Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 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

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor known to promote the proliferation and differentiation of precursors of granulocytes and monocytes. GM-CSF at standard doses (125-500 micrograms/m2) alleviates neutropenia secondary to cytotoxic chemotherapy, myelodysplastic syndromes, and aplastic anemia, but has minimal effect on anemia or thrombocytopenia. GM-CSF at doses < 30 micrograms/m2 has been reported to improve platelet counts in some patients exhibiting cytopenia related to hematologic disorders such as aplastic anemia and myelodysplastic syndrome. Low-dose GM-CSF (10-20 micrograms/m2) was evaluated in 20 patients with transfusion-dependent thrombocytopenia persisting after myeloablative cytotoxic chemotherapy or with disease-related cytopenia. Seven patients (35%) responded as defined by a reduction in the platelet transfusion requirements by at least 75%. Low-dose GM-CSF did not significantly increase neutrophil counts or decrease red blood cell transfusion requirements. These results indicate that low-dose GM-CSF has a thrombopoietic effect in about one-third of patients with platelet transfusion-dependent thrombocytopenia which has not been observed at higher doses.
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PMID:Effect of low-dose granulocyte-macrophage colony-stimulating factor (LD-GM-CSF) on platelet transfusion-dependent thrombocytopenia. 794 85

Marrow samples from 89 patients with aplastic anemia (AA) were evaluated for their ability to grow stromal layers in standard long-term marrow cultures (LTMCs). Results were highly variable: 6.8% failed to grow any stromal cells (group I); 42.5% either failed to grow to confluency or appeared to have a decreased number of adipocytes and/or macrophages (group II); and 52.8% appeared as normal confluent cultures with fibroblasts, adipocytes, and macrophages (group III). Analyses of patient data suggested that group I patients had a longer disease duration and poorer survival (P = .07). Enzyme-linked immunosorbent assay analysis of cytokine production was performed on 20 of the normal-appearing AA LTMCs and 12 LTMCs established from normal donors. Significant differences between the AA and control groups were apparent for macrophage inflammatory protein-1 alpha (MIP-1 alpha), interleukin-1 receptor antagonist (IL-1ra), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and leukemia-inhibitory factor (LIF). The most dramatic differences observed were elevated levels of MIP-1 alpha and GM-CSF and decreased levels of IL-1ra, particularly after IL-1 alpha stimulation. In contrast, IL-1 alpha stimulation of AA LTMCs produced levels of IL-6, LIF, and G-CSF comparable with those of controls. These data suggest that defects exist within the microenvironment of some AA marrows. Whether the majority of these defects are the cause or consequence of aplasia is not clear. However, we speculate that some of these abnormalities may contribute to the maintenance of the hypoplastic state and, in extreme cases, prevent engraftment of donor marrow.
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PMID:Aplastic anemia: analysis of stromal cell function in long-term marrow cultures. 794 23

We studied the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by peripheral blood mononuclear cells from 48 patients with aplastic anemia by using an enzyme-linked immunosorbent assay. Detectable concentrations of spontaneous GM-CSF production, ranging from 1.0 to 480 pg/ml (mean +/- SD, 51 +/- 100 pg/ml), were observed in 45 of 48 patients. These concentrations were not significantly different from those observed in normal controls. Phytohemagglutinin-stimulated production of GM-CSF in patients with aplastic anemia, ranged from 1.0 to 2,610 pg/ml (mean +/- SD, 754 +/- 550 pg/ml), which was significantly higher than in normal controls (p < 0.01). The spontaneous production of GM-CSF increased following antilymphocyte globulin (ALG) treatment in 7 of the 11 ALG responders and in 4 of the 14 nonresponders (p = 0.08). The present observations support the hypothesis that ALG functions as an inducer of hematopoietic growth factor in order to restore hematopoiesis.
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PMID:In vitro granulocyte-macrophage colony-stimulating factor production by peripheral blood mononuclear cells in aplastic anemia. 797 14

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

As phase II study, we treated 18 patients with myelodysplastic syndrome (MDS) and 37 patients with aplastic anemia (AA) with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 14-28 days. Administration of rhGM-CSF resulted in a dose-dependent increase in circulating granulocyte counts, which was statistically significant in patients with AA. There were no consistent changes in monocyte and lymphocyte counts. Although no increase in both thrombocyte and erythrocyte counts was detected in the majority of the patients, a response of both lineages to rhGM-CSF, in addition to granulocyte lineage, was observed in 3 patients. Drug-associated adverse events developed in 28 patients (51%). The most frequent adverse event was fever. In general, the treatment with rhGM-CSF was well tolerated. The results suggest that rhGM-CSF is effective for patients with MDS and AA.
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PMID:Phase II study of recombinant human granulocyte-macrophage colony-stimulating factor in myelodysplastic syndrome and aplastic anemia. 821 99

It has been reported that bone marrow and serum of patients with aplastic anemia or chronic myeloproliferative disorders contain an abnormal concentration of cytokines. In the present study, we tried to isolate mouse bone marrow stromal cell lines that were stably transformed with a variety of cytokine genes and that expressed them constitutively. From mouse bone marrow stromal cell lines MBA-1, MBA-13, and 14F1.1, we isolated clones secreting interleukin-3 (IL-3), IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte (G)-CSF. Interferon-gamma (IFN-gamma)-producing stable transformants could not be established from 14F1.1 cells in spite of repeated transfection trials. At early stages of transfection, 14F1.1 cells did secrete IFN-gamma; however, exogenously added mouse IFN-gamma could not inhibit 14F1.1 cell growth. We discovered that chromosomal DNA isolated from 14F1.1 after transfection with the mouse IFN-gamma gene was fragmented. This is characteristic of cells undergoing apoptotic cell death. DNA fragmentation was also observed in 14F1.1 cells transfected with the human IFN-gamma gene. These results indicate that intracellular IFN-gamma induces apoptotic cell death of 14F1.1 stromal cells.
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PMID:Transfection of interferon-gamma gene in a mouse bone marrow stromal preadipocyte cell line causes apoptotic cell death. 840 30

To clarify the role of growth factors in the pathophysiology of aplastic anemia we measured serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in 33 aplastic anemia patients by a specific and sensitive enzyme-linked immunosorbent assay. GM-CSF serum levels of patients with aplastic anemia were significantly higher than in healthy volunteers. GM-CSF levels were correlated with the severity of aplastic anemia but not with the absolute neutrophil count. Since T lymphocytes are one of the main sources of GM-CSF, our data provide further evidence for in vivo T lymphocyte activation in aplastic anemia. GM-CSF serum levels are higher in patients responding to immunosuppressive treatment than in nonresponders. Elevated serum GM-CSF might be predictive of a good response to immuno-suppressive therapy. GM-CSF serum levels are lower immediately after treatment with antilymphocyte globulin/antithymocyte globulin (ALG/ATG) than corresponding pretreatment values. Thus we cannot confirm the hypothesis that ALG/ATG effects in vivo are mediated by stimulating the release of growth factors. We conclude that in aplastic anemia the primary defect is a failure in GM-CSF response rather than in GM-CSF supply.
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PMID:Granulocyte-macrophage colony-stimulating factor in the sera of patients with aplastic anemia. 846 22

Dyskeratosis congenita is a congenital multisystem disorder, characterized by skin pigmentation, dystrophic nails, and leukoplakia. Hematologic abnormalities progressing to severe pancytopenia play a significant role in the poor prognosis of afflicted patients. We report on a patient with dyskeratosis congenita and severe aplastic anemia, complicated by life threatening infection. The patient was treated with recombinant granulocyte-macrophage colony-stimulating factor. This therapy resulted in a moderate and transient improvement in absolute neutrophil counts. Current concepts regarding the pathogenesis and etiology of dyskeratosis congenita are discussed, while reviewing the available therapeutic options.
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PMID:Treatment of the hematological manifestations of dyskeratosis congenita. 848 9

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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