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

Synchronous cultures of Plasmodium falciparum were successively labelled with ((35)S)-methionine and both the supernatants and the pellets of infected red blood cells were collected. The release of TCA-precipitable material in the culture supernatants was low during the development of ring forms and trophozoites, increased during schizogony, and was maximum at the time of schizont rupture and merozoite reinvasion. Analysis of the supernatants by SDS - PAGE and autoradiography showed that both polypeptides common to the various developmental stages of the parasite and schizont/merozoite-specific polypeptides were released. Polypeptides of relative molecular mass 140 000, 82 000 and, to a lower degree, 41 000 were present in high amounts in the culture supernatants. These polypeptides have been shown to be the target of monoclonal antibodies that are able to inhibit the growth of P. falciparum cultures, and may be involved in protective immunity. The released polypeptides may also be used as target antigens in immunodiagnostic tests aiming at the detection of malaria infection.
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PMID:Plasmodium falciparum polypeptides released during in vitro cultivation. 634 Aug 46

Mitochondria of malaria parasites generate a membrane potential through an electron transport system that is a possible target of primaquine and a new anti-malarial drug, atovaquone. However, little information is available for conclusive understanding of the respiratory chain in Plasmodium mitochondria. In the present study, we cloned and characterized from Plasmodium falciparum the genes for the catalytic subunits, SDHA for the flavoprotein (Fp) and SDHB for iron-sulfur protein (Ip), of succinate-ubiquinone oxidoreductase (complex II), which is a marker enzyme for mitochondria and links the TCA cycle and respiratory chain directly. Each of the two genes contains a single open reading frame (ORF), which are located on different chromosomes, 1860 nucleotides on chromosome 10 for SDHA and 963 nucleotides on chromosome 12 for SDHB. The expression of these genes in asynchronous erythrocytic stage cells was confirmed by observation of 3.3 and 2.4 kb transcripts from the SDHA and SDHB genes, respectively. The SDHA and SDHB genes encode proteins of 620 (Fp) and 321 (Ip) amino acids with molecular masses of 69.2 and 37.8 kDa, respectively. A mitochondrial presequence essential for the import of mitochondrial proteins encoded by nuclear DNA, as well as almost all the conserved amino acids indispensable for substrate binding and the catalytic reaction were found in these peptides, indicating the functional importance of this enzyme in the parasite. Interestingly, a P. falciparum-specific insertion and a unicellular organism-specific deletion were found in the amino acid sequence of Fp. This is the first report of the primary structure of the protozoan succinate dehydrogenase.
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PMID:Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. 1077 96

Recent findings that levels of brain lactate and alanine were elevated in murine cerebral malaria led us to investigate the effect of dichloroacetate (DCA; 60 mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain metabolites, and on the survival of mice infected with Plasmodium berghei ANKA which normally causes lethal cerebral malaria. DCA significantly reduced brain lactate and alanine levels when administered to infected mice, had no effect on the TCA cycle-related metabolites glutamate, GABA and aspartate and was associated with increased brain glutamine levels: 40% of mice thus treated survived the normally lethal infection.
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PMID:Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a 1H-NMR study. 1093 96

The detection of antigen in the urine is increasingly being used for diagnosis of parasitic infections. A urinary antigen has recently been demonstrated in visceral leishmaniasis (VL), using a latex agglutination test. The results of our study show that the detected antigen is: heat-stable, precipitates with acetone and ethanol but not TCA, is sensitive to periodate and acid hydrolysis but not to pronase E, lipase, or neuraminidase. The antigen is a low molecular weight glycoconjugate that can be extracted by phenol-water, partitions into the aqueous phase when extracted with Triton X-114 or chloroform/methanol, and can be labelled by biotin hydrazide. Since this urinary antigen cannot be characterised by conventional SDS-PAGE and Western blotting, we used an affinity transfer blotting system in which antigens were captured onto nitro-cellulose paper previously coated with a specific antibody. Using this system a low molecular weight antigen (LMWA) spanning an area of the nitro-cellulose membrane corresponding to molecular weight of 5-20 kDa was detected in the urine of VL patients (from Nepal, Sudan, Brazil, Yemen and Spain) and of experimentally infected animals. No LMWA was detected in the urine of patients with malaria, schistosomiasis, or other nonparasitic diseases including typhoid and brucellosis. Immunoprecipitation, using antibody-coated latex, followed by immunoblotting showed that the LMWA is the target antigen in the previously described latex agglutination test ('KATEX'). The antigen is detectable in both the promastigote and amastigote stages of the parasite. Monoclonal antibodies (mAbs) against Leishmania glycoconjugates strongly react with this molecule. These results suggest that the detected antigen is highly specific and diagnostic for VL.
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PMID:Antigenuria in visceral leishmaniasis: detection and partial characterisation of a carbohydrate antigen. 1203 73

The dinoflagellates are an important group of eukaryotic, single celled algae. They are the sister group of the Apicomplexa, a group of intracellular parasites and photosynthetic algae including the malaria parasite Plasmodium. Many apicomplexan mitochondria have a number of unusual features, including the lack of a pyruvate dehydrogenase and the existence of a branched TCA cycle. Here, we analyse dinoflagellate EST (expressed sequence tag) data to determine whether these features are apicomplexan-specific, or if they are more widespread. We show that dinoflagellates have replaced a key subunit (E1) of pyruvate dehydrogenase with a subunit of bacterial origin and that transcripts encoding many of the proteins that are essential in a conventional ATP synthase/Complex V are absent, as is the case in Apicomplexa. There is a pathway for synthesis of starch or glycogen as a storage carbohydrate. Transcripts encoding isocitrate lyase and malate synthase are present, consistent with ultrastructural reports of a glyoxysome. Finally, evidence for a conventional haem biosynthesis pathway is found, in contrast to the Apicomplexa, Chromera and early branching dinoflagellates (Perkinsus, Oxyrrhis).
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PMID:An analysis of dinoflagellate metabolism using EST data. 2308 81

Malaria is a global infectious disease that threatens the lives of millions of people. Transcriptomics, proteomics and functional genomics studies, as well as sequencing of the Plasmodium falciparum and Homo sapiens genomes, have shed new light on this host-parasite relationship. Recent advances in accurate mass measurement mass spectrometry, sophisticated data analysis software, and availability of biological pathway databases, have converged to facilitate our global, untargeted biochemical profiling study of in vitro P. falciparum-infected (IRBC) and uninfected (NRBC) erythrocytes. In order to expand the number of detectable metabolites, several key analytical steps in our workflows were optimized. Untargeted and targeted data mining resulted in detection of over one thousand features or chemical entities. Untargeted features were annotated via matching to the METLIN metabolite database. For targeted data mining, we queried the data using a compound database derived from a metabolic reconstruction of the P. falciparum genome. In total, over one hundred and fifty differential annotated metabolites were observed. To corroborate the representation of known biochemical pathways from our data, an inferential pathway analysis strategy was used to map annotated metabolites onto the BioCyc pathway collection. This hypothesis-generating approach resulted in over-representation of many metabolites onto several IRBC pathways, most prominently glycolysis. In addition, components of the "branched" TCA cycle, partial urea cycle, and nucleotide, amino acid, chorismate, sphingolipid and fatty acid metabolism were found to be altered in IRBCs. Interestingly, we detected and confirmed elevated levels for cyclic ADP ribose and phosphoribosyl AMP in IRBCs, a novel observation. These metabolites may play a role in regulating the release of intracellular Ca(2+) during P. falciparum infection. Our results support a strategy of global metabolite profiling by untargeted data acquisition. Untargeted and targeted data mining workflows, when used together to perform pathway-inferred metabolomics, have the benefit of obviating MS/MS confirmation for every detected compound.
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PMID:Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum. 2359 22

A significant fraction of global population is under the threat of malaria. Majority of annual death is due to the more complicated form of the infection i.e. the cerebral form, also known as Cerebral Malaria (CM). Host parasite interaction is known to cause a cascade of events in various tissues like brain, liver, kidney, and spleen. We have employed (1)H NMR based metabolomics to understand the specific perturbations of various tissues in CM. In our previous paper we have delineated the differences between CM vis-a-vis non-cerebral malaria (NCM) mice in serum, liver and brain. In this paper we focus on their differences of metabolic profile in kidney and spleen as kidney dysfunction and splenomegaly are known to be associated to neurological outcome of the disease. Moreover we have also looked into how the biological compartments (kidney, spleen and serum) interact with each other. The various metabolites involved in such interactions and their correlational aspects across the compartments have been studied in CM, NCM and control mice. The idea was to find out the specific pathways that are altered in CM mice. Our results demonstrate that both the kidney as well as spleen metabolism are differentially perturbed in CM with respect to NCM. The results point out that glutamate levels are decreased in CM mice with respect to NCM mice both in case of spleen and kidney while creatine, myo-inositol and betaine levels are increased in kidney of CM mice with respect to NCM mice. From the analysis of Multiway Principal Component Analysis (MPCA) we see that lipid metabolism and TCA cycle is altered in kidney and spleen.
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PMID:Metabolic perturbations of kidney and spleen in murine cerebral malaria: (1)H NMR-based metabolomic study. 2403 68