{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:19:05Z","timestamp":1791325145530,"version":"4.3.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rationale: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause of death in chronic obstructive pulmonary disease (COPD). However, the pathophysiology of failure of the diaphragm to generate force in COPD is in part unclear. Objectives: The present study investigated contractile function and myosin heavy chain content of diaphragm muscle single fibers from patients with COPD. Methods: Skinned muscle fibers were isolated from muscle biopsies from the diaphragm of eight patients with mild to moderate COPD and five patients without COPD (mean FEV1 % predicted, 70 and 100%, respectively). Contractile function of single fibers was assessed, and afterwards, myosin heavy chain content was determined in these fibers. In diaphragm muscle homogenates, the level of ubiquitin-protein conjugation was determined. Results: Diaphragm muscle fibers from patients with COPD showed reduced force generation per cross-sectional area, and reduced myosin heavy chain content per half sarcomere. In addition, these fibers had decreased Ca2 \u00a0+ sensitivity of force generation, and slower cross-bridge cycling kinetics. Our observations were present in fibers expressing slow and 2A isoforms of myosin heavy chain. Ubiquitin-protein conjugation was increased in diaphragm muscle homogenates of patients with mild to moderate COPD. Conclusions: Early in the development of COPD, diaphragm fiber contractile function is impaired. Our data suggest that enhanced diaphragm protein degradation through the ubiquitin-proteasome pathway plays a role in loss of contractile protein and, consequently, failure of the diaphragm to generate force.<\/jats:p>","DOI":"10.1164\/rccm.200502-262oc","type":"journal-article","created":{"date-parts":[[2005,4,22]],"date-time":"2005-04-22T20:33:37Z","timestamp":1114202017000},"page":"200-205","source":"Crossref","is-referenced-by-count":194,"title":["Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"172","author":[{"given":"Coen A. C.","family":"Ottenheijm","sequence":"first","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo M. A.","family":"Heunks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary C.","family":"Sieck","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhi","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Degens","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"de Boo","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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Richard","family":"Dekhuijzen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Epidemiology, and Biostatistics, and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands; and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,7,15]]},"reference":[{"key":"2026032606010207000_BIB1","first-page":"1241","volume-title":"Nat Med","year":"1998"},{"key":"2026032606010207000_BIB2","first-page":"905","volume-title":"Am Rev Respir Dis","year":"1991"},{"key":"2026032606010207000_BIB3","first-page":"43","volume-title":"Monaldi Arch Chest Dis","year":"1997"},{"key":"2026032606010207000_BIB4","first-page":"961","volume-title":"Am J Respir Crit Care Med","year":"1996"},{"key":"2026032606010207000_BIB5","first-page":"L527","volume-title":"Am J Physiol","year":"1998"},{"key":"2026032606010207000_BIB6","first-page":"1799","volume-title":"N Engl J Med","year":"1997"},{"key":"2026032606010207000_BIB7","first-page":"371","volume-title":"Eur Respir J","year":"1999"},{"key":"2026032606010207000_BIB8","first-page":"1205","volume-title":"J Appl Physiol","year":"2002"},{"key":"2026032606010207000_BIB9","first-page":"533","volume-title":"Nature","year":"1971"},{"key":"2026032606010207000_BIB10","first-page":"3265","volume-title":"Proc Natl Acad Sci USA","year":"1988"},{"key":"2026032606010207000_BIB11","first-page":"862","volume-title":"Nat Rev Cancer","year":"2002"},{"key":"2026032606010207000_BIB12","first-page":"2124","volume-title":"N Engl J Med","year":"2004"},{"key":"2026032606010207000_BIB13","first-page":"A241","volume-title":"Am J Respir Crit Care Med","year":"2004"},{"key":"2026032606010207000_BIB14","first-page":"33","volume-title":"Acta Physiol Scand","year":"1998"},{"key":"2026032606010207000_BIB15","first-page":"1894","volume-title":"J Appl Physiol","year":"1999"},{"key":"2026032606010207000_BIB16","first-page":"2233","volume-title":"J Appl Physiol","year":"2001"},{"key":"2026032606010207000_BIB17","first-page":"657","volume-title":"J Appl Physiol","year":"2001"},{"key":"2026032606010207000_BIB18","first-page":"1506","volume-title":"J Appl Physiol","year":"2002"},{"key":"2026032606010207000_BIB19","first-page":"1256","volume-title":"Am J Respir Crit Care Med","year":"2001"},{"key":"2026032606010207000_BIB20","first-page":"932","volume-title":"Eur Respir J","year":"2004"},{"key":"2026032606010207000_BIB21","first-page":"695","volume-title":"J Appl Physiol","year":"2000"},{"key":"2026032606010207000_BIB22","first-page":"706","volume-title":"Am J Respir Crit Care Med","year":"2003"},{"key":"2026032606010207000_BIB23","first-page":"853","volume-title":"Physiol Rev","year":"2000"},{"key":"2026032606010207000_BIB24","first-page":"1897","volume-title":"N Engl J Med","year":"1996"},{"key":"2026032606010207000_BIB25","first-page":"227S","volume-title":"J Nutr","year":"1999"},{"key":"2026032606010207000_BIB26","first-page":"357","volume-title":"Proc Nutr Soc","year":"2004"},{"key":"2026032606010207000_BIB27","first-page":"907","volume-title":"Cell","year":"2004"},{"key":"2026032606010207000_BIB28","first-page":"154","volume-title":"Am J Respir Crit Care Med","year":"2004"},{"key":"2026032606010207000_BIB29","first-page":"1453","volume-title":"Am J Respir Crit Care Med","year":"1994"},{"key":"2026032606010207000_BIB30","first-page":"920","volume-title":"Eur Respir J","year":"2003"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/172\/2\/200\/67497808\/ajrccm_172_2_200.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/172\/2\/200\/67497808\/ajrccm_172_2_200.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:01:14Z","timestamp":1774519274000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/172\/2\/200\/8538040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2005,7,15]]},"published-print":{"date-parts":[[2005,7,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200502-262oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,7]]},"published":{"date-parts":[[2005,7]]}}}