Departmental Papers (Vet)
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In addition to providing sophisticated medical treatments for animals of every size and kind, we believe veterinarians play an integral part in ensuring public health and food safety at both local and global levels, recognizing and controlling foreign and newly emerging diseases of livestock and poultry, including diseases transmissible from animals to people.
Our mission comprises teaching, healing, and scientific investigation. We believe that as veterinarians, we not only practice medicine and conduct groundbreaking research to advance all medicine, we teach the next generation to do the same.
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PublicationCriteria for Development of Animal Models of Diseases of the Eye(1980-12-01) Aguirre, Gustavo D PublicationCloning and Characterization of the cDNA Encoding the α-Subunit of cGMP-Phosphodiesterase in Canine Retinal Rod Photoreceptor Cells(1996-05-09) Wang, Weiquan; Acland, Gregory M; Aguirre, Gustavo D; Ray, Kunal PublicationThe Pathology of the Feline Model of Mucopolysaccharidosis VI(1980-12-01) Haskins, Mark E; Aguirre, Gustavo D; Jezyk, Peter F; Patterson, Donald FThree cats with feline arylsulfatase-B-deficient mucopolysaccharidosis were studied by light and transmission electron microscopy. Membrane-bound cytoplasmic inclusions were present in hepatocytes, bone marrow granulocytes, vascular smooth muscle cells, and fibroblasts in skin, cornea, and cardiac valves. Central nervous system lesions were restricted to mild ventricular dilatation, perithelial cell vacuolation, and, in one animal, cord compression by vertebral exostoses. The lesions in these cats closely resembled those described in human patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). PublicationAccelerating the Deactivation of Salmonella enterica Serovar Newport and Escherichia coli O157:H7 in Dairy Manure by Modifying pH or Temperature(2012-01-01) Toth, John D; Aceto, Helen W; Rankin, Shelley C; Dou, Zhengxia; DebRoy, ChitritaTo assess methods for control of disease-causing bacteria in animal manures prior to field application, we manipulated the temperature or adjusted pH of dairy manure to high (3.5 to 5) or low (10 to 12) values with aluminum sulfate or hydrated lime, and inoculated the manure with Salmonella enterica serovar Newport or Escherichia coli O157:H7, then incubated the manure at ambient temperature. At pH 4.2, S. Newport was eliminated within 6 days; however at pH >4.2 S. Newport was suppressed only temporarily and recovered to concentrations near the unamended controls. pH required to eliminate E. coli O157:H7 was 4.5. Both pathogens were killed by pH 11.0. The pathogens were eliminated within 2 weeks when inoculated manure was incubated at 37°C, whereas at 22°C and 4°C, the organisms persisted for much longer periods. S. Newport survived for over 300 days at 4°C, which has implications for manure spreading in colder seasons. PublicationExonic SINE Insertion in STK38L Causes Canine Early Retinal Degeneration (erd)(2010-12-01) Goldstein, Orly; Aguirre, Gustavo D; Kukekova, Anna V; Acland, Gregory MFine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal or abnormal photoreceptor development. Loss of STK38L function in erd provides novel potential insights into the role of the STK38L pathway in neuronal and photoreceptor cell function, and suggests that genes in this pathway need to be considered as candidate genes for hereditary retinal degenerations. PublicationCloning of Canine Galactokinase (GALK1) and Evaluation as a Candidate Gene for Hereditary Cataracts in Labrador Retrievers(2005-06-01) Sidjanin, Duska J; Aguirre, Gustavo D; McElwee, John L; Miller, BrianWe identified a pedigree of Labrador retrievers (LR) that develop hereditary cataracts between 6 and 18 months of age. In humans, galactokinase deficiency is an autosomal recessive disorder characterized by juvenile onset of cataracts.1 In order to evaluate GALK1 as a candidate gene, we cloned and sequenced the canine GALK1 gene and tested a single nucleotide polymorphism (SNP) in the gene for segregation with cataracts in the LR pedigree. PublicationEvaluation of Adeno-Associated Viral Vectors for Liver-Directed Gene Transfer in Dogs(2011-08-22) Bell, Peter; Haskins, Mark E; Gao, Guangping; Sleeper, Margaret M; Wang, Lili; Wang, Huan; Calcedo, Roberto; Vandenberghe, Luk H; Chen, Shu-Jen; Weisse, Chick; Withnall, Elanor; Wilson, James MThis study evaluated six adeno-associated viral (AAV) vectors expressing green fluorescent protein (GFP) from the liver-specific thyroid hormone–binding globulin (TBG) promoter made with novel capsids in canine liver-directed gene transfer. Studies in 1.5-month-old dogs, which were administered vector through a peripheral vein, showed that AAV8 capsid vectors had the most favorable performance profiles. Interestingly, the absolute levels of hepatocyte transduction achieved with AAV8 were lower in dogs compared with what had been achieved in mice and nonhuman primates. Additional studies were performed with AAV8 delivered into the hepatic artery in adult dogs, with higher doses of vector used to assess potential dose-limiting toxicities. These studies showed good transduction on day 7 in one dog that apparently was lost by day 28 in another dog through the generation of GFP-specific T cells. Each adult dog was carefully monitored for any hemodynamic changes associated with vector infusion. Both animals demonstrated mild to moderate hypotension and bradycardia, which appeared to be anesthesia-related, making it difficult to evaluate contributions of the vector. PublicationA Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration in Dogs(2013-08-01) Goldstein, Orly; Aguirre, Gustavo D; Jordan, Julie Ann; Acland, Gregory MPurpose: To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog. Methods: Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated. Results: The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on three chromosomes. Homozygosity and linkage disequilibrium analyses favored one chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non-stop mutation (c.1216T>C), which would result in the addition of 25 amino acids (p.*405Rext*25). Conclusions: Identification of this non-stop SAG mutation in dogs affected with retinal degeneration establishes this canine disease as orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans, and offers opportunities for genetic therapeutic intervention. PublicationAge-Dependent Disease Expression Determines Remodeling of the Retinal Mosaic in Carriers of RPGR Exon ORFn15 Mutations(2009-08-01) Beltran, William; Aguirre, Gustavo D; Acland, Gregory MPURPOSE. To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. METHODS. Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. RESULTS. A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches an increased density of cones was found to persist over time. Patches of disease gradually disappeared so that by 39 weeks of age the overall retinal morphology, albeit thinner, had improved lamination. In older XLPRA2 carriers (≥8.8 years), extended regions of severe degeneration occurred in the peripheral/mid-peripheral retina. In XLPRA1 carriers, opsin mislocalization and rare events of rod death were detected by TUNEL assay at 20 weeks of age; however, only patchy degeneration was seen by 1.4 years and was still apparent at 7.8 years. CONCLUSIONS. The time of onset and the progression of the disease differed between the two models. In the early-onset form (XLPRA2) the morphologic appearance of the retinal mosaic changed as a function of age, suggesting that structural plasticity persists in the early postnatal canine retina as mutant photoreceptors die. In the late-onset form (XLPRA1), patches of disease persisted until later ages. PublicationPersistent Left Cranial Vena Cava in Dogs: Angiocardiography, Significance, and Coexisting Anomalies(1963) Buchanan, James WPersistent left cranial venae were observed in angiocardiograms of 3 dogs at the University of Pennsylvania Veterinary Hospital. Although this vessel seldom has clinical significance, it is hoped this report will spare others the confusion caused by the first case in this series. These 3 dogs and 5 out of 7 others had significant cardiovascular anomalies in addition to persistent left cranial venae cavae.