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)

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-/- mice are an invaluable model for exploring the effects of systemic GM-CSF deficiency. Their lung phenotype exactly reproduces the abnormalities seen in human pulmonary alveolar proteinosis (PAP). However, GM-CSF-/- mice also have significant systemic functional abnormalities. These include immune defects which result in a reduced susceptibility to a range of experimentally induced autoimmune disorders. These immunological defects are also functionally manifest as an impaired ability to resolve a range of infections under certain conditions, usually implicating cellular effectors, including Listeria, Group B streptococcus, adenovirus, Pneumocystis carinii, and malaria. These observations are consistent with the known propensity for patients with PAP to develop a range of opportunistic infections. Conversely, the diminished immunological response to inflammatory stimuli may be beneficial in some settings by limiting inflammatory cell recruitment and pro-inflammatory mediator-release. GM-CSF-/- mice also have distinct fertility defects, manifest as reduced litter size and an increased rate of early fetal loss. These observations may be clinically relevant for women affected by PAP and further support the evaluation of the role of GM-CSF in human reproduction. These observations reinforce the importance of clinicians viewing PAP as a state of systemic functional GM-CSF deficiency, albeit with prominent pulmonary manifestations, rather than purely a 'lung disease'. These systemic manifestations of GM-CSF deficiency should also be considered when deciding on the choice between pulmonary or systemic delivery of GM-CSF as therapy for PAP, as only systemic drug delivery has the potential capacity to correct the systemic manifestations of GM-CSF deficiency in these patients.
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PMID:Extra-pulmonary aspects of acquired pulmonary alveolar proteinosis as predicted by granulocyte-macrophage colony-stimulating factor-deficient mice. 1642 63

Primary immunodeficiencies (PIDs) have traditionally been defined according to their immunologic phenotype. Far from being concluded, the search for human genes that, when mutated, cause PID is actively being pursued. During the last year, four novel genetic defects that cause severe combined immunodeficiency and severe congenital neutropenia have been identified. At the same time, the immunologic definition of primary immunodeficiencies has been expanded by the recognition that genetic defects affecting innate immunity may result in selective predisposition to certain infections, such as mycobacterial disease, herpes simplex encephalitis, and invasive pneumococcal infections. Studies of genetically determined susceptibility to infections have recently shown that immunologic defects may also account for novel infectious phenotypes, such as malaria or leprosy. Finally, a growing body of evidence indicates that primary immunodeficiencies may present with a noninfectious clinical phenotype that may be restricted to single organs, as in the case of atypical hemolytic uremic syndrome or pulmonary alveolar proteinosis. Overall, these achievements highlight the importance of human models, which often differ from the corresponding animal models.
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PMID:Recent advances in primary immunodeficiencies: identification of novel genetic defects and unanticipated phenotypes. 1919 May 30