{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:43:55Z","timestamp":1789983835376,"version":"4.0.1"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6056,"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":[[1999,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The aim of this study was to develop a model of selective duct damage restricted to hormone\u2013responsive segments corresponding to the ducts damaged in primary biliary cirrhosis (PBC). Carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) was fed by gavage to rats, and 2, 7, 14, and 28 days later, small and large cholangiocytes were isolated. Apoptosis was determined <jats:italic toggle=\"yes\">in situ<\/jats:italic> by morphology and in purified cholangiocytes by assessment of nuclear fragmentation by 4,6\u2013diamidino\u20132\u2013phenylindole (DAPI) staining. Cholangiocyte proliferation was evaluated <jats:italic toggle=\"yes\">in situ<\/jats:italic> by morphometry of liver sections stained for cytokeratin\u201319 (CK\u201319) and by proliferating cellular nuclear antigen (PCNA) staining in liver sections and in purified cholangiocytes by PCNA gene expression. Ductal secretion was assessed by measurement of secretin receptor (SR) gene expression and secretin\u2013induced cyclic adenosine 3\u2032,5\u2032\u2013monophosphate (cAMP) synthesis and secretin\u2013induced choleresis. Two days after CCl<jats:sub>4<\/jats:sub> administration, there was an increased number of small ducts, but a reduction of large ducts. Apoptosis, observed only in large ducts, was associated with decreased DNA synthesis and ductal secretion. Conversely, small cholangiocytes expressed <jats:italic toggle=\"yes\">de novo<\/jats:italic> the SR gene and secretin\u2013stimulated cAMP synthesis 2 days after CCl<jats:sub>4<\/jats:sub> treatment. Proliferation of large cholangiocytes was delayed until 7 days, which was associated with a transient increase in ductal secretion <jats:italic toggle=\"yes\">in vivo<\/jats:italic>.CCl<jats:sub>4<\/jats:sub> effects on cholangiocytes were reversed by day 28. CCl<jats:sub>4<\/jats:sub>treatment causes a decrease in large duct mass as a result of a higher rate of apoptosis and absence of initial proliferation in large cholangiocytes. These processes were concomitant with a decrease of ductal secretion in large cholangiocytes. Small cholangiocytes appear resistant to CCl<jats:sub>4<\/jats:sub>\u2013induced apoptosis, and proliferate and transiently compensate for loss of proliferative and secretory activity of large cholangiocytes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510290242","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:39:45Z","timestamp":1090971585000},"page":"307-319","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":96,"title":["Acute Carbon Tetrachloride Feeding Selectively Damages Large, But Not Small, Cholangiocytes From Normal Rat Liver"],"prefix":"10.1097","volume":"29","author":[{"given":"Gene D.","family":"LeSage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Glaser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Marucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziga","family":"Tretjak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Caligiuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Rodgers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo Lynne","family":"Phinizy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Baiocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lasater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ugili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Alpini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"BIB1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0168-8278(96)80014-6","volume":"24","author":"Benedetti","year":"1996","journal-title":"J Hepatol"},{"key":"BIB2","first-page":"623","volume-title":"The Liver: Biology and Pathobiology","author":"Alpini","year":"1994","unstructured":"The biology of the biliary epithelia. 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