{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:04:25Z","timestamp":1761609865015,"version":"3.37.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":9193,"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":[[1990,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Liver\u2013kidney microsomal\u20131 autoantibodies characterize a subgroup of autoimmune chronic active hepatitis. The liver antigen of liver\u2013kidney microsomal\u20131 antibodies has been identified as cytochrome P450 db1, a microsomal enzyme catalyzing the oxidative metabolism of more than 20 drugs, including debrisoquine, sparteine and bufuralol. A genetic polymorphism (debrisoquin\u2013sparteine polymorphism) is responsible for the lack of P450 db1 protein in the livers of 5% to 10% of Caucasians, leading to impaired drug metabolism and a distinct poor metabolizer phenotype. We investigated whether liver\u2013kidney microsomal\u20131 positive autoimmune chronic active hepatitis patients express functionally intact P450 db1 in their livers. In four patients with liver\u2013kidney microsomal\u20131 positive chronic active hepatitis, but not in five patients with various liver\u2013kidney microsomal\u20131 negative liver diseases, the presence of circulating liver\u2013kidney microsomal\u20131 antibodies was confirmed by immunofluorescence, radioimmunoassay and immunoblotting analysis using recombinant P450 db1. Moreover, only sera from liver\u2013kidney microsomal\u20131 positive autoimmune chronic active hepatitis patients strongly inhibited the enzymatic activity of P450 db1 in human liver microsomes <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. Immunoblotting detected 50\u2013kd P450 db1 protein in liver biopsy specimens from all patients. The <jats:italic toggle=\"yes\">in vivo<\/jats:italic> function of P450 db1 was investigated by determining the metabolic ratio for sparteine and its 2\u2013dehydro and 5\u2013dehydro metabolites in 12\u2013hr urine samples after oral administration of sparteine sulfate. <jats:italic toggle=\"yes\">In vivo<\/jats:italic> P450 db1-mediated drug metabolism was of the extensive metabolizer phenotype and did not differ significantly between liver\u2013kidney microsomal\u20131 positive (metabolic ratio = 1.15 \u00b1 0.32) and liver\u2013kidney microsomal\u20131 negative (metabolic ratio = 1.18 \u00b1 0.48) patients. Thus patients with liver\u2013kidney microsomal\u20131 positive chronic active hepatitis express functionally intact P450 db1 in their livers. However, the activity of this enzyme is not significantly diminished <jats:italic toggle=\"yes\">in vivo<\/jats:italic> by circulating liver\u2013kidney microsomal\u20131 autoantibodies that react with the active site of P450 db1 and inhibit its function <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. (Hepatology 1990;12:127-132).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840120120","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T23:27:00Z","timestamp":1172964420000},"page":"127-132","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":71,"title":["Patients With Type Ii Autoimmune Hepatitis Express Functionally Intact Cytochrome P\u2013450 Db1 That Is Inhibited by Lkm\u20131 Autoantibodies In Vitro But Not In Vivo"],"prefix":"10.1097","volume":"12","author":[{"given":"Michael","family":"Manns","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Zanger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Gerken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin F.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meyer Karl-H.","family":"Zum B\u00fcschenfelde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urs A.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Eichelbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840120120-BIB1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0140-6736(87)92024-1","volume":"1","author":"Manns","year":"1987","journal-title":"Lancet"},{"key":"10.1002\/hep.1840120120-BIB2","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.1840070626","volume":"7","author":"Homberg","year":"1987","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840120120-BIB3","doi-asserted-by":"crossref","first-page":"8256","DOI":"10.1073\/pnas.85.21.8256","volume":"27","author":"Zanger","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840120120-BIB4","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1172\/JCI113949","volume":"83","author":"Manns","year":"1989","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840120120-BIB5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/dna.1.1989.8.1","volume":"8","author":"Nebert","year":"1989","journal-title":"DNA"},{"author":"Meyer","key":"10.1002\/hep.1840120120-BIB6","unstructured":", , , . Genetic polymorphisms of drug metabolism. In: Popper H, Schaffner F, eds. Progress in Liver Disease, [In press]."},{"key":"10.1002\/hep.1840120120-BIB7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00562059","volume":"16","author":"Eichelbaum","year":"1979","journal-title":"Eur J Clin Pharmacol"},{"key":"10.1002\/hep.1840120120-BIB8","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0140-6736(77)91430-1","volume":"2","author":"Maghoub","year":"1977","journal-title":"Lancet"},{"key":"10.1002\/hep.1840120120-BIB9","first-page":"243","volume":"0890\u20139083","author":"Eichelbaum","year":"1988","journal-title":"ISI Atlas of Science"},{"key":"10.1002\/hep.1840120120-BIB10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/331442a0","volume":"331","author":"Gonzalez","year":"1988","journal-title":"Nature"},{"key":"10.1002\/hep.1840120120-BIB11","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1021\/bi00415a010","volume":"27","author":"Zanger","year":"1988","journal-title":"Biochemistry"},{"key":"10.1002\/hep.1840120120-BIB12","first-page":"600","volume":"57","author":"Manns","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840120120-BIB13","doi-asserted-by":"crossref","first-page":"5340","DOI":"10.1073\/pnas.85.14.5240","volume":"85","author":"Skoda","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840120120-BIB14","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/clpt.1987.34","volume":"41","author":"Osikowska-Evers","year":"1987","journal-title":"Clin Pharmacol Ther"},{"key":"10.1002\/hep.1840120120-BIB15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.3109\/00498258609050252","volume":"16","author":"Eichelbaum","year":"1986","journal-title":"Xenobiotica"},{"key":"10.1002\/hep.1840120120-BIB16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/clpt.1989.5","volume":"45","author":"Kroemer","year":"1989","journal-title":"Clin Pharmacol Ther"},{"key":"10.1002\/hep.1840120120-BIB17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1073\/pnas.84.2.551","volume":"84","author":"Beaune","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840120120-BIB18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1056\/NEJM198007103030202","volume":"303","author":"Vergani","year":"1980","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840120120-BIB19","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/hep.1840090503","volume":"9","author":"Loeper","year":"1989","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840120120-BIB20","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/BF00615971","volume":"29","author":"Leeman","year":"1986","journal-title":"Eur J Clin Pharmacol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840120120","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199007000-00019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T15:30:35Z","timestamp":1738942235000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199007000-00019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,7]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1990]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840120120","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[1990,7]]}}}