Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were

Objective. To phenotypically characterize ADAMTS-4-and ADAMTS-5-double-knockout mice, and to determine the effect of deletion of ADAMTS-4 and ADAMTS-5 on the progression of osteoarthritis (OA) in mice.Methods. Mice lacking the catalytic domain of ADAMTS-4 and ADAMTS-5 were crossed to generate ADAMTS-4/5-double-knockout animals. Twelve-weekold and 1-year-old male and female ADAMTS-4/5-double-knockout mice were compared with age-and sex-matched wild-type (WT) mice by evaluating terminal body weights, organ weights, clinical pathology parameters, PIXImus mouse densitometry findings, and macroscopic and microscopic observations. ADAMTS-4/5-double-knockout mice were challenged by surgical induction of joint instability to determine the importance of these genes in the progression of OA. Articular and nonarticular cartilage explants from WT and ADAMTS-4/5-double-knockout mice were treated with interleukin-1 (IL-1) plus retinoic acid ex vivo, to examine proteoglycan degradation.Results. There were no genotype-related phenotype differences between ADAMTS-4/5-double-knockout and WT mice through 1 year of age, with the exception that female ADAMTS-4/5-double-knockout mice had a lower mean terminal body weight at the 12-week time point. Eight weeks after surgical induction of joint instability, OA was significantly less severe in ADAMTS-4/5-doubleknockout mice compared with WT mice. Following stimulation of cartilage explants with IL-1 plus retinoic acid, aggrecanase-mediated degradation in ADAMTS-4/5-double-knockout mice was ablated, to a level comparable with that in ADAMTS-5-knockout mice.Conclusion. Dual deletion of ADAMTS-4 and ADAMTS-5 generated mice that were phenotypically indistinguishable from WT mice. Deletion of ADAMTS-4/5 provided significant protection against proteoglycan degradation ex vivo and decreased the severity of murine OA. These effects in the ADAMTS-4/5-doubleknockout mice were comparable with those observed with deletion of ADAMTS-5 alone.

ABSTRACT:Iridoviruses of the genus Ranavirus are well known for causing mass mortality events of fish and amphibians with sporadic reports of infection in reptiles. This article describes five instances of Ranavirus infection in chelonians between 2003 and 2005 in Georgia, Florida, New York, and Pennsylvania, USA. Affected species included captive Burmese star tortoises (Geochelone platynota), a free-ranging gopher tortoise (Gopherus polyphemus), free-ranging eastern box turtles (Terrapene carolina carolina), and a Florida box turtle (Terrepene carolina bauri). Evidence for Ranavirus infection was also found in archived material from previously unexplained mass mortality events of eastern box turtles from Georgia in 1991 and from Texas in 1998. Consistent lesions in affected animals included necrotizing stomatitis and/or esophagitis, fibrinous and necrotizing splenitis, and multicentric fibrinoid vasculitis. Intracytoplasmic inclusion bodies were rarely observed in affected tissues. A portion of the major capsid protein (MCP) gene was sequenced from each case in 2003-2005 and found to be identical to each other and to Frog virus 3 (FV3) across 420 base pairs. Ranavirus infections were also documented in sympatric species of amphibians at two locations with infected chelonians. The fragment profiles of HindIIIdigested whole genomic DNA of Ranavirus, isolated from a dead Burmese star tortoise and a southern leopard frog (Rana utricularia) found nearby, were similar. The box turtle isolate had a low molecular weight fragment that was not seen in the digestion profiles for the other isolates. These results suggest that certain amphibians and chelonians are infected with a similar virus and that different viruses exist among different chelonians. Amphibians may serve as a reservoir host for susceptible chelonians. This report also demonstrated that significant disease associated with Ranavirus infections are likely more widespread in chelonians than previously suspected.

Abstract. Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications (P ϭ 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.Key words: Dogs; grade; histopathology; mastocytoma.Mast cell tumors (MCTs) are the most common cutaneous tumors of the dog. 13 These tumors vary widely in their behavior, from nearly benign to highly invasive and metastatic. It has been recognized for more than 30 years that histologic grading is prognostic for the behavior of canine cutaneous MCTs. 3,6,10 The 2 most widely recognized grading systems classify MCTs into 3 grades based on histologic characteristics, including cellularity, cell morphology, invasiveness, mitotic activity, and stromal reaction. 3,10 Both grading systems correlate with the survival rate of canine patients with MCTs and histologic grade is the most important factor in determining the staging tests and adjunctive therapy that will be recommended for a dog with a cutaneous MCT. 9,13 Because of the importance of histologic grade in prognosis and decision making in the therapeutic management of dogs with MCTs, it is essential that veterinarians understand the variability among pathologists in assigning grades to MCTs. In a previous study, it was demonstrated that there was significant variation in the histologic grades assigned to the same 60 canine cutaneous MCTs by 10 veterinary pathologists at 1 institution. 8 Because variation in histologic grading was significantly associated with the use of different references describing grading systems, it was hypothesized that if all pathologists utilized the same reference for grading, there would be improved agreement in the grades as- signed to canine cutaneous MCTs. The objective of this study was to determine whether variation among veterinary pathologists in the histologic grading of canine cutaneous MCTs could be eliminated by uniform use of a single grading scheme.Ten veterinary pathologists independently graded the same 60 canine cutaneous MCTs as grade I, II, or III using the Patnaik classifications (Table 1). 10 These were the same 10 veterinary pathologists who participated in the previous study to evaluate variation among pathologists in histologic grading of canine cutaneous MCTs. 8 Four of these pathologists were from the University of Georgia College of Veterinary Medicine (UGA-CVM) Department of Pathology, 5 were from...

Objective. Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor ␣ (TNF␣) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNF␣ blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNF␣ blockade-induced exacerbation of skin inflammation in murine psoriasislike skin disease. Methods. Skin inflammation was induced in