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)

Elucidation of the complete amino acid sequence of TSP has suggested plausible explanations for all of the earlier observations on TSP structure and has already suggested new and interesting avenues of investigation aimed at determining the precise function and mechanism of TSP action as a matrix protein. The potential for Ca++-regulated exposure of the RGDA sequence could represent a new level of control for this important recognition system. We have already shown that the binding of TSP to collagen is modulated by the binding of Ca++ to this region of TSP. That is, high Ca++ results in a lower affinity of TSP for collagen, whereas lower Ca++ concentrations enhance the affinity of this interaction. The highly conserved, although short, 15-residue segment, which is nearly identical to region II of the sporozoite malaria protein, may indicate that TSP interacts with a receptor on liver cells, which the malaria parasite uses to gain its initial toehold in the body. If so, this would be another example of pathogenic organisms using a preexisting host recognition system to gain entry to cells where it can multiply. The collagen propeptide-like segment occurs in the collagen-binding domain of TSP and thus may represent the site at which TSP interacts with the collagens. These speculations form the starting point for many exciting lines of experimentation, which will provide us with a better understanding of the role of TSP in hemostasis, in the matrix of a variety of cells, and in development.
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PMID:Structure of human thrombospondin: complete amino acid sequence derived from cDNA. 368 18

Multiresistant Plasmodium falciparum malaria is a major threat to travelers to subSaharan Africa. However, even if chemoprophylaxis does not prevent clinical malaria in some individuals, it does lead to a reduction in the severity of the disease.1 In Sweden, we have recently seen five patients with malaria (three due to P. ovale and two due to P. falciparum) who have used homeopathic drugs for prophylaxis during visits to West Africa. We are concerned about this incidence and afraid that reduced confidence in modern medical malaria prophylaxis will encourage some individuals to try totally ineffective alternatives. Three women (57, 40, and 39 years old) visited Guinea Conacry in January 1995 as members of a group of 24 persons learning about African dances. The 57-year-old woman took mefloquine irregularly but vomited each time after intake. She also used Spenglersan M, which is a homeopathic drug that is administered (one drop daily in the bend of the arm) as malaria prophylaxis. The two other women used Spenglersan M only. They all fell ill with P. ovale malaria despite ongoing intake. Spenglersan M is said to contain both antigen from P. falciparum and antibodies against the parasite diluted to 1:1,000,000,000 concentration. The fourth case was a 26-year-old man who visited Ghana and Burkina Faso in October and November 1994. He used China D-6 for prophylaxis. This is a homeopathic preparation of the bark from the cinchona tree. Not even trace amounts of quinine were found in the tablets with a very sensitive high-performance liquid chromatographic method.2 Four days after returning from Africa he fell ill with P. falciparum malaria and received sulphadoxine-pyrimethamine treatment. After clinical relapse (RI), mefloquine was given and the patient was eventually cured. The fifth case was a 34-year-old woman admitted to hospital because of P. falciparum malaria after a visit to Guinea Conacry in January 1995. She had taken a homeopathic drug, Charaka comp 118, as prophylaxis. The drug is said to contain different extracts from herbs diluted 30 times. At first she refused to stay in hospital, but 2 days later she was readmitted and treated in the intensive care unit because of severe malaria with hypotonia and anemia. She had hyperparasitemia with 23% infected erythrocytes. Exchange transfusion was done, quinine was given, and the patient recovered without sequelae. The mortality is about 1% in people with P. falciparum infection.3 We therefore urge the readers to stand up against the dangerous use of homeopathic drugs and instead motivate travelers to use protective malaria prophylaxis.
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PMID:Homeopathic Resistant Malaria. 981 26

Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undue mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.
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PMID:Induction of mosquitocidal activity in mice immunized with Anopheles gambiae midgut cDNA. 1265 23

The Anopheles gambiae adult peritrophic matrix protein 1 (AgAper1) regulatory elements were used to drive the expression of phospholipase A2 (PLA2), a protein known to disrupt malaria parasite development in mosquitoes. These AgAper1 regulatory elements were sufficient to promote the accumulation of PLA2 in midgut epithelial cells before a blood meal and its release into the lumen upon blood ingestion. Plasmodium berghei oocyst formation was reduced by approximately 80% (74-91% range) in transgenic mosquitoes. Blood-seeking behaviour and survival of AgAper1-PLA2 transgenic mosquitoes were comparable to sibling wild-type mosquitoes, while fertility was substantially lower. Ultrastructural studies suggest that decreased fitness is a consequence of internal damage to midgut epithelial cells.
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PMID:Driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with AgAper1 regulatory elements. 1592 96

Plasmodium falciparum, the causative agent of malaria, relies on a sophisticated protein secretion system for host cell invasion and transformation. Although the parasite displays a secretory pathway similar to those of all eukaryotic organisms, a classical Golgi apparatus has never been described. We identified and characterised the putative Golgi matrix protein PfGRASP, a homologue of the Golgi re-assembly stacking protein (GRASP) family. We show that PfGRASP is expressed as a 70 kDa protein throughout the asexual life cycle of the parasite. We generated PfGRASP-GFP-expressing transgenic parasites and showed that this protein is localised to a single, juxtanuclear compartment in ring-stage parasites. The PfGRASP compartment is distinct from the ER, restricted within the boundaries of the parasite and colocalises with the cis-Golgi marker ERD2. Correct subcellular localisation of this Golgi matrix protein depends on a cross-species conserved functional myristoylation motif and is insensitive to Brefeldin A. Taken together our results define the Golgi apparatus in Plasmodium and depict the morphological organisation of the organelle throughout the asexual life cycle of the parasite.
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PMID:Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP. 1630 23

The inner membrane complex (IMC) is a unifying morphological feature of all alveolate organisms. It consists of flattened vesicles underlying the plasma membrane and is interconnected with the cytoskeleton. Depending on the ecological niche of the organisms, the function of the IMC ranges from a fundamental role as reinforcement system to more specialized roles in motility and cytokinesis. In this article, we present a comprehensive evolutionary analysis of IMC components, which exemplifies the adaptive nature of the IMCs' protein composition. Focusing on eight structurally distinct proteins in the most prominent "genus" of the Alveolata-the malaria parasite Plasmodium-we demonstrate that the level of conservation is reflected in phenotypic characteristics, accentuated in differential spatial-temporal patterns of these proteins in the motile stages of the parasite's life cycle. Colocalization studies with the centromere and the spindle apparatus reveal their discriminative biogenesis. We also reveal that the IMC is an essential structural compartment for the development of the sexual stages of Plasmodium, as it seems to drive the morphological changes of the parasite during the long and multistaged process of sexual differentiation. We further found a Plasmodium-specific IMC membrane matrix protein that highlights transversal structures in gametocytes, which could represent a genus-specific structural innovation required by Plasmodium. We conclude that the IMC has an additional role during sexual development supporting morphogenesis of the cell, which in addition to its functions in the asexual stages highlights the multifunctional nature of the IMC in the Plasmodium life cycle.
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PMID:Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite. 2238 54

The development of malaria vaccines is challenging, partly because the immunogenicity of recombinant malaria parasite antigens is low. We previously demonstrated that parasite antigens integrated into a tricomponent immunopotentiating complex increase antiparasitic immunity. In this study, the B domains of a group G Streptococcus (SpG) strain and Peptostreptococcus magnus (PpL) were used to evaluate whether vaccine efficacy is influenced by the type of immunoglobulin-binding domain (IBD) in the tricomponent complex. IBDs were fused to a pentameric cartilage oligomeric matrix protein (COMP) to increase the binding avidity of the complexes for their targets. The COMP-IBD fusion proteins generated (COMP-SpG and COMP-PpL and the previously constructed COMP-Z) bound a large fraction of splenic B lymphocytes but not T lymphocytes. These carrier molecules were then loaded with an ookinete surface protein of Plasmodium vivax, Pvs25, by chemical conjugation. The administration of the tricomponent complexes to mice induced more Pvs25-specific serum IgG than did the unloaded antigen. The PpL complex, which exhibited a broad Ig-binding spectrum, conferred higher vaccine efficacy than did the Z or SpG complexes when evaluated with a membrane feed assay. This study demonstrates that this tricomponent immunopotentiating system, incorporating IBDs as the B-lymphocyte-targeting ligands, is a promising technology for the delivery of malaria vaccines, particularly when combined with an aluminum salt adjuvant.
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PMID:Tricomponent complex loaded with a mosquito-stage antigen of the malaria parasite induces potent transmission-blocking immunity. 2452 83