Ku80 and p53 suppress medulloblastoma that arise independent of Rag-1-induced DSBs.

Ku80 maintains the genome by repairing DNA double-strand breaks (DSBs) through nonhomologous end joining (NHEJ), a pathway that repairs nonspecific DSBs and Rag-1 Rag-2 (Rag)-specific DSBs. As a result, Ku80 deletion results in phenotypes characteristic of defective repair for both nonspecific DSBs (gamma-radiation hypersensitivity and genomic instability) and Rag-specific DSBs (immunodeficiency). ku80(-/-) mice also exhibit neuronal apoptosis, but we do not know the type of DSBs responsible for this response. In spite of genomic instability and immunodeficiency, cancer incidence is not increased in ku80(-/-) mice. However, deletion of the tumor suppressor, p53 greatly increases pro-B-cell lymphoma in ku80(-/-) mice due to IgH/c-Myc translocations suggesting that responses to Rag-specific DNA DSBs suppress cancer. Like suppression of pro-B-cell lymphoma, neuronal apoptosis requires p53 presenting the intriguing possibility that Rag-specific DSBs mediate neuronal development as they do lymphocyte development. Here we delete Rag-1 from ku80(-/-)p53(-/-) mice to differentiate the impact nonspecific vs Rag-specific DSBs have on ku80(-/-) mice. We find that deleting Rag-1 prevents pro-B cell lymphoma confirming Rag-induced DSBs induce this form of cancer. Both the triple mutant mice and the p53(-/-)rag-1(-/-) mice exhibit T-cell lymphoma and medulloblastoma; incidence of T-cell lymphoma is the same for both cohorts whereas incidence of medulloblastoma is higher for the triple-mutant cohort. Thus, p53-mediated neuronal apoptosis likely suppresses medulloblastoma in Ku80-deleted mice and Ku80 likely suppresses medulloblastoma by repairing nonspecific DNA DSBs instead of Rag-specific DSBs. Our observations are the first to show that Ku80 suppresses cancer caused by nonspecific DNA damage and we present a novel mouse model for medulloblastoma.

Unusual immunophenotype of a soft tissue sarcoma in a European polecat (Mustela putorius).

The most commonly reported tumors in ferrets are carcinomas, followed by round cell tumors. Soft tissue sarcomas are reported and characterized much less frequently. Because domesticated ferrets (Mustela putorius furo) are direct descendants of European polecats (Mustela putorius), the types and prevalence of tumors are expected to be similar in the two species. Presented here is a case report of unusual immunohistochemical staining characteristics of an abdominal wall leiomyosarcoma in a close relative of domestic ferrets, the European polecat. Sections of tissue were preserved in 10% buffered formalin, embedded in paraffin, and sectioned at 5 mm. Routine staining with hematoxylin and eosin and several immunohistochemical tests were performed to identify the tumor tissue of origin. Although the tumor did not stain with antibody to desmin, further staining for smooth muscle actin was consistent with a smooth muscle origin. To the authors' knowledge, this report is the first description of a leiomyosarcoma in the European polecat. This report emphasizes the importance of using additional secondary markers to accurately diagnose anaplastic tumors.

Laryngeal granuloma in a bull.

Dyspnea in an adult bull caused by a large laryngeal granuloma was corrected by use of a surgical technique that allowed resection of the mass without ventral laryngotomy. Endoscopy was used for visualization of the mass during the oral surgery. The technique may be performed in the field.

Pancreatic adenocarcinoma with osseous metaplasia in a ferret.

A poorly differentiated pancreatic adenocarcinoma with regional lymphatic, hepatic, enteric and pulmonary metastases was diagnosed in an adult European ferret (Mustela putoris furo). The ferret showed clinical signs including a progressive, marked abdominal enlargement owing to ascites. Microscopic findings included intralesional osseous metaplasia. Exocrine pancreatic neoplasms in ferrets are rarely reported compared with neoplasms with endocrine differentiation.

A multichromatic stain for Lowicryl K4M embedded tissues.

A staining procedure using celestine blue and chromotrope 2R for Lowicryl K4M embedded tissues is presented. The stain produces a reliable multichromatic stain for light microscopy on Lowicryl embedded semithin sections.

Equine zygomycosis caused by Conidiobolus lamprauges.

A 15-year-old Arabian mare from southern Louisiana with a 2-month history of periodic epistaxis and severe weight loss had a large, fibrosing, granulomatous mass containing numerous nodules ("kunkers") projecting dorsally into the nasopharynx, and was euthanized at the owner's request. In addition to these kunkers, the mass contained a single trematode tentatively identified as Fasciola hepatica. Several kunkers were removed, washed thoroughly in sterile water and embedded in nutrient agars; the fungus that grew out of them was identified as Conidiobolus lamprauges Drechsler (Entomophthorales: Ancylistaceae). This is the first report of C. lamprauges from any vertebrate mycosis, and only the third Conidiobolus species reported from vertebrates. Unlike many other entomophthoraleans, the fungus isolated from this mycosis grew well at 37 degrees C. The possible means by which Conidiobolus species may infect vertebrates is discussed. These mycoses probably result most often from chronic exposure during sleep to conidia discharged from fungal growth on decaying plant material in the bedding.

Verminous vasculitis, pneumonia and pulmonary infarction in a cynomolgus monkey after treatment with ivermectin.

An apparently healthy cynomolgus monkey (Macaca fascicularis) died 2 hours after routine inhalation anesthesia and implantation of a femoral catheter. Gross necropsy findings included patchy raised areas of severe pulmonary hemorrhage and consolidation. Filarioid nematodes (Edesonfilaria malayensis) were located in pulmonary blood vessels and in numerous 0.1-2 cm fibrous cysts on the pleural surfaces of the lungs, pericardium, diaphragm, retroperitoneum, and in the urinary bladder wall. Microscopic lesions included verminous vasculitis, pulmonary infarcts and pneumonia. Many of the nematodes were more necrotic than the surrounding host tissue. During quarantine, 17 days before surgery, the monkey had been given a single dose of ivermectin (200 micrograms/Kg, intramuscular) as an anthelminthic for gastrointestinal nematodes. It is postulated that many of the filarioid nematodes were killed by this treatment. These parasitic emboli caused pulmonary infarction and the severe inflammatory reaction. The resulting pulmonary disease compromised pulmonary function and contributed to death after anesthesia. This complication should be considered if monkeys possibly harboring filarioid nematodes are treated with ivermectin.

Subacute nonsuppurative hepatitis associated with hepatitis B virus infection in two cynomolgus monkeys.

Subacute, nonsuppurative hepatitis was diagnosed in a cynomolgus monkey (Macaca fascicularis) based on histopathologic examination of a liver biopsy specimen. Clinical signs of illness included anorexia, lethargy and hepatomegaly. Abnormal laboratory findings included elevations of serum liver enzymes, bilirubin and a monocytosis. Circulating antibody (anti-HBs) against Hepatitis B surface antigen (HBsAg) was present in serum and antigens reactive with anti-HBsAg antiserum were found in the liver using an immunoperoxidase technique. Of the remaining 18 healthy monkeys in the same room, another cynomolgus monkey was HBsAg seropositive. Both of the seropositive monkeys involved arrived on the same shipment from Indonesia and had been quarantined and housed together continuously during the preceding two years.

Pneumonia in goats caused by Mycoplasma mycoides subspecies mycoides.

Mycoplasma mycoides subspecies mycoides (large-colony type) was isolated from the lungs of a goat with pneumonia. Clinical signs included inappetence, weakness, listlessness, coughing, dyspnea, pyrexia, slight nasal discharge, and lameness. Tylosin (4 mg/kg of body weight) was administered each day for 4 days, resulting in slow recovery. Three weeks later, the clinical signs recurred and the kid was anemic. It was given a single blood transfusion and tylosin was administered daily. The kid's health status was steadily declined and it died after 6 days' treatment. At necropsy, the lungs were edematous and congested. Histopathologic findings were those of septicemia and pneumonia.

Fatal Yersinia pseudotuberculosis infection in captive bushbabies.

Fatal Yersinia pseudotuberculosis infection was diagnosed in 3 bushbabies (Galago crassicaudatus) in a large prosimian colony. The clinical signs were diarrhea, dyspnea, hyperthermia, dehydration, and lethargy. Histologically, the disease was characterized by lesions of ulcerative enterocolitis, necrotizing hepatitis, splenitis, lymphadenitis, and nonsuppurative pneumonitis.

Spontaneous cholangiocarcinoma in a ring-tailed lemur (Lemur catta).

A cholangiocarcinoma in the liver with metastasis to the regional lymph nodes was found in a male ring-tailed lemur (Lemur catta). The liver was partially replaced by a gray-white, coarsely lobulated mass. Microscopically, the tumor consisted of well circumscribed lobules of anaplastic, low cuboidal cells occasionally arranged in duct-like structures. The tumor did not involve the gallbladder.