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)

We studied the effects of several cytokines on the development of granulocyte-macrophage (GM) progenitors using the serum-deprived culture. SCF plays an important role in the GM-CSF- or IL-3-dependent production of neutrophils and macrophages. In vitro colony assay also suggests an increase in sensitivity of GM progenitors to cytokines (GM-CSF, IL-3, G-CSF and/or SCF) in a patient with juvenile chronic myelogenous leukemia. A high level of serum IFN-gamma was associated with leukopenia and thrombocytopenia in a patient with hemophagocytic syndrome. Based on the evidence that IFN-gamma significantly inhibited the proliferation of GM progenitors, IFN-gamma-mediated suppression was suggested as one of the mechanisms causing cytopenia. In patients with aplastic anemia and neutropenia, an increase of serum G-CSF levels was observed when neutrophils decreased remarkably in number. However, the serum SCF levels were constant in these patients. A failure of SCF to enhance colony growth in some patients with aplastic anemia implies qualitative abnormalities of hematopoietic progenitors.
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PMID:[Abnormalities in regulation system of granulopoiesis]. 768 32

The colony-stimulating factors (CSFs) have emerged as effective drugs in a variety of clinical situations. These drugs stimulate the production and activity of haematopoietic cells in vitro and in vivo. Two members of this group, granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been approved in the US and Europe for use following cytotoxic chemotherapy and autologous bone marrow transplantation. Other uses of the CSFs include myelodysplastic syndromes, aplastic anaemia, the acquired immunodeficiency syndrome (AIDS) and cyclic and congenital neutropenias. Although CSFs have generally been well tolerated in clinical use there are a number of theoretical concerns, including disease acceleration, biased stem cell commitment and bone marrow exhaustion. New CSFs are currently under development. Combinations of growth factors in the future may maximise effectiveness while minimising toxicity.
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PMID:Use and toxicity of the colony-stimulating factors. 768 34

Haematological dyscrasias remain important because they are potentially fatal. Their accurate reporting is required to confirm the cause-effect relationship of suspected adverse drug reactions (ADRs); to estimate their incidence; and, by risk-benefit analysis of such events, to introduce preventive measures to reduce their impact. Limitations within the available data on haematological ADRs are reviewed and some suggestions made for improvement. The drugs most commonly associated with haematological dyscrasias are listed. An understanding of the pathogenesis of haematological dyscrasias is essential for their effective management and these are briefly reviewed. Features common to the management of the different types of haematological dyscrasia include the early involvement of a haematologist and drug information pharmacist and the accurate identification and early withdrawal of any likely offending agent. Guidelines for the management of drug-induced aplastic anaemia, agranulocytosis, thrombocytopenia and haemolytic anaemia are presented and the potential value of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF; GM-CSF) in the management of agranulocytosis is specifically mentioned. Finally, general principles are discussed whereby serious haematological ADRs might be prevented. These include: the importance of continuing education for drug prescribers; policies on the restricted prescribing of likely offending agents; the use of written instructions for patients; and, the use of haematological monitoring. The guidelines presented in this article should be adapted to meet local circumstances and would prove suitable subjects for audit of their effectiveness.
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PMID:Idiosyncratic drug-induced haematological abnormalities. Incidence, pathogenesis, management and avoidance. 772 54

Normal blast colony-forming cells (BI-CFC) bind to stroma cultured in the presence of methylprednisolone (MP+) but not to MP- stroma. In aplastic marrow, the incidence of BI-CFC is variable (0-4 x normal values) and there is no consistent relationship with the CFU-GM (granulocyte-macrophage colony-forming cell) content. Normal stroma require MP to induce BI-CFC binding function and form fat cells whereas MP- stroma grown from 4/9 aplastic patients formed fat cells and bound BI-CFC. The 5/9 aplastic cases that did not form fat cells spontaneously also bound BI-CFC moderately better than normal stroma. This suggests that the haemopoietic microenvironment in aplastic anaemia responds physiologically to bone marrow failure by increasing its haemopoietic support capacity.
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PMID:Stem cells and the microenvironment in aplastic anaemia. 801 28

We have examined the effect of mast cell growth factor (MGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3), singly or in combination, on the growth of normal and aplastic anemia (AA) bone marrow in clonogenic assay and long-term bone marrow culture (LTBMC). MGF stimulated colony-forming unit-granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and mixed colony-forming unit (consisting of granulocyte-macrophage and erythroid elements) (CFU-GEM) colony formation from both normal and AA marrow. The three-factor combination stimulated the greatest number of colonies. Marrow from less severely affected AA patients was stimulated to produce the highest number of colonies, and a normal response was possible if progenitors were present. When added to LTBMC, MGF alone had little effect. GM-CSF and IL-3 stimulated increased numbers of progenitor cells harvested each week from normal and AA LTBMC. This resulted in normal colony numbers in some patients, the majority of whom were less severely affected than the patients who did not respond in LTBMC. The three-factor combination was additive for normal CFU-GM production. However, no further increases in AA LTBMC resulted from the addition of MGF to GM-CSF and IL-3. The partial correction in clonogenic assay with MGF in some AA patients raises the possibility of therapeutic benefit. We failed to demonstrate increased progenitor cell numbers in AA LTBMC, however. Further studies may overcome possible limitations to progenitor cell proliferation.
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PMID:In vitro response of normal and aplastic anemia bone marrow to mast cell growth factor and in combination with granulocyte-macrophage colony-stimulating factor and interleukin-3. 811 28

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

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

The case history, laboratory findings and clinical course of a patient with pure red cell aplasia (PRCA) combined with myasthenia gravis and thymoma are reported herein. In vitro study revealed bilineage complement-dependent IgG inhibitor(s) in both the granulocyte-macrophage and erythroblastic progenitor cells. His serum showed high anti-acetylcholine receptor antibody levels associated with activity of myasthenia gravis as well as PRCA. Patient history of thymectomy 7 years previously followed by extensive cutaneous candidiasis with abnormal T lymphocyte subsets (decreased T4/T8 ratio and increased number of activated T lymphocytes) in both the bone marrow and peripheral blood suggested primary T lymphocyte dysfunction, whereas the erythropoiesis was not inhibited by T lymphocytes. This case is of interest in the context of a possible immunological pathogenesis for other hematopoietic disorders, including some cases of aplastic anemia.
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PMID:Bilineage hematopoietic inhibitor and T lymphocyte dysfunction in a patient with pure red cell aplasia, myasthenia gravis and thymoma. 844 Mar 42

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA.
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PMID:Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia. 853 89

We investigated the effect of the human ligand for flt-3 (FL) on the committed progenitor colony formation of normal bone marrow (BM) (n = 9) and BM from four aplastic anaemia (AA) and three Diamond-Blackfan anaemia (DBA) patients. Methylcellulose committed progenitor cell assays were carried out using FL alone and in combinations with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and c-kit ligand (KL). FL alone had a limited, though significant, effect on the production of granulocyte-macrophage colony-forming unit (CFU-GM) colonies from normal BM and showed an additive effect with IL-3 and GM-CSF separately, but not in combination. FL did not increase the stimulation of KL and did not have an effect on the production of erythroid progenitor colonies. FL had no effect on the AA and DBA BMs studied.
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PMID:The effect of human flt-3 ligand on committed progenitor cell production from normal, aplastic anaemia and Diamond-Blackfan anaemia bone marrow. 855 52


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