{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:57:16Z","timestamp":1791169036963,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6179,"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":[[1998,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>While the clinical features of sclerosing cholangitis secondary to opportunistic infections of the biliary tree in patients with acquired immunodeficiency syndrome (AIDS) are well known, the mechanisms by which microbial pathogens such as <jats:italic toggle=\"yes\">Cryptosporidium parvum<\/jats:italic> associated with this syndrome actually cause disease are obscure. We established an <jats:italic toggle=\"yes\">in vitro<\/jats:italic> model of biliary cryptosporidiosis employing a human biliary epithelial cell line. Using morphological and biochemical techniques, we examined the interaction of <jats:italic toggle=\"yes\">C. parvum<\/jats:italic> with cultured human cholangiocytes. When the apical plasma membrane of polarized, confluent monolayers of human biliary epithelial cells was exposed to <jats:italic toggle=\"yes\">C. parvum<\/jats:italic> oocysts that had been excysted <jats:italic toggle=\"yes\">in vitro<\/jats:italic>, sporozoites attached to and invaded the cells in a time-, dose-, temperature-, and pH-dependent manner. The infectious process was both plasma membrane domain- and cell-specific, because no attachment or invasion occurred when the basolateral membrane of cholangiocytes was exposed to the parasite, or when a human hepatocyte cell line (HepG2) was used. Time-lapse video microscopy and scanning electron microscopy (SEM) showed that sporozoite attachment was rapid, involved extensive cholangiocyte membrane ruffling, and culminated in parasite penetration into a tight-fitting vacuole formed by invagination of the plasma membrane similar to those found in naturally occurring infection <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Transmission electron microscopy (TEM) showed that <jats:italic toggle=\"yes\">C. parvum<\/jats:italic> organisms formed parasitophorus vacuoles and were able to undergo a complete reproductive cycle, forming both asexual and sexual reproductive stages. Unexpectedly, direct cytopathic effects were noted in infected monolayers, with widespread programmed cell death (i.e., apoptosis) of biliary epithelial cells as assessed both morphologically and biochemically beginning within hours after exposure to the organism. The novel finding of specific cytopathic invasion of biliary epithelia by <jats:italic toggle=\"yes\">C. parvum<\/jats:italic> may be relevant to the pathogenesis and possible therapy of the secondary sclerosing cholangitis seen in AIDS patients with biliary cryptosporidiosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510280402","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:29:40Z","timestamp":1090970980000},"page":"906-913","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism"],"prefix":"10.1097","volume":"28","author":[{"given":"Xian-Ming","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Tietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"McNiven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas M.","family":"Jefferson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Mahle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F.","family":"LaRusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"BIB1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4612-2732-8_1","volume":"3","author":"Flanigan","year":"1993","journal-title":"Prog Clin Parsitol"},{"key":"BIB2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0169-4758(93)90211-W","volume":"9","author":"Petersen","year":"1993","journal-title":"Parasitol Today"},{"key":"BIB3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1055\/s-2007-1007393","volume":"12","author":"Cello","year":"1992","journal-title":"Semin Liver Dis"},{"key":"BIB4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/BF01690873","volume":"14","author":"Lopez-Velez","year":"1995","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"BIB5","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/0002-9343(86)90695-9","volume":"80","author":"Cockerill","year":"1986","journal-title":"Am J Med"},{"key":"BIB6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1056\/NEJM199601043340104","volume":"334","author":"Vakil","year":"1996","journal-title":"N Engl J Med"},{"key":"BIB7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0025-7125(16)30377-7","volume":"76","author":"Gellin","year":"1992","journal-title":"Med Clin North Am"},{"key":"BIB8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0020-7519(94)E0059-V","volume":"25","author":"O'Donoghue","year":"1995","journal-title":"Int J Parasitol"},{"key":"BIB9","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.1128\/IAI.59.12.4610-4613.1991","volume":"59","author":"Buraud","year":"1991","journal-title":"Infect Immun"},{"key":"BIB10","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1128\/AAC.34.8.1498","volume":"34","author":"McDonald","year":"1990","journal-title":"Antimicrob Agents Chemother"},{"key":"BIB11","first-page":"g1060","volume":"266","author":"Grubman","year":"1994","journal-title":"Am J Physiol"},{"key":"BIB12","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/hep.510260413","volume":"26","author":"Harnois","year":"1997","journal-title":"Hepatology"},{"key":"BIB13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/infdis\/169.1.170","volume":"169","author":"Adams","year":"1994","journal-title":"J Infect Dis"},{"key":"BIB14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1574-6968.1994.tb06833.x","volume":"118","author":"Upton","year":"1994","journal-title":"FEMS Microbiol Lett"},{"key":"BIB15","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1128\/IAI.59.1.234-239.1991","volume":"59","author":"Flanigan","year":"1991","journal-title":"Infect Immun"},{"key":"BIB16","doi-asserted-by":"crossref","first-page":"4506","DOI":"10.1128\/IAI.62.10.4506-4514.1994","volume":"62","author":"Griffiths","year":"1994","journal-title":"Infect Immun"},{"key":"BIB17","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1093\/infdis\/171.4.976","volume":"171","author":"Guarino","year":"1995","journal-title":"J Infect Dis"},{"key":"BIB18","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1128\/AEM.63.5.2029-2037.1997","volume":"63","author":"Rochelle","year":"1997","journal-title":"Appl Environ Microbiol"},{"key":"BIB19","first-page":"303","volume":"74","author":"Vroman","year":"1996","journal-title":"Lab Invest"},{"key":"BIB20","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1172\/JCI117579","volume":"94","author":"Patel","year":"1994","journal-title":"J Clin Invest"},{"key":"BIB21","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0016-5085(86)91112-1","volume":"90","author":"Marcial","year":"1986","journal-title":"Gastroenterology"},{"key":"BIB22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0168-8278(05)80518-5","volume":"17","author":"Bouche","year":"1993","journal-title":"J Hepatol"},{"key":"BIB23","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/clinids\/21.4.852","volume":"21","author":"French","year":"1995","journal-title":"Clin Infect Dis"},{"key":"BIB24","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/0016-5085(91)90678-E","volume":"100","author":"Hasan","year":"1991","journal-title":"Gastroenterology"},{"key":"BIB25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0016-5085(93)90412-6","volume":"104","author":"Argenzio","year":"1993","journal-title":"Gastroenterology"},{"key":"BIB26","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1086\/593695","volume":"175","author":"Verdon","year":"1997","journal-title":"J Infect Dis"},{"key":"BIB27","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/08820139709022691","volume":"26","author":"Alonso","year":"1997","journal-title":"Immunol Invest"},{"key":"BIB28","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1006\/expr.1994.1107","volume":"79","author":"Ragland","year":"1994","journal-title":"Exp Parsitol"},{"key":"BIB29","first-page":"153","volume":"8","author":"Estaquier","year":"1997","journal-title":"Eur Cytokine Netw"},{"key":"BIB30","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/intimm\/8.6.887","volume":"8","author":"Khan","year":"1996","journal-title":"Int Immunol"},{"key":"BIB31","doi-asserted-by":"crossref","first-page":"744","DOI":"10.4049\/jimmunol.154.2.744","volume":"154","author":"Lopes","year":"1995","journal-title":"J Immunol"},{"key":"BIB32","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1172\/JCI119557","volume":"100","author":"Zychlinsky","year":"1997","journal-title":"J Clin Invest"},{"key":"BIB33","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.4049\/jimmunol.152.10.5014","volume":"152","author":"Wang","year":"1994","journal-title":"J Immunol"},{"key":"BIB34","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.4049\/jimmunol.156.10.3986","volume":"156","author":"Watson","year":"1996","journal-title":"J Immunol"},{"key":"BIB35","doi-asserted-by":"crossref","first-page":"s51","DOI":"10.1172\/JCI119522","volume":"100","author":"Kagnoff","year":"1997","journal-title":"J Clin Invest"},{"key":"BIB36","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/IAI.65.1.298-304.1997","volume":"65","author":"Keane","year":"1997","journal-title":"Infect Immun"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510280402","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199810000-00002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:23:15Z","timestamp":1733052195000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199810000-00002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1998]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510280402","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1998,10]]}}}