@article{cullen_williams_zadrozny_otstot_solomon_sills_hong_2011, title={H-ras Consensus Sequence and Mutations in Primary Hepatocellular Carcinomas of Lemurs and Lorises}, volume={48}, ISSN={["0300-9858"]}, DOI={10.1177/0300985810388526}, abstractNote={The authors have determined a consensus sequence for exons 1 and 2 of H-ras from captive lemurs and lorises and evaluated samples of nonneoplastic liver and hepatocellular carcinomas (HCC) from affected animals for mutations in these exons. Frozen liver samples were collected from 20 animals representing 9 different species with a sex distribution of 10 males and 10 females. A total of 26 liver samples, including 11 normal livers, 9 HCC, and 6 samples from nonneoplastic regions of liver from animals with HCC, were evaluated. This is the first report of the consensus sequence for exons 1 and 2 of H-ras in prosimians, and the authors have determined that it is identical to that of human H-ras and differs only slightly from the chimpanzee sequence. Point mutations were identified in 6 of the 9 HCC samples examined with codons 7, 22, 32, 56, 61, 84, and 96 affected. Two carcinomas had double mutations, and one tumor had triple mutations. One HCC had a mutation in codon 61, which is identical to a recognized affected codon for an H-ras “hot spot” in rodent neoplasia that has also been reported in human tumors. Although not statistically different, metastasis occurred in 5 of 6 HCC with H-ras mutation and only 1 of 3 HCC without mutations. There were 4 silent mutations that did not contain changes in the encoded amino acids, 2 of which were found in nonneoplastic regions of tumor-bearing liver.}, number={4}, journal={VETERINARY PATHOLOGY}, author={Cullen, J. M. and Williams, C. and Zadrozny, L. and Otstot, J. T. and Solomon, G. G. and Sills, R. C. and Hong, H-H. L.}, year={2011}, month={Jul}, pages={868–874} }
 @article{zadrozny_williams_remick_cullen_2010, title={Spontaneous Hepatocellular Carcinoma in Captive Prosimians}, volume={47}, ISSN={["1544-2217"]}, DOI={10.1177/0300985809359380}, abstractNote={Spontaneous hepatocellular carcinoma has been reported as a relatively common neoplasm in prosimians; however, the cause is unknown. To investigate possible pathogenic mechanisms, the authors performed a review of all adult animals from a captive prosimian population that had postmortem examinations over the past 10 years. They performed a detailed histologic evaluation of all suspected proliferative liver lesions and diagnosed hepatocellular carcinoma in 14 of 145 lemurs (9.7%). Affected animals ranged between the ages of 6 and 40 years old. The tumors had an unusually aggressive growth pattern for animal species; metastasis to the lungs or mediastinum was evident in 7 of 14 animals. Thirty-one animals—9 with hepatocellular carcinomas and 22 age-matched controls without hepatic neoplasia—were tested to evaluate the relationship between hepatic iron stores (as well as other trace metals) and the presence of hepatocellular carcinoma. There was no difference between the hepatic iron, copper, or molybdenum in lemurs with hepatocellular carcinoma and those without, suggesting that iron is not a key element in the pathogenesis of liver tumor formation. Analysis of 22 serum samples from animals with and without liver tumors indicated no evidence of active infection with a hepadnavirus, the virus family that includes hepatitis B virus. Hepatitis C virus and aflatoxin B1 were considered as potential causes and ruled out owing to lack of associated histopathologic lesions. In conclusion, hepatocellular neoplasia is relatively common in captive prosimians, although previously suspected etiologies seem unlikely.}, number={2}, journal={VETERINARY PATHOLOGY}, author={Zadrozny, L. M. and Williams, C. V. and Remick, A. K. and Cullen, J. M.}, year={2010}, month={Mar}, pages={306–311} }
 @article{oberkirchner_linder_zadrozny_olivry_2010, title={Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide}, volume={21}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77956458558&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2009.00876.x}, abstractNote={Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucagonoma-associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11-year-old golden retriever dog with pancreatic glucagonoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1-3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma-associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non-resectable or relapsing pancreatic glucagonoma-associated NME.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Oberkirchner, Ursula and Linder, Keith E. and Zadrozny, Leah and Olivry, Thierry}, year={2010}, month={Oct}, pages={510–516} }
 @article{elangbam_job_zadrozny_barton_yoon_gates_slocum_2008, title={5-Hydroxytryptamine (5HT)-induced valvulopathy: Compositional. valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats}, volume={60}, ISSN={["0940-2993"]}, DOI={10.1016/j.etp.2008.03.005}, abstractNote={Several drugs have been linked to valvulopathy in humans, including therapeutic agents for obesity, Parkinson's disease and migraine. There is increasing evidence that the 5-hydroxytryptamine 2B receptor (5HT2BR) activation and/or increased circulating 5HT (5-hydroxytryptamine) may play a significant role in the pathogenesis of drug-induced valvulopathy. In the present study, we investigated whether 7-day 5HT subcutaneous injections led to structural and compositional abnormalities in conjunction with transcriptomic modulation of 5HT2BR and 5HT transporter (5HTT) genes in the aortic and mitral valves of Sprague-Dawley (SD) rats. Subcutaneous injections of 5HT for 7 days resulted in thickening and compositional alteration of aortic and mitral valves in SD rats. More specifically, valve-leaflets from 5HT-treated rats had greater valve thickness, a higher amount of glycosaminoglycans (GAGs) and a lower amount of collagen. The compositional alteration was associated with up-regulation and down-regulation of 5HT2BR and 5HTT genes, respectively. The present study strongly suggests that the activation of 5HT2BR and inhibition of 5HTT played a significant role in the pathogenesis of 5HT-induced valvulopathy in SD rats. Thus, these findings further highlight the necessity and/or utilization of animal models to screen potential valvular effects of serotonergic compounds.}, number={4-5}, journal={EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY}, author={Elangbam, Chandikumar S. and Job, Lauren E. and Zadrozny, Leah M. and Barton, Joanna C. and Yoon, Lawrence W. and Gates, Lisa D. and Slocum, Nikki}, year={2008}, month={Aug}, pages={253–262} }
 @article{zadrozny_stauffer_armstrong_jones_gookin_2006, title={Neutrophils do not mediate the pathophysiological sequelae of Cryptosporidium parvum infection in neonatal piglets}, volume={74}, ISSN={["1098-5522"]}, url={http://europepmc.org/abstract/med/16988224}, DOI={10.1128/IAI.00153-06}, abstractNote={ABSTRACT Cryptosporidium parvum is a minimally invasive protozoal pathogen of intestinal epithelium that results in villus atrophy, mucosal lipid peroxidation, diarrhea, and diminished barrier function. Influx of neutrophils is a consistent feature of human and animal cryptosporidiosis, and yet their contribution to the pathological sequelae of infection has not been investigated. Accordingly, we used an established neonatal piglet model of C. parvum infection to examine the role of neutrophils in disease pathogenesis by inhibiting their recruitment and activation in vivo using a monoclonal anti-CD18 antibody. Infected piglets were treated daily with anti-CD18 or isotype control immunoglobulin G and euthanized at peak infection, at which time neutrophil infiltrates, lipid peroxidation, severity of infection, and intestinal barrier function were quantified. C. parvum infection resulted in a significant increase in mucosal neutrophil myeloperoxidase activity that was prevented by treatment of piglets with anti-CD18 antibody. Neutrophil recruitment was dependent on mucosal superoxide formation (prevented by treatment of infected piglets with superoxide dismutase). Neutrophils did not contribute to peroxynitrite formation or peroxidative injury of C. parvum-infected mucosa and had no impact on the severity of epithelial infection, villus atrophy, or diarrhea. The presence of neutrophils in C. parvum-infected mucosa was associated with enhanced barrier function that could not be attributed to mucosal elaboration of prostaglandins or stimulation of their synthesis. These studies are the first to demonstrate that neutrophilic inflammation arising in response to infection by a noninvasive epithelial pathogen results in physiologic rather than pathological effects in vivo.}, number={10}, journal={INFECTION AND IMMUNITY}, author={Zadrozny, Leah M. and Stauffer, Stephen H. and Armstrong, Martha U. and Jones, Samuel L. and Gookin, Jody L.}, year={2006}, month={Oct}, pages={5497–5505} }