Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow cells from patients with leukemia, myelodysplastic syndromes, cancer, and other disorders on a phase I clinical trial with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were assessed in vitro for numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, and for growth patterns (colony-to-cluster ratio) of CFU-GM, cycling rates of CFU-GM, and responsiveness in vitro to colony-stimulating and colony-inhibiting factors. The colony-to-cluster ratio of CFU-GM and the dose-response curves of CFU-GM to stimulation by rhGM-CSF in vitro did not change during the clinical trial. However, the percentage of CFU-GM in DNA synthesis, which is a measure of the proliferative rates of these cells, determined by the high specific activity tritiated thymidine kill technique in vitro, was markedly enhanced in a reversible fashion after administration in vivo of rhGM-CSF. The increased cycling rates of CFU-GM were consistent with the induced increase in neutrophil counts in these patients that has been reported elsewhere. Additionally, marrow CFU-GM from patients given rhGM-CSF in vivo were increased in sensitivity to inhibition in vitro by recombinant human H-subunit (acidic) ferritin in two of eight cases, and were increased in sensitivity to inhibition by lower dosages of recombinant human tumor necrosis factor alpha in all patients evaluated. The sensitivity of CFU-GM to inhibition in vitro by recombinant human interferon gamma and prostaglandin E1 did not change during the clinical trial. These studies demonstrate that the rhGM-CSF is having an effect on CFU-GM in the patients on the phase I clinical trial. This information may be of significance in planning future clinical studies combining rhGM-CSF with chemotherapy and/or other biotherapy.
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PMID:Growth characteristics of marrow hematopoietic progenitor/precursor cells from patients on a phase I clinical trial with purified recombinant human granulocyte-macrophage colony-stimulating factor. 326 May 58

Leukocyte-derived inhibitory activity inhibiting the entry of normal progenitor cells of granulocytes and macrophages (CFU-GM) into the S-phase of a cell cycle was investigated in 16 patients with different forms of myelodysplastic syndrome (MDS). The presence of this inhibitory activity was analysed in medium conditioned with low-density cells obtained from peripheral blood of MDS patients. The inhibition rate was measured by 3H-thymidine suicide technique with subsequent cultivation of pretreated cells in semisolid agar medium. Low-density cells from MDS patients of various types were studied: from the twelve patients with refractory anaemia (RA or RAS) only three were positive, one patient with chronic myelomonocytic leukaemia (CMML) was negative while one patient with refractory anaemia with excess of blasts (RAEB) and two patients with RAEB in transformation (RAEB-T) were positive with respect of the described test. In two patients with RA, who underwent a long-term investigation, the production of leukocyte-derived inhibitory activity preceded the development of disease into RAEB or RAEB-T. In five positive cases, supernatants were incubated with antiserum against human placental ferritin; with one exception, the inhibitory activity was neutralized.
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PMID:Leukocyte-derived inhibitory activity in patients with myelodysplastic syndrome. 362 Jul 12

The oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been given daily for 3-11 months to 6 transfusion dependent iron loaded patients (myelodysplasia (MDS) 2, Diamond-Blackfan anaemia 1, thalassaemia intermedia 1, thalassaemia major 2). Daily doses of 3 g, 2 x 2 g and 3 x 2 g were administered for the first 2-7 months. Daily doses of 2 x 3 g were also used for periods up to 4 months. Urine iron excretion following 3 g of L1 was found to be related to the number of previous transfusions but not to serum ferritin or the amount of L1 excreted. In each case 24 h urinary iron excretion in response to 3 g L1 ranged from 5-21 mg in MDS, 13-25 mg in a thalassaemia intermedia and a Diamond-Blackfan patient and 16-110 mg in thalassaemia major patients. Further increases of urinary iron were observed in all the patients when the daily dose was increased. Serum ferritin levels have fluctuated but overall have remained unchanged. Biochemical assessment did not show any major abnormalities ascribed to L1 except from subnormal serum zinc levels in two patients and white blood cell absorbate in another. In a separate study we have compared urinary L1 and iron excretions in 7 transfusional iron loaded patients. In all the cases the concentration of L1 was in excess of iron and higher than the level required for 100% iron binding. There was no other apparent correlation between the concentrations of L1 and iron in the urines studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral iron chelation therapy with deferiprone. Monitoring of biochemical, drug and iron excretion changes. 789 73

BACKGROUND. Tumor necrosis factor (TNF) and interleukin-1 beta (IL-1) are two cytokines with erythropoietic inhibitory activity which may be involved in the pathogenesis of some types of anemia that may respond to recombinant erythropoietin (r-EPO). The aim of the present study was to evaluate whether TNF and IL-1 serum levels are related to clinical response in patients with myelodysplastic syndromes (MDS) receiving r-EPO. TNF and IL-1 serum levels were measured by means of immunoenzymatic assays in 26 patients affected by MDS and treated with r-EPO administered subcutaneously at dosages up to 1050 U/kg a week, for at least two months. Four patients (15%) showed a significant response, with an increase of hemoglobin > 2 g/dL and complete suspension of transfusions. Higher mean serum levels of both TNF (54.2 +/- 93 vs 4.2 +/- 7.9 pg/mL, p < 0.001) and IL-1 (114 +/- 58.5 vs 36.1 +/- 21.7 pg/mL, p < 0.001) were measured in MDS patients than in a group of 42 normal controls. However, responders showed significantly lower mean levels of TNF (8.2 +/- 9.6 vs 58.5 +/- 65.2 pg/mL, p < 0.05) and IL-1 (30 +/- 24.8 vs 127.8 +/- 51.4 pg/mL, p < 0.001) than those of non responders. In terms of absolute values, all responders evidenced undetectable or normal levels of both cytokines. No relationship was found between TNF or IL-1 and values of hemoglobin, serum erythropoietin, ferritin, soluble transferrin receptor or transfusional requirements. MDS patients who respond to r-EPO have lower serum levels of TNF and IL-1 than those who do not respond.
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PMID:Low serum levels of tumor necrosis factor and interleukin-1 beta in myelodysplastic syndromes responsive to recombinant erythropoietin. 792 77

Ferritin H (heavy) and L (light) subunits in red cells were determined in normal subjects, patients with myelodysplastic syndrome (MDS) and other haematological disorders by means of enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to ferritin H and L subunits. The mean contents of ferritin H and L subunits in red cells in healthy individuals were H 8.0 + 0.8 attogram (ag)/cell (lag = 10 x 10(-18)g)(mean +/- SE), L 4.8 +/- 0.4 ag/cell respectively. The values of both subunits in normal male (H 10.5 +/- 1.3 ag/cell, L 5.9 +/- 0.7 ag/cell) were significantly higher than those of normal female (H 5.4 +/- 0.8 ag/cell, L 3.9 +/- 0.5 ag/cell). Significantly elevated H and L subunit contents in red cells were observed in patients with refractory anemia (RA)(H 138.2 +/- 72.0 ag/cell, L 57.0 +/- 20.9 ag/cell) and refractory anemia with excess of blasts (RAEB)(H 97.4 +/- 36.9 ag/cell, L 49.3 +/- 18.4 ag/cell) as compared with those of normal subjects. On the other hand, both parameters decreased in patients with iron deficiency anemia (IDA)(H 2.4 +/- 0.3 ag/cell, L 1.5 +/- 0.3 ag/cell). H/L ratio in patients with RA (2.7 +/- 0.5) was significantly higher than those of normal subjects (1.8 +/- 0.1) indicating relative increase of red cell ferritin H subunit in patient with MDS. The measurement of red cell ferritin H and L subunits by ELISA could be useful for evaluating dyserythropoiesis or ineffective hemopoiesis in MDS.
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PMID:[Clinical significance of red cell ferritin H and L subunits in myelodysplastic syndrome]. 792 83

Serum ferritin concentration had been known to represent the amount of total body iron and has been clinically used as a parameter to evaluate the iron storage pool in a whole body. Glycosylated (secreted) and non-glycosylated (non-secreted) forms of serum ferritin (sFt) have been reported by others based on the difference in their affinity to concanavalin-A binding. In this report, we assessed the amount of glycosylated serum ferritin (Glyco-sFt) and the ratio (%) of Glyco-sFt/in hematopoietic disorders including iron overloads (n = 10), leukemias (n = 36), malignant lymphomas (n = 10), multiple myelomas (n = 3) and myelodysplastic syndromes (n = 12). A high percentage of Glyco-sFt was observed in normal healthy controls (n = 18, 78.1 +/- 7.4%) and iron-overloads (61.1 +/- 17.8%) as compared with that in hematopoietic malignancies (43.8 +/- 23.4%, p < 0.001). The amount of Glyco-sFt in iron-overloads was higher than that in hematopoietic malignancies with hyperferritinemia (p < 0.005). These data demonstrated that the same part of serum ferritin in hematopoietic malignancies was the non-secreted form and appeared to be derived from tumor cell lysis. We conclude that assessment of Glyco-Ft is a useful parameter to distinguish iron-overloads from malignant hematopoietic disorders both displaying hyperferritinemia.
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PMID:[The clinical significance of glycosylated ferritin in iron overloads and hematopoietic malignancies]. 793 60

Post-transfusional iron overload is a real problem for doctors in charge of transfusions, as shown by the survey we led in twenty French blood banks. Deferoxamine remains the most efficient chelator, but can be prescribed only in a parenteral way. It is now proved that continuous infusions, intravenous or subcutaneous, are preferable to intermittent injections as far as iron excretion is concerned. In our study, we selected 15 polytransfused patients for dysmyelopoiesis. 13 cases were analysed by measuring the serum ferritin level. A clear decrease was noted, as well as a relative normalization of serum alanine amino transferases. However, if this treatment is effective and well tolerated, the problem is that it obviously requires the patient's compliance. It seems important to us to optimize prevention and treatment of post-transfusional iron overload through a consensus.
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PMID:[Post-transfusion hemochromatosis. Results of a study carried out in Blood Transfusion Centers. Analysis of 15 cases treated with subcutaneous perfusion of Desferal. Working group "Transfusion Techniques and Therapeutics"]. 818 55

Anemia is a common complication of patients with multiple myeloma (MM) and myelodysplastic syndrome (MDS). Most of these patients often require blood transfusion. 12 patients, including 7 cases of MM and 5 cases of MDS, were treated with rhEPO 10,000 micrograms three times a week for 15 weeks. The hemoglobin in 6 of 7 cases of MM steadily increased and eventually reached normal level without blood transfusion. The number of erythroid precursors in bone marrow was increased significantly and serum ferritin concentration was decreased gradually during EPO administration. However 5 patients with MDS did not show any response to EPO. The adverse side effects were hardly observed in any patients received EPO treatment. It is suggested that rhEPO is a promising preparation for treating MM-associated anemia rather than MDS-associated anemia.
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PMID:[Erythropoietin treatment of anemia associated with multiple myeloma (MM) and myelodysplastic syndrome (MDS)]. 822 21

The purpose of this study was to improve erythropoiesis in patients with anemia due to myelodysplastic syndromes (MDS). We treated 13 patients first with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 6 weeks, then with recombinant human erythropoietin (rhEpo) and rhGM-CSF for the next 12 weeks. Five patients had refractory anemia (RA), 3 refractory anemia with ringed sideroblasts (RAS), and 5 refractory anemia with excess of blasts (RAEB). Ten patients were transfusion-dependent at the time of inclusion. Eleven patients completed this phase II study. Five responded with an increase in hemoglobin level (3 patients) or a reduction in transfusion requirement (2 patients). We registered no response in the remaining 6 patients during treatment. Patients responding to combined treatment had relatively low concentrations of plasma Epo and plasma ferritin before treatment with rhEpo and a normal karyotype throughout the study. Long-term bone marrow cultures did not predict the response. Still, responders seemed to have a higher number of colony-forming progenitors than nonresponders. In conclusion, combined therapy with rhGM-CSF and rhEpo may stimulate hematopoiesis and correct or improve anemia in some patients with MDS.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes. 823 92

The red cell ferritin (rFt) level in 10 patients with refractory anemia (RA) was measured and analyzed by column isoelectric focusing (IEF). The levels in 9 of the 10 patients (90.0%) were higher than the upper limit in healthy controls (MV +/- SD: male 14.3 +/- 10.3 ag/cell, female 7.5 +/- 3.6 ag/cell). The isoelectric point (pI) of rFt determined by IEF in healthy subjects ranged from 5.1 to 5.7. However, the pI ranges for RA patients varied widely; the pI value was thought to correlate with the severity of the morphological abnormalities of bone marrow (BM) erythroblasts. That is, the greater the proportion of morphologically abnormal erythroblasts with respect to all erythroid precursors, the lower the pI range for rFt. The rFt content was not related to serum iron, transferrin saturation, serum ferritin, reticulocyte count, red cell iron content, or BM erythroblast count. These data suggest that rFt synthesis in RA patients is influenced by factor(s) other than iron; this is considered an essential feature of erythropoiesis in myelodysplastic syndrome (MDS).
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PMID:Quantitative and qualitative studies of red cell ferritin in refractory anemia of myelodysplastic syndrome. 834 42


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