Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gamma chain compositions of the fetal hemoglobins of 2453 newborn babies from East Asian countries (1350 babies), from Italy, Yugoslavia, Bulgaria, and Georgia (417 Caucasian babies), and 686 black babies from Georgia were determined by high pressure liquid chromatography. Unusual results for a limited number of babies were confirmed by chemical analyses, and were evaluated further by family studies. Statistical analyses indicated high gene frequencies for the A gamma T chain in Italian (f = 0.237), Yugoslavian and Bulgarian (f = 0.238), and white Georgia babies (f = 0.224), a lower frequency in Japan (f = 0.178), and India (f = 0.173), and particularly in mainland China (f = 0.079). The A gamma T gene frequency in normal (AA) Black babies was 0.102. When a beta S or beta C mutation was also present this frequency was greatly decreased, particularly in babies with the AC condition (f = 0.036). These results suggest the near absence of the A gamma T mutation on the chromosome also carrying the beta C determinant. Most babies had the expected G gamma values which vary between 60 and 80%, but several (mainly black) babies had higher values (between 80 and 90%), while one normal black baby had a G gamma value of (nearly) 100%. This condition may be a form of A gamma +1-thalassemia and has been discussed in detail elsewhere (Blood 58:491-500, 1981). Thirty-five clinically normal (mainly Chinese, Indian, and Japanese) babies had G gamma values of about 40%. Twenty-six babies had A gamma I values of about 60%, while the remaining nine babies had A gamma T and A gamma I chains in a ratio of either 1 to 2 or 1 to 1. Two additional newborns did not produce any G gamma chains, but had only A gamma I chains or A gamma T chains. Family studies failed to indicate a specific hematological abnormality. These unusual ratios between the G gamma and A gamma (either A gamma I or A gamma T) chains have led to speculations regarding possible genetic abnormalities present in these infants.
 ...
PMID:The occurrence of different levels of G gamma chain and of the A gamma T variant of fetal hemoglobin in newborn babies from several countries. 618 75

We describe the clinical and hematological findings in a 5-year-old boy with G gamma A gamma delta beta thalassemia, a G gamma A gamma heterocellular form of HPFH, beta(0) thalassemia, and albinism. Clinically he manifested only the characteristics of beta-thalassemia trait and not the typical picture of doubly heterozygous beta thal/delta beta thal. The simultaneous presence of heterocellular HPFH improves gamma chain synthesis, thus reducing the alpha chain excess. It is also possible that gene expression can be modified by the presence of other genetic anomalies.
 ...
PMID:Unusual combination of genetic defects in a Sicilian boy: G gamma delta beta thalassemia, G gamma A gamma heterocellular HPFH, beta (0) thalassemia, and albinism. 619 18

Isopycnic separations of red cells from cord bloods, and from patients with sickle cell anemia, different forms of HPFH, S-beta O-thalassemia, and a beta +-thalassemia homozygosity were made in order to evaluate the distribution of Hb F and the relative levels of G gamma and A gamma chains over the cell fractions. As expected, the cord blood data showed decreased levels of both Hb-F and G gamma chains in the top cell fractions since the beta leads to gamma and high G gamma: A gamma low G gamma: A gamma switches are operative around the time of birth. Complete cell fractionations were made on the blood of three SS patients with low G gamma values (40%) and three SS patients with high G gamma values (60%). The proportion of G gamma chain was constant in all cell fractions, while the Hb-F level was higher in cells with higher densities. The difference in the quantities of the three types of gamma chain in the fetal hemoglobins of two SS patients with an A gamma T heterozygosity, one having a low G gamma value and the other a high G gamma level, can be explained by assuming an alteration in a regulatory mechanism. Considerable variation both in the level of Hb F and in the percentage of G gamma chain was observed in two G gamma A gamma-HPFH heterozygotes with a relatively low G gamma percentage of 30%; an inverse relationship was present between the two parameters. Such a phenomenon was not evident for the G gamma A gamma-HPFH homozygote, and also did not exist in two additional G gamma A gamma-HPFH heterozygotes with an associated alpha-thalassemia-2 heterozygosity who had a similar amount of Hb F but with higher G gamma values of about 50%. The difference in G gamma values between these two categories of G gamma A gamma-HPFH could be due to a higher affinity of the G gamma chains over A gamma chains for a slightly decreased amount of alpha chains as in an alpha-thalassemia-2 heterozygosity. 2 heterozygosity. Although an increased synthesis of Hb-F with G gamma chains was again observed after in vitro incubation of reticulocytes with [35S]methionine none of the isolated cell fractions contained a Hb F with the alpha 2 G gamma 2 composition.
 ...
PMID:The distribution of fetal hemoglobin and the types of gamma chain in red cell fractions separated by gradient centrifugation from blood of patients with sickle cell anemia and other hemoglobinopathies. 619 88

We have studied patients with beta-thalassemia from a Lebanese population having a high rate of consanguineous matings. This population exhibits both elevated and normal levels of Hb A2 associated with high levels of Hb F in homozygotes. The clinical course of the anemia suggests that this population consists of the severe Mediterranean type. Twenty-three unrelated homozygous beta-thalassemia patients investigated for globin synthetic ratios, consisted of 18 beta+ and 5 beta 0 with a non-alpha/alpha range of 0.158-0.465 and 0.25-0.41, respectively. The percentage of G gamma chains in Hb F was determined for 21 of these patients and a mean value of 59% G gamma chain content was found.
 ...
PMID:Globin synthetic ratios in homozygous beta-thalassemia patients from Lebanon. 620 28

A symptomless Iranian patient homozygous for beta thalassaemia has haematological changes similar to the beta thalassaemia trait. This remarkably mild phenotype is probably the result of coexistent alpha thalassaemia and increased gamma chain synthesis. Restriction endonuclease mapping analysis of the beta globin genes indicates that the patient is homozygous for a single nucleotide substitution at the 5' donor splice junction in the second intervening sequence of the beta globin gene. No other changes were observed in the non-alpha globin gene cluster. It seems unlikely that the augmented gamma chain synthesis in this patient is related to the molecular defect responsible for this beta o thalassaemia.
 ...
PMID:The molecular basis for beta o thalassaemia intermedia in an Iranian individual. 628 64

G gamma, A gamma and beta globin chain synthesis has been investigated in the peripheral blood and bone marrow from eight beta-thalassaemia homozygotes. In five out of eight cases total gamma chain synthesis was higher in the peripheral blood than in the bone marrow; in seven out of eight cases A gamma chain synthesis was markedly higher in the marrow than in the peripheral blood. These data suggest that ineffective erythropoiesis selects F-cells synthesizing the largest amounts of G gamma chains, while A gamma producing cells are preferentially destroyed in the marrow.
 ...
PMID:G gamma and a gamma globin chain synthesis in bone marrow and peripheral blood of beta-thalassaemia homozygotes. 712 65

Hemoglobin synthesis was studied in culture of early erythroid precursors (BFU-E) from the blood of nine patients exhibiting sickle cell anemia and of 14 with various types of beta-thalassemia. The results concerning gamma gene expression and plating efficiency in heterozygotes for sickle cell anemia were similar to those of normal adults (gamma/alpha = 0.05; 65 BFU-E colonies/10(6) plated cells) while, in contrast, homozygotes for sickle cell disease exhibited average values higher than the controls (gamma/alpha = 0.18; 80 BFU-E colonies/10(6) plated cells). However, the results were very heterogeneous from one subject to another. In heterozygotes for beta-thalassemia, gamma gene expression and plating efficiency were both slightly higher than those for normal individuals (gamma/alpha = 0.095; 129 BFU-E colonies/10(6) plated cells). In patients homozygous for beta-thalassemia, a marked increase in plating efficiency and gamma-chain synthesis was constantly observed (gamma/alpha = 0.41; 221 BFU-E colonies/10(6) plated cells). The high proportion of gamma chain synthesis was not related to a positive selection of F cells, since the gamma/alpha ratio remained constant during the in vitro erythroid maturation. Furthermore, a major increase in free alpha chain proteolysis can be ruled out, since the beta/alpha ratio was of the same order of magnitude in culture and in freshly drawn cells. Thus, the increased Hb F synthesis in vitro was the consequence of a true stimulation of gamma gene expression, which permitted partial correction of the globin chain imbalance. Ultrastructural studies in two homozygotes for beta-thalassemia showed a marked decrease in the abnormalities of the erythroblasts derived from erythroid precursors in vitro in comparison to those from fresh bone marrow samples. In particular, Heinz bodies were much less numerous and a high frequency of mature erythroblasts and reticulocytes was observed in culture. These results support the view that, in sickle cell anemia and beta-thalassemia, a high potential for gamma gene expression exists and can be expressed in culture.
 ...
PMID:Beta-thalassemia and sickle cell disease in culture of early erythroid precursors: hemoglobin synthesis and ultrastructural study. 718 47

We examined globin chain synthesis in erythroid bursts (BFU-E) of patients with heterozygous alpha or beta thalassaemia. BFU-E were cloned from circulating mononuclear cells, labelled with [3H]leucine and globin chains purified by gel filtration and column chromatography. In six patients heterozygous for beta thalassaemia, globin synthesis in BFU-E was nearly balanced, with an alpha/non alpha ratio of 1.05 +/- 0.12. These BFU-E produced 33.8 +/- 12.7% gamma globin chain, an amount similar (P > 0.05) to that found in 10 controls with sickle cell anaemia (25.6 +/- 6.7) but greater (P > 0.05) than that of five normal controls (17.2 +/- 2.2). The balanced globin synthesis appeared due to the large amounts of gamma chain made by BFU-E. In two alpha thalassaemia carriers, who also had sickle cell trait, the BFU-E alpha/non-alpha ratio was 0.67 and 0.79. These BFU-E produced 15% and 20% gamma chain and 39% and 45% betaS globin. The synthesis of betaS globin in BFU-E exceeded the erythrocyte levels of 20% and 29% HbS and indicated nearly equal expression of betaA and betaB globin genes in these proliferating erythroid precursors. This provides further evidence that the low levels of HbS in sickle cell carriers with alpha thalassaemia are due to post-translational events resulting from the differing affinity of betaS and betaA globin for alpha chain and the destruction of excessive betaS chain.
 ...
PMID:Globin biosynthesis in erythroid bursts of heterozygous alpha or beta thalassaemia. 743 46

Three flow cytometric methods of counting F cells were evaluated in the settings of an external laboratory assessment scheme. The laboratories to participate with a different method were located in Oxford (method O), Athens (method A) and Jerusalem, (method J). Two monoclonal anti-gamma chain antibodies were used: monoclonal antibody produced by P. Beverley (Oxford) (BEV) and an antibody provided by Bioatlantic S.A.R.L. (France) (BIO). The specimens tested were mixtures in five predefined ratios of a sample with homozygous deltabeta-thalassemia with 100% F cells with a sample with no F cells. A central independent laboratory prepared and distributed the aliquots (at room temperature) to the participating centers within 2 (O), 3 (A), and 6 (J) days. The performance of the three methods was evaluated by: 1) deviation indices, 2) relative accuracy, as percent difference of the counts from the target values, and 3) bias and linearity by linear regression of the counts versus the target values [parameters: slope (s), y-intercept (y), R squared (Rs), and F ratio]. The highest score of performance was obtained by method A with both monoclonal antibodies.
 ...
PMID:Cross evaluation of three flow cytometric F cell counting methods performed by different laboratories. 985 27

This paper summarizes the results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the Republic of Macedonia. Over the past 40 years, population surveys of more than 22,000 participants (school children and workers) from all over the country, have shown that the average incidence of beta-thalassemia (thal) trait is 2.6%, ranging from less than 1% in the northeast to 10% in the south. The frequency of deltabeta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.3%. Screening of 9,619 newborns has shown that the frequency of alpha-thal trait is 1.5%, of which alpha-thal-2 is 1.45% and alpha-thal-1 is 0.05%. The molecular basis of the different forms of beta-thal and other hemoglobinopathies has been completely defined. Among the Macedonians, over 450 beta-thal chromosomes have been studied. Fifteen different beta-thal mutations have been detected, four of which [IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-I-1 (G-->A), codon 39 (C-->T)] account for 85% of all beta-thal chromosomes. Among the Albanians, 48 beta-thal chromosomes have been studied. Eight different mutations have been detected, four of which [codon 39, -30 (T-->A), IVS-I-110, IVS-I-1] account for 85% of all beta-thal chromosomes. Four new mutations [-101 (C-->A), -87 (C-->G), -30, polyadenylation signal (poly A) (AATAAA-->AATGAA)] have been characterized. Molecular analyses of DNA from over 20 unrelated cases with deltabeta-thal have shown that this condition is caused by a 13 kb deletion (Sicilian type); in two families a deletion of 18 to 23 kb (Macedonian type of deltabeta-thal) was discovered. Molecular analyses of alpha-thal in the Republic of Macedonia have shown the following types of molecular defects: 20.5 kb deletion, 17.5 kb deletion, 3.7 kb deletion, poly A mutation (AATAAA-->AATGAA), and Hb Icaria [alpha142, Term-->Lys, TAA-->AAA (alpha2)]. The incidence of abnormal hemoglobins (Hbs) in the Republic of Macedonia is 0.4%. Three different alpha chain variants among 10 families, seven different beta chain variants among 33 families, two gamma chain variants in two newborns, one variant with an extended alpha chain, and Hb Lepore among 105 families, have been observed. Structural analysis of numerous cases with Hb Lepore showed that the variant was of the Washington-Boston type.
 ...
PMID:Thalassemias and other hemoglobinopathies in the Republic of Macedonia. 1736


<< Previous 1 2 3 4 5 Next >>