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)

Admission screening was performed on 684 Chinese-Canadian patients for thalassemia, abnormal hemoglobins and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Thirty-six healthy Chinese adults were also studied. The incidence of beta-thalassemia minor (hemoglobin A(2) greater than 3.5%) was 3.8%. Presumptive alpha-thalassemia minor (demonstration of occasional red cells containing hemoglobin H inclusion bodies) was found in 6.7%. Two patients had findings consistent with alpha-beta-thalassemia. The incidence of G-6-PD deficiency (abnormal methemoglobin reduction test) in adult males was 4.7%. In a parallel study the incidence of hemoglobin Bart's in 310 Chinese newborns was 6.8%. Two mutant hemoglobins were found - hemoglobin E and hemoglobin J (Bangkok).
 ...
PMID:Thalassemia and G-6-PD deficiency in Chinese-Canadians: admission screening of a hospital population. 556 48

Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.
 ...
PMID:beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0]. 616 92

Comparisons were made of drug-induced oxidation of purified hemoglobins A, S, E, and F. Repetitive spectral scans of reaction mixtures containing menadione showed that Hb E was the most reactive and Hb F was the least reactive of the hemoglobins studied. Hb E oxidation was only slightly faster than normal, but it produced much larger relative quantities of low-spin ferric hemoglobin (hemichromes). Hb F oxidation was considerably slower than normal but produced normal amounts of hemichromes relative to methemoglobin. Precipitation occurred in the order E greater than S greater than A greater than F. The abnormally slow rate of Hb F oxidation was even more striking when the oxidant was acetylphenylhydrazine (APH), and the sensitivity of the reaction to catalase was severely diminished. These hemoglobins thus exhibit entirely different reaction profiles during drug-induced oxidation. The amino acid substitution in Hb E alters the globin tertiary structure, so that hemichromes can more readily form, whereas the decreased susceptibility to oxidative denaturation of Hb F appears related to the absence of a site that normally reacts with hydrogen peroxide to increase oxidation rate. Such Hb F stability is consistent with the mild phenotypic expression of doubly heterozygous beta-thalassemia/HPFH and Hb S/HPFH. The role of Hb E instability in altered red cell morphology relative to the thalassemia-like deficit of beta globin mRNA has not been entirely resolved. Nevertheless, the clinical repercussions of the abnormal properties of Hb E are mild, and they may be involved with the prevalence of this hemoglobin in Southeast Asia as a balanced polymorphism in which the advantage to heterozygotes is, as yet, unclear.
 ...
PMID:Differences in the reaction sequences associated with drug-induced oxidation of hemoglobins E, S, A, and F. 619 77

Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene. We now report an uncommon beta-thalassemia gene that contains a deletion of this nucleotide. Thus, one mutation (GAG leads to GTG) produces sickle-cell anemia, while the other (GAG leads to GG) eliminates beta-globin production. These data establish that different alterations affecting one specific nucleotide can produce either an abnormal hemoglobin or beta-thalassemia. Moreover, the nucleotide sequence comprising codons 6-8 of the beta-globin gene appears to be particularly susceptible to mutations affecting nucleotide number.
 ...
PMID:beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. 631 Sep 91

In this study, we carried out alpha-globin gene mapping in 12 heterozygotes for Hb J Sardegna and in 5 double heterozygotes for this variant and beta-thalassemia. Then, we correlated the Hb pattern with the alpha and beta-globin genotype. In heterozygotes for Hb J Sardegna with a deletion of a single alpha-globin gene (alpha alpha/-alpha) the amount of the abnormal Hb was significantly (p much less than 0.001) higher than in heterozygotes for this variant with a full complement of 4 alpha-globin structural genes (27.5% versus 20.4%). Double heterozygotes for the abnormal hemoglobin and beta-thalassemia with a full complement of 4 alpha-globin structural genes tended to have lower amount of the abnormal Hb than heterozygotes for this variant who do not have beta-thalassemia.
 ...
PMID:Hemoglobin constitution of double heterozygotes for alpha or beta-thalassemia and Hb J Sardegna. 654 32

A modification of an existing (micro) CM-cellulose chromatographic procedure is introduced for the quantitation of hemoglobin Bart's (or gamma 4) in blood samples of newborn babies. Normal newborn with four active alpha chain genes (alpha alpha/alpha alpha) have small amounts (average 0.55%) of this abnormal hemoglobin while increased percentages are present in newborn with an alpha-thalassemia-2 heterozygosity (alpha 0 alpha/alpha alpha; average 1.55%) or an alpha-thalassemia-2 homozygosity (alpha 0 alpha/alpha 0 alpha; average 4.65%). The identification of hemoglobin Bart's in normal newborn was made by high-performance liquid chromatography, and the absence of contaminating non-hemoglobin proteins was confirmed by electrophoresis and additional chromatographic experiments. This rapid procedure is useful for the detection and differentiation at time of birth of the different alpha chain deficiencies which are common among various populations in the world.
 ...
PMID:Carboxymethyl-cellulose microchromatography for the quantitation of hemoglobin Bart's (gamma 4) and its use in the detection of the alpha-thalassemia conditions. 689 10

In humans the alpha-globin genes are duplicated and closely linked. Whereas individuals heterozygous for most alpha-chain mutations possess approximately 25% abnormal hemoglobin, heterozygotes for the alpha-chain variant Hb G Philadelphia synthesize either 33% or 50% Hb G. Both variable gene dosage and interaction with alpha-thalassemia have been proposed to explain this observation. To differentiate between these models, we have performed restriction endonuclease mapping and hematological studies on individuals with Hb G from four families. In every case the alpha G locus was carried on an EcoRI or EcoRI + BamHI fragment approximately 4 kilobases shorter than that bearing the two linked alpha A loci of hematologically normal individuals. Bgl II digestion revealed that the alpha G gene is the only alpha locus on the affected chromosome. Erythrocyte indices and alpha/beta synthesis ratios indicated that the alpha G chromosome confers alpha-thalassemia. In addition to the alpha G gene, subjects who synthesized 33% Hb G possessed two alpha A genes on the homologous chromosome and exhibited the mild form of alpha-thalassemia trait ("silent carrier"). Subjects who synthesized 50% Hb G possessed a single alpha A gene trans to the alpha G locus and displayed the more pronounced form of alpha-thalassemia trait. One subject, who synthesized 100% alpha G chains and had Hb G-Hb H disease, was found to have a single nonfunctional alpha gene trans to the alpha G gene. Thus the proportion of Hb G synthesized by heterozygotes is determined by interaction with alpha-globin gene deletions cis and trans to the alpha G locus.
 ...
PMID:Proportion of hemoglobin G Philadelphia (alpha 268 Asn leads to Lys beta 2) in heterozygotes is determined by alpha-globin gene deletions. 693 89

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.
 ...
PMID:The effect of abnormal hemoglobins on the membrane regulation of cell hydration. 703 77

An Indian family is described in which the father has a delta chain abnormal hemoglobin which is the result of a mutation of the delta gene in cis to a beta-thalassemia heterozygosity. The abnormality concerns a substitution of the Asp residue in position 99 (G1) by an Asn residue. A similar substitution has been found in the beta chain of Hb Kempsey (alpha 2 beta 2 99 Asp replaced by Asn). The observed abnormality results in a greatly increased oxygen affinity of this newly discovered Hb A2 variant.
 ...
PMID:Hb A2-Canada or alpha 2 delta 2 99(G1) Asp replaced by Asn, a newly discovered delta chain variant with increased oxygen affinity occurring in cis to beta-thalassemia. 712 31

Clinical, hematological and genetic studies were carried out on 40 patients with symptomatic sickle-cell disease, selected on the basis of a predominant HbS fraction and absence of other abnormal hemoglobin variants. Family studies showed they included 26 homozygotes for the sickle-cell gene (SS) and 14 double heterozygotes for both the sickle-cell and the (0)beta-thalassemia genes ((S)(0)beta-thalassemia). Comparison of the two groups revealed the more common occurrence of splenomegaly, lower MCV and mCH, and higher HbA2 in (S)(0)beta-thalassemia. Total hemoglobin was slightly lower in SS disease but the difference was not significant. Fetal hemoglobin (HbF) was moderately elevated to similar levels in both groups. These results suggest a high incidence of S beta (0)-thalassemia in certain Brazilian mixed populations and confirm the severity of the double heterozygous state. The distinction between the two disorders is often difficult, but can be made on the basis of the hematological data taken together with family studies.
 ...
PMID:Clinical, hematological and genetic features of sickle-cell anemia and sickle cell-beta thalassemia in a Brazilian population. 741 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>