Differential genetic regulation of canine hip dysplasia and osteoarthritis.

BACKGROUND: Canine hip dysplasia (HD) is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA). The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 721 dogs, including both an association and linkage population, were genotyped. The association population included 8 pure breeds (Labrador retriever, Greyhounds, German Shepherd, Newfoundland, Golden retriever, Rottweiler, Border Collie and Bernese Mountain Dog). The linkage population included Labrador retrievers, Greyhounds, and their crosses. Of these, 366 dogs were genotyped at ∼22,000 single nucleotide polymorphism (SNP) loci and a targeted screen across 8 chromosomes with ∼3,300 SNPs was performed on 551 dogs (196 dogs were common to both sets). A mixed linear model approach was used to perform an association study on this combined association and linkage population. The study identified 4 susceptibility SNPs associated with HD and 2 SNPs associated with hip OA. CONCLUSION/SIGNIFICANCE: The identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1) reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.

Virologic survey of dogs with naturally acquired idiopathic conjunctivitis.

OBJECTIVE: To determine the frequency of viral detection in conjunctival samples from client-owned domestic dogs with naturally acquired idiopathic conjunctivitis and to identify signalment, historical, and clinical findings positively associated with viral detection. DESIGN: Case-control study. ANIMALS: 30 dogs with naturally acquired idiopathic conjunctivitis and a control population of 30 dogs without ocular disease. PROCEDURES: Complete physical and ophthalmic examinations were performed for each dog. Conjunctival swab specimens were analyzed by use of virus isolation and PCR assays for the following viruses: canine adenovirus-2 (CAV-2), canine distemper virus, canine herpesvirus-1 (CHV-1), canine parainfuenza virus, canine respiratory coronavirus, infuenza A virus, and West Nile virus. Signalment, clinical, and historical information was recorded and compared between study groups. RESULTS: Viruses were detected by either virus isolation or PCR methods significantly more frequently in conjunctival samples from dogs with conjunctivitis (7/30 [23.3%]) than dogs without conjunctivitis (0/30 [0%]). Canine herpesvirus-1 was isolated from 2 conjunctival samples and detected by use of PCR assay in 5 conjunctival samples. Canine adenovirus-2 was isolated from 1 conjunctival sample and detected by use of PCR assay in 2 conjunctiva samples. Sexually intact dogs and frequent exposure to dogs outside the household were positively associated with viral detection in the conjunctivitis group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that CHV-1 and CAV-2 are common etiologic agents of conjunctivitis in domestic dogs. Risk factors for viral conjunctivitis in dogs reflected increased exposure to other dogs and opportunities for contact with infectious secretions.

Eurytrema procyonis and pancreatitis in a cat.

A young adult male domestic shorthair cat was presented for physical examination, routine vaccinations, and a fecal examination. Physical examination revealed no significant abnormalities. Eggs of the raccoon pancreatic fluke Eurytrema procyonis were detected by fecal flotation. Results of a complete blood count and serum biochemistry panel were normal. Abdominal sonography revealed an enlarged hypoechoic pancreas with a hyperechoic rim, and a distended and thickened pancreatic duct. Serum pancreatic lipase immunoreactivity (PLI) was increased. These findings supported the possibility of fluke-associated pancreatitis. Treatment with praziquantel/pyrantel/febantel was associated with resolution of sonographic abnormalities and normalization of PLI.

Clevudine inhibits hepatitis delta virus viremia: a pilot study of chronically infected woodchucks.

In a small controlled study, clevudine, a potent inhibitor of hepadnaviruses, including hepatitis B virus and woodchuck hepatitis virus, suppressed hepatitis delta virus (HDV) viremia in chronically infected woodchucks. Suppression was correlated with the marked reduction of woodchuck hepatitis virus surface antigen in individual animals, consistent with the concept that repression of surface antigen expression may be a useful antiviral strategy for HDV.

Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection.

The Eastern woodchuck ( Marmota monax ) harbors a DNA virus (Woodchuck hepatitis virus [WHV]) that is similar in structure and replicative life cycle to the human hepatitis B virus (HBV). Like HBV, WHV infects the liver and can cause acute and chronic hepatitis. Furthermore, chronic WHV infection in woodchucks usually leads to development of hepatocellular carcinoma (HCC) within the first 2-4 years of life. The woodchuck model has been important in the preclinical evaluation of safety and efficacy of the antiviral drugs now in use for treatment of HBV infection and continues to serve as an important, predictive model for innovative forms of therapy of hepatitis B using antiviral nucleosides and immune response modifiers alone or in combination. Almost all woodchucks that become chronic WHV carriers after experimental neonatal inoculation develop HCC with a median HCC-free survival of 24 months and a median life expectancy of 30-32 months. The woodchuck model of viral-induced HCC has been used effectively for the development of new imaging agents for enhancement of detection of hepatic neoplasms by ultrasound and magnetic resonance imaging. The chemoprevention of HCC using long-term antiviral nucleoside therapy has been shown in the woodchuck, and "proof of principal" has been established for some of the innovative, molecular methods for treatment of HCC. The model is available for fundamental investigations of the viral and molecular mechanisms responsible for hepatocarcinogenesis and should have substantial value for future development of innovative methods for chemoprevention and gene therapy of human HCC.

Taenia crassiceps Infection in the Woodchuck: A Retrospective Study of 13 Cases.

Abstract- Large, fluctuant, fluid-filled subcutaneous masses containing hundreds of Taenia crassiceps cysticerci were detected in 13 woodchucks trapped in central New York and Maryland. The axillary region (7 of 13 animals) and adjacent lateral thoracic wall (4 of 13 animals) were most frequently affected. One animal had a focal parasitic granuloma in the lung and another had numerous cysticerci present within the hepatic parenchyma. Histologically, parasite sections were surrounded by varying degrees of fibrosis and mild scattered to coalescing lymphocytic aggregates were present in the adjacent subcutaneous tissues. There was minimal infiltration of subcutaneous lesions into the underlying musculature. Scanning electron microscopy of the parasites indicated the presence of numerous developing buds in the area of the posterior bladder. Scanning and transmission electron microscopy indicated that cysticerci were covered with a dense coating of microtriches. Taenia crassiceps lesions were found in 13 (2.6 per cent) of 501 trapped woodchucks, and in none of 293 colony-born woodchucks. No relationship between Taenia crassiceps infection and woodchuck hepatitis virus infection could be established. Résumé- Des masses sous-cutanées volumineuses, fluctuantes, remplies de liquides, contenant des centaines de cysticerques de Taenia crassiceps furent découvertes chez 13 marmottes capturées au centre de l'Etat de New-York et dans le Maryland. La région axillaire (7 des 13 animaux) et la paroi thoracique latérale adjacente (4 des 13 animaux) étaient les plus fréquemment atteintes. Un animal avait un granulome parasitaire focal dans un poumon et un autre avaient de nombreux cysticerques dans le parenchyme hépatique. D'un point de vue histologique, les sections de parasite étaient entourées par une fibrose d'importance variable, et des aggrégats lymphocytaires modérés, dispersés ou coalescents, étaient présents dans les tissus sous-cutanés adjacents. Il y avait une infiltration minimale des lésions sous-cutanées dans les muscles sous-jacents. La microscopie électronique à balayage montra la présence de nombreux bourgeons en développement dans la zone postérieure de la vessie. La microscopie électronique à balayage et par transmission indiqua que les cysticerques étaient couverts par un enduit dense de microtriches. Des lésions dûes àTanenia crassiceps furent découvertes chez 2.6% (13 sur 501) des marmottes capturées, et 0% (0 sur 293) des marmottes nées en captivité. Aucune relation entre l'infestation par Taenia crassiceps et l'hépatite infectieuse virale de la marmotte ne put être établie. Zusammenfassung- Bei 13 im Zentrum von New York und Maryland gefangenen Waldmurmeltieren wurden große, fluktuierende, flüssigkeits-gefüllte subcutane Massen festgestellt, die Hunderte von Taenia crossiceps cysticerci enthielten. Am häufigsten waren der Axillarbereich (boi 7 von 13 Tieren) und die angrenzende seitliche Brustwand (bei 4 von 13 Tieren) betroffen. Ein Murmeltier hatte ein fokales parasitäres Granulom in der Lunge, ein anderes zahlreiche Cysticerci im Leberparenchym. Im histologischen Bild zeigten sich von verschieden starken Fibrosen umgebene Parasitenausschnitte und leicht verstreute bis konfluierende Lymphozytenaggregate im angrenzenden subcutanen Gewebe. Die darunterliegende Muskulatur wurde nur minimal von den subcutanen Läsionen infiltriert. Unter dem Rasterelektronenmikroskop zeigten die Parasiten zahlreiche sich entwickelnde Knospen im Bereich der hinteren Blase. Im Rasterelektronenmikroskop und im Transmissions-Elektronenmikroskop waren die Cysticeri mit einer dichten Schicht aus Mikrotrichen bedeckt. Taenia crassiceps-Läsionen wurden bei 2.6% (13 von 501) der gefangenen und bei 0% (0 von 293) der koloniegeborenen Waldmurmeltiere nachgewiesen. Ein Zusammenhang zwischen der Taenia crassiceps - Infektion und einer Waldmurmeltier-Hepatitis-Virusinfektion konnte nicht festgestellt werden. Resumen En 13 marmotas capturados en Nueva York y en Maryland se detectaron masas subcutáneas de gran tamaño, llenas de líquido y que contenían cientos de cisticercos de Taenia crassiceps. Las zonas más afectadas fueron la región axilar (7 de 13 animales) y la pared torácica adyacente (4 de 13 animales). Un animal presentaba un granuloma parasitario focal en un pulmón y otro presentaba numerosos cisticercos en el parénquima hepático. Histológicamente, los parásitos aparecían rodeados por una reacción fibrosa de diferente intensidad y en el tejido subcutáneo próximo se observaban agregados linfocitarios. La musculatura subyacente no aparecía afectada. Estudios de microscopía electrónica de transmisión y de barrido demostraron que los cisticercos estaben recubiertos por una densa capa de microtricos. Lesiones producidas par Taenia crassiceps se detectaron en el 2,6% (13 de 501) de los capturados y en el 0% (0 de 293) de los procedentes de un criadero. No se pudo demostrar relación alguna entre la infestación con Taenia crassiceps y la infección con el virus de la hepatitis de las marmotas.

Spontaneous Neoplastic and Hyperplastic Skin Lesions of the Woodchuck.

Abstract- In a retrospective postmortem survey of laboratory woodchucks (Marmota monax), four neoplastic and one hyperplastic skin lesions were identified. These included two lipomas and single cases each of squamous cell carcinoma, apocrine gland adenoma and sebaceous gland hyperplasia. Three animals were male, the other two female. Animals ranged from 2 to 7 years of age. Four animals were negative for markers of woodchuck hepatitis virus (WHV). The other, a 7-year-old female with an axillary lipoma, was a chronic carrier. Four neoplasms were discrete masses; the digital squamous cell carcinoma was more extensive, infiltrative and interfered with prehension. The low incidence of skin tumours (0.8 per cent) parallels that described in other laboratory rodent species. Résumé- Une étude rétrospective portant sur des autopsies de marmottes de laboratoire (Marmota monax) a permis la mise en évidence de 4 lésions néoplasiques et d'une lésion hyperplasique de la peau. Il s'agissait de deux lipomes ainsi que de cas isolés d'épthélioma spinocellulaire, d'adénome apocrine et d'hyperplasie sébacée. Trois animaux étaient des mäles et deux, des femelles. L'äge variait de 2 à 7 ans. Quatre animaux étaient négatifs au marqueur de l'hépatite virale de la marmotte (WHV). Le cinquième, une femelle de 7 ans présentant un lipome axillaire, était un porteur chronique. Quatre des néoplasies étaient des masses discrètes; l'épithélioma spinocellulaire du doigt était plus extensif, infiltrant et gênait la préhension. La faible incidence des tumeurs cutanées (0,8%) est identique à celle que l'on décrit chez d'autres rongeurs de laboratoire. Zusammenfassung- In einer retrospektiven postmortalen Untersuchung von Labor-Murmeltieren (Marmota monax) wurden vier neoplastische und eine hyperplastische Hautveränderung festgestellt. Darunter waren zwei Lipome und einzelne Fälle von jeweils einem Plattenepithelkazinom, einem apokrinen Adenom und einer Talgdrüsenhyperplasie. Drei Tiere waren männlich, die beiden anderen weiblich. Das Alter der Tiere lag zwischen 2 und 7 Jahren. Vier der Tiere reagierten negativ auf Murmeltier-Hepatitis-Virus-Marker (WHV). Ein weiteres 7 Jahre altes weibliches Tier mit einem Lipom im Achselbereich war chronischer Träger. Vier der Neubildungen stellten diskrete Massen dar; das Plattenepithelkarzinom im Fußbereich war ausgedehnter, infiltrativ wachsend und beeinträchtigte die Greifbewegungen. Das geringe Vorkommen von Hauttumoren (0,8%) entspricht demjenigen, das bei anderen Nagern beschrieben wurde. Resumen En un estudio retrospectivo postmortem de marmotas de laboratio (Marmota monax) se identificaron cuatro lesiones neoplásicas cutáneas y una lesión cutánea de tipo hiperplásico. Entre estas se encontraban dos lipomas y casos individuales de carcinoma de células escamosas, adenoma de glándulas apocrinas e hiperplasia de glándulas sebáceas. Tres animales eran machos y los dos restantes eran hembras. La edad de los animales oscilaba entre los dos y los siete años. Cuatro animales fueron negativos para maracadores del virus de la hepatitis de la marmota. El otor, una hembra de 7 años de edad con un lipoma axilar, era un portador crónico. Cuatro neoplasias eran masas bien delimitadas mientras que el carcinoma de células escamosas digital era aprehensión. Esta baja incidencia de neoplasias cutánea en la marmota (0,8%) es semejante a la descrita en otros roedores de laboratorio.