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

The bone marrow macrophages of patients with homozygous beta-thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated alpha-chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily-iron-loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly-synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division.
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PMID:Some features of bone marrow macrophages in patients with homozygous beta-thalassaemia. 20 37

Minor fetal hemoglobins in red cell hemolysates of newborn and adults with elevated levels of Hb F have been separated and quantitated by Biorex 70 column chromatography. In addition to Hb F1, other minor hemoglobin zones eluting before F1, pre-F1, and after F1, post-f1 have been observed. The relative amounts of the two pre-F1 zones and F1 are higher in the red cells of adults with 97--100% Hb F (homozygous hereditary persistence of fetal hemoglobin, homozygous deltabeta-thalassemia and homozygous beta0-thalassemia) than in the red cells of an adult with homozygous beta+-thalassemia with 66% Hb F, a child with a trisomy-D-13 having 38% Hb F, and in two newborn. Hb F was glycosylated in vitro with [14C]glucose or [14C] glucose 6-phosphate, and was acetylated using chicken reticulocyte lysate or a crude acetyltransferase preparation isolated from the same lysate with [14C]acetyl-CoA as substrate. Chromatographic analyses indicated that the Hb F1 zone can be formed both by glycosylation and acetylation of Hb F, and that pre-F1 zones can be products of the reaction of Hb F with phosphorylated glycolytic intermediates. Biosynthesis of minor hemoglobins in reticulocytes was studied with [14C]leucine in the presence and absence of cycloheximide and by pulse-chase. The resulting data indicate that Hb F1 synthesis is dependent upon Hb F synthesis and that the posttranslational modification may take place at an early stage in Hb F synthesis.
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PMID:On the chromatographic heterogeneity of human fetal hemoglobin. 42 12

Hemoglobin (Hb) Indianapolis is an extremely labile beta-chain variant, present in such small amounts that it was undetectable by usual techniques. Clinically, it produces the phenotype of severe beta-thalassemia. Biosynthetic studies showed a beta:alpha ratio of 0.5 in reticulocytes and about 1.0 in marrow after a 1-h incubation. These results, similar to those seen in typical heterozygous beta-thalassemia, suggested that betaIndianapolis was destroyed so rapidly that its net synthesis was essentially zero. To examine the kinetics of globin synthesis, reticulocyte incubations of 1.25--20 min were performed with [3H]leucine. The betaIndianapolis:beta A ratio at 1.25 min was 0.80 suggesting that beta Indianapolis was synthesized at a near normal rate. At 20 min, this ratio was 0.46 reflecting rapid turnover of beta Indianapolis. The erythrocyte ghosts from these incubations contained only betaIndianapolis and alpha-chains, and the proportion of betaIndianapolis decreased with time, indicating loss of betaIndianapolis. Pulse-chase studies showed little change in beta A:alpha ratio and decreasing betaIndianapolis:alpha and betaIndianapolis:beta A with time. The half-life of betaIndianapolis in the soluble hemoglobin was approximately equal to 7 min. There was also rapid loss of beta Indianapolis from the erythrocyte membrane. From these results, it may be inferred that betaIndianapolis is rapidly precipitated from the soluble cell phase to the membrane, where it is catabolized. Heterozygotes for beta 0-thalassemia usually have minimal hematologic abnormalities, whereas heterozygotes with betaIndianapolis, having a similar net content of beta-chain, have severe disease. The extremely rapid precipitation and catabolism of betaIndianapolis and the resulting excess of alpha-chains, both causing membrane damage, may be responsible for the severe clinical manifestations associated with this variant. It seems likely that other, similar disturbances in the primary sequence of globin polypeptide chains may produce clinical findings similar to those seen with hemoglobin Indianapolis and thus produce the phenotype of severe beta-thalassemia.
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PMID:Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia. 44 35

Three patients with a relatively mild form of beta O-thalassemia who did not require regular blood transfusions are described. Globin synthesis was studied by gel filtration and urea-carboxymethylcellulose chromatography of stroma-free hemolysates prepared from peripheral blood and bone marrow cells labeled in vitro with 14C-leucine. gamma/alpha Synthetic ratios in peripheral blood were in the same range as in patients with the severe clinical form of beta O-thalassemia, while gamma/alpha synthetic ratios in bone marrow cells were higher than in that group of patients. The size of the free alpha-chain pool measured in one case was smaller than in other patients with "classical" Cooley anemia. It is concluded that the severity of the clinical course in beta O-thalassemia does not correlate with the imbalance in alpha verus gamma chain synthesis in peripheral blood and is determined by the synthetic ratio in bone marrow cells, where the bulk of hemoglobin synthesis takes place.
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PMID:Beta O-thalassemia intermedia. 66 61

Whether the trimodality in the relative concentration of the hemoglobin variant Hb Leslie in heterozygotes (Huisman, Hemoglobin 1:349-382, 1977) is due to a polymorphism of the alpha-chain structural genes was investigated by conventional incubation of reticulocytes with 14C-leucine. In addition, an aliquot from each of the incubations was incubated under the same conditions but without isotope. Three Hb Leslie heterozygotes with presumably four, three (heterozygous alpha-thalassemia-2), and two (homozygous alpha-thalassemia-2) active alpha-chain genes and with 33%, 22% and 11% Hb Leslie respectively, and one patient with the Hb Leslie beta(0)-thalassemia condition with more than 85% Hb Leslie were studied. The data indicate that betaLeslie chains have a lower affinity for alpha chains that betaA chains. A concomitant alpha-chain deficiency results in a reduced incorporation of betaLeslie chains into the tetrameric Hb Leslie molecules, while the quantity of Hb Leslie produced correlates with the degree of alpha-chain deficiency. Excess of betaLeslie chains is preferentially degraded.
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PMID:Is the trimodality of Hb Leslie (alpha 2 beta 2 131 Gln---O) in heterozygotes the result of a variable number of active alpha-chain genes? Evidence for posttranslational control of hemoglobin synthesis. 74 78

Patients whose red-cell indices are suggestive of thalassaemia trait, but who have a normal haemoglobin electrophoretic pattern, may be carriers of alpha-thalassaemia. A diagnosis of alpha-thalassaemia trait was made in 44 such patients, using the incorporation of [3H]leucine by reticulocytes to measure the relative rates of synthesis of the alpha- and beta-chains of adult haemoglobin. Patients with alpha-thalassaemia trait had a reduced rate of synthesis of the alpha-chains, with a mean alpha/beta specific activity ratio of 0.79+/-SD 0.07. The mean alpha/beta specific activity ratio of 20 control subjects was 1.06+/-SD 0.08. The diagnostic value of the haemoglobin H(Hb H) preparation was assessed in proven alpha-thalassaemia heterozygotes of various races. A high proportion of 'false negative' results in Indian and Negro heterozygotes indicated that the Hb H preparations is a highly unreliable screening test for use in a multi-racial population. There was no significant difference in the mean level of Hb A2 in alpha-thalassaemia heterozygotes (2.0+/0SD 0.6) compared with that of the control group (2.1+/0SD0.5). Comparison of data from patients with alpha- and beta-thalassaemia traits showed that alpha-thalssaemia trait is the milder disorder, in terms of its effects of red-cell morphology, red-cell indices and degree of globin chain imbalance. Amongst individual patients with alpha-thalassaemia trait, there was no correlation between the alpha/beta specific activity ratio and the red-blood-cell(RBC) d the red-blood-cell (RBC) count, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). This suggests that the alpha/beta ratio cannot be used to distinguish between carriers of a mild gene ('silent carriers') and carriers of a more severe disease. This is the first sutdy to characterize alpha-thalassaemia trait in Indians, in whom it appears to be a common disorder. Haematologically, alpha-thalassaemia trait in Indians is milder than that seen in Chinese and the fact that haemoglobin Bart's hydrops fetalis does not occur in Indians makes it likely that the genetics of Indian alpha-thalassaemia differ from those of the Chinese disease. A possible genetic model for Indian alpha-thalassaemia is discussed and the identification of the homozygote is seen as the first step in the determination of the underlying molecular defect.
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PMID:Alpha-thalassaemia trait in various racial groups in the United Kingdom: characterization of a variant of alpha-thalassaemia in Indians. 97 33

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.
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PMID:Prenatal diagnosis of hemoglobinopathies. A review of 15 cases. 99 41

The syndrome thalassemia intermedia can be the clinical expression of heterozygosity for different tyes of thalassemia, beta-thalassemia and hereditary persistence of fetal hemoglobin, beta-thalassemia and Hb-Lepore, and in blacks it may even represent a true beta-thalassemia homozygote. This report describes thalassemia intermedia in a white male due to beta-thalassemia and an unstable hemoglobin. Chain-synthesis studies showed an excess of alpha-chain production over beta-chain production in the propositus and his mother but balanced chain synthesis in the clinically normal father, who is heterozygous for the unstable hemoglobin. The unstable hemoglobin was found to be beta14 (A11) Leu leads to Pro, which has previously been described in a clinically normal African woman, and named Hb-Saki. This hemoglobin is not distinguishable from Hb-A on routine electrophoresis at alkaline or acid pH and tests for unstable hemoglobins are necessary for its detection. The increasing list of such hemoglobin variants and previous cases of heterozygosity for beta-thalassemia and unstable hemoglobins are reviewed.
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PMID:Thalassemia intermedia caused by heterozygosity for both beta-thalassemia and hemoglobin Saki [beta 14 (A11) Leu replaced by Pro]. 99 17

In Thailand, two types of high Hb A2-beta-thalassemia genes: beta0-thalassemia (beta0-thal) or classical beta-thalassemia and beta+-thalassemia (beta+-thal) or mild beta-thalassemia exist. This study presents hematologic data and globin chain synthesis in peripheral blood of the genuine beta+-thal heterozygotes in comparison with those of the beta0-thal heterozygotes. Thirty individuals of Thai and Chinese extraction with the beta+-thal heterozygosity were hematologically examined. The hematologic means of hemoglobin concentration, MCV, MCH, MCHC, Hb A2 and alkali denaturation hemoglobin of the beta+-thal traits were, 11.7 g%, 67.8 mu3, 21.5 gammagamma, 32.1%, 4.94% and 1.20% respectively. These were not statistically different from those of the beta0-thal traits of our previous study(1). The globin chain synthesis in reticulocytes were performed by incorporation of 3H-Leucine for 3 hours. The mean of total radioactivity alpha/beta ratio in 11 normal controls was 1.07 +/- SD 0.03. The mean of alpha/beta ratio in 9 beta+-thal traits was 2.03 +/- SD 0.10 which was significantly different from that in 7 beta0-thal traits of 2.28 +/- SD 0.07. Our globin chain synthesis thus appears to be helpful of discriminating the beta+-thal trait from the beta0-thal trait.
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PMID:beta+-Thalassemia trait: hematologic and hemoglobin synthesis studies. 105 72

To determine whether beta-thalassemia can be detected in the fetus, blood was obtained from abortuses of normal mothers and of mothers with beta-thalassemia trait. The red cells were incubated with radioactive leucine and the globin chains were analyzed by radiochromatography. Two independent methods were utilized to correct the results for contamination by maternal radioactive beta-chain, and the corrected beta/gamma ratios were compared to a previously established range of normal fetal beta/gamma synthetic ratios obtained by similar measurements in pure fetal cells. In the erythroid cells of three fetuses from mothers with beta-thalassemia trait, the beta/gamma synthetic ratio was normal in two. The third had a beta/gamma ratio of 0.04 at 10 1/2 weeks, a 50% reduction, consistent with fetal beta-thalassemia trait. Two other fetuses, derived from parents both of whom had beta-thalassemia trait, were also studied. One had a beta/gamma ratio of 0.029 at 8 weeks, a 65% reduction, also consistent with beta-thalassemia trait. The cells of the other had a ratio of essentially zero at 11 weeks, highly suggestive of homozygous beta-thalassemia. Although further experience will be needed to distinguish the homozygous and heterozygous states reliably, it now appears that the beta-thalassemia gene is expressed in the first trimester. Therefore these data suggest that the antenatal diagnosis of beta-thalassemia is becoming an attainable goal.
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PMID:Expression of the beta-thalassemia gene in the first trimester fetus. 105 53


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