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R J Wilson

Publications and source records attributed to R J Wilson.

At least 145 records · Page 8Linked to original sources

Serotyping Plasmodium falciparum malaria with S-antigens.

The heat-stable proteins known as S-antigens which are associated with Plasmodium falciparum malarial infections in man show considerable serological diversity. Usually, different S-antigens appear in separate malarial episodes in individuals exposed to reinfection. The antigens have a worldwide distribution in endemic areas but the restricted number and characteristic specificity of S-antigens recovered from experimentally infected Aotus monkeys suggest that these antigens might provide suitable markers for serotyping isolates of P. falciparum. Two kinds of evidence to support this idea are presented here. First, S-antigens which characterise an isolate of parasites are shown to retain their specificity over long periods of passage either in vivo or in vitro. Second, predictable mixtures of S-antigens can be recovered from cultures of P. falciparum after deliberately mixing isolates which each give rise to characteristic S-antigens.

Animals↗

Reduced lectin binding on erythrocytes of monkeys infected with malaria.

The number of binding sites for Axinella lectin (specific for D-galactose) on monkey erythrocytes containing schizonts of Plasmodium knowlesi was found to be reduced by about a third, from approximately 11 X 10(6) sites on normal erythrocytes to approximately 8 X 10(6) sites on parasitized erythrocytes. In contrast, only minor differences were found in the amounts of iodinatable external proteins. The results indicate that there is a general reduction of accessible sugars to which lectins may bind on parasitized erythrocytes.

Animals↗

Malarial antigens on infected erythrocytes.

Absorption experiments with washed membranes derived from erythrocytes infected with schizonts of Plasmodium knowlesi (PE) showed that the antigen responsible for agglutination of PE in SICA tests is firmly bound to membranes. Further experiments demonstrated that the number of antibody binding sites at the surface of parasitized erythrocytes can be measured using iodinated globulins. The conditions under which this could be achieved have been defined and a preliminary estimate of the number of high affinity surface antigen sites (greater than or equal to 10(4) per cell) has been made. Suggestions are given for further work to obtain a more accurate value.

Agglutination↗

Endopeptidases from Plasmodium knowlesi.

Extracts of rhesus monkey erythrocytes infected with Plasmodium knowlesi were fractionated by polyacrylamide gel electrophoresis (PAGE) and several zones of endopeptidase activity were demonstrated by an imprint-digest method. The enzymes were active only under acid conditions; activity was detected at pH 3.2 but not between pH 6.4 and 8.9 using haemoglobin, albumin or erythrocyte lysate as the substrate. Optimized PAGE conditions separated highly active parasite enzymes with Rf values of 73, 63 and 53 (+/- 7%), as well as a red cell endopeptidase, Rf44. Of two other minor bands of activity, one was associated with platelets.

Animals↗

The increased susceptibility of young red cells to invasion by the malarial parasite Plasmodium falciparum.

The relationship between red cell age and susceptibility to invasion by the malarial parasite Plasmodium falciparum has been examined by several different methods including short-term cultures of parasitized human blood. The results indicate that reticulocytes and young red cells are more susceptible to invasion by this parasite as compared with metabolically older cell populations. This is contrary to the current belief that red cells of all ages are invaded indiscriminately by P. falciparum. This observation has important theoretical, clinical and practical implications; its mechanism remains as yet unclear.

Age Factors↗

Fractionation and characterization of Plasmodium falciparum antigens.

In human malarial infections, the immunological importance of modified host cell components and of parasite antigens that may be released on spontaneous rupture of infected erythrocytes in vivo is not known. It is difficult, however, to analyse antigens extracted from entire parasitized red cells because of contamination with normal red cell constituents, notably haemoglobin. To overcome this problem, a simple chromatographic procedure has been developed that concentrates antigens and radiolabelled parasite products in a separate fraction from haemoglobin. Details are also given of investigations of two different kinds of antigen associated with Plasmodium falciparum. One antigen known to be immunogenic in man is shown to be associated with membranes. The other antigen is poorly immunogenic in man and other animals and is shown to be a soluble, rather stable, acidic protein.

Animals↗

Differentiation of gametocytes in microcultures of human blood infected with Plasmodium falciparum.

Gametocytes differentiated from ring-stage parasites in microcultures of human blood infected with Plasmodium falciparum. Immature gametocytes could be distinguished morphologically from late asexual trophozoites after approximately 40 h of culture. Differentiation into crescentic forms took several days and the incorporation of [3H]-isoleucine by developing gametocytes was demonstrated. About 1% of red cells contained gametocytes at the maxiumum densities attained. Differentiation of gametocytes occurred either directly from rings placed in culture or from the progeny of subsequent cycles of schizogony and invasiton in vitro. The latter occurrence was confirmed by the development of gametocytes in marker fetal red cells added to cultures, although fetal red cells provide a less favorable environment than those with HbA for growth of the parasites.

Erythrocytes↗

Co-existent eosinophilic gastroenteritis and hypothalamic-pituitary dysfunction.

A case of eosinophilic gastroenteritis in a 42-year-old man is described. The patient had diarrhoea, faecal blood loss, a protein-losing enteropathy, malabsorption of fat, xylose and vitamin B12. Co-existent hypopituitarism, diabetes insipidus and hypothalamic dysfunction was demonstrated. Complete clinical recovery occurred with pituitary replacement therapy alone. The association of this endocrine abnormality with the picture of eosinophilic gastroenteritis has not previously been described.

Adult↗

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↗

Preservation of intraerythrocytic forms of malarial parasites by one-step and two-step cooling procedures.

Ring, trophozoite, and schizont stages of Plasmodium knowlesi were cooled in dimethyl sulfoxide either by direct immersion in liquid nitrogen or by a two-step method in which the cells were held at temperatures slightly below 0 degrees C for different lengths of time before they were cooled to -196 degrees C. After the direct plunge treatment, thawed trophozoites and schizonts were found to be extensively damaged. Their survival was markedly increased by holding them at -31 degrees C for 30 min before plunging them into liquid nitrogen. Freeze-substitution showed that cells cooled by the two-step procedure were grossly shrunken and had relatively few intracellular ice cavities. Large amounts of ice formed in trophozoites and schizonts preserved by direct immersion in liquid nitrogen. The two-step protocols investigated did not improve the survival of ring-stage parasites, 25-50% of which survived rapid cooling to -196 degrees C. Infected cell agglutination tests were carried out with frozen and thawed schizonts. Variant specificity was demonstrated with cells that had been plunged directly to -196 degrees C, but cells cooled by the two-step method tended to agglutinate spontaneously.

Animals↗

Factors affecting the mechanical stability of the cemented acetabular component in total hip replacement.

In thirty-six dissected hips from cadavera, six types of fixation of the prosthetic acetabular component to the acetabular tissue were devised, utilizing combinations of a variety of technical procedures: decorticating the cartilage, intruding the cup, reaming the bone, and perforating the residual bone tissue with anchoring holes (for cement). Mechanical tests showed that the greatest stability was achieved when the prosthetic cup was completely intruded, when all articular cartilage was removed and the socket was reamed, and when anchoring holes for cement were devised.

Acetabulum↗

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↗