Biomedical subjects
J D Stace
Publications and source records attributed to J D Stace.
The development and ultrastructure of Plasmodium falciparum damaged in vitro by human "crisis" sera and by chloroquine.
P. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Intra-erythrocytic parasite damage was seen by light and electron microscopy. The significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.
Malaria control and primary health care.
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Specificities of antibodies boosted by acute Plasmodium falciparum infection in man.
In the search for antibodies correlating with host-protective immunity to Plasmodium falciparum in man, sera from individuals in Papua New Guinea were analyzed at the time of infection and in the convalescent period following infection. Titers of antibody were determined by enzyme linked immunoassay (ELISA), and the specificities of antibodies was examined by gel electrophoresis of immunoprecipitates. In the majority of cases, convalescence was associated with an increase in antibody titer and one-dimensional gel analysis of immunoprecipitated biosynthetically labeled parasite antigens demonstrated the variability in specificity of the antibody response in the two types of serum samples from different individuals. A protein of Mr 96,000 which has previously been identified as a candidate host-protective antigen was not clearly seen in immunoprecipitates generated with acute serum, even in samples with high titers of antibody assessed by ELISA. Antibodies to a protein Mr 96,000 were present in some, but not all convalescent sera. Two-dimensional gel analysis was more sensitive in detecting a boost in antibody response to minor antigens (e.g., an acidic protein Mr approximately equal to 230,000). This approach has not led to identification of antibody specificities to major antigens which are invariably boosted by infection and drug cure, but has identified antibody specificities in acute sera which are inadequate in quantity or quality to inhibit parasite growth.
Studies on malaria in Papua New Guinea: comparison of the surface glycoproteins on red blood cells from infected and uninfected individuals.
The levels of erythrocyte membrane sialic acid from 17 patients with Plasmodium falciparum malaria and 1 with Plasmodium vivax malaria, in Papua New Guinea, have been compared with 9 uninfected controls. The amounts of radioactivity incorporated into the major erythrocyte glycoproteins by the periodate/NaB3H4 or galactose oxidase plus neuraminidase/NaB3H4 methods were unchanged by malaria infection. The electrophoretic mobilities of these proteins also were unaffected. Several new glycoprotein bands with molecular weights (mol. wt) of 160,000, 89,000, 46,000, 42,000 and 33,000 Daltons were labelled on the surface of erythrocytes from infected individuals; however, none of these bands appeared in all malarious samples. Sialic acid levels on the erythrocyte membrane were also measured by exhaustive neuraminidase treatment and quantitative assay of released sialic acid. The amount of sialic acid was raised in 1 infected individual, within the normal range for Europeans in 4 others, and below this range with 3 patients. Apparently, extensive removal or modification of sialic acid on the surface of uninfected erythrocytes does not occur in human malaria, in contrast to the results obtained in earlier studies with the lethal murine malarias.
Immunoprecipitation of biosynthetically-labelled proteins from different Papua New Guinea Plasmodium falciparum isolates by sera from individuals in the endemic area.
The human serum antibody response to Plasmodium falciparum infection in Papua New Guinea has been studied by electrophoretic analysis of immunoprecipitated biosynthetically-labelled malaria proteins from three different isolates maintained in long-term in vitro culture. Differences in protein antigenic composition in different lines have been described and simplified by examination of antigens recognized only by hyperimmune serum. An in vitro assay has been used to screen various human sera containing antimalarial antibody for their ability to inhibit parasite growth and the immunoprecipitation profiles of non-inhibitory sera have been compared with those of a hyperimmune serum pool. In the discussion, emphasis is placed on the value of immunoprecipitation analyses using clinically-defined sera with known in vitro function in the identification of antigens which may be responsible for the induction of host-protective immunity.
Reduction in malaria parasite rate in young children by distribution of prophylactic amodiaquine through voluntary village workers.
In Madang Province PNG voluntary dispensers in 36 villages distributed weekly amodiaquine to young children over 12 month period (July 1977 - June 1978). The tablets were distributed each week for over 70% of the study period. The slide positive rate for malarial parasites was markedly reduced from 29% to 3.7%.
Short term in vitro cultivation of malaria parasites in Papua New Guinea for preparation of biosynthetically-labelled parasite antigens.
Short term in vitro cultivation has been used successfully for biosynthetic labelling of TCA precipitable macromolecules of Papua New guinean isolates of Plasmodium falciparum. Conditions satisfactory for completion of the asexual erythrocytic cycle were achieved with aa minimum of sophisticated equipment. The techniques used are described in detail and mention is made of possible applications to assessment of chloroquine resistance and the mode of action of inhibitory antisera.