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Biomedical subjects

C A Facer

Publications and source records attributed to C A Facer.

At least 37 records · Page 2Linked to original sources

Erythrocyte sialoglycoproteins and Plasmodium falciparum invasion.

Human erythrocytes with a deficiency in glycophorin A (En(a-) cells) and glycophorin B (S-s-U- and S-s-U+ cells) show significant resistance in vitro to invasion by Plasmodium falciparum merozoites. Treatment of normal erythrocytes with trypsin and chymotrypsin also reduced invasion. Trypsinization of S-s- and En(a-) red cells, a process which removes the T1 peptide of glycophorins A and C, produced cells almost refractory to invasion. The human K562 erythroleukaemia cell line, which also expresses glycophorin A, was not invaded and possible explanations for this result are discussed. It is suggested that determinants carried on the red cell sialoglycoproteins (glycophorins A, B and C), in particular the T1 peptide of glycophorins A and C, play an essential role in attachment and invasion by P. falciparum merozoites. The oligosaccharide components found on this peptide may play a role in the initial binding between red cell and merozoites.

Animals↗

Merozoites of P. falciparum require glycophorin for invasion into red cells.

The importance of the red cell membrane sialoglycoproteins in the invasion of P. falciparum merozoites has been assessed. Human erythrocytes deficient in glycophorin A (En(a-)cells) or B (S-s-U-, S-s-U+ cells) showed significant resistance to invasion. Treatment of normal erythrocytes with trypsin and chymotrypsin also reduced invasion. These results indicate that determinants carried on glycophorins A, B and C play an essential role in the successful invasion into human red cells. Sugar components present on glycophorin, in particular N-acetyl glucosamine and N-acetyl galactosamine, as shown by specific sugar and antibody inhibition studies, appear to act as important determinants for attachment to the erythrocyte. This implicates a protein(s) on the merozoite surface membrane which has the properties of a lectin.

Chymotrypsin↗

Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of erythrocyte-bound IgG.

The cause of direct Coombs (DAT) positivity in West African (Gambian) children has been investigated. Results obtained from a comparison of two groups of primary school children, one from an area hyperendemic for P. falciparum malaria and the other partially protected from malaria, indicate an association between a high incidence of DAT positivity and P. falciparum parasitaemia with raised serum antibody titres to falciparum schizonts. Erythrocytes taken from children with a high IgG DAT titre were subjected to acid elution and the eluates examined for IgG content and antigen specificity. Eluted IgG had specific antibody activity against P. falciparum schizont antigen as demonstrated by means of the indirect fluorescent antibody technique. Cross-reaction was not observed with either P. falciparum gametocytes or P. malariae schizonts. No blood group specificity could be demonstrated in either the red cell eluates or serum taken from children with DAT positive red cells. The results provide convincing evidence which implicates falciparum malaria in the aetiology of Coombs positivity in Gambian children. It is probable that erythrocyte sensitization results from passive attachment of circulating complement-fixing malaria antigen-antibody complexes.

Agglutinins↗

Direct antiglobulin reactions in Gambian children with P. falciparum malaria. III. Expression of IgG subclass determinants and genetic markers and association with anaemia.

The IgG subclass and Gm allotype distribution of red cell-bound IgG molecules from Gambian children with past or present falciparum malaria has been determined. The results show that the antibody is polyclonal with some predominance of the IgG2 and IgG4 subclasses. A restriction towards IgG2 antibodies may indicate specificity for a schizont-derived antigen which is carbohydrate in nature. Not all the allotypes normally carried by the G3m(b) allele could be demonstrated on IgG3-sensitized cells, a finding which remains unexplained. Expression of G3m(10), (11) and (14) allotypes of the IgG3 molecule was noted. Sensitization of red cells with IgG1 molecules correlated with the presence of anaemia but red cells sensitized with IgG2, IgG3 or IgG4 usually came from children with haematological findings within the normal range for that population. The implications of the results are discussed with reference to the few reports on the subclass and Gm allotype of malaria-specific IgG.

Age Factors↗

Incidence of abnormal haemoglobin traits among Gambian children.

The electrophoretic mobility of haemoglobin from 343 Gambian children between the ages of two months and ten years has been investigated. The incidence of Hb-S and Hb-C traits is described and compared with earlier reports on the distribution of these traits in The Gambia. One child was identified as having the rare haemoglobin, Hb-A + N.

Child↗

Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. I. Incidence and class specificity.

Gambian children with past or present Plasmodium falciparum malaria were investigated for the incidence of Coombs positivity using monospecific antisera. Approximately 50% were positive and the most frequent form of erythrocyte sensitization was with C3d. Other specificities, EIgG, EIgGC3d and EIgGC4bC3d were less common. Erthyrocytes were never found sensitized with IgA or IgM. There was no correlation between a positive test and age, tribal status or level of parasitaemia at presentation, although a positive test was often found in association with anaemia. Sensitized erythrocytes were present in the circulation for a period of up to 6 weeks following initial observation. The mechanism of erythrocyte sensitization is not known, but the results suggest a Type III complex-mediated hypersensitivity involving parasite antigen-antibody complexes. It is likely that these reactions contribute to the pathogenesis of the anaemia in falciparum malaria.

Anemia↗

Fibrinogen and fibrinogen/fibrin degradation products in the urine of rabbits infected with Trypanosoma (trypanozoon) brucei.

Studies have been carried out on the urine of rabbits infected with Trypanosoma (Trypanozoon) brucei to determine whether fibrinogen or fibrinogen/fibrin degradation products (FDP) could be detected. No fibrinogen was found but during the last two weeks of this 7-week infection low levels of FDP were present in the urine which did not exceed 5 microgram/ml. Rabbit urine was shown to contain a potent proteolytic enzyme capable of breaking down rabbit fibrinogen and both early and late FDP were present in the cleavage products. No deposits of fibrin were detected in the kidney, but casts were present in the urine suggesting renal damage. The most likely explanation of the urinary FDP is that either an increase in the glomerular permeability occurs allowing filtration of plasma FDP or a local fibrinogenolysis in the kidney tubules.

Animals↗