Search PubMed⌕ Search

Biomedical subjects

D J Weatherall

Publications and source records attributed to D J Weatherall.

At least 217 records · Page 12Linked to original sources
PubMed1984

Population and genetic studies suggest a single origin for the Indian deletion beta thalassaemia.

In a study of beta thalassaemia in the Asian Indian immigrant populations in the U.K., 23 out of 125 beta-thalassaemic chromosomes (18%) were of the Indian deletion beta type (600 bp deletion involving the 3' end). The individuals with beta thalassaemia had originated from various parts of India and Pakistan. However, all those individuals with deletion beta thalassaemia were from Sind and the adjacent area of Gujarat. Analysis of restriction fragment length polymorphisms in the beta globin gene cluster showed that all the 23 deletion beta thalassaemia chromosomes had an identical haplotype. These findings suggest a single origin for the Indian deletion beta thalassaemia.

Chromosome Deletion↗
PubMed1984

(A gamma delta beta) thalassaemia: similarity of phenotype in four different molecular defects, including one newly described.

Globin gene mapping of DNA from families with (A gamma delta beta) thalassaemia has revealed a previously unreported gene deletion responsible for this condition. The deletion removes the A gamma, delta and beta genes and while its 5' end is in a similar position to that described in a previous deletion of this type, the 3' ends of the two deletions are quite different. In addition we have observed further examples of two other previously described deletions which result in this disorder. Phenotypic comparisons of families with (A gamma delta beta) thalassaemia, in which the molecular basis has been defined, show a remarkable similarity among the four different deletion defects, with important implications with regard to the mechanism by which deletions allow the continued expression of gamma genes.

Adolescent↗
PubMed1984

Characterization of an Indian (delta beta)0 thalassaemia.

The molecular basis of delta beta thalassaemia in an Indian family is shown here to be due to a previously undescribed deletion within the beta globin gene complex. Starting 3 kilobases from the 3' end of the A gamma gene, the deletion removes the delta and beta globin genes and continues to an unknown extent in the 3' direction. Heterozygotes for this deletion have about 25% Hb F with a G gamma:A gamma ratio of 70:30 while interaction with beta+ thalassaemia results in the clinical picture of thalassaemia intermedia.

Child↗
PubMed1984

Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring.

The elongated alpha-globin chains of hemoglobin Constant Spring (alpha cs chain of HbCS ) are produced in low amounts such that the alpha cs-gene acts as a form of alpha-thalassemia; yet in the homozygous state the pathophysiological effects of this mutant are more severe than in the corresponding conditions that result from alpha-globin gene deletions. In studies designed to examine this discrepancy, we have demonstrated that a significant proportion of red cells produced in an HbCS homozygote has a much reduced red cell life span. Contrary to previous reports, we have been able to demonstrate the expected deficit in alpha-chain production in this condition and have shown that both the cessation of globin chain synthesis in vitro and the destruction of the excess beta-chains occur unusually rapidly. Comparison with various deletion forms of alpha-thalassemia suggests that, in terms of intracellular globin chain precipitates and free beta-chain pool, homozygous HbCS red cells more closely resemble those of HbH disease, with three of the four alpha-genes inactivated, than they do the more comparable alpha-thalassemia carriers with only two genes deleted.

Adult↗
PubMed1984

Allelic variation and linkage properties of a highly polymorphic restriction fragment in humans.

The region between the human zeta-globin gene and the pseudo-zeta gene contains a stretch of tandemly reiterated 36 base-pair sequence elements. The structure of this locus offers the potential for unequal crossover events or slippage during replication to generate allelic variation in the length of restriction fragments spanning this region. The extent of allelic variation at this locus has been investigated in different populations at a high level of resolution. As many as ten discrete fragment lengths were observed whereas only three had been detected previously at a lower level of resolution. The linkage of alleles at this locus to closely flanking markers indicates that they are inherited as stable Mendelian traits over many generations, and therefore this and similar regions may provide highly polymorphic markers which will be of great value in genetic analysis of the human genome.

Alleles↗
PubMed1984

Interaction of the alpha alpha alpha globin gene haplotype and sickle haemoglobin.

We have studied the interaction of the alpha alpha alpha/alpha alpha gene arrangement with various beta globin genotypes (AA, AS, AC, SS and SC). Whereas this interaction has no detectable clinical or haematological effects in subjects with AA, SS or SC genotypes it is associated with a significantly increased level of Hb S or Hb C in heterozygotes for these variants. These findings indicate that the additional alpha globin gene in the alpha alpha alpha gene arrangement is functional.

Adolescent↗
PubMed1984

Iron absorption in non-transfused iron loading anaemias: prediction of risk for iron loading, and response to iron chelation treatment, in beta thalassaemia intermedia and congenital sideroblastic anaemias.

A variable rate of iron loading, reaching toxic levels in some patients, was seen in a series of non-transfused patients with beta thalassaemia intermedia or sideroblastic anaemia. The degree of anaemia was a poor guide to the risk of iron overload. However the extent of erythroid hyperplasia, judged by ferrokinetic studies or more simply by bone marrow aspiration, was useful in predicting both the rate of iron loading and the need for iron chelation therapy.

Absorption↗
PubMed1984

Feasibility of antenatal diagnosis of beta thalassaemia by DNA polymorphisms in Asian Indian and Cypriot populations.

The feasibility of using restriction fragment length polymorphisms ( RFLPs ) for the antenatal diagnosis of beta thalassaemia in the U.K.-resident Cypriot and Asian Indian populations has been determined. Seven polymorphic restriction endonuclease sites in the beta globin gene cluster were analysed in 20 Cypriot and 42 Asian patients and their parents and the combination of polymorphic sites (haplotype) for each chromosome determined. It was found that 76% of the Asian and 35% of the Cypriot families had DNA polymorphisms which would allow antenatal diagnosis of a homozygous beta thalassaemic fetus, and that in the majority of the remaining families there was a 50% chance of a successful diagnosis of either a normal or a heterozygous fetus. These results indicate that RFLP analysis of fetal DNA is a useful method for antenatal diagnosis of beta thalassaemia in families with either a normal or homozygous beta thalassaemia child, especially in the Asian population in the U.K.

Child↗
PubMed1983

Aplastic crisis due to parvovirus infection in pyruvate kinase deficiency.

A thirteen-year-old boy with congenital haemolytic anaemia due to pyruvate kinase (PK) deficiency had an aplastic crisis. A serum parvovirus-like virus (SPLV) was demonstrated in the blood by electron microscopy and, subsequently, IgM and IgG antibodies to the prototype SPLV B19 were detected. In an attempt to define the level of erythropoiesis that is involved in parvovirus-induced bone marrow suppression, the levels of circulating early erythroid progenitors (burst forming units erythroid, BFU-E) were monitored during the crisis and recovery period. The virus-containing plasma inhibited the formation of BFU-Es from non-immune subjects and this effect was neutralised by convalescent serum. Colony forming units granulocyte-macrophage (CFU-GM) were also inhibited but this was probably non-specific since neutralisation did not reverse the effect. These experiments, together with the clinical data, suggest a selective effect of SPLV at the stage of erythroid progenitors.

Adolescent↗
PubMed1983

The molecular basis for the clinical diversity of beta thalassaemia in Cypriots.

Much of the clinical variability in the course of homozygous beta thalassaemia in the Cypriot population can be accounted for by the interaction of alpha thalassaemia and by the existence of different molecular forms of beta thalassaemia. Most severe forms of the disorder result from the homozygous state for the common Mediterranean type of beta thalassaemia. One particularly mild form of beta thalassaemia, which also occurs in other Mediterranean populations, results from a single base change at position 6 in the first intervening sequence of the beta-globin gene. These observations provide a basis for the development of a programme for first-trimester antenatal diagnosis using oligonucleotide probes.

Adolescent↗
PubMed1983

Lectin-like polypeptides of P. falciparum bind to red cell sialoglycoproteins.

Attempts to control human malaria by immunological means could be compromised by antigenic variability within and between different strains of malarial parasites1. A useful alternative approach might be to block parasite antigens which are important in the mechanisms of invasion of red cells. As the major human parasite Plasmodium falciparum is highly specific for human red cells, isolation of the proteins involved in the recognition of red cells by this parasite might be of particular value. Recent studies suggest that the major red cell sialoglycoproteins (SGPs), glycophorins A, B and possibly C, may carry the sites recognized by the parasite2-4. Furthermore, because certain carbohydrates present on SGPs such as N-acetylglucosamine are able to block invasion by the parasite5, they may be involved in the initial interaction between parasite and red cell. We have now identified parasite proteins which bind to SGP or N-acetylglucosamine on Sepharose 4B columns. Three proteins, of molecular weights (MWs) 140,000 (140K), 70K and 35K, seem to be specifically bound by N-acetylglucosamine.

Acetylglucosamine↗
PubMed1983

Iron overload in mild sideroblastic anaemias.

Life-threatening iron overload may occur without severe anaemia in patients with sideroblastic disorders. Assessment of erythroid expansion in bone-marrow aspirates may be as useful as ferrokinetic studies in predicting both the risk of iron loading and the need for prophylactic phlebotomy or iron-chelation therapy.

Adult↗