Departmental Papers (Vet)
At Penn Vet, we think differently about veterinary medicine.
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.
We believe future veterinarians should serve as the frontline, guarding against bio- and agro-terrorism and working to protect the environment, all the while advancing the forefront of biomedical research. At Penn Vet, we lead the way for veterinarians of tomorrow.
PublicationExonic SINE Insertion in STK38L Causes Canine Early Retinal Degeneration (erd)(2010-12-01) Goldstein, Orly; Aguirre, Gustavo D; 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. PublicationA Better Index of Body Adiposity(2011-05-01) Bergman, Richard N; Stefanovski, Darko; Buchanan, Thomas A; Sumner, Anne E; Reynolds, James C; Sebring, Nancy G; Xiang, Anny H; Watanabe, Richard MObesity is a growing problem in the United States and throughout the world. It is a risk factor for many chronic diseases. The BMI has been used to assess body fat for almost 200 years. BMI is known to be of limited accuracy, and is different for males and females with similar %body adiposity. Here, we define an alternative parameter, the body adiposity index (BAI = ((hip circumference)/((height)1.5)–18)). The BAI can be used to reflect %body fat for adult men and women of differing ethnicities without numerical correction. We used a population study, the “BetaGene” study, to develop the new index of body adiposity. %Body fat, as measured by the dual-energy X-ray absorptiometry (DXA), was used as a “gold standard” for validation. Hip circumference (R = 0.602) and height (R = −0.524) are strongly correlated with %body fat and therefore chosen as principal anthropometric measures on which we base BAI. The BAI measure was validated in the “Triglyceride and Cardiovascular Risk in African-Americans (TARA)” study of African Americans. Correlation between DXA-derived %adiposity and the BAI was R = 0.85 for TARA with a concordance of C_b = 0.95. BAI can be measured without weighing, which may render it useful in settings where measuring accurate body weight is problematic. In summary, we have defined a new parameter, the BAI, which can be calculated from hip circumference and height only. It can be used in the clinical setting even in remote locations with very limited access to reliable scales. The BAI estimates %adiposity directly. 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; DebRoy, Chitrita; Dou, ZhengxiaTo 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. PublicationClinico-Pathologic Conference: Chronic Nephritis in a Bull(1961-10-15) Marshak, Robert; Buchanan, James W; Sauer, R. M PublicationConsistency of the Disposition Index in the Face of Diet Induced Insulin Resistance: Potential Role of FFA(2011-03-30) Stefanovski, Darko; Richey, Joyce M; Woolcott, Orison; Lottati, Maya; Zheng, Dan; Harrison, Lisa N; Ionut, Viorica; Kim, Stella P; Bergman, Richard NObjective Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. Methods In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance. Results Hypercaloric high fat feeding in dogs resulted in modest weight gain, and an increase in adipose tissue with no change in the non-adipose tissue size. To compensate for the drop in insulin sensitivity, there was a significant rise in plasma insulin, which can be attributed in part to a decrease in the metabolic clearance rate of insulin and increased insulin secretion. In this study we observed complete compensation for high fat diet induced insulin resistance as measured by the disposition index. The compensatory hyperinsulinemia was coupled with significant changes in plasma FFAs and no change in plasma glucose. Conclusions We postulate that early in the development of diet induced insulin resistance, a change in plasma FFAs may directly, through signaling at the level of β-cell, or indirectly, by decreasing hepatic insulin clearance, result in the observed hyperinsulinemic compensation. PublicationRadiation Hybrid Mapping of Cataract Genes in the Dog(2006-05-24) Hunter, Linda S; Aguirre, Gustavo D; Johnson, Jennifer L; Zangerl, Barbara; Galibert, Francis; Andre, Catherine; Kirkness, Ewen; Talamas, Elijah; Acland, Gregory MPurpose: To facilitate the molecular characterization of naturally occurring cataracts in dogs by providing the radiation hybrid location of 21 cataract-associated genes along with their closely associated polymorphic markers. These can be used for segregation testing of the candidate genes in canine cataract pedigrees. Methods: Twenty-one genes with known mutations causing hereditary cataracts in man and/or mouse were selected and mapped to canine chromosomes using a canine:hamster radiation hybrid RH5000 panel. Each cataract gene ortholog was mapped in relation to over 3,000 markers including microsatellites, ESTs, genes, and BAC clones. The resulting independently determined RH-map locations were compared with the corresponding gene locations from the draft sequence of the canine genome. Results: Twenty-one cataract orthologs were mapped to canine chromosomes. The genetic locations and nearest polymorphic markers were determined for 20 of these orthologs. In addition, the resulting cataract gene locations, as determined experimentally by this study, were compared with those determined by the canine genome project. All genes mapped within or near chromosomal locations with previously established homology to the corresponding human gene locations based on canine:human chromosomal synteny. Conclusions: The location of selected cataract gene orthologs in the dog, along with their nearest polymorphic markers, serves as a resource for association and linkage testing in canine pedigrees segregating inherited cataracts. The recent development of canine genomic resources make canine models a practical and valuable resource for the study of human hereditary cataracts. Canine models can serve as large animal models intermediate between mouse and man for both gene discovery and the development of novel cataract therapies. PublicationPosterior Lenticonus in the Dog(1973-07-01) Aguirre, Gustavo D; Bistner, Stephen IPosterior lenticonus is a congenital defect of the posterior lenticular surface. The posterior cortical and capsular regions of the lens have a circumscribed conelike or globular protrusion of variable size. Opacities may be present in the region of the conus. The defect has been reported in man, rabbits, calves and mice. This report documents 2 cases in unrelated dogs. The possible mechanism for the formation of this defect is discussed. PublicationAn Assessment of Ammonia Emissions from Dairy Facilities in Pennsylvania(2001-01-01) Ferguson, James D; Dou, Zhengxia; Ramberg, Charles FA survey of 715 Holstein dairy farms in Pennsylvania was used to construct demographics for the average Holstein dairy farm. The average Holstein dairy farm was composed of 69 lactating cows; 11 nonlactating, pregnant cows; 44 heifers; and 18 calves. Milk production averaged 27.3 kg (60.0 lb). Crop area averaged 73.6 ha. Milk production, crop area and type, average county yields, and herd animal groups were used to construct a typical feeding program for these farms. Typical rations were constructed for six feeding groups (three milk production groups, one nonlactating group, two heifer groups) to meet milk production, pregnancy, and growth requirements. Rations were constructed based on three forage qualities (excellent, average, and poor) typically observed on Pennsylvania dairy farms. Data for animal description (milk production, body weight, growth, and pregnancy status) and ration components and amounts consumed for each animal group were input into the excretion model of the Dairy Nutrient Planner computer program (DNP). Excretion of fecal N and dry matter (DM), urinary N, and total P and K were produced for each animal group and used to assess potential volatile losses of N. Work at the Marshak Dairy, New Bolton Center, indicates the majority of urinary N is rapidly lost as ammonia from dairy facilities. Based on this observation, the losses of N as ammonia were estimated to be 4.63, 4.62, and 4.28 tonne/year for the farm with excellent, average, and poor quality forages, respectively. Volatile losses of N may be reduced most by controlling levels of urea in urine. Urinary N may be reduced through dietary manipulation of protein and carbohydrate sources. Conversion of urea to ammonia may be reduced by altering the pH of barn floors and gutters. Entrapment of ammonia may be accomplished by acidification of manure slurry. Atmospheric ammonia contributes to acid rain, eutrophication of estuaries and lakes, and particulate air pollution. Reduction of ammonia emissions from dairy barns can significantly reduce atmospheric pollution and improve air and water quality. PublicationBEST1 Gene Therapy Corrects a Diffuse Retina-Wide Microdetachment Modulated by Light Exposure(2018-03-20) Guziewicz, Karina E; Cideciyan, Artur V; Beltran, William A; Komáromy, András M; Dufour, Valerie L; Swider, Malgorzata; Iwabe, Simone; Sumaroka, Alexander; Kendrick, Brian T; Ruthel, Gordon; Chiodo, Vince A; Heon, Elise; Hauswirth, William W; Jacobson, Samuel GMutations in the BEST1 gene cause detachment of the retina and degeneration of photoreceptor (PR) cells due to a primary channelopathy in the neighboring retinal pigment epithelium (RPE) cells. The pathophysiology of the interaction between RPE and PR cells preceding the formation of retinal detachment remains not well-understood. Our studies of molecular pathology in the canine BEST1 disease model revealed retina-wide abnormalities at the RPE-PR interface associated with defects in the RPE microvillar ensheathment and a cone PR-associated insoluble interphotoreceptor matrix. In vivo imaging demonstrated a retina-wide RPE-PR microdetachment, which contracted with dark adaptation and expanded upon exposure to a moderate intensity of light. Subretinal BEST1 gene augmentation therapy using adeno-associated virus 2 reversed not only clinically detectable subretinal lesions but also the diffuse microdetachments. Immunohistochemical analyses showed correction of the structural alterations at the RPE-PR interface in areas with BEST1 transgene expression. Successful treatment effects were demonstrated in three different canine BEST1 genotypes with vector titers in the 0.1-to-5E11 vector genomes per mL range. Patients with biallelic BEST1 mutations exhibited large regions of retinal lamination defects, severe PR sensitivity loss, and slowing of the retinoid cycle. Human translation of canine BEST1 gene therapy success in reversal of macro- and microdetachments through restoration of cytoarchitecture at the RPE-PR interface has promise to result in improved visual function and prevent disease progression in patients affected with bestrophinopathies.