{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:42:15Z","timestamp":1788975735114,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T00:00:00Z","timestamp":1118793600000},"content-version":"vor","delay-in-days":5858,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[1989,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have examined the relationship between (a) histochemically demonstrable copper using rubeanic add, (b) copper\u2010associated protein (CAP) using orcein, and (c) immunoreactive metallothionein (MT) using DNP hapten sandwich staining and have correlated these with histological lesions in 95 liver biopsies from patients with conditions associated with hepatic copper retention, 4 fetal livers, and 25 historically normal adult controls.<\/jats:p><jats:p>No copper or CAP was present in normal adult liver but periportal CAP was present in fetal liver. MT was present in hepatocytes of normal livers with a predominantly perivenular (centrilobular) cytoplasmic distribution varying in staining intensify; all fetal hepatocytes stained strongly for MT.<\/jats:p><jats:p>Fifty\u2010two of 95 (55 per cent) abnormal livers contained CAP and 42 (44 per cent) contained both CAP and copper. In CAP\u2010positive livers, the commonest histological lesions were piecemeal necrosis and cholestasis.<\/jats:p><jats:p>CAP was present in (a) 15\/15 cases of primary biliary cirrhosis including early cases with minimal pathology; and (b) 5\/5 cases of Wilson's disease, 6\/6 cases of biliary atresia, and 3\/9 cases of sclerosing cholangitis. In other conditions, it was present in 25\u201350 per cent of cases.<\/jats:p><jats:p>MT distribution was abnormal in most CAP\u2010positive livers. Necrotic hepatocytes were intensely MT\u2010positive and in Wilson's disease had a characteristic appearance.<\/jats:p>","DOI":"10.1002\/path.1711580208","type":"journal-article","created":{"date-parts":[[2005,6,22]],"date-time":"2005-06-22T09:42:57Z","timestamp":1119433377000},"page":"131-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Metallothionein and copper in liver disease with copper retention\u2014a histopathological study"],"prefix":"10.1002","volume":"158","author":[{"given":"Margaret E.","family":"Elmes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna P.","family":"Clarkson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas J.","family":"Mahy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Jasant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,15]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(19)30524-4"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)91863-2"},{"key":"e_1_2_1_4_2","first-page":"313","volume-title":"Metals and the Liver","author":"Smallwood RA","year":"1978"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38240-6"},{"key":"e_1_2_1_6_2","first-page":"715","article-title":"The significance of variations in the distribution of copper in liver disease","volume":"99","author":"Goldfischer S","year":"1980","journal-title":"Am J Pathol"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.31.8.784"},{"key":"e_1_2_1_8_2","first-page":"318","article-title":"Copper and copper associated proteins in primary biliary cirrhosis","volume":"2","author":"Janssens AR","year":"1982","journal-title":"Liver (Copenhagen)"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.38.6.653"},{"key":"e_1_2_1_10_2","first-page":"991","volume-title":"Histochemistry, Theoretical and Applied","author":"Pearse AGE","year":"1985"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.17.10.787"},{"key":"e_1_2_1_12_2","first-page":"299","article-title":"Histochemical localisation of copper with rubeanic acid","volume":"5","author":"Uzman LL","year":"1956","journal-title":"Lab lnvest"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01004596"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86907-7"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(78)90119-0"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(85)90001-0"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.36.1.18"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)70797-2"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.42.1.253"},{"key":"e_1_2_1_20_2","first-page":"191","volume-title":"Pigments in Pathology","author":"Porta EA","year":"1969"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2190539"},{"key":"e_1_2_1_22_2","unstructured":"ElmesME HaywoodS ClarksonJP FuentalbaK JasaniB.Copper tolerance in rats\u2010a histochemical and immunocytochemical study. In Hurley LS Keen CL Lonnerdal B Rucker RB. eds.Trace Elements in Man and Animals VI In press."},{"key":"e_1_2_1_23_2","first-page":"548","volume-title":"Ultrastructural Pathology of the Cell and Matrix","author":"Ghadialiy FN","year":"1982"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1711580208","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1711580208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:18:48Z","timestamp":1761056328000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1711580208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,6]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1989,6]]}},"alternative-id":["10.1002\/path.1711580208"],"URL":"https:\/\/doi.org\/10.1002\/path.1711580208","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,6]]},"assertion":[{"value":"1988-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}