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Biomedical subjects

D J Weatherall

Publications and source records attributed to D J Weatherall.

At least 343 records · Page 19Linked to original sources
PubMed1977

Pattern of maternal F-cell production during pregnancy.

Maternal haemoglobin F production has been monitored in 11 normal pregnancies, with an immunofluorescent technique. In all cases there was a significant increase in the number of F-cells which reached a peak at 18-22 weeks' gestation. Comparison of the numbers of F-cells with the percentage haemoglobin F determined chemically indicated that the increase in maternal haemoglobin F synthesis results from an increased production of F-cells rather than from an increased synthesis of haemoglobin F by the F-cells. There was a highly significant increase in the number of F-cells in a pregnant beta-thalassaemia heterozygote.

Erythrocyte Count↗
PubMed1977

Haemoglobin Radcliffe (alpha2beta299(Gi)Ala): a high oxygen-affinity variant causing familial polycythaemia.

Three members of an Oxfordshire family have polycythaemia. In each case their whole-blood oxygen affinity is increased. This is due to a previously undescribed haemoglobin variant which has been named haemoglobin Radcliffe (alpha2beta299(Gl)Ala). In addition to having a high oxygen affinity haemoglobin Radcliffe shows virtually no haem-haem interaction and a diminished Bohr effect. It is synthesized at the same rate and is as stable as haemoglobin A. X-ray analysis indicates that crystals of deoxyhaemoglobin Radcliffe are isomorphous with those of deoxyhaemoglobin A. Solutions of haemoglobin Radcliffe were also studied by high-resolution proton nuclear magnetic resonance spectroscopy. The structure/function relationships of haemoglobin Radcliffe are discussed in the light of these studies.

Adult↗
PubMed1977

Mild sickle-cell anaemia in Iran associated with high levels of fetal haemoglobin.

Sixteen subjects, with sickle-cell anaemia, all Iranians (ages 3 to 56 years), with very mild symptomatology are reported. Some of the subjects had been totally asymptomatic. Splenomegaly was noted in 9 cases. There was an increase in the mean level of fetal haemoglobin (18%); this is the probable explanation for the mild phenotype. In 29 subjects with sickle-cell trait, the level of HbF was also significantly raised as compared with normal (1-6% vs. 0-6%). The mechanism of increased synthesis of HbF is unknown. The findings are similar to those reported in the Shiite Moslems of Saudi Arabia suggesting that in these populations there is a genetically-determined ability to produce high levels of Hb F in the presence of the sickle-cell gene.

Adolescent↗
PubMed1977

G gamma delta beta thalassaemia and g gamma HPFH (Hb Kenya type): comparison of 2 new cases.

Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.

Adult↗
PubMed1977

Invasion and growth of Plasmodium falciparum in different types of human erythrocyte.

The susceptibility of human red blood cells to invasion by Plasmodium falciparum was investigated in microtissue cultures with different populations of erythrocytes containing fetal haemoglobin (HbF). Preferential invasion of HbF-containing erythrocytes was observed with umbilical cord blood. The parasites showed no preference for HbF cells in blood from a subject with hereditary persistence of fetal haemoglobin (HPFH). By contrast, a significant preference for HbA-containing erythrocytes was found with blood from young infants. Further experiments demonstrated that falciparum parasites preferentially invade "young" erythrocytes. This could explain the distribution of parasites found in blood containing HbF, because HbF-containing erythrocytes are "younger" on average in cord blood, "older" in the blood of infants, and of the same average age as HbA-containing cells in HPFH. We concluded that the susceptibility of human erythrocytes to invasion by P. falciparum is not correlated with the presence of HbF, but that aging of red cells in vivo decreases their susceptibility to invasion. Semi-quantitative measurements were made of parasite growth in cells containing HbA or HbF. The growth of individual parasites in cells containing HbF was significantly retarded. This might confer a selective advantage on individuals with thalassaemia and sickle cell trait, in which HbF levels are raised in early life.

Animals↗
PubMed1977

Inheritance of F cell frequency in heterocellular hereditary persistence of fetal hemoglobin: an example of allelic exclusion.

Two kindreds are described in which F cell frequency is inherited. These families differ in ethnic origin, the mean quantity of HbF per F cell, and in G gamma: A gamma ratios. Heterozygotes have approximately 50% F cells while homozygotes have close to 100%. Semiquantitative single cell immunodiffusion assays establish that F cells contain all of the HbF found in heterozygotes. Our finding that the gene for this heterocellular form of hereditary persistence of fetal hemoglobin is expressed in only half the cells provides the first example of allelic exclusion known apart from immunoglobulin expression.

Black People↗
PubMed1976

A model for the persistence or reactivation of fetal haemoglobin production.

Normal adults may have two distinct erythroid precursor populations, a major one which produces only adult haemoglobin (HbA), and another which produces HbA and fetal haemoglobin (H0F) (F cells). Persistence or apparent reactivation of HbF production in adults results from differential selection of these F cells, except in those rare conditions which are due to specific deletions of D.N.A. involved in suppression of gamma-chain synthesis. The increase in HbF which results from a genetically determined increase in F cells appears to ameliorate sicke-cell anaemia or beta thalassaemia. Augmentation of the F-cell population might offer a therapeutic approach to these disorders.

Adult↗
PubMed1976

Fetal haemoglobin and malaria.

The distribution and growth of Plasmodium falciparum was compared in red blood-cells containing either adult or fetal haemoglobins. In in-vitro cultures, cord blood-cells were invaded more readily, but there was a paucity of parasites in cells containing haemoglobin F in the blood of infected infants aged 3-6 months. These findings suggest that P. falciparum may preferentially invade young, metabolically active erythrocytes. There was a significant retardation of parasite growth in vitro in cells containing haemoglobin F. This latter finding suggests a further mechanism for the resistance to malaria in the first months of life and for high gene frequencies (in areas in which malaria was endemic) of the thalassaemias and related haemoglobinopathies in which the rate of decline of fetal-haemoglobin production is retarded.

Adult↗
PubMed1976

Presence of gene for beta globin in homozygous beta0 thalassaemia.

In one southern Italian and one Pakistani patient with homozygous beta0 thalassaemia in which no detectable beta-globin synthesis occurs and no beta-globin messenger RNA is found, the gene for beta globin has been shown to be present using complementary DNA. This demonstrates that for these patients the imbalance in chain synthesis is not attributable to a gene deletion.

DNA↗
PubMed1976

Delta-beta-thalassemia is due to a gene deletion.

DNA has been prepared from peripheral blood or cultured skin fibroblasts obtained from three Sicilian and one Greed deltabeta-thalassemia homozygotes. Globin-gene analysis was carried out using a cDNAbeta probe, and the results indicate that deltabeta-thalassemia has arisen from a deletion of the beta-globin genes. A similar result was obtained using DNA prepared from cultured skin fibroblasts from an individual homozygous for the Negro form of hereditary persistence of fetal hemoglobin (HPFH). In both cases, the deletion has spared the Ggamma and Agamma loci directing the gamma chains of hemoglobin F, but it has not been possible to demonstrate any difference between the size of the deletion involved in the production of delta-beta-thalassemia and that which gave rise to HPFH. These experiments provide further direct evidence that deletions of critical areas of the gamma-delta-beta gene cluster result in persistent gamma chain synthesis in adult life.

Chromosome Aberrations↗