Matches in SemOpenAlex for { <https://semopenalex.org/work/W2003721011> ?p ?o ?g. }
Showing items 1 to 76 of
76
with 100 items per page.
- W2003721011 endingPage "497" @default.
- W2003721011 startingPage "492" @default.
- W2003721011 abstract "The protein dystrophin is absent in the muscles of patients with Duchenne muscular dystrophy (DMD) as well as dystrophin-deficient mice with muscular dystrophy (mdx mice). The mdx mouse diaphragm closely resembles the human DMD phenotype and thus provides a useful model for studies of dystrophin gene replacement. Recombinant adenovirus vectors (AdVs) hold promise as a means for delivering a functional dystrophin gene to muscle. As an initial step toward this goal, we have determined the efficiency and functional consequences of AdV-mediated reporter gene transfer to the diaphragm in both normal and mdx adult mice. At 1 week after AdV administration, there was a high level of transgene expression in the diaphragm. One month later, however, elimination of transgene expression was observed along with a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. In order to further elucidate the cellular mechanisms underlying these findings, the effects of AdV gene inactivation (by ultraviolet (UV) irradiation) and interference with host T-lymphocyte subsets were examined. Both UV-inactivation of AdV and CD8+ T-cell deficiency were found to significantly alleviate AdV-induced reductions in diaphragm force-generating capacity. Brief (2 day) administration of a neutralizing antibody against host CD4+ T-cells also produced a trend towards mitigation of AdV-induced contractile dysfunction. In addition, transgene expression one month after AdV delivery was significantly enhanced with inhibition of either CD4+ or CD8+ T-cell function. The data suggest two major sources of reduced force generation after recombinant adenovirus vector-mediated gene transfer to muscle: 1) a cytotoxic component associated with recombinant adenovirus vector transcriptional activity; and 2) an immune-based component of more delayed onset that is primarily dependent upon CD8+ T-cell activity. These results have important implications for the design of future generation vectors and the potential need for immunosuppressive therapy after recombinant adenovirus vector mediated dystrophin gene transfer to Duchenne muscular dystrophy patients." @default.
- W2003721011 created "2016-06-24" @default.
- W2003721011 creator A5043498859 @default.
- W2003721011 date "1998-02-01" @default.
- W2003721011 modified "2023-09-27" @default.
- W2003721011 title "Respiratory muscles as a target for adenovirus-mediated gene therapy" @default.
- W2003721011 doi "https://doi.org/10.1183/09031936.98.11020492" @default.
- W2003721011 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9551759" @default.
- W2003721011 hasPublicationYear "1998" @default.
- W2003721011 type Work @default.
- W2003721011 sameAs 2003721011 @default.
- W2003721011 citedByCount "11" @default.
- W2003721011 countsByYear W20037210112015 @default.
- W2003721011 crossrefType "journal-article" @default.
- W2003721011 hasAuthorship W2003721011A5043498859 @default.
- W2003721011 hasBestOaLocation W20037210111 @default.
- W2003721011 hasConcept C102230213 @default.
- W2003721011 hasConcept C104317684 @default.
- W2003721011 hasConcept C111599444 @default.
- W2003721011 hasConcept C121332964 @default.
- W2003721011 hasConcept C135983454 @default.
- W2003721011 hasConcept C150194340 @default.
- W2003721011 hasConcept C153911025 @default.
- W2003721011 hasConcept C157138929 @default.
- W2003721011 hasConcept C161733203 @default.
- W2003721011 hasConcept C164292776 @default.
- W2003721011 hasConcept C203014093 @default.
- W2003721011 hasConcept C24890656 @default.
- W2003721011 hasConcept C2778750056 @default.
- W2003721011 hasConcept C2778943923 @default.
- W2003721011 hasConcept C2779030066 @default.
- W2003721011 hasConcept C2780394045 @default.
- W2003721011 hasConcept C54355233 @default.
- W2003721011 hasConcept C86803240 @default.
- W2003721011 hasConcept C95444343 @default.
- W2003721011 hasConceptScore W2003721011C102230213 @default.
- W2003721011 hasConceptScore W2003721011C104317684 @default.
- W2003721011 hasConceptScore W2003721011C111599444 @default.
- W2003721011 hasConceptScore W2003721011C121332964 @default.
- W2003721011 hasConceptScore W2003721011C135983454 @default.
- W2003721011 hasConceptScore W2003721011C150194340 @default.
- W2003721011 hasConceptScore W2003721011C153911025 @default.
- W2003721011 hasConceptScore W2003721011C157138929 @default.
- W2003721011 hasConceptScore W2003721011C161733203 @default.
- W2003721011 hasConceptScore W2003721011C164292776 @default.
- W2003721011 hasConceptScore W2003721011C203014093 @default.
- W2003721011 hasConceptScore W2003721011C24890656 @default.
- W2003721011 hasConceptScore W2003721011C2778750056 @default.
- W2003721011 hasConceptScore W2003721011C2778943923 @default.
- W2003721011 hasConceptScore W2003721011C2779030066 @default.
- W2003721011 hasConceptScore W2003721011C2780394045 @default.
- W2003721011 hasConceptScore W2003721011C54355233 @default.
- W2003721011 hasConceptScore W2003721011C86803240 @default.
- W2003721011 hasConceptScore W2003721011C95444343 @default.
- W2003721011 hasIssue "2" @default.
- W2003721011 hasLocation W20037210111 @default.
- W2003721011 hasLocation W20037210112 @default.
- W2003721011 hasOpenAccess W2003721011 @default.
- W2003721011 hasPrimaryLocation W20037210111 @default.
- W2003721011 hasRelatedWork W1963803693 @default.
- W2003721011 hasRelatedWork W1983555241 @default.
- W2003721011 hasRelatedWork W1988900658 @default.
- W2003721011 hasRelatedWork W1991669378 @default.
- W2003721011 hasRelatedWork W2003721011 @default.
- W2003721011 hasRelatedWork W2034273480 @default.
- W2003721011 hasRelatedWork W2048777176 @default.
- W2003721011 hasRelatedWork W2153888458 @default.
- W2003721011 hasRelatedWork W2396795223 @default.
- W2003721011 hasRelatedWork W2517644652 @default.
- W2003721011 hasVolume "11" @default.
- W2003721011 isParatext "false" @default.
- W2003721011 isRetracted "false" @default.
- W2003721011 magId "2003721011" @default.
- W2003721011 workType "article" @default.