Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell-mediated inhibition of granulomonopoietic progenitors (CFU-GM) was studied in vitro in 27 patients with severe aplastic anaemia (AA). In nine out of 13 responders to anti-thymocyte globulin (ATG), cultured T-cells obtained prior to therapy, as well as their conditioned medium strongly suppressed both normal allogeneic and autologous CFU-GM (the latter obtained after marrow recovery). Addition of anti-interferon-gamma to the cultures abolished the suppressive effect on CFU-GM. After ATG therapy, no similar inhibitory effect was detected. Employing the panning method with monoclonal antibodies (CD4+ for inducer/helper and CD8+ for cytotoxic/suppressor T-cells) we were able to show that the cells responsible for in vitro CFU-GM inhibition were included in the cytotoxic/suppressor T-cell subpopulation. Cultured T-cells and their conditioned medium obtained from 14 non-responders to ATG did not show CFU-GM suppression. The mean interferon (IFN) levels in the T-cell conditioned media of ATG-responders was 625 +/- 125 mu/ml while in non-responders the level was 45 +/- 15 mu/ml (normal control levels 43 +/- 24 mu/ml). Freshly isolated peripheral blood lymphocytes from either group did not show any in vitro inhibitory effect. The response rate to ATG was statistically significant when the generation in culture of high versus low IFN production was compared (P = 0.0001). Experiments with T-cells obtained from heavily transfused thalassaemia major, and myelodysplastic syndrome patients, as well as normal volunteers, also did not demonstrate any suppression of CFU-GM. Our results indicate that the response rate to ATG is significantly higher in patients with AA who have an abnormal regulation of interferon-gamma (g-IFN) production.
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PMID:In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin. 313 95

The unstimulated and induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), IL-3, IL-6, stem cell factor (SCF), IL-1beta, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was determined after culture of blood mononuclear cells from 22 patients with severe beta-thalassaemia in a regular transfusion programme, five non-regularly transfused patients with beta-thalassaemia intermedia and nine normal persons. A distinct pattern of cytokine production in thalassaemic patients was detected, namely a low unstimulated production of all cytokines and a significant increase in the stimulated production of IFN-gamma, TNF-alpha and IL- 1beta; these abnormalities were more pronounced in the more heavily transfused older patients. The increased production of the above cytokines, which usually characterize the acute response to infectious agents and have a negative effect on erythropoiesis, may explain the deterioration of anaemia found in thalassaemic patients during acute infections.
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PMID:A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with beta-thalassaemia. 906 38

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and interferon-gamma (IFN-gamma) were estimated by conventional ELISA kits in 60, 42, and 58 Thai patients, respectively, with beta(o)-thalassemia HbE and found to be above the normal range in 13%, 21%, and 33% of the patients, respectively. Using high-sensitivity ELISA systems, an additional 10 beta(o)-thal/HbE patients were compared with 9 controls for concentrations of circulating TNF-alpha and IL-1beta, and 9 and 5 patients, respectively, but only 1 and none of the controls, respectively, showed values above the normal ranges. In patients with abnormally high IFN-gamma levels, basal hemoglobin values were significantly lower than in those with normal levels of the cytokine (mean +/- SEM: 6.03+/-0.24 vs. 7.08+/-0.18, p < 0.05), although circulating concentrations of soluble transferrin receptors (sTrF) and absolute reticulocyte counts were similar in the two groups. Patients with raised or normal levels of TNF-alpha, IL-1alpha, or IL-1beta had similar basal hemoglobin values. In a phagocytosis assay, monocytes of patients with raised serum levels of IFN-gamma showed significantly more attached or ingested IgG-coated red cells than those of patients with normal concentrations of the cytokine (mean +/- SEM: 192+/-22 vs. 140+/-14 per 100 monocytes, p < 0.05). Moreover, in 3 of 4 of the former patients, the number of attached or ingested IgG-coated red cells per 100 monocytes was above the 95% reference limit for the latter patients. The results suggest that IFN-gamma aggravates the anemia of beta(o)-thal/HbE by activating mononuclear phagocytes for destruction of red cells but not by inhibiting erythropoiesis. The elevated serum levels of TNF-alpha and IL-1 could contribute to complications of the disease, such as cachexia and thromboembolic phenomena.
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PMID:Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta(o)-thalassemia/HbE and their clinical significance. 1009 Mar 95

This study was designed to estimate interferon-gamma (INF-gamma) levels among polytransfused haematology cases. Cases were selected from the haematology unit of Alexandria main university hospital, Egypt. Complete blood counts, estimation of INF-gamma and hepatitis B and C virus (HBV and HCV) status were conducted on 20 unsplenectomized patients with gamma-thalassaemia major and 20 patients with acute myeloid leukaemia (AML) in the maintenance phase and 20 healthy subjects. Mean haemoglobin levels and red blood cell counts were significantly higher in the control group than the AML and thalassaemia groups, while white blood cell counts were significantly lower in the control group than the case groups. Two AML patients (10%) and 1 thalassaemia patient (5%) were HBV-positive, while 5% of both case groups were HCV-positive. Mean values of INF-gamma were significantly different between AML, thalassaemia major and control groups: 5517 (SD 1142) pg/mL, 1024 (SD 249) pg/mL and 2980 (SD 604) pg/mL respectively.
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PMID:Quantitative estimation of interferon-gamma levels among Egyptian polytransfused haematology cases. 2461 30