@article{brown_van winkle_cecere_rushton_brachelente_cullen_2010, title={Congenital Hepatic Fibrosis in 5 Dogs}, volume={47}, ISSN={["0300-9858"]}, DOI={10.1177/0300985809353313}, abstractNote={ Congenital hepatic fibrosis is a disorder of biliary system development histologically characterized by diffuse periportal to bridging fibrosis with numerous small often-irregular bile ducts and reduction in the number of portal vein branches. The condition results from abnormal development of the ductal plate, the embryonic precursor to the interlobular bile ducts. It has rarely been reported in veterinary species, and it has never been reported in dogs. This article describes 5 cases of a ductal plate malformation in dogs consistent with congenital hepatic fibrosis. On light microscopy, all 5 livers had severe bridging fibrosis with a marked increase in the number of small bile ducts, which often had irregular, dilated profiles reminiscent of the developing ductal plate. In addition, 80% (4 of 5) of cases lacked typical portal vein profiles. Cytokeratin 7 and proliferating cell nuclear antigen immunohistochemistry was performed on the 3 cases for which paraffin-embedded tissue was available. The bile duct profiles were strongly positive for cytokeratin 7 in all 3 cases, and they were negative for proliferating cell nuclear antigen or only had rare positive cells. All 5 dogs presented with clinical signs of portal hypertension. Congenital hepatic fibrosis should be considered in the differential diagnosis in young dogs that present with portal hypertension and lesions that may have been interpreted as bridging biliary hyperplasia or extrahepatic biliary obstruction. }, number={1}, journal={VETERINARY PATHOLOGY}, author={Brown, D. L. and Van Winkle, T. and Cecere, T. and Rushton, S. and Brachelente, C. and Cullen, J. M.}, year={2010}, month={Jan}, pages={102–107} }
 @article{cullen_brown_kissling_foley_rizzo_marion_parron_french_2009, title={Aflatoxin B1 and/or Hepatitis B Virus Induced Tumor Spectrum in a Genetically Engineered Hepatitis B Virus Expression and Trp53 Haploinsufficient Mouse Model System for Hepatocarcinogenesis}, volume={37}, ISSN={["1533-1601"]}, DOI={10.1177/0192623309333137}, abstractNote={ The authors investigated the spectrum of tumors and Trp53 mutations in genetically engineered models using the FVB/N mouse that expressed the hepatitis B virus genome and/or carried a Trp53 null and wildtype allele and/or were exposed to aflatoxin B1. Liver tumor incidence was increased when all three risk factors were present. Without aflatoxin B1 exposure, neither Trp53 haploinsufficiency nor HBV expression affected liver tumor development. Liver tumor prevalence increased with aflatoxin B1 exposure ( p < .001), as thirteen of fourteen mice with liver tumors were initiated with aflatoxin B1. Liver tumors were more frequent in males (12/190) than females (2/170). Seventy-three mice developed sarcomas. Trp53 haploinsufficiency was associated with increased sarcoma incidence in males and females ( p < .001). In Trp53 haploinsufficient mice, the HBV transgene increased the risk of sarcoma in males and females ( p < .001). Lymphoma was significantly increased in Trp53 haploinsufficient FVB/N mice. There was no loss of heterozygosity at the wildtype Trp53 locus in twenty-five sarcomas or four hepatocellular tumors examined. No mutations were identified in the mRNA (exons 2–11) of Trp53 in six liver neoplasms or twenty-four sarcomas. In this model system, HBV expression affected only hepatocellular neoplasia in association with both aflatoxin B1 initiation and p53 haploinsufficiency. }, number={3}, journal={TOXICOLOGIC PATHOLOGY}, author={Cullen, John M. and Brown, Danielle L. and Kissling, Grace E. and Foley, Julie F. and Rizzo, Jennifer and Marion, Patricia L. and Parron, Vandy I. and French, John E.}, year={2009}, month={Apr}, pages={333–342} }