bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of an Orbital T-cell Rich B-cell Lymphoma to a B-cell Lymphoma in a Dog
Authors: Aquino S. M. , Hamor R. E. , Valli V. E. , Kitchell B. E. , Tunev S. S. , Bailey K. L. , Ehrhart E. J.
Published: April 2003

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36- positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1—1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.
Pulmonary Microcystic Hamartoma in an Adult Dog
Authors: Takahashi K. , Maeda K. , Nakamura S. , Fujita M. , Orima H. , Tagawa M. , Kuwahara M. , Nakashima N. , Maita K.
Published: April 2003

Microcystic hamartoma was detected as a tumorlike mass in the left caudal lung lobe of a 12- year-old mixed-breed dog. Histologically, the mass was characterized by microcysts of various sizes that mimicked alveoli and were surrounded by thin fibrous septal tissue. However, unlike the adjacent lung parenchyma, bronchial or bronchiolar trees were absent, and the septal vascular channels were extremely underdeveloped. Immunohistochemically, the cells lining the microcysts were consistently positive for cytokeratin but not for vimentin, whereas the septal fibroblast-like cells were negative for cytokeratin and positive for vimentin. Electron microscopy confirmed that the microcysts were lined with a layer of type I and type II mature pneumocytes. This is the first description of the detailed morphologic features of microcystic hamartoma.
Retrospective Study of 338 Canine Oral Melanomas with Clinical, Histologic, and Immunohistochemical Review of 129 Cases
Authors: Ramos-Vara J. A. , Beissenherz M. E. , Miller M. A. , Johnson G. C. , Pace L. W. , Fard A. , Kottler S. J.
Published: April 2003

Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocyticassociated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.
Malignant Teratoid Medulloepithelioma in a Llama
Authors: H. Hendrix D. V. , Bochsler P. N. , Saladino B. , Cawrse M. A. , Thomas J.
Published: April 2003

A lesion was identified in the eye of a juvenile llama, and preliminary clinical findings included anterior uveitis and an exudative retinal detachment suggestive of infectious disease. However, histopathologic evaluation of the enucleated globe revealed an intraocular neoplasm composed of primitive neuroepithelium forming ribbons, cords, and rosettes, heteroplastic elements including spindle cells in a loose myxomatous matrix, and islands of well-differentiated hyaline cartilage. Immunohistochemically, neoplastic cells were positive for vimentin and neuron-specific enolase. Spindle cells were multifocally positive for desmin and muscle specific actin, indicating differentiation towards myofibers. These findings are consistent with a diagnosis of malignant teratoid medulloepithelioma, an extremely rare ocular neoplasm that affects children and young animals.
Hypotensive Infarction of the Spinal Cord in a Rhesus Macaque (Macaca mulatta)
Authors: Zeiss C. J. , Shomer N. H. , Homberger F. R.
Published: April 2003

A 6.5-year-old male rhesus macaque (Macaca mulatta) was presented with acute paraplegia following a surgical procedure. During surgery, he experienced an acute hypotensive episode that required 3 hours of supportive therapy before hemodynamic stability was restored. Paraplegia remained unchanged until euthanasia 72 hours later. At necropsy, spinal cord segments T10-S3 had acute, massive panmedullary necrosis, which involved most of the central and middle spinal cord, sparing the peripheral white matter. Additional lesions included arterial border zone necrosis of the brain, centrilobular hepatic necrosis, and proximal renal tubular necrosis. The histologic findings of central spinal cord necrosis with a preserved rim of white matter is consistent with severely decreased flow in the anterior spinal artery. Such lesions can result from episodes of generalized hypoperfusion. Possible factors contributing to the hypotensive episode in this case included the addition of xylazine to ketamine and atropine in the preanesthetic medication, positioning during anesthesia, and decreased blood pressure during surgery.
Cerebral Vascular Hamartomas in Five Dogs
Authors: Smith S. H. , Van Winkle T.
Published: April 2003

Vascular hamartomas are considered developmental lesions rather than true neoplasms. Reports of such anomalies in the canine brain are scarce, and their classification is confusing. This case series of vascular hamartomas from the brains of five dogs was characterized using histochemistry and immunohistochemistry, in addition to gross and microscopic findings. All five hamartomas were located in the telencephalon, three in the pyriform lobe, without any predilection for the left or right side. Each hamartoma consisted of a proliferation of thin-walled vessels which varied in caliber. These vessels were elastin-negative, with varying amounts of collagen and no muscular component. In four of the five hamartomas, lining cells were actin- and factor VIII-positive. All five hamartomas contained glial fibrillary acid protein (GFAP)-positive parenchyma at moderate to high frequency, and four contained neurofilament-positive axons between component vessels. This report shows that vascular hamartomas in the canine brain are structural malformations for which immunohistochemistry is useful for accurate classification.
Special Considerations in the Evaluation of the Hematology and Hemostasis of Mutant Mice
Authors: Car B. D. , Eng V. M.
Published: April 2003

The study of mutant mice with altered or deficient hematopoietic or hemostatic gene products provides a challenge to the researcher, particularly when genetic alterations lead to lethal phenotypes. The following review provides a framework for understanding murine hematopoiesis, based on work with mutant mice, and details experimental approaches used to evaluate these animals. Mice with deficiencies in hemostatic and fibrinolytic system proteins are discussed, and the investigation of their phenotypes is reviewed.
Canine Model and Genomic Structural Organization of Glycogen Storage Disease Type Ia (GSD Ia)
Authors: Kishnani P. S. , Faulkner E. , VanCamp S. , Jackson M. , Brown T. , Boney A. , Koeberl D. , Chen Y.-T.
Published: April 2003

A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6-phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans ~ 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5′ region was sequenced and contains several putative response element motifs homologous to the human 5′ region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy.
Physeal Dysplasia with Slipped Capital Femoral Epiphysis in 13 Cats
Authors: Craig L. E.
Published: April 2003

Separation of the femoral capital epiphysis is associated with severe trauma in most species. This report describes 13 cats with slipped capital femoral epiphysis characterized by a distinctive lesion in the physeal cartilage. The lesion consists of irregular clusters of chondrocytes separated by abundant matrix on both the epiphyseal and metaphyseal side of the cleavage site. The affected population in this study is 85% male, 90% overweight, 23% Siamese, and 4.5–24 months old. The histopathology and demographics are similar to slipped capital femoral epiphysis in humans, which most often affects overweight adolescent boys.
Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype
Authors: Burgess S. C. , Basaran B. H. , Davison T. F.
Published: April 2003

Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 61 (resistant) and 15I and 72 (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 72 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 61 and 72 had a similar MLS distribution in the cytolytic phase, although scores were greater in line 72. At the time lymphomas were visible in line 72, histologic lesions in line 61 were regressing. AV37+ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37+ cell numbers increased in lines 72 and 15I but decreased in lines 61 and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4+. After this time, line 72 and 15I lesions increased in size and most cells were CD4+; line 61 and N lesions decreased in size and most cells were CD8+. In all genotypes, AV37 immunostaining was weak in lesions with many CD8+ cells, suggesting that AV37 antigen expression or AV37+ cells were controlled by CD8+ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 72 > 15I > 61 > N.
Multiple Epulides in 13 Cats
Authors: A. Colgin L. M. , Schulman F. Y. , Dubielzig R. R.
Published: April 2003

Epulides account for 0-7.8% of tumors in surveys of feline oral neoplasms. A review of the literature revealed no reports of multiple epulides in cats. Multiple, concurrent epulides were diagnosed microscopically in 13 cats. Fibromatous and ossifying epulides were diagnosed in 11 of 13 cats and fibromatous epulides were diagnosed in 2 of 13 cats. Microscopically, these epulides were nonencapsulated, well-vascularized, infiltrative, highly cellular neoplasms that expanded the gingiva and were composed of haphazardly arranged, spindle-shaped to stellate cells amid a dense, collagenous stroma. Osseous foci were a feature in the fibromatous and ossifying epulides. The mitotic rate was low and there was marked hyperplasia of the overlying gingiva with a prominent downgrowth of epithelial cords. These tumors recurred in 8 of 13 cats following surgical excision. While uncommon, multiple epulides in cats have a high incidence of recurrence but do not appear to have metastatic potential.
Immunohistochemical Detection of Tumor Suppressor Gene p53 Protein in Feline Injection Site-associated Sarcomas
Authors: Nambiar P. R. , Jackson M. L. , Ellis J. A. , Chelack B. J. , Kidney B. A. , Haines D. M.
Published: April 2003

Sarcomas associated with injection sites are a rare but important problem in cats. Immunohistochemical detection of p53 protein may correlate to mutation of the p53 tumor suppressor gene, a gene known to be important in oncogenesis. The expression of nuclear p53 protein in 40 feline injection site-assocated sarcomas was examined by immunohistochemical staining. In 42.5% (17/40), tumor cell nuclei were stained darkly; in 20% (8/40), tumor cell nuclei were stained palely; and in 37.5% (15/40), tumor cell nuclei were unstained. Immunohistochemical detection of p53 protein in a proportion of injection site-associated sarcomas suggests that mutation of the p53 gene may play a role in the pathogenesis of these tumors.
Expression of E- and P-selectin in Tumor Necrosis Factor—induced Dermatitis in Dogs
Authors: Tremblay C. , Paradis M. , Doré M.
Published: April 2003

Adhesion molecules on endothelial cells play an important role in leukocyte recruitment in several inflammatory processes. Vascular selectins mediate the initial adhesion of leukocytes to the blood vessel wall during their extravasation into inflamed tissues, and in vitro studies in dogs have shown that selectin expression can be induced by cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). The objective of this study was to determine whether vascular selectins are induced by cytokines in vivo in a cutaneous model of inflammation in dogs. Skin biopsies were collected from nine dogs at various time points after an intradermal injection of TNF-α (10 ng/site) or phosphate-buffered saline containing 0.1% bovine serum albumin, and immunohistochemistry was performed using anti-P-selectin (MD3) and anti-E-selectin (CL37) monoclonal antibodies. In all animals, TNF-α induced an inflammatory reaction that was maximal at 12 hours and then decreased by 24 and 48 hours. Control skin displayed no expression of E- and P-selectin, whereas TNF-α induced the expression of P-selectin and E-selectin on dermal vessels that was highest at 12 hours and 3 hours, respectively ( P < 0.05). Numerous platelet aggregates recognized by the anti-P-selectin antibody were present in the lumina of vessels and in perivascular tissues. These results demonstrate that TNF-α can induce the expression of P- and E-selectin in vivo in dog skin and suggest that these selectins are involved in leukocyte recruitment in canine dermatitis.
GM1-gangliosidosis in Alaskan Huskies: Clinical and Pathologic Findings
Authors: Müller G. , Alldinger S. , Moritz A. , Zurbriggen A. , Kirchhof N. , Sewell A. , Baumgärtner W.
Published: April 2003

Three Alaskan Huskies, two females and one male, were diagnosed with GM1-gangliosidosis. Clinically, diseased animals exhibited proportional dwarfism and developed progressive neurologic impairment with signs of cerebellar dysfunction at the age of 5–7 months. Skeletal lesions characterized by retarded enchondral ossification of vertebral epiphyses were revealed by radiographs of the male dog at 5.5 months of age. Histologic examination of the central nervous system (CNS) revealed that most neurons were enlarged with a foamy to granular cytoplasm due to tightly packed vacuoles that displaced the Nissl substance. Vacuoles in paraffin-embedded sections stained positively with Luxol fast blue and Grocott's method, and in frozen sections vacuoles were periodic acid–Schiff positive. Foamy vacuolation also occurred within neurons of the autonomic ganglia. Extracerebral cells such as macrophages and peripheral lymphocytes also displayed foamy cytoplasm and vacuolation. In the CNS of diseased animals, a mild demyelination and axonal degeneration was accompanied by a significant astrogliosis ( P < 0.05) in the gray matter as compared with age- and sex-matched control dogs. There was also a significant loss ( P < 0.05) of oligodendrocytes in the gray and white matter of affected animals as compared with controls. Ultrastructurally, the neuronal storage material consisted of numerous circular to concentric whorls of lamellated membranes or stacks of membranes in parallel arrays. GM1-gangliosidosis in Alaskan Huskies resembles β-galactosidase deficiency in other canine breeds, and these CNS disorders may be a consequence of neuronal storage and disturbed myelin processing.
Adrenal Teratoma in Four Domestic Ferrets (Mustela putorius furo)
Authors: Williams B. H. , Yantis L. D. , Craig S. L. , Geske R. S. , Li X. , Nye R.
Published: April 2003

Teratomas are histologically complex neoplasms that are composed of structures derived from multiple germ cell layers (ectoderm, mesoderm, and endoderm). These neoplasms are uncommon in domestic animals and are usually found in the gonads. This paper describes teratomas of the adrenal gland in four domestic ferrets ( Mustela putorius furo). Three of four of the neoplasms contained tissues from ectodermal, mesodermal, and endodermal germ cell layers; two of four contained rudimentary teeth. In one case, malignant epithelial cells had metastasized to local lymph nodes. Teratomas, although uncommon, should be included in the differential diagnosis for adrenal neoplasms in domestic ferrets.
Comparative Examination of Cats with Feline Leukemia Virus-associated Enteritis and Other Relevant Forms of Feline Enteritis
Authors: Kipar A. , Kremendahl J. , Jackson M. L. , Reinacher M.
Published: April 2003

Cats with feline leukemia virus (FeLV)–associated enteritis (FAE), enteritis of other known viral etiology (parvovirus [PV], enteric coronavirus [CoV]), and enteritis of unknown etiology with histologic features similar to those of FAE and PV enteritis (EUE) and FeLV-negative and FeLV-positive cats without enterocyte alterations were examined. Amount and types of infiltrating leukocytes in the jejunum and activity and cellular constituents of mesenteric lymph nodes, spleen, and bone marrow were determined. PV and CoV infections were confirmed by immunohistologic demonstration of PV and CoV antigen, ultrastructural demonstration of viral particles in the intestinal content, and in situ hybridization for PV genome. FeLV infection was detected by immunohistology for gp70, p27, and p15E. Latent FeLV infection was excluded by polymerase chain reaction methods for exogenous FeLV DNA. Enterocyte lesions involved the crypts in cats with PV enteritis, FAE, and EUE and the villous tips in cats with CoV enteritis. Inflammatory infiltration was generally dominated by mononuclear cells and was moderate in the unaltered intestine and in cats with PV enteritis and marked in cats with FAE, CoV enteritis, and EUE. In cats with EUE, myeloid/histiocyte antigen-positive macrophages were relatively numerous, suggesting recruitment of peripheral blood monocytes. Lymphoid tissues were depleted in cats with PV enteritis and with EUE but were normal or hyperplastic in cats with FAE. Bone marrow activity was decreased in cats with PV enteritis; in cats with FAE or EUE and in FeLV-positive cats without enterocyte alterations, activity was slightly increased. In cats with FAE and PV enteritis, a T-cell-dominated response prevailed. EUE showed some parallels to human inflammatory bowel disease, indicating a potential harmful effect of infiltrating macrophages on the intestinal epithelium.
Comparison of Tissue Stages of Hepatozoon americanum in the Dog Using Immunohistochemical and Routine Histologic Methods
Authors: Panciera R. J. , Mathew J. S. , Cummings C. A. , Duffy J. C. , Ewing S. A. , Kocan A. A.
Published: April 2003

American canine hepatozoonosis is caused by Hepatozoon americanum, a recently described species of apicomplexan protozoan parasite. An immunohistochemical procedure using a polyclonal antibody to sporozoites of H. americanum clearly identified asexual stages of H. americanum in canine striated muscle. The method also detects hepatozoa present in naturally infected coyotes and raccoons and reacts with certain other apicomplexans. Use of this immunohistochemical procedure confirms the canine intermediate host-parasite relationships that were presumptively established using conventional histopathologic methods.
Refinement of an Orthotopic Lung Cancer Model in the Nude Rat
Authors: March T. H. , Marron-Terada P. G. , Belinsky S. A.
Published: April 2003

Over 85% of people with lung cancer eventually succumb to this disease, largely because current chemotherapies are ineffective. The testing and validation of promising new approaches generally rely on achieving responses with cell lines in vitro or in tumor xenografts in nude mice. However, quite often the results seen with these models are not recapitulated in the clinic, thus necessitating the need for better animal models of lung cancer for preclinical testing of new therapies. One promising model is that of orthotopic lung cancer, where xenografts of human lung cancer are established in lungs of immunodeficient rodents. The problems associated with this model include poor rates of engraftment, limited tumor multiplicity, and a heightened risk for surgical trauma. The purpose of our study was to develop an efficient approach to engraftment of orthotopic tumors throughout the lungs of the Rowett nude rat. Initially, we augmented immunosuppression in the rats with whole-body X-irradiation and then used orotracheal cannulas to intratracheally instill human cancer cells from the Calu-6 cell line. This protocol produced a low rate of engraftment and low tumor multiplicity. The hypothesis that slight disruption of the pulmonary epithelium or the surfactant layer would allow better tumor engraftment was tested by coadministration of either pancreatic elastase or ethylenediaminetetraacetic acid (EDTA) along with the cell instillations. Lung tumor engraftment was evaluated 8 weeks after instillation. The inclusion of elastase or EDTA with the Calu-6 cells resulted in an 80–100% engraftment rate, respectively. Coadministration of EDTA resulted in significantly larger and greater numbers of tumors/lung than those in elastase-treated animals. Temporal studies demonstrated that small nodules were scattered throughout the lung parenchyma 5 weeks after instilling Calu-6 cells and EDTA. These nodules grew to coalesce and form large masses that effaced >75% of the parenchyma at 9 weeks postinstillation. The refinements made through our studies have led to the development of an orthotopic lung cancer model that should facilitate the evaluation of novel therapies designed to treat or impede lung cancer development.
Fusobacteriosis in Captive Wild-caught Pronghorns (Antilocapra americana)
Authors: Edwards J. F. , Davis D. S. , Roffe T. J. , Ramiro-Ibañez F. , Elzer P. H.
Published: April 2003

An outbreak of Fusobacterium necrophorum-induced septicemia occurred in a group of 40 captive wild-caught pronghorns ( Antilocapra americana). Primary pododermatitis or necrotic stomatitis progressed to produce fatal septicemia with metastatic lesions in the forestomachs, lung, liver, and cecum in 38 of the animals. Two remaining animals were euthanatized because of chronic pododermatitis. Housing the animals in a pasture previously used by bovids and heavy rains with persistence of ground water pools in the pasture were contributing factors in the pathogenesis of this outbreak.
Retroviral Particles in Neoplasms of Burmese Pythons (Python molurus bivittatus)
Authors: Chandra A. M. S. , Jacobson E. R. , Munn R. J.
Published: April 2003

Neoplastic diseases associated with retroviruses were diagnosed in four Burmese pythons ( Python molurus bivattatus) from a single collection. Snake No. 1 was a 7-year-old female with recurrent undifferentiated mesenchymal round cell tumor (lymphosarcoma) of the oral cavity. At necropsy, similar neoplastic masses were evident in the uterus and ovary, and there was diffuse involvement of the spleen. Snake No. 2 was a 4.5-yearold female that was euthanatized because of complications following resection of a segmental colonic adenocarcinoma. Snake No. 3 was a 5-year-old female that was euthanatized because of a large transitional cell carcinoma of the right kidney. Snake No. 4 was a 19-year-old female that was euthanatized following recurrence of an intermandibular fibrosarcoma. Ultrastructural examination revealed few to numerous extracellular and intracellular (intravacuolar) type C-like retroviral particles in all tumors. Tumors were about 90–95 nm in diameter, with an electron-dense core and bilaminar external membrane. The relationship of the intraneoplastic viral particles to the etiology of the tumors is uncertain.
Immunohistochemical Characterization of Canine Hyperplastic Hepatic Lesions and Hepatocellular and Biliary Neoplasms with Monoclonal Antibody Hepatocyte Paraffin 1 and a Monoclonal Antibody to Cytokeratin 7
Authors: Ramos-Vara J. A. , Miller M. A. , Johnson G. C.
Published: April 2003

Immunostaining with monoclonal antibody (MoAb) hepatocyte paraffin 1 (Hep Par 1) and an MoAb to cytokeratin 7 (CK7) was performed on 105 formalin-fixed, paraffin-embedded canine hyperplastic and neoplastic hepatic lesions. Hep Par 1 was detected in 12/12 hyperplastic nodules, 17/17 hepatocellular adenomas, and 37/40 hepatocellular carcinomas. The staining was disseminated, granular, and cytoplasmic. This antibody did not react with normal or neoplastic biliary epithelium. Other hepatic tumors or tumors metastatic to the liver did not bind Hep Par 1 except one metastatic intestinal carcinoma. MoAb to CK 7 stained all hyperplastic biliary epithelium and benign cholangiocellular tumors (5/5) and 14/18 cholangiocellular carcinomas. One hepatocellular carcinoma had cells positive for both Hep Par 1 and CK 7. Liver was the only normal tissue tested that reacted with MoAb Hep Par 1. Only five nonhepatic tumors (one adrenocortical carcinoma, one interstitial cell tumor of the testis, one melanoma, and two salivary adenocarcinomas) of 277 tumors tested had focal/multifocal staining for Hep Par 1. Prolonged fixation did not alter the staining with Hep Par 1. We conclude that Hep Par 1 is a specific and sensitive marker for canine hepatocellular tumors and allows distinction between hepatocellular and biliary neoplasms.
Ovine Adenovirus Serotype 7-associated Mortality in Lambs in the United States
Authors: Debey B. M. , Lehmkuhl H. D. , Chard-Bergstrom C. , Hobbs L. A.
Published: April 2003

Adenoviral infections were diagnosed in three neonatal lambs that died spontaneously, and no other etiologic agents were identified. Clinical signs were anorexia, weakness, abdominal distention, and sudden death. Microscopic lesions consisted of multifocal necrotizing hepatitis, multifocal subacute interstitial nephritis, and loss of enterocytes from intestinal villi. Adenovirus inclusions were identified by light microscopy in the kidneys only. Adenoviral antigen, however, was identified in the liver, kidney, and intestine of the lambs by immunohistochemical techniques. An ovine adenovirus serotype 7, not previously isolated from sheep in the United States, was characterized from these lambs.
Characterization of Sublethal Microcystin-LR Exposure in Mice
Authors: Guzman R. E. , Solter P. F.
Published: April 2003

Microcystin-LR (MCLR) is a potent hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. The histology of acute lethal toxicity has been well characterized, but histology is limited regarding sublethal exposure. Balb/C mice were given a single sublethal dose of MCLR (45 μg/kg) and euthanized at 2, 4, 12, and 24 hours after exposure. Centrilobular to midzonal hepatocellular hypertrophy with loss of cytosolic vacuolation consistent with glycogen depletion occurred at 2 hours. At 4 hours, central lobular hepatocytes exhibited eccentric areas of eosinophilic cytoplasmic condensation that were partially aggregated around the outer nuclear membrane. The areas were weakly positive for cytokeratin and somewhat resembled the Mallory bodies of alcoholic human hepatitis. Small numbers of apoptotic hepatocytes were seen at 24 hours. The toxin was detectable by immunohistochemistry (IHC) as early as 2 hours and was colocalized with the areas of hepatocellular hypertrophy. Intense nuclear staining occurred at 4 hours; this was no longer evident after 12 hours. Strong staining of apoptotic bodies occurred at 24 hours. Mice that received two daily doses had a marked increase in apoptotic hepatocytes in the centrilobular areas. Lesions at four and seven doses consisted of marked hepatocytomegaly and karyomegaly with parenchymal disarray and cytosolic vacuolation. IHC revealed diffuse staining throughout the liver parenchyma consistent with toxin accumulation. An anti-MCLR monoclonal antibody detected bands at the 40-kDa mark in nuclear extracts that were identified as protein phosphatases 1 and 2A by western blotting, consistent with a covalent interaction between MCLR and nuclear protein phosphatases.
A Novel Nonsuppurative Meningoencephalitis in Young Greyhounds in Ireland
Authors: Callanan J. J. , Mooney C. T. , Mulcahy G. , Fatzer R. , Vandevelde M. , Ehrensperger F. , Mcelroy M. , Toolan D. , Raleigh P.
Published: April 2003

Fourteen 4- to 18-month-old vaccinated Greyhounds (10 males, 4 females) from three kennels in southern Ireland presented over a 2-year period with acute or insidious onset neurological signs. Head tilting, ataxia, recumbency, circling, and blindness were commonly observed, and animals were dull, dehydrated, and had lost weight. Hematologic and biochemical parameters reflected dehydration but were otherwise unremarkable. Microscopic examination revealed severe diffuse and focal gliosis and gemistocytosis accompanied by mononuclear cell perivascular cuffing in caudate nucleus and cortical gray matter of the cerebrum and in the periventricular gray matter of the anterior brainstem. Milder lesions were noted in the caudal brainstem, cranial spinal cord, and in the molecular layer of the cerebellum. This was accompanied by a lymphocyte and plasma cell infiltration of the cerebral and cerebellar meninges. Demyelination, neuropil necrosis, neuronophagia, and vasculitis were not observed. No inclusion bodies, fungi, or protozoal cysts were seen. Additional serologic and molecular pathology tests also failed to determine a cause, suggesting that these cases may represent a previously undiagnosed condition in the dog.
Morphologic and Molecular Characterization of Salmonella typhimurium Infection in Neonatal Calves
Authors: Santos R. L. , Zhang S. , Tsolis R. M. , Bäumler A. J. , Adams L. G.
Published: April 2003

The host response to Salmonella plays a major role in the outcome of infection. The present study was undertaken to further characterize Salmonella typhimurium infection in neonatal calves at both the morphologic and the molecular level using the ligated ileal loop model. Eight 4–5-week-old male Holstein calves underwent laparotomy, and loops were prepared in the ileum. The loops were either inoculated with an S. typhimurium strain pathogenic for cattle or injected with sterile LB broth as control. Samples for histology, transmission and scanning electron microscopy, and RNA extraction were collected at various time points between 5 minutes and 12 hours postinfection. Invasion of both M cells and enterocytes began at 15 minutes postinfection. No specific cell type was the main target for invasion. Intracellular bacteria were observed in the lamina propria after 1 hour postinfection. A severe acute neutrophilic response was associated with invasion of the Peyer's patches. Upregulated expression of CXC chemokines (interleukin [IL]-8, growth-related oncogenes, [GRO] α and γ, and granulocyte chemotactic protein [GCP]2) was detected by reverse transcription polymerase chain reaction beginning at 1 hour postinfection. Expression of proinflammatory (IL-1β, IL-18, and tumor necrosis factor [TNF]α) and anti-inflammatory (IL-10, IL-1Ra, and IL-4) cytokines was also assessed. A marked increase in expression of IL-1β was observed, whereas the profile of expression of IL-18 and TNFα did not change after infection. Upregulation of IL-1Ra and IL-4 but not of IL-10 was observed. These findings indicate that infection of bovine ligated ileal loops with S. typhimurium results in an acute neutrophilic inflammatory response that is associated with the upregulation of CXC chemokines (IL-8, GROα and γ, and GCP2), IL-1β, IL-1Ra, and IL-4.
Interleukin 4-Producing CD4+ T Cells in the Skin of Cats with Allergic Dermatitis
Authors: Roosje P. J. , Dean G. A. , Willemse T. , M. G. Rutten V. P. , Thepen T.
Published: April 2003

Lesional skin of cats with allergic dermatitis has a cellular infiltrate and a CD4/CD8 ratio comparable to that in humans with atopic dermatitis. CD4+ helper T cells and in particular cells belonging to the Th2 subset play an important role in disease pathogenesis in humans. We investigated the cytokine pattern of CD4+ T cells in situ, with special emphasis on the putative presence of cells producing interleukin 4 (IL4), in cats with allergic dermatitis. Immunohistochemical procedures were used to determine that CD4+ T cells in lesional and nonlesional skin of cats with allergic dermatitis can produce IL4, as occurs in humans. Lesional and nonlesional skin of cats with allergic dermatitis had significantly more IL4+ T cells ( P = 0.001) than did skin of healthy control cats. Double staining indicated that all IL4+ cells were positive for pan-T or CD4 markers. Double labeling for mast cell chymase and IL4 stained primarily different cells. Western blotting demonstrated cross-reactivity between the antibody against human IL4 and a feline recombinant IL4. These results indicate that IL4 is primarily produced by CD4+ T cells and is also present in clinically uninvolved skin, indicating a role in the pathogenesis of allergic dermatitis in cats.
Complex Polysaccharide Inclusions in Skeletal Muscle Adjacent to Sarcomas in Two Dogs
Authors: Valentine B. A. , Bildfell R. J. , Cooper B. J. , Giger U. , Fischer K. A.
Published: April 2003

Inclusions of periodic acid-Schiff-positive, amylase resistant material were found within skeletal muscle fibers adjacent to an osteosarcoma in the proximal femur of an 8-year-old intact female Cocker Spaniel dog (dog No. 1) and adjacent to a synovial cell sarcoma of the stifle joint in a 7-year-old spayed female Bouvier des Flandres dog (dog No. 2). Inclusions were pale blue-gray with hematoxylin and eosin stain and formed irregular inclusions, replacing up to approximately 80% of the fiber diameter. Inclusions from dog No. 2 were of non-membrane-bound granular to filamentous material that occasionally formed discrete, elongate electrondense masses. The features of these inclusions were similar to those of materials previously described as complex polysaccharide, polyglucosan bodies, amylopectin, and Lafora bodies. Evidence for a generalized metabolic disorder was not found in these two dogs, suggesting that storage of complex polysaccharide can occur as a relatively nonspecific response to metabolic alterations in skeletal muscle in a variety of conditions.
Angiolipomatous Tumors in Dogs and a Cat
Authors: Liggett A. D. , Frazier K. S. , Styer E. L.
Published: April 2003

Variants of lipoma are uncommon, although fibrolipoma and infiltrative lipoma have been well documented. This report describes two cases of rare angiolipoma in dogs and the first documentation of angiofibrolipoma and infiltrating angiolipoma in a cat and a dog, respectively. Tumors were solitary, and most were located on the thorax of middle-aged patients. Angiolipomas were composed of mature adipose tissue mixed with variable numbers of blood vessels. In addition to the adipose and vascular components, the angiofibrolipoma contained bundles of collagenous connective tissue. The infiltrative angiolipoma had a primary mass external to the muscle and was histologically similar to a mixed intramuscular hemangioma that was confined to the muscle. Both disrupted bundles of striated muscle and were associated with segmental degeneration and loss of myofibers.
Pathogenesis of Avian Pneumovirus Infection in Turkeys
Authors: Jirjis F. F. , Noll S. L. , Halvorson D. A. , Nagaraja K. V. , Shaw D. P.
Published: April 2003

Avian pneumovirus (APV) is the cause of a respiratory disease of turkeys characterized by coughing, ocular and nasal discharge, and swelling of the infraorbital sinuses. Sixty turkey poults were reared in isolation conditions. At 3 weeks of age, serum samples were collected and determined to be free of antibodies against APV, avian influenza, hemorrhagic enteritis, Newcastle disease, Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma meleagridis, Ornithobacterium rhinotracheale, and Bordetella avium. When the poults were 4 weeks old, they were inoculated with cell culture–propagated APV (APV/Minnesota/turkey/2a/97) via the conjunctival spaces and nostrils. After inoculation, four poults were euthanatized every 2 days for 14 days, and blood, swabs, and tissues were collected. Clinical signs consisting of nasal discharge, swelling of the infraorbital sinuses, and frothy ocular discharge were evident by 2 days postinoculation (PI) and persisted until day 12 PI. Mild inflammation of the mucosa of the nasal turbinates and infraorbital sinuses was present between days 2 and 10 PI. Mild inflammatory changes were seen in tracheas of poults euthanatized between days 4 and 10 PI. Antibody to APV was detected by day 7 PI. The virus was detected in tissue preparations and swabs of nasal turbinates and infraorbital sinuses by reverse transcription polymerase chain reaction, virus isolation, and immunohistochemical staining methods between days 2 and 10 PI. Virus was detected in tracheal tissue and swabs between days 2 and 6 PI using the same methods. In this experiment, turkey poults inoculated with tissue culture-propagated APV developed clinical signs similar to those seen in field cases associated with infection with this virus.
Alveolar Type II Cells Expressing Jaagsiekte Sheep Retrovirus Capsid Protein and Surfactant Proteins Are the Predominant Neoplastic Cell Type in Ovine Pulmonary Adenocarcinoma
Authors: Platt J. A. , Kraipowich N. , Villafane F. A. , DeMartini J. C.
Published: April 2003

Ovine pulmonary adenocarcinoma is caused by jaagsiekte sheep retrovirus. To gain insight into the histogenesis and viral pathogenesis of this neoplasm, the tumor cell phenotypes and differentiation state were correlated with the distribution of jaagsiekte sheep retrovirus capsid protein in neoplastic and normal cells of the lung in nine naturally occurring and 12 experimentally induced cases of ovine pulmonary adenocarcinoma. Overall, 82% of tumor cells had ultrastructural features consistent with alveolar type II cells, 7% of tumor cells had features of Clara cells, and 11% of tumor cells were insufficiently differentiated to classify. The proportion of the neoplastic cell phenotypes varied within tumors, and no tumor consisted of a morphologically uniform cell population. To further characterize the neoplastic cell population, sections of tumors were immunostained with antibodies to surfactant protein A, surfactant protein C, and Clara cell 10-kd protein. Overall, surfactant proteins A and C were expressed in 70% and 80% of tumor cells, respectively, whereas Clara cell 10-kd protein was expressed in 17% of tumor cells. Jaagsiekte sheep retrovirus capsid protein was detected in 71% of tumor cells and in macrophages (5/21 tumors examined) and in nonneoplastic alveolar and bronchiolar cells (6/14 tumors). Expression of this viral protein in neoplastic cells, classified morphologically and by immunophenotyping primarily as of the alveolar type II lineage, implies an important role for specific virus–cell interactions in the pathogenesis of ovine pulmonary adenocarcinoma.
Genital Tract Smooth Muscle Tumors Are Common in Zoo Felids but Are Not Associated with Melengestrol Acetate Contraceptive Treatment
Authors: Chassy L. M. , Gardner I. A. , Plotka E. D. , Munson L.
Published: April 2003

In a survey of gynecologic lesions in female zoo felids conducted to determine if the widely used progestin contraceptive melengestrol acetate (MGA) had adverse effects, numerous leiomyomas and leiomyosarcomas were detected. This current study aimed to characterize the morphologic features of these tumors, determine their prevalence, and assess if MGA was a risk factor for their genesis. Genital tracts from 219 zoo felids representing 23 species were evaluated, and leiomyomas were detected in 24% of the felids. Leiomyomas were often multiple and occurred in the myometrium, ovary, or adjacent broad ligament. The risk of developing leiomyomas increased with age, but MGA treatment or parity had no effect. Five other felids had leiomyosarcomas. Leiomyosarcomas were distinguished from poorly demarcated leiomyomas by the presence of local invasion, metastasis, and cellular atypia, but necrosis and mitotic rate were not distinguishing criteria. Four of five felids with leiomyosarcomas had been treated with MGA. These results indicate that leiomyomas are common spontaneous lesions in the genital tracts of zoo felids and their genesis is not linked to MGA exposure. Whether progression to malignancy is promoted by MGA warrants further investigation.
Intracranial Lymphomas in Simian Retrovirus-Positive Macaca fascicularis
Authors: Paramastri Y. A. , Wallace J. M. , Salleng K. J. , Wilkinson L. M. , Malarkey D. E. , Cline J. M.
Published: April 2003

Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. 1 for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.
Malignant Nerve-Sheath Tumor with Divergent and Glandular Differentiation in a Dog: A Case Report
Authors: Patnaik A. K. , Zachos T. A. , Sams A. E. , Aitken M. L.
Published: April 2003

Malignant nerve-sheath tumor with divergent differentiation including epithelial components was diagnosed in an 8-year-old Labrador retriever. The myelographic, morphologic, and immunohistochemical findings confirmed the diagnosis. The tumor was located in the peripheral nerve roots at the first and second lumbar vertebrae. The dog survived for 161 days after resection of the tumor.
Primary Infection, Latency, and Reactivation of Bovine Herpesvirus Type 5 in the Bovine Nervous System
Authors: Perez S. E. , Bretschneider G. , Leunda M. R. , Osorio F. A. , Flores E. F. , Odeón A. C.
Published: April 2003

Bovine herpesvirus type 5 (BHV-5) infection in calves causes meningoencephalitis, a fatal disease highly prevalent in South America. To study the pathogenesis of BHV-5 infection in cattle, 12 calves (group 1: acute infection) and 11 calves (group 2: latent infection) were intranasally inoculated with an Argentinean BHV-5 isolate at 108 and 104.7 tissue culture infective doses, respectively; six calves (control group) were mock infected. At 3 months postinoculation, all of the calves in group 2 and three calves in group 3 were given dexamethasone to reactivate the virus. The animals were euthanatized between days 6 and 17 postinoculation (group 1) and between days 6 and 16 postreactivation (group 2). Seventy-five percent and 91% of animals in groups 1 and 2, respectively, excreted BHV-5 in nasal and ocular discharges. Following dexamethasone administration, 45% of calves shed virus in both types of secretions. Spontaneous virus reactivation and shedding was observed in one calf. Neurologic signs consisting of circling, teeth grinding, ptyalism, jaw chomping, tongue protrusion, and apathy were observed in two animals in group 1 and, during the reactivation period, in four animals in group 2. Macroscopic findings consisted of softening of the cerebral tissue, meningeal hemorrhages and swelling, and edema and hemorrhages of prescapular, retropharyngeal and submandibular lymph nodes. Histologic lesions consisted of meningitis, mononuclear perivascular cuffing, neuronophagia, satellitosis, gliosis, hemorrhage, and necrosis and edema. Lesions in anterior cerebral cortex, medulla, and pons were consistently seen in all the animals of group 1. In the acutely infected animals, lesions in the diencephalon appeared at day 10 postinoculation, whereas in the latently infected calves these lesions were observed as early as at day 6 postreactivation. Latently infected animals developed lesions simultaneously in anterior cortex, medulla, pons, and diencephalon, showing a remarkable difference from the acutely infected group. Trigeminal ganglionitis appeared relatively early in animals of both groups (day 7 postinoculation in group 1 and day 8 postreactivation in group 2).