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Biomedical subjects

D J Weatherall

Publications and source records attributed to D J Weatherall.

At least 253 records · Page 14Linked to original sources
PubMed1982

Glycophorin as a possible receptor for Plasmodium falciparum.

Human red cells deficient in glycophorin B are partly resistant to invasion by Plasmodium falciparum and become completely resistant when glycophorin A is removed from their surface by trypsin treatment. Similar treatment of cells which have a hybrid glycophorin molecule renders them glycophorin-deficient and resistant to invasion. Tn and Wrb -ve cells with defined alterations in glycophorin A or B are also resistant to invasion. These findings suggest that both glycophorins A and B are involved in parasite invasion, indicate which parts of these molecules may be involved in this process, and provide the basis for a tentative model of parasite/red-cell interactions.

Blood Group Antigens↗
PubMed1982

Multiple arrangements of the human embryonic zeta globin genes.

Rearrangements which are most readily explained by homologous crossover between misaligned segments of DNA in the region of the human embryonic zeta (zeta) globin genes have been identified in individuals of three different racial origins. These recombination events have resulted in a surprisingly high prevalence of chromosomes with single (0.4%) and triplicated (1.3%) zeta genes with apparently no significant effect on the phenotype.

Chromosomes, Human, 16-18↗
PubMed1982

The interaction of alpha-thalassemia and homozygous sickle-cell disease.

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (alpha-/alpha-), may be heterozygous for alpha-thalassemia 2 (alpha-/alpha alpha), or may have a normal alpha-globin-gene complement (alpha alpha/alpha alpha). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin A2, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled cell counts, and serum total bilirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (alpha-/alpha alpha) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in other two subgroups. These data confirm previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.

Adolescent↗
PubMed1982

Survival and desferrioxamine in thalassaemia major.

A small randomised trial and observation of all patients homozygous for beta-thalassaemia in Britain born in or before 1963 indicated that those patients who had received average weekly doses of more than 4 g of desferrioxamine over the previous few years were less likely to die in the near future than were patients of similar ages who had received less, or no, desferrioxamine.

Adolescent↗
PubMed1982

Linkage analysis of nondeletion hereditary persistence of fetal hemoglobin.

Nondeletion forms of hereditary persistence of fetal hemoglobin may result from regulatory disorders of globin gene expression. The defects in two such conditions were localized by demonstrating a tight genetic linkage between the disorders and polymorphic restriction endonuclease sites within the beta-like globin gene complex. In one instance, the defect probably occurred outside the region of DNA between the epsilon- and beta-globin genes.

Chromosome Deletion↗
PubMed1982

The British type of non-deletion HPFH: characterization of developmental changes in vivo and erythroid growth in vitro.

Further studies of a unique British family with a rare type of hereditary persistence of fetal haemoglobin (HPFH) have confirmed that this condition appears to result from a regulatory defect affecting globin gene expression. Adult heterozygotes for this disorder have 3.5-10.0% Hb F while homozygotes have 18-21% Hb F and in both cases the Hb F contained predominantly A gamma chains (89-94%). In all other respects these individuals were haematologically normal. Two obligate heterozygotes were studied from birth, at which time both the proportion of Hb F and the G gamma/A gamma ratio were completely normal. There was a delayed decline in Hb F which continued well into childhood and a parallel decline in the proportion of G gamma chains. The growth of erythroid bursts showed no difference in number, size or erythropoietin responsiveness between homozygous HPFH, heterozygous HPFH or normal family members. Haemoglobin synthesis in these bursts showed the normal pattern of asynchrony between gamma and beta chain synthesis but there was an overall increase in gamma chain production in the HPFH cases, particularly the homozygotes, compared to normal. In addition, the abnormal G gamma/A gamma ratio was faithfully reproduced in vitro. This condition appears to result, therefore, from a regulatory abnormality affecting the postnatal repression of gamma chain synthesis.

Adolescent↗
PubMed1982

Restriction endonuclease maps of the beta-like globin gene cluster in the British and Greek forms of HPFH, and for one example of G gamma beta + HPFH.

We report here restriction endonuclease maps of the beta-like globin gene cluster for the British form of HPFH and for a case of G gamma beta + HPFH, and also confirm and extend previous reports of the map for the Greek form of HPFH. These results show that all these conditions belong to a group lacking any substantial deletion or rearrangement of DNA sequence in this gene cluster. The absence of any gross disruption of the structure of this region of the genome, together with evidence that the HPFH genotype is either allelic with, or closely linked to, the beta-like globin gene cluster, suggests that the responsible lesions are nearer to being purely regulatory in nature than in forms of HPFH due to substantial deletions. Thus these conditions promise to provide less equivocal evidence about the regulation of beta-like globin gene expression than has so far been available.

Chromosome Mapping↗
PubMed1982

Haemoglobin Constant Spring has an unstable alpha chain messenger RNA.

Haemoglobin Constant Spring (Hb CS) is a variant with an elongated alpha-chain associated with an alpha + thalassaemia phenotype. The amount of alpha mRNA relative to beta mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of alpha + thalassaemia. In a patient with Hb CS-H disease there was greater alpha/beta mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the alpha mRNA in the patient's peripheral blood was derived from the alpha 1 (alpha A) gene. The data suggest that alpha CS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3' non-coding region during translation.

Female↗
PubMed1982

The direct antiglobulin test in P. falciparum malaria.

The direct antiglobulin test (DAT) was performed on 134 Gambian children with P. falciparum malaria. 52 children had a positive DAT and in 25 this was due to the adherence of C3 to their red cells whilst 13 had sensitization with IgG as well as C3. Sensitization with C4 alone or associated with IgG and/or C3 was only rarely found. The haemoglobin levels and reticulocyte counts were not significantly different in patients with a positive DAT from those with a negative DAT. The children with positive IgG DAT, however, were of a significantly older age group and had significantly higher parasitaemias at presentation than children with complement components only or with a negative DAT. In vitro assay of phagocytosis by peripheral blood monocytes (PBM) showed that PBM from malarious patients were less active in phagocytosis than normal male adult Caucasian PBM. Neither PBM from malarious patients nor normal adult Caucasians PBM showed phagocytosis of cells from DAT positive malarious children. The same in vitro assay was used to test for the presence of opsonizing anti-schizont antibodies in the sera of these children and in adult Gambians. This revealed the presence of a schizont specific opsonizing antibody in the sera of adult Gambians and in the sera of children with a positive DAT due to IgG but not in sera of patients with a negative IgG. These findings indicate that a positive IgG DAT in malaria does not necessarily lead to excess haemolysis of non-parasitized red cells. The presence of a schizont opsonizing antibody, leading to in vitro phagocytosis, in the sera of children with a positive DAT and in sera from adult Gambians indicates a relationship between the development of the positive DAT and acquisition of protective malarial immunity.

Adolescent↗
PubMed1982

The interaction of alpha thalassaemia with heterozygous beta thalassaemia.

The alpha globin genotypes of 55 beta thalassaemia heterozygotes have been determined by restriction endonuclease analysis to identify those with interacting alpha thalassaemia genes. A comparison of the haematological and haemoglobin synthesis findings of individuals with normal alpha genotypes (alpha alpha/alpha alpha) with those with one (-alpha/alpha alpha) or two (-alpha/-alpha) alpha genes deleted shows that the latter two groups have more balanced globin chain synthesis ratios, higher haemoglobin levels, and larger, better haemoglobinized red cells. This suggests that the degree of globin chain imbalance is a significant factor in determining the red cell characteristics in heterozygous beta thalassaemia. Screening programmes for thalassaemia, based on the detection of low MCVs, could miss cases of the interaction of alpha and beta thalassaemia.

Chromosome Mapping↗
PubMed1982

The molecular basis for beta o thalassaemia intermedia in an Iranian individual.

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.

Adult↗
PubMed1982

Globin gene mapping in normal Hb A2 types of beta-thalassaemia.

Globin-gene mapping of DNA from 13 families with normal Hb A2 beta-thalassaemia (both type 1 and type 2) failed to detect any difference from normal in their globin-gene arrangement. We conclude that deletions such as those responsible for gamma beta-thalassaemia or a 'silent' Hb Lepore are not responsible for this type of beta-thalassaemia in Greece.

Chromosome Mapping↗
PubMed1982

Cell cycle distribution of erythroblasts in P. falciparum malaria.

The cell cycle distribution of the erythroblasts of 6 Gambian children with P. falciparum malaria was determined using the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The data showed evidence of a perturbation of erythroblast kinetics in all 6 children. The abnormalities were more marked in the children with chronic malaria than in those with acute malaria and predominantly affected the early polychromatic erythroblasts. The disturbances observed in chronic malaria included an increased proportion of cells in the G2 phase and an arrest during the progress of some cells through the S phase. The latter defect was not seen in the children with acute malaria.

Acute Disease↗