{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:19:08Z","timestamp":1791109148859,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6209,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The p21 protein is a universal inhibitor of cyclin-dependent kinases and of cell-cycle progression and is involved in numerous growth-inhibitory pathways in cell culture systems. Recent studies suggest that p21 regulates hepatocyte cell cycle progression in models of liver regeneration. The present study was designed to investigate the possible involvement of p21 in the control of hepatocyte proliferation in human liver diseases. To examine that, the expression of p21 in clinical liver biopsy specimens was determined by immunohistochemistry. This was correlated with hepatocyte Ki-67 immunostaining (a marker of hepatocyte proliferation <jats:italic toggle=\"yes\">in vivo<\/jats:italic>) as well as histologic features. Little p21 or Ki-67 expression was detected in normal human liver or in specimens of nonalcoholic steatohepatitis. In patients with alcoholic hepatitis, increased expression of p21, but not of Ki-67, was observed. In specimens with chronic hepatitis C, hepatocyte p21 expression was significantly correlated with Ki-67 immunostaining, as well as with the degree of inflammation and fibrosis. These results indicate that hepatocyte p21 expression is upregulated in response to hepatic injury and correlates with histologic markers of proliferation and disease activity. This study provides evidence that p21 plays a role in the regulation of hepatocyte proliferation in human liver diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510280320","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:27:57Z","timestamp":1090970877000},"page":"738-743","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":55,"title":["Expression of cyclin-dependent kinase inhibitor p21 in human liver"],"prefix":"10.1097","volume":"28","author":[{"given":"Gretchen S.","family":"Crary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"BIB1","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1126\/science.274.5293.1672","volume":"274","author":"Sherr","year":"1996","journal-title":"Science"},{"key":"BIB2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/374131a0","volume":"374","author":"Morgan","year":"1995","journal-title":"Nature"},{"key":"BIB3","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1101\/gad.9.10.1149","volume":"9","author":"Sherr","year":"1995","journal-title":"Genes Dev"},{"key":"BIB4","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/369520a0","volume":"369","author":"Pines","year":"1994","journal-title":"Nature"},{"key":"BIB5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0959-437X(96)90011-8","volume":"6","author":"Harper","year":"1996","journal-title":"Curr Op Gen Develop"},{"key":"BIB6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","volume":"276","author":"Michalopoulos","year":"1997","journal-title":"Science"},{"key":"BIB7","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/BF01307524","volume":"36","author":"Callea","year":"1991","journal-title":"Dig Dis Sci"},{"key":"BIB8","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/0016-5085(92)90775-T","volume":"102","author":"Kawasaki","year":"1992","journal-title":"Gastroenterology"},{"key":"BIB9","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/hep.510230625","volume":"23","author":"Farinati","year":"1996","journal-title":"Hepatology"},{"key":"BIB10","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0016-5085(92)90852-P","volume":"103","author":"Tarao","year":"1992","journal-title":"Gastroenterology"},{"key":"BIB11","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/1097-0142(19940215)73:4<1149::AID-CNCR2820730405>3.0.CO;2-9","volume":"73","author":"Tarao","year":"1994","journal-title":"Cancer"},{"key":"BIB12","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/hep.510230510","volume":"23","author":"Delhaye","year":"1996","journal-title":"Hepatology"},{"key":"BIB13","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0140-6736(94)92025-7","volume":"343","author":"Fang","year":"1994","journal-title":"Lancet"},{"key":"BIB14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/hep.510250311","volume":"25","author":"Albrecht","year":"1997","journal-title":"Hepatology"},{"key":"BIB15","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1038\/sj.onc.1201728","volume":"16","author":"Albrecht","year":"1998","journal-title":"Oncogene"},{"key":"BIB16","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1101\/gad.10.3.245","volume":"10","author":"Wu","year":"1996","journal-title":"Genes Dev"},{"key":"BIB17","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1097\/00000478-199512000-00007","volume":"19","author":"Batts","year":"1995","journal-title":"Am J Surg Pathol"},{"key":"BIB18","first-page":"2910","volume":"55","author":"el-Deiry","year":"1995","journal-title":"Cancer Res"},{"key":"BIB19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1600-0676.1997.tb00772.x","volume":"17","author":"Kaita","year":"1997","journal-title":"Liver"},{"key":"BIB20","first-page":"825","volume":"148","author":"Fredersdorf","year":"1996","journal-title":"Am J Pathol"},{"key":"BIB21","doi-asserted-by":"crossref","first-page":"7353","DOI":"10.1128\/MCB.17.12.7353","volume":"17","author":"Timchenko","year":"1997","journal-title":"Mol Cell Biol"},{"key":"BIB22","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1093\/oxfordjournals.jbchem.a021639","volume":"121","author":"Kano","year":"1997","journal-title":"J Biochem"},{"key":"BIB23","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1006\/bbrc.1996.1738","volume":"228","author":"Sawada","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"BIB24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/bbrc.1996.1140","volume":"225","author":"Kitano","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"BIB25","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1093\/carcin\/17.10.2157","volume":"17","author":"Obata","year":"1996","journal-title":"Carcinogenesis"},{"key":"BIB26","first-page":"951","volume":"8","author":"Serfas","year":"1997","journal-title":"Cell Growth Differ"},{"key":"BIB27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1124\/mol.51.1.69","volume":"51","author":"Ma","year":"1997","journal-title":"Mol Pharmacol"},{"key":"BIB28","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1172\/JCI117806","volume":"95","author":"Schwaller","year":"1995","journal-title":"J Clin Invest"},{"key":"BIB29","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1073\/pnas.92.12.5545","volume":"92","author":"Datto","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BIB30","doi-asserted-by":"crossref","first-page":"29386","DOI":"10.1074\/jbc.270.49.29386","volume":"270","author":"Russo","year":"1995","journal-title":"J Biol Chem"},{"key":"BIB31","doi-asserted-by":"crossref","first-page":"31915","DOI":"10.1074\/jbc.271.50.31915","volume":"271","author":"Qui","year":"1996","journal-title":"J Biol Chem"},{"key":"BIB32","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1126\/science.7863339","volume":"267","author":"Marx","year":"1995","journal-title":"Science"},{"key":"BIB33","first-page":"1609","volume":"7","author":"Gorospe","year":"1996","journal-title":"Cell Growth Differ"},{"key":"BIB34","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/sj.onc.1201287","volume":"15","author":"Guo","year":"1997","journal-title":"Oncogene"},{"key":"BIB35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/ng0197-78","volume":"15","author":"Zeng","year":"1997","journal-title":"Nature Genetics"},{"key":"BIB36","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1128\/MCB.15.7.3823","volume":"15","author":"Guo","year":"1995","journal-title":"Mol Cell Biol"},{"key":"BIB37","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1101\/gad.10.7.804","volume":"10","author":"Timchenko","year":"1996","journal-title":"Genes Dev"},{"key":"BIB38","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1101\/gad.10.2.142","volume":"10","author":"Liu","year":"1996","journal-title":"Genes Dev"},{"key":"BIB39","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.272.5262.719","volume":"272","author":"Chin","year":"1996","journal-title":"Science"},{"key":"BIB40","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1006\/bbrc.1996.1546","volume":"2","author":"Blagosklonny","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"BIB41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1128\/MCB.17.1.355","volume":"17","author":"Maki","year":"1997","journal-title":"Mol Cell Biol"},{"key":"BIB42","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1096\/fasebj.10.5.8621056","volume":"10","author":"Kren","year":"1996","journal-title":"FASEB J"},{"key":"BIB43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/375159a0","volume":"375","author":"Luo","year":"1995","journal-title":"Nature"},{"key":"BIB44","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/369574a0","volume":"369","author":"Waga","year":"1994","journal-title":"Nature"},{"key":"BIB45","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/381804a0","volume":"381","author":"Shim","year":"1996","journal-title":"Nature"},{"key":"BIB46","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1101\/gad.9.8.935","volume":"9","author":"Macleod","year":"1995","journal-title":"Genes Dev"},{"key":"BIB47","first-page":"604","volume":"57","author":"Gray-Bablin","year":"1997","journal-title":"Cancer Res"},{"key":"BIB48","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1101\/gad.8.15.1750","volume":"8","author":"Zhang","year":"1994","journal-title":"Genes Dev"},{"key":"BIB49","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1101\/gad.11.7.847","volume":"11","author":"LaBaer","year":"1997","journal-title":"Genes Dev"},{"key":"BIB50","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1091\/mbc.6.9.1197","volume":"6","author":"Poon","year":"1995","journal-title":"Mol Biol Cell"},{"key":"BIB51","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0039-6060(97)90334-2","volume":"122","author":"Ehrenfried","year":"1997","journal-title":"Surgery"},{"key":"BIB52","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0046-8177(97)90280-X","volume":"27","author":"Palazzo","year":"1997","journal-title":"Hum Pathol"},{"key":"BIB53","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/hep.510250314","volume":"25","author":"Hui","year":"1997","journal-title":"Hepatology"},{"key":"BIB54","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/sj.gt.3300403","volume":"4","author":"Ohno","year":"1997","journal-title":"Gene Ther"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510280320","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199809000-00020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:23:56Z","timestamp":1733052236000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199809000-00020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1998]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510280320","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1998,9]]}}}