Medicine and Health Sciences Commons^™

Consequences And Management Of Canine Brachycephaly In Veterinary Practice: Perspectives From Australian Veterinarians And Veterinary Specialists, Anne Fawcett, Vanessa Barrs, Magdoline Awad, Georgina Child, Laurencie Brunel, Erin Mooney, Fernando Martinez-Taboada, Beth Mcdonald, Paul Mcgreevy

Paul McGreevy, PhD

This article, written by veterinarians whose caseloads include brachycephalic dogs, argues that there is now widespread evidence documenting a link between extreme brachycephalic phenotypes and chronic disease, which compromises canine welfare. This paper is divided into nine sections exploring the breadth of the impact of brachycephaly on the incidence of disease, as indicated by pet insurance claims data from an Australian pet insurance provider, the stabilization of respiratory distress associated with brachycephalic obstructive airway syndrome (BOAS), challenges associated with sedation and the anaesthesia of patients with BOAS; effects of brachycephaly on the brain and associated neurological conditions, dermatological conditions associated …

Prevalence Of Non Helicobacter Pylori Species In Patients Presenting With Dyspepsia, Javed Yakoob, Zaigham Abbas, Rustam Khan, Shagufta Naz, Zubair Ahmad, Muhammad Islam, Safia Awan, Fatima Jafri, Wasim Jafri

Zubair Ahmad

Background: Helicobacter species associated with human infection include Helicobacter pylori, Helicobacter heilmannii and Helicobacter felis among others. In this study we determined the prevalence of H. pylori and non-Helicobacter pylori organisms H. felis and H. heilmannii and analyzed the association between coinfection with these organisms and gastric pathology in Patients presenting with dyspepsia. Biopsy specimens were obtained from Patients with dyspepsia on esophagogastroduodenoscopy (EGD) for rapid urease test, histology and PCR examination for Helicobacter genus specific 16S rDNA, H. pylori phosphoglucosamine mutase (glmM) and urease B (ureB) gene of H. heilmannii and H. felis. Sequencing of PCR products of H. …

Naturalizing Anthropomorphism: Behavioral Prompts To Our Humanizing Of Animals, Alexandra C. Horowitz, Marc Bekoff

Marc Bekoff, PhD

Anthropomorphism is the use of human characteristics to describe or explain nonhuman animals. In the present paper, we propose a model for a unified study of such anthropomorphizing. We bring together previously disparate accounts of why and how we anthropomorphize and suggest a means to analyze anthropomorphizing behavior itself. We introduce an analysis of bouts of dyadic play between humans and a heavily anthropomorphized animal, the domestic dog. Four distinct patterns of social interaction recur in successful dog–human play: directed responses by one player to the other, indications of intent, mutual behaviors, and contingent activity. These findings serve as a …

Window Into Retinal Studies, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa.

Safety In Nonhuman Primates Of Ocular Aav2-Rpe65, A Candidate Treatment For Blindness In Leber Congenital Amaurosis, Samuel G. Jacobson, Sanford L. Boye, Tomas S. Aleman, Thomas J. Conlon, Caroline J. Zeiss, Alejandro J. Roman, Artur V. Cideciyan, Sharon B. Schwartz, András M. Komáromy, Michelle Doobrajh, Andy Y. Cheung, Alexandar Sumaroka, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Shalesh Kaushal, Albert M. Maguire, Terence R. Flotte, William W. Hauswirth

Gustavo D. Aguirre, VMD, PhD

Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV- RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2. RPE65 in RPE65 -mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vector-related toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular …

Photoreceptor Cell Death, Proliferation And Formation Of Hybrid Rod/S-Cone Photoreceptors In The Degenerating Stk38l Mutant Retina, Ágnes I. Berta, Kathleen Boesze-Battaglia, Sem Genini, Orly Goldstein, Paul J. O'Brien, Ágoston Szél, Gregory M. Acland, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell …

Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair R. Philip, Sarah J. P Lindauer, Susan E. Pearce-Kelling, Roberts F. Mullins, Alexander S. Graphodatsky, Daniel Ripoll, Jeanette S. Felix, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human and …

Long-Term Restoration Of Rod And Cone Vision By Single Dose Raav-Mediated Gene Transfer To The Retina In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jean Bennett, Tomas S. Aleman, Artur V. Cideciyan, Jeannette Bennicelli, Nadine S. Dejneka, Susan E. Pearce-Kelling, Albert M. Maguire, Krzysztof Palczewski, William W. Hauswirth, Samuel G. Jacobson

Gustavo D. Aguirre, VMD, PhD

The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no …

Free-Roaming Dogs In Developing Countries: The Benefits Of Capture, Neuter, And Return Programs, Jennifer Jackman, Andrew N. Rowan

Jennifer Jackman, Ph.D.

This chapter provides an overview of animal welfare and public health problems associated with free-roaming dog populations and strategies to resolve these problems. Placing CNR programs in the context of earlier dog and rabies control methods, the chapter explores CNR’s potential to overcome some of the shortcomings of earlier approaches and to improve animal welfare, reduce dog population growth, and prevent the spread of rabies and other canine-transmitted diseases. Constraints and current debates on current implementation of CNR programs are also examined.

A Single Base Pair Mutation Encoding A Premature Stop Codon In The Mis Type Ii Receptor Is Responsible For Canine Persistent Mullerian Duct Syndrome, Wenfang Wu, Shengqin Wan, Pujar Shashikant, Mark Haskins, Donald Schlafer, Mary Lee, Vicki Meyers-Wallen

Mary M. Lee

Mullerian inhibiting substance (MIS), a secreted glycoprotein in the transforming growth factor-beta family of growth factors, mediates regression of the Mullerian ducts during embryonic sex differentiation in males. In persistent Mullerian duct syndrome (PMDS), rather than undergoing involution, the Mullerian ducts persist in males, giving rise to the uterus, fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited …

Mast Cell Stabilization Decreases Cardiomyocyte And Lv Function In Dogs With Isolated Mitral Regurgitation., Betty Pat, Cheryl Killingsworth, Yuanwen Chen, James D Gladden, Greg Walcott, Pamela C Powell, Thomas Denney, Himanshu Gupta, Ravi Desai, Michael Tillson, A Ray Dillon, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog.

METHODS AND RESULTS: MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis …

Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …

Role Of Sec61alpha In The Regulated Transfer Of The Ribosome-Nascent Chain Complex From The Signal Recognition Particle To The Translocation Channel, Weiqun Song, David Raden, Elisabet Mandon, Reid Gilmore

Elisabet Mandon

Targeting of ribosome-nascent chain complexes to the translocon in the endoplasmic reticulum is mediated by the concerted action of the signal recognition particle (SRP) and the SRP receptor (SR). Ribosome-stripped microsomes were digested with proteases to sever cytoplasmic domains of SRalpha, SRbeta, TRAM, and the Sec61 complex. We characterized protein translocation intermediates that accumulate when Sec61alpha or SRbeta is inactivated by proteolysis. In the absence of a functional Sec61 complex, dissociation of SRP54 from the signal sequence is blocked. Experiments using SR proteoliposomes confirmed the assembly of a membrane-bound posttargeting intermediate. These results strongly suggest that the Sec61 complex regulates …

Supervillin (P205): A Novel Membrane-Associated, F-Actin-Binding Protein In The Villin/Gelsolin Superfamily, Kersi N. Pestonjamasp, Robert K. Pope, J. D. Wulfkuhle, Elizabeth J. Luna

Elizabeth J. Luna

Actin-binding membrane proteins are involved in both adhesive interactions and motile processes. We report here the purification and initial characterization of p205, a 205-kD protein from bovine neutrophil plasma membranes that binds to the sides of actin filaments in blot overlays. p205 is a tightly bound peripheral membrane protein that cosediments with endogenous actin in sucrose gradients and immunoprecipitates. Amino acid sequences were obtained from SDS-PAGE-purified p205 and used to generate antipeptide antibodies, immunolocalization data, and cDNA sequence information. The intracellular localization of p205 in MDBK cells is a function of cell density and adherence state. In subconfluent cells, p205 …

Metabolic Labeling Of Rod Outer Segment Phospholipids In Miniature Poodles With Progressive Rod-Cone Degeneration (Prcd), Mary Wetzel, Christian Fahlman, Paul O'Brien, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD