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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The surface proteins and glycoproteins of red cells from Plasmodium berghei-infected blood have been radio-isotope labelled and compared with those of normal mouse erythrocytes using the following protein labelling probes: lactoperoxidase-catalysed radio-iodination of tyrosyl residues, periodate oxidation and NaB3H4 reduction of sialic acid and oxidation of galactosyl/N-acetylgalactosaminyl residues by galactose oxidase with subsequent NaB3H4 reduction. During P. berghei infection, new tyrosyl-labelled proteins with apparent molecular weights (Mr) of 60 000, 54 000, 40 000 and 27 500 appeared on the surface of most, if not all, red cells in the blood. Purified multinucleate cells (mostly reticulocytes) differed only in that they also had a surface protein with Mr of 83 000. However, this molecule is thought to be specific to mouse reticulocytes rather than derived from parasites. In contrast to the relatively minor changes detected with radio-iodination, striking changes in glycoprotein radio-isotope labelling resulted from infection. All of the red cells in infected blood of greater than 20% parasitaemia lost their periodate-sensitive glycoprotein sialic acid. With some samples there was little change in glycoprotein labelling by the galactose oxidase method, provided neuraminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infected cells which has been inferred in many haemosporidial infections, including malaria.
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PMID:Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Plasmodium berghei infections of BALB/c mice. 700

The prevalence of antibodies against (i) human red blood cells (RBC) of A and B groups, (ii) trypsinized O Rh+ RBC and (iii) neuraminidase treated O Rh+ RBC were investigated both in sera of Africans from a malaria endemic area of Upper Volta and in sera of Europeans with acute malaria from a Paris hospital. An increased frequency of high titres of haemagglutinins was observed against A and B as well as O Rh+ trypsinized human RBC, thus confirming previously published results. In addition, agglutination of neuraminidase treated RBC showed that the titres were increased in about 40% of Africans studied and in about 80% of patients with acute malaria. Using agglutination with a specific anti-T lectin and inhibition with two ligands, it was found that sera of malarious patients contain high titres of antibodies directed against the T antigen of neuraminidase treated RBC. The mechanisms of appearance of high titres of autohaemagglutinins in malaria and their possible interference in the anaemia associated with this disease are discussed.
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PMID:High titres of anti-T antibodies and other haemagglutinins in human malaria. 717 12

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.
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PMID:Studies on malaria in Papua New Guinea: comparison of the surface glycoproteins on red blood cells from infected and uninfected individuals. 732 24

Lactoperoxidase-catalysed radio-iodination was used to compare the surface proteins on red cells from Plasmodium yoelii-infected with normal BALB/c mice. The profile of radio-iodinated proteins separated by SDS-polyacrylamide gel electrophoresis was different for infected blood of similar parasitaemia from mice inoculated with different doses of the parasite. Inoculation with different doses of the parasite. Inoculation with the lower dose resulted in the appearance of a major radio-iodinated protein of apparent molecular weight (Mr) 76 000 which was labelled to a similar extent on uninfected red cells from infected blood and purified multinucleate infected cells. Several minor radio-iodinated bands, with identical mobilities to the minor bands on normal BALB/c erythrocytes, were also present on red cells from this infected blood. In contrast, the higher inoculation dose produced changes in the minor labelled bands, and the band with Mr of 76 000 was absent. In this case, the minor radio-iodinated proteins of the normal BALB/c erythrocyte (with Mr of 65 000, 57 000, 48 000, 38 000 and 32 000) were replaced by a series of bands with Mr of 60 000, 50 000, 43 000 and 28 000 on both uninfected and infected red cells. These differences with inoculation dose may be related to the different duration of these infections, the development of anaemia and the extent of pathological changes at the erythrocyte surface. P. yoelii infection caused a marked loss in periodate-dependent labelling of sialoglycoproteins on most, if not all, red cells in infected blood. There was also a large decrease in galactose oxidase-dependent glycoprotein labelling with or without neuraminidase treatment. These changes in the carbohydrate groups on red cell membrane glycoproteins may be linked to the excessive loss of both uninfected and infected red cells during some malaria infections.
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PMID:Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Plasmodium yoelii infections of BALB/c mice. 744 94

A cell-ELISA was developed using monolayers of glutaraldehyde-fixed normal as well as Plasmodium berghei-infected mouse erythrocytes for quantification and characterization of anti-erythrocytic autoantibodies in murine malaria. Testing normal (NMS) and peak parasitaemic sera (PPS) on erythrocyte monolayers treated with trypsin, sodium meta periodate, neuraminidase or heat, and competitive inhibition of antibodies with soluble sialic acid, revealed that some anti-erythrocytic antibodies (which increase during the parasitaemic phase of infection) recognize N-acetyl neuraminic acid (NANA) residues on host erythrocytes. High levels of antibodies to NANA covalently conjugated to bovine serum albumin (BSA) were detectable in PPS. Such antibodies could be significantly absorbed out by preincubation of PPS with mouse erythrocytes (MRBC). Antibodies in PPS, when affinity-purified on a column of Fetuin-Agarose, were found to be reactive to normal as well as parasitized erythrocyte monolayers. Immunoglobulin isotyping and IgG subgroup typing revealed that most of the anti-erythrocytic autoantibodies in NMS were IgM and IgA, while in PPS there was an appreciable increase in IgG2a and IgG3. Affinity-purified anti-NANA antibodies reacted with DNA when tested in an ELISA. There was a significant positive correlation between anti-erythrocytic antibody and DNA-binding levels in NMS as well as PPS. The DNA-binding antibodies in PPS could be effectively absorbed out by preincubation of sera with fresh MRBC. Affinity determination of anti-erythrocytic antibodies eluted from MRBC revealed binding characteristics in the following order: MRBC > single-stranded DNA > double-stranded DNA.
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PMID:Murine malaria: anti-erythrocytic antibodies recognize N-acetyl neuraminic acid residues. 750 18

We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8+ T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8+ T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.
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PMID:Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity. 752 9

Invasion of erythrocytes by malaria parasites involves multiple receptor-ligand interactions. To elucidate these pathways, we made use of four parasite clones with differing specificities for invasion, erythrocytes that are mutant for either glycophorin A or B, and enzyme modification of the erythrocyte surface with neuraminidase and trypsin. Neuraminidase alone abolishes invasion of two parasite clones (Dd2, FCR3/A2); these invade after trypsin treatment alone. A third clone (7G8) is unable to invade trypsin-treated erythrocytes. The fourth clone (HB3) can invade after either neuraminidase or trypsin treatment. The receptor for invasion of trypsin-treated erythrocytes was explored in two ways: treatment of trypsin-treated normal cells with neuraminidase, and trypsin treatment of glycophorin B-deficient cells. Both treatments eliminated invasion by all clones, indicating that the trypsin-independent pathway uses sialic acid and glycophorin B. To identify parasite proteins involved in the different pathways, erythrocyte binding assays were performed with soluble parasite proteins from each clone. Based on binding assays using erythrocytes that lack glycophorin A, the parasite protein known as EBA-175 appears to bind predominantly to glycophorin A. In contrast, the glycophorin B pathway does not appear to involve EBA-175, as binding of EBA-175 was similarly reduced to trypsin-treated normal and trypsin-treated glycophorin B-deficient erythrocytes. Thus, the glycophorin B-dependent, sialic acid-dependent invasion of trypsin-treated normal erythrocytes uses a different parasite ligand, indicating two or more sialic-dependent pathways for invasion. Clone 7G8, which cannot invade trypsin-treated erythrocytes, may be missing the ligand for invasion via glycophorin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycophorin B as an EBA-175 independent Plasmodium falciparum receptor of human erythrocytes. 807 23

Red blood cell (RBC) adhesion to the vascular endothelium is increased in several pathologic conditions, including sickle cell disease and malaria. However, RBC interactions with components of the subendothelial matrix are not well-characterized. Under in vitro flow conditions of 1 dyne/cm2, washed RBCs bound to the purified adhesive molecules thrombospondin (TSP) and laminin. Sickle RBCs had the greatest adhesion of all tested RBCs. The adhesion of sickle RBCs to immobilized TSP was inhibited by the anionic polysaccharides high molecular weight (MW) dextran sulfate and chondroitin sulfate A, but not other anionic polysaccharides of similar structure and/or charge density. These data were consistent with the RBC adhesive molecule being a sulfated glycolipid. Therefore, TSP-binding lipids from normal and sickle RBCs were isolated and characterized. The TSP-binding lipid was purified by alkaline methanolysis, anion exchange chromatography and preparative thin layer chromatography (TLC). A homogeneous band on TLC was identified using a specific overlay TSP-binding assay. TSP binding to the purified lipid was stable to bass and neuraminidase treatment, labile to acid treatment, and was inhibited by high MW dextran sulfate, similar to that seen with intact RBCs binding to immobilized TSP under conditions of flow. In addition, soluble laminin bound to the purified RBC lipid. This acidic TSP- and laminin-binding lipid(s) isolated from both sickle and normal RBC membranes may contribute to erythrocyte interactions with the subendothelial matrix, hereby participating in the pathogenesis of vaso-occlusive diseases.
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PMID:Increased adhesion of erythrocytes to components of the extracellular matrix: isolation and characterization of a red blood cell lipid that binds thrombospondin and laminin. 863 62

Sialic acid on the red cell surface plays a major role in invasion by the malaria parasite Plasmodium falciparum. The NeuAc(alpha 2,3) Gal motif on the O-linked tetrasaccharides of the red cell glycophorins is a recognition site for the parasite erythrocyte-binding antigen (EBA-175). Consequently, the interaction of P. falciparum and the red cell might share homology with that of the influenza virus. The cellular interactions of P. falciparum were examined for their sensitivity to 4-guanidino-2,3-didehydro-D-N-acetyl neuraminic acid (4-guanidino Neu5Ac2en), a potent inhibitor of influenza virus sialidase. Parasite invasion and subsequent development was unaffected by the sialidase inhibitor. The inhibitor did not affect rosette formation of parasite-infected erythrocytes with uninfected cells nor their cytoadherence to C32 melanoma cells. Furthermore, we were unable to confirm the presence of a previously reported parasite sialidase using sensitive fluorometric or haemagglutination assays, neither was any malarial trans-sialidase identified. We conclude that P. falciparum possesses neither sialidase nor trans-sialidase activity and that an inhibitor of influenza virus sialidase has no effect on important cellular interactions of this parasite.
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PMID:Plasmodium falciparum lacks sialidase and trans-sialidase activity. 867 33

Approaches to improve the efficacy of the current (killed) influenza virus vaccines include the generation of cold-adapted and genetically engineered influenza viruses containing specific attenuating mutations. It is hoped that these genetically altered viruses, in which the hemagglutinin and neuraminidase genes from circulating strains have been incorporated by reassortment, can be used as safe live influenza virus vaccines to induce a long-lasting protective immune response in humans. In addition, genetically engineered influenza viruses may provide a means for expressing foreign antigens. Immunization of mice with recombinant influenza and vaccinia viruses expressing specific antigens of Plasmodium yoelii resulted in a dramatic protective immune response against malaria in this model. Mice immunized with recombinant influenza viruses expressing human immunodeficiency virus (HIV) epitopes generated long-lasting HIV-specific serum antibodies and secretory IgA in the secretory nasal, vaginal, and intestinal mucosa. These results suggest that genetically engineered influenza viruses may be developed for use as live virus vaccines against influenza as well as other diseases.
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PMID:Development of novel influenza virus vaccines and vectors. 924 Jun 94


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