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C I Newbold

Publications and source records attributed to C I Newbold.

At least 73 records · Page 4Linked to original sources
PubMed1987

Possible pitfalls in the identification of glycophorin-binding proteins of Plasmodium falciparum.

Plasmodium falciparum proteins that bind to the putative erythrocyte receptor (glycophorin) have been identified in several laboratories by their ability to bind to glycophorin immobilized on aminoethyl-BioGel (AE-BioGel). We here report that several parasite proteins bind to AE-BioGel in the absence of coupled glycophorin. Binding is apparently due to the strong ion-exchange properties of the matrix, and is sensitive to ionic conditions such as the degree of equilibration of the matrix and the pH. The parasite proteins that bind to the blank column under appropriate conditions include proteins with the serological activities of S-antigen and Ag 23, which also bind to glycophorin-coupled AE-BioGel. In the light of these results, the glycophorin-binding specificity of these and other proteins reported to bind to glycophorin-coupled AE-BioGel will have to be reevaluated, preferably using a different support matrix.

Carrier Proteins↗
PubMed1987

Antigenic cross reactivity between p195 and a distinct protein of 100 kDa in Plasmodium falciparum.

A monoclonal antibody raised against merozoites of Plasmodium falciparum clone T9/96 was shown to react with an extremely strain specific epitope on a 195 kDa protein synthesized only by late trophozoites and schizonts. This protein was shown to exhibit all of the characteristics attributed to the molecule known variously as merozoite surface protein precursor, polymorphic schizont antigen and p195. The monoclonal antibody also identified a cross-reactive epitope on a distinct protein of 100 kDa in ring stage parasites which was shown to be synthesized throughout the asexual cycle and was not a processing product of p195. One-dimensional peptide mapping studies suggested that these two proteins share a degree of common sequence or structure.

Animals↗
PubMed1985

Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum.

Intraspecies antigenic diversity in the blood stages of the human malaria parasite Plasmodium falciparum was investigated using a collection of murine monoclonal antibodies and clones of the parasite. The results were as follows: (a) The schizont and merozoite stages of the parasite express on their surface clonally restricted antigens detectable by strain-specific antibodies in indirect immunofluorescence tests. (b) These restricted antigens are phenotypically stable characteristics of clones grown in vitro. (c) The molecules carrying the specific antigens were isolated by immunoprecipitation and were found to be parasite proteins ranging in size from Mr 190,000 to 200,000 between clones. (d) Comparative immunoprecipitation and peptide mapping of these molecules showed that each parasite clone expresses a protein that is antigenically and structurally distinct from the equivalent products of several other clones. (e) The different clonal products are, however, immunologically interrelated, since they possess determinants in common with all tested isolates of the parasite. (f) These polymorphic molecules are closely related to a previously described schizont protein of P. falciparum that is posttranslationally cleaved into fragments located on the merozoite surface. These findings show the existence of a family of related polymorphic schizont antigens (PSA) of P. falciparum, whose expression is clonally restricted, and indicate that these proteins have regions of constant and variable antigenicity. We propose that a system of immunological classification of the parasite can be developed based on the polymorphism of these proteins.

Animals↗
PubMed1984

A possible molecular basis for strain specific immunity to malaria.

A 250 kDa antigen implicated in the induction of protective immunity to Plasmodium chabaudi was examined with a panel of 11 monoclonal antibodies in cloned parasite lines. 2 antibodies cross-reacted with the different parasite lines while 9 were specific for one line. This antigenic diversity was correlated with major differences in one dimensional peptide maps between the purified antigen from different lines of parasites. The peptide maps also revealed some apparently conserved structure which may have been responsible for the antigenic cross reactivity. Using cloned lines of P. falciparum and a second series of monoclonal antibodies, similar antigenic and structural diversity was evident in the equivalent antigen from the important human pathogen. These findings are discussed with relationship to the induction of protective immunity to malaria.

Animals↗
PubMed1983

Maturation of the intracellular parasite and antigenicity.

The protein antigens synthesized by the malarial parasite change as the parasite matures, with a number of proteins showing strict stage-specificity. A detailed correlation between the stage-specificity of protein synthesis and parasite structure has yet to be established, but a number of proteins synthesized in the cycle are lost selectively during merozoite escape and reinvasion. These antigens are presumably associated with structures utilized and ultimately lost during this process. Particular interest has focused on some greater than 200K proteins identified as being on the surface of infected erythrocytes and internally and on the surface of merozoites. Smaller parasite proteins have also been identified in the erythrocyte membrane. The erythrocyte itself, including its membrane, is much modified by parasite growth. Changes include the presence of new cytoplasmic structures and differences in the surface labelling and isoantigenic characteristics of the surface membrane. An appreciation of the variability and specificity of exposed parasite antigens, and their relationship to newly exposed isoantigens, is central to our understanding of protective immunity to malaria.

Animals↗
PubMed1983

Serological cross-reaction between high molecular weight proteins synthesized in blood schizonts of Plasmodium yoelii, Plasmodium chabaudi and Plasmodium falciparum.

A 230 000 molecular weight (MW) Plasmodium yoelii protein, a 250 000 MW P. chabaudi protein and a 195 000 MW P. falciparum protein, identified using monoclonal antibodies, have similar characteristics, and have been implicated as protective antigens. In this study the serological relationship between these proteins was investigated by Western transfer analysis. The monoclonal antibodies specific for each of the high molecular weight proteins did not cross-react with antigens of the other two parasites, but a polyvalent mouse serum raised against the purified 230 000 MW P. yoelii protein cross-reacted with the high molecular weight proteins of P. chabaudi and P. falciparum and also with the fragments derived from these proteins. This result indicates that these proteins belong to the same class of malaria parasite antigen.

Amino Acid Sequence↗
PubMed1983

Intraerythrocytic development and antigenicity of Plasmodium falciparum and comparison with simian and rodent malaria parasites.

Using sorbitol-synchronised cultures and metabolic labelling with [35S]methionine, the stage specificity of polypeptides synthesised by the intraerythrocytic stages of Plasmodium falciparum was studied. We confirmed that the synthesis of many polypeptides is restricted to defined morphological stages of parasite development, while other polypeptides are synthesised more or less throughout the cycle. The synthesis of at least 6 polypeptides was confined to the period of differentiation of mature trophozoites to schizonts and merozoites. Polypeptides synthesised by a cloned long-term passage isolate were very similar to those of a recently cultured uncloned isolate. Comparison of polypeptides synthesized during differentiation of mature trophozoites to schizonts and merozoites by P. falciparum with those of P. chabaudi and P. knowlesi showed that while P. chabaudi and P. knowlesi synthesised a 250 000 molecular weight polypeptide at this stage the apparently equivalent polypeptide of P. falciparum was of significantly lower molecular weight being 200 000. Using a surface immunoprecipitation technique, it was shown that this 200 000 mol. wt. polypeptide was accessible to antibodies on the surface of erythrocytes infected with mature trophozoites and schizonts. A 150 000 mol. wt. polypeptide was also accessible to antibodies. By comparing polypeptides synthesised during the differentiation of mature trophozoites to schizonts and merozoites with those recovered in the ring stage parasites after schizogony and erythrocyte invasion, it was shown that this 200 000 mol. wt. polypeptide and 140 000 and 120 000 mol. wt. polypeptides were not taken into the erythrocyte by the invading merozoite. The importance of these polypeptides in terms of the parasite biology and in the induction and expression of immunity to malaria is discussed.

Animals↗
PubMed1983

A lectin-like receptor is involved in invasion of erythrocytes by Plasmodium falciparum.

Glycophorin both in solution and inserted into liposomes blocks invasion of erythrocytes by the malaria parasite Plasmodium falciparum. Furthermore, one sugar, N-acetyl-D-glucosamine (GlcNAc), completely blocks invasion of the erythrocyte by this parasite. GlcNAc coupled to bovine serum albumin to prevent the sugar entering infected erythrocytes was at least 100,000 times more effective than GlcNAc alone. Bovine serum albumin coupled to lactose or bovine serum albumin alone had no effect on invasion. These results suggest that the binding of P. falciparum to erythrocytes is lectin-like and is determined by carbohydrates on glycophorin.

Animals↗
PubMed1982

Stage specific protein and nucleic acid synthesis during the asexual cycle of the rodent malaria Plasmodium chabaudi.

The asexual, intraerythrocytic stage of Plasmodium chabaudi develops synchronously in CBA mice. This in vivo synchrony has been exploited in in vitro pulse-labelling experiments to investigate the stage specificity of macromolecular synthesis by malaria parasites. Groups of mice were infected on day 0 with P. chabaudi and on day 3, individual mice were killed at three hour intervals, and the parasitised blood labelled in vitro for 2 h with radioactive precursors of protein or nucleic acid synthesis. By taking 11 samples covering one and one-third parasite division cycles, it was shown that the synthesis of many parasite polypeptides was restricted to defined morphological stages of parasite development. Other polypeptides were synthesised more or less continuously during the growth cycle. The synthesis of at least 6 polypeptides was confined to schizont or merozoite differentiation. RNA synthesis was shown to increase in rate steadily during parasite growth and to fall sharply during merozoite invasion. Approximately 40% of DNA synthesis was shown to occur during trophozoite growth, but the majority (60%) was confined to a short 4-6 h period at or just before schizogony.

Animals↗
PubMed1982

Identification of a schizont- and species-specific surface glycoprotein on erythrocytes infected with rodent malarias.

Erythrocytes infected with mature trophozoites of Plasmodium chabaudi and reticulocytes infected with P. berghei were labelled metabolically in vitro with [35S]methionine. The labelled cells were incubated with normal and immune serum and washed to remove unbound antibody. Solubilisation of the antibody-coated cells in detergent was followed by co-precipitation of antibody/antigen complexes and analysis of the immunoprecipitates by SDS-PAGE and fluorography. One major parasite polypeptide of 250 000 daltons was found to be exposed to antibody in both species. A labelled band of the same molecular weight could be identified by immunoprecipitation and SDS-PAGE analysis of P. chabaudi-infected cells that had been surface-labelled with periodate/NaB3H4. This molecule also incorporated [3H]glucosamine in short term cultures of mature parasitised erythrocytes. The results suggest that a 250 000 dalton glycoprotein which is synthesised only by late trophozoites or schizonts is exposed either on the surface of the infected erythrocyte, the surface of the merozoite, or both. Furthermore, the exposed portion of the molecule was not immunologically cross-reactive in the two Plasmodium species, but some cross reaction was detectable in total parasite lysates. The significance of these findings to protective immunity is discussed.

Animals↗
PubMed1982

Monoclonal antibodies that protect in vivo against Plasmodium chabaudi recognize a 250,000-dalton parasite polypeptide.

Twenty monoclonal antibodies have been prepared to the erythrocytes from CBA/Ca mice infected with the rodent malaria Plasmodium chabaudi. By immunofluorescence, 15 of these antibodies recognized parasite antigens expressed only during the development of mature trophozoites to schizonts and merozoites, 2 recognized parasite antigens that were expressed throughout most of the intraerythrocytic cycle, and 3 recognized the membranes of all infected and uninfected erythrocytes. By immunoprecipitation of [35S]methionine-labeled, parasitized erythrocytes, parasite antigens recognized by all of the antiparasite antibodies were characterized. Eleven precipitated a 250,000-dalton parasite polypeptide which was synthesized and expressed late in the intraerythrocytic cell cycle and which appeared to be the major coat protein of the merozoites. In passive protection experiments, transfer of hyperimmune serum before infection with the parasite resulted in a delay in the rise of parasitemia, reduction in peak parasitemias, and a delay in the clearance of the parasitemia. Two monoclonal antibodies to the 250,000-dalton polypeptide had a similar but not as marked effect on parasitemia when given as a single dose before infection. When mixed and administered throughout the course of infection, their effects were greater. They had no influence on the course of Plasmodium berghei KSP11 parasitemia. Monoclonal antibodies to other parasite antigens and normal erythrocyte antigens failed to have a significant and reproducible effect on P. chabaudi parasitemia. The results suggest that this 250,000-dalton malaria parasite antigen may be important in the induction and expression of antibody-mediated immunity to malaria.

Animals↗
PubMedDate not supplied

The interaction between Plasmodium falciparum and P. vivax in children on Espiritu Santo island, Vanuatu.

Studies of the prevalence and incidence of malaria were conducted in children < 10 years old living in 10 rural villages on the island of Espiritu Santo, Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout the year but the relative contributions of the 2 major species were highly dependent on season. Plasmodium falciparum predominated in the long wet season (November-May) and P. vivax in the dry season (June-October). Case definitions for malaria, derived using a multiple logistic regression method, showed that parasite densities associated with clinical disease were low; case definitions for P. falciparum (> 1000 parasites/microL in children > 1 year old and > 500 microL in infants) and P. vivax (> 500 parasites/microL at all ages) were both associated with a specificity and sensitivity of > 90%. Like prevalence data, malaria morbidity was highly seasonal; 80% of clinical P. falciparum infections occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed infections were rare. Malaria was important cause of morbidity with children < 5 years old experiencing 1.3-3.0 episodes of clinical malaria per year and 23% of fevers being attributable to malaria in this age group. Children aged 5-9 years continued to suffer one episode of clinical malaria per year. The peak incidence of P. vivax malaria occurred earlier in life than the peak incidence of P. falciparum malaria. The possible interactions between these 2 parasite species are discussed.

Animals↗
PubMedDate not supplied

Environmental and entomological risk factors for the development of clinical malaria among children on the Kenyan coast.

Several malariometric studies have examined the impact on human-vector contact of house construction, demographics, bed net and insect repellent use. However, few studies have documented the significance of these proximate determinants on the risks of clinical disease. We undertook a matched case-control study of the risks of both mild clinical malaria and severe life-threatening malaria according to a range of putative factors which would influence the frequency of child-vector encounters in Kilifi district on the Kenyan coast. Among 394 severe disease cases, 380 age-matched mild disease cases, and their respective location and age-matched community controls, we were unable to demonstrate any statistically significant effect upon disease outcome of house construction, presence of domestic animals, or bed net use. Higher population density within a 250 m radius of the homes conferred significant protection from the risks of developing severe malaria compared to community controls. The risks of developing severe malaria compared to the community controls and the transition from mild to severe disease were statistically significantly lower in those who reported use of mosquito coils, local repellents or aerosol insecticides. We concluded that it is likely that the impact of household features on disease outcome is dependent upon both the density of infecting mosquitoes and acquired immunity within a given locality.

Case-Control Studies↗