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Biomedical subjects

C A Facer

Publications and source records attributed to C A Facer.

17 recordsLinked to original sources

Cytotoxicity of human natural killer (NK) cell subsets for Plasmodium falciparum erythrocytic schizonts: stimulation by cytokines and inhibition by neomycin.

Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.

Animals

In vitro analysis of Epstein-Barr virus: host balance in patients with acute Plasmodium falciparum malaria. I. Defective T-cell control.

Peripheral blood lymphocytes from healthy, Epstein-Barr virus (EB-virus)-seropositive donors and from patients with acute Plasmodium falciparum malaria were tested for their cytotoxicity towards autologous EB-virus-infected B-cells using an in vitro regression assay. Of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. Of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. Analysis of the lymphocyte subsets showed a high incidence of inverted CD4:CD8 ratios in the patient group due to an absolute rise in the CD8 population. This data suggests that the immunosuppressive effects of acute malaria extend to defective control over EB-virus. The relevance of the observations to the aetiology of EB-virus-associated, endemic Burkitt's lymphoma (eBL) is discussed.

Acute Disease

Abnormal features of peripheral blood films from Gambian children with malaria.

A series of peripheral blood films taken from Gambian children with either acute or low-grade Plasmodium falciparum infections were examined for abnormal features of the red and white cells. Hypochromia and polychromasia with cytoplasmic stippling were predominant features in both groups. Lymphocytosis, granulocytosis and plasmacytosis were common white cell abnormalities. An additional feature in films from patients with acute malaria was the presence of numerous atypical lymphocytes. A comparison of the features in the two groups indicated that some abnormalities are associated with an acute attack of malaria and that others have a nutritional or genetic aetiology.

Child

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