FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3100886528> ?p ?o ?g. }

• W3100886528 abstract "According to a recent estimate by the World Health Organisation, by the year 2000 tuberculosis (TB) will kill 4 million people a year. This dramatic increase, from 3 million in 1992 to 4 million by year 2000, is an alarming signal for health workers. Endocrinological abnormalities have been observed in TB that may explain the tendency for patients to develop an inappropriate TH2 response to M. tuberculosis. These abnormalities include a fall in the ratio of antiglucocorticoid hormones (dehydroepiandrosterone; DHEA) to glucocorticoid, and a marked decrease in conversion of the major glucocorticoid cortisol to inactive cortisone. This project was designed to investigate the significance for human tuberculosis of these two endocrine changes. Three approaches were used. 1) The antiglucocorticoid properties of DHEA and some of its metabolites, were tested in order to select the optimum metabolite and schedule for in vivo experiments in tuberculosis in mice. 2) The ability of live M. tuberculosis to convert DHEA sulphate (present in human serum at up to 4 µg/ml) into active metabolites was examined; 3) The hypothesis that the enzyme that interconverts cortisol and cortisone in the lung is susceptible to local regulation by cytokines was tested. Antiglucocorticoid effects of DHEA and a series of its metabolites were tested in vivo for their ability to protect the thymus from apoptosis induced by corticosterone, and to block the effects of glucocorticoid on non-specific inflammation. The metabolite 3 β,17β-androstenediol (AED) proved most active. The optimum dose level was identified and has since proved strongly protective in a model of murine tuberculosis that is used by collaborators in Mexico. These metabolites were then tested in vitro for their effects on proliferation and cytokine production by murine and human lymphocytes, alone or in the presence of glucocorticoid. DHEA and AED increased the production of IFNy by murine splenocytes, and antagonised the inhibitory effects of cortisol on IFNỿ production by human T cells. The in vivo model has subsequently confirmed that AED upregulates TH1 and proinflammatory cytokines, while downregulating TH2 cytokine release. Mycobacterium tuberculosis cleaved DHEA to a number of metabolites, visualised by thin layer chromatography, including AED and reduced forms of AED that were identified by gas chromatography and mass spectrometry. 11β-HSD activity was measured in different organs at different intervals after intravenous challenge with live BGC. On day three conversion to cortisone in the lung was reduced in the BCG group compared to normal mice, indicating that the activity of 11β-HSD was mainly dehydrogenase. However 10 days later the activity shifted towards reductase since conversion to cortisone was markedly increased not only in lung but also in spleen and thymus. The equilibrium point (i.e. the ratio of cortisol to cortisone) did not change in liver or kidney. These results suggest that 11β-HSD is regulated during the inflammatory response induced by live BCG. The above data are discussed in relation to the immunological abnormalities that accompany human tuberculosis, and the effects of manipulating the AED/corticosterone balance in the murine tuberculosis model. They help to explain the changing pattern of immunopathology in human tuberculosis of different ages, and correlation of these disease patterns with age-related changes in DHEAS levels." @default.
• W3100886528 created "2020-11-23" @default.
• W3100886528 creator A5084055195 @default.
• W3100886528 date "1998-01-01" @default.
• W3100886528 modified "2023-09-23" @default.
• W3100886528 title "Tuberculosis, anti-glucocorticoids and the immune system" @default.
• W3100886528 hasPublicationYear "1998" @default.
• W3100886528 type Work @default.
• W3100886528 sameAs 3100886528 @default.
• W3100886528 citedByCount "0" @default.
• W3100886528 crossrefType "dissertation" @default.
• W3100886528 hasAuthorship W3100886528A5084055195 @default.
• W3100886528 hasConcept C126322002 @default.
• W3100886528 hasConcept C134018914 @default.
• W3100886528 hasConcept C142724271 @default.
• W3100886528 hasConcept C150903083 @default.
• W3100886528 hasConcept C203014093 @default.
• W3100886528 hasConcept C207001950 @default.
• W3100886528 hasConcept C2776992908 @default.
• W3100886528 hasConcept C2777477808 @default.
• W3100886528 hasConcept C2777911890 @default.
• W3100886528 hasConcept C2777975735 @default.
• W3100886528 hasConcept C2779283022 @default.
• W3100886528 hasConcept C2780004078 @default.
• W3100886528 hasConcept C2780352252 @default.
• W3100886528 hasConcept C2780484280 @default.
• W3100886528 hasConcept C2780841215 @default.
• W3100886528 hasConcept C2781069245 @default.
• W3100886528 hasConcept C46699223 @default.
• W3100886528 hasConcept C59493245 @default.
• W3100886528 hasConcept C71315377 @default.
• W3100886528 hasConcept C71924100 @default.
• W3100886528 hasConcept C86803240 @default.
• W3100886528 hasConcept C8891405 @default.
• W3100886528 hasConceptScore W3100886528C126322002 @default.
• W3100886528 hasConceptScore W3100886528C134018914 @default.
• W3100886528 hasConceptScore W3100886528C142724271 @default.
• W3100886528 hasConceptScore W3100886528C150903083 @default.
• W3100886528 hasConceptScore W3100886528C203014093 @default.
• W3100886528 hasConceptScore W3100886528C207001950 @default.
• W3100886528 hasConceptScore W3100886528C2776992908 @default.
• W3100886528 hasConceptScore W3100886528C2777477808 @default.
• W3100886528 hasConceptScore W3100886528C2777911890 @default.
• W3100886528 hasConceptScore W3100886528C2777975735 @default.
• W3100886528 hasConceptScore W3100886528C2779283022 @default.
• W3100886528 hasConceptScore W3100886528C2780004078 @default.
• W3100886528 hasConceptScore W3100886528C2780352252 @default.
• W3100886528 hasConceptScore W3100886528C2780484280 @default.
• W3100886528 hasConceptScore W3100886528C2780841215 @default.
• W3100886528 hasConceptScore W3100886528C2781069245 @default.
• W3100886528 hasConceptScore W3100886528C46699223 @default.
• W3100886528 hasConceptScore W3100886528C59493245 @default.
• W3100886528 hasConceptScore W3100886528C71315377 @default.
• W3100886528 hasConceptScore W3100886528C71924100 @default.
• W3100886528 hasConceptScore W3100886528C86803240 @default.
• W3100886528 hasConceptScore W3100886528C8891405 @default.
• W3100886528 hasLocation W31008865281 @default.
• W3100886528 hasOpenAccess W3100886528 @default.
• W3100886528 hasPrimaryLocation W31008865281 @default.
• W3100886528 hasRelatedWork W1584385177 @default.
• W3100886528 hasRelatedWork W1972377838 @default.
• W3100886528 hasRelatedWork W1974385782 @default.
• W3100886528 hasRelatedWork W1981016329 @default.
• W3100886528 hasRelatedWork W1982993395 @default.
• W3100886528 hasRelatedWork W1988279766 @default.
• W3100886528 hasRelatedWork W1988352585 @default.
• W3100886528 hasRelatedWork W1993225288 @default.
• W3100886528 hasRelatedWork W2002077512 @default.
• W3100886528 hasRelatedWork W2011949041 @default.
• W3100886528 hasRelatedWork W2015757726 @default.
• W3100886528 hasRelatedWork W2064035782 @default.
• W3100886528 hasRelatedWork W2079086956 @default.
• W3100886528 hasRelatedWork W2095712197 @default.
• W3100886528 hasRelatedWork W2161165236 @default.
• W3100886528 hasRelatedWork W2466533624 @default.
• W3100886528 hasRelatedWork W2908723960 @default.
• W3100886528 hasRelatedWork W3196617692 @default.
• W3100886528 hasRelatedWork W3212738664 @default.
• W3100886528 hasRelatedWork W3162650760 @default.
• W3100886528 isParatext "false" @default.
• W3100886528 isRetracted "false" @default.
• W3100886528 magId "3100886528" @default.
• W3100886528 workType "dissertation" @default.