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)

Sera from 27 rhesus monkeys immunized in various ways against the H strain of Plasmodium knowlesi were analyzed by quantitative crossed immunoelectrophoresis. The reaction of the sera was compared with a reference immune serum only reactive with P. knowlesi-specific 65,000-Mr glycoprotein-immune component 13 (gp65/ic13) in membranes of infected rhesus monkey erythrocytes. Triton X-100-solubilized, 125I-labeled membranes of schizont-infected erythrocytes were used as an antigen. Sera from 9 or 10 monkeys immunized by repeated infections with P. knowlesi reacted with gp65/ic13. In 6 of 10 sera, anti-gp65/ic13 was the only antibody reacting with host cell membrane proteins. In contrast, vaccination of 15 monkeys with predominantly sexual stages or trophozoites of P. knowlesi in Freund complete adjuvant resulted in protection against blood challenges in 7 monkeys, only 2 of which contained precipitating antibody against gp65/ic13. None of the sera from monkeys not protected by infections or vaccinations contained detectable levels of precipitating antibodies against gp65/ic13. Our data indicate that gp65/ic13 acts as a prominent immunogen in vivo during natural p. knowlesi infections of rhesus monkeys. There is a positive correlation suggested between anti-gp65/ic13 antibody and protection in the monkeys analyzed. This correlation does not apply to monkeys protected against P. knowlesi malaria by vaccination, pointing to other effective immune defense mechanisms.
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PMID:Rhesus monkeys protected against Plasmodium knowlesi malaria produce antibodies against a 65,000-MrP. knowlesi glycoprotein at the surface of infected erythrocytes. 730 38

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

The surface glycoprotein CD36 (GPIV) is known to mediate the adhesion of Plasmodium falciparum malaria-infected red blood cells and to be a receptor for extracellular matrix proteins such as collagen and thrombospondin. The murine monoclonal IgM antibody NL07, which is specific for CD36, has now been shown to also be a potent inhibitor of the adhesion of P falciparum malaria-infected red blood cells to C32 melanoma cells. Treatment of platelets with NL07 monoclonal antibody resulted in rapid degranulation, release of ATP and serotonin, increase in [Ca2+]i, and tyrosine phosphorylation of a substrate protein of 130 kD. In about one-half of the experiments, activation with NL07 resulted in the formation of small aggregates of 10 to 30 platelets, whereas in the other half of the experiments, large aggregates were seen similar to those induced by adenosine diphosphate (ADP) and these large aggregates could be converted to the small aggregates by ATP alpha S or by AP-2 or other antibodies against GPIIb and/or IIIa. Microaggregates of 2 to 5 platelets were seen with Glanzmann's platelets that constitutively lack GPIIb/IIIa. Aggregate formation was not seen with heat-treated serum, in the presence of anti C1q antibodies, or when using C5-, C8-, or C9-deficient human sera. Although activation of platelets with purified complement components results in a slow morphologic change without aggregation, involvement of CD36 results in rapid complement-mediated activation leading to formation of small aggregates that is largely independent of GPIIb/IIIa and that, under certain circumstances, proceeds to the formation of large ADP-dependent aggregates.
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PMID:Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07. 750 21

We studied the brains of rhesus monkeys infected with the primate malaria parasite Plasmodium fragile. Electron microscopy showed that, in these animals, erythrocytes infected with P. fragile undergo sequestration and that parasitized red blood cells adhere to endothelial cells in the cerebral microvessels by means of knobs. Cerebral microvessels with sequestered parasitized red blood cells were shown by immunohistochemical analysis to possess the platelet glycoprotein CD36, thrombospondin, and intracellular adhesion molecule-1. The formation of rosettes also was observed in the cerebral microvessels. In a fashion similar to human cerebral malaria, P. fragile produced neurological symptoms in the animals. Thus, rhesus monkeys infected with P. fragile, like those monkeys infected with Plasmodium coatneyi, can be used as a primate model to study human cerebral malaria.
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PMID:A nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with Plasmodium fragile. 751 25

1. The major serum proteins which bind halofantrine were identified by size exclusion chromatography. In addition, the binding affinity of halofantrine to human erythrocytes and serum proteins was measured by an erythrocyte partitioning technique. The influence of serum-drug binding on the distribution of halofantrine in whole blood was estimated by simulating several disease-related changes in the levels of the most important binding proteins. 2. The chromatographic resolution of serum preincubated with halofantrine allowed a quantitative analysis of binding to low density lipoproteins, high density lipoproteins, alpha 1-acid glycoprotein and albumin using the erythrocyte partitioning technique. Very low density lipoproteins did not bind halofantrine to a significant extent. 3. In whole blood halofantrine is bound to serum proteins (83%) and to erythrocytes (17%). Low density lipoproteins (affinity constant nKP = 44.4 l g-1) and high density lipoproteins (nKP = 14.4 l g-1) were the most important binding proteins in serum. alpha 1-acid glycoprotein (nKP = 4.39 l g-1) and albumin (nKP = 0.27 l g-1) had relatively low binding affinities. 4. The concentration of serum proteins influences both the fraction of unbound drug and the fraction of drug associated with the erythrocytes. Changes in serum protein concentrations often encountered in malaria are likely to increase both the unbound fraction and the fraction bound to the erythrocytes.
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PMID:The antimalarial drug halofantrine is bound mainly to low and high density lipoproteins in human serum. 766 88

To test whether the requirements for GPI-attachment are the same in mammalian cells and parasitic protozoa, we expressed the GPI-linked variant surface glycoprotein (VSG) of Trypanosoma brucei (T. brucei) in COS cells. Although large amounts of VSG were produced, only a small fraction became GPI-linked. This impaired processing is not due to the VSG ectodomain since replacement of the VSG GPI-signal with that of decay accelerating factor (DAF) produced GPI-linked VSG. Further, whereas fusion of the DAF GPI-signal to the COOH-terminus of human growth hormone (hGH) produces GPI-linked hGH, an analogous fusion using the VSG GPI-signal does not, indicating that the VSG GPI-signal functions poorly in mammalian cells. By constructing chimeric VSG-DAF GPI-signals and fusing them to the COOH-terminus of hGH, we show that of the two critical elements that comprise the GPI-signal--the cleavage/attachment site and the hydrophobic domain--the former is responsible for the impaired activity of the VSG GPI-signal in COS cells. To confirm this, we show that the VSG GPI-signal can be converted to a viable signal for mammalian cells by altering the amino acid configuration at the cleavage/attachment site. We also show that when fused to hGH, the putative GPI-signal from the malaria circumsporozoite (CS) protein produces low levels of GPI-anchored hGH, suggesting that the CS protein is indeed GPI-linked, but that the CS protein GPI-signal, like the VSG-signal, functions poorly in COS cells.
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PMID:The requirements for GPI-attachment are similar but not identical in mammalian cells and parasitic protozoa. 808 Dec 28

The general features of the glycosylphosphatidylinositol (GPI) signal have been conserved in evolution. To test whether the requirements for GPI attachment are indeed the same in mammalian cells and parasitic protozoa, we expressed the prototype GPI-linked protein of Trypanosoma brucei, the variant surface glycoprotein (VSG), in COS cells. Although large amounts of VSG were produced, only a small fraction became GPI linked. This impaired processing is not caused by the VSG ectodomain, since replacement of the VSG GPI signal with that of decay accelerating factor (DAF) produced GPI-linked VSG. Furthermore, whereas fusion of the DAF GPI signal to the COOH terminus of human growth hormone (hGH) produces GPI-linked hGH, an analogous hGH fusion using the VSG GPI signal does not, indicating that the VSG GPI signal functions poorly in mammalian cells. By constructing chimeric VSG-DAF GPI signals and fusing them to the COOH terminus of hGH, we show that of the two critical elements that comprise the GPI-signal--the cleavage/attachment site and the COOH terminal hydrophobic domain--the former is responsible for the impaired activity of the VSG GPI signal in COS cells. To confirm this, we show that the VSG GPI signal can be converted to a viable signal for mammalian cells by altering the amino acid configuration at the cleavage/attachment site. We also show that when fused to the COOH terminus of hGH, the putative GPI signal from the malaria circumsporozoite (CS) protein produces low levels of GPI-anchored hGH, suggesting that the CS protein is indeed GPI linked, but that the CS protein GPI signal, like the VSG-signal, functions poorly in COS cells. The finding that the requirements for GPI attachment are similar but not identical in parasitic protozoa and mammalian cells may allow for the development of selective inhibitors of GPI-anchoring that might prove useful as antiparasite therapeutics.
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PMID:Requirements for glycosylphosphatidylinositol attachment are similar but not identical in mammalian cells and parasitic protozoa. 816 50

Serum retinol concentrations decrease during illness and thus may not accurately reflect the vitamin A status of populations with a high prevalence of illness. To quantify the contribution of illness to low serum retinol in a field study of children aged 6-59 mo in northern Ghana, serum retinol values were compared with two indicators of recent illness; symptoms reported by parents and acute-phase protein concentrations in serum. Serum retinol was not associated with symptoms of illness but showed a significant negative correlation with both alpha 1-acid glycoprotein (AGP) and serum amyloid A (SAA). Elevated AGP was associated with a 24% decrease in mean serum retinol. A large proportion of asymptomatic children had elevated AGP or SAA concentrations, suggesting that subclinical infections may have had important effects on serum retinol. A significant negative correlation between malaria parasite density and serum retinol indicated that malaria may have been one of the subclinical infections responsible. Measurement of AGP may improve interpretation of serum retinol data from populations with a high prevalence of morbidity.
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PMID:Influence of morbidity on serum retinol of children in a community-based study in northern Ghana. 833 47

The lack of efficient mechanisms for stable genetic transformation of medically important insects, such as anopheline mosquitoes, is the single most important impediment to progress in identifying novel control strategies. Currently available techniques for foreign gene expression in insect cells in culture lack the benefit of stable inheritance conferred by integration. To overcome this problem, a new class of pantropic retroviral vectors has been developed in which the amphotropic envelope is completely replaced by the G glycoprotein of vesicular stomatitis virus. The broadened host cell range of these particles allowed successful entry, integration, and expression of heterologous genes in cultured cells of Anopheles gambiae, the principle mosquito vector responsible for the transmission of over 100 million cases of malaria each year. Mosquito cells in culture infected with a pantropic vector expressing hygromycin phosphotransferase from the Drosophila hsp70 promoter were resistant to the antibiotic hygromycin B. Integrated provirus was detected in infected mosquito cell clones grown in selective media. Thus, pantropic retroviral vectors hold promise as a transformation system for mosquitoes in vivo.
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PMID:Pantropic retroviral vectors integrate and express in cells of the malaria mosquito, Anopheles gambiae. 865 Feb 40


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