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

Erythrocytes infected with Plasmodium vivax show unique ultrastructural changes which include membranous structures in the host cell cytosol, called clefts, and caveola-vesicle complexes (CVC) in the infected erythrocyte membrane. It has been suggested that the latter structures correspond with the Schuffner's dots observed on Giemsastained thin films. The subcellular localization of a 28 kDa and a 95 kDa antigen of the erythrocytic stages of P. vivax was determined by post-embedding immunoelectron microscopy. Four monoclonal antibodies (MAbs) (2H12.B4,2H8.E10, 1H4.B6, and 4C12.G4) against the 95 kDa protein reacted with the vesicles of CVC and vesicles scattered in the cytoplasm of the infected erythrocytes. Two other MAbs (4C12.B10 and 4D7.B1) against a 28 kDa protein reacted with the cytoplasmic clefts and were also reactive with the vesicles and electron dense materials in parasitophorous vacuole. These parasite-induced structures make a contribution to the movement of some malaria proteins from the parasite to the erythrocyte surface.
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PMID:Immunoelectron microscopic localization of vivax malaria antigens to the clefts and caveola-vesicle complexes of infected erythrocytes. 305 54

Cytidine diphosphate-diacylglycerol (CDP-DAG), an obligatory intermediate compound in the biosynthesis of the major anionic and zwitterionic phospholipids, is synthesized by CDP-DAG synthase (CDS). The gene encoding CDS was isolated from the human malaria parasite Plasmodium falciparum, based on sequence conservation to CDS from other organisms. The P. falciparum gene is located as a single copy on chromosome 14. The open reading frame (ORF) of PfCDS gene encodes a putative protein of 667 amino acids and 78 kDa. Only the C-terminal 422 amino acids share 40% homology with eukaryotic CDSs. The very long and non-conserved N-terminal region of 245 amino acids is hydrophilic and contains asparagine-rich and repetitive sequences. Two mRNA of 3.5 and 4 kb were detected. Transcription is developmentally regulated during the asexual intraerythrocytic cycle, being the weakest in the ring-stage. PfCDS enzyme activities in infected erythrocytes correlates with the transcription pattern, consistent with an increased synthesis of phospholipids in trophozoites and schizonts. Antisera raised against two synthetic peptides from the C-terminal region of PfCDS detected a single protein of 51 kDa in Western blot analysis, specific for parasitized erythrocytes. A protein of 28 kDa was recognized by an antiserum against an N-terminal peptide, indicating that PfCDS is proteolytically processed. Expression of 51- and 28-kDa proteins was developmentally regulated similar to regulation of the transcripts and the enzyme activity. The conserved C-terminal region of PfCDS, cloned into a eukaryote expression vector and transfected in COS-7 cells, showed a two-fold increase CDP-DAG synthase activities, indicating that the isolated gene most likely encoded the P. falciparum CDS enzyme.
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PMID:Characterization of Plasmodium falciparum CDP-diacylglycerol synthase, a proteolytically cleaved enzyme. 1098 48

Following gametogenesis and fertilisation in the bloodmeal within the mosquito midgut, the newly formed zygotes of the malaria parasite develop into motile invasive ookinetes. During this development, surface molecules are synthesised de novo including molecules of 21-28 kDa from the zygote-ookinete stages. An antiserum recognising a 26 kDa protein of Plasmodium berghei was used to clone the corresponding gene from a cDNA library, which was shown to be identical to the reported Pbs25 gene sequence. We show here that Pbs25 was detectable in preparations of gametes 30 min post-gametocyte activation, expression continued on zygotes, ookinetes and oocysts indicating there is a significant overlap of expression of the two immunogenic zygote-ookinete proteins belonging to the P25/28 protein family of sexual stage antigens. Biochemical analysis of Pbs25 demonstrates the presence of a malaria-specific glycosylphosphatidylinositol (GPI) anchor. Antibodies recognising Pbs25 impaired parasite development in the mosquito.
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PMID:Characterisation and expression of pbs25, a sexual and sporogonic stage specific protein of Plasmodium berghei. 1098 52

The epidemiological coexistence of schistosomiasis and malaria is frequently observed in developing countries. Co-infection with malaria in children could influence the development of acquired immunity associated with the resistance or the pathology of schistosomiasis. In the present study, performed during May to June 1996 in Senegal, the humoral immune response to Schistosoma haematobium 28 kDa glutathione S-transferase (Sh28GST) vaccinal antigen and to soluble egg antigens (SEA) has been evaluated in individuals infected by S. haematobium. Specific immunoglobulin G3 (IgG3) and IgE responses were significantly higher in co-infected children with Plasmodium falciparum compared with children infected with S. haematobium only. In addition, circulating levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble tumor necrosis factor receptor II (sTNF-RII), 3 parameters associated with schistosomiasis morbidity, were significantly increased in co-infected children. Taken together, this study indicated that malaria co-infection can both influence the acquired specific immune response to schistosome antigens and unbalance the regulation of inflammatory factors closely involved in schistosomiasis pathology.
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PMID:Malaria co-infection in children influences antibody response to schistosome antigens and inflammatory markers associated with morbidity. 1522 60

Malaria caused by protozoan parasites belonging to the genus Plasmodium is a dreaded disease, second only to tuberculosis. The emergence of parasites resistant to commonly used drugs and the lack of availability of vaccines aggravates the problem. One of the preventive approaches targets adhesion of parasites to host cells and tissues. Adhesion of parasites is mediated by proteins called adhesins. Abrogation of adhesion by either immunizing the host with adhesins or inhibiting the interaction using structural analogs of host cell receptors holds the potential to develop novel preventive strategies. The availability of complete genome sequence offers new opportunities for identifying adhesin and adhesin-like proteins. Development of computational algorithms can simplify this task and accelerate experimental characterization of the predicted adhesins from complete genomes. A curated positive dataset of experimentally known adhesins from Plasmodium species was prepared by careful examination of literature reports. "Controversial" or "hypothetical" adhesins were excluded. The negative dataset consisted of proteins representing various intracellular functions including information processing, metabolism, and interface (transporters). We did not include proteins likely to be on the surface with unknown adhesin properties or which are linked even indirectly to the adhesion process in either of the training sets. A nonhomology-based approach using 420 compositional properties of amino acid dipeptide and multiplet frequencies was used to develop MAAP Web server with Support Vector Machine (SVM) model classifier as its engine for the prediction of malarial adhesins and adhesin-like proteins. The MAAP engine has six SVM classifier models identified through an exhaustive search from 728 kernel parameters set. These models displayed an efficiency (Mathews correlation coefficient) of 0.860-0.967. The final prediction P(maap) score is the maximum score attained by a given sequence in any of the six models. The results of MAAP runs on complete proteomes of Plasmodium species revealed that in Plasmodium falciparum at P(maap) scores above 0.0, we observed a sensitivity of 100% with two false positives. In P. vivax and P. yoelii an optimal threshold P(maap) score of 0.7 was optimal with very few false positives (upto 5). Several new predictions were obtained. This list includes hypothetical protein PF14_0040, interspersed repeat antigen, STEVOR, liver stage antigen, SURFIN, RIFIN, stevor (3D7-stevorT3-2), mature parasite-infected erythrocyte surface antigen or P. falciparum erythrocyte membrane protein 2, merozoite surface protein 6 in P. falciparum, circumsporozoite proteins, microneme protein-1, Vir18, Vir12-like, Vir12, Vir18-like, Vir18-related and Vir4 in P. vivax, circumsporozoite protein/thrombospondin related anonymous proteins, 28 kDa ookinete surface protein, yir1, and yir4 of P. yoelii. Among these, a few proteins identified by MAAP were matched with those identified by other groups using different experimental and theoretical strategies. Most other interspersed repeat proteins in Plasmodium species had lower P(maap) scores. These new predictions could serve as new leads for further experimental characterization (MAAP webserver: http://maap.igib.res.in).
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PMID:MAAP: malarial adhesins and adhesin-like proteins predictor. 1787 44

The P28 family of proteins are 28 kDa proteins expressed on the surface of sexual stages--zygote, ookinete and young oocyst stages--of Plasmodium species when the parasite resides inside the mosquito midgut. Together with P25 proteins, P28 proteins protect the parasite from the harsh proteolytic environment prevailing inside the mosquito midgut. Vaccines against these proteins induce antibodies in vertebrate hosts that are capable of inhibiting parasite development in the mosquito midgut, thus preventing transmission of the parasite from the mosquito to another human host. These transmission-blocking vaccines are helpful in reducing the burden caused by malaria, which affects 300-600 million, and kills 1-3 million, people annually. The purpose of this study was to structurally characterise six members of the P28 family of ookinete surface proteins with the help of homology modelling, to compare these proteins in terms of transmission blocking and host parasite interactions, and to analyse phylogenetic relationships within the P28 family and with the P25 family. Our results indicate that all the members of the P28 family studied have four EGF domains arranged in triangular fashion with a very big C loop present in EGF domain IV, which could serve as a diagnostic feature of the P28 family as this loop is absent in the P25 family of ookinete surface proteins. The models of the P28 family of ookinete surface proteins obtained may help in understanding the biology of the parasite inside the mosquito midgut, and in designing transmission-blocking vaccines against malaria in the absence of experimentally determined structures of these important surface proteins.
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PMID:A very large C-loop in EGF domain IV is characteristic of the P28 family of ookinete surface proteins. 1905 32

Peter Agre, born in 1949 in Northfield Minnesota, shared the 2003 Nobel Prize in Chemistry with Roderick MacKinnon for his discovery of aquaporins, the channel proteins that allow water to cross the cell membrane. Agre's interest medicine was inspired by the humanitarian efforts of the Medical Missionary program run by the Norwegians of his home community in Minnesota. Hoping to provide new treatments for diseases affecting the poor, he joined a cholera laboratory during medical school at Johns Hopkins. He found that he enjoyed biomedical research, and continued his laboratory studies for an additional year after medical school. Agre completed his clinical training at Case Western Hospitals of Cleveland and the University of North Carolina, and returned to Johns Hopkins in 1981. There, his serendipitous discovery of aquaporins was made while pursuing the identity of the Rhesus (Rh) antigen. For a century, physiologists and biophysicists had been trying to understand the mechanism by which fluid passed across the cell's plasma membrane. Biophysical evidence indicated a limit to passive diffusion of water, suggesting the existence of another mechanism for water transport across the membrane. The putative "water channel," however, could not be identified. In 1988, while attempting to purify the 30 kDa Rh protein, Agre and colleagues began investigating a 28 kDa contaminant that they believed to be a proteolytic fragment of the Rh protein. Subsequent studies over the next 3-4 years revealed that the contaminant was a membrane-spanning oligomeric protein, unrelated to the Rh antigen, and that it was highly abundant in renal tubules and red blood cells. Still, they could not assign a function to it. The breakthrough came following a visit with his friend and former mentor John Parker. After Agre described the properties of the mysterious 28 kDa protein, Parker suggested that it might be the long-sought-after water channel. Agre and colleagues tested this idea by expressing the protein in Xenopus oocytes, which typically have low water permeability. When the test oocytes were placed in a hypotonic solution, they swelled and exploded, thus revealing the function of the unknown protein as a water channel, which they named aquaporin. The Nobel Prize enabled Agre to take his research and scientific interests in new directions. He felt that over the years his work had continually taken him further from his original interests in third-world diseases, so he shifted his focus back in that direction. He now serves as the director of the Malaria institute at Johns Hopkins where he has applied his knowledge to the study of the malarial parasite and the Anopheles mosquito, which both express aquaporins. In addition, since winning the Nobel Prize, he has enjoyed increased opportunities for bringing science to the public and for "encouraging young people to go into science."
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PMID:The 2009 Lindau Nobel Laureate Meeting: Peter Agre, Chemistry 2003. 2001 May 39

To develop a vivax malaria vaccine for blocking malarial transmission, the ookinete surface protein Pvs28 was cloned from Korean malaria patients using polymerase chain reaction. The Pvs28 gene consists of 726bp and encodes 241 amino acids. It was subcloned into the expression vector pQE30 and expressed in Escherichia coli. The expressed recombinant protein, rPvs28, has a molecular weight of about 28 kDa in SDS-PAGE analysis. A monoclonal antibody against rPvs28 was produced using BALB/c mice. It inhibited sporozoite development in Anopheles sinensis mosquitoes (n = 81) which is one of the malaria vectors in Korea, with relatively high antibody titer against rPv28 persisting for more than 6 months. These results indicate that rPvs28 induces an immune response in mice that effectively blocks sporozoite development in mosquitoes. Therefore it could be a vaccine candidate for preventing vivax malaria in Korea.
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PMID:The role of Pvs28 in sporozoite development in Anopheles sinensis and its longevity in BALB/c mice. 2080 Nov 17