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 aim of the present study was to test the effect of cyclosporin A (CyA) in vitro on CFU-GM growth from patients with severe aplastic anemia (SAA). For this purpose, bone marrow (BM) cells from 9 SAA patients and 5 healthy individuals were incubated with or without CyA and then cultured for CFU-GM growth in the presence of exogenous recombinant human GM-CSF (30 ng/ml). SAA patients were tested before or after treatment with CyA, or after treatment with antilymphocyte globulin (ALG). In 3 patients responding to CyA, the addition of CyA in vitro enhanced colony growth from 13 +/- 10 to 40 +/- 20/10(5) BM cells (p = 0.01) - the median increment of colony formation was 2.4-fold. In 5 ALG responders, CyA produced no increment of CFU-GM growth (from 14 +/- 26 to 15 +/- 16/10(5) BM cells, p = 0.1). CyA did not enhance significantly CFU-GM growth in normal controls (from 57 +/- 45 to 58 +/- 81/10(5) BM cells, p = 0.9). In conclusion, it would appear that some patients with SAA can respond to CyA in vivo and in vitro, and ALG responders are not necessarily among these. This is in keeping with different mechanisms of action of CyA and ALG and possibly with the existence of distinct pathogenetic pathways in SAA.
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PMID:Severe aplastic anemia (SAA): response to cyclosporin A (CyA) in vivo and in vitro. 201 76

To evaluate the role of cytokines in patients with aplastic anemia, colony stimulating activities (CSA) and interferon-gamma (IFN-gamma) in cultured media of lymphocytes with phytohemagglutinin (PHA-LCM) were measured with methylcellulose culture method in 20 patients (age 3 to 69 years). The CSA for granulocyte/macrophage (GM-CSA) in patients was equivalent to that of normal donors, while low burst promoting activity (BPA) was observed in PHA-LCM from 7 adult patients (61 +/- 17%). The ability of BPA production varied widely in 13 children (97 +/- 37%). In some patients, low production of BPA improved after successful treatment of antilymphocyte globulin. The IFN-gamma in PHA-LCM disclosed no significant difference between patients and normal donors. From these results, low production of BPA may have a role in the development of AA in certain patients. It is also suggested that therapy with recombinant cytokines such as GM-CSF and IL-3, detected as BPA in our culture system, could be effective for those patients.
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PMID:[Effect of humoral factors produced by lymphocytes on hematopoietic progenitor cells--productive ability of colony stimulating activities and interferon-gamma by blood mononuclear cells in patients with aplastic anemia]. 211 75

The influence of GM-CSF on bone marrow cultures from 13 patients with aplastic anemia, MDS and acute leukemia was studied in a short-term suspension culture system. In each case combined cytogenetic and proliferation analyses were performed with respect to the question, whether chromosome aberrations play a role in the in vitro response to GM-CSF and in order to search for stimulating effects on malignant cells. The responsiveness was compared of aplastic and myelodysplastic cultures on the one hand and of leukemic cells on the other. Our results show that myelodysplastic and aplastic cells display a tendency for reduced susceptibility to GM-CSF as compared to healthy controls, while in leukemic bone marrow the response to the growth factor was significantly enhanced, indicating a leukemia-specific response pattern. In the majority of leukemias analyzed, the presence of cytogenetically abnormal cells in cultures with excessive response to GM-CSF can be taken as a proof for stimulation of malignant cells. The significance of these findings for pathogenesis and prognosis in aplastic anemia, myelodysplasia and leukemia is discussed.
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PMID:Karyotype and in vitro-response to GM-CSF. Analysis of bone marrow cultures in leukemia, myelodysplasia and aplastic anemia. 218 May

Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected. Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia. 220 31

We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10(-4) M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10(-7) M), nitroso-CAP (NO-CAP) (60% at 5 x 10(-6) M) and NPAP (35% at 10(-5) M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10(-6) M) and NO-CAP (5 x 10(-6) M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia.
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PMID:Interaction of chloramphenicol and metabolites with colony stimulating factors: possible role in chloramphenicol-induced bone marrow injury. 226 72

GM-CSF has been used in clinical trials to assess its role in promoting the proliferation and differentiation of marrow cells and enhancing the functional activities of granulocytes and monocytes. These studies have indicated that GM-CSF may prove useful in the management of cancer patients by preventing or treating myelosuppression following cancer chemotherapy and in patients with myelodysplasia or aplastic anaemia. As well as determining the efficacy of GM-CSF as a therapeutic agent, these studies are also providing insights into the possible roles of GM-CSF in vivo. Pharmacokinetic studies of GM-CSF in patients with advanced cancer and myelodysplasia suggest that the ratio of efficacy to toxicity of GM-CSF can be modified by changing either the dose or the method of administration.
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PMID:The potential role of granulocyte-macrophage colony stimulating factor (GM-CSF) in cancer chemotherapy. 227 11

The family of colony stimulating factors and interleukins influence all aspects of hematopoietic cell proliferation and differentiation. In most instances these hematopoietic growth factors have overlapping, pleiotropic effects and frequently regulate early progenitor cell proliferation and mature cell function. Currently, seven of these factors are in clinical trial: erythropoietin for treatment of anephric anemia, IL-2 in conjunction with LAC therapy, and IL-1, IL-3, G-CSF, GM-CSF, and M-CSF for stimulation of myelopoiesis and granulocyte-macrophage function after chemotherapy, irradiation, or bone marrow transplantation in patients with cancer. G-CSF and GM-CSF have also proved effective in treatment of congenital and idiopathic neutropenias and have had some efficacy in treatment of myeloid leukemias, myelodysplastic disorders, aplastic anemia, and acquired immunodeficiency syndrome (AIDS).
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PMID:Hematopoietic growth factors in cancer. 240 5

Colony-stimulating factors (CSFs) are a family of regulatory glycoprotein hormones that promote the proliferation and differentiation of hemopoietic progenitor cells and augment the functions of mature effector cells in vitro. The recent cloning of human genes and the availability of sufficient quantities of recombinant purified growth factors have made it possible to evaluate their therapeutic potential in cytopenic states. Initial studies with GM-CSF have demonstrated its ability to increase neutrophil, monocyte, and eosinophil counts in patients with acquired immune deficiency syndrome (AIDS), myelodysplastic syndrome (MDS), and aplastic anemia. Both GM-CSF and G-CSF reduce the duration of neutropenia following chemotherapy and accelerate hematopoietic recovery in patients undergoing intensive chemotherapy and autologous bone marrow transplantation. Studies are now ongoing to determine the optimal dose, route, schedule of administration, and long-term effects. While the appropriate settings for the use of different CSFs remain to be determined, the initial results of clinical trials are of great interest and suggest that hematopoietic growth factors will play an important role in several clinical arenas.
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PMID:Clinical applications of colony-stimulating factors. 268 11

24 patients who were treated with antilymphocyte globulin (ALG) for severe aplastic anaemia (SAA) were tested for endogenous release of granulocyte colony stimulating activity (G-CSA) prior to, and at various intervals after treatment. CSA-production in vitro was induced with autologous serum as a source of 'releaser' activity, avoiding the use of plant mitogens. Before treatment, G-CSA-release was highly variable. Though mean values were higher in the 17 patients who subsequently responded to ALG treatment than in the six non-responders, this difference was not statistically significant. In the 17 responders, G-CSA-release strongly increased prior to improvement of peripheral blood counts. In one responder patient tested-before, and at regular intervals after ALG, CSA-release was high before, abnormally low at 7 d and increased again to high values before the onset of bone marrow reconstitution. In six patients who did not respond to ALG-treatment, G-CSA release decreased after treatment, and a second course of ALG was ineffective when given during this low CSA-phase. Five of the 24 patients developed paroxysmal nocturnal haemoglobinuria (PNH) at 9 months to 3 years after ALG-treatment. In all, the onset of PNH was associated with very low G-CSA-release, whether it had been high or low before treatment. We conclude that low-CSA-release after ALG treatment is a poor prognostic sign. It either indicates progression of marrow failure or heralds PNH. Such patients may be candidates for early bone marrow transplantation or treatment with G-CSF or GM-CSF.
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PMID:Complete recovery of marrow function after treatment with anti-lymphocyte globulin is associated with high, whereas early failure and development of paroxysmal nocturnal haemoglobinuria are associated with low endogenous G-CSA-release. 278 75

Clinical usefulness of G-CSF, GM-CSF and M-CSF was summarized. These CSFs had been demonstrated to accelerate the recovery from neutropenia after anti-cancer chemotherapy and bone marrow transplantation. CSFs were also effective in some patients with aplastic anemia, myelodysplastic syndrome (MDS) and idiopathic neutropenia among children. An increase of neutrophils was observed in these patients responding to CSFs. Few patients with aplastic anemia and MDS, however, responded to G-CSF with an increase of reticulocytes and thrombocytes in addition to neutrophils. Combination of G-CSF with anti-leukemic agents for the treatment of refractory and relapsed acute non-lymphocytic leukemia (ANLL) or as the conditioning for bone marrow transplantation to refractory ANLL patients was found to be quite effective. Possible usage of GM-CSF and M-CSF for cancer treatment by stimulating anti-cancer functions of monocytes-macrophages was also discussed. Furthermore, GM-CSF and M-CSF were demonstrated to decrease serum cholesterol level in rabbits as well as in patients. Possible mechanism of this cholesterol-lowering effect was also discussed.
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PMID:[Colony stimulating factor]. 281 7


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