Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice.

The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue.

Remission of histiocytic ulcerative colitis in Boxer dogs correlates with eradication of invasive intramucosal Escherichia coli.

BACKGROUND: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology. HYPOTHESIS: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission. ANIMALS: Seven Boxer dogs with HUC. METHODS: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli. RESULTS: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7 + or - 3.06 mg/kg q24 h, for 9.5 + or - 3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17-62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed. CONCLUSIONS AND CLINICAL RELEVANCE: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli.

Hypokalaemic paresis, hypertension, alkalosis and adrenal-dependent hyperadrenocorticism in a dog.

Generalised paresis, severe hypokalaemia and kaliuresis, metabolic alkalosis and hypertension, characteristic of mineralocorticoid excess, were identified in a dog with hyperadrenocorticism due to a functional adrenocortical carcinoma. Aldosterone concentration was decreased and deoxycorticosterone concentration increased in the presence of hypokalaemia. These metabolic abnormalities resolved with resection of the carcinoma. Mineralocorticoid excess in dogs with hyperadrenocorticism is generally considered to be of little clinical significance but resulted in the acute presentation of this patient. The possible pathogenesis of mineralocorticoid excess in this case of canine hyperadrenocorticism is discussed.

Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville).

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electron-dense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohistochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB.

Klossiella quimrensis (Apicomplexa: Klossiellidae) causes renal coccidiosis in western barred bandicoots Perameles bougainville (Marsupialia: Peramelidae) in Western Australia.

Previous studies have described a range of Klossiella species parasitic in marsupial hosts. Klossiella quimrensis is the etiologic agent of renal coccidiosis in the peramelid marsupial hosts Isoodon obesulus and Perameles gunnii in Eastern Australia, but there is no previous report of klossiellosis in Western Australian peramelids. This study describes klossiellosis diagnosed by histology of renal tissue sections collected during necropsy of 20 Perameles bougainville between 2000 and 2005. Sporonts, sporoblasts, and macrogametes were identified within parasitophorous vacuoles of epithelial cells located near the renal corticomedullary junction. The prevalence of renal coccidiosis in P. bougainville diagnosed by renal histology is estimated at 30%. Only a single unsporulated sporocyst was detected by examination of cystocentesis-collected urine, indicating that microscopic evaluation of urine samples is an insensitive diagnostic test for detection of K. quimrensis in P. bougainville. This infection in P. bougainville is indirectly associated with mild multifocal interstitial lymphohistiocytic nephritis and is likely to be only minimally pathogenic in otherwise healthy individuals. Our study also extends the host and geographic range of K. quimrensis to include P. bougainville and Western Australia.

Disseminated cryptococcosis including osteomyelitis in a horse.

A 4-year-old Arab mare was diagnosed with disseminated cryptococcosis, including osteomyelitis of the proximal phalanx of the left hind limb, osteomyelitis with associated soft tissue granuloma of a rib and disseminated, large cryptococcal nodules in the lungs. The lesion in the dorsoproximal aspect of the proximal phalanx had a large area of cortical lysis with spiculated periosteal new bone and extensive soft tissue swelling. The affected rib had a pathological fracture. Cryptococcal osteomyelitis has not been previously reported in horses but should be considered as a differential diagnosis, particularly in endemic regions.

The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii).

A disfiguring and debilitating neoplastic condition known as devil facial tumor disease (DFTD) has been discovered in wild Tasmanian Devils (Sarcophilus harrisii) across 51% of its natural range, with population declines of up to 80% in some areas (C. Hawkins, personal communication). Between 2001 and 2004, 91 cases were examined. The tumors presented as large, solid, soft tissue masses usually with flattened, centrally ulcerated, and exudative surfaces. They were typically multicentric, appearing first in the oral, face, or neck regions. Histologically, the tumors were composed of circumscribed to infiltrative nodular aggregates of round to spindle-shaped cells, often within a pseudocapsule and divided into lobules by delicate fibrous septae. They were locally aggressive and metastasized in 65% of cases. There was minimal cytologic differentiation among the tumor cell population under light and electron microscopic examination. The results indicate DFTD to be an undifferentiated soft tissue neoplasm.

The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian Devil (Sarcophilus harrisii).

Immunohistochemical techniques were used to characterize the disfiguring and debilitating fatal neoplastic disease, devil facial tumor disease (DFTD), which has recently affected a significant proportion of the wild population of Tasmanian Devils (Sarcophilus harrisii). The diagnostic values of a number of immunohistochemical stains were employed to further characterize 50 representative cases. The neoplasms were negative for cytokeratin (0/48), epithelial membrane antigen (0/42), von Willebrand factor (vWF) (0/11), smooth muscle actin (SMA) (0/26), desmin (0/47), glial fibrillary acid protein (0/13), CD16 (0/13), CD57 (0/43), CD3 (0/18), and LSP1 (0/16). DFTD cells were positive for vimentin (50/50), S-100 (41/48), melan A (11/39), neuron specific enolase (35/35), chromogranin A (12/12) and synaptophysin (29/30). The cells were negative for amyloid (0/30) and stained negatively with Singh's silver (0/34) but were weakly argyrophilic (3/40) using Grimelius histochemical stain. These staining characteristics are consistent with cells of neuroectodermal origin.

Successful management of histiocytic ulcerative colitis with enrofloxacin in two Boxer dogs.

Two Boxer dogs with histologically confirmed histiocytic ulcerative colitis were treated with enrofloxacin, one as sole therapy and one in conjunction with prednisolone, after failure of standard therapy. Clinical remission occurred rapidly in both dogs after commencement of enrofloxacin and in one case where repeat colonoscopy was performed the endoscopic appearance of the mucosa was normal within 2 weeks. Histological examination of the colonic mucosa in this dog after 7 months showed resolution of the cellular infiltration characteristic of histiocytic ulcerative colitis. Histological improvement following therapy in Boxer dogs with histiocytic ulcerative colitis has not been reported previously.

Atypical multiple, papilliform, xanthomatous, cutaneous neoplasia in a goose (Anser anser).

An 18-month-old, male greylag goose was presented for assessment of multiple, semi-pedunculated cutaneous masses limited to non-feathered areas of skin. Initial biopsy and histopathology revealed a mesenchymal neoplasm suggestive of lipoblastomatosis or atypical xanthoma. Immunohistochemistry was unsuccessful in determining the tissue type of origin. Surgical resection of all masses was prevented by the mucocutaneous location of several masses. Chemotherapy using intralesion cisplatin was unsuccessful in resolving the masses but was well-tolerated by the goose. Serum lipid and lipoprotein analysis revealed a persistent hypercholesterolaemia and hypertriglyceridaemia without biochemical evidence of an underlying metabolic disease. The persistent hyperlipidaemia may have contributed to the formation of the masses identified in this case.

Focal eosinophilic proctitis with associated rectal prolapse in a pony.

Focal intramural nodules were palpated in the rectal wall of a 12-year-old pony mare presented for rectal prolapse. Eosinophilic proctitis was diagnosed by examination of fine needle aspirates and biopsy of the largest rectal nodule. After treatment with a course of corticosteroids, the rectal nodule and accompanying peripheral eosinophilia resolved. There was no recurrence of the condition during the follow-up period of 20 months. Focal eosinophilic proctitis appeared to be an unusual cause of tenesmus and rectal prolapse in this case.

Thoracic actinomycosis (arcanobacteriosis) or nocardiosis causing thoracic pyogranuloma formation in three dogs.

OBJECTIVE: To describe three cases of canine thoracic actinomycosis (arcanobacteriosis) or nocardiosis in which the primary pathological lesion was a pyogranulomatous abscess in the mediastinum. Clinical signs, difficulties in diagnosis, treatment and prognosis are examined. Comparisons are made between human and veterinary literature to assist in formulating a rational treatment plan. DESIGN: Retrospective clinical study. PROCEDURE: Review of case records from 1984 to 1998. RESULTS: Three dogs presented with large intrathoracic pyogranulomas producing variable clinical signs, not necessarily associated with the respiratory tract. Ages ranged from 2 to 5 years old. Two dogs responded to surgical opening and passive drainage of the abscess, or surgical excision of the granuloma with associated structures, and medical therapy. One dog died intra-operatively. CONCLUSION: A combination of surgical and antimicrobial therapy may carry a fair-to-good prognosis for thoracic granuloma caused by actinomycosis (arcanobacteriosis) or nocardiosis. The extent of surgery should be based on assessment of individual cases and must include surgical biopsy for histology and culture to enable a specific diagnosis to be made. Complete surgical excision is not necessarily required. Prolonged antimicrobial therapy is indicated.

Granulosa cell tumour in two speyed bitches.

Granulosa cell tumours are uncommon ovarian tumours in the bitch and are rare in speyed bitches. This case report describes two cases of granulosa cell tumour in bitches that were speyed at less than 1-year-of-age. Both animals presented with persistent vulval bleeding. Although the majority of granulosa cell tumours are large enough to be palpated by the time of presentation, both tumours were relatively small. Granulosa cell tumour is a possible complication of incomplete ovarian excision at the time of ovariohysterectomy. In cases of granulosa cell tumour in previously speyed bitches, with no evidence of metastases, tumour resection should be curative. Ovaries should be double-checked at the initial ovariohysterectomy to ensure all normal ovarian tissue has been excised.

The spread of transgene expression at the site of gene construct injection.

Seven 2-day-old golden retriever pups were given focal intramuscular injections of a first generation adenovirus-dystrophin minigene construct and adenovirus-beta-galactosidase construct as a 2:1 mixture into the left anterior tibial muscle. The spread of transgene expression within the anterior tibial muscle was compared with the spread of methylene blue dye after identical injection into the contralateral muscle. Transgene expression 5-7 days after intramuscular injection was shown to extend between 5.8 and 11.6 mm along the biopsied muscle length (range of biopsy lengths 11.1-12.2 mm). The level of transgene expression at 2-2.5-mm intervals from the site of injection was significantly related to the distance from the site of injection (dystrophin, P = 0.009; beta-galactosidase, P = 0.015). The spread of methylene blue dye within the anterior tibial muscle < or =24 h after identical intramuscular injection demonstrated a similar pattern to the transgene expression, with dye staining measured between 5.5 and 8.5 mm along the muscle sample length (range of biopsy lengths 5.6-15.6 mm). The greatest transgene expression and dye staining was measured 2-2.5 mm proximal to the site of injection with a maximum of 23% of muscle fibers expressing the dystrophin transgene, 95.2% expressing the beta-galactosidase transgene, and 98% of the tissue section stained with methylene blue dye. These results suggest transgene expression after focal intramuscular injection is relatively localized around the site of injection. Further research is required to develop techniques that will provide transgene expression throughout the length and breadth of a muscle.

Laryngeal rhabdomyoma in a dog.

A 4-year-old spayed female Golden Retriever was presented for investigation of progressive loss of bark, continuous panting and increased upper respiratory noise. Examination of the larynx and pharynx under general anaesthesia identified a spherical 5 x 3 cm mass involving the right arytenoid cartilage. Cytological examination of fine needle aspirates from the mass suggested the tumour was a carcinoma, however histological examination in association with immunoperoxidase and histochemical staining identified the mass as a laryngeal rhabdomyoma.

High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: prolongation of expression with immunosuppression.

Replication-deficient adenovirus vectors (AdV) have been successfully used to transfer a truncated human dystrophin cDNA to skeletal muscle of dystrophin-deficient mdx mice. A dystrophin-deficient golden retriever dog model (GRMD) has been identified, which, unlike the mouse model, leads to a clinicopathological phenotype similar to that of Duchenne muscular dystrophy (DMD). We show for the first time that high-level dystrophin expression in skeletal muscle of GRMD dogs can be achieved by AdV-mediated gene transfer. However, a humoral and cellular immune response of the host against antigens of viral and transgene origin (similar to that occurring in mdx mice after AdV-mediated dystrophin gene transfer) leads to a decline of dystrophin expression over a 2-month period. Immunosuppression by cyclosporin significantly prolonged transgene expression. The GRMD model may help to solve the open questions pertaining to dystrophin gene transfer such as systemic delivery and improvement of muscle function before human trials for gene replacement therapy in DMD may be considered.

Finite element modeling of the glenoid component: Effect of design parameters on stress distribution.

A two-dimensional plane stress model of the natural glenoid was developed with finite element analysis to observe the stress distributions under various loading conditions. Different glenoid prosthetic designs were evaluated with the use of the finite element model in an attempt to elucidate key features for an improved design. These included a keel model, a stair-stepped model, and a wedge model. In addition to the evaluation of these designs, different interfaces were introduced to simulate various environments of the prostheses, and different material combinations were studied. Based on the finite element analysis, the following design parameters were found to be important: (1) an all-polyethylene implant appears to provide a more physiologic stress distribution for nonaxial loads if no soft tissue is present; (2) the presence of a soft-tissue layer causes higher stresses; (3) the stair-stepped and wedge models produced a more natural stress distribution compared with the keel design; and (4) screw orientation was not a significant design parameter.

Bronchial rupture in children following blunt chest trauma. Report of five cases with emphasis on radiologic findings.

We present five patients with fracture of the bronchus, in whom the diagnosis of bronchial rupture was first suggested because of persistent leakage of air, atelectasis of a segment of the lung or of the entire lung, mediastinal and deep cervical emphysema. In all patients the bronchoscopy was essential to confirm the diagnosis and to determine the full extent of injury.