Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of dietary p-aminobenzoic acid (PABA), protein, methionine and threonine on Plasmodium berghei infection in mice were investigated. Animals were fed diets containing 12 or 20% casein supplemented with PABA (0 or 2 mg/kg diet), methionine (0 or 15 mg/g casein) and threonine (0, 7.5, 27.5 or 47.5 mg/g casein). Percent mortality was lower in rats fed diets without PABA than in those fed diets containing PABA. All further experiments were conducted without supplemental PABA. While the mean day of death was greater in the groups fed 12% casein, percent mortality in these groups was nearly twofold higher than in the groups fed 20% casein. The presence or absence of 15 mg methionine per gram casein had no effect on percent mortality, mean day of death, or percent parasitemia, regardless of dietary casein level. Supplementation of threonine at any level to the 12% casein diet with supplemental methionine resulted in mortality rates similar to those from animals fed the 20% casein diets, but percent mortality was not altered by threonine in the absence of supplemental methionine. The mean day of death of animals fed 20% casein increased with increments of added threonine. Methionine had no influence on this phenomenon. It is concluded that the quantity of dietary protein and the quality of its amino acid composition can have profound effects on the susceptibility of mice to malaria.
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PMID:Effects of p-aminobenzoic acid, methionine, threonine and protein levels on susceptibility of mice to Plasmodium berghei. 393 51

Cloned lines of the rodent malaria parasite Plasmodium chabaudi (denoted AS and CB) have been used to investigate the strain specificity of immunity to malaria. One defined difference between these lines is their expression of serologically and structurally distinct forms of an Mr 250Kd parasite-encoded antigen. This antigen is a member of a family of schizont/merozoite-associated polypeptides which have been implicated in the induction of protective immunity to rodent, simian and human malaria parasites. CBA/Ca mice were immunized by either (a) purified P. chabaudi AS-250Kd antigen, (b) chronic AS infection or (c) irradiated nonreplicating AS-parasitized erythrocytes. Post-immunization sera were examined by immunoprecipitation of 35S-methionine-labelled parasites, and the mice challenged with either AS or CB parasites. On challenge, mice developed a parasitaemia, the level of which was determined in part by isolate specificity, but only mice in groups (b) and (c) later developed a response which transcended AS/CB differences. The implications of these findings for the nature of exposed parasite antigens and the induction of protective immunity to malaria is discussed.
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PMID:Variability in parasite protein antigen structure and protective immunity to malaria. 399 99

The S antigen of a Papua New Guinean isolate of Plasmodium falciparum was identified by immunoblotting as the dominant antigen in culture supernatants. An antigen identical in molecular weight (Mr 220,000), isoelectric point (pI 4.2), and immunoreactivity with sera from individuals exposed to malaria was expressed by four Papua New Guinean isolates and one isolate of unknown origin. The Mr 220,000 antigen was not detected in culture supernatants derived from two isolates from Thailand and one from Ghana. The Mr 220,000, pI 4.2 S antigen may characterize a subpopulation of parasites common to many isolates of P. falciparum, which is selected for by continuous culture in vitro. A variant S antigen, 30 kilodaltons larger but with similar immunoreactivity, was expressed by 1 of 26 clonal populations derived by limit-dilution culture from one of the Papua New Guinean isolates of P. falciparum. The characteristics of the S antigen, defined by immunoblotting, allowed it to be identified in two-dimensional separations of [35S]methionine-labeled parasite proteins, thus confirming the parasite origin of the antigen.
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PMID:Characterization of an S antigen synthesized by several isolates of Plasmodium falciparum. 619 63

Synchronous cultures of Plasmodium falciparum were successively labelled with ((35)S)-methionine and both the supernatants and the pellets of infected red blood cells were collected. The release of TCA-precipitable material in the culture supernatants was low during the development of ring forms and trophozoites, increased during schizogony, and was maximum at the time of schizont rupture and merozoite reinvasion. Analysis of the supernatants by SDS - PAGE and autoradiography showed that both polypeptides common to the various developmental stages of the parasite and schizont/merozoite-specific polypeptides were released. Polypeptides of relative molecular mass 140 000, 82 000 and, to a lower degree, 41 000 were present in high amounts in the culture supernatants. These polypeptides have been shown to be the target of monoclonal antibodies that are able to inhibit the growth of P. falciparum cultures, and may be involved in protective immunity. The released polypeptides may also be used as target antigens in immunodiagnostic tests aiming at the detection of malaria infection.
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PMID:Plasmodium falciparum polypeptides released during in vitro cultivation. 634 Aug 46

A range of 22 mouse anti-P. falciparum monoclonal antibodies have been characterized by indirect immunofluorescence and immunoprecipitation. On the basis of these studies, 5 groups of antibodies and 6 classes of antigen were defined. Group I antibodies give, bright, uniform, generalised staining of all blood stages including gametocytes. Three of these antibodies precipitate a metabolically labelled molecule(s) of 35 kDa. One precipitates a 50 kDa antigen. Group II antibodies, which give strong localised immunofluorescence in merozoites, and a weak diffuse pattern in earlier stages, precipitate biosynthetically labelled molecules of 160 kDa. Group III antibodies react with all asexual stages. With merozoites they produce intense staining around the perimeter, both in fixed and unfixed preparations. They precipitate biosynthetic molecules of 190 kDa. Group IV antibodies are identical to Group III except they are stage restricted to schizonts and merozoites. They also precipitate 190 kDa antigens. These, however, in contrast to group III, are readily accessible to 125I-lactoperoxidase labelling. One antibody also precipitates a set of smaller peptides. Finally, Group V antibodies produce very bright ill-defined staining of pigment-containing parasites, as well as of inclusions in the red cell. They precipitate a series of molecules of 160, 60 and 35 kDa which are readily accessible to 125I. The 160 kDa molecule is also labelled by [35S]methionine. These results are discussed in the context of the development of a malaria vaccine and immunodiagnostic tests.
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PMID:Antigens of the erythrocytes stages of the human malaria parasite Plasmodium falciparum detected by monoclonal antibodies. 635 Aug 71

The capacity of Plasmodia to synthesize sialic acids was investigated by adding radioactive acetate to short-term in vitro cultures of the intraerythrocytic asexual forms of three malaria parasites (the human malaria Plasmodium falciparum in Aotus trivirgatus erythrocytes; the simian malaria P. knowlesi in rhesus monkey erythrocytes; the rodent malaria P. berghei in mouse erythrocytes) and to cultures of extracellular zygotes of the avian malaria P. gallinaceum. Radioactive acetate was added to normal rhesus monkey erythrocytes and to cells of the murine myeloma NS-1 for comparison. Although [1-14C]-acetate labeled many proteins with each malaria parasite and the NS-1 cells, analysis of purified sialic acids revealed that only with the NS-1 cells was radioactivity incorporated into sialic acids. Furthermore, N-acetyl[6-3H]mannosamine was not incorporated into sialic acids or malarial glycoproteins when added to P. knowlesi cultures. All of the malaria parasites underwent growth or differentiation during these experiments as measured by [35S]methionine uptake into protein and by light microscopy. Extracellular parasites largely free of erythrocyte membranes were prepared to determine whether Plasmodia contain sialic acids that are not labeled by exogenous precursors. Purified merozoites of P. knowlesi and zygotes of P. gallinaceum did not contain detectable amounts of sialic acids on chemical analysis. Thus, although we could show that Plasmodia can incorporate radioactive sugars such as glucosamine, galactose and mannose into proteins, presumably glycoproteins, they do not synthesize sialic acids or sialo-glycoproteins, nor do they contain sialo-glycoconjugates of host origin.
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PMID:Malaria parasites do not contain or synthesize sialic acids. 637 Aug 20

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.
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PMID:Intraerythrocytic development and antigenicity of Plasmodium falciparum and comparison with simian and rodent malaria parasites. 637 23

Monolayers of human erythrocytes (E) infected with Plasmodium falciparum were briefly fixed with 1% glutaraldehyde and air dried. They were then exposed to sera from patients with P. falciparum malaria or from donors immune to this parasite and tested in an indirect immunofluorescence assay (IFA). Parasites in infected E were made visible by counterstaining with ethidium bromide. Immunofluorescence (IF) was restricted to the surface of infected E. No antibody binding was detected unless the E were dried, suggesting that the relevant antigens were not available on the outer layers of the E surface. Staining over large parts of the E surface was seen already when the merozoite penetrated noninfected cells and was strong in E containing early stages of the parasite (rings, trophozoites). It was weak or absent from E containing schizonts. Antibodies in sera from different parts of Africa, Colombia, or Sweden reacted similarly with E infected with a Tanzanian P. falciparum strain kept in culture for many years and with parasitized E freshly drawn from African, Swedish, or Colombian patients. All sera from residents of a holoendemic area (Liberia) were IFA positive. In contrast, some sera from Colombian or Swedish patients with primary infection gave negative results. The results of the IFA and of an enzyme-linked immunosorbent assay in which fixed and dried E were the targets were well-correlated, suggesting that the same antibodies were detected by these assays. The antigens involved in the IFA were susceptible to pronase but not to trypsin or neuraminidase. E surface IF was inhibited by lysates of infected E, merozoite extracts, or soluble antigens present in P. falciparum culture supernatants but not by lysates of normal E or ghost extracts. The inhibitory antigens were heat stable (100 degrees C, 5 min). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting of either antigen-enriched preparations from culture supernatants or merozoite extracts showed that antibodies eluted from monolayers of infected E reacted consistently with a predominant polypeptide of Mr 155,000 and two to four minor polypeptides of lower molecular weights. Metabolic labeling of the parasites with 75Se-methionine indicated that these antigens were parasite derived. We conclude that the antigens involved in these reactions are released from bursting schizonts or merozoites and are deposited in the E membrane in the course of invasion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum. 637 12

IgG from a donor clinically immune to Plasmodium falciparum malaria strongly inhibited reinvasion in vitro of human erythrocytes by the parasite. When added to monolayers of glutaraldehyde-fixed and air-dried erythrocytes infected with the parasite, this IgG also displayed a characteristic immunofluorescence restricted to the surface of infected erythrocytes. Elution of the IgG adsorbed to such monolayers gave an antibody fraction that was 40 times more efficient in the reinvasion inhibition assay (50% inhibition titer, less than 1 microgram/ml) than the original IgG preparation. The major antibody in this eluate was directed against a parasite-derived antigen of Mr 155,000 (Pf 155) deposited by the parasite in the erythrocyte membrane in the course of invasion. A detailed study of IgG fractions from 11 donors with acute P. falciparum malaria or clinical immunity revealed the existence of an excellent correlation between their capacities to stain the surface of infected erythrocytes, their titers in reinvasion inhibition, and the presence of antibodies to Pf 155 as detected by immunoblotting. No such correlations were seen when the IgG fractions were analyzed for immunofluorescence of intracellular parasites or for the presence of antibodies to other parasite antigens as detected by immunoprecipitation of [35S]methionine-labeled and NaDodSO4/PAGE-separated parasite extracts. The results suggest that Pf 155 has an important role in the process of erythrocyte infection and that host antibodies to this antigen may efficiently interfere with this process.
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PMID:Human antibodies to a Mr 155,000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion. 639 31

Infection with Plasmodium berghei malaria is severely inhibited in rats fed on a low protein diet. A range of amino acid supplements was added to a 4.2% casein diet to determine whether the relationship between level of infection and protein content could be attributed to the dietary amounts of the essential amino acids. Significant increases in levels of infection were achieved by supplementation with specific combinations of amino acids. Threonine was most effective in increasing the degree of parasitaemia but its effect was further enhanced when it was combined with dietary excess of certain other amino acids, notably valine, isoleucine and methionine.
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PMID:Increased severity of malaria infection in rats fed supplementary amino acids. 639 37


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