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)

Various ultrastructural abnormalities were found in the erythroblasts of three homozygotes for haemoglobin C (HbC), one patient with HbC/beta(+)-thalassaemia and one patient with HbC/beta (0) thalassaemia. These included a coarsely granular or reticular appearance and altered electron-density of the heterochromatin, loss of parts of the nuclear membrane, and oozing of nuclear material into the cytoplasm. In addition, the two patients with HbC/beta-thalassaemia, but not the others, showed precipitated intracytoplasmic alpha-chains in a few profiles of polychromatic erythroblasts and marrow reticulocytes. Electron microscope autoradiographic studies of bone marrow cells from two of the patients with HbC disease and the patient with HbC/beta (0)-thalassaemia showed a marked depression or failure of incorporation of 3H-leucine into protein in some of the ultrastructurally abnormal erythroblasts. This impairment of protein synthesis may lead to alterations in the erythroblast membrane that are involved in the recognition and phagocytosis of the abnormal erythroblasts by macrophages.
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PMID:Ultrastructural abnormalities and arrest of protein biosynthesis in some erythroblasts from homozygotes for haemoglobin C and double heterozygotes for haemoglobin C and beta-thalassaemia. 208 81

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual hematologic values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha 0-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha (+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (--MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (--SEA) and (--SPAN) and the "no-deletion" thalassaemias.
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PMID:[Analysis of a program for atypical familial microcytosis. Molecular basis of alpha-thalassemia]. 227 39

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual haematimetric values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha zero-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha(+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (- -MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (- -SEA) and (- -SPAN) and the "no-deletion" thalassaemias.
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PMID:[Analysis of a program for atypical familial microcytosis. Molecular basis for alpha-thalassemia. GEHBTA]. 236 92

Hb Suan-Dok [alpha 2(109)(G16)Leu-greater than Arg beta 2] has an alpha-thalassemia-like effect due to low production and instability of the altered alpha-globin chain. Since the Hb Suan-Dok mutation (CTG-greater than CGG) creates a new Sma I restriction site, it was possible to diagnose the mutation by restriction analysis. The location in the alpha 2-globin gene was confirmed. The distribution of alpha-globin gene anomalies and a beta-thalassemia gene in the original family, deduced from examinations at the protein level, was verified by DNA analysis.
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PMID:Direct demonstration of the HB Suan-Dok mutation in the alpha 2-globin gene by restriction analysis with Sma I. 238 13

Molecular analysis of the beta-globin genes from a patient with a beta-thalassemia phenotype showed that a single nucleotide mutation (CTG-CCG) at codon 110 in one of the genes resulted in a leucine to proline substitution. The same mutation with a similar phenotype, was observed in her mother and sister, by Southern blotting analysis of DNAs digested with Mspl, the recognition site of which was created by this base substitution. This indicates a close relationship between this mutation and the beta-thalassemia phenotype. No anomalous peak of radioactivity was detected by reverse-phase high-performance liquid chromatography (HPLC) in the patient's reticulocytes incubated with isotopically labeled amino acid. The leucine-proline (Leu-Pro) substitution probably disrupts the G-helix and in turn interferes with globin contact points. The uncombined beta-globin chain would be rapidly destroyed and the beta-thalassemia phenotype would follow.
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PMID:A novel globin structural mutant, Showa-Yakushiji (beta 110 Leu-Pro) causing a beta-thalassemia phenotype. 282 77

Red cell volume distribution curves were studied in alpha-thalassaemic mice (Hbath-J/+ mice) and normal mice (+/+ mice) of various ages. Individual Hbath-J/+ mice could not be reliably distinguished from their +/+ littermates on the basis of modal cell volume either at birth or during the first 3 weeks of life. However, between the ages of 4 and 30 weeks Hbath-J/+ mice displayed a degree of microcytosis that enabled them to be readily distinguished from their normal littermates using the criterion of modal red cell volume. Preliminary studies of alpha:beta globin chain synthesis ratios given by blood reticulocytes of Hbath-J/+ and +/+ mice after incubation with 3H-leucine for 5 min and 2 h suggest that there is little or no proteolysis of excess beta-chains in the alpha-thalassaemic mouse. Electron microscope studies revealed that the erythroblasts, marrow reticulocytes and circulating red cells of Hbath-J/+ but not +/+ mice contain stellate and branching intracytoplasmic inclusions, presumed to consist of precipitated beta-chains. These inclusions were ultrastructurally similar to the inclusions which have been previously reported in the erythroblasts and marrow reticulocytes of people with various alpha-thalassaemia syndromes. The proportion of erythropoietic cell profiles with inclusions was higher in Hbath-J/+ mice (in which two of the four alpha-globin genes are deleted) than in Thai patients with HbH disease (in whom there is usually a deletion of three of the four alpha-globin genes); this finding is probably related to a relatively low proteolytic capacity in the more mature mouse erythroid cells when compared with human cells. The presence of inclusion-containing red cells (mainly reticulocytes) in the peripheral blood of unsplenectomized Hbath-J/+ animals contrasts with the absence of such cells in unsplenectomized patients with alpha-thalassaemia I trait and HbH disease; this difference seems to be at least partly due to a poorly-developed pitting function in the mouse spleen.
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PMID:Red cell volume distribution curves and intracellular globin chain precipitation in the alpha-thalassaemic mouse, Hbath-J. 300 53

We have investigated the natural killer (NK) activity of both fractionated (Percoll density gradient) and unfractionated mononuclear cells from patients with beta-thalassemia major who are iron overloaded as a consequence of chronic transfusion therapy. These patients were found to have significantly decreased NK activity against K562 targets at all effector:target ratios tested (p less than 0.001). Both splenectomized and nonsplenectomized patients had normal proportions of Leu-11b-staining (NK) cells. Since they had normal to elevated absolute white cell and lymphocyte counts, a change in the absolute number of NK cells could not account for the decreased killing. We also found that the decrease in NK activity was transfusion related (r = -0.603, p less than 0.005). To determine whether or not this decrease in NK activity could be related to iron overload, we preincubated patient effector cells with desferrioxamine (DFO) or 2,3-dihydroxybenzoic acid (DHB) for 6 hr before addition of K562 targets. Both of these iron-chelating agents consistently increased the NK activity of cells from thalassemia patients. DHB had the greater effect, being able to increase patient NK activity to virtually normal levels. On the other hand, preincubation of cells from normal controls with DHB caused only a slight increase in NK activity, while similar treatment with DFO had little or no effect. When target cells were preincubated with the chelating agents before addition of either normal or patient effector cells, no change in cytotoxicity was seen, demonstrating that the chelating agents act at the effector cell level. Furthermore, if the chelating agents were saturated with iron prior to preincubation with the effectors, no increase in the cytotoxicity of thalassemic NK cells was observed. These results indicate that thalassemia patients have a reversible, transfusion-related decrease in NK function which may arise as a consequence of iron overload.
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PMID:Decreased natural killer activity in thalassemia major: a possible consequence of iron overload. 300 97

Patients with thalassemia who receive multiple blood transfusions are at risk for the acquired immunodeficiency syndrome. Peripheral blood lymphocyte subpopulations were studied in 22 multitransfused thalassemic patients; 10 patients were without splenectomy and 12 were studied after splenectomy. Both groups were negative for anti-HIV. Four additional patients who were found positive for anti-HIV and ten healthy controls were also included in this study. Patients without splenectomy compared to controls and to patients after splenectomy showed a significant decrease of both percentage (p less than 0.001) and absolute numbers (p less than 0.001) of Leu-7+ cells without significant abnormalities of T4/T8 ratio (1.56 +/- 0.4). Patients after splenectomy compared to controls and to patients without splenectomy showed a significant increase of the absolute numbers of lymphocytes and lymphocytes subsets T11+, T3+, T4+, T8+ and SmIg+ cells. In the seropositive patients for HIV only a significant increase of the absolute number of T8+ cells was observed while the T4/T8 ratio was 1.24 +/- 0.73. The decrease in the percentage of Leu-7+ cells in patients without splenectomy correlated inversely to the total amount of blood transfused. In conclusion patients with thalassemia had normal T4/T8 ratio and did not show the abnormal immunologic profile that has been reported in haemophiliacs.
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PMID:Immune status of Greek patients with beta-thalassemia major negative for anti-HIV. 310 26

We studied 111 cases of Hb H disease from different families using Bam HI and Bgl II restriction enzymes. The results showed that 76 cases (68.5%) were of the deletion type, eight cases (7.2%) had Hb Constant Spring (Hb CS), and 27 cases (24.3%) were of the nondeletion and Hb CS types (alpha T). Distribution of the alpha-thalassemia-2 (alpha-thal-2) gene varies with the different regions in China. The rightward deletion (alpha -3.7) is found chiefly in Guangdong Province, the leftward deletion (alpha -4.2) mostly in Jiangxi Province, and the nondeletional type in Guangxi Province where the Han nationality is most prominent. We studied the nondeletional Hb H type by DNA gene mapping, digestion with Msp I, and hybridization with a 32P-alpha probe for the presence of the Hb Quong Sze [alpha 125(H8)Leu----Pro] mutation. It appears that none of these alpha-thal-2 genes contain the Hb Quong Sze mutation.
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PMID:The types and distribution of alpha-thalassemia-2 in China. 320 88

We have analyzed the sequence of the beta globin gene of a chromosome that is linked to the occurrence of an inclusion body beta-thalassemia characterized in the heterozygote by moderate anemia, severe red cell abnormalities, splenomegaly, inclusion body formation, elevated Hb A2 levels, and an increased in vitro alpha/beta chain synthetic ratio. The data indicate a change in codon 114 from CTG (Leu) to -GG that resulted in a frameshift and the presumed synthesis of an abnormal beta chain that is 156 residues long with a completely different C-terminal amino acid sequence. The change in codon 114 gives a -GGGCCC- sequence that creates a new ApaI site; the resulting 2.6-kilobase fragment has been observed in all subjects with this thalassemia condition. Protein structural analyses failed to demonstrate any trace of the abnormal beta chain, even in reticulocytes and nucleated red cells that were isolated by density gradient centrifugation. The inclusion bodies appear to contain mainly normal alpha chains. It is assumed that the structure of the beta-Geneva chain prevents it from combining with normal alpha chains; this results in a rapid breakdown of the abnormal protein during the early stages of red cell maturation and an accumulation of free alpha chains.
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PMID:Inclusion body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta 114. 340 99


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