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)

Tumor necrosis factor (TNF) is a cytokine produced mainly by activated monocytes/macrophages. We review here data obtained in four experimental models analyzed in our laboratory: cerebral malaria, graft-versus-host disease, BCG infection, and bleomycin-induced pulmonary fibrosis. We have shown that the triggering of these pathological conditions requires activation of T lymphocytes and overproduction of TNF, since these syndromes are associated with increased production of TNF mRNA and can be prevented either by T-cell depletion or by in vivo administration of neutralizing anti-TNF antibodies. These observations suggest that TNF is a central mediator in various immunopathological conditions and thus widen the field of T-cell mediated pathology.
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PMID:[Tumor necrosis factor (TNF) and pathology; its relationships with other cytokines]. 248 41

Noncardiogenic pulmonary edema is an uncommon but serious complication of falciparum malaria. A case of fatal noncardiogenic pulmonary edema complicating falciparum malaria is presented in which the unfavorable outcome resulted from rapidly developing pulmonary fibrosis, documented through open-lung biopsy. Possible mechanisms of lung injury in falciparum malaria include: impaired perfusion and tissue hypoxia in the pulmonary microcirculation caused by reduced effective circulating volume; abnormal autonomic effects on the lung resulting from reduced blood flow in the central nervous system; immunologic injury to alveolar-capillary structures; and morphologic changes in the surface membranes of infected erythrocytes leading to sequestration of parasitized erythrocytes in vascular beds and pulmonary capillary damage. That pulmonary involvement in falciparum malaria is usually associated with high-grade parasitemia, concurrent cerebral involvement, and delay in institution of antimalarial therapy emphasizes the importance of early diagnosis and treatment.
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PMID:Noncardiogenic pulmonary edema and pulmonary fibrosis in falciparum malaria. 354 68

Monoclonal antibodies (mAb) have revolutionised many areas of medicine, particularly research and diagnostics. Murine, human and humanized mAb have all been developed. The most important clinical applications to date have been in the fields of transplantation and oncology. Experimental and limited clinical trials suggest mAb are emerging as a new therapeutic strategy in the critically ill. Antibodies against a variety of bacteria or their products are potentially useful in gram-positive and gram-negative shock. Anti-cytokine and anti-neutrophil adhesion molecule mAb may be effective not only in septic shock but also in other conditions associated with acute inflammation and cytokine release, e.g., acid aspiration, ischaemia/reperfusion injury (myocardial infarction, haemorrhagic shock, aortic aneurysm repair). Antibodies inhibiting neutrophil adhesion may also be efficacious in asthma, pulmonary fibrosis, meningitis and cerebral malaria. The use of these and other mAb in intensive care is an exciting prospect and future clinical studies will determine the extent of their role in the management of the critically ill.
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PMID:Monoclonal antibodies--immunotherapy for the critically ill. 812 30

Various molecules expressed on the surface of platelets have been shown to mediate the protective or deleterious role of these cells in immuno-inflammatory mechanisms. Increasing evidence points to the involvement of the cell adhesion molecules, gpIIb-IIIa, P-selectin, CD31, LFA-1, and CD36 in the interaction between platelets and endothelial cells as well as other cell types. The possible role of these molecules in the ability of platelets to support endothelium and to protect against tumour necrosis factor mediated cytolysis or parasitic invasion are reviewed. The involvement of platelets as effectors of tissue damage in cerebral malaria, lipopolysaccharide induced pathology, and pulmonary fibrosis is also discussed. This has then been extended to include the intercellular mechanisms underpinning their pathogenic role in metastasis, transplant rejection, stroke, brain hypoxia, and related conditions. A better understanding of the complex regulation and hierarchical organisation of these various platelet adhesion molecules may prove useful in the development of new approaches to the treatment of such diseases.
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PMID:Role of platelet adhesion in homeostasis and immunopathology. 935 Mar

Tumor necrosis factor-alpha (TNF) is known to be an important mediator in the pathogenesis of several inflammatory diseases. Vascular endothelial cells represent a major target of TNF effects. Platelet sequestration has been found in brain microvessels during experimental cerebral malaria and lung in experimental pulmonary fibrosis, implying that it may participate in TNF-dependent microvascular pathology. In this study, we investigated the mechanisms of platelet-endothelial interaction, using co-cultures between platelets and TNF-activated mouse brain microvascular endothelial cells (MVECs). Adhesion and fusion of platelets to MVECs was evidenced by electron microscopy, dye transfer, and flow cytometry. It was induced by TNF and interferon-gamma and depended on LFA-1 expressed on the platelet surface and ICAM-1 expressed on MVECs. The adhesion and fusion also led to the transfer of platelet markers on the MVEC surface, rendering these more adherent for leukocytes, and to an enhanced MVEC sensitivity to TNF-induced injury. These results suggest that platelets can participate in TNF-induced microvascular pathology.
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PMID:Platelets play an important role in TNF-induced microvascular endothelial cell pathology. 935 66