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)

The protein composition of ghosts, inside-out vesicles (IOV), and membrane skeletons (MS) of erythrocytes (RBC) from splenectomized (spx) and nonsplenectomized (non-spx) patients with beta-thalassemia major and beta-thalassemia intermedia was determined. Ghosts from spx thalassemia intermedia patients had a significant increase in their globin content (which was mostly heme reactive) and contained extra polypeptides in the protein 4.2 to 5 and 6-globin areas. The Triton-extracted MS from all of the thalassemic patients showed two major abnormalities: they retained up to twice the amount of protein 3 when compared with controls; they had a significant increase in their globin content, the concentration of which was independent of their protein 3 content. Analysis of the IOV revealed no differences between those prepared from normal controls and those of the patients. MS from spx thalassemia intermedia patients were grossly abnormal when examined by scanning electron microscopy and they exhibited aggregates of material that on transmission electron microscopy suggested the presence of globin precipitates. We propose that, although the integral protein composition, as reflected in the IOV, from severely affected beta-thalassemics is intact, their MS assembly is deranged. The altered skeletal structure of thalassemic RBC could result from attachment of denatured globin to the skeleton components. These abnormalities may contribute to the premature cell death seen in severe beta-thalassemia.
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PMID:Erythrocyte membrane skeleton abnormalities in severe beta-thalassemia. 359 63

Dodge ghosts and their Triton extracted cytoskeletons (TS) were obtained from RBC of splenectomized (spx) and non-splenectomized (non-spx) patients with beta thalassemia intermedia. No major abnormalities were seen in the polypeptide pattern of Dodge ghosts of the thalassemic patients apart from increased globin content in the spx patients (P = 0.004). There was also a large increase of globin content in the TS of both spx and non-spx patients, while the spectrin content of the TS was markedly decreased from 22 +/- 2.8% in the spx patients compared to 39 +/- 2% in the controls (P = 0.006). At least part of the globin was not found at the normal band 3-binding site. The mean Ca++ content in spx and non-spx controls was approximately 6.0 micromoles ca/liter RBC, as compared to 26 +/- 7.6 (P less than 0.001) in the non-spx and 85 +/- 24 in the spx thalassemic patients (P less than 0.001). (Ca++Mg++)-ATPase activity was in the same range in RBC of patients and controls. Membrane protein phosphorylation was examined by incubation of intact cells with (32P)Pi. There was decreased labeling of several protein bands in thalassemic RBC which are labeled in normal RBC. New phosphorylation peptides also appeared. On the other hand, there were no major differences in the phosphorylation of isolated membranes including phosphorability of spectrin. The possible etiology and consequences of the newly described RBC membrane changes in thalassemia is discussed.
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PMID:Alterations in structure, function, and Ca++ content of thalassemic red blood cells. 614 9

In a Greek family three cases of beta-thalassaemia intermedia were diagnosed as resulting from the interaction of a typical high HbA2-beta-thalassaemia with an atypical (silent) beta-thalassaemia gene. Following electrophoresis of globins on an acid-urea-Triton-acrylamide system, an otherwise silent beta-like variant was revealed in the carriers of the atypical thalassaemia gene and in the intermediates; it amounted to 33% of the non-alpha chains in the former and to c. 75% in the latter. The provisional name Hb Knossos is suggested for this abnormality.
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PMID:'Silent' beta-thalassaemia caused by a 'silent' beta-chain mutant: the pathogenesis of a syndrome of thalassaemia intermedia. 710 38

A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA2 suggestive of beta-thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal beta-chain only when run on PAGE urea Triton. As expected, alpha/beta-globin mRNA ratios were influenced by the concomitant presence of an alpha-globin gene pathology and the beta0 thalassemia and not by the presence of the beta-globin variant which apparently is clinically silent.
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PMID:Hb Iraq-Halabja beta10 (A7) Ala-->Val (GCC-->GTC): a new beta-chain silent variant in a family with multiple Hb disorders. 1039 11