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)

Recombinant human erythropoietin (r-HuEPO) was administered in two phases to 12 patients with chronic renal insufficiency (creatinine clearances of 0.17-0.51 ml/second [10-30 ml/minute]) and uremic anemia. In addition to the routine tests done as part of a multicenter clinical trial, our patients had serial red cell mass measurements, quantitation of bone marrow stem cells, and marrow cytogenetic analysis. During the first eight weeks (acute phase), an equal number of patients was randomized to placebo or one of three doses of r-HuEPO (50, 100 or 150 unit/kg intravenously three times weekly). All three patients receiving 150 unit/kg responded by increasing their packed cell volume (PCV) to the normal range within eight weeks. There were lesser responses in PCV at the two lower doses of r-HuEPO and no response in the placebo group. The 51Cr red cell mass also increased significantly in a dose-related manner in patients receiving r-HuEPO but did not change in the placebo group. Marrow studies revealed increases in erythroid, megakaryocyte, and granulocyte-monocyte progenitor cells in those patients on r-HuEPO, but no mutagenic effects were seen. Subsequently, ten patients received open label r-HuEPO. During this maintenance phase, all ten achieved or maintained a normal PCV. Several adverse events occurred, but none were definitely linked to r-HuEPO. Recombinant human erythropoietin is an effective and potent treatment of anemia caused by renal failure.
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PMID:Treatment of the anemia of predialysis patients with recombinant human erythropoietin: a randomized, placebo-controlled trial. 317 33

In this communication, we describe an unusual patient with a reported lifelong history of anemia. Investigation of the pathogenesis of this patient's bone marrow failure provided an interesting opportunity to determine the role of T cells in the regulation of human blood cell production. Phenotyping of the patient's mononuclear cells revealed severe T cell hypoplasia in both the peripheral blood and bone marrow. The patient's bone marrow was capable of producing 50-60% of the normal numbers of burst-forming units--erythroid (BFU-E) in the presence of optimal concentrations of erythropoietin, suggesting that marrow BFU-E formation is in part independent of T cells. Addition of small numbers of class I identical donor T cells enhanced BFU-E cloning efficiency to a level observed in normal controls. This enhancing effect was supplied by a T4+ (CD4) population of donor cells. The addition of donor T cells partially corrected the inability of patient marrow cells to produce megakaryocyte and mixed colonies. These studies suggest that prolonged T cell hypoplasia might deprive marrow progenitor and stem cells of a necessary enhancing effect that is required for sustained normal hematopoiesis. Such a T cell defect in rare instances may result in bone marrow failure.
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PMID:Influence of T lymphocytes on hematopoiesis in a patient with T cell hypoplasia. 325 44

The alkaline phosphatase-antialkaline phosphatase (APAAP) immunocytochemical staining technique was used to look for circulating cells of megakaryocyte lineage in peripheral blood smears from 67 cases of myelodysplasia. Small numbers of micromegakaryocytes positive for platelet glycoprotein IIIa were found in 23 cases. These cells superficially resemble small lymphoid cells and are hence difficult or impossible to recognise in conventional Romanowsky stained smears. Circulating micromegakaryocytes were found most commonly in more aggressive types of myelodysplasia (such as refractory anaemia with excess blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEB-t], and their presence may therefore indicate a poor prognosis. Because of the simplicity of this immunocytochemical labelling technique, it could be of wide use in the initial assessment of patients with myelodysplasia, and possibly for the early detection of acute leukaemic transformation.
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PMID:Circulating micromegakaryocytes in myelodysplasia. 332 97

Patients with the anemia of end-stage renal disease (ESRD) fail to display an appropriate compensatory increase in red cell production. In order to investigate the extent to which the impaired erythropoietic response is determined at the progenitor cell level, we determined the frequencies of marrow colony-forming cells in 11 anemic and 3 non-anemic, dialysis-dependent ESRD patients and 10 healthy individuals. In addition, we measured serum levels of erythropoietin (Epo) by radioimmunoassay. There were no significant differences (P greater than 0.1) between normal and ESRD groups in the frequencies of primitive or late erythroid (BFU-E and CFU-E, respectively), granulocyte-macrophage, and megakaryocyte progenitors, CFU-E/BFU-E ratios, or serum Epo levels. In contrast, 5 non-uremic patients with chronic anemia comparable in severity to the anemic ESRD patients had serum Epo levels and CFU-E/BFU-E ratios that were significantly increased (P less than 0.05 and P less than 0.001, respectively) in comparison to the normal controls and ESRD patients. Pre-dialysis serum and plasma from both ESRD groups were as supportive of autologous erythroid and non-erythroid colony growth in vitro as normal serum and plasma; inhibition was not observed. We conclude that the relative numbers of erythroid and non-erythroid progenitors and the majority of serum Epo levels are unchanged from normal in patients with the anemia of ESRD. However, their normal CFU-E/BFU-E ratio reflects an inadequate compensatory erythropoietic response due to their inability to appropriately increase Epo production in response to anemia. Inhibitors of autologous erythroid colony formation were not detected in ESRD serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The anemia of end-stage renal disease: hematopoietic progenitor cell response. 339 87

We studied a patient with a long history of ethanol abuse who presented to the hospital with profound weakness, anaemia and thrombocytopenia. Evaluation of these problems revealed the patient's bone marrow to be hypercellular but severely iron depleted and almost totally devoid of morphologically recognizable megakaryocytes. However, we were able to detect the presence of non-morphologically recognizable, immature megakaryocytes in the same sample using an immunochemical detection technique. This circumstance allowed us to study the relative importance of both megakaryocyte maturation and peripheral blood platelet count on the production of megakaryocyte colony stimulating activity (Meg-CSA), a putative regulator of the megakaryocyte colony forming unit (CFU-M). The results of our investigations disclosed a rapid decline in serum Meg-CSA levels which preceded recovery of the platelet count and appeared to coincide with the maturation of megakaryocytes into the morphologically recognizable pool. The effect of ETOH on the patient's CFU-M cloning efficiency was also studied. ETOH in amounts up to 454 mg/dl did not inhibit cloning of the patient's peripheral blood CFU-M in plasma clot cultures. Our results suggest that regulation of Meg-CSA production is a complex function which appears to be dependent on a number of factors including the level of megakaryocyte maturation in the marrow. We also speculate that ethanol associated thrombocytopenia may occasionally be brought about by a disruption in the process of megakaryocyte maturation at the level of a progenitor more mature than the CFU-M.
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PMID:Transitory hypomegakaryocytic thrombocytopenia: aetiological association with ethanol abuse and implications regarding regulation of human megakaryocytopoiesis. 348 65

The polyamine spermine has been reported to be the inhibitor of in vitro erythropoiesis present in uremic serum. We have employed a panel of hematopoietic colony-forming assays to evaluate the specificity of the inhibitory activity. Spermine and its precursor spermidine when added to culture inhibited mouse and human erythroid (CFU-E and BFU-E), granulocyte-macrophage, and megakaryocyte colony growth in a non-specific, dose-dependent fashion. Erythroid and non-erythroid colony growth were equally sensitive to spermine- and spermidine-induced inhibition. Increasing concentrations in culture of erythropoietin and mitogen-stimulated leukocyte-conditioned medium, a source of colony-stimulating activity, failed to overcome the in vitro inhibition. Although anemia is characteristic of chronic renal failure (CRF), leukopenia and thrombocytopenia are not. Therefore, we conclude that the non-specific inhibitory activity of spermine and spermidine, as defined by in vitro colony assays, is either of no pathophysiologic significance in the anemia of CRF, or else there are unrecognized repair mechanisms in vivo which maintain granulopoiesis and thrombopoiesis at normal levels.
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PMID:Spermine and spermidine are non-specific inhibitors of in vitro hematopoiesis. 356 Jun 47

The Belgrade laboratory rat (b/b rat) has hereditary, hypochromic, microcytic anemia with a variety of red cell abnormalities. Although this anemic syndrome has been recently ascribed to the defective delivery of iron to the developing red cell, the basic hematopoietic defect is still unknown. In this article we present evidence that the b/b rat has an additional hematologic defect. We have found that the megakaryocyte number in the marrow of the b/b rat is decreased to one half that of the normal rat, but the maturation rate of recognizable megakaryocytes is accelerated and the size is increased. The platelet count is moderately reduced. These findings indicate that megakaryocytopoiesis in the anemic b/b rat is abnormal and suggest that the genetic defect may involve the progenitors of the megakaryocyte cell lineage. Alternatively, the megakaryocytic abnormalities may be secondary to the severe anemia.
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PMID:Abnormal megakaryocytopoiesis in the Belgrade laboratory rat. 396 52

The antiviral drug ribavirin (1, beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) produced significant hematologic effects when administered to rhesus monkeys by intramuscular injection over 10 days in doses of 30 or 100 mg/kg/day. The monkeys developed dose-related progressive anemia and thrombocytosis associated with marrow erythroid hypoplasia and megakaryocyte hyperplasia. In addition, bone marrow examination revealed phagocytosis of erythroid elements by histiocytes; vacuolization of erythroid precursors, and to a lesser extent precursors of other cell types; and occasional erythroid precursors with megaloblastoid appearance. The alterations were transient and disappeared on discontinuation of the drug.
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PMID:Morphological alterations in blood and bone marrow of ribavirin-treated monkeys. 643 84

Three patients developed blastic transformation of essential thrombocythemia (tET). Morphological studies in all patients showed that the majority of blasts had either myeloblastic or myelomonoblastic differentiation. Immunologic assays of hematopoietic cells were performed in two patients. In patient 1, 86% of peripheral blood mononuclear cells (predominantly blasts) reacted with a monoclonal antibody specific for granulocytes and monocytes (MMA), and 15% of mononuclear cells reacted with Tab, a monoclonal antibody specific for megakaryocyte-platelet glycoproteins (PGP) IIb and IIIa. In patient 2, 41.5% of peripheral blood mononuclear cells (predominantly blasts) were MMA-positive, 22.5% were Tab-positive, and 40% reacted with rabbit anti-human PGP. These results suggest either that two subpopulations of blast cells exist in tET, or that blast cells simultaneously express surface markers of myeloblastic/monoblastic and megakaryoblastic differentiation. In these three and in nine previously reported cases of tET, neither age, sex, nor previous therapy were obvious etiologic factors. tET occurred 24.2 +/- 14.4 mo after diagnosis of essential thrombocythemia, and a majority of patients had hepatomegaly and/or splenomegaly, anemia, leukocytosis, and thrombocytopenia. Leukemic cell morphology was myeloblastic and/or monoblastic in 12/12 patients, 5/12 had marrow fibrosis. Despite various treatments, death occurred in 3.6 +/- 2.7 mo; one patient had a brief complete remission.
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PMID:Blastic transformation of essential thrombocythemia: dual expression of myelomonoblastic/megakaryoblastic phenotypes. 653 50

Idiopathic thrombocytopenia purpura (ITP) was diagnosed in 54 dogs. Bleeding was associated with platelet counts less than or equal to 30,000/mm3, and occurred most frequently at mucosal surfaces and in the skin. Other hematologic changes were variable, the most common being regenerative anemia with leukocytosis. Bone marrow examination revealed variable megakaryocyte numbers, but hyperplasia was most commonly observed. Results of the platelet factor 3 test were positive in only 7 of 25 dogs so tested. Treatment included various combinations of corticosteroid, vincristine, cyclophosphamide, and splenectomy. The dogs could be classified into 4 groups on the basis of the course of disease: (1) 14 dogs that died or were euthanatized during the first episode of thrombocytopenia, (2) 17 dogs that recovered after a single episode of thrombocytopenia (acute ITP), (3) 8 dogs in which thrombocytopenia recurred over a period of up to 8 months before recovering (acute, recurrent ITP), and (4) 15 dogs that experienced repeated episodes of ITP for periods of up to 8 years (chronic ITP).
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PMID:Canine idiopathic thrombocytopenia: clinical observations and long-term follow-up in 54 cases. 654 41


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