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Despite the high prevalence of feline pancreatic disease, no detailed description on the histopathologic nature of this disease is currently available in the literature. In this study we characterize the distribution and histopathologic changes commonly found in feline pancreases, correlate the lesions with age and gastrointestinal GI and extra-gastrointestinal disease, and compare the pancreatic lesions in cats with those in humans. The entire pancreas was removed and examined from 115 cats presented for necropsy irrespective of the cause of death. Histologic sections from left limb, right limb, and body were scored for lesions of acute (AP) and chronic pancreatitis (CP) with a scoring system based on similar systems used in human and veterinary literature. The lesions of CP in cats resemble CP in humans, with fibrosis being more prominent than inflammatory changes. Cystic degeneration gradually increased as other lesions of CP were more prominent. A distinct nodular change of zymogen depletion and acinar cell dysplasia not associated with pancreatitis was prominent in 15.6% of the pancreases. Histologically, AP consisted of neutrophilic inflammation associated with interstitial edema and necrosis of mesenteric fat.An overall prevalence of 67%, and 45% in clinically normal animals, was identified. CP was found in 69 (60.0%) pancreases, and 58 (50.4%) had CP only, with a significant correlation between age and occurrence of CP. There was a statistically significant higher prevalence of CP in the left limb in animals with gastrointestinal disease. AP was present in 18 animals (15.7%) of which 7 animals had AP only (6.1%).

Although metastases to the adrenals are common in humans, they have not been thoroughly studied in animals. The purpose of this retrospective study was to document the types of malignant tumors that metastasize to canine, feline, equine, and bovine adrenals, and the rate at which they do so. The average rate of adrenal involvement in metastatic cancer was 112/534 (21.0%) in dogs, 12/81 (14.8%) in cats, 18/67 (26.9%) in horses, and 5/16 (31.3%) in cattle. In dogs, 26 different tumor types metastasized to the adrenals. Pulmonary, mammary, prostatic, gastric, and pancreatic carcinomas, and melanoma had the highest rates of metastasis to the adrenal glands in dogs. Hemangiosarcoma and melanoma had high rates of adrenal involvement in horses. In cats and cattle, relevant data were only available for lymphoma. Adrenal metastases usually occurred in the late stages of the disease. One dog had developed Addison's disease (hypoadrenocorticism) secondary to lymphoma. Metastatic lesions represented 126/472 (26.7%) of canine, 12/20 (60.0%) of feline, 21/80 (26.3%) of equine, and 5/9 (55.5%) of bovine adrenal neoplasms. This study shows that adrenal glands should be thoroughly examined during both clinical work-up and postmortems when disseminated neoplasia is suspected.

Bilateral chronic granulomatous nephritis and meningoencephalitis were diagnosed on necropsy of a 2-year-old male Great Dane dog. The causative agent was identified as Balamuthia mandrillaris, based on morphologic features, immunohistochemical staining, and deoxyribonucleic acid detection using the polymerase chain reaction with newly designed primer pairs. Trophozoite and cystic forms of the amoeba were evident within the kidneys and brain parenchyma. This is the first report on a B. mandrillarisinfection in a dog.

Tumors of the adrenal cortex account for 10–20% of the naturally occurring Cushing's syndrome diagnosed in dogs. Differentiating between adrenocortical adenoma and carcinomas is often difficult. The purposes of this study were to determine which histopathologic criteria can be used as markers for malignancy in canine adrenocortical tumors and the relevance of the proliferation marker, Ki-67, for differentiation between cortical adenomas and carcinomas. Twenty-six adrenocortical carcinomas, 23 adenomas, and 11 normal adrenal glands were examined. Morphologic criteria significantly associated with adrenocortical carcinomas included a size larger than 2 cm in diameter, peripheral fibrosis, capsular invasion, trabecular growth pattern, hemorrhage, necrosis, and single-cell necrosis, whereas hematopoiesis, fibrin thombi, and cytoplasmic vacuolation were significantly associated with adrenocortical adenomas. The mean (± SD) proliferation index, measured by immunohistochemistry for the Ki-67 antigen, was 9.3 ± 6.3% in carcinomas, 0.76 ± 0.83% in adenomas, and 0.58 ± 0.57% in normal adrenal glands. The Ki-67 proliferation index was significantly higher in carcinomas compared with adenomas and normal adrenal glands. A threshold value of the proliferation index of 2.4% reliably separated carcinomas from adenomas. Based on these results, it appears that thorough evaluation of morphologic features combined with immunohistochemical assessment of the proliferation index is extremely useful for differentiating between adrenocortical adenomas and carcinomas in dogs.

A peripheral primitive neuroectodermal tumor (pPNET), most consistent with a human Ewing's sarcoma, is described in a 5-month-old male Australian Shepherd puppy. The first tumor site detected was in the left frontal bone of the skull with apparent subsequent rapid metastases to multiple sites in the axial and appendicular skeleton and bone marrow, kidneys, and perihyphophyseal meninges. Radiographically, all bone lesions were lytic and there was also a humeral bone fracture. Histologically, the tumor was diagnosed as a small round blue cell tumor. At this stage, the differential diagnosis included a lymphoma, rhabdomyosarcoma, and a PNET of the peripheral nervous system. However, the cells had positive expression of triple neurofilament antigens as detected immunocytochemically. The cells were negative for a broad panel of canine-specific leucocyte cell marker antigens for desmin, smooth muscle actin, synaptophysin, and CD99. Ultrastructurally, the cells contained occasional dense core neurosecretory granules and intermediate filaments with intercellular desmosomal-like junctions and abundant glycogen clusters. Based on the age of the dog, the clinical history, the distribution of gross lesions, histologic characteristics of a small round blue cell tumor, and immunocyto-chemical and ultrastructural evidence of neuroectodermal differentiation, a diagnosis of a pPNET similar to a human Ewing's sarcoma was made.

ABSTRACTIleocolitis associated with spiral bacteria identified as an Anaerobiospirillumsp. was found in six cats. Two cats had acute onset of gastrointestinal signs characterized by vomiting and diarrhea in one cat and vomiting in another cat, one cat had chronic diarrhea that was refractory to medical therapy; one cat had acute onset of anorexia and lethargy, and two cats had clinical signs that were not related to the gastrointestinal tract. The presence of an Anaerobiospirillumsp. was demonstrated on the basis of ultrastructural morphology of spiral bacteria associated with intestinal lesions and PCR amplification of a genus-specific 16S rRNA gene from affected tissues from each cat. The colons of three clinically healthy cats without lesions and one cat with mild colitis not associated with spiral bacteria were negative for Anaerobiospirillumspp. in the same assay. Comparative nucleotide sequence analysis of cloned PCR products from three affected cats further suggested that the spiral bacteria were closely related to Anaerobiospirillum succiniciproducens.

Seventy-seven feline transplant kidney specimens, obtained from 1 to 3,183 days (9 years) after transplantation, were reevaluated histologically and classified on the basis of the Banff '97 guidelines for human renal transplant kidneys. Overall, this classification system appeared useful in detecting rejection reactions and confirmed the finding in humans that biopsies can diagnose subclinical rejection and therefore are an important diagnostic tool for the follow up of renal transplants. However, on the basis of serum creatinine values, the severity of the acute or active and chronic lesions was not accurately reflected by this scoring system. This is thought to be due to the significant differences in histologic rejection patterns, especially in acute or active rejection, in cats when compared with humans. Tubulitis, lymphocytic glomerulitis, and vasculitis, which are the main pillars of the Banff '97 acute or active rejection scoring system, are either rare or not found in cats. The presence of significant necrotizing glomerulitis and vasculitis in feline renal transplants might imply that the rejection is complicated by acute antibody-mediated rejection. Alternatively, cyclosporine toxicity also should be considered because some of these kidneys show other signs of cyclosporine toxicity. Finally, the significance of subcapsular and interlobular phlebitis, rarely described in human rejection reactions but a distinct entity in cats, is unknown. From this study, it is clear that there are significant differences in the histology of acute or active rejection between humans and cats and that a better understanding of the histologic appearance of renal allografts will be especially beneficial for treatment and prognostic purposes.

The clinical, gross morphological, histological and immunohistochemical characteristics of an ameloblastic carcinoma in a 30-year-old Quarter Horse mare are reported. This tumour was fast growing, locally invasive and destructive. Histologically, it showed an infiltrative pattern of large islands, broad sheets and, at the periphery, small cords of moderately pleomorphic round, oval to spindle-shaped cells. Immunohistochemical evaluation revealed positive labelling for vimentin, cytokeratin 5/6 and cytokeratin 14. In the oral cavity of human beings, this immunolabelling pattern is unique for the embryonal enamel organ and tumours of ameloblastomatous epithelial origin, which strongly supports the diagnosis of equine ameloblastic carcinoma.

Neoplastic and hyperplastic disorders that affect multiple endocrine tissues in a single individual are well described in humans but less so in domestic animals. Multiple endocrine neoplasia (MEN) in humans is a genetically determined syndrome characterized by the appearance of benign or malignant proliferations within two or more endocrine glands. The primary endocrine tumors that are characteristic of MEN arise from cells that share the capacity for amine precursor uptake and decarboxylation. Here we describe the case of a 22-year-old Thoroughbred mare that died during an unattended parturition and subsequently was presented for necropsy at the University of California, Davis, Veterinary Medical Teaching Hospital. A C-cell (medullary) thyroid adenoma, pheochromocytoma, and multicentric bilateral nodular hyperplasia of the adrenal medulla were present, findings that are remarkably similar to those of human MEN syndrome. Mortality during pregnancy in women with undiagnosed pheochromocytoma is high (approximately 50%), typically because of hypertension and/or hemorrhage associated with catecholamine release from the tumor. Similarly, the mare in this report died of hemorrhage subsequent to parturition. A retrospective evaluation of endocrine tumors in horses that underwent necropsy at the Veterinary Medical Teaching Hospital from 1987 to 1997 was undertaken to identify additional possible cases of MEN in horses. Data from this retrospective evaluation suggest that co-existence of hyperplasias and neoplasias of the thyroid and adrenal glands, similar to MEN syndrome of humans, also occurs with some frequency in the horse.

Lipopolysaccharides (LPS) are amphiphilic molecules in the outer leaflet of the bacterial outer membrane. Recently, an early role for LPS in the folding of outer membrane porin PhoE was demonstrated in vitro. In order to elucidate the molecular mechanism of LPS-protein interactions, folding of PhoE protein was studied with a large set of well characterized LPS chemotypes. We demonstrate that negative charges in the inner core region contribute to the high efficiency of folding of PhoE protein. In addition, the supramolecular structure of the LPS aggregate seems to be important. LPS with a lipid A part that prefers a lamellar or a direct micellar structure and a high state of order of its acyl chains is much less efficient to support folding as compared with LPS with lipid A that prefers a non-lamellar structure and a low acyl chain order. These in vitro data indicate that extensive interactions between the core and lipid A region of LPS with the protein are required to support protein folding. The LPS-PhoE binding might be promoted by the presence of hydroxy fatty acids in the lipid A moiety of LPS.

To identify the requirements for the biogenesis of outer‐membrane proteins in Gram‐negative bacteria, the sorting and assembly of the trimeric, pore‐forming protein PhoE was studied in vitro. Purified lipopolysaccharide (LPS) in combination with low amounts of Triton X‐100 and divalent cations induced the formation of folded monomers. LPS of deep‐rough strains was far less efficient in the formation of folded monomers than wild‐type LPS was. These folded monomers could be converted into heat‐stable trimers upon addition of outer membranes and higher amounts of Triton X‐100. Trimerization could precede the insertion step. These in vitro data suggest that the assembly in vivo proceeds sequentially by (i) formation of a folded monomer by interaction with LPS; (ii) sorting of the folded monomers to assembly sites in the outer membrane; (iii) trimerization; and (iv) insertion.

The assembly of the in vitro synthesized outer membrane protein PhoE into purified outer membranes was investigated. The assembly appeared to be strongly stimulated by the presence of low amounts of Triton X-100 (optimal 0.08%, w/v). The role of Triton X-100 in the in vitro system was further examined. Pretreating outer membranes with Triton X-100 did not make the membranes competent for correct assembly, indicating that the detergent did not act on the membrane but at the protein level. PhoE became assembly-incompetent with a half-life of approximately 12 min and 90 s at 37 degrees C in the absence and presence, respectively, of 0.08% Triton X-100. Apparently, Triton X-100 induces an assembly-competent state in the PhoE protein with a very short half-life. Furthermore, the efficiency of correct assembly of PhoE was greatly reduced when outer membranes of deep rough lipopolysaccharide mutants were used, indicating an important role of lipopolysaccharides in the assembly of the porin.