bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Viral Antigen in Placenta and Fetus of Cattle Acutely Infected with Bovine Viral Diarrhea Virus
Authors: Fredriksen B. , Press C. M. , Sandvik T. , Ødegaard S. A. , Løken T.
Published: April 2003

The reproductive organs and fetuses of seven Norwegian Red heifers were investigated for the presence of bovine viral diarrhea virus (BVDV) antigen during the time of initial transplacental transmission of the virus. The heifers were inoculated with a noncytopathogenic BVDV at day 85/86 of gestation and were slaughtered at day 7, 10, 14, 18, or 22 postinoculation (pi). Cryostat sections of uterus, ovaries, placentomes, intercotyledonary fetal membranes, and fetal organs were examined using immunohistochemical techniques. A double immunofluorescence technique was used to identify cells that showed staining with antibodies against the leukocyte common antigen CD45 or the intermediate filament vimentin and BVDV antigens. The earliest stage of infection at which BVDV antigen could be detected in the fetuses was 14 days pi. At this stage, BVDV antigen was detected in cells of mesenchymal origin in the lungs and in large cells that morphologically resembled immature megakaryocytes in the liver. In the intercotyledonary fetal membranes and in the placentomes, BVDV antigen was not detected until 18 and 22 days pi, respectively. BVDV antigen was not detected in maternal tissue from any of the heifers. The present results indicate that fetal infection with BVDV can take place without preceding or simultaneous high concentrations of BVDV in uterus or placenta of acutely infected heifers.
Electron Microscopic and Immunohistochemical Localization of Marek's Disease (MD) Herpesvirus Particles in MD Skin Lymphomas
Authors: Cho K.-O. , Ohashi K. , Onuma M.
Published: April 2003

Skin lymphomas induced in 11 specific-pathogen-free chickens by inoculation at 1 day of age with Marek's disease virus (MDV) were biopsied weekly and examined by electron microscopy and immuno-histochemistry. In the sequentially biopsied lymphomas, immature MDV particles (abortive replication) were found only in the nuclei of necrotic lymphoblasts within necrotizing neoplasms. The necrotizing lymphomas were observed in two of the 11 experimental birds and were associated with prominent vascular endothelial cell injury, including fibrinoid necrosis of blood vessels. Nonnecrotizing lymphomas biopsied sequentially from the 11 experimental birds did not contain virus particles of any kind in the lymphoblasts and had no distinct vascular lesions. Immunohistochemically, MDV early antigen (pp38), but not late antigens (glycoproteins B and C), was detected only in the necrotizing lymphomas. These findings indicate that abortive MDV replication mainly occurred in necrotic lymphoblasts, which might have been induced by ischemia.
Disseminated Rhodococcus equi Infection in Two Goats
Authors: Davis W. P. , Steficek B. A. , Watson G. L. , Yamini B. , Madarame H. , Takai S. , Render J. A.
Published: April 2003

Rhodococcus equi infection was diagnosed in two goats from the same herd. At necropsy, numerous caseating granulomas were disseminated throughout the liver, lungs, abdominal lymph nodes, medulla of right humerus, and the right fifth rib of goat No. 1, and the liver of goat No. 2. Histopathologic examination confirmed the presence of multiple caseating granulomas in these organs. Numerous gram-positive and Giemsapositive coccobacilli were identified within the cytoplasm of macrophages. Aerobic bacterial cultures of the liver and lung from both goats yielded a pure growth of R. equi. R. equi antigens were immunohistochemically identified in caseating granulomas from both goats. However, the 15- to 17-kd virulence antigens of R. equi were not detected, suggesting possible infection by an avirulent strain of this organism.
Thymic Cysts in Harbor Porpoises (Phocoena phocoena) from the German North Sea, Baltic Sea, and Waters of Greenland
Authors: Wunschmann A. , Siebert U. , Frese K.
Published: April 2003

Thymic cysts have not been previously reported in harbor porpoises ( Phocoena phocoena). Two hundred forty stranded or "by-caught" harbor porpoises originating from the German North Sea and Baltic Sea and 14 animals from the waters of Greenland were necropsied. Thymuses of 78 porpoises of the North Sea and Baltic Sea were considered suitable for histopathologic examination based on the extent of postmortem autolysis. Immunohistochemistry using an anti-cytokeratin antibody was employed to demonstrate thymic epithelial structures in selected cases. Thymic macrocysts were rare and were only found in animals ≥7 years of age. Thymic microcysts, lined by a single cytokeratin-positive cell layer, were common in involuting thymuses, and the prevalence increased with advancing age. Thymic cysts might have arisen from degenerating Hassall's corpuscles or condensed epithelial reticulum. Thymuses were easily identified macroscopically in most adult healthy harbor porpoises, suggesting that physiological thymic involution proceeds slowly in this species.
A Comparison of the Morphologic Effects of Serpulina hyodysenteriae or its Beta-hemolysin on the Murine Cecal Mucosa
Authors: Hutto D. L. , Wannemuehler M. J.
Published: April 2003

Studies were carried out to compare the early morphologic changes in the cecal mucosa of mice either infected with Serpulina hyodysenteriae or exposed to the β-hemolysin of S. hyodysenteriae. Sixty-five 12–24-week-old C3H/HeOuJ mice were infected with S. hyodysenteriae by gastric intubation. Two mice were necropsied every hour for 30 hours following infection. S. hyodysenteriae was isolated from the cecal contents of each mouse at all time points. Macroscopic lesions were first apparent at 14 hours postinfection (PI), and light microscopic lesions were first apparent at 10 hours PI, earlier than has been previously reported. Ultrastructural changes, first evident at 6 hours PI, included disarray and loss of microvilli and terminal web, with dilatation of intercellular spaces. Luminal bacteria were translocated through epithelial cells to the lamina propria, where capillaries exhibited changes indicative of increased permeability. In another experiment, solutions containing between 2,500 and 25,000 hemolytic units of purified S. hyodysenteriae hemolysin were placed within the lumen of surgically closed murine ceca ( n = 10); ceca were collected for examination 3 hours following treatment. Ultrastructural changes consisted of loss of microvilli and terminal web and marked vacuolation and exfoliation of epithelial cells. Significant numbers of necrotic and apoptotic epithelial cells were present, and epithelial cells internalized moderate numbers of bacteria. The hemolysin of S. hyodysenteriae induces some of the same early ultrastructural changes in the cecal epithelium of mice as occur following infection with S. hyodysenteriae. Based on the observed bacterial translocation, luminal bacteria also appear to play a unique role in lesion development in this model.
Classification and Behavior of Canine Mammary Epithelial Neoplasms Based on Life-span Observations in Beagles
Authors: Benjamin S. A. , Lee A. C. , Saunders W. J.
Published: April 2003

As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.
Nodular Pneumocystis carinii Pneumonia in SIV-infected Macaques
Authors: Yanai T. , Simon M. A. , Doddy F. D. , Mansfield K. G. , Pauley D. , Lackner A. A.
Published: April 2003

Pneumocystis carinii (PC) pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome (AIDS) in humans and macaques. An unusual nodular type of PC pneumonia was observed in two simian immunodeficiency virus (SIV)-inoculated rhesus macaques ( Macaca mulatta). These animals developed clinical signs of simian AIDS, including anorexia, weight loss, dyspnea, and collapse. Grossly, both animals had multifocal tan-white nodules 1–10 mm in diameter scattered throughout the lungs. One animal had similar nodules involving the diaphragm and thoracic wall. The lungs were characterized by severe PC pneumonia with numerous large nodules consisting of foamy material that compressed adjacent tissue. The nodules had central areas of necrosis and lysis of alveolar septa. Varying degrees of necrotizing vasculitis were observed in areas of nodular PC pneumonia. The presence of PC in intra-alveolar spaces and nodular lesions was confirmed by immunohistochemistry. No evidence of other agents, including viral inclusions, bacteria, fungi, and lung mites, was detected. The animal with the most severe nodular PC pneumonia had vascular involvement with extrapulmonary spread to the diaphragm, thoracic wall, and regional lymph nodes. This unusual type of nodular PC pneumonia has been rarely seen in human AIDS patients.
Histomorphometry and Quantification of Nucleolar Organizer Regions in Bovine Thyroid Containing Methylthiouracil Residues
Authors: Serakides R. , Nunes V. A. , Santos R. L. , Cassali G. D. , Neto P. P. Costa
Published: April 2003

In order to study the morphology and morphometry and to characterize and quantify the nucleolar organizer regions (NORs) of bovine thyroids containing methylthiouracil (MTU) residues, five animals were orally treated with a suspension of MTU (5 g/animal/day) for 20 days (group A). This treatment protocol was interrupted 5 days before the the animals were slaughtered. Six animals receiving placebos composed group B. A third group (group C) was composed of normal thyroids obtained from a slaughterhouse. All glands were previously assessed for detection of antithyroid residues by chromatography, and only those glands from MTU-treated animals were positive. Follicles of glands from group A showed wide variation in size and shape. There was a predominance of small follicles covered by multiple layers of columnar cells, sometimes forming papillary projections into the lumen, characterizing severe interfollicular and intrafollicular adenomatosis. Many follicles had vacuolated cells with nuclei showing karyolysis or pyknosis and reduced amounts of a low-density and very excavated colloid. They also showed higher follicular epithelia and larger proportions of their structural components when compared with glands of groups B and C. In the thyroids from group A, the argyrophilic nucleolar organizer region-associated proteins (AgNORs) were greater in number, with small ones scattered all over the nucleus. Although the size of AgNORs in thyroids from groups B and C was variable, these AgNORs were fewer and larger than were those in glands from group A. In conclusion, the MTU induces proliferation and regressive changes in follicular cells, and the AgNOR technique is efficient to distinguish different degrees of thyroid hyperplasia.
Cerebral Larva Migrans in a Raccoon (Procyon lotor)
Authors: Hamir A. N. , Snyder D. E. , Lichtenfels J. R.
Published: April 2003

During 1997, gross and histopathologic examinations were performed on an adult female raccoon ( Procyon lotor) that was live-trapped in Corvallis, Oregon. Multifocal eosinophilic granulomas indicative of neural and visceral larva migrans were observed. However, within these granulomas, the presence of parasitic larva was seen only in the cerebrum. Morphologic characteristics indicated that the nematode was an ascarid larva. However, it was smaller than the larva of Baylisascaris sp. This appears to be the first documented case of cerebral larva migrans in a raccoon.
Herpesvirus Infection in Tortoises (Malacochersus tornieri and Testudo horsfieldii)
Authors: Une Y. , Uemura K. , Nakano Y. , Kamiie J. , Ishibashi T. , Nomura Y
Published: April 2003

Large numbers of pancake tortoises ( Malacochersus tornieri) and Horsfield tortoises ( Testudo horsfieldii) in three consignments imported into Japan died soon after arrival. Some tortoises in the first consignment were dead on arrival. Postmortem examination of two of the pancake tortoises and four of the Horsfield tortoises revealed necrotizing lesions of the oral mucosa in both species, primarily in the tongue. Eosinophilic to amphophilic inclusion bodies were visible in the nuclei of mucosal epithelial cells in the lesions. Similar inclusion bodies were observed in the liver, spleen, adrenal glands, stomach, lungs, kidneys, small and large intestines, pancreas, and cerebrum of the pancake tortoises and in the liver, spleen, and pancreas of the Horsfield tortoises. Electron microscopic examination of the cells containing inclusion bodies showed herpesvirus-like particles about 100 nm in diameter in the cytoplasm. Nested polymerase chain reaction analysis using a herpesvirus consensus primer method confirmed the presence of a characteristic herpesvirus base sequence in tissue from these lesions.
Feline Papillomas and Papillomaviruses
Authors: Sundberg J. P. , Van Ranst M. , Montali R. , Homer B. L. , Miller W. H. , Rowland P. H. , Scott D. W. , England J. J. , Dunstan R. W. , Mikaelian I. , Jenson A. B.
Published: April 2003

Papillomaviruses (PVs) are highly species- and site-specific pathogens of stratified squamous epithelium. Although PV infections in the various Felidae are rarely reported, we identified productive infections in six cat species. PV-induced proliferative skin or mucous membrane lesions were confirmed by immunohistochemical screening for papillomavirus-specific capsid antigens. Seven monoclonal antibodies, each of which reacts with an immunodominant antigenic determinant of the bovine papillomavirus L1 gene product, revealed that feline PV capsid epitopes were conserved to various degrees. This battery of monoclonal antibodies established differential expression patterns among cutaneous and oral PVs of snow leopards and domestic cats, suggesting that they represent distinct viruses. Clinically, the lesions in all species and anatomic sites were locally extensive and frequently multiple. Histologically, the areas of epidermal hyperplasia were flat with a similarity to benign tumors induced by cutaneotropic, carcinogenic PVs in immunosuppressed human patients. Limited restriction endonuclease analyses of viral genomic DNA confirmed the variability among three viral genomes recovered from available frozen tissue. Because most previous PV isolates have been species specific, these studies suggest that at least eight different cat papillomaviruses infect the oral cavity (tentative designations: Asian lion, Panthera leo, P1PV; snow leopard, Panthera uncia, PuPV-1; bobcat, Felis rufus, FrPV; Florida panther, Felis concolor, FcPV; clouded leopard, Neofelis nebulosa, NnPV; and domestic cat, Felis domesticus, FdPV-2) or skin (domestic cat, F. domesticus, FdPV-1; and snow leopard, P. uncia, PuPV-2).
Localized Amyloidosis in Canine Mammary Tumors
Authors: Taniyama H. , Kitamura A. , Kagawa Y. , Hirayama K. , Yoshino T. , Kamiya S.
Published: April 2003

Histopathologic and immunohistochemical examinations were performed on localized amyloidosis associated with mammary tumors in two dogs. These tumors were identified as adenoma and adenocarcinoma. An acellular, amorphous pale eosinophilic material (amyloid) was observed in the lumina of acini lined by neoplastic cells and in the stroma of the tumors. Concentrically laminated pale eosinophilic bodies (corpora amylacea) were also found in the lumina of the acini. Amyloid and corpora amylacea stained positively with Congo red with and without 5% potassium permanganate pretreatment and revealed a green birefringence under polarized light. Corpora amylacea showed an occasional Maltese-cross pattern. Immunohistochemically, amyloid and corpora amylacea usually stained positively with anti-bovine α-casein antibody but negatively with anti-human amyloid AA, anti-bovine κ-light and λ-light chains, anti-human lactoferrin, anti-human transferrin, anti-human secretory component, and anti-human polyglucosan antibodies. These findings suggested that the amyloid deposition in these canine mammary tumors was related to lactating casein.
Scanning Electron Microscopy and Fluorescent In Situ Hybridization of Experimental Brachyspira (Serpulina) pilosicoli Infection in Growing Pigs
Authors: Jensen T. K. , Møller K. , Boye M. , Leser T. D. , Jorsal S. E.
Published: April 2003

Two groups of six 8-week-old pigs were challenged with 1×109 cfu Brachyspira ( Serpulina) pilosicoli or Serpulina intermedia daily for 3 consecutive days to study the pathology of porcine colonic spirochetosis by scanning electron microscopy (SEM) and fluorescent in situ hybridization (FISH) with oligonucleotide probes targeting ribosomal RNA specific for B. pilosicoli and the genus Brachyspira/ Serpulina. Six pigs served as noninoculated controls. The animals were euthanatized successively between postinoculation days 14 and 24. B. pilosicoli was reisolated in feces from all of the inoculated pigs; however, only two pigs developed transient watery diarrhea. S. intermedia was reisolated from four of the inoculated pigs, but clinical signs were not observed. Gross examination of the B. pilosicoli–infected pigs revealed dilated large intestines with a hyperemic mucosa, whereas the large intestines of the S. intermedia–inoculated pigs and the control pigs appeared normal. SEM examination of B. pilosicoli–infected pigs revealed degenerated epithelial cells and spirochetal colonization of the colonic mucosa in four pigs. By FISH, B. pilosicoli cells were found colonizing and invading the surface epithelium and the crypts in all the pigs. Spirochetal crypt colonization markedly exceeded the occurrence of spirochetes on the mucosal surface. SEM examination of S. intermedia–inoculated pigs revealed no abnormalities, and Serpulina cells were detected only sporadically in the otherwise normal-appearing mucosa of four pigs by FISH. The results provide further evidence that B. pilosicoli is associated with colitis in pigs, although the gross lesions are mild. The spirochete is capable of colonizing the large intestine, inducing mucosal damage, invasion of the crypt and surface epithelium, and focal infiltration of the lamina propria. In addition, the study shows the applicability of FISH for specific identification of B. pilosicoli in formalin-fixed tissue.
Immunohistochemical Detection of p53 Tumor-Suppressor Protein is a Poor Indicator of Prognosis for Canine Cutaneous Mast Cell Tumors
Authors: Ginn P. E. , Fox L. E. , Brower J. C. , Gaskin A. , Kurzman I. D. , Kubilis P. S.
Published: April 2003

Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin–biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion ( P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter ( P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.
Inactivation of p53 and Retinoblastoma Family Pathways in Canine Osteosarcoma Cell Lines
Authors: Levine R. A. , Fleischli M. A.
Published: April 2003

Canine osteosarcoma (OS) has been used as a model system for the study of cancer biology and treatment despite the lack of information regarding its pathogenesis. Expression of tumor suppressor genes known to participate in malignant transformation were studied in five different OS cell lines. Each of the cell lines exhibited properties of transformed cells, and those that were tested grew in soft agarose and formed osteoid-containing tumors when injected subcutaneously into nude mice. p53 function was determined to be defective in each cell line as indicated by the lack of induction of p53-responsive genes, p21 and mdm2, following treatment with 5-fluorouracil. p53 mRNA and protein levels were elevated in three cell lines and were extremely low in two cell lines. p53 protein overexpression correlated with the presence of mutations within the DNA binding domain. Four cell lines appeared to contain normal retinoblastoma ( Rb) mRNA and Rb protein and no detectable p16 mRNA or protein. In contrast, the remaining cell line contained high levels of p16 mRNA and protein and significantly reduced levels of Rb, p107, and p130 proteins. These results underscore the importance of inactivating p53 and Rb family pathways in canine OS and suggest that unlike human OS, cells derived from canine OS contain mutations that simultaneously inactivate all three Rb family members.
Experimental Brucella abortus Induced Abortion in a Llama
Authors: Gidlewski T. , Cheville N. F. , Rhyan J. C. , Miller L. D. , Gilsdorf Michael J.
Published: April 2003

Brucella abortus infection has not been documented in llamas. This report describes the abortion of the only pregnant animal in a group of 12. The llama was infected by inoculating 1 × 108 viable B. abortus organisms into the conjunctival sac. Forty-three days postinfection, the llama aborted a fetus of approximately 8 months gestational age. Brucella organisms were isolated from the placenta and all fetal specimens examined. These organisms were also isolated from the dam's mammary gland and numerous lymph nodes when the llama was necropsied 42 days later. Microscopically, there was a moderate, multifocal, lymphocytic and histiocytic, subacute placentitis with marked loss of trophoblastic epithelial cells. The superficial chorioallantoic stroma contained abundant necrotic and mineralized debris as well as numerous swollen capillaries protruding multifocally from the denuded surface. Immunohistochemistry revealed that these capillaries, as well as sloughed and intact trophoblasts, were expanded by large numbers of Brucella organisms. Brucellar antigen was also detected in occasional macrophages in the fetal kidney and lung. Ultrastructurally, bacteria labeled by an antibody-based colloidal gold procedure were located within degenerate capillaries, within necrotic leukocytes, and extracellularly in the placental stroma.
Caprine Genital Leiomyosarcoma
Authors: Whitney K. M. , Valentine B. A. , Schlafer D. H.
Published: April 2003

An aged Saanen doe was euthanized following repeated severe hemorrhage from the vulva. Necropsy examination revealed mural thickening of tubular genitalia with firm, protruding intralumenal masses containing blood-filled cavitations, and effacement of normal cervical architecture. Histologically, uterine and cervical masses comprised a variably dense population of mildly pleomorphic spindle cells forming interlacing streams supported by variably dense collagenous stroma. Immunoperoxidase staining of neoplastic cells was positive for muscle-specific actin, supporting the diagnosis of low-grade leiomyosarcoma. Months later, the doe's twin was likewise euthanized due to persistent bleeding from the vulva associated with a large vulvar mass having histopathologic features similar to those of the previous case. The clinical, gross, and histologic findings are similar to five cases of caprine genital leiomyosarcoma identified in retrospectively analyzed case material. Analysis of caprine tumor accessions over 20 years demonstrated a significantly higher incidence of genital leiomyosarcoma within the Saanen breed.
Expression of Viral Proteins in Feline Leukemia Virus-associated Enteritis
Authors: Kipar A. , Kremendahl J. , Grant C. K. , von Bothmer I. , Reinacher M.
Published: April 2003

Fourteen cases of feline leukemia virus (FeLV)-associated enteritis were immunohistologically examined for the expression of FeLV proteins gp70, p27, and p15E in the jejunum, mesenteric lymph nodes, spleen, and bone marrow. Results were compared with those of FeLV-infected cats without intestinal alterations. Other viral infections and specific bacterial, fungal, and parasitic infections were excluded by standard microbiologic methods, histopathology, immunohistology, and in situ hybridization. In FeLV-associated enteritis, FeLV gp70 and p15E were strongly expressed in intestinal crypt epithelial cells. In contrast, FeLV-positive cats without intestinal alterations showed only faint staining for gp70 and p15E and comparatively strong p27 expression in these cells. Findings suggest a direct relation between FeLV infection and alterations in intestinal crypt epithelial cells that may be attributed to the envelope proteins gp70 and p15E and/or their precursor protein. Distinct similarities to the intestinal changes in the experimentally induced FeLV-feline AIDS syndrome are obvious, suggesting that naturally occurring feline AIDS variants may be responsible for FeLV-associated enteritis.
Primary Epitheliotropic T-cell Lymphoma of the Urinary Bladder in a Dog
Authors: Maiolino P. , DeVico G.
Published: April 2003

A 7-year-old, intact female mixed-breed dog was presented for evaluation of hematuria. Physical examination revealed a suprapubic mass. Ultrasonographic examination showed a large lobular mass occupying the urinary bladder. At the owners' request, the dog was euthanatized and a postmortem examination was performed. Necropsy confirmed the presence of a lobular mass of about 5- to 6-cm diameter protruding into the lumen of the bladder. Histologically, the mass was composed of a large number of atypical lymphoid cells in the lamina propria and mucosal epithelium. Immunohistochemically, the neoplastic cells expressed CD3 but not CD79α or keratin and vimentin, supporting a diagnosis of T-cell lymphoma.
p53 Gene Mutations Occurring in Spontaneous Benign and Malignant Mammary Tumors of the Dog
Authors: Muto T. , Wakui S. , Takahashi H. , Maekawa S. , Masaoka T. , Ushigome S. , Furusato M.
Published: April 2003

Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5–8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.
Equine Viral Arteritis
Authors: Del Piero F.
Published: April 2003

Equine viral arteritis (EVA) can cause prominent economic losses for the equine industry. The purpose of this review is to provide the pathologist some familiarity with the clinical history, lesions, pathogenesis, and diagnosis of EVA. EVA is caused by an arterivirus (equine arteritis virus, EAV), and the vascular system is the principal but not unique viral target. EVA has variable presentations, including interstitial pneumonia, panvasculitis with edema, thrombosis and hemorrhage, lymphoid necrosis, renal tubular necrosis, abortion, and inflammation of male accessory genital glands. EAV antigen (EAVAg) can be demonstrated within the cytoplasm of epithelial cells such as alveolar pneumocytes, enterocytes, adrenal cortical cells, trophoblasts, thymus stroma, renal tubular cells, and male accessory genital gland cells. It can be also demonstrated within endothelia, in vascular, myometrial, and cardiac myocytes, macrophages, dendritelike cells of lymphoid organs, and chorionic mesenchymal stromal cells. In young and adult horses, following colonization of macrophages, the virus spreads systemically using circulating monocytes and enters the endothelium and tunica media of blood vessels, histiocytes, and dendritelike cells. Eventually, the virus multiplies within renal tubular cells. Lesions are uncommon in the aborted fetus; if present, they are mild, and EAVAg is frequently not detectable within fetal tissues and placenta. The clinical presentation and lesions of EVA may resemble those of other diseases. Complete pathologic examination associated with immunohistochemistry, virus isolation, and, especially in cases of abortion, serology will guarantee a directed and accurate diagnosis.
Ganglion Cysts in a Juvenile Dog
Authors: Cho K.-O. , Park N. Y. , Kang M. I. , Umemura K. , Itakura C.
Published: April 2003

Ganglion cysts were diagnosed in a 4-month-old male Afghan Hound. Grossly, the subcutaneous ovoid cysts around the caudal right elbow joint and left ischiatic tuberosity had abundant mucinous fluid and internal folding. The lesions recurred twice around the elbow joint after surgical removal. Neither cyst communicated with the joint cavity. Histologically, the cyst wall consisted of inner myxomatous and outer immature connective tissue. Some parts of the cyst wall had various stages of myxoid metaplasia of collagen tissue leading to new cyst formation. Ultrastructural study revealed that cells in the myxoid metaplastic lesion had well-developed cytoplasmic secretory elements, including abundant rough endoplasmic reticulum, Golgi apparatus, and many smooth-walled vesicles. These ganglion cysts apparently resulted from the metaplasia of fibroblasts to secreting cells.
A Pleomorphic Adenoma of the Lacrimal Gland in a Dog
Authors: Hirayama K. , Kagawa Y. , Tsuzuki K. , Kotani T. , Azuma Y. , Yoshino T. , Taniyama H.
Published: April 2003

A 13-year-old female mongrel dog had a pleomorphic adenoma of the lacrimal gland in the right upper orbit. The tumor measured 3.8 X 3.0 X 3.3 cm, appeared white, round, and firm, and pressed the right globe and surrounding tissues. Histopathologically, the tumor had a thin connective tissue capsule and was composed of tubules with two cell types, some resembling luminal epithelial cells making up the tubular structures and the other of myoepithelial cells. Epithelial tubules were disposed in an adenomatous fashion and separated from each other by proliferating pleomorphic myoepithelial cells. Immunohistochemically, large numbers of the luminal epithelial cells revealed an immunopositive reaction against keratin/cytokeratin (AE1/AE3), and some epithelial cells reacted against cytokeratin 14. Spindle-shaped myoepithelial cells revealed an immunopositive reaction against cytokeratin 14, α-smooth muscle actin, and vimentin. A small number of myoepithelial cells reacted against desmin. S-100 protein immunopositivity was frequently found in luminal epithelial cells and rarely in the pleomorphic myoepithelial cells. Glial fibrillary acidic protein positivity was commonly found in myoepithelial cells, myxoid matrices, and intracystic materials, but not in luminal epithelial cells.
Relationship of Lymphoid Lesions to Disease Course in Mucosal Feline Immunodeficiency Virus Type C Infection
Authors: Obert L. A. , Hoover E. A.
Published: April 2003

Feline immunodeficiency virus (FIV) infection typically has a prolonged and variable disease course in cats, which can limit its usefulness as a model for human immunodeficiency virus infection. A clade C FIV isolate (FIV-C) has been associated with high viral burdens and rapidly progressive disease in cats. FIVC was transmissible via oral-nasal, vaginal, or rectal mucosal exposure, and infection resulted in one of three disease courses: rapid, conventional/slow, or regressive. The severity of the pathologic changes paralleled the disease course. Thymic depletion was an early lesion and was correlated with detection of FIV RNA in thymocytes by in situ hybridization. The major changes in thymic cell populations were depletion of p55+/S100+ dendritic cells, CD3- cells, CD4+/CD8- cells, and CD4+/CD8+ cells and increases in apoptosis, CD45R+ B cells, and lymphoid follicles. In contrast to thymic depletion, peripheral lymphoid tissues often were hyper-plastic. Mucosally transmitted FIV-C is thymotropic and induces a spectrum of lymphoid lesions and disease mirroring that seen with the human and simian immunodeficiency virus infections.
Reduced Formation of Granulomata in γδ T Cell Knockout BALB/c Mice Inoculated with Mycobacterium avium subsp. paratuberculosis
Authors: Tanaka S. , Itohara S. , Sato M. , Taniguchi T. , Yokomizo Y.
Published: April 2003

The role of γδ T cells in the bovine immune response to Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) infection is poorly understood. Accordingly, using BALB/c mice that are innately susceptible to M. paratuberculosis, we compared wild-type and γδ T cell knockout BALB/c mice to study the protective roles of γδ T cells in M. paratuberculosis infection. Ten-week-old mice were inoculated intraperitoneally with either a low dose (4 × 106 colony-forming units [CFU]/mouse) or a high dose (4 × 109 CFU/mouse) of M. paratuberculosis strain ATCC 19698. Histopathologic and morphometric examinations showed reductions in the number and area of granulomatous lesions in the liver of the knockout mice at 18 weeks after inoculation with either the low or the high dose of the mycobacteria. Furthermore, at 18 weeks after inoculation, the bacterial load in the spleens of the knockout mice inoculated with the high dose was significantly lower than that of wild-type mice. No differences were found in bacterial load between the knockout and the wild-type mice in the low-dose groups. In contrast, in the livers of wild-type mice inoculated with either the low or high mycobacterial dose, increased areas of epithelioid granulomata were observed and the granulomata became disseminated widely during the experimental period. These findings in model mice suggest that γδ T cells, rather than restricting mycobacterial growth, may play a crucial role in development of epithelioid granulomata similar to those seen consistently in bovine paratuberculosis. The results of this study may have relevance to our understanding of the pathogenesis of paratuberculosis in ruminants, in which a prominent number of γδ T cells exist in the lymphoid system.
Persistent Hyperplastic Tunica Vasculosa Lentis and Persistent Hyperplastic Primary Vitreous in Transgenic Line TgN3261Rpw
Authors: H. Colitz C. M. , Malarkey D. E. , Woychik R. P. , Wilkinson J. E.
Published: April 2003

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice.
Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)
Authors: Wozniak E. , McBride J. , DeNardo D. , Tarara R. , Wong V. , Osburn B.
Published: April 2003

The relationship between a retroviral infection and the development of nonviral intracytoplasmic inclusion bodies was studied in a Boa constrictor model. Twelve juvenile age- and size-matched inclusion body disease (IBD)-negative boas were randomly divided into three groups. Each group was inoculated intraperitoneally with 1 ml of an IBD virus (IBDV)-infected liver homogenate or 1 ml of normal boa liver homogenate (sham-inoculated control) or was left untreated. All boas were monitored for development of IBD by daily examination and serial liver biopsy over 1 year. The 4 IBDV-inoculated boas became IBDV and inclusion positive by 10 weeks postinoculation. The average size and density of inclusion bodies increased with the duration of infection. Ultrastructurally, inclusion bodies, 2 mm in diameter consisted of intracytoplasmic aggregates of granular electron-dense material that were not membrane limited. Larger inclusions (3–6 μm in diameter) were characterized as membrane-bound aggregates of amorphous to granular electron-dense material admixed with membranelike fragments. The sham-inoculated and untreated control snakes did not become inclusion or IBDV positive. Direct comparison of the protein electrophoretograms of IBDV-infected and normal boa tissues demonstrated a prominent 68-kd protein band unique to infected inclusion-positive tissues. Monoclonal antibodies directed against the 68-kd protein band specifically labeled inclusion bodies. The results of this study demonstrate that IBD inclusions represent an intracytoplasmic accumulation of an antigenically distinct IBDV-associated protein.
Leukoencephalitis and Vasculitis with Perivascular Demyelination in a Weimaraner Dog
Authors: Berrocal A. , Montgomery D. L. , Pumarola M.
Published: April 2003

Aseptic and noninfectious diseases of the central nervous system are being recognized with increasing frequency. After multiple episodes of neurologic illness, this 7-year-old Weimaraner dog was euthanatized and submitted for postmortem examination. Lesions in the central nervous system were found mainly in the white matter of the cerebral cortex and cervical spinal cord and represented acute and more chronic injury. Necrotizing vasculitis with fibrinoid change and a marked neutrophilic infiltrate dominated the acute lesions. More chronic changes consisted of perivascular demyelination and accumulation of foamy macrophages with positive staining for myelin. An immune-complex (Arthus-type) vasculitis is suspected.
Pulmonary Cryptosporidiosis in Simian Immunodeficiency Virus—infected Rhesus Macaques
Authors: Yanai T. , Chalifoux L. V. , Mansfield K. G. , Lackner A. A. , Simon M. A.
Published: April 2003

Cryptosporidiosis is a common opportunistic infection in the gastrointestinal tract of human and nonhuman primates with AIDS. Pulmonary infection associated with Cryptosporidium spp. has not been previously reported in monkeys. Two macaques experimentally infected with simian immunodeficiency virus (SIV) had lesions containing cryptosporidial organisms involving the trachea, lungs, bile ducts, pancreas, and intestine. The pulmonary sections revealed moderate to severe bronchopneumonia associated with cryptosporidiosis. Numerous 2-4 μm oval Cryptosporidium spp. organisms were present in the cytoplasm of alveolar macrophages, multinucleated giant cells, and intestinal epithelial cells. Giant cells were positive for SIV by in situ hybridization. These are the first reported cases of cryptosporidiosis with involvement of pulmonary parenchyma in SIV-infected macaques.
Mediastinal Plasma Cell Tumor in a Sheep
Authors: Pérez J. , Méndez A. , Luque I. , Mozos E.
Published: April 2003

An extramedullary plasmacytoma was found in a 10-year-old sheep. The tumor involved the mediastinum, where a 25 × 15 × 10-cm encapsulated mass was found. The lungs had multiple metastases ranging from 0.5 to 2 cm in diameter, and the portal vein contained a 10-cm-long mass. The cytologic and histopathologic analyses were consistent with a moderately differentiated plasmacytoma. The immunophenotype of the tumor cells was lambda light chain IgG+, CD79a-, and CD3-. Occasional granulomas were observed at the periphery of the mediastinal and pulmonary tumors. Microbiologic culture yielded growth of Corynebacterium from these granulomas. This is the first report of plasmacytoma in sheep. The tumor most likely arose from mediastinal lymph nodes and metastatized to the lungs and portal vein.
Metastatic Calcification in a Dog Attributable to Ingestion of a Tacalcitol Ointment
Authors: Hilbe M. , Sydler T. , Fischer L. , Naegeli H.
Published: April 2003

A 22-week-old 21-kg female Bernese Mountain Dog ingested a topical antipsoriatic preparation containing the synthetic vitamin D analog tacalcitol. The dog died after a history of lethargy, recumbency, paresis of the hindlimbs, increased rectal temperature, dyspnea, and hematemesis. Histologic examination revealed metastatic calcification in the kidneys, lungs, myocardium, brain, stomach, and tear glands. The appearance of soft tissue mineralization in multiple organs is consistent with hypercalcemia derived from excessive vitamin D uptake. Oral toxicity studies for tacalcitol in the dog are not available, but the present report emphasizes the extraordinary toxic risk of drugs containing this vitamin D analog to dogs.
Two Genetic Defects in αIIb Are Associated with Type I Glanzmann's Thrombasthenia in a Great Pyrenees Dog: A 14-base Insertion in Exon 13 and a Splicing Defect of Intron 13
Authors: Lipscomb D. L. , Bourne C. , Boudreaux M. K.
Published: April 2003

Glannzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder caused by qualitative or quantitative deficiencies of the platelet membrane glycoprotein αIIbβ3. This is the first report of a molecular genetic basis for type I GT in dogs. As previously reported, a thrombasthenic Great Pyrenees dog (dog No. 1) experienced uncontrolled epistaxis despite results of coagulation screening tests, platelet quantitation, and von Willebrand factor quantitation that were within reference ranges. Platelet aggregation was minimal in response to agonists. Flow cytometry, autoradiography, and immunoblot experiments demonstrated either marked reduction or absence of glycoproteins αIIb and β3. In this study, we report the presence of a 14-base insertion in exon 13 and defective splicing of intron 13 in the αIIb gene of two thrombasthenic dogs (Nos. 1 and 8). The insertion disrupted the fourth αIIb calcium-binding domain, caused a shift in the reading frame and resulted in a premature termination codon. Possible consequences of this mutation include decreased αIIb mRNA stability and production of truncated αIIb protein that lacks the transmembrane and cytoplasmic domains and a large portion of the extracellular domain. We identified the dam, sire, and three littermates of dog No. 8 as carriers of the αIIb mutation. Canine αIIb and β3 genes share significant homology with the genes in human beings, making canine GT an excellent translational model for human GT. A defined molecular basis for canine GT will enhance ongoing gene therapy research and increase the understanding of structure-function relationships of this integrin.
Transitional Cell Carcinoma of the Urinary Bladder in a Thoroughbred, with Intra-abdominal Dissemination
Authors: Patterson-Kane J. C. , Tramontin R. R. , Giles R. C. , Harrison L. R.
Published: April 2003

A 14-year-old Thoroughbred gelding with a history of acute onset of hematuria was presented for necropsy. Transitional cell carcinoma of the urinary bladder with intra-abdominal dissemination was diagnosed. Tumor masses were observed on the splenic capsule and surrounding the distal abdominal aorta. Tumor cells showed diffuse cytoplasmic reactivity for cytokeratin but were negative for epithelial membrane antigen, carcinoembryonic antigen, tumor-associated glycoprotein 72, and vimentin.
Evaluating Mutant Mice: Anatomic Pathology
Authors: Brayton C. , Justice M. , Montgomery C. A.
Published: April 2003

As the human and mouse genome projects approach their goals, initiatives in functional genomics are advancing. When the nucleotide sequences are available, identification of gene functions will assume even greater importance. Determination of gene products and their proximal biochemical functions provide a part of the picture, but determination of their functions in the context of the whole organism is the ultimate goal. The manipulated mouse genome has become accepted as a model for understanding the genetic basis of human conditions and diseases. Consequently, biomedical research institutions have seen significant increases in the use of mice since the early 1980s, and these increases are largely attributable to the use of genetically modified mice. The role of comparative pathology in research on mutant mouse models of disease is increasing in response to these trends. Evaluation and phenotypic characterization of mutant mice, via clinical and anatomic pathology techniques, will be an important component of functional genomics initiatives.