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

Two conditions are liable to lower the alpha:beta globin biosynthesis ratio in reticulocytes: iron deficiency and alpha-thalassaemia. The present paper studies the effect of haemin on reticulocytes from 12 patients who have alpha-thalassaemia and/or are iron deficient. The alpha:beta globin biosynthesis ratio was improved in all these cases. 4 showed initially an alpha:beta synthesis ratio usually associated with alpha-thalassaemia type-1; on the addition of haemin the ratio rose to that associated with alpha-thalassaemia type-2. In the other 8 patients the ratio was initially typical for alpha-thalassaemia type-2, and on addition of haemin the ratio became normal. It is suggested that in iron deficient patients a diagnosis of alpha-thalassaemia type-1 or type-2 cannot be made unless haemin has been added to the test system. If this is not done iron deficiency alone can cause the alpha:beta globin synthesis ratio to resemble that associated with alpha-thalassaemia type-2, and iron deficiency in combination with alpha-thalassaemia type-2 can cause the ratio to resemble that typical for alpha-thalassaemia type-1. Reticulocytes from 8 alpha-thalassaemic patients without iron deficiency did not show a marked haemin effect (less than 5%), and in 1 patient with iron overload, the ratio actually fell by about 10%.
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PMID:Interaction between iron deficiency and alpha-thalassaemia: the in vitro effect of haemin on alpha-chain synthesis. 9 95

Human cellular DNA fragments from cells of normal subjects and patients with thalassemia obtained by restriction enzyme digestion were analyzed for their globin gene content. The fragments were separated on agarose gels, transferred to nitrocellulose filters, hybridized to globin [(32)P]cDNA, and radioautographed. One to ten picograms of globin gene sequences were detectable. With EcoRI digestion, eight to nine cellular DNA fragments were found to contain globin genes. Three of these contained beta-like gene sequences assayed with beta globin cDNA probe. One beta-like fragment was absent in DNA from a homozygous subject for hemoglobin Lepore. Two of the three beta gene-containing fragments present in normal DNA were absent in DNA from a patient with hereditary persistence of fetal hemoglobin. The same two fragments containing beta-like genes were absent from deltabeta thalassemic DNA and one new fragment containing beta-like genes was found. Together with results obtained by hybridization of these DNAs in solution, the data are consistent with deletion of specific restriction human DNA fragments in subjects with these disorders and a greater deletion of beta-like gene sequences in subjects with hereditary persistence of fetal hemoglobin than in those with deltabeta thalassemia.
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PMID:Changes in restricted human cellular DNA fragments containing globin gene sequences in thalassemias and related disorders. 27 14

Thalassemia is characterized by unequal rates of synthesis of the alpha and beta globin chains that are part of the hemoglobin tetramer. In the type of thalassemia due to a defect in beta-chain synthesis (beta-thalassemia), this imbalance results in a relative exoess of alpha-chains. We have studied the susceptibility of excess free alpha-chains to proteolysis. Incubation of isotopically labeled peripheral blood lysates from individuals with beta-thalassemia trait in the presence of bone marrow or normoblast lysates from thalassemic or hematologically normal individuals resulted in a decrease in the alpha/beta ratio and a loss of free alpha-chain radioactivity. Neither contamination with leukocytes nor higher ATP contents in young erythrocytes appeared to be responsible for this activity in normoblasts and bone marrow. We propose that erythroid precursor cells possess proteolytic activity that is markedly diminished in mature cells. This activity serves an important control function in the regulation of hemoglobin synthesis. It accounts at least in part for the more balanced synthesis of alpha- and beta-chains observed in bone marrow than in peripheral blood in heterozygous beta-thalassemia. It also plays a fine-tuning role in maintaining balanced synthesis in non-thalassemic erythrocytes.
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PMID:Proteolytic activity in erythrocyte precursors. 27 45

Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2--6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in alpha globin production with an average alpha/beta ratio of 0.31 (range 0.22--0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either alpha-thal-1 (average MCV 65.2 fl; range 59--70) or alpha-thal-2 (average MCV 79.6 fl; range 74--88). A subject with altha-thal-1 trait had an alpha/beta ratio of 0.56; the average for five cases of alpha-thal-2 was 0.73. One other family member was thought to be homozygous for alpha-thal-2 trait and exhibited an MCV of 65 fl with an alpha/beta ratio of 0.5. These data reconfirm that in Blacks with alpha thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in alpha and beta globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater alpha globin production in that population of thalassaemics.
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PMID:Alpha thalassaemia in American blacks: a study of a family with five cases of haemoglobin H disease. 42 29

Globin mRNA isolated from a number of beta0 thalassemia patients of different ethnic origins was analyzed by RNA-cDNA hybridization and, in two cases, by fingerprint analysis of 125I-labeled mRNA. Quantitation of the relative amounts of alpha- and beta-mRNA by hybridization to purified alpha-and beta-cDNA revealed that in approximately half the cases, there was less than 1% as much beta-mRNA as alpha-mRNA. In the rest of the cases, low levels of beta-like mRNA were detected in amounts 4-12% as abundant as alpha-mRNA. There was variability in the yield of beta-like mRNA in patients of the same racial group, in the same patient at different times and in similarly affected siblings: beta-mRNA was virtually absent in some samples, whereas low but significant levels were found in other samples. In one patient, beta-like mRNA was not detected in peripheral blood RNA, but was present in the RNA of bone marrow cells. In one case, the thermal stability of the beta0 thalassemia mRNA-beta-cDNA hybrid was measured and found to be slightly lower than that of the authentic beta-mRNA-beta-cDNA hybrid. In none of the cases tested was there synthesis of beta-globin chains directed by beta0 thalassemia mRNA in a cell-free protein-synthesizing system, even when beta-like mRNA was detected in the sample by hybridization assays. mRNA from two patients was labeled in vitro with 125I, digested with T1 RNAase and fractionated in two dimensions. Analysis of the resulting fingerprints revealed the presence of prominent alpha chain-specific oligonucleotides without detectable beta chain-specific oligonucleotides, and thereby confirmed the results of hybridization assays showing absent or very low levels of beta-mRNA in the same RNA samples. Our results support the concept that beta0 thalassemia is heterogeneous in its molecular basis even within the same racial group: in some patients, it is associated with absent beta globin mRNA, whereas in other patients, it is associated with low but significant levels of nonfunctional beta or beta-like globin mRNA. The variable amounts of beta-like mRNA detected in different samples from the same patient, and in patients with the same genotype, indicate that as yet undefined factors can influence the yield of beta-like mRNA observed in beta0 thalassemia.
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PMID:Variability in the amount of beta-globin mRNA in beta0 thalassemia. 66 42

In patients with betao thalassaemia from Ferrara, beta globin mRNA sequences are either absent or structurally abnormal while in betao thalassaemia in Catania, beta globin mRNA sequences are present. In deltabeta thalassaemia there is a deletion of beta-like globin genes, while in betao Catania DNA, no beta globin gene deletion is detectable.
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PMID:Abnormal or absent beta mRNA in betao Ferrara and gene deletion in delta beta thalassaemia. 98 35

Globin mRNAs were isolated from circulating reticulocytes both from rats carrying a homozygous, recessive mutation causing a severe thalassemia-like syndrome and from normal rats. After first identifying the rat globin chains as alpha or beta chains, the translational products primed by both polysomal and nonpolysomal mRNAs in wheat germ 30000 x g supernatant were analyzed: the ratio of alpha to beta globin mRNAs found in polysomes isolated from mutant rats is identical to the ratio of their products synthesized in vivo while the ratio of these mRNAs is quite different in the nonpolysomal fraction, the latter being enriched in alpha globin mRNA. No difference is found in the ratio of alpha and beta globin mRNAs in the polysomal and nonpolysomal RNA isolated from normal rats, both being identical to the ratio of their products synthesized in vivo. One third of the total amount of mRNA found in mutant cells is not in polysomes as compared to only 6 percent for the mRNA from normal lysates. These results suggest that a translational control mechanism is involved although the decreased globin synthesis in b/b anemia can not be fully accounted for by its operation.
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PMID:Rat b/b anemia: translation of normal and anemic globin mRNA in wheat-germ cell-free system. 100 56

Purified alpha and beta globin complementary DNAs (cDNAs) have been separated from total radioactively labeled human globin cDNA using mRNA purified from liver of a hydrops fetalis (alpha thalassemia). The beta cDNA hybridizes to the hydrops fetalis mRNA while the alpha cDNA remains single-stranded. the purified alpha and beta cDNAs were assayed for their purity by their hybridization to mRNA prepared from reticulocytes of nonthalassemia, alpha thalassemia, and beta thalassemia subjects. The results indicate that the separated cDNAs are selective in hybridization to alpha or beta globin mRNAs, respectively. The previously reported deficiency of globin mRNA in thalassemia cells has been confirmed with these purified cDNAs. The purified alpha and beta cDNAs were hybridized to cellular DNA to non-thalassemia, beta+ thalassemia, and hydrops fetalis (alpha thalassemia) DNA. The alpha cDNA hybridized to hydrops fetalis liver DNA to a much lower extent that beta cDNA, confirming the previously reported deletion of alpha globin genes in hydrops fetalis. By contrast, both the alpha and beta DNA probes hybridized to the same extent to spleen DNA from non-thalassemia and from beta+ thalassemia patients. Between two and five globin genes in non-thalassemia and beta+ thalassemia DNA hybridize to beta cDNA and one to five to alpha cDNA. These studies indicate that in beta+ thalassemia, there is no detectable deletion in beta globin genes. The genetic defect in beta+ thalassemia appears to be due to either repression of transcription of beta globin genes or abnormal processing of beta globin mRNA.
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PMID:Relative numbers of human globin genes assayed with purified alpha and beta complementary human DNA. 105 26

The extent of variability in the number of human hemoglobin (Hb) alpha chain loci has not yet been conclusively determined. There is evidence that in some populations individuals may possess two alpha-chain loci, while in other populations only one locus is present. Electrophoresis of peripheral blood from 53 heterozygotes for Hb G Philadelphia (alpha 68 Asn leads to Lys) revealed that the proportion of Hb G is trimodally distributed, with modes at approximately 20, 30, and 40% Hb G. Familial, hematologic, and statistical studies suggest that hte proportion of Hb G is not random but is genetically controlled and inversely correlated with mean cell volume. Two alternative genetic models are proposed to explain these findings: one assums alpha-thalassemia, while the other postulates variability in the number of alpha-chain loci in the American Black population. Biosynthetic studies of blood from 15 subjects revealed balanced synthesis of alpha and beta globin chains in heterozygotes from all three classes, strongly supporting variable gene dosage rather than alpha-thalassemia as the mechanism underlying the observed trimodality in the proportion of Hb G. Incompatibilities between out results and current concepts of alpha-thalassemia are discussed in the context of differences between Black compared with Oriental and Italian forms of Hb H disease.
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PMID:Trimodality in the proportion of hemoglobin G Philadelphia in heterozygotes: evidence for heterogeneity in the number of human alpha chain loci. 106 76

In one southern Italian and one Pakistani patient with homozygous beta0 thalassaemia in which no detectable beta-globin synthesis occurs and no beta-globin messenger RNA is found, the gene for beta globin has been shown to be present using complementary DNA. This demonstrates that for these patients the imbalance in chain synthesis is not attributable to a gene deletion.
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PMID:Presence of gene for beta globin in homozygous beta0 thalassaemia. 124 58


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