Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured serum erythropoietin levels serially in 31 renal-transplant recipients treated with cyclosporine, using the recently developed recombinant human erythropoietin-based radioimmunoassay. The mean (+/- SEM) serum erythropoietin concentration in these patients before transplantation (14 +/- 2 U per liter) was similar to that in normal subjects who did not have anemia. A transient postoperative 9-fold increase (range, 0- to 74-fold) in the serum erythropoietin levels was followed by a smaller (3-fold) and sustained (28 +/- 3 days) second elevation. The initial increase occurred in the absence of graft function and was not accompanied by an erythropoietic response, whereas the second increase was associated with graft recovery and the complete resolution of the anemia. Serum erythropoietin levels returned to normal as the hematocrit rose above 0.32. Thereafter, the hematocrit continued to rise toward normal, while the serum erythropoietin levels remained normal. The patients in whom erythrocytosis or iron-deficiency anemia developed had persistently elevated serum erythropoietin levels. We conclude that in patients who have undergone renal transplantation, slight increases in endogenous erythropoietin levels induce erythropoiesis to the same extent as do large doses of exogenous erythropoietin in patients with uremia. Moreover, once initiated, erythropoiesis in renal-transplant recipients may be sustained by normal serum erythropoietin levels. These results suggest that the restoration of renal function improves the erythropoietic response to erythropoietin.
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PMID:Serum erythropoietin levels after renal transplantation. 266 10

Five patients undergoing long-term hemodialysis with transfusional iron overload received treatment for 18 weeks with a regimen of recombinant human erythropoietin (150 U/kg) and regular phlebotomy to maintain the hematocrit value at 25% and reduce the total body iron burden. In the 149 phlebotomy sessions performed in these patients, a mean of 228 +/- 8 ml (mean +/- SEM) of whole blood was removed; it had a hematocrit value of 27.7% +/- 0.2%. The iron content of the erythrocytes removed (erythrocyte iron concentration, 787 +/- 11 micrograms/ml in 133 samples) accounted for more than 99% of the total iron removal by phlebotomy. Serum iron (serum iron concentration, 1.57 +/- 0.09 micrograms/ml in 65 samples) accounted for an insignificant fraction of the total iron removed. The iron removed at each phlebotomy session averaged 49.1 +/- 2.0 mg, similar to the amount of iron removed with deferoxamine administration in patients undergoing dialysis who had iron overload, but without the potential for adverse side effects reported with long-term deferoxamine therapy. Total iron removal during the 18 weeks of this study ranged from 732 to 2797 mg. Mean serum ferritin level decreased from 3189 +/- 1076 micrograms/L to 1676 +/- 342 micrograms/L (p less than 0.02, Wilcoxon signed rank test). When compared with a group of five patients without transfusional iron overload who received recombinant human erythropoietin and did not undergo therapeutic phlebotomy, the patients with iron overload had much greater iron losses and a larger decrease in serum ferritin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transfusional iron overload in patients undergoing dialysis: treatment with erythropoietin and phlebotomy. 275 6

The relationship of serum erythropoietin (Ep) levels to hematocrit and glomerular (GFR) filtration rate was evaluated in patients with chronic renal disease. The Ep level was measured by radioimmunoassay in 119 blood samples from 48 patients obtained over a period of up to 5 years. Hematocrit values correlated significantly with the GFR, but serum Ep levels did not change with a decline in the GFR. Significant anemia was noted only when the GFR fell below 20 ml/min/1.73 m2. Episodes of spontaneous acute hypoxic stress were observed in six patients with chronic renal failure. Serum Ep levels obtained during these episodes (mean +/- SEM: 273 +/- 76 mU/ml) were tenfold higher than Ep levels during stable steady-state chronic renal failure (26 +/- 6 mU/ml), even though Ep levels were inappropriately low for the degree of anemia in the stable state. Our findings suggest that the tissue oxygenation-Ep-hematocrit feedback mechanism operates at a lower set point in patients with chronic renal failure in comparison with normal subjects.
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PMID:Relation of serum erythropoietin levels to renal excretory function: evidence for lowered set point for erythropoietin production in chronic renal failure. 319 6

Effects of an acute increase in blood O2 affinity on erythropoietin production were studied in normoxic and hypoxic male rats. Blood O2 affinity was increased by exchange-transfusion with blood from sodium cyanate treated rats. P50 was lowered to 27.6 torr (pH 7.4, PCO2 = 40 torr, 37 degrees C) in the recipients compared to 41.8 torr in control rats exchange transfused with normal blood. Hypoxia was induced by exposure to simulated high altitude (4750 or 7000 m) for 16 h. Erythropoietin was determined by in vivo bioassay. In rats with normal blood O2 affinity, plasma erythropoietin was undetectable at 300 m, 0.26 +/- 0.10 U/ml at 4750 m (mean +/- SEM; n = 7), and 3.52 +/- 0.58 U/ml at 7000 m (n = 10). Plasma erythropoietin titers were significantly enhanced in rats with high blood O2 affinity at 300 m (0.05 +/- 0.01 U/ml; n = 4) and moderately increased at 4750 m (0.57 +/- 0.12 U/ml; n = 7), but unchanged at 7000 m (3.88 +/- 0.74 U/ml; n = 10). These results indicate that a high blood O2 affinity reduces the O2 delivery to the cells controlling erythropoietin production in normoxia and moderate hypoxia. However, this is offset at severe hypoxia most likely by an improved O2 loading to the blood.
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PMID:Erythropoietin production in normoxic and hypoxic rats with increased blood O2 affinity. 400 4

The activity capable of promoting the growth of human erythroid burst-forming cells (BFU-E) in culture was measured in the sera from 39 patients with aplastic anemia (AA) and compared with similar activity in patients with various other hematologic disorders and 31 normal subjects. Burst-promoting activity (BPA) was determined by its ability to support erythroid burst growth from adherent cell-depleted normal human marrow cells. The results were expressed as the percentage of burst growth supported by test serum compared with cultures established in the presence of 20% test serum and 2.5% phytohemagglutinin-stimulated lymphocyte conditioned medium. The mean BPA level in normal serum was 18.5% (1.5 +/- SEM) and was not significantly different from BPA levels in patients with various forms of nonhypoplastic anemia or polycythemia (10.2% +/- 1.2%). In contrast, 15 of the 39 patients with AA had elevated BPA levels, ranging from 40.0% to 106.0%. These elevated levels did not correlate with serum erythropoietin or hematocrit values, white blood cell count, platelet count, time from diagnosis, or the presence or numbers of BFU-E in circulation. The BPA was shown not to be T cell growth factor (interleukin-2), and the effect was not blocked by the addition of cyclosporine to culture, consistent with a direct effect of this activity on BFU-E. When the 39 patients with AA were treated with antithymocyte globulin, 20 obtained a complete or partial remission. BPA levels determined from sera obtained before treatment did not correlate with response or duration of survival but did correlate with granulocyte-macrophage colony-stimulating activity (GM-CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors in human serum. erythroid burst-promoting activity in normal subjects and in patients with severe aplastic anemia. 404 96

In order to quantitate early erythroid progenitor cells in paroxysmal nocturnal hemoglobinuria (PNH), we have cultured peripheral blood mononuclear cells from 7 PNH patients in a 0.8% methylcellulose medium containing erythropoietin, 2 U/ml. In our experimental conditions, the number of erythroid colonies obtained per 5 X 10(5) mononuclear cells plated was 20.1 +/- 1.9 (SEM) in normal subjects and 2.8 +/- 0.56 (SEM) in PNH patients. In plates from PNH subjects, 38 of 117 showed no growth of erythroid colonies, whereas plates from normal subjects always had colonies. Our findings suggest that PNH patients, despite their hemolytic condition, have a depleted erythroid precursor compartment, and this may play a major role in the pathogenesis of their anemia.
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PMID:Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria. 708 35

In the absence of conclusive assays capable of determining the functionality of ex vivo expanded human hematopoietic progenitor cells, we combined cell tracking with the membrane dye PKH2, immunostaining for CD34, and limiting dilution analysis to estimate the frequency of long-term hematopoietic culture-initiating cells (LTHC-ICs) among de novo-generated CD34+ cells. Umbilical cord blood (CB) and bone marrow (BM) CD34+ cells were stained with PKH2 on day 0 and cultured with stem cell factor (SCF) and interleukin-3 (IL-3) in short-term stromal cell-free suspension cultures. Proliferation of CD34+ cells in culture was tracked through their PKH2 fluorescence relative to day 0 and the continued expression of CD34. As such, it was possible to identify cells that had divided while maintaining the expression of CD34 (CD34+PKH2dim) and others that expressed CD34 but had not divided (CD34+PKH2bright). In all such cultures, a fraction of both BM and CB CD34+ cells failed to divide in response to cytokines and persisted in culture for up to 10 days as CD34+PKH2bright cells. Between days 5 and 7 of culture, CD34+PKH2bright and CD34+PKH2dim cells were sorted in a limiting dilution scheme into 96-well plates prepared with medium, SCF, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor, and erythropoietin. Cells proliferating in individual wells were assayed 2 weeks later for their content of clonogenic progenitors and the percentage of negative wells was used to calculate the frequency of LTHC-ICs in each population. Among fresh isolated BM and CB CD34+ cells, the frequencies of LTHC-ICs were 2.01% +/- 0.98% (mean +/- SEM) and 7.56% +/- 2.48%, respectively. After 5 to 7 days in culture, 3.00% +/- 0.56% of ex vivo-expanded BM CD34+PKH2bright cells and 4.46% +/- 1.10% of CD34+PKH2dim cells were LTHC-ICs. In contrast, the frequency of LTHC-IC in ex vivo expanded CB CD34+ cells declined drastically, such that only 3.87% +/- 2.06% of PKH2bright and 2.29% +/- 1.75% of PKH2dim cells were determined to be initiating cells after 5 to 7 days in culture. However, when combined with a calculation of the net change in the number of CD34+ cells in culture, the sum total of LTHC-ICs in both BM and CB cells declined in comparison to fresh isolated cells, albeit to a different degree between the two tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evaluation of ex vivo expansion potential of cord blood and bone marrow hematopoietic progenitor cells using cell tracking and limiting dilution analysis. 753 90

Endogenous erythropoietin (EPO) secretion can still be modulated in patients with end-stage renal failure but only in response to strong stimuli. Thus even anephric dialysis patients are able to increase EPO production acutely when exposed to a marked hypoxic stimulus. The present study was designed to test the hypothesis that a decrease of plasma calcium or the administration of various antihypertensive agents might be able to induce acute changes of plasma EPO concentration. Four groups of chronic hemodialysis patients were studied. Eight patients volunteered for the induction of an acute, transient hypocalcemia via a calcium-free dialysate during the initial 60 min of a regular dialysis session of 240 min. Plasma immunoreactive (i) EPO, total calcium, and intact parathyroid hormone (iPTH1-84), as well as blood ionized calcium and blood gases were measured before as well as 30, 60, 120 and 240 min after the start of dialysis. In addition, plasma iEPO was measured 48 h after the session. Patients of group 2 (n = 6), group 3 (n = 6), and group 4 (n = 7) received the day after a hemodialysis session a single dose of either acetazolamide, furosemide, or enalapril, respectively, and their plasma iEPO was determined before and 3, 6 and/or 24 h after drug administration. In group 1, plasma total calcium decreased from 2.39 +/- 0.07 mM (mean +/- SEM) to 1.98 +/- 0.02 and 1.83 +/- 0.03 mM after 30 and 60 min of dialysis, respectively, and blood ionized calcium from 1.28 +/- 0.04 to 1.02 +/- 0.03 and 0.92 +/- 0.04 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No acute change of serum erythropoietin in response to hypocalcemia or antihypertensive agents in uremic patients. 756 3

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis. 861 62


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