Abstract
Bovine papilloma virus-2 (BPV-2) DNA has been found in both normal bovine urothelium and naturally occurring carcinomas of the bovine urinary bladder. The BPV-2 oncoprotein E5, however, is expressed only in the cancer cells, indicating a possible role for E5 in tumorigenesis. Borzacchiello and colleagues studied the BPV-2 viral E5 protein in bovine urothelial tumors and found that E5 forms a stable complex in vivo with the activated (phosphorylated) form of the platelet derived growth factor β (PDGF β) receptor. E5 colocalizes with the PDGF β receptor in bovine neoplastic urothelial cells. Although the PDGF β receptor is present in both normal and neoplastic bladder tissue, phosphorylation of PDGF β receptor was observed only in the neoplastic cells. Together these data support a role for involvement of BPV-2 E5 in the development of bovine urothelial tumors. This model will be useful for further exploring the mechanisms of papillomavirus-induced carcinogenesis and for testing vaccine strategies for prevention and control.
Borzacchiello G, Russo V, Gentile F, Roperto F, Venuti A, Nitsch L, Campo MS, Roperto S. Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor β receptor in naturally occurring bovine urinary bladder tumors. Oncogene advance online publication, 3 Oct 2005 (DOI 10.1038/sj.onc.1209152).
The threat of an avian influenza A virus (subtype H5N1) pandemic has been widely publicized. Evidence in humans and felids suggests that the virus may exhibit an expanded tissue tropism in mammals that is not restricted to the respiratory tract. To test this hypothesis Rimmelzwaan and colleagues experimentally inoculated domestic cats with H5N1 intratracheally and by feeding virus-infected chicks. A thorough histopathologic analysis revealed widespread virus replication that was not confined to the respiratory system. Severe necrosis and inflammation were observed in respiratory, nervous, cardiovascular, urinary, digestive, lymphoid and endocrine tissues. In addition, sentinel cats also developed lesions. Virus isolation procedures revealed shedding from multiple sites, suggesting that the virus can be transmitted by the digestive tract in addition to respiratory secretions. The information from this report will be important in understanding the pathogenesis of H5N1 infection in mammals and developing adequate approaches in response to the current outbreak.
Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RAM, Osterhaus ADME, Kuiken T. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol
The domestic dog displays remarkable diversity with respect to morphology, physiology and behavior. With the recent publication of a high-quality draft sequence of the canine genome, man's best friend will make valuable contributions to comparative medicine and to our understanding of the evolutionary forces that have impacted all mammals. This draft, derived from a female boxer, covers approximately 99% of the euchromatic canine sequence. Extensive comparison to the genomes of humans, chimpanzees and rodents has already highlighted important areas of interest such as highly conserved non-coding regions clustered near key developmental genes. Using partial sequences from other breeds, over 2.5 million single nucleotide polymorphisms (SNPs) have been identified. The canine genome sequence is a remarkable resource that will surely accelerate the identification of disease-causing genes in dogs and other species. For those not directly involved in canine genetic studies, this article contains fascinating information related to the evolution and biology of the domestic dog and the entire family Canidae.
Lindblad-Toh K, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature
Somatic mutations in the adenomatous polyposis coli (APC) gene contribute to human colorectal cancer, and germline APC mutations are responsible for the development of familial adenomatous polyposis syndrome. Heterozygous APC mice develop tumors in the small intestine and are used extensively to study gastrointestinal tumor biology. There is increasing interest in using the zebrafish (Danio rerio) as an alternative to transgenic mice to investigate a wide variety of diseases, including cancer. The short generation time, large number of progeny, lower cost and transparent embryos make the zebrafish a unique model. Because homozygosity for APC is embryonic lethal in zebrafish, Anna-Pavlina Haramis developed a zebrafish model with one mutated APC gene. The apc +/− fish developed intestinal and hepatic adenomas that share remarkable histopathologic similarity to human tumors and those of min mice. Immunohistochemical analysis confirmed high levels of β-catenin and c-myc in these tumors. This study demonstrates the usefulness of genetically engineered zebrafish models.
Haramis APG, Hurlstone A, van der Velden Y, Begthel H, van den Born M, Offerhaus GJA, Clevers HC. Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia. EMBO reports advance online publication, 27 Jan 2006 (doi:10.1038/sj.embor.7400638).
Intrahepatic and extrahepatic congenital portosystemic shunts (PSS) are seen predominantly in large and small breed dogs, respectively. Liver samples from 58 dogs with congenital PSS were examined by Baade et al. Histopathological findings in both types of shunts were similar and included portal vein hypoplasia, proliferation of arterioles and ductules, lymphangiectasis, mild fibrosis and hepatocellular atrophy. A panel of immunohistochemical markers demonstrated increased expression of alpha-smooth muscle actin as well as the presence of desmin in hepatic stellate cells of dogs with PSS compared to normal dogs. Livers with PSS also had increased amounts of perisinusoidal extracellular matrix. Some dogs with PSS underwent partial occlusion surgery. Post-surgical liver biopsies from these dogs were similar to the pre-surgical specimens with some decrease in the degree of hepatocellular degeneration. The characterization of the morphological and immunohistochemical changes secondary to congenital PSS will aid in the diagnosis of this condition and may provide useful information regarding the pathophysiological response of the liver to alterations in vascular flow.
Baade S, Aupperle H, Grevel V, Schoon HA. Histopathological and immunohistochemical investigations of hepatic lesions associated with congenital portosystemic shunt in dogs. J Comp Pathol