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)

A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage-colony stimulating factor (GM-CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c-kit and IL-6 receptors, in long-term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes. Disorders studied include Fanconi's anaemia (FA, n = 16), idiopathic aplastic anaemia (AA, n = 11), Seckel's syndrome (n = 2), dyskeratosis congenita (n = 2), Shwachman-Diamond syndrome (n = 1), thrombocytopenia with absent radii syndrome (n = 1), acquired amegakaryocytosis (n = 1), paroxysmal nocturnal haemoglobinuria (n = 1) and acquired agranulocytosis (n = 1). IL-6 and GM-CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL-6 and GM-CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients' groups and controls in expression of the other cytokines or cytokine receptors studied.
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PMID:The expression of cytokine and cytokine receptor genes in long-term bone marrow culture in congenital and acquired bone marrow hypoplasias. 751 72

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

We have studied the production of human granulocyte colony-stimulating factor (hG-CSF). Enzyme immunoassay showed that hG-CSF was produced by primary bone marrow stromal cells, peripheral blood monocytes, fibroblasts, and endothelial cells in vitro. These cells produced variable levels of hG-CSF depending on the type of inducers. Interestingly, in situ hybridization showed that only a small proportion of bone marrow stromal cells and blood monocytes expressed a large amount of hG-CSF mRNA. Secondly, we have estimated serum hG-CSF level and clearance of exogenous hG-CSF in patients with various hematological disorders. Endogenous hG-CSF was undetectable (< 30 pg/ml) in sera of normal volunteers. On the other hand, the serum hG-CSF level was elevated in infection, malignancy, and neutropenia, suggesting the presence of reactive, ectopic, and unknown mechanisms for hG-CSF production, respectively. The half-life of recombinant hG-CSF was prolonged in disorders with reduced myeloid cell mass, especially in aplastic anemia, whereas it was shortened in myeloid leukemia, and in recovery phase after chemotherapy. This finding suggests the possibility of receptor-mediated consumption of hG-CSF in vivo. These in vitro and in vivo studies on hG-CSF would be of value for understanding the pathophysiological roles of hG-CSF.
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PMID:[Pharmacokinetics of hematopoietic growth factors and granulopoiesis. The pathophysiology of human granulocyte colony-stimulating factor]. 768 33

In this study we review our present understanding of the effect of stem cell factor (SCF) on the in vitro growth of hemopoietic progenitors from patients with acquired severe aplastic anemia (SAA). We have run three separate sets of experiments. First, we have tested the expression of receptor mRNAs for granulocyte-macrophage colony stimulating factor/interleukin 3 (GM-CSF/IL-3) and for c-kit protein on bone marrow (BM) cells from SAA patients. Molecular analysis revealed the presence of normal transcripts for alpha and beta chains of GM-CSF/IL-3 receptor and for c-kit protein by Northern blot analysis. Second, we have tested the in vitro response to SCF of BM cells derived from 11 SAA patients: SCF induced a significant enhancement of erythroid burst forming unit (BFU-E) growth (8 to 29, p = 0.01) and allowed the formation of granulocyte/erythroid/macrophage/megakaryocyte (GEMM) colonies which were not scored in baseline culture conditions (0 to 8, p = 0.01). Granulocyte-macrophage colony forming unit (CFU-GM) growth was also enhanced (4 to 20, p = 0.3). This was true for patients both at diagnosis and after antilymphocyte globulin (ALG) treatment. We concluded that SCF can promote the in vitro growth of hemopoietic progenitors in patients with acquired SAA. Third, we have tested the response to SCF of peripheral blood (PB) hemopoietic progenitors collected from patients receiving in vivo long-term treatment with granulocyte CSF (G-CSF). When PB cells were plated directly in the presence of GM-CSF there was no colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro effect of stem cell factor on colony growth from acquired severe aplastic anemia. 769 24

A 65-year-old female with severe aplastic anemia induced by gold salt, whose hematopoietic recovery was initiated by rhGM-CSF therapy, was reported. The patient has been given a total of 500 mg of gold-sodium thiomalate for treatment of her rheumatoid arthritis. Two months after the final administration of it, she was admitted to our hospital with complaints of palpitation and shortness of breath. The hemogulobin was 5.9 g/dl, the platelet count was 0.5 x 10(4)/microliter, and the leukocyte count was 800/microliters with 19% neutrophils. Her bone marrow showed aplasia, and both of Ham and sugar-water tests were positive. Three times of bolus-methylprednisolone treatment, with or without methenolone acetate, resulted in no definite improvement of peripheral pancytopenia and marrow aplasia. Subsequent subcutaneous rhGM-CSF, 300 micrograms daily for 28 days with oral prednisolone 5 mg and methenolone acetate 40 mg daily, initiated hematopoietic recovery of all three cell lineages in both peripheral blood and bone marrow. The same doses of prednisolone and methenolone acetate were continued after rhGM-CSF administration, and three months later peripheral cytopenia and positive Ham and sugar-water tests disappeared completely.
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PMID:[Initiation of hematopoietic recovery by recombinant human granulocyte-macrophage colony-stimulating factor in a case of severe aplastic anemia induced by gold salt]. 771 74

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

We reviewed the clinical courses of 38 children with acquired aplastic anemia (AA). The patients were classified according to the severity criteria by the Japanese Ministry of Health and Welfare (JMHW) Study Group (22 severe, 15 moderate, 1 mild). Early death was observed only in severe cases. Eight of the non-severe cases progressed to severe in 0.5-125 months, and the long-term survival rate of non-severe AA did not differ from that of severe AA. The frequency of lymphocytes in the bone marrow was significantly higher, and the peripheral blood neutrophil count was lower in patients who died within a year, and these patients should be treated as very severe. These findings suggest that the JMHW Study Group criteria are useful for identifying AA patients with a poor prognosis, but even non-severe cases should be repeatedly evaluated. Sixteen of the 33 patients treated with corticosteroids and/or anabolic steroids (AS) showed hematological recovery. Bolus methylprednisolone (mPSL) therapy was effective in one of the 8 patients. Allogenic marrow transplant (BMT) was performed on 3 patients. One died from sepsis and engraftment was not achieved in the other two. Trilineage recovery was obtained in 3 of 6 patients treated with rhG-CSF and rhEPO with or without AS, and hemopoiesis has been maintained 6-12 months after discontinuation in 2 cases. In the other 3 patients, the neutrophil count showed transient increase. Therefore, the treatment for severe AA patients, who have no sibling donor for BMT, should be started with the combination therapy including these cytokines.
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PMID:The clinical course of acquired aplastic anemia in childhood; a retrospective study. 789 28

Growth and differentiation of hematopoietic progenitor cells is regulated by a complex network of stimulatory and inhibitory cytokines. Bone marrow failures can be due to a decrease of stimulators or an increase of inhibitors. T cells produce both, hematopoiesis stimulating and inhibiting cytokines. Therefore, a role of T cells in regulating hematopoiesis can only be assumed if the gene expression of these antagonistic acting cytokines can be differentially induced in T cells. To establish a model of selective cytokine induction, we investigated the induction of IFN gamma as inhibitor and GM-CSF as stimulator of hematopoiesis in T cells. Our results showed that IFN gamma mRNA accumulates in T cells which have been pre-activated via the signal transduction unit CD3, but not in unstimulated T cells. This accumulation depends on the expression of the high affinity IL2 receptor which is including the IL2 receptor alpha-chain (IL2R alpha, CD25). In a study on children with constitutional (CAA) versus acquired aplastic (EAA) anemia, we investigated the relevance of this model for the pathogenesis of aplastic anemia in childhood. We compared the following parameters: 1. Incidence of hematopoietic progenitor cells and cloning efficiency, 2. activation status and IL2R alpha expression of bone marrow T cells, 3. T cell cytokine expression profile. Our results show: 1. The relative incidence of bone marrow progenitor cells is decreased in children with CAA and normal in children with EAA. 2. Clonogenic growth of hematopoietic progenitor cells is suppressed in children with EAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental principles of therapy-oriented pathogenetic classification of aplastic anemia in childhood]. 796 17

We have used recombinant human (rh) GM-CSF in two 12-year-old Fanconi's aplastic anaemia patients. They had not received any previous therapy except blood transfusions. Each patient was given three 21 d courses of rh-GM-CSF, the first two at a dose of 3.5 micrograms/kg/d and the third at 7 micrograms/kg/d s.c. There were significant increases in WBC and absolute neutrophil counts after the first week of rh-GM-CSF which lasted as long as the treatment was continued. Following the cessation of treatment, WBC and ANC dropped rapidly. We conclude that rh-GM-CSF can be used in FAA, especially in severely neutropenic cases.
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PMID:GM-CSF in the treatment of Fanconi's anaemia. 798 33

Megakaryocyte progenitor growth in 42 patients with myeloproliferative disorders (MPD), including 23 essential thrombocythaemia (ET), eight polycythaemia vera (PV), six chronic myelogenous leukaemia (CML) and five primary myelofibrosis (PMF), was studied in vitro using plasma clot assay and serum-free agar culture. Spontaneous megakaryocyte colonies (CFU-MK) were found in 34/40 (80%) blood and 14/18 (77.8%) bone marrow plasma clot cultures, and also observed in 27/35 (77.1%) blood and 10/18 (55.6%) bone marrow serum-free agar cultures. In the blood of 27 patients with MPD (15 ET, four PV, four CML and four PMF) and the bone marrow of 10 patients (five ET, four CML and one PV), spontaneous colony formation was observed in both plasma clot and serum-free agar cultures. However, spontaneous CFU-MK was only found in plasma clot culture, but not in agar culture in two blood (one ET and one CML) and four bone marrow cultures (one ET, two PV, one CML). The colony numbers were greatly increased in the presence of aplastic anaemia serum (AAS) under both conditions. In 17 patients (12 ET, two CML and three PV) with spontaneous megakaryocyte colonies, anti-cytokine antibody neutralizing experiments were carried out in blood cultures. Anti-IL3, anti-IL6 and anti-GM-CSF antibody, alone or in combination, at different concentrations (1, 5 and 10 micrograms/ml), were added into plasma clot or agar cultures without exogenous stimulating growth factors. The results showed that the numbers of spontaneous megakaryocyte colonies were not significantly decreased in the presence of these monoclonal antibodies in the cultures. The data indicated that the megakaryocyte progenitor growth in MPD under in vitro conditions was heterogenous, and independent of exogenous stimulatory factors in most patients and that optimal megakaryocyte colony development in MPD still requires exogenous growth factors. Three possibilities are discussed with regard to the phenomenon that the spontaneous colony formation was not decreased with the addition of anti-IL3, anti-IL6 and anti-GM-CSF antibodies.
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PMID:Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM-CSF. 799 86


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