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 acute-phase response to infection alters the plasma concentrations of most biochemical measures of iron status, rendering assessment of status difficult. Soluble transferrin receptors (TfR) may be an exception but have not been examined longitudinally during the major metabolic and inflammatory changes which occur during clinical malaria. Blood samples were collected daily during hospitalization, and again at a follow-up 2-6 weeks after discharge, from adult, mainly European, patients (n = 49) who developed uncomplicated Plasmodium falciparum malaria following visits to endemic areas. Parasitaemia and plasma concentrations of ferritin, TfR, C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT) were measured. The concentrations of CRP, AGP and ACT correlated highly (P < 0.001) with each other and with plasma ferritin, and were significantly higher (P < 0.05) at all time points in hospital compared to the follow-up. TfR concentration correlated negatively and significantly (P < 0.05) with AGP and CRP but not with ACT or ferritin, and was significantly lower (around 30%) at all time points in hospital compared to follow-up, although in only 1 subject did it ever fall outside the normal reference range. In areas where both iron deficiency and clinical episodes of malaria are common, plasma TfR values need to be interpreted cautiously as indicators of iron status.
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PMID:Impact of acute malaria on plasma concentrations of transferrin receptors. 1097 4

Sequestration of malaria-infected erythrocytes in the peripheral circulation has been associated with the virulence of Plasmodium falciparum. Defining the adhesive phenotypes of infected erythrocytes may therefore help us to understand how severe disease is caused and how to prevent or treat it. We have previously shown that malaria-infected erythrocytes may form apparent autoagglutinates of infected erythrocytes. Here we show that such autoagglutination of a laboratory line of P. falciparum is mediated by platelets and that the formation of clumps of infected erythrocytes and platelets requires expression of the platelet surface glycoprotein CD36. Platelet-dependent clumping is a distinct adhesive phenotype, expressed by some but not all CD36-binding parasite lines, and is common in field isolates of P. falciparum. Finally, we have established that platelet-mediated clumping is strongly associated with severe malaria. Precise definition of the molecular basis of this intriguing adhesive phenotype may help to elucidate the complex pathophysiology of malaria.
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PMID:Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. 1117 32

We characterize a novel hemocyte-specific acute phase glycoprotein from the malaria vector, Anopheles gambiae. It shows substantial structural and functional similarities, including the highly conserved thioester motif, to both a central component of mammalian complement system, factor C3, and to a pan-protease inhibitor, alpha2-macroglobulin. Most importantly, this protein serves as a complement-like opsonin and promotes phagocytosis of some Gram-negative bacteria in a mosquito hemocyte-like cell line. Chemical inactivation by methylamine and depletion by double-stranded RNA knockout demonstrate that this function is dependent on the internal thioester bond. This evidence of a complement-like function in a protostome animal adds substantially to the accumulating evidence of a common ancestry of immune defenses in insects and vertebrates.
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PMID:Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. 1125 25

A 31-kDa glycoprotein antigen was purified by electrophoresing the crude extract of Parastrongylus cantonensis adult worms in a 12% SDS-polyacrylamide gel, identifying the 31-kDa component with prestained molecular weight standards, cutting the desired gel strip, and then isolating it by electroelution. Antigen fraction of 31 kDa was re-electrophoresed, transferred to a nitrocellulose membrane and found to be reactive with only the sera from patients with parastrongyliasis. No reactive band was observed with the sera from other related parasitic infections, eg, gnathostomiasis, toxocariasis, filariasis, paragonimiasis, cysticercosis and malaria, and the normal healthy control sera. This antigen fraction isolated showed 100% sensitivity and 100% specificity in the enzyme-linked immunosorbent assay (ELISA) for the detection of 31-kDa specific antibody in the sera from patients with parastrongyliasis. The P. cantonensis antigen of 31 kDa has been obtained by this means with a high degree of purity and applied successfully in conventional ELISA for the specific immunodiagnosis of human parastrongyliasis.
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PMID:Purification of a specific immunodiagnostic Parastrongylus cantonensis antigen by electroelution from SDS-polyacrylamide gels. 1155 81

Anemia is an important complication of malaria, and its pathogenesis is not well understood. To gain insight into potential age-related relationships between tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), erythropoietin, and anemia during acute malaria, 273 children of ages 12 to 120 months presenting with acute, uncomplicated malaria in Kampala, Uganda, were monitored at enrollment and 3 and 7 days later. Younger children had higher geometric mean erythropoietin, TNF-alpha, and alpha(1)-acid glycoprotein (AGP) concentrations than older children. Univariate regression analysis revealed that age, log(10) erythropoietin levels, IL-10/TNF-alpha ratio, and AGP levels were each significantly associated with hemoglobin levels at baseline. Hemoglobin concentrations were inversely correlated with the log(10) erythropoietin level at all three visits. For the older age groups, higher levels of TNF-alpha were significantly associated with higher IL-10 levels at all three visits, but this relationship was significant only at baseline for younger children. These data suggest that younger children do not maintain IL-10 production in response to the inflammatory process, and this mechanism may contribute to the more severe anemia found in younger children. Acute malaria is an illness whose incidence and severity are largely age dependent. Further studies are needed to understand the relationships between age-related immune responses to malaria and their role in the pathogenesis of malarial anemia.
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PMID:Anemia and interleukin-10, tumor necrosis factor alpha, and erythropoietin levels among children with acute, uncomplicated Plasmodium falciparum malaria. 1168 58

The adherence of Plasmodium falciparum-infected RBC (IRBC) to postcapillary venular endothelium is an important determinant of the pathogenesis of severe malaria complications. Cytoadherence of IRBC to endothelial cells involves specific receptor/ligand interactions. The glycoprotein CD36 expressed on endothelial cells is the major receptor involved in this interaction. Treatment of CD36-expressing cells with reducing agents, such as DTT and N-acetylcysteine, was followed by CD36 conformational change monitorable by the appearance of the Mo91 mAb epitope. Only a fraction of the surface expressed CD36 molecules became Mo91 positive, suggesting the presence of two subpopulations of molecules with different sensitivities to reduction. The Mo91 epitope has been localized on a peptide (residues 260-279) of the C-terminal, cysteine-rich region of CD36. Treatment with reducing agents inhibited the CD36-dependent cytoadherence of IRBC to CD36-expressing cells and dissolved pre-existent CD36-mediated IRBC/CD36-expressing cell aggregates. CD36 reduction did not impair the functionality of CD36, since the reactivity of other anti-CD36 mAbs as well as the binding of oxidized low density lipoprotein, a CD36 ligand, were maintained. The modifications induced by reduction were reversible. After 14 h CD36 was reoxidized, the cells did not express the Mo91 epitope, and cytoadherence to IRBC was restored. The results indicate that IRBCs bind only to a redox-modulated fraction of CD36 molecules expressed on the cell surface. The present data indicate the therapeutic potential of reducing agents, such as the nontoxic drug N-acetylcysteine, to prevent or treat malaria complications due to IRBC cytoadhesion.
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PMID:Cytoadherence of Plasmodium falciparum-infected erythrocytes is mediated by a redox-dependent conformational fraction of CD36. 1171 19

Trypanosomes do not inhabit or grow in anopheles mosquitoes, the vector for the transmission of Plasmodium parasites the causative agent for malaria. The possession of lytic factors by the anopheline mosquito was thus considered. Head and midgut sections prepared in phosphate buffered saline were tested for trypanocidal action against T. congolense. While the head section was inactive towards the trypanosomes, the midgut extract at 0.2 mg ml(-1) diminished the motility of the parasites within 2 min of incubation; killing 50% of the population after 5 min. At 0.5 mg ml(-1) of the extract, about 90% of the parasites were killed within 2 min of incubation. The midgut fraction was subjected to a purification protocol involving successive chromatography on: octyl-sepharose, reactive brown agarose and fetuin-agarose columns. A final trypanocidal active fraction (gp45), which moved homogeneously during electrophoresis as a 45-kDa protein, was recovered from the fetuin-agarose column. The protein reacted positively with thiobarbituric acid, which suggests it is a sialoglycoprotein. Desialylation of the glycoprotein nullified its trypanocidal activity on T. congolense. Similarly, when the saccharides, lactose, methyl-beta-galactoside, lactulose, methyl-umbelliferyl-beta-galactoside (MU-Gal), were included in the culture medium, they inhibited the gp45 trypanocidal activity. Asialo-fetuin and asialo-RBC also inhibited the gp45-induced killing of T. congolense cells. The potential use of anopheline 45 kDa protein in the production of transgenic tsetse flies (Glossina spp.) in the control of trypanosomiasis is discussed.
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PMID:A 45-kDa midgut glycoprotein from Anopheles albimanus mosquito mediates the killing of trypanosomes. 1212 3

CD40 ligand (CD40L), a glycoprotein involved in B cell proliferation, antigen presenting cell activation, and Ig class switching, is important in the immune response to infection. Rare coding mutations in CD40L can lead to life-threatening immunodeficiency but the potential for common variants to alter disease susceptibility remains to be explored. To identify polymorphisms in CD40L, we sequenced 2.3 kb of the 5' flanking region and the first exon of the gene in DNA samples from 36 Gambian females and one chimpanzee. Diversity was lower than the average reported for other areas of the X chromosome, and only two polymorphisms were identified. The polymorphisms were genotyped in DNA samples from 957 Gambian individuals, cases and controls from a study of severe malaria. A significant reduction in risk for severe malaria (OR = 0.52, P = 0.002) was associated with males hemizygous for the CD40L-726C. Analysis by transmission disequilibrium test of 371 cases, for whom DNA from both parents was also available, confirmed the result was not due to stratification (P = 0.04). A similar but non-significant trend was found in females. This preliminary association of a common variant in CD40L with a malaria resistance phenotype encourages further genetic characterization of the role of CD40L in infectious disease.
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PMID:CD40L association with protection from severe malaria. 1214 Jul 47

The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
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PMID:Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. 1255 30

Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.
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PMID:Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes. 1293 71


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