Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a low-molecular-weight heparin, faxiparin (Nadroparin), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1-20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro, and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also acted synergistically with heparin cofactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4 d at 0.1-25 IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis.
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PMID:Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in vitro and in vivo in mice. 781 73

The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in adult aplastic anemia patients whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously every day at a dose of 3,000IU/body for two weeks, and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. In cases in whom Hb concentration increased by more than 1g/dl or whose transfusion requirements reduced to less than 50%, treatment was judged to be effective. The whole rate of efficacy was 34.5% (10/29). Response to epoetin alpha treatment was better in patients whose symptoms were relatively mild. Mild cases responded to the treatment with 6,000IU/body/day, although a dosage of 24,000IU/body/day was required in moderate or severe cases. Neither serious adverse effect nor abnormal laboratory findings were observed. These results suggest that high dose subcutaneous epoetin alpha treatment is effective for the aplastic anemia in terms of increasing Hb concentration and reducing blood transfusions.
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PMID:[Effects of rHuEPO on aplastic anemia: results of a phase II clinical study]. 823 Jul 42

An immunologic crossreactant of erythropoietin seemed to develop and persist in serum samples from a patient during treatment and remission of idiopathic aplastic anemia. It had a steeper slope to radioimmunoassay log-dose response lines and a larger molecular size than erythropoietin. On fractionation of serum, the apparent crossreactant was bound by staphylococcal Protein A at pH 7.5 and recovered by elution from it at pH 3.0. Adsorption of serum from the patient, and from one of two similarly affected children, with rabbit IgG linked to agarose appeared to remove completely the apparent crossreactant. These treated sera gave radioimmunoassay log-dose response lines essentially parallel to that given by the International Reference Preparation (IRP) for erythropoietin and estimates of immunoreactive erythropoietin appropriate to the normal hemoglobin concentrations. The apparent crossreactant of erythropoietin is thus accounted for by heterophilic antibodies to rabbit IgG. These developed in the patient following treatment with rabbit antilymphocyte globulin but seem to have arisen spontaneously in the children. Thus iatrogenic and idiopathic antibodies to rabbit IgG interfered in a radioimmunoassay for erythropoietin in serum through their ability to react with the radioimmunoassay anti-erythropoietin antiserum raised in rabbits.
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PMID:Invalidity from nonparallelism in a radioimmunoassay for erythropoietin accounted for by human serum antibodies to rabbit IgG. 824 69

Because GM-CSF possesses burst-promoting activity (BPA) and megakaryocyte colony-stimulating activity (Meg-CSF) as well as stimulating activity on granulocyte-macrophage progenitors, and erythropoietin (Epo) has thrombopoietin-like activity, the combination therapy of GM-CSF and Epo seems to be more effective for stimulating erythropoiesis and thrombocytopoiesis in patients with pancytopenia. For this reason, the combination therapy of recombinant human GM-CSF (rhGM-CSF) and rhEpo was performed in two patients with refractory anemia (RA) and aplastic anemia (AA). Epo-unresponsive anemia was remarkably improved by adding rhGM-CSF to Epo and the effect lasted for 1 1/2 months in a patient with RA, but severe anemia occurred again immediately after the discontinuation of Epo. The neutralizing antibodies against GM-CSF were not demonstrated at the phase when anemia re-progressed in this patient. In a patient with AA, anemia and thrombocytopenia, which were refractory to previous administration of rhGM-CSF, responded to the combined administration of GM-CSF and Epo. Although the effects were maintained for 3 1/2 months, the anemia and thrombocytopenia became worse again after the administration of rhGM-CSF was changed from daily to every other day. These findings suggest the usefulness of combination therapy of GM-CSF and Epo for patients with pancytopenia.
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PMID:Combination therapy with rhGM-CSF and rhEpo for two patients with refractory anemia and aplastic anemia. 824 8

In the past anabolic steroids were the first-choice treatment for pancytopenic disorders that were often poorly classified. They are now superseded by other more recently developed methods of treatment--for example bone marrow transplantation and immunosuppression. This contrasts to the authors' experience, and to that of many other haematologists, who have noted anabolic steroid-induced responses in patients who were unsuitable for or unresponsive to the new treatments. Anabolic steroids did not, however, demonstrate an obvious effect in recent controlled trials involving patients with aplastic anaemia. Their use with immunosuppressive treatment is currently under investigation. Although anabolic steroids rarely reverse the course of anaemia in a myelodysplastic syndrome, even a slight haemopoietic improvement is desirable. Children with Fanconi's anaemia may benefit from a reduced transfusion requirement. Uraemic patients may experience significant side effects on standard erythropoietin (epo) treatment. There have been no controlled trials comparing epo versus anabolic steroids or epo versus epo in conjunction with anabolic steroids. Data from uncontrolled studies indicate a better response to anabolic steroids in children and females than in men. In spite of the fact that anabolic steroids have been used for almost 30 years, they should be carefully re-evaluated in scientifically controlled trials to test their efficacy and to compare them with the new treatments. Such trials, however, are impeded by the limited knowledge available with regard to pharmacological parameters and optimal treatment schedules.
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PMID:Anabolic steroids and blood cell production. 825 51

All cases of transient erythroblastopenia in children less than 10 years of age, diagnosed in Sweden during the years 1987-89, were identified. Almost all (51/53) were less than 3 years of age. In this group, the incidence was 4.3/100 000, which is the same as that of acute lymphatic leukaemia. No geographical, but a possible temporal, cluster was seen in 1989. The anaemia was severe in some cases; haemoglobin concentration was less than 40 g/l in 8 of 53 children. Thrombocytosis and neutropenia were common and were attributed to high endogenous erythropoietin activity. Thirty-seven of 53 children were given a blood transfusion. All children recovered and no complications or relapses were seen. Transient erythroblastopenia of childhood is a benign disease, and it is important to make a correct diagnosis to prevent unnecessary anxiety for leukaemia or aplastic anaemia.
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PMID:Transient erythroblastopenia of childhood in Sweden: incidence and findings at the time of diagnosis. 833 93

We evaluated a newly developed enzymeimmunoassay for serum erythropoietin (Epo) and investigated relationship between Epo levels and hematological disorders. This method has several advantages including simplicity, high sensitivity, good precision. Moreover, the procedure requires only about 2.5 hours. Samples from 134 healthy subjects showed a normal logarithmic distribution, and its normal range was 4.5 approximately 21.3 mU/ml. The levels of Epo in normal subjects and various hematological disorders were as follows: 10.5 +/- 4.1 (mean +/- SD mU/ml) in normal subjects, 2.2 +/- 1.7 in polycythemia vera (PV), 6.1 +/- 3.1 in essential thrombocythemia, 17.8 +/- 27.3 in chronic myelogeneous leukemia, 3.6 +/- 1.8 in stress erythrocytosis, 39.4 and 14.1 in two cases of primary myelofibrosis, 1289 +/- 4798 in iron deficiency anemia and 6564 +/- 10870 in aplastic anemia. In patients with PV, serum Epo were low and did not correlate with hemoglobin concentration. However, inverse correlation was found between changes of Epo levels and hemoglobin levels in most patients. In cases in which PV progressed into myelofibrosis, anemia developed and Epo levels increased accordingly. These results suggest that the method is thought to be useful and reliable for the diagnosis and monitoring of PV and related hematological disorders.
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PMID:[Evaluation of a one step sandwich enzymeimmunoassay for serum erythropoietin--serum erythropoietin values in polycythemia vera and related hematological disorders]. 835 12

The regulation of megakaryocytopoiesis and platelet production has not yet been clearly elucidated. Several cytokines have been shown to be capable of producing megakaryocyte colonies from bone marrow [i.e. Interleukin (IL)-3, granulocyte-macrophage (GM)-colony-stimulating factor (CSF), erythropoietin (Epo)]. In addition, other activities have been reported to stimulate megakaryocyte precursors, yet a megakaryocyte-CSF (Meg-CSF) has not been purified to homogeneity and IL-3, GM-CSF and/or Epo often contaminate purification attempts which could account for the activities. A Meg-CSF has been isolated from the urine of patients with aplastic anaemia and purified by sequential ultrafiltration, cation exchange, G-50 chromatography, preparative PAGE, chromatofocusing and cation exchange HPLC. The activity of this material is 2-4 x 10(4) CFU-Meg/mg as measured in a murine marrow, serum-containing assay. This activity also stimulates CFU-Meg in the absence of adherent accessory cells and in serum-free cultures, indicative of the direct stimulation on CFU-Meg. Immunoassays, colony forming assays, and proliferation assays demonstrate that purified Meg-CSF has no GM-CSF, IL-3, M-CSF, G-CSF or IL-1 alpha, -3, -6, -9 and -11. In confirmation of these results, neutralizing antibody to IL-6 also did not abrogate Meg-CSF activity. Therefore the previously-reported megakaryocyte colony-stimulating activity in purified aplastic anaemia patient urine is due to a unique cytokine: Meg-CSF.
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PMID:Megakaryocyte colony-stimulating factor (Meg-CSF) is a unique cytokine specific for the megakaryocyte lineage. 839 18

Blood erythropoietin (EPO) concentration was measured by radioimmunoassay in 513 patients with various diseases. Untreated polycythemia vera showed lower EPO concentration than normal. Aplastic anemia (AA) revealed the highest EPO level among all anemic diseases in relation to hematocrit value. EPO level of AA patients who underwent bone marrow transplantation was as low as normal subjects even when the anemia has not fully recovered. Paroxysmal nocturnal hemoglobinuria (PNH) showed unusually high EPO concentration among hemolytic anemias. In normal subjects, blood EPO concentration showed a diurnal rhythm that was higher at night than during the daytime. These findings suggest the diagnostic usefulness of measurement of EPO in blood diseases.
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PMID:[Clinical usefulness of measurement of erythropoietin in blood]. 841 44

The cell cycle status of human erythroid precursors generated in a two-step liquid culture was studied by a double-labeling flow cytometric technique. Following a first phase, where peripheral blood mononuclear cells were cultured in the presence of a combination of growth factors, not including erythropoietin (Epo), the cells were washed and recultured in a second phase in the presence of Epo. This procedure resulted in a stimulation of the proliferation and maturation of erythroid precursors. In the presence of optimal concentrations of Epo (2 U/mL), a high percentage (> 40%) of cells were found in the S phase of the cell cycle until day 10. Then, as a result of maturation, the proportion of cells in S gradually decreased, reaching less than 2.0% by day 21. At this time, the culture consisted of > 95% hemoglobin-containing, nonproliferating, orthochromatic normoblasts. Cell cycle analysis of this normoblast population demonstrated a bimodal distribution; while the majority of the cells had a diploid (2C) DNA content, i.e., cells in G1 (or G0) phase, a sizable fraction was tetraploid (4C) corresponding to cells in G2. In contrast, in cultures stimulated with physiological concentrations of Epo (around 50 mU/mL), all the terminally differentiated cells were arrested at the G1 phase. These results suggest that Epo is an essential growth-promoting factor for erythroid precursors, but supraphysiological concentrations, such as present in vivo in severe anemia (e.g., aplastic anemia) or after Epo administration, may be associated with development of normoblasts with abnormal DNA content.
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PMID:Stimulation of erythroid progenitors by high concentrations of erythropoietin results in normoblasts arrested in G2 phase of the cell cycle. 841 55


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