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

The soluble amphiphilic glycoprotein, Ag1 (gp60), purified from supernatants of in vitro cultures of Plasmodium falciparum has a molecular mass of 60 kDa and did not exhibit size variation in the different P. falciparum isolates tested by immunoblotting. Ag1 was shown to interact with the lectin Erythrina christagalli agglutinin, which is specific for carbohydrates bearing beta-D-galactose(1-4)-D-N-acetylglucosamine. Indirect immunofluorescence studies showed that Ag1 is located on the surface of trophozoites and schizonts but not on the surface of merozoites. Ag1 is recognized by human immune sera from six different malaria-endemic regions. Ag1 induces in vitro proliferation of lymphocytes from malaria-immune individuals in an antigen-specific manner.
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PMID:Biochemical characterization, localization and immunostimulating properties of a soluble glycoprotein, Ag1, isolated from in vitro cultures of Plasmodium falciparum. 225 Dec 41

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.
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PMID:Urinary proteins of tubular origin: basic immunochemical and clinical aspects. 225 76

A high-performance liquid chromatographic (HPLC) assay was developed for pyrimethamine in plasma, red blood cells (RBCs), and buffer for the purpose of studying its plasma protein binding and RBC partitioning. Pyrimethamine (1000 ng/ml) was 94% bound to plasma proteins on average, depending on the pH of plasma. A comparison of the lower and upper range of plasma concentrations that would be achieved after a malaria prophylaxis dosing regimen (25 mg/week) showed that the fraction unbound was significantly lower at 120 ng/ml than at the upper plasma concentration of 360 ng/ml, 3.5 vs 4.9%, respectively. Nonlinear regression of the effect of albumin concentration (g/L) on plasma binding yielded the equation: fraction unbound = 1/[(0.421 * albumin concentration) + 1] (R2 = 0.99). There was no binding to normal levels of alpha 1-acid glycoprotein (AAG). The mean ratio of the concentration of pyrimethamine in RBCs to that in plasma (RBC:plasma ratio) was 0.42, while the mean RBC:buffer ratio was 5.2. Binding to hemolysate did not account for all of the RBC uptake, suggesting that binding to or partitioning into RBC membranes may be important. Because pyrimethamine binding depends on both albumin concentration and pyrimethamine concentration in the plasma, these studies predict greater free fractions of pyrimethamine associated with the higher doses given for toxoplasmosis (75 mg/day) and with the hypoalbuminemia associated with AIDS and malaria.
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PMID:Binding of pyrimethamine to human plasma proteins and erythrocytes. 228 Oct 36

Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite from splenic destruction and may play a role in the pathogenesis of cerebral malaria. Correlates of sequestration have been developed in vitro using cultured human endothelium and an amelanotic melanoma cell line. Knobless strains (K-) of P. falciparum fail to sequester in vivo and to bind to cells in vitro. We now present evidence that the receptor for cytoadherence is the glycoprotein, thrombospondin. Aotus monkey or human erythrocytes containing knobby (K+) but not Aotus erythrocytes containing knobless strains of P. falciparum bind to immobilized thrombospondin. Neither binds to the adhesive proteins laminin, fibronectin, factor VIII/von Willebrand factor or vitronectin. Both soluble thrombospondin and anti-thrombospondin antibodies inhibit binding of parasitized Aotus erythrocytes to immobilize thrombospondin and to melanoma cells which secrete thrombospondin.
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PMID:Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. 241 70

DNA fragments from human malaria parasites were cloned into lambda gt11 to produce a genomic DNA expression library. A pool of monoclonal antibodies (mAbs) recognizing three domains of the 195-kDa major merozoite surface glycoprotein (gp195) reacted with seven clones expressing malaria antigens. mAbs recognizing the 83-kDa product of gp195 reacted with the clones, but mAbs recognizing a glycosylated 45-kDa and a nonglycosylated 45-kDa domain did not. Restriction enzyme mapping revealed that the clones contained overlapping segments encoding about 70% of the gene beginning at the 5' end and ending at an EcoRI restriction enzyme site 3.3 kilobase pairs downstream. The mAbs recognizing the 83-kDa domain reacted differently with the clones, allowing the mapping of three epitopes, one of which was repetitive. Affinity-purified antibodies were selected from immune monkey serum with recombinant expression proteins adsorbed to nitrocellulose filters. When used to probe electrophoretic immunoblots of parasite extracts, these antigen-selected antibodies reacted with specific sets of processed products of gp195, including those associated with the 83- and the nonglycosylated 45-kDa domains. This information, combined with the mAb epitope map, allowed a tentative scheme for processing gp195 from the Camp strain to be proposed.
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PMID:Epitope map and processing scheme for the 195,000-dalton surface glycoprotein of Plasmodium falciparum merozoites deduced from cloned overlapping segments of the gene. 242 62

Merozoites of the human malaria parasite Plasmodium falciparum express on their surface several antigens derived from a polymorphic glycoprotein precursor of Mr 185,000 synthesised earlier on by trophozoites and schizonts. A panel of 18 monoclonal antibodies against a range of different specificities of the precursor was used to characterise its mature products in spontaneously released merozoites. Merozoites released by [35S]methionine or [14C]glucosamine-labelled schizonts, or surface 125I-labelled purified merozoites, were extracted in detergents, and the antigens were detected by immunoprecipitation or Western blotting. We show that a nonglycosylated peptide of Mr 80,000 and two glycosylated fragments of Mr 40,000 and Mr 16,000, all derived from the precursor, are exposed on the surface of the mature merozoite. Precipitations from extracts in different detergents indicate that the 80 and 40 kDa fragments can form a non-covalent complex with each other and two additional major surface antigens of 36 and 22 kDa. Several antibodies react strongly with the complex but not with its dissociated subunits, thus indicating presence of conformational epitopes. Other epitopes are positively mapped on different dissociated subunits by immunoprecipitation and Western blotting. The 80 and 40 kDa antigens each carry a different polymorphic marker epitope, and both of these markers are absent on the 16 kDa fragment. The 40 and 16 kDa glycoproteins share common epitopes, and the latter may be derived from the former fragments. Only epitopes present on the 16 kDa antigen, but not those specific for the larger fragments, are detectable by immunofluorescence in the ring-stage. This indicates that the whole or a part of the 16 kDa antigen remains on the parasite through the invasion process.
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PMID:Fragments of the polymorphic Mr 185,000 glycoprotein from the surface of isolated Plasmodium falciparum merozoites form an antigenic complex. 243 53

Schizonts of the malaria parasite Plasmodium falciparum synthesize a 195 kDa surface glycoprotein (gp195) that is processed into several smaller products including one of 83 kDa, which, in the case of the Camp strain, is sequentially processed into 73 and 67 kDa products. gp195 and its processing intermediates larger than 83 kDa were not precipitated from culture supernates, but the 83 and 73 kDa products were precipitated by three monoclonal antibodies (McAbs). The 83 and 73 kDa products were affinity purified from culture supernates by adsorbing to McAb 7B2 coupled to Affigel 10 and eluting either with 0.2 N acetic acid, pH 2.8, or with 3 M potassium isothiocyanate (KSCN). The epitope recognized by McAb 7B2 was denatured by acid elution but could be regenerated by treating with 8 M urea followed by dialysis. The implications of renaturing antigens to regenerate epitopes should be considered in studies on the purification, function and immunogenicity of malaria antigens.
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PMID:Characterization of gp195 processed products purified from Plasmodium falciparum culture supernates. 244 21

Racemic verapamil and close structural derivatives gallopamil and devapamil completely reverse chloroquine-resistance in falciparum malaria at 1-2 micromolar concentrations. If the R-(+) isomers of these calcium channel inhibitors are used, chloroquine-resistance is again completely reversed at similar doses. However, these R-(+) isomers do not bind to cardiovascular calcium channels which are stereospecific for the S-(-) isomer of the drugs. Further since calcium channel inhibition is not involved, toxicity associated with this activity can be avoided. Therefore it is possible that a series of R-(+) isomers could be found that alter the resistant state without possessing significant toxicity. It is postulated that these lipophilic drugs are interacting with the mechanism of resistance, possibly a multidrug resistance glycoprotein pump.
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PMID:Reversal of chloroquine resistance in falciparum malaria independent of calcium channels. 245 7

A short-term in vitro culture system that allows for significant re-invasion of target erythrocytes by Plasmodium vivax was used to study the role of the Duffy blood group antigen as a ligand for merozoite invasion by this human malaria species. Using human Duffy-positive and -negative erythrocytes, various primate erythrocytes, enzymatic modification of erythrocytes, and mAb that defines a new Duffy determinant (Fy6) we conclude that the erythrocyte glycoprotein carrying Duffy determinants is required as a ligand for the invasion of human erythrocytes by P. vivax merozoites. Blockade of invasion by Fab fragments of the anti-Fy6 mAb equal to that of the intact molecule and the correlation of P. vivax susceptibility with the presence of the Fy6 determinant suggests this epitope or a nearby domain may be an active site on the Duffy glycoprotein. However, as for P. knowlesi, there is evidence that an alternate pathway for P. vivax invasion of simian erythrocytes may exist.
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PMID:In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax. 246 69

Plasmodium falciparum-infected erythrocytes (IE) specifically adhere to vascular endothelium in vivo and to human endothelial cells, some human melanoma cell lines, and human monocytes in vitro. The tissue cell receptor for a ligand on the surface of the infected erythrocytes is an Mr 88,000 glycoprotein (GP88) recognized by the MAb OKM5, which also blocks cytoadherence of IE. Isolated, affinity-purified GP88 (CD36) competitively blocks cytoadherence and when absorbed to plastic surfaces, specifically binds P. falciparum IE. Additionally, monoclonal and polyclonal antibodies to GP88 block cytoadherence to both target cells and immobilized GP88. Binding to GP88 by IE is unaffected by the absence of calcium or the absence of thrombospondin, a putative mediator for cytoadherence of P. falciparum IE. Thus, GP88 (CD36), which has been demonstrated to be the same as platelet glycoprotein IV, interacts directly with P. falciparum IE, presumably via a parasite-induced ligand exposed on the surface of the infected erythrocytes. CD36 is shown to be present on brain endothelium in both individuals without malaria and individuals with cerebral malaria. This would suggest that factors other than just cerebral sequestration of IE play an initiating role in the genesis of cerebral malaria.
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PMID:A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. 247 74


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