bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pagetoid Variant of Urothelial Carcinoma In Situ of Urinary Bladder in a Cow
Authors: Borzacchiello G. , Ambrosio V. , Galati P. , Poggiali F. , Venuti A. , Roperto F.
Published: April 2003

A case of urothelial carcinoma in situ of urinary bladder is reported in a 10-year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow.
Primary Canine and Feline Nervous System Tumors: Intraoperative Diagnosis Using the Smear Technique
Authors: Vernau K. M. , Higgins R. J. , Bollen A. W. , Jimenez D. F. , Anderson J. V. , Koblik P. D. , LeCouteur R. A.
Published: April 2003

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.
Evidence for the Localization of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Antigen and RNA in Ovarian Follicles in Gilts
Authors: Sur J.-H. , Doster A. R. , Galeota J. A. , Osorio F. A.
Published: April 2003

The pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV) infection in ovary was studied in sexually mature, cycling, nonsynchronized gilts infected with the PRRSV 16244B, a virulent field strain. Previous studies have shown that PRRSV can be isolated from ovaries and is transplacentally passed from gilts to the fetuses. The cause of infertility following PRRSV infection is not known. In this study, we identified the tropism of PRRSV in ovarian tissue from experimentally infected gilts in samples collected between 7 and 21 days postinfection (DPI). Tissues were collected and examined by virus isolation, in situ hybridization (ISH), immunohistochemistry (IHC), and double labeling to identify PRRSV-infected cell types. PRRSV was isolated in ovarian follicles at 7 days DPI. The IHC and ISH indicated that PRRSV-positive cells in ovaries were predominantly macrophages, which were numerous in atretic follicles. No evidence of infection and/or perpetuation of PRRSV in ova was observed, indicating that the female gonad is an unlikely site of persistence. No alteration of the normal ovarian architecture that would support a possible role of PRRSV infection in porcine female infertility was observed.
Viral Replication and Lesions in BALB/c Mice Experimentally Inoculated with Porcine Circovirus Isolated from a Pig with Postweaning Multisystemic Wasting Disease
Authors: Kiupel M. , Stevenson G. W. , Choi J. , Latimer K. S. , Kanitz C. L. , Mittal S. K.
Published: April 2003

Eight-week-old BALB/c mice were either sham inoculated (control mice) or were inoculated intraperitoneally (IP) and intranasally (IN) with a single (sPCV mice) or multiple (mPCV mice) doses of porcine circovirus 2 (PCV2). Four control mice and 4 sPCV mice were sacrificed 7, 14, 28, and 42 days postinoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. In addition, 7-day and 14-day pregnant BALB/c mice were either sham inoculated (control mice) or were inoculated IP and IN with a single dose of PCV2. Newborn mice were euthanatized 1, 8, and 15 days after birth. Necropsies were performed on all euthanatized mice and tissues were collected for histopathology, electron microscopy, in situ hybridization, and polymerase chain reaction (PCR). PCV2 replicated in 8-week-old BALB/c mice that were inoculated with PCV2 and caused fetal infection when inoculated into pregnant BALB/c mice at 7 days and 14 days of gestation. PCV was detected by in situ hybridization and PCR in sPCV mice on days 7, 14, 28, and 42 PI; in mPCV mice on day 42 PI; and in newborn mice from mothers inoculated with PCV at 7 days and 14 days of gestation at 1, 8, and 15 days after birth, but not in control mice. No clinical signs or gross lesions were found in sPCV or mPCV mice during the study. Microscopic lesions in sPCV mice and mPCV mice were characterized by expansion of germinal centers in lymphoid organs with large numbers of histiocytic cells and lymphoblasts, apoptosis of histiocytic cells in germinal centers, and mild lymphoid depletion of the paracortex. PCV nucleic acid was detected in the nuclei and cytoplasm of histiocytes and apoptotic cells in germinal centers in lymphoid tissues as well as in the nuclei of hepatocytes in the liver, in the nuclei of renal tubular epithelial cells, and in the cytoplasm of single lymphocytes in the thymus. Congenitally infected mice only had PCV nucleic acid detected in putative Kupffer cells in livers.
Pathobiology of A/Chicken/Hong Kong/220/97 (H5N1) Avian Influenza Virus in Seven Gallinaceous Species
Authors: L. Perkins L. E. , Swayne D. E.
Published: April 2003

Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/ 220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease. Grossly, the most severe and consistent lesions included splenomegaly, pulmonary edema and congestion, and hemorrhages in enteric lymphoid areas, on serosal surfaces, and in skeletal muscle. Histologic lesions were observed in multiple organs and were characterized by exudation, hemorrhage, necrosis, inflammation, or a combination of these features. The lung, heart, brain, spleen, and adrenal glands were the most consistently affected, and viral antigen was most often detected by immunohistochemistry in the parenchyma of these organs. The pathogenesis of infection with the HK/220 HPAI virus in these species was twofold. Early mortality occurring at 1-2 days postinoculation (DPI) corresponded to severe pulmonary edema and congestion and virus localization within the vascular endothelium. Mortality occurring after 2 DPI was related to systemic biochemical imbalance, multiorgan failure, or a combination of these factors. The pathobiologic features were analogous to those experimentally induced with other HPAI viruses in domestic poultry.
Cutaneous DNA Vaccination Against Ebola Virus by Particle Bombardment: Histopathology and Alteration of CD3-positive Dendritic Epidermal Cells
Authors: Steele K. E. , Stabler K. , VanderZanden L.
Published: April 2003

We analyzed the localization of gold particles, expression of immunogenic protein, and histopathologic changes after vaccinating guinea pigs and mice with a DNA vaccine to the Ebola virus glycoprotein administered by cutaneous particle bombardment. Gold particles were deposited in all layers of the epidermis and in the dermis. Those in the epidermis were lost as the damaged layers sloughed, while those in the dermis were phagocytized by macrophages. Glycoprotein was demonstrated by immunohistochemistry primarily in keratinocytes in the epidermis and hair follicle epithelium and less frequently in dermal macrophages, fibroblasts, sebocytes, and cells that appeared to be Langerhans cells. The number of cells that expressed glycoprotein increased between 4 and 8 hours postvaccination, then decreased to near zero by 48 hours. The vaccine sites were histologically divisible into three zones. The central portion, zone 1, contained the most gold particles in the dermis and epidermis and had extensive tissue damage, including full-thickness epidermal necrosis. Zone 2 contained fewer gold particles in the epidermis and dermis and had less extensive necrosis. The majority of cells in which glycoprotein was expressed were in zone 2. Zone 3 contained gold particles only in the epidermis and had necrosis of only a few scattered cells. Regeneration of the epidermis in damaged areas was evident at 24 hours postvaccination and was essentially complete by day 5 in the mice and day 10 in the guinea pigs. Inflammatory changes were characterized by hemorrhage, edema, and infiltrates of neutrophils initially and by infiltrates of lymphocytes and macrophages at later times. In zone 1, inflammation affected both the epidermis and dermis. Peripherally, inflammation was relatively limited to the epidermis. CD3-positive dendritic epidermal cells were demonstrated in the epidermis and superficial hair follicles of unvaccinated immunocompetent mice and beige mice but not of SCID mice. These cells disappeared from all but the most peripheral portions of the vaccine sites of vaccinated mice within 24 hours. They reappeared slowly, failing to reach numbers comparable with unvaccinated mice by 35 days postvaccination. The epidermis of control guinea pigs also had CD3-positive cells, but they did not have dendrites. These findings should contribute to a better understanding of the mechanisms operating in response to DNA vaccination by particle bombardment.
Aural-pharyngeal Polyps Associated with Cryptosporidium Infection in Three Iguanas (Iguana iguana)
Authors: Uul E. W. , Jacobson E. , Bartick T. E. , Micinilio J. , Schimdt R.
Published: April 2003

Cryptosporidium spp. infection was associated with aural-pharyngeal polyps in three iguanas ( Iguana iguana). All iguanas were presented for masses protruding from the ear canal, and the disease was characterized by a chronic clinical course. The masses consisted of nests of cystic glands surrounded by abundant fibrous connective tissue and lined by hyperplastic cuboidal to pseudostratified columnar epithelium that was moderately to heavily colonized by cryptosporidial organisms. Electron microscopy revealed that the majority of organisms were trophozoites.
Clinical, Biochemical, and Molecular Aspects of Glanzmann's Thrombasthenia in Humans and Dogs
Authors: Boudreaux M. K. , Lipscomb D. L.
Published: April 2003

Glanzmann's thrombasthenia (GT) is an inherited, intrinsic platelet function defect that involves the platelet glycoprotein complex IIb–IIIa, also known as the fibrinogen receptor and the integrin αIIbβ3. The defect was originally described by Dr. Glanzmann in humans in 1918 as a bleeding disorder that differed clinically from other known coagulopathies. Over the decades that followed, researchers determined the biochemical and molecular basis for the disease in humans. Otterhounds with thrombasthenic thrombopathia, described in the 1960s, were the only animal model that closely resembled the disease described in humans until 1996. At that time, a Great Pyrenees dog was identified with unequivocal clinical and biochemical features of Type I GT. The cDNA encoding for glycoproteins IIb and IIIa were sequenced in normal dogs in 1999, allowing for identification of specific mutations causing Type I GT in both Otterhounds and Great Pyrenees dogs. Knowing the molecular basis for Type I GT in dogs as well as the cDNA sequences in normal dogs should enhance the understanding of structure/function relationships of the αIIbβ3 integrin and provide an excellent animal model for studies aimed at correction of GT in humans. The following review focuses on the structure and function of this platelet receptor and reviews the molecular, biochemical, and clinical aspects of Glanzmann's thrombasthenia in humans and dogs.
Feline Cutaneous Fibropapillomas: Clinicopathologic Findings and Association with Papillomavirus Infection
Authors: Schulman F. Y. , Krafft A. E. , Janczewski T.
Published: April 2003

Twenty-three feline cutaneous fibropapillomas with histologic features similar to equine sarcoids were diagnosed. They were characterized by dermal fibroblastic proliferation with overlying, often ulcerated hyperplastic epidermis. Electron microscopic findings supported the fibroblastic nature of the neoplastic cells. The 23 tumors came from 20 cats and were submitted from veterinary clinics in Wisconsin and Minnesota. These tumors occurred most commonly in young cats and were found primarily on the head, neck, and digits. Fifteen of the 17 cats for which breed was reported were domestic shorthair cats. In 11/20 cases, there was confirmed exposure to cattle. Local recurrence of the tumor following surgical excision was reported in 7 of the 18 cats for which follow-up information was available. Metastasis was not documented in any of the cases. Two of the 19 tumors tested by polymerase chain reaction (PCR) had no amplifiable DNA. The remaining 17 were positive for papillomavirus by PCR. No papillomavirus DNA was detected in three other feline skin tumors (cutaneous mast cell tumor, malignant lymphoma, and fibrosarcoma) that served as controls. This is the first report of detection of papillomavirus in feline tumors that have clinicopathologic features similar to equine sarcoids.
Pathogenesis of Two Strains of Lion (Panthera leo) Morbillivirus in Ferrets (Mustela putorius furo)
Authors: Evermann J. F. , Leathers C. W. , Gorham J. R. , Mckeirnan A. J. , Appel M. J. G.
Published: April 2003

Canine distemper virus (CDV) was previously considered to have a host range restricted to the canid family. In 1994, the virus was associated with sporadic outbreaks of distemper in captive felids. However, after severe mortality occurred in the Serengeti lions ( Panthera leo), attention became focused on the pathogenesis of the virus and a concerted effort was made to identify the virus as CDV or a closely related feline morbillivirus. The present study was designed to explore the susceptibility of ferrets to challenge with two morbilliviruses isolated from lions and the protective effects of a modified-live mink distemper vaccine. Because mortality in ferrets infected with pathogenic CDV approaches 100%, the ferret was selected as a test animal. Two strains of lion morbillivirus were used as a challenge, A92-27/20 (California lion isolate) and A94-11/13 (Serengeti lion isolate). The two strains of lion morbillivirus were antigenically related to CDV (Rockborn strain), and ferrets were susceptible to both of the viruses when inoculated intraperitoneally. The inoculated ferrets were anorectic at 5–6 days postinoculation (PI), exhibited oculonasal discharge at 9–12 days PI, and became moribund at 12–22 days PI. Severe bilateral conjunctivitis was the typical clinical sign. Inclusion bodies characteristic of morbillivirus (eosinophilic, intranuclear, and intracytoplasmic) were distributed in many epithelial cells, including those of the skin, conjunctiva, gallbladder, liver, pancreas, stomach, trachea, lung, urinary bladder, and kidney. Virus was reisolated from selected lung tissues collected at necropsy and identified by CDV-specific immunofluorescence. Ferrets vaccinated with the mink distemper vaccine (Onderstepoort strain) were protected from challenge with the two lion strains, adding further support to the premise that the viruses are closely related to CDV.
Immunohistochemical Detection of Apolipoprotein B-100 and Immunoglobulins (IgA, IgM, IgG) in the Splenic Arteries of Aging Dogs
Authors: Sako T. , Uchida E. , Kagawa Y. , Hirayama K. , Takahashi T. , Nakade T. , Niiyama M. , Izumisawa Y. , Taniyama H.
Published: April 2003

Accumulation of lipids and hyalinosis in the splenic arteries of aged dogs are frequently detected by routine histopathologic examinations. The purpose of this study was to pinpoint the localization of canine apolipoprotein B-100 (CApoB-100) and immunoglobulins (IgA, IgM, IgG) in the splenic arteries of aging dogs ( n = 80) through the use of immunohistochemical techniques. CApoB-100 deposits were found in the subendothelial space, extracellular matrix, and atheromatous lesions in the tunica media of the arteries in dogs ≥ 6 years of age. Foamy cytoplasm of the infiltrated macrophages was also CApoB-100 immunopositive. In dogs ≥10 years of age, almost all central arteries were CApoB-100 immunopositive. Hyaline deposits within the wall were characterized by immunopositivity against canine IgA, IgM, IgG, and albumin. Lipid accumulation in splenic arteries may be an age-related lesion and a precursor of the atheromatous plaques associated with splenic hemorrhage and infarcts later in life. In addition, deposition of immunoglobulins, probably mediated by immune complexes, may play an important role in the development of canine vascular diseases similar to human disease.
Feline Hodgkin's-like Lymphoma: 20 Cases (1992–1999)
Authors: Walton R. M. , Hendrick M. J.
Published: April 2003

We identified 20 cases of feline lymphadenopathy that conform to many clinical and histologic manifestations of human Hodgkin's disease. Histologic subtypes encountered included lymphocyte predominance (nine cases), mixed cellularity (nine cases), and nodular sclerosis (two cases). Two cases were not easily classified; fibrous bands were present, but the absence of nodules supported a subclassification of mixed cellularity Hodgkin's disease. Immunohistochemical staining of the tissues using antibodies against the pan T-cell antigen CD3, the human B-lymphocyte antigen 36 (BLA.36), the pan B-lymphocyte and plasma cell marker CD79a, and a myeloid antigen (MAC387) confirmed the phenotypic heterogeneity of the tumor. Classic Reed–Sternberg (RS) cells and mononuclear, multinucleate, and lacunar cell variants did not stain with any of the antibodies used. In contrast, lymphohistiocytic RS variants (L+H cells) reacted positively to BLA.36 and CD79a B-cell markers. Eighteen of 20 affected cats were ≥6 years of age (range, 1-14 years). A sex predilection could not be identified. These findings support the existence of Hodgkin's-like lymphoma in the cat. Proper identification of this disease in the cat will enable further characterization of clinical features and biologic behavior to determine whether there are significant differences in the treatment and prognosis of feline Hodgkin's-like lymphoma compared with non-Hodgkin's lymphoma.
Evaluation of Proliferative Disorders in Canine Bone Marrow by Use of Flow Cytometric Scatter Plots and Monoclonal Antibodies
Authors: Weiss D. J.
Published: April 2003

The combination of flow cytometric scatterplot analysis and specific monoclonal antibodies was used to evaluate the lineage of cells from six dogs with proliferative disorders of bone marrow. Scatterplot analysis was used to identify mature and immature myeloid and erythroid cells. The immunophenotype of cells in the immature myeloid gate was determined by labeling cells with four monoclonal antibodies. These results were compared to results of cytologic and cytochemical evaluation. The immunophenotype of a dog with a diagnosis of myelogenous leukemia was a cluster of differentiation–18 (CD-18) positive, CD-14 negative, Thy-1 negative, and a major histocompatibility complex (MHC) class II negative. The immunophenotype of a dog with a diagnosis of myelomonocytic leukemia was CD-18 positive, CD-14 positive, Thy-1 positive, and MHC class II positive. Although this phenotype clearly differentiated myelomonocytic leukemia from myelogenous leukemia, it was similar to the immunophenotype of dogs with a diagnosis of malignant histiocytosis or hemophagocytic syndrome. The immunophenotype of two dogs with myelodysplastic syndrome was CD-18 positive and CD-14 negative. Results for Thy-1 and MHC class II were variable. As additional lineage-specific monoclonal antibodies become available, immunophenotyping should become a valuable tool for determination of the lineage of cells in canine myeloproliferative disorders.
Localization of the Initial Developmental Stages of Loma salmonae in Rainbow Trout (Oncorhynchus mykiss)
Authors: Sánchez J. G. , Speare D. J. , Markham R. J. F. , Wright G. M. , Kibenge F. S. B.
Published: April 2003

The intracellular microsporidian parasite Loma salmonae affects salmonids of the genus Oncorhynchus and is a significant cause of economic losses in pen-reared Chinook salmon ( O. tshawytscha) in British Columbia. Loma salmonae infection is easily recognized by the xenomas that form in the gills, but early stages of infection are difficult to detect in histologic sections. In situ hybridization (ISH), using an L. salmonae-specific digoxigenin-labeled single-stranded DNA probe, was used to detect the parasite during the early stages of infection. Loma salmonae was detected in the gut mucosal epithelium as early as 24 hours postexposure (PE), and it localized in the lamina propria of the intestine within 24 hours of infection. After the parasite was detected in the lamina propria, dividing merogonic stages in infected cells in the heart were detected by ISH as early as 2 days PE, providing the first evidence of parasitaemia and hematogenous distribution of this parasite in infected blood cells. The parasites inside the infected cells appeared to be undergoing merogony as they passed through the heart, indicating that proliferation may start at the site of infection, before the parasite arrives to the gills for their final developmental phase. This is the first time that L. salmonae passage through the intestinal wall and migration to the heart has been visualized; however, the identity of the cells harboring the parasite has yet to be determined.
Clinicopathologic and Electron Microscopic Study of Cutaneous Neuroendocrine (Merkel Cell) Carcinoma in a Cat with Comparisons to Human and Canine Tumors
Authors: Patnaik A. K. , Post G. S. , Erlandson R. A.
Published: April 2003

Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the basis of morphologic and electron microscopic findings. The cat was euthanatized 321 days after surgical excision of the tumor. The tumor's malignancy contrasted with the benign nature of Merkel cell tumors reported in dogs and was consistent with the malignancy of Merkel cell tumors reported in humans.
Spontaneous Neoplasms in Captive African Cane Rats (Thryonomys swinderianus Temminck, 1827)
Authors: Jori F. , Cooper J. E.
Published: April 2003

Despite the increasing importance of cane rat ( Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known. A survey of a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the observation of several suspected tumors and the confirmation of three cases of neoplasms. Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such a short period is uncommon. Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication. Although the etiology remains undetermined, these cases are described to provide baseline data on the pathology of this species in captivity.
Immunohistochemical Detection of Inhibin-α, -βB, and -βA Chains and 3β-hydroxysteroid Dehydrogenase in Canine Testicular Tumors and Normal Testes
Authors: Taniyama H. , Hirayama K. , Nakada K. , Numagami K. , Yaosaka N. , Kagawa Y. , Izumisawa Y. , Nakade T. , Tanaka Y. , Watanabe G. , Taya K.
Published: April 2003

Immunohistochemical detection of inhibin-α, -βA and -βB chains and 3β-hydroxysteroid dehydrogenase (HSD) was carried out on primary testicular tumors from 15 dogs and normal testes from three adult dogs. Histopathologically, the tumors were composed of three types: Leydig cell tumors in five dogs, Sertoli cell tumors in five dogs, and seminoma in five dogs. In normal testes, immunostaining against inhibin-α, -βA, and -βB chains and 3β-HSD revealed positive reactivity in the cytoplasm of Leydig cells. In testicular tumors, immunoreactive cells against inhibin-α, -βA, and -βB chains and 3β-HSD were localized in all Leydig cell tumors but not in any Sertoli cell tumors or seminomas. The results of radioimmunoassay for plasma inhibin in dogs with Leydig cell tumors showed higher concentrations than those in dogs with Sertoli cell tumors and seminomas and those in normal dogs. The concentration of inhibin in the plasma was markedly decreased by the surgical removal of the Leydig cell tumor in one dog. Our findings suggest that inhibin is synthesized by normal and neoplastic Leydig cells in the canine testis, and the secreted inhibin may be inhibin A and inhibin B.
Gastrointestinal Stromal Tumors in Equids
Authors: Del Piero F. , Summers B. A. , Cummings J. F. , Mandelli G. , Blomme E. A.
Published: April 2003

Eleven gastrointestinal neoplasms from 10 aged horses and 1 pony were examined grossly, histologically, immunohistochemically, and (in two cases) ultrastructurally. Clinical signs were associated with two neoplasms, and the other nine tumors were incidental findings at laparotomy or necropsy. The neoplasms were solitary (9/11) or multifocal (2/11), well demarcated, serosal or mural masses of stomach (1), jejunum (1), ileum (3), cecum (5), and/or colon (2). Microscopic examination revealed discrete spindle cells arranged in compact patterns with fascicles and whorls or cribriform pattern with fascicles and rare palisades, often with a myxoid interstitial matrix. Three tumors infiltrated between the muscularis interna and the muscularis externa at the myenteric plexi. All neoplasms were vimentin positive, 3/11 were S-100 positive, 2/11 were muscle actin positive, and no neoplasm was positive for glial fibrillary acid protein, desmin, factor VIII, chromogranin, or neuron-specific enolase. Of the two tumors studied ultrastructurally, one contained an admixture of smooth muscle cells and cells resembling Schwann cells, and the second was populated by homogeneous fusiform mesenchymal cells separated by homogeneous matrix. Gastrointestinal stromal tumors (GIST) have been recognized in humans, more recently in dogs and nonhuman primates, and now in equids. Most of these tumors are comprised of a loosely arranged network of spindled cells separated by myxoid matrix. GIST may be composed of myogenic, neurogenic, combined myogenic and neurogenic, and undifferentiated mesenchymal cells.
MIB-1 Labeling Index in Feline Dysplastic and Neoplastic Mammary Lesions and Its Relationship with Postsurgical Prognosis
Authors: Millanta F. , Lazzeri G. , Mazzei M. , Vannozzi I. , Poli A.
Published: April 2003

Samples from feline normal, dysplastic, and neoplastic mammary tissues were used to investigate the usefulness of MIB-1 labeling index (MIB-1 I) as a prognostic indicator. Forty-eight queens bearing invasive carcinomas were included in a 2-year follow-up study. Mammary lesions were classified according to the World Health Organization system, and invasive carcinomas were further graded on the basis of the degree of tubule formation, the degree of nuclear and cellular pleomorphism, and mitotic count. Additional sections were immunostained using MIB-1 antibody, and MIB-1 I was expressed as a percentage of positive nuclei. In normal mammary gland tissues, the mean MIB-1 I was <1%. A low proliferation rate was found in all mammary adenosis and in situ carcinomas, and the highest rates were observed in feline mammary hypertrophy and invasive carcinomas. Twenty-one (43.7%) of the queens bearing invasive carcinomas were still alive at the end of the trial, and 27 (56.2%) had died. The MIB-1 I was not significantly correlated with clinical outcome, age, histologic type, or grading of the tumors, but a borderline correlation was observed with invasion of lymphatic vessels. Univariate analysis showed that high MIB-1 I was also not associated with decreased overall survival, whereas the grading system of the tumors had high predictive value ( P = 0.0040) for postsurgery survival. The lack of correlation between MIB-1 I and postsurgery survival suggests that this marker alone is not sufficient to determine a correct prognosis in feline mammary carcinomas, even if it is a useful proliferation marker.
Pathology of Sarcocystis neurona in Interferon-Gamma Gene Knockout Mice
Authors: Fritz D. L. , Dubey J. P.
Published: April 2003

Pathologic changes were studied in 27 interferon-gamma gene knockout mice 34–54 days after being fed graded doses of Sarcocystis neurona sporocysts derived from a naturally infected opossum. The target tissue for S. neurona infection was the central nervous system. Characteristic histopathologic changes present in all mice consisted of an inflammatory infiltrate consisting of mostly neutrophils and macrophages, fewer eosinophils, and rare multinucleated giant cells. Intralesional protozoa and scattered subacute perivascular cuffs were present. Where the infiltrates were extensive, neuropil rarefaction was frequent. Pathologic changes were much more frequent and severe in the caudal portion of the brain, especially in the cerebellum, than in the middle and cranial portions. Changes were present in all spinal cords examined (10 of 10). Lesions were equally distributed in white and gray matter of the brain and spinal cord and their meningeal linings.
Trigeminal and Polyradiculoneuritis in a Dog Presenting with Masticatory Muscle Atrophy and Horner's Syndrome
Authors: Panciera R. J. , Ritchey J. W. , Baker J. E. , Digregorio M.
Published: April 2003

A 9-year-old, spayed female, Airedale Terrier was euthanatized and necropsied after a progressive clinical course that included Horner's syndrome of the left eye and unilateral atrophy of the masticatory muscles. Although gross lesions were limited, a polyradiculoneuritis and ganglionitis that was most severe in the trigeminal nerves and ganglia were confirmed histologically. The inflammatory infiltrate consisted predominantly of macrophages and B and T lymphocytes that were phenotypically confirmed by immunostaining. Horner's syndrome was the result of damage to postganglionic sympathetic fibers that were incorporated in segments of the inflamed trigeminal nerve and its ophthalmic branch. Histologically, the character and distribution of the inflammation was similar to previously described syndromes of suspected immune-mediated etiology in humans and animals.
Keloidal Fibromas and Fibrosarcomas in the Dog
Authors: Mikaelian I. , Gross T. L.
Published: April 2003

Sixteen dogs (2–12 years of age) presented with one ( n = 15) or two ( n = 1) cutaneous nodules ( n = 16) or a dermal plaque ( n = 1). Intact males ( n = 9) and neutered males ( n = 4) were more affected than were females ( n = 3). Histologically, these lesions were characterized by focal dermal and subcutaneous deposition of thick hyalinized collagen fibers intermingled with fibroblasts, and in 13 of 17 lesions, a variable number of CD18-positive cells were interpreted as reactive macrophages. Fibroblasts in three dogs formed intersecting fascicles, interpreted as evidence of malignant transformation. The terms keloidal fibroma and keloidal fibrosarcoma can be applied to these lesions. Excision was curative in five dogs with keloidal fibroma for which follow-up was available. However, because malignant transformation may occur, wide excision of canine keloidal lesions is warranted.
The Influence of Age on the Cytology of the Liver in Healthy Dogs
Authors: Stockhaus C. , Teske E. , Van Den Ingh T. , Rothuizen J.
Published: April 2003

Liver cytology was evaluated in 28 healthy dogs 1–14 years of age with normal liver structure and function. Smears were stained with May-Grünwald-Giemsa. Hepatocytes had distinct cell borders, and cells did not overlap. Cells with two nuclei and cells with intranuclear crystalloid structures were observed regularly. Cytoplasm contained small numbers of vacuoles characteristic of glycogen and lipid and small amounts of pigment consistent with ceroid or bile. Nuclei were uniform. Small numbers of biliary epithelial cells were seen in most samples. Lymphocytes and neutrophils occurred in small numbers, with lipocytes, mast cells, fibrocytes, mesothelial cells, eosinophils, and Kupffer macrophages seen less frequently. Mean parenchymal cell sizes were significantly greater in older dogs, but no age-related differences were observed in nuclear size. Older dogs also had a significantly increased number of nuclei per cell. There were more neutrophils in young and old dogs than in middle-aged dogs.
Cardiomyopathy in Broiler Chickens Congenitally Infected with Avian Leukosis Virus Subgroup J
Authors: Stedman N. L. , Brown T. P.
Published: April 2003

Dilated cardiomyopathy and ascites in broiler chickens are frequently associated with rapid growth and pulmonary hypertension, but can be associated with some avian leukosis virus (ALV) infections. The novel subgroup J of ALV has a high cardiac tropism, but dilated cardiomyopathy has not been reported previously. We report a dilated cardiomyopathy incidence of 11.1% in broiler chickens congenitally infected with ALV subgroup J (ALV-J). Gross lesions included severe body weight suppression, cardiomegaly with biventricular dilation, right ventricular hypertrophy, visceral congestion, and ascites. Cardiac myocytes and Purkinje fibers contained 2- to 10-μm intracytoplasmic magenta inclusions that contained ALV-J-specific nucleic acid. Ultrastructurally, inclusions contained ribosomes and immature virions and were associated with myofibril disruption and disarray. Peracute centrilobular hepatic necrosis was present in most cases. ALV-J-associated cardiomyopathy may involve a direct viral effect on cardiac myocytes and Purkinje fibers.
Feline Vaccine-associated Fibrosarcoma: Morphologic Distinctions
Authors: Couto S. S. , Griffey S. M. , Duarte P. C. , Madewell B. R.
Published: April 2003

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for α-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.
SIV-associated Lymphomas in Rhesus Monkeys (Macaca mulatta) in Comparison with HIV-associated Lymphomas
Authors: Kahnt K. , Mätz-Rensing K. , Hofmann P. , Stahl-Hennig C. , Kaup F.-J.
Published: April 2003

A retrospective study was performed to characterize malignant lymphomas of 16 Simian immunodeficiency virus (SIV)-infected rhesus monkeys ( Macaca mulatta), 2–9 years of age, on the basis of clinical data, histologic and immunophenotypic results, and cell death indices compiled with the TdT-mediated X-duTP nick end labeling method. We particularly focused on providing immunohistochemical evidence of expression products of EBNA2, Bcl2, c-Myc, P21, P53, and Bc16. Results were compared with data from the literature on human HIV-associated lymphomas. According to the updated Kiel classification, the lymphomas were classified as 11 centroblastic lymphomas, three immunoblastic lymphomas, one Burkitt-like lymphoma, and one immunocytoma. Using antibodies to CD20, the B-cell origin of tumor cells was demonstrated. SIV antigen was not demonstrated in the tumor cells. Infection with rhesus lymphocryptovirus was present in 94% of the monkeys. Lymphomas revealed expression of Bc12 in 15/16 (94%), c-Myc in 14/16 (88%), P21 in 10/16 (63%), P53 in 12/16 (75%), and Bc16 in 1/16 (6%) monkeys. This study provided evidence that the expression of these gene products, which are thought to play an important role in cell proliferation and apoptosis in HIV- and non-HIV-associated lymphomas, are also involved in the pathogenesis of lymphomas in SIVinfected rhesus monkeys. A tentative relationship between the described gene products and the cell death indices was established for the expression of Bc12. The present primate model represents a suitable animal model for studying the pathogenesis of AIDS-associated lymphomas.
Inducible Nitric Oxide Synthase and Nitrotyrosine in Listeric Encephalitis: A Cross-species Study in Ruminants
Authors: Pfister H. , Remer K. A. , Brcic M. , Fatzer R. , Christen S. , Leib S. , Jungi T. W.
Published: April 2003

Listeria monocytogenes (LM) is a Gram-positive facultative intracellular bacterium that causes fatal meningoencephalitis in humans and ruminants. A current paradigm predicts that intracellular bacteria are controlled by nitric oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase (iNOS). The ability of macrophages (MΦ) to express iNOS shows extreme interspecies variability. Here the expression of iNOS and synthesis of NO was studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed by a subset of MΦ in cerebral microabscesses in all three species. The level of iNOS expression and the density of cells per lesion expressing iNOS was highest in cattle, intermediate in sheep, and lowest in goats. The accumulation of nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions of cattle but not in those of small ruminants. The density of iNOS-expressing cells in lesions was inversely correlated with the number of bacteria. No species differences were observed in regard to reactive oxygen intermediate (ROI) production by stimulated granulocytes, using the flow cytometric dihydrorhodamine-123 (DHR) method indicating ROI generation. Thus, the marked species differences in iNOS expression, NT accumulation, and LM content in lesions of ruminants with listeric encephalitis are explained by different amounts of ROI produced. It suggests that variations in the ability of MΦ to synthesize NO are of pathophysiological significance in listeriosis.
Clinical, Microscopic, and Molecular Aspects of Canine Leproid Granuloma in the United States
Authors: Foley J. E. , Borjesson D. , L Gross T. , Rand C. , Needham M. , Poland A.
Published: April 2003

Leproid granulomas from seven dogs in the United States were evaluated. Gross characteristics included nodular and ulcerated dermal and subcutaneous lesions primarily on the caudal aspects of the pinnae and to a lesser extent on the muzzle, face, and forelimbs. In all except one dog, there was complete regression of the lesions within 6 months, either with no therapy or after surgical resection. Cytology or histopathology revealed pyogranulomatous inflammation with few to many acid-fast mycobacterial bacilli within macrophages. The organisms could not be cultivated in vitro. DNA sequencing of part of the 16S ribosomal RNA gene region revealed 99–100% homology among fragments from five of these dogs and fragments from dogs in the South Pacific. This syndrome occurs in dogs in North America and the prognosis is excellent, in contrast to the prognosis for rapid-growing or tuberculous mycobacteriosis.
Prognostic Significance of a New Histologic Grading System for Canine Osteosarcoma
Authors: Kirpensteijn J. , Kik M. , Rutteman G. R. , Teske E.
Published: April 2003

Histologic grade is an important determinant in clinical outcome of human osteosarcoma (OS). In this study, the histologic characteristics of primary and metastatic canine OS were evaluated using a new classification system. Histologic characteristics were classified in 166 primary and 34 metastatic canine OS. Prognostic variables for clinical outcome were determined using multivariate analysis. Most OS were histologically characterized by severe to extreme cellular pleomorphism, a variable number of mitoses, small to moderate amounts of matrix, a high percentage of tumor cells, and minimal to moderate amounts of necrosis. Tumor invasion into vessels was present in 117/152 (71%) tumors, and 12/50 (24%) of the regional lymph nodes had evidence of metastasis. Classification of the 166 tumors resulted in seven (4%) grade I, 34 (21%) grade II, and 125 (75%) grade III OS. In the multivariate analysis, histologic grade III OS and elevated pretreatment plasma alkaline phosphatase (AP) levels were independent predictors of clinical outcome. Dogs with high-grade tumors and elevated AP should be carefully evaluated for the presence of metastatic disease before starting adjunctive therapy protocols.
Encephalomyelitis Associated with Akabane Virus Infection in Adult Cows
Authors: Lee J. K. , Park J. S. , Choi J. H. , Park B. K. , Lee B. C. , Hwang W. S. , Kim J. H. , Jean Y. H. , Haritani M. , Yoo H. S. , Kim D. Y.
Published: April 2003

Between August and September 2000, five 2–7-year-old cows in Korea exhibited neurologic signs and were diagnosed as infected with Akabane virus based on the results of histopathology, immunohistochemistry, serology, and reverse transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry and RT-PCR were equally effective and sensitive for diagnosing Akabane virus infection during the early stage of infection. Typical lymphohistiocytic inflammation characterized by perivascular mononuclear cell infiltration, gliosis, neuronophagia, and neuronal loss was noted in the brain and the ventral horn gray matter of the spinal cord. The lesions in the brain were most prominent in the pons and medulla oblongata. Akabane virus antigen was detected in the brain and spinal cord, mainly in degenerating neurons and glial cells. RTPCR analysis revealed a target band of expected size in four cows. This is the first report on an outbreak of natural Akabane virus infection in adult cattle.
Cutaneous Vasoproliferative Lesions in Goats
Authors: Bildfell R. J. , Valentine B. A. , Whitney K. M.
Published: April 2003

In a retrospective survey of caprine neoplastic disease, eight masses were diagnosed as cutaneous vascular tumors. The typical clinical presentation was a solitary raised, bleeding mass. No predilection with regard to age, breed, sex, or anatomic location was found. Reevaluation of the microscopic features of the masses resulted in diagnoses of hamartoma (2), hemangioma (4), and hemangiosarcoma (2). An endothelial cell origin was confirmed in all seven tumors tested immunohistochemically for factor VIII-related antigen. Although rarely reported, goats display a range of cutaneous vascular growth abnormalities similar to those observed in other domestic animals.
Cyclooxygenase-2 Expression in Spontaneous Intestinal Neoplasia of Domestic Dogs
Authors: Mcentee M. F. , Cates J. M. , Neilsen N.
Published: April 2003

Cyclooxygenase-2 (Cox-2) is commonly upregulated during human colorectal tumorigenesis, and its contribution to this process has been clearly demonstrated in genetic mouse models. The only other species that naturally develops intestinal cancer with any frequency is the domestic dog. Intestinal carcinogenesis in humans has been strongly linked to environmental factors such as diet, which may be shared by household pets. We have previously reported that β-catenin is overexpressed in the neoplastic epithelium of canine colorectal polyps, as it is in humans and rodents. We now show that Cox-2 is also upregulated in the majority of these lesions. Thirteen out of 20 colorectal adenomas (65%) contained immunohistochemically detectable Cox- 2 protein restricted to the nonneoplastic tumor stroma, including myofibroblasts and β-smooth muscle actin-negative mesenchymal cells morphologically consistent with macrophages and/or fibroblasts. In contrast to benign polyps, seven of 15 adenocarcinomas (47%) also expressed Cox-2 in the neoplastic epithelium. These changes duplicate molecular changes in human intestinal tumorigenesis and substantiate a fundamental role for both β-catenin and Cox-2 in intestinal neoplasia.
Histopathology and Biologic Behavior of Pleomorphic Cutaneous Mast Cell Tumors in Fifteen Cats
Authors: Johnson T. O. , Schulman F. Y. , Lipscomb T. P. , Yantis L. D.
Published: April 2003

Most feline cutaneous mast cell tumors (CMCT) are behaviorally benign; however, there is a subset of these tumors with marked pleomorphism (previously termed poorly differentiated) that have been reported to be more aggressive. In this study, pleomorphic CMCT from 15 cats were identified from surgical biopsy submissions, and follow-up clinical data were obtained for 14 of these cats. Pleomorphic CMCT were discrete dermal nodules composed of sheets of pleomorphic round cells. Tumors from all 15 cats contained markedly cytomegalic and karyomegalic cells; 9/15 tumors (60%) contained multinucleated tumor giant cells. Typical mast cell granules were easily identified in sections stained with hematoxylin and eosin and with metachromatic stains and based on ultrastructural evaluation in cytomegalic as well as smaller tumor cells, indicating that the tumors were not poorly differentiated. The mitotic rate was very low (<1 mitosis per 10 high-power fields [hpf]) in 14 of 15 tumors (93%). Affected cats were 6–19 years old (mean age = 11.5 years), and there was no breed or sex predilection. Two cats had local recurrence. The only cat that had a pleomorphic CMCT with a high mitotic rate (1–2 mitoses/hpf) subsequently developed numerous other dermal neoplasms and was euthanatized. In this study, the large majority of feline pleomorphic CMCT were behaviorally benign. Mitotic rate is likely an important prognostic indicator of CMCT behavior.