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)

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.
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PMID:Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts. 615 61

An immunoperoxidase technique was used to detect hypnozoites and liver schizonts of the primate malaria species Plasmodium vivax and P. cynomolgi bastianellii in Carnoy's-fixed sections. Anti-P. cynomolgi serum and a peroxidase-conjugated anti-monkey IgG serum rendered 7-day pre-erythrocytic forms clearly visible. The technique retains the specificity of the immunofluorescence method while having the advantage of a permanent preparation. Detection of hyponozoites by this alternative method provides further evidence for their plasmodial nature.
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PMID:Identification of hypnozoites and tissue schizonts of Plasmodium vivax and P. cynomolgi by the immunoperoxidase method. 619 80

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

A method is described for the visualization of red blood cells infected with Plasmodium falciparum ingested by monocytes or polymorphonuclear leukocytes (PMN) after in vitro incubation. Smears were stained with peroxidase followed by 4,6-diamino-2-phenylindole (DAPI) staining specific for DNA. Monocytes or PMN were identified under normal illumination by the peroxidase stain and the nuclei of these cells as well as the parasites were identified by means of the DAPI stain with ultraviolet light. Using this method we found that monocytes and PMN from normal blood donors preferentially phagocytose plasmodium falciparum infected red blood cells in the presence of sera from subjects living in areas endemic for malaria.
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PMID:Assessment of immune phagocytosis of Plasmodium falciparum infected red blood cells by human monocytes and polymorphonuclear leukocytes. A method for visualizing infected red blood cells ingested by phagocytes. 635 19

The effect of normal human peripheral blood polymorphonuclear leucocytes on in vitro multiplication of Plasmodium falciparum malaria parasites was investigated. It was shown that normal neutrophils were able to phagocytose parasitized erythrocytes and free parasites and thus inhibit in vitro multiplication of the parasite. Stimulation of the neutrophils by phorbol myristate acetate, a potent stimulus of leucocyte oxidative metabolism, resulted in enhanced inhibition of parasite growth. Superoxide dismutase, scavenger of superoxide anion, catalase, inhibitor of hydrogen peroxide, and sodium azide, inhibitor of myeloperoxidase, did not abrogate the inhibitory ability of the neutrophils. The results indicate that polymorphonuclear leucocytes play an important role in the defence against P. falciparum malaria.
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PMID:Enhanced inhibition of in vitro multiplication of Plasmodium falciparum by stimulated human polymorphonuclear leucocytes. 638 Aug 30

Previous investigations on the mechanism by which the host mounts an immune response against the human malaria parasite Plasmodium falciparum have not resolved whether cell-mediated responses, in the absence of circulating anti-Plasmodial antibodies, can effect the destruction of the intraerythrocytic parasite. We report that the intraerythrocytic parasite P. falciparum is lethally susceptible to the imposition of oxygen-dependent and oxygen-independent factor(s) released by interferon-gamma-activated, monocyte-derived human macrophages. In addition, trophozoite-schizont stage intraerythrocytic parasites were killed on exposure to small amounts of H2O2 generated in cell-free enzyme assays. Although parasiticidal activity was markedly enhanced by the addition of lactoperoxidase and KI, killing was abrogated by the addition of catalase. The ability of freshly isolated human monocytes, monocyte-derived macrophages (MDM), and lymphokine-activated MDM to kill or inhibit the growth and multiplication of the malaria parasites was assessed. Parasites were killed when exposed to monocytes or lymphokine-activated MDM, but not when exposed to nonactivated macrophages. The capacity to activate MDM for microbicidal activity was abrogated on neutralization of crude lymphokines or recombinant interferon-gamma with a monoclonal antibody prepared against interferon-gamma. The intraerythrocytic parasites surviving the cytotoxicity assay were inhibited in their development and appeared to be degenerating, a characteristic of "crisis" forms. Killing of P. falciparum correlated positively with the magnitude of the oxidative response, as evidenced by the reduction of nitroblue tetrazolium to formazan in the mononuclear phagocytes, and by the detection of secreted H2O2. Of particular interest was the observation that only the later developing stage of the intracellular parasite triggered the respiratory burst in the absence of antibody. A role for oxygen-independent parasiticidal factors was suggested by the finding that lymphokine-activated macrophages from a patient with chronic granulomatous disease were able to partially inhibit the growth of P. falciparum, although oxidative metabolism in these cells was impaired.
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PMID:Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. 643 Oct 3

A micro enzyme-linked immunosorbent assay utilizing antigen dotted onto nitrocellulose filter discs (Dot-ELISA) was developed for the rapid diagnosis of visceral leishmaniasis. Leishmania donovani promastigotes applied to filter discs in volumes of 1 microliter were placed in 96-well microtiter plates, blocked with bovine serum albumin, then incubated with 4-fold dilutions of patient sera. After incubation with peroxidase-conjugated anti-human antibody, washing and addition of precipitable substrate, positive reactions appeared as blue dots on a white background which were easily read by eye. The procedure is performed at room temperature, takes about 2 h and is economical. At a reciprocal diagnostic titer of greater than or equal to 32, 41 of 42 (98%) leishmaniasis patients were positive, and positive titers ranged from 512 to 524,288. Control sera from healthy individuals showed 1 of 50 (2%) false positive reactions. Sera from patients with African trypanosomiasis, Chagas' disease, and lupus erythematosus were cross-reactive in the Dot-ELISA. No cross-reactivity was noted with sera from patients with amebiasis, coccidioidomycosis, cutaneous leishmaniasis, viral hepatitis, hydatidosis, malaria, schistosomiasis, syphilis, toxoplasmosis or trichinosis. In replicate experiments, 90% of 167 sera tested did not vary in titer. This rapid and inexpensive test should prove to be an important field diagnostic technique for visceral leishmaniasis.
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PMID:Dot enzyme-linked immunosorbent assay (Dot-ELISA): a micro technique for the rapid diagnosis of visceral leishmaniasis. 654 6

Mature asexual stages of the malaria parasite Plasmodium Knowlesi synthesize proteins of Mr 180 000-225 000 that are expressed on the outer membrane of infected erythrocytes and which vary antigenically such that different parasite clones are specifically agglutinated with homologous antibody. Other non-agglutinable clones have been prepared which fail to express variant antigen on infected cells. Two agglutinable clones of different variant antigen phenotypes and a non-agglutinable cone were examined to determine the proportion of total malarial proteins represented by variant antigens. Malarial proteins were labelled with various radioactive amino acids and the sodium dodecyl sulphate--polyacrylamide gel patterns for the three clones compared by fluorography. The patterns were indistinguishable, the variant antigens being undetectable in analyses of total malarial proteins. Furthermore, these antigens were not detected by Coomassie Blue-staining of total cellular proteins after electrophoresis. Sodium dodecyl sulphate and Triton X-100 extracts of labelled cells were immunoprecipitated using a panel of sera of defined agglutination specificity. The variant antigens could not be detected in the fluorographic patterns of total malarial antigens immunoprecipitated by these sera. In contrast, after lactoperoxidase catalysed radio-iodination of intact schizont-infected cells, the 125I-variant antigens on the cell surface were identified by demonstrating their accessibility both to antibody and to trypsin with intact cells. Thus, the variant antigens are quantitatively very minor malarial proteins that can only be detected by methods which selectively analyse the subset of proteins on the erythrocyte surface.
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PMID:Protein antigens of Plasmodium knowlesi clones of different variant antigen phenotype. 671 54

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

In the present study, we describe a polymerase chain reaction (PCR)-based enzyme-linked immunosorbent assay for the detection of malaria infection. The target region of the 18S ribosomal DNA is amplified by a PCR using an 18S rRNA, genus-specific, biotinylated (5') and an unlabeled primer (3') pair. The detection probes are digoxigenin-labeled DNA oligonucleotides derived from species-specific rRNA sequences. The amplified fragments are allowed to hybridize with the species-specific, digoxigenin-labeled oligonucleotide probes. The oligo/DNA complex is allowed to bind onto streptavidin-coated microtiter plates, followed by incubation with a peroxidase-streptavidin conjugate and a colorimetric-peroxidase substrate. The resulting test demonstrated specificity for the four human Plasmodium species, and was able to detect a level of parasitemia of at least 0.0001% in a laboratory-induced P. falciparum infection in monkeys. This liquid hybridization assay is sensitive, specific, simple, and reliable, with wide applicability in epidemiologic studies, accurate detection of mixed infections, detection of low-level parasitemia, and evaluation of chemotherapy and vaccine efficacy.
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PMID:Polymerase chain reaction and a liquid-phase, nonisotopic hybridization for species-specific and sensitive detection of malaria infection. 787 40


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