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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24-48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha-globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.
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PMID:Isolation and in vitro differentiation of human erythroid precursor cells. 126 Jan 33

Colony assays in methylcellulose (semisolid medium) of erythroid precursors and granulocyte-macrophage precursors from the peripheral blood of 34 patients with beta-thalassemia major and 31 age-matched normal controls were studied. In patients homozygous for beta-thalassemia, a significant increase of circulating erythroid progenitor cells to 3-5 times of normal controls was observed. Furthermore, the number of circulating colony forming units-granulocyte-macrophage (CFU-GM) and colony forming units-mixed (CFU-Mixed) also increased significantly. In these subjects, there was a linear relationship between the number of burst forming units-erythroid (BFU-E) and CFU-GM. The serum level of erythropoietin (EPO) was also significantly higher than that of normal controls (p < 0.05). The increased hematopoiesis, indicated by an increased number of circulating hematopoietic progenitor cells and an elevated serum level of EPO, suggests that the physiologic regulation of erythropoiesis still operated in patients with beta-thalassemia major.
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PMID:Peripheral blood hematopoietic progenitor cells in beta-thalassemia major. 146 Mar 23

Serum immunoreactive erythropoietin (EPO) was measured sequentially in 8 patients with thalassaemia major. The EPO levels were distinctly increased before transfusion; they did not significantly change just after transfusion, but subsequently decreased. Pretransfusion EPO levels were similar to those observed in patients with non renal non inflammatory anaemias of the same severity. Our results show that production of EPO is appropriately increased in thalassaemia major and confirm that stimulation of endogenous erythropoiesis is not completely suppressed by the hypertransfusion regimen commonly used in this disease. As hyperstimulated ineffective erythropoiesis may lead to invalidating complications, we suggest that serum EPO measurements, which are now easily and reliably performed, should be used in monitoring the therapy of thalassaemia major.
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PMID:Serum immunoreactive erythropoietin level: a new parameter for monitoring transfusion management of thalassaemia. 178 Feb 35

Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was previously reported in normal human adult erythroblast colonies ("bursts") generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies focused on the reactivation of HbF synthesis in normal adult erythroid bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in FCS+ methylcellulose culture. Reactivation is almost totally suppressed when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E growth in FCS+ Mo- culture). In both experimental conditions, the proliferation of lymphocytes and macrophages interspersed among colonies is drastically reduced, and the cloning efficiency of granulocyte-macrophage (GM) progenitors is sharply diminished. In either case, addition of biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose-related increase of HbF synthesis up to the level in FCS+ culture, with even more elevated values on delayed addition of Ep. A dose-related increase was also observed in erythroblast clones generated by highly purified BFU-E. These results suggest that reactivation of HbF synthesis in normal adults is at least in part mediated by GM-CSF. Furthermore, they imply intriguing hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they raise the possibility of reactivation of HbF synthesis in beta-thalassemia and sickle cell anemia by GM-CSF therapy.
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PMID:Granulocyte-macrophage colony-stimulating factor reactivates fetal hemoglobin synthesis in erythroblast clones from normal adults. 247 26

Extramedullary hematopoiesis (EMH) is observed in people suffering from severe anemia of prolonged duration and appears to be a compensatory mechanism for disturbed medullary hematopoiesis. The hemoglobinopathies (such as thalassemia, spherocytosis, and sickle cell disease), neoplastic diseases such as leukemia and lymphoma, and others, including myelofibrosis and osteitis fibrosa cystica, are associated with EMH. These diseases and their resultant anemia have in common the ability to stimulate erythropoietin production, which in turn may stimulate hematopoiesis in organs of mesenchymal origin. The liver and spleen are the most common sites of EMH; however, other sites, including the falx cerebri, thoracic cavity, retroperitoneal area and pelvis have been reported. When present, intrathoracic EMH is most frequently associated with thalassemia. Spinal cord compression and hemothorax have also been reported as complications of intrathoracic EMH.
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PMID:Asymptomatic intrathoracic extramedullary hematopoiesis: a report of three cases. 262 Nov 1

Hemopoiesis is studied in vitro mainly in semisolid culture, where hemopoietic progenitors develop into discrete colonies. We describe a liquid culture system that supports the proliferation and maturation of human erythroid progenitors. We seeded mononuclear cells from the peripheral blood (PB) of patients with beta-thalassemia in liquid medium in the presence of conditioned medium from human bladder carcinoma cells. Seven days later, RBCs, normoblasts, granulocytes, and monocytes disappeared, and the number of lymphocytes dropped considerably. In contrast, erythroid colony-forming cells increased fourfold to tenfold. The next step entailed the removal of colony-stimulating factor (CSF) and CSF-secreting cells, the exclusion of macrophages by harvesting nonadherent cells, and the lysis of T lymphocytes by treatment with monoclonal rat antihuman lymphocyte antibodies (CAMPATH-1) and complement. Reculture of the remaining cells in liquid medium supplemented with recombinant erythropoietin (EPO) resulted in the exclusive development of erythroid cells, with myeloid cells reduced to less than 2%. Stainable hemoglobin (Hb) appeared on day 3, with over 85% of the population containing hemoglobin by day 11 and the cell number increasing from 0.2 X 10(6) to 3 X 10(6) mL. By permitting the manipulation of culture conditions and components and increasing the cell yield, the liquid system may facilitate quantitative analysis of growth kinetics as well as biochemical and immunologic characterization of the developing erythroid cell.
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PMID:Proliferation and maturation of human erythroid progenitors in liquid culture. 291 Mar 52

In guinea pig bone marrow cultures with heterozygous alpha-thalassemic serum, 59Fe uptake values are elevated above iron values of cultures with serum of normal subjects. These results show that erythropoietin (EP) activity values in heterozygous alpha-thalassemia are comparable to those previously observed by ourselves in heterozygous beta-thalassemia despite of the different Hb concentration in these thalassemic syndromes. This points to the existence of signals which regulate Ep synthesis independently of Hb levels.
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PMID:Erythropoietin levels in heterozygous alpha-thalassemia. 310 56

Colonies derived from erythroid burst-forming units (BFU-E) synthesize fetal hemoglobin (HbF) in amounts that far exceed in vivo levels. There is some evidence that HbF synthesis is controlled at the level of a primitive erythroid precursor cell. Dexamethasone may potentiate the development of BFU-E. Since a means of augmenting HbF production in sickle cell anemia or severe beta-thalassemia would be of great therapeutic value, we studied the effects of dexamethasone on HbF and gamma-globin chain synthesis in BFU-E from patients with sickle cell anemia and controls. HbF was measured by radioimmunoassay of BFU-E lysate and gamma-chain synthesis by the incorporation of 3H-leucine into globin, which was then purified by gel filtration and column chromatography. Dexamethasone (10(-9) M) produced an increase in the number of BFU-E in 16 of 19 subjects when compared with numbers of BFU-E cultured with only erythropoietin. The individual BFU-E were larger and contained more subcolonies. Dexamethasone did not increase HbF or gamma-chain synthesis, and there was no relationship between proliferation of BFU-E and augmented HbF production. Thus, although dexamethasone augmented the development of erythroid bursts, there was no increment in HbF.
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PMID:Effects of dexamethasone on fetal hemoglobin synthesis in peripheral blood erythroid burst-forming units. 616 63

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.
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PMID:The relationship between human spleen and blood erythroid burstforming units (BFU-E). 668 75

A patient with thalassemia intermedia and haemosiderosis is reported. This patient did not receive transfusions or iron therapy. The iron absorption and the plasma iron turnover (PIT) were increased. Transfusions were carried out in order to decrease the amount of abnormal erythropoiesis. After that, the erythropoietin and PIT were decreased to normal levels and the iron absorption also returned to normal. The data presented suggest that increased erythropoiesis was responsible for the abnormally high iron absorption and subsequently for the haemosiderosis of the patient presented.
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PMID:Iron overload in a non-transfused patient with thalassaemia intermedia. 708 77


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