equivalent to the effect demonstrated by 50 mU of recombinant human erythropoietin (rhEpo) or 200 U of recombinant interleukin 3 (rIL-3). For in vivo studies, anemia was produced in CD-1 male mice by administering AZT in drinking water (1.5 mg/ml). Treatment with vitamin E (50 mg/kg body weight) or Epo (0.4 U per mouse) was initiated 24 h later and continued for five consecutive days. Seventh day bone marrow cells from femurs were assayed for CFU-E-derived colonies. Both vitamin E and Epo significantly increased the number of CFU-E-derived colonies by 75% and 86% of control, respectively, indicating that these agents were approximately similar in protecting the bone marrow from AZT-induced toxicity.
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PMID:Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E. 189 52

Close on the heals of the first successful reports of recombinant human erythropoietin (rHuEPO) use in dialysis-associated anemia, concern surfaced that raising the hematocrit level could threaten both the safety and efficacy of hemodialysis. Theoretical considerations prompted the conclusion that by decreasing the plasma water space available for dialysis, removal of plasma solutes would decrease in direct proportion to the increase in hematocrit. Predictions of thrombotic disaster were also aired, citing the increase in blood viscosity expected after correction of anemia. After 18 months of widespread use of rHuEPO in the United States, clinical experience has shown that correction of anemia can be accomplished without serious impact on either safety or efficacy in both conventional and high efficiency/high dialysis. Although predialysis concentrations of creatinine, phosphate, and potassium may increase whenever the hematocrit increases substantially, the magnitude of the rise is limited. Increased predialysis solute concentrations, which may be caused by either decreased dialyzer efficiency or increased dietary intake due to improved appetite, are readily managed by increasing dialysis blood flow rate, dialyzer surface area, and dialysis time. Since these measures may have little effect on increased phosphate levels, increased administration of phosphate binders may be required. However, by way of caution, the ready dialyzability of urea renders the predialysis blood urea nitrogen (BUN), as well as urea kinetics, relatively unaffected by the change in hematocrit, thereby masking adverse effects on other solutes. Fortunately, serious thrombotic consequences have not been seen, probably because anticoagulation is adequately managed by routine increases in heparin utilization.
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PMID:Impact of erythropoietin on the dialysis prescription. 192 83

The anaemia induced by 3'-azido-3'dideoxythymidine (AZT) is poorly understood. We have used a murine model of AIDS, infection of female C57BL/6 mice with LP-BM5 murine leukaemia (MuLV) virus, to determine if AZT-induced anaemia is due, in part, to decreased responsiveness of erythropoietic precursors (BFU-e) to erythropoietin (EPO). Mice in the early stage of LP-BM5 MuLV disease were given AZT in their drinking water at 1.0 and 2.5 mg/ml. AZT produced anaemia in both groups, in a dose-dependent fashion. Despite the anaemia, the number of splenic and bone marrow BFU-e in AZT treated mice increased up to five-fold over levels observed in infected untreated animals after 15 d of treatment. Colony formation by splenic and bone marrow BFUe was stimulated at lower concentrations of EPO in mice receiving AZT for 15 d than for infected, untreated mice. By day 30, sensitivity of both splenic and bone marrow BFU-e of treated animals returned to that observed from cells of infected untreated animals. The mean plasma levels of EPO observed in AZT treated mice were appropriate for the degree of anaemia observed when compared with phenylhydrazine (PHZ) treated mice. The numbers of BFU-e and the percentage of bone marrow erythroblasts observed were comparable in AZT and PHZ treated mice with similar degrees of anaemia. However, reticulocytosis was inappropriate for the degree of anaemia observed in AZT treated infected mice. AZT-induced peripheral anaemia in the face of increased numbers of BFU-e and increased levels of plasma EPO suggest a lesion in terminal differentiation.
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PMID:Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice. 200 15

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.
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PMID:[Effects of ethylene glycol on drug metabolizing enzymes in rat liver]. 202 9

Four patients with primary pulmonary hypertension, microangiopathic hemolysis, and thrombocytopenia were seen at the Charleston (WVa) Area Medical Center between 1983 and 1988. Characteristic laboratory and clinical features of these patients were the following: mild anemia, reticulocytosis, low serum haptoglobin value, microangiopathic red blood cell changes on peripheral blood smear, mild to moderate thrombocytopenia, normal clotting studies (ie, prothrombin time, partial thromboplastin time, fibrinogen), negative direct Coombs' test, negative glucose water test, normal serum urea nitrogen and creatinine levels, lack of improvement of hemolysis and thrombocytopenia in response to vasodilators or calcium channel blockers, and severe plexiform lesions in the pulmonary vasculature with fibrin deposition at autopsy. The hemolysis and thrombocytopenia probably developed as a result of flow through the fibrin deposition in the plexiform lesions in the pulmonary circulation and subsequent shearing of red blood cells and platelets.
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PMID:Primary pulmonary hypertension. Its association with microangiopathic hemolytic anemia and thrombocytopenia. 204 24

Aluminium and iron overload is often seen among long-term haemodialysis patients. Untreated non-de-aluminized dialysis water or the intake of large amounts of aluminium hydroxide as phosphate binders are the most common reasons for hyper-aluminaemia. Iron overload is mainly a result of multiple blood transfusions given to correct renal anaemia. In chronic dialysis patients, hypochromic anaemia is one of the clinical manifestations of a long-term overload of aluminium and perhaps of other metals, e.g. iron. We used deferoxamine (DFO) to chelate aluminium and excessive iron in 17 patients on chronic haemodialysis. Two grams of DFO was administered weekly in the form of an i.v. infusion during the last hour of the dialysis session. The mean serum aluminum concentration decreased from 407.3 micrograms/l to 184.2 micrograms/l within 3 years of treatment, the mean serum ferritin concentration from 1,563 micrograms/l to 487 micrograms/l within 2 years. Anaemia was corrected concomitantly with an increase in the haemoglobin level, which rose from 71.7 g/l to 80.8 g/l. The mean corpuscular volume increased from 83.8 fl to 91.3 fl. The need for blood transfusion also decreased significantly in all patients after the institution of DFO therapy. The clinical manifestations of aluminium and iron overload disappeared and the quality of life improved. No major side-effects were observed.
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PMID:Correction of haemodialysis-associated anaemia by deferoxamine. Effects on serum aluminum and iron overload. 207 70

Childhood lead poisoning is a man-made disease whose magnitude has not yet been measured in Chile. In the U.S.A. it has been estimated that 4 percent of children have elevated blood lead levels and that among poor black children, this rate is as high as 18 percent. The main sources of symptomatic lead poisoning are lead-based paint used in interior and exterior house surfaces, airborne lead from leaded gasoline and industrial emissions. Lead can be transferred from any source to soil and dust. Other sources of lead are contaminated food and water, occupational sources, and lead glazed pottery. Neurological symptoms (hyperactivity, distractibility, lower intellectual development), psychological difficulties (behavioral deficits), hematologic abnormalities (reduction in the biosynthesis of heme, anemia), and metabolic changes (reduction in concentration of 1-25 dihydroxy vitamin D and in the metabolism of erythrocyte pyrimidine) have been shown to occur in lead poisoning. Recent data suggests that prenatal exposure to lead my be related to minor congenital abnormalities, tumors of the kidney, and growth abnormalities.
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PMID:[Lead exposure and its effects on child health]. 207 88

Toxicity of environmental pollutants may be expressed as combined effects of a chemicals. Benzene, a proven hematotoxic agent, frequently occurs with toluene in cocontaminated groundwater. Groups of CD-1 male mice were exposed continuously for 4 weeks to benzene (166 mg/l), toluene (80 and 325 mg/l), and combinations of benzene (166 mg/l) + toluene (80 mg/l or 325 mg/l) in drinking water. Benzene-induced anemia was alleviated by simultaneous toluene treatment. Leukopenia and lymphopenia were observed in the case of benzene only and benzene + toluene (80 mg/l)-treated mice. The cytopenia, however, was less severe in the benzene + toluene (325 mg/l)-treated group. Immunotoxicity induced by benzene treatment alone was characterized by involution of thymic mass and suppressions of both B- and T-cell mitogeneses, mixed lymphocyte culture response to alloantigens, the tumor lytic ability of cytotoxic T-lymphocytes as determined by 51Cr-release assay, and antibody production response to T-dependent antigen (sheep red blood cells). IL-2 secretion by Con A-stimulated mouse T-cells was decreased in the benzene-treated group. Toluene (325 mg/l) completely inhibited these adverse effects when it was coadministered with benzene, while the low dose of toluene (80 mg/l) did not protect against benzene-induced depressions of immune functions. Toluene administered alone at levels up to 325 mg/l showed no obvious immunotoxic effects. Results of this study demonstrated that toluene, in sufficient amounts, has an antagonistic effect on benzene immunotoxicity.
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PMID:Subclinical effects of groundwater contaminants. III. Effects of repeated oral exposure to combinations of benzene and toluene on immunologic responses in mice. 214 47

The rotational dynamics of TEMPAMINE can be used to study directly the intracellular environment. The extracellular signal from TEMPAMINE is broadened away by the use of potassium ferricyanide which does not enter the cell. The EPR signal which results when 1 mM TEMPAMINE, 120 mM ferricyanide, and erythrocytes are mixed together arises from TEMPAMINE only in the intracellular aqueous space. The relative viscosity measured by the motion of TEMPAMINE in various control environments is: water at 37 degrees C = 1; human plasma at 37 degrees C = 1.1; internal aqueous environment of washed erythrocytes or whole blood at 37 degrees C = 4.92 +/- 0.32. Erythrocytes can be fractionated by density. In sickle-cell anemia (SS), the percentage of cells we find with density greater than 1.128 g/ml is 15-40%, in normals (AA) and sickle trait (AS) 1%. By direct spin-label measurements with TEMPAMINE we show, for the first time, that the relative internal viscosity (eta mu) of these dense erythrocytes is markedly elevated and density-dependent. Our results show that (1) eta mu increases with increasing cell density; (2) eta mu obtained from sickle cells is higher than eta mu obtained from normal cells at a given density, and this effect is greater at 37 degrees C than at 20 degrees C; (3) eta mu is proportional to MCHC, but eta mu in erythrocytes is higher than eta mu obtained from in vitro preparations of hemoglobin S at equivalent concentrations. We conclude that the relative internal viscosity of erythrocytes is affected by three factors: the state of cell hydration, the amount of hemoglobin polymer present, and the potential interactions of the cell membrane with intracellular hemoglobin.
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PMID:Direct measurement of the internal viscosity of sickle erythrocytes as a function of cell density. 216 86


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