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 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

Ajoene, (E, Z) -4, 5, 9-trithiadeca-1, 6, 11-triene 9 oxide, is a compound originally isolated from ethanolic extracts of garlic that impairs platelet aggregation by inhibiting the functional exposure of platelet integrins GPIIb/IIIa. In vitro, Ajoene is toxic for several tumoral cell lines, and exert an antiproliferative effect on T. cruzi and murine malaria parasites. Here we show that Ajoene strongly inhibited the proliferation induced in human lymphocytes by the mitogens phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and anti-CD3, and the capping formation induced in B lymphocytes by anti-IgM antibodies. On macrophages, Ajoene was also found to partially inhibit the lypopolysaccharide-induced production of Tumor Necrosis Factor (TNF), and to decrease the phagocytic activity of thioglycolate-elicited mouse peritoneal macrophages for IgG-opsonized, human erythrocytes. Ajoene also partially prevented the lytic effect of human and rabbit TNF on Actinomycin D-treated WEHI 164 cells. These results strongly suggest that Ajoene is a potent modulator of membrane-dependent functions of immune cells.
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PMID:Effects of Ajoene on lymphocyte and macrophage membrane-dependent functions. 904 57

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

Thrombocytopenia frequently appear in severe malaria. The reasons of low blood platelets count are different and its results of hypersplenism, subclinical course of intravascular coagulation (DIC). Thrombocytopenia from "consumption" is consequence of sequestration of blood platelets in blood vessels of lungs and cerebral. We examination 29 years old men, who was as forest worker in islands on Indonesia. He was treated with recurrent, poliethiological malaria (Plasmodium falciparum, Plasmodium vivar) and severe thrombocytopenia (17.0 G/L) without hepatosplenomegalia. Antiplatelet antibody was examined in blood serum by ELISA methods (GTI - PAKPLUS. In blood serum was detected IgG antibody agai nstglicoprotein receptors on surface of blood platelets GPIIb/IIIa, GPIV, GPIb/IX, GPV, GPIa/IIa. Chronic infections of Plasmodium may conduct to autoimmune destruction of blood platelets.
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PMID:[Autoimmune thrombocytopenia in recurrent polietiological malaria (Plasmodium falciparum, Plasmodium vivax)]. 1688 56

Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-alpha, but not IL-1beta or lymphotoxin-alpha (LT-alpha), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-alpha injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies.
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PMID:A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. 1827 70

Rapid advances in the field of nanotechnology promise revolutionary improvements in the diagnosis and therapy of neuroinflammatory disorders. An array of iron oxide nano- and microparticle agents have been developed for in vivo molecular magnetic resonance imaging (mMRI) of cerebrovascular endothelial targets, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and the glycoprotein receptor GP IIb/IIIa expressed on activated platelets. Molecular markers of glioma cells, such as matrix metalloproteinase-2 (MMP-2), and markers for brain tumor angiogenesis, such as alpha (v) beta (3) integrin (alpha(v)beta(3)), have also been successfully targeted using nanoparticle imaging probes. This chapter provides an overview of targeted, iron oxide nano- and microparticles that have been applied for in vivo mMRI of the brain in experimental models of multiple sclerosis (MS), brain ischemia, cerebral malaria (CM), brain cancer, and Alzheimer's disease. The potential of targeted nanoparticle agents for application in clinical imaging is also discussed, including multimodal and therapeutic approaches.
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PMID:Chapter 4 - Applications of nanotechnology in molecular imaging of the brain. 2030 29