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

The synthesis of fetal hemoglobin was investigated in in vitro cultures of erythroid precursors isolated from peripheral blood of normal individuals, newborns and of subjects with different hemoglobinopathies. Synthesis of hemoglobin was assessed by 35s-methionine labeling of cultures and measurement of the radioactivity incorporated into the hemoglobins A2, A, F and S isolated by column chromatography on DE 52 cellulose. The erythroid precursors from most of the studied individuals cultured in in vitro system responded with synthesized an average of 15% of Hb F while cultures from newborns produced an average of 60% of Hb F in comparison of 73% of Hb F in peripheral blood of the same newborns. Erythroid precusors from subjects heterozygotes for beta-thalassemia, heterozygotes for HPFH, and homozygotes for Hb S produced an average of 20%, 43% and 30% of Hb F, respectively, in comparison of 7%, 14% and 9% of Hb F, respectively, present in the RBC of the same individuals. These data support the previously published results (6-11) that erythroid bursts in culture reactivate the structural genes for the gamma chain synthesis.
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PMID:[Preferential synthesis of fetal hemoglobin in in vitro cultures of erythroid precursors from peripheral blood of healthy persons and those with hemoglobinopathies]. 9 30

The study of 176 subjects with beta-thalassemia, associated or not with a hemoglobinopathy, shows great diversity. The hemoglobin C thalassemias are less severe and form a fairly homogeneous group. Sickle cell thalassemia cases have more marked anemia and the disease takes on more varied forms, no doubt because the main mechanism of the anemia, the hyperhemolysis, is influenced by several factors which have a variable effect on the clinical picture. Unassociated thalassemias seem the most polymorphic. Although it seems that in certain foci the beta-thalassemias are fairly stereotyped, this first study shows in Algeria great heterogeneity. All forms are observed both clinically and in the laboratory. Present classifications have not supplied a sufficiently operative model. It is not doubt necessary to await further progress in the laboratory to classify these diseases more precisely.
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PMID:[Clinical and biological aspects of beta-thalassemia. Apropos of 176 cases]. 19 8

In this paper are brought the results obtained in two Parisian hospitals during a survey of abnormal hemoglobins in 540 immigrant workers coming from Africa, mostly from Mali, Mauritania and Senegal. All the subjects investigated were male and between 20 and 40 years old. The studies were performed following internationally standardized technics. The most frequent abnormalities were: Hb S found in 16.3%, Hb C (6.6%), alpha-thalassemia trait (3.1%) and beta-thalassemia trait (3.1%). Some rare abnormalities were also found: delta-chain variants, hereditary persistance of foetal hemoglobin, Hb Hope and Hb Grady. This work emphasizes the high frequency of the different hemoglobin disorders in this population. The easy diagnostic of electrophoretically detectable variants is compared to the more complex situation of thalassemia leading probably to an under estimation of the percentage.
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PMID:[Hemoglobinopathies in West-African immigrant workers in France (author's transl)]. 21 87

Molecular analysis of normal and abnormal human globin genes and their gene products has recently provided information on the precise genetic events that result in hemoglobinopathies. In the case of structurally abnormal hemoglobins, the following mechanisms can be invoked: single nucleotide base substitutions leading to amino acid replacement or chain termination variants; nucleotide deletions (or additions) leading to deletion and frameshift variants; and nonhomologous crossing over leading to the production of fused globin chains. The molecular basis of the thalassemia syndromes, disorders characterized by absent or decreased synthesis of alpha- or beta-globin chains, is quite heterogeneous. In some cases globin gene deletions have been demonstrated; whereas in others there is probably either a defect in globin gene transcription or a defect in nuclear globin messenger RNA (mRNA) processing, mRNA transport or globin mRNA stability. In one form of beta(0)-thalassemia a nonsense mutation has recently been demonstrated, and other cases are also associated with some as yet undetermined functional abnormality of beta-globin mRNA.
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PMID:Molecular genetics of human hemoglobin synthesis. 38 60

Many mutant hemoglobins and hemoglobinopathies can be identified with a high degree of specificity in the routine clinical laboratory. The most frequent abnormalities--those involving Hb S or C--are usually easily detectable in small amounts of sample analyzed by two simple methods of electrophoresis: cellulose acetate at pH 8.5 and citrate agar at pH 6. Some rarer mutants, e.g., Hb O, Hope, and Camden, can also be recognized by these two methods. Presumptive identification of other relatively frequent mutants, such as Hb D Los Angeles (Punjab) and Hb G Philadelphia, can be accomplished with additional data obtained from globin electrophoresis on cellulose acetate in acidic and alkaline buffers containing urea and 2-mercaptoethanol (or dithioerythritol). Electrophoretic profiles are presented of about a dozen hemoglobins likely to be encountered in screening programs in the U.S. Methods are also presented for identifying other genetic hemoglobin abnormalities--various types of thalassemia, Hb M, unstable hemoglobins, and those of the newborn.
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PMID:Methods for detection of hemoglobin variants and hemoglobinopathies in the routine clinical laboratory. 40 71

In the 1976 hemoglobinopathy proficiency testing survey of the Center for Disease Control (CDC), whole-blood samples from hematologically normal adults and from individuals heterozygous for beta-thalassemia were shipped to survey participants. The object of this survey was to determine the state of the art for technics used to quantitate hemoglobin A2 (Hb A2) and to test the ability of laboratories to differentiate between blood samples having normal Hb A2 levels and those having elevated levels (i.e., those from individuals with beta-thalassemia trait). The results of Hb A2 quantitation obtained from 183 volunteer participant laboratories were compared with those obtained from 24 reference laboratories. Individual values varied greatly among laboratories and among methods for both normal and elevated Hb A2 samples. The results returned by many laboratories were not within 2 SD of the reference laboratory mean and also were not sufficiently accurate to differentiate between the normal blood samples and those with beta-thalassemia trait. The results suggest that methods for quantitating Hb A2 need to be standardized and a suitable method for determining laboratory performance found.
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PMID:Quantitation of hemoglobin A2. An interlaboratory study. 45 72

Prenatal diagnosis of the hemoglobinopathies has been increasingly reported. This article discusses those ethical issues stemming from pregnancy studies by fetoscopy or placental aspiration: diagnostic accuracy and safety for mother and fetus, abortion of the fetus diagnosed as homozygous for thalassemia or sickle cell diseases, and access to prenatal diagnosis for those who cannot afford it. The author's position on these issues attempts to mediate between the poles in current ethical debate on abortion in public policy.
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PMID:Prenatal diagnosis of the hemoglobinopathies: ethical issues. 47 61

The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with G gamma chains having glycine in position 136 and Hb F with A gamma chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides G gamma T-15 and A gamma T-15 (which include the Gly leads to Ala polymorphism at position 136) from a digest of microquantitites of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the G ygamma and A gamma chains by erythroid colonies derived from cloned Burst Forming Units (bfu-e) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the G gamma A gamma-HPFH heterozygosity. The G gamma to A gamma ratio in the Nb F produced in cultures of cells from G gamma delta beta-thalassemia or G gamma-HPFH heterozygotes was lower and that from A gamma-HPFH heterosygotes was higher than the ratios in the Hb F of the corresponding peripheral blood cells. Mixtures of G gamma and A gamma chains were present in cell cultures of SS patients, beta+-thalassemia homozygotes and G gamma A gamma-HPFH heterozygotes in a ratio similar to that in the Hb F of mature red cells. These data suggest that erythroblasts in BFU-E derived colonies reactivate all available gamma chain structural genes, both in cis and in trans to the abnormal determinant. Hb F biosynthesis by adult blood samples concerns primarily the G gamma chains. This was particularly striking for blood samples in which erythroblasts were absent and the biosynthesis took place in fetal reticulocytes. Thus, the F-retuculocytes in blood of A gamma-HPFH heterozygotes with about 5% Hb F of the A gamma type produced primarily Hb F with G gamma chains. Similar differences were observed for G gamma A gamma-HPFH heterozygotes and, less strinkingly, for SS patients. A satisfactory explanation for this observation has not yet been obtained.
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PMID:The synthesis of fetal hemoglobin types in red blood cells and in BFU-E derived colonies from peripheral blood of patients with sickle cell anemia, beta+ - and delta beta-thalassemia, various forms of hereditary persistence of fetal hemoglobin, normal adults and newborn. 50 Mar 69

Routine laboratory investigations of hemoglobinopathies include Hb electrophoresis for abnormal hemoglobins, determination of Hb A2 (alpha 2 delta 2) for beta-thalassemia traits, staining for Hb H (beta 4) inclusions for alpha-thalassemia traits and estimation of Hb F (alpha 2 lambda 2) for the presence of hereditary persistence of fetal hemoglobin genes (HPFH). Frequently, analytical column chromatography and alpha/beta hemoglobin chain synthesis are used in the studies of more complicated hemoglobinopathies. This communication outlines the procedures used in this laboratory for the diagnosis of a case of Hb CC-alpha-thalassemia.
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PMID:Laboratory diagnosis of HB CC-alpha-thalassemia. 51 45

Frequencies of various hemoglobinopathies were examined in a total of 1,922 individuals of Eti-Turk origin by electrophoretical techniques. Hemoglobin A2 (Hb A2) and hemoglobin F (Hb F) determinations were also performed in 651 and 1,642 cases, respectively. Mean hemoglobin S (Hb S) frequency was found to be 15.3%. Variations among the different age groups were insignificant. Hemoglobin E (Hb E) and beta-thalassemia frequencies wer 0.47 and 1.23%, respectively. Hemoglobin Hacettepe and hemoglobin D were found once. Red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 6.5% of males.
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PMID:Hemoglobin S and some other hemoglobinopathies in Eti-Turks. 61 18


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