bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Mesenchymal (Nonangiomatous/Nonlymphomatous) Neoplasms Occurring in the Canine Spleen: Anatomic Classification, Immunohistochemistry, and Mitotic Activity Correlated with Patient Survival
Authors: Spangler W. L. , Culbertson M. R. , Kass P. H.
Published: January 2010

Surgical submissions from canine splenectomy cases spanning a 3-year period (1988–1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of nonangiomatous and nonlymphomatous origin were selected for morphologic classification, mitotic index determination, immunohistochemical analysis, and patient survival determination. In 76/87 cases, patient survival information was available, and the mitotic index was determined in 83/87 cases. Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the cases. Morphologic classification of these lesions in standard HE preparations yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma-myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma (1/87). A lack of distinct morphologic characteristics among many of the neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma contrasted these groups with the relatively unambiguous features that distinguished the other sarcoma groups. Using immunohistochemical staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin), specific staining often overlapped extensively within the neoplastic groups of fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The biological behavior of all tumors examined could be placed into three categories of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with prolonged survival intervals; (2) malignant tumors (fibrosarcoma, undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic sarcoma, and liposarcoma), showing severely truncated survival (median 4 months with 80–100% mortality after 12 months; and (3) intermediate survival periods (median 12 months with 50% 1 year survival) attributed to a single group of neoplasm, the mesenchymomas. The biological behavior of primary splenic nonangiomatous, nonlymphomatous sarcomas was most closely correlated with observed mitotic index. Splenic neoplasms of this type with a mitotic index < 9 showed significantly ( P < 0.0001) longer survival intervals than those with an index > 9. With the exception of osteosarcoma, all anatomically defined tumor groups contained one or more specimens with a mitotic index < 9. The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival.
Astrocytes: Form, Functions, and Roles in Disease
Authors: Montgomery D. L.
Published: January 2010

Astrocytes, once relegated to a mere supportive role in the central nervous system, are now recognized as a heterogeneous class of cells with many important and diverse functions. Major astrocyte functions can be grouped into three categories: guidance and support of neuronal migration during development, maintenance of the neural microenvironment, and modulation of immune reactions by serving as antigen-presenting cells. The concept of astrocytic heterogeneity is critical to understanding the functions and reactions of these cells in disease. Astrocytes from different regions of the brain have diverse biochemical characteristics and may respond in different ways to a variety of injuries. Astrocytic swelling and hypertrophy-hyperplasia are two common reactions to injury. This review covers the morphologic and pathophysiologic findings, time course, and determinants of these two responses. In addition to these common reactions, astrocytes may play a primary role in certain diseases, including epilepsy, neurological dysfunction in liver disease, neurodegenerative disorders such as Parkinson's and Huntington's diseases, and demyelination. Evidence supporting primary involvement of astrocytes in these diseases will be considered.
Distribution of Antigen in Cattle Infected with Rinderpest Virus
Authors: Brown C. C. , Torres A.
Published: January 2010

Five Holstein heifers (approximately 8 months of age and weighing 225–275 kg) were inoculated subcutancously with 1,000 TCID50, of rinderpest virus, virulent Kabete O strain. They become clinically ill 2 to 5 days post-inoculation, with fever (40 C to 41.5 C), conjunctivitis, and diarrhea. All were euthanatized when moribund at 6 days postinoculation. The following tissues were collected in formalin, embedded in paraffin, and subsequently subjected to histopathologic and immunohistochemical examination: tongue, buccal mucosa, soft palate, esophagus, rumen, abomasum, duodenum, jejunum with and without Peyer's patch, ileum, cecum, proximal colonic lymphoid patch, spiral colon, eyelid, gall bladder, spleen, tonsil, trachea, lungs, and numerous lymph nodes. Immunohistochemical examination was accomplished using a primary rabbit anit-rinderpest antibody, and either a peroxidase-diaminobenzidine or alkaline phosphatase-Vector Red detection substrate system. In the lymph nodes, spleen, and tonsil, depletion of lymphocytes from all areas was extensive, with antigen most prominent in persisting reticular cells throughout the tissues. In the intestine, necrotizing and ulcerative changes in the mucosa were extensive and widespread. Damage was most severe in areas overlying lymphoid patches. In both small and large intestine, antigen was distributed predominantly in epithelial cells, histiocytic cells in the lamina propria, and in remaining reticular cells of lymphoid patches. In oral mucosa. there were multiple ulcerations and numerous multinucleate syncytial cells, both containing and without antigen. Lungs and trachea had subtle yet consistent necrosis of epithelial cells, with antigen often distributed in a circumferential manner in epithelium of bronchioles.
Acute Interstitial Pneumonia in Mink Kits Inoculated with Defined Isolates of Aleutian Mink Disease Parvovirus
Authors: Alexandersen S. , Larsen S. , Aasted B. , Uttenthal A. , Bloom M. E. , Hansen M.
Published: January 2010

The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions, interstitial edema, and hyaline membrane formation was experimentally reproduced in mink kits infected as newborns with five different isolates of ADV. Four hundred forty-nine newborn mink kits were included in the study, of which 247 were necropsied. The lesions caused by the different isolates were indistinguishable by histopathologic examination, but the incidence (50–100%) and severity (mortality of 30–100%. n = 218) of disease among the mink kits varied. Also, the content of ADV antigens in the lungs of infected kits varied among the groups. According to these features, the examined isolates could be placed in groups of high and low virulence. ADV-K, ADV-Utah I, and ADV-DK were in a highly virulent group producing a mortality of 90–100% ( n = 110) in mink inoculated as newborns. ADV-GL and ADV-Pullman belonged to a group of low virulence, with an incidence of clinical disease of 50–70% and a mortality of approximately 30–50% ( n = 118) in kits inoculated as newborns. The mortality in the control group receiving a mock inoculum was around 12% ( n = 34). The period from infection to development of fatal disease varied from approximately 12 days for the highly virulent isolates up to around 20 days for the isolates of low virulence. The 107 mink kits that survived inoculation with ADV as newborns developed lesions typical of classical Aleutian disease irrespective of the ADV isolate used. The lesions consisted of chronic immune complexmediated glomerulonephritis and infiltrations with mononuclear cells, including plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchusassociated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia.
Ileal Lymphoma in Swine
Authors: Tanimoto T. , Minami A. , Yano S. , Ohtsuki Y.
Published: January 2010

Eleven cases of alimentary lymphoma affecting the ileum were observed among 26 cases of swine lymphoma detected by meat inspection in Kochi, Japan. The ileal lymphomas were located in the Peyer's patches, along with early involvement of regional lymph nodes, and showed a characteristic pattern of follicular invasion leading to diffuse growth. Following the National Cancer Institute Working Formulation, 10 neoplasms were classified as diffuse, large, noncleaved cell lymphomas and one neoplasm was a diffuse, mixed, small to large cell lymphoma. Both types of lymphoma featured numerous intermingled “starry sky” histiocytes. The lymphoma cells tended to infiltrate into the muscular layer of the ileum in an “Indian file” pattern. Two cases also showed transserosal metastasis into the abdomen and leukemic change. The lymphoma cells showed membrane positivity for alkaline phosphatase and diffuse cytoplasmic staining for acid phosphatase and nonspecific esterase. Monoclonal intracytoplasmic immunoglobulins were demonstrated in nine neoplasms (IgM-λ in seven, IgG-λ in one, and IgG-λ in one). In the areas of follicular invasion, an attenuated network of follicular dendritic cells was visualised via an antiserum against the β subunit of S-100 protein. Ultrastructurally, strands of dilatated rough endoplasmic reticulum and scattered or clustered dense bodies were noted. When compared with feline and human alimentary lymphoma, including Burkitt's lymphoma, the present neoplasms possessed distinctive features, such as originating in Peyer's patches, transserosal metastasis, and predominantly large B cell type with IgM-λ type immunoglobulin expression, although some features were similar.
Prognosis of Canine Mast Cell Tumors: A Comparison of Three Methods
Authors: Simoes J. P. C. , Schoning P. , Butine M.
Published: January 2010

In this study, age, sex, recurrence, metastasis, death rate, and histologic patterns were in agreement with those of previous reports on canine mast cell tumors. Histologic grading, mitotic index, chromosome nucleolar organizer regions stained with silver (AgNORs), and anti-proliferating cell nuclear antigen (PCNA) were evaluated as indicators of prognosis. Histologic grading, AgNORs estimated in 100 cells, and PCNA-labeled fraction estimated in five high power fields (HPFs) were significantly different between recurring and nonrecurring tumors. Those prognostic factors were also significantly different between tumors that metastasized and those that did not. The survival time was lower in dogs with mast cell tumors with histologic grade 3 (Patnaik's), AgNOR counts higher than 2.25, and PCNA count in five HPFs higher than 261. The significance of these factors as markers for prognosis determined by logistic regression analysis differed with the time period considered. By combining the three most significant prognostic factors in a prognostic index, three models were obtained to determine the probability of nonrecurrence at 3, 6, and 9 months after surgery. The models were accurate in the prediction of the outcome of up to 80% of mast cell tumors. The use of these models provides a less subjective means of prognosticating mast cell tumors than the use of any one component alone.
Involution and Cystic Transformation of the Thymus in the Bottlenose Dolphin, Tursiops truncatus
Authors: Cowan D. F.
Published: January 2010

The thymus glands of 10 bottlenose dolphins, Tursiops truncatus, collected along the Texas Gulf coast were examined using standard histologic and immunocytochemical methods. The thymus gland of Tursiops persists into adult life, represented by medulla and progressively thinning cortex. A network of epithelial cells, including Hassal bodies, is demonstrable using polyclonal anti-cytokeratin antibody. The network condenses, with loss of lymphoid cells as involution progresses. Cysts arise within the condensed network. These cysts, found in eight of 10 animals, increase in number and size with increasing body size. Body size tends to reflect age. Thymic cysts typically have an irregular shape when small but tend to become spherical as they enlarge. Theey may be lined by squamous epithelium of variable thickness. Eventually, the cysts become macroscopic and filled with a colloidlike material and may largely replace the thymus, which may be identified by noncystic remnants adjacent to the cysts.
Bovine Pulmonary Blastomas: Histomorphologic Description and Immunohistochemistry
Authors: Kelley L. C. , Puette M. , Langheinrich K. A. , King B.
Published: January 2010

Three adult female dairy cattle with pulmonary blastomas were evaluated. The gross lesions at postmortem were described as multiple white circumscribed masses throughout the lungs, with pleural involvement in one cow and lymph node metastasis in the other two cows. Histologically, the tumors contained a dual population of mesenchymal and epithelial neoplastic cells. Epithelial cells formed nests, tubules, and formations resembling bronchioles of normal lung. Mesenchymal cells were spindle shaped with oval nuclei and fibrillar eosinophilic cytoplasm, were large rounded cells with multiple round nuclei and granular eosinophilic cytoplasm, or appeared blast-like, with large hyperchromatic nuclei and amphophilic cytoplasm. The tumors varied greatly in appearance from one field to another within the same tumor. Epithelial cells stained positively with anii-cytokeratin antibodies. Some spindle-shaped mesenchymal cells exhibited smooth muscle cell differentiation with positive staining with anti-vimentin, anti-muscle-specific actin, and anti-smooth muscle actin antibodies, whereas other rounded mesenchymal cells expressed striated muscle cell differentiation with multiple nuclei and positivity to anti-neuron-specific enolase and anti-muscle-specific actin antibodies. The variable expression of the intermediate filaments and cytoplasmic enzymes indicates multiple pathways of differentiation in the pulmonary blastomas.
Antigen Expression in Normal and Neoplastic Canine Tissues Defined by a Monoclonal Antibody Generated against Canine Mesothelioma Cells
Authors: Liu K. X. , Bird A. E. Church , Lenz S. D. , McDonough S. P. , Wolfe L. G.
Published: January 2010

Monoclonal antibody (MAb) 3B5 generated against canine mesothelioma cells was applied to canine tumors and normal tissues via immunohistochemical and immunoblotting techniques to evaluate antigen binding. By use of an avidin-biotin immunoperoxidase complex (ABC) method, immunoreactivity was noted in reactive mesothelial cells and in normal tissues was observed primarily in mesothelial cell linings, endothelial cells, and smooth muscle of blood vessels and soft tissues; the reactivity was nearly equivalent in frozen or formalin-fixed, paraffin-embedded tissue sections. Use of the ABC method on formalin-fixed, paraffin-embedded tumors yielded moderate to strong cytoplasmic immunostaining of neoplastic cells in 10/11 (91%) mesotheliomas, 18/23 (78%) hemangiosarcomas, 4/10 (40%) intestinal and lung carcinomas, and ≤20% of hemangiomas, leiomyosarcomas, leiomyomas, mammary carcinomas, and squamous cell carcinomas. No immunostaining of tumor cells was observed in fibrosarcomas, hemangiopericytomas, perianal gland carcinomas, and melanomas. Immunoblotting was performed on samples that demonstrated strong immunoreactivity with MAb 3B5 by the ABC method: mesothelioma, hemangiosarcoma, urinary bladder (smooth muscle), and lung (alveolar capillaries). These analyses showed that MAb 3B5 bound a major antigen of 78 kilodaltons (kd) and minor antigens at 56 and 54 kd in normal and neoplastic tissues. The preliminary immunohistochemical results suggest that MAb 3B5 may possess utility in diagnosis of mesotheliomas and hemangiosarcomas, discrimination of cell types in proliferative serosal lesions, and demonstration of vascularity or angiogenesis in neoplastic and inflammatory lesions.
Ovine Lentivirus (Maedi-visna Virus) Protein Expression in Sheep Alveolar Macrophages
Authors: Luján L. , Begara I. , Collie D. D. S. , Watt N. J.
Published: January 2010

The expression of gag (p15, p25) and env gene products in ovine lentivirus-infected cells was studied in 20 adult Texel ewes seropositive to maedi-visna virus and 10 seronegative matched controls. Bronchoalveolar lavage was performed to recover alveolar cell pools from which cytocentrifuge preparations were made, Single and double immunocytochemical techniques were applied to study viral replication and coexpression of viral markers with markers for macrophages, lymphocytes, and major histocompatibility complex (MHC) class II. Alveolar macrophages of eight of 20 infected sheep (40%) were positive for viral protein expression. The percentage of positive macrophages varied from < 1% to 12% of the total population of macrophages. Viral protein expression was not detected in lymphocytes or other cell types. A relationship between virus-replicating macrophages and differential expression of MHC class II molecules, upregulated in ovine lentivirus infection, could not be established. Pathology was evaluated in nine infected ewes. Animals with the highest levels of positive cells had moderate or severe lymphoid interstitial pneumonia. However, sheep with similar degrees of lesions had lower percentages of positive macrophages or were negative for viral protein detection. These results support the idea that a partial or even a complete loss in the restriction mechanism of maedi-visna virus in lungs can occur in some individuals.
Experimental Transmission of Enzootic Intranasal Tumors of Goats
Authors: De las Heras M. , García de Jalón J. A. , Minguijón E. , Gray E. W. , Dewar P. , Sharp J. M.
Published: January 2010

The successful experimental transmission of enzootic intranasal tumor (EIT) from goat to goat is described. Ten kids, less than 48 hours old, from a flock free of the disease and seronegative for ruminant lentiviruses were inoculated intranasally or intrasinusally with either nasal fluid from goats with naturally occurring EIT or EIT retrovirus concentrated from such fluids. EIT was induced in three kids after 12-24 months. The EIT retrovirus was demonstrated in tumor material from each of the three kids by western blotting and electron microscopy. All kids were seronegative for ruminant lentiviruses.
Susceptibility of Porcine Ileal Enterocytes to the Cytotoxin ofSerpulina hyodysenteriaeand the Resolution of the Epithelial Lesions: An Electron Microscopic Study
Authors: Bland A. P. , Frost A. J. , Lysons R. J.
Published: January 2010

The cytotoxin from Serpulina hyodysenteriae was injected into ileal loops of eight germ-free pigs, and the effects on the villi were observed after 1, 3, and 18 hours of exposure. The mature vacuolated villus enterocytes of the proximal part of the absorptive villi were most susceptible to the lethal effects of the cytotoxin and were extensively exfoliated. The enterocytes at the base of the villi, the goblet cells, and the follicle-associated epithelium of the dome villi, particularly the M cells, were less affected. As the enterocytes were shed, the villi progressively shortened and the basement membrane became extensively folded. The absorptive villi were markedly stunted at 3 hours, and flattened goblet cells predominated at the site of restitution of the lesion. The myofibroblasts were also damaged, apparently subsequent to the exfoliation of the enterocytes. There was no further damage at 18 hours. The absorptive villi were stunted and were devoid of the large interstitial spaces of the normal lamina propria; the enterocytes were generally columnar, and at the apex of each villus there was an accumulation of goblet cells. There was a preponderance of M cells at the apices of the dome villi. Restitution of the lesions was not as rapid as observed in in vitro systems. The changes observed indicated that as the proximal enterocytes of the absorptive villi were shed, the loss of hydrostatic forces in the lamina propria allowed the myofibroblasts to collapse the villi by progressively retracting the basement membrane. This reduced the surface area to be covered during restitution. Resolution of the lesions was still incomplete after 18 hours.
Clinical and Morphologic Findings of Familial Goiter in Bongo Antelope (Tragelaphus eurycerus)
Authors: Schiller C. A. , Montali R. J. , Doi S. , Grollman E. F.
Published: January 2010

Inherited defects of thyroglobulin synthesis resulting in congenital goiter are well described in certain breeds of domestic ungulates and in human beings. Goiter associated with synthesis of an abnormal thyroglobulin and the presence of thyroidal albumin was identified in five closely related bongo antelopes ( Tragelaphus eurycerus). The goiter had an adult onset, and the affected bongos appeared to remain euthyroid with normal serum T3 and T4 values, normal serum cholesterol concentrations, and nonelevated concentrations of circulating thyroid stimulating hormone (TSH). Goitrous bongos had significant reproductive difficulties, including reduced cyclic activity and prolonged gestations, but were otherwise normal. Over the course of the disease, the thyroid glands greatly enlarged (up to 10 × 20 cm) and became polycystic. Microscopically, there was an admixture of giant colloid-filled follicles and follicles of normal size lined with variable follicular epithelium ranging from squamoid to mildly to moderately hyperplastic. The pathogenesis of goiter in the bongo may reflect a mixture of genetic predisposition coupled with environmental factors, including a period of exposure to a goitrogen.
Clostridium difficileInfection in Hamsters Fed an Atherogenic Diet
Authors: Blankenship-Paris T. L. , Walton B. J. , Hayes Y. O. , Chang J.
Published: January 2010

Diarrhea and unexpected death were encountered in a group of young Syrian hamsters ( Mesocricetus auratus) used for hyperlipoproteinemia and atherosclerosis research. The animals were fed an atherogenic diet containing 18% saturated fat and 0.366% cholesterol. Mortality began 45 days after hamsters were placed on this atherogenic diet. The atherogenic studies were aborted at 74 days because of high mortality. Toxigenic Clostridium difficile was isolated from animals found dead or euthanatized because of illness. Signs observed were unexpected death and acute liquid diarrhea. Characteristic pathologic changes were necrosis and hemorrhage of the intestinal mucosa with acute inflammation. Hepatic lipidosis was a consistent finding presumed to be associated with the consumption of the atherogenic diet. The study was repeated by placing 23 hamsters on the atherogenic diet and 10 hamsters on the control diet. In animals fed the atherogenic diet, the average time to mortality differed between studies, but clinical signs, gross and histologic lesions, culture findings, and toxin results in both atherogenic diet groups were similar. C. difficile was not isolated from the feeds. No antibiotics were found in the atherogenic diet. The results from these studies suggest that hamsters fed an atherogenic diet have increased susceptibility to disease caused by C. difficile as compared with hamsters fed a normal fat and cholesterol diet.
Effects of thePasteurella multocidaToxin on Osteoblastic Cells in vitro
Authors: Sterner-Kock A. , Lanske B. , Überschär S. , Atkinson M. J.
Published: January 2010

Pasteurella multocida toxin induces localized osteolysis in the turbinate bones of swine. Osteolysis appears to be due to an increased level of osteoclastic bone resorption, although osteoblast activity may also be impaired. We studied the effects of purified toxin on the osteoblastic phenotype of the ROS 17/2.8 rat osteoblastic osteosarcoma cell line. Treatment of both embryonic bovine lung cells and a nonosteoblastic rat osteosarcoma cell line (ROS 25/1) with nanomolar doses of toxin produced marked cytotoxic actions. In the osteoblastic ROS 17/2.8 cells, this level of toxin reduced expression of an osteoblastic marker (alkaline phosphatase), was associated with matrix mineralization, but had no cytopathologic action. The osteoblastic cell population may be resistant to a direct cytotoxic effect but is nevertheless a target for toxin action.
The Lesions of Locoweed (Astragalus mollissimus), Swainsonine, and Castanospermine in Rats
Authors: Stegelmeier B. L. , Molyneux R. J. , Elbein A. D. , James L. F.
Published: January 2010

To better characterize and compare the toxicity of and lesions produced by locoweed ( Astragalus mollissimus) with those of swainsonine and a related glycoside inhibitor, castanospermine, 55 Sprague-Dawley rats were randomly divided into 11 groups of five animals each. The first eight groups were dosed via subcutaneous osmotic minipumps with swainsonine at 0,0.1,0.7,3.0,7.4, or 14.9 mg/kg/day or with castanospermine at 12.4 or 143.6 mg/kg/day for 28 days. The last three groups were fed alfalfa or locoweed pellets with swainsonine doses of 0, 0.9, or 7.2 mg/kg/day for 28 days. Swainsonine- and locoweed-treated rats gained less weight, ate less, and showed more signs of nervousness than did controls. Histologically, these animals developed vacuolar degeneration of the renal tubular epithelium, the thyroid follicular cells, and the macrophage-phagocytic cells of the lymph nodes, spleen, lung, liver, and thymus. Some rats also developed vacuolation of neurons, ependyma, adrenal cortex, exocrine pancreas, myocardial epicytes, interstitial cells, and gastric parietal cells. No differences in lesion severity or distribution were detected between animals dosed with swainsonine and those dosed with locoweed. Rats dosed with castanospermine were clinically normal; however, they developed mild vacuolation of the renal tubular epithelium, the thyroid follicular epithelium, hepatocytes, and skeletal myocytes. Special stains and lectin histochemical evaluation showed that swainsonine- and castanospermine-induced vacuoles contained mannose-rich oligosaccharides. Castanospermine-induced vacuoles also contained glycogen. These results suggest that 1) swainsonine causes lesions similar to those caused by locoweed and is probably the primary locoweed toxin; 2) castanospermine at high doses causes vacuolar changes in the kidney and thyroid gland; and 3) castanospermine intoxication results in degenerative vacuolation of hepatocytes and skeletal myocytes, similar to genetic glycogenosis.
Immumohistochemical Detection and Localization of Prion Protein in Brain Tissue of Sheep With Natural Scrapie
Authors: van Keulen L. J. M. , Schreuder B. E. C. , Meloen R. H. , Poelen-van den Berg M. , Mooij-Harkes G. , Vromans M. E. W. , Langeveld J. P. M.
Published: January 2010

A converted form of the normal cellular prion protein (PrP) accumulates in the brains of sheep with scrapie. We describe an immunohistochemical method for identifying scrapie-associated PrP (PrPSc) in periodate-lysine-paraformaldehyde-fixed brain tissue, which provides adequate preservation of tissue morphology. After pretreatment of tissue sections with formic acid and hydrated autoclaving, we located PrPSc in the brains of 50 sheep with natural scrapie by use of antipeptide antisera raised against ovine PrP. No PrP was seen in 20 sheep without histopathologic signs of scrapie. PrP80 that did not stain for amyloid was present in the cytoplasm and at the cell membrane of both neurons and astrocytes. Large amounts of PrPSc were seen at the cell membrane of neurons in the medulla oblongata and pons, whereas PrPSc accumulated at the cell membrane of astrocytes of the glial limitans in all brain regions. PrPSc that stained for amyloid was located in the walls of blood vessels and perivascularly in the brains of 32 (64%) of 50 sheep, mainly in the thalamus and never in the pons or medulla oblongata. No apparent topographic relationship existed between PrPSc that stained for amyloid and PrPSc accumulation associated with neurons or astrocytes. In all scrapie-affected sheep, PrPSc was present in brain regions with vacuolation, but it could also be detected in regions with minimal or no vacuolation. We conclude that the immunohistochemical detection of PrP can be an important confirmative test in scrapie diagnosis.
Rabies-induced Spongiform Change and Encephalitis in a Heifer
Authors: Foley G. L. , Zachary J. F.
Published: January 2010

A 1-year-old mixed breed heifer was presented to the Veterinary Medical Teaching Hospital at the University of Illinois with a 3-day history of abnormal mentation and aggressive behavior. Based on the history and clinical examination, euthanasia and necropsy were recommended. The differential diagnoses included rabies, pseudorabies, and a brain abscess. The brain was removed within 60 minutes of death, and the section submitted for fluorescent antibody testing was positive for rabies virus antigen. Residual brain tissue was immersion fixed in 10% neutral buffered formalin. Histologic examination revealed a marked perivascular and meningeal lymphocytic meningoencephalitis and locally extensive spongiform change of the gray matter affecting the neuropil and neuron cell bodies. The most severely affected regions with spongiform change were the thalamus and cerebral cortex. No Negri bodies were found in any sections. Since the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom, there has been an increased surveillance of bovine neurologic cases in an effort to assess if BSE has occurred in the USA. In areas where rabies virus is endemic, rabies should be included as a possible differential diagnosis in cases of spongiform changes of the central nervous system.
Amyloid Deposits in the Gastrointestinal Tract of Aging Dogs
Authors: Tani Y. , Uchida K. , Uetsuka K. , Nakamura S. , Nakayama H. , Goto N. , Doi K.
Published: January 2010

Pathologic features, immunohistochemical characteristics, and incidence of gastrointestinal amyloid deposition were investigated in 78 canine necropsies, including 43 males and 35 females ranging from 2 months to 20 years of age. In 31 of 78 dogs, amyloid protein was accumulated in or around vessel walls located in submucosal and muscular layers of the alimentary tract and mesenteric tissues. These deposits did not seem to affect the function(s) of the digestive tract histologically. The deposits showed congophilia and green birefringence under polarized microscopy. Transmission electron microscopy revealed randomly arranged amyloid fibrils 6-10 nm in diameter around a blood vessel. Congophilia was retained even after oxidation with potassium permanganate, suggesting that this protein is not the AA form of amyloid. Although immunohistochemical studies were performed using antibodies to canine amyloid apolipoprotein AI and synthetic human β amyloid peptide, the immunochemical nature of the protein was not determined. The mean ages of both male and female dogs with gastrointestinal amyloid deposition were higher than those of their normal counterparts ( P < 0.001), and the incidence of deposition in elderly dogs was higher than that in young dogs ( P < 0.005). However, there was no sex predilection with respect to both the mean age of the dogs with deposition and the incidence of occurrence. The mechanism(s) and importance of this form of amyloid deposition remain unclear.
Osteochondrodysplasia Occurring in Transgenic Mice Expressing Interferon-γ
Authors: Nii A. , Reynolds D. A. , Young H. A. , Ward J. M.
Published: January 2010

In addition to various biological activities, interferon-γ (IFN-γ) inhibits bone resorption and collagen synthesis. We produced a transgenic mouse line expressing the murine IFN-γ gene and protein in the bone marrow and thymus. Forty-five transgenic FVB/NCr mice, 23 days-9 months of age, were studied for anomalies in the skeletal system. The transgenic mice had short, wide, and deformed long bones. Young transgenic mice had epiphyseal plates severely thickened with zones of hypertrophy and degeneration with irregular metaphyseal borders. Cartilagenous masses were also observed in the metadiaphyseal marrow cavities. These lesions were primarily seen in long bones and ribs. Adult transgenic mice had residues of degenerated cartilagenous masses in the diaphyses. Many osteoclasts with well-developed ruffled borders were present on the metaphyseal cartilagenous masses in young transgenic mice. Adult transgenic mice had less prominent primary spongiosa with fewer osteoclasts at the metaphysis as compared with nontransgenic controls. The cortical bones of the transgenic mice were thinner and more immature compared with controls. Transgenic mice also had fractures, disruption of the epiphyseal plate, and degeneration of articular cartilage. Thus, the IFN-γ transgenic mice developed a complex chondro-osseous lesion that was diagnosed as osteochondrodysplasia. The lesions may originate from primarily decreased matrix synthesis in bone and cartilage and also possible osteoclast-related changes caused by IFN-γ overexpression in the bone marrow. Our IFN-γ transgenic mouse will be a useful model to investigate the role of IFN-γ in bone metabolism.
Histopathologic and Ultrastructural Alterations of White Liver Disease in Sheep Experimentally Depleted of Cobalt
Authors: Kennedy S. , McConnell S. , Anderson H. , Kennedy D. G. , Young P. B. , Blanchflower W. J.
Published: January 2010

Many cobalt-deficient sheep develop liver lesions known as ovine "white liver" disease, but the etiology of these changes is controversial. It has been suggested that cofactors are required for development of liver damage in cobalt-deficient sheep. In this study, one group of lambs ( n=5) was fed a diet low in cobalt (4.5 μg/kg) while a group of control lambs ( n=4) received the same diet after it had been supplemented with cobalt (1000 μg/kg). All cobalt-depleted lambs had reduced growth rate, anorexia, lacrimation, and alopecia, and they eventually became emaciated (mean body weight at end of study: 83% of initial body weight). Plasma concentrations of bilirubin and serum activity of glutamate-oxaloacetate transferase were elevated in these animals, while plasma concentrations of vitamin B12 were reduced (less than 220 pmol/L from day 42). Fatty degeneration of the liver associated with reduced concentrations of vitamin B12 (14.5 pmol/g) was seen in these animals at necropsy at 196 days. Microscopic liver lesions included accumulation of lipid droplets and lipofuscin particles in hepatocytes, dissociation and necrosis of hepatocytes, and sparse infiltration by neutrophils, macrophages, and lymphocytes. Ultrastructural hepatocytic alterations included swelling, condensation and proliferation of mitochondria, hypertrophy of smooth endoplasmic reticulum, vesiculation and loss of arrays of rough endoplasmic reticulum, and accumulation of lipid droplets and lipofuscin granules in cytoplasm of hepatocytes. No liver lesions were seen in control lambs. The results of this study indicate that cofactors are not a prerequisite to development of hepatic damage in cobalt-deficient sheep. Reduced activities of the vitamin B12-dependent enzymes, methylmalonyl CoA mutase and methionine synthase, and lipid peroxidation are of likely pathogenetic importance in the development of the lesions.
Epizootic Vacuolar Myelinopathy of the Central Nervous System of Bald Eagles (Haliaeetus leucocephalus) and American Coots (Fulica americana)
Authors: Thomas N. J. , Meteyer C. U. , Sileo L.
Published: January 2010

Unprecedented mortality occurred in bald eagles ( Haliaeetus leucocephalus) at DeGray Lake, Arkansas, during the winters of 1994-1995 and 1996-1997. The first eagles were found dead during November, soon after arrival from fall migration, and deaths continued into January during both episodes. In total, 29 eagles died at or near DeGray Lake in the winter of 1994-1995 and 26 died in the winter of 1996-1997; no eagle mortality was noted during the same months of the intervening winter or in the earlier history of the lake. During the mortality events, sick eagles were observed overflying perches or colliding with rock walls. Signs of incoordination and limb paresis were also observed in American coots ( Fulica americana) during the episodes of eagle mortality, but mortality in coots was minimal. No consistent abnormalities were seen on gross necropsy of either species. No microscopic findings in organs other than the central nervous system (CNS) could explain the cause of death. By light microscopy, all 26 eagles examined and 62/77 (81%) coots had striking, diffuse, spongy degeneration of the white matter of the CNS. Vacuolation occurred in all myelinated CNS tissue, including the cerebellar folia and medulla oblongata, but was most prominent in the optic tectum. In the spinal cord, vacuoles were concentrated near the gray matter, and occasional swollen axons were seen. Vacuoles were uniformly present in optic nerves but were not evident in the retina or peripheral or autonomic nerves. Cellular inflammatory response to the lesion was distinctly lacking. Vacuoles were 8-50 μm in diameter and occurred individually, in clusters, or in rows. In sections stained by luxol fast blue/periodic acid-Schiff stain, the vacuoles were delimited and transected by myelin strands. Transmission electron microscopy revealed intramyelinic vacuoles formed in the myelin sheaths by splitting of one or more myelin lamellae at the intraperiodic line. This lesion is characteristic of toxicity from hexachlorophene, triethyltin, bromethalin, isonicotinic acid hydrazide, and certain exotic plant toxins; however, despite exhaustive testing, no etiology was determined for the DeGray Lake mortality events. This is the first report of vacuolar myelinopathy associated with spontaneous mortality in wild birds.
Apoptosis Induced In Vivo During Acute Infection by Porcine Reproductive and Respiratory Syndrome Virus
Authors: Sur J.-H. , Doster A. R. , Osorio F. A.
Published: January 2010

We studied apoptosis caused by porcine reproductive and respiratory syndrome virus (PRRSV) in vivo, focusing on the tissues that constitute the main targets for infection: lung and lymphoid tissues. Previous investigators have shown that the PRRSV glycoprotein p25, encoded by PRRSV open reading frame 5, induces apoptosis when expressed in COS-1 cells. Results of studies conducted in our laboratory indicate the simultaneous occurrence of PRRSV-induced alterations of spermatogenesis and apoptotic death of germinal epithelial cells in the testicle. In this study, the goal was to determine whether virus-induced apoptosis is a direct mechanism of cell death caused by PRRSV in infected pigs. Eight 3-week-old pigs were intranasally inoculated with PRRSV 16244B, a highly virulent field strain. Lung, tonsil, bronchial lymph node, spleen, and heart were assessed histologically at 4 and 7 days postinfection. To characterize PRRSV-infected cells and apoptotic cell death, we used immunohistochemical methods for detection of viral antigen, DNA electrophoresis for detection of DNA fragmentation, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-fluorescein nick end labeling method for in situ detection of DNA strand breaks, and electron microscopy for ultrastructural morphologic studies. PRRSV infection resulted in widespread apoptosis in the lungs and lymphoid tissues of infected pigs. Virus infection-induced apoptotic cells were more abundant than PRRSV-infected cells in all tissues. DNA laddering was detected in lung and lymphoid tissues. However, double-labeling experiments demonstrated that the majority of apoptotic cells did not colocalize with PRRSV-infected cells. Our findings suggest the presence of an indirect mechanism in the induction of apoptosis for PRRSV.
Experimental Old Dog Encephalitis (ODE) in a Gnotobiotic Dog
Authors: Axthelm M. K. , Krakowka S.
Published: January 2010

Experimental infection of a gnotobiotic Beagle dog with the neurovirulent R252 strain of canine distemper virus (R252-CDV) resulted in long-term central nervous system (CNS) infection; cerebral and brain stem lesions were consistent with old dog encephalitis (ODE). Eight clinical cycles of relapsing cortical and subcortical signs were documented over 33 months and were corroborated by the presence of both chronic and active inflammatory demyelinating lesions within the neuraxis. Immunocytochemistry revealed that CDV antigen was restricted to neurons. Attempts to use fresh brain tissue to directly transmit the infection to CDV-susceptible gnotobiotic dogs were unsuccessful. Reisolation of infectious virus from the infected dog required prolonged culture and coculture of brain explant cells with CDV-susceptible Vero cell monolayers. These findings demonstrate that ODE is a variant of virulent CDV-induced canine neurologic disease that can evolve de novo within the CNS of subclinically infected dogs in the absence of external sources of reinfection. The highly cell-associated nature of the virus, when first recovered from this dog, suggests that the virus was present within the CNS in a replication-defective form.
Intestinal Lesions in a Horse Associated with Eastern Equine Encephalomyelitis Virus Infection
Authors: Poonacha K. B. , Gregory C. R. , Vickers M. L.
Published: January 2010

The primary lesions of eastern equine encephalomyelitis (EEE) virus infection in the horse are limited to the brain and spinal cord. Intestinal lesions in addition to the changes in the central nervous system were found in a 6-month-old male Tennessee Walking Horse. One week prior to death, this colt was vaccinated for EEE virus, western equine encephalomyelitis virus, influenza virus, equine rhinopneumonitis virus, and tetanus. The clinical signs consisted of ataxia and rear-end weakness, with a body temperature of 102.8 F. Gross lesions consisted of yellowish discoloration, swelling, edema, and hemorrhage of the brain stem and dark discoloration of the gray matter of the spinal cord. Microscopic lesions in the small intestine were mainly in the muscular layer and consisted of multifocal areas of myonecrosis and lymphomonocytic infiltration with a few focal areas of mild fibrous connective tissue proliferation. Occasional focal mild perivascular lymphocytic infiltration was observed in the submucosa. Lesions in the brain and spinal cord consisted of widespread areas of perivascular lymphomonocytic cuffing, focal areas of necrosis, neutrophilic infiltration, hemorrhage, neuronal degeneration, and gliosis. Hepatic changes consisted of periportal lymphocytic infiltration and mild vacuolar degeneration of hepatocytes. EEE virus was isolated from the intestine and detected by DNA in situ hybridization.
Cerebellar Medulloblastoma with Multiple Differentiation in a Dog
Authors: Steinberg H. , Galbreath E. J.
Published: January 2010

A 4-year-old female, spayed Border Collie Dog was brought to the Veterinary Medical Teaching Hospital for evaluation of a progressive head tilt and ataxia that were unresponsive to therapy. Neurologic examination localized a right-sided lesion. The owner refused additional diagnostic tests, and necropsy was performed after euthanasia. Gross findings included atrophy of the temporal muscles and a moderately well delineated, 2.5- X 1.5- X 1.0-cm, gray soft-tissue mass compressing the right cerebellar hemisphere and dorsal hindbrain, resulting in massive dilatation of the lateral, third, and fourth ventricles and hydrocephalus. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal to fusiform cells with typical morphologic characteristics of medulloblastoma and interspersed areas containing myelinated axons and cells with glial and neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with glial and neuronal differentiation.
Cystic Prostatic Disease Associated with Adrenocortical Lesions in the Ferret (Mustela putorius furo)
Authors: Coleman G. D. , Chavez M. A. , Williams B. H.
Published: January 2010

A review of case materials at the Armed Forces Institute of Pathology identified six cases of prostatitis in domestic ferrets ( Mustela putorius furo). Five of these ferrets (83%) had one or more cysts and the remaining ferret had a paraprostatic cyst. Three of the six ferrets (50%) exhibited various degrees of prostatic squamous metaplasia. Inflammation ranged from subacute to chronic-active or pyogranulomatous. In addition to the prostatic lesions, hyperplastic and/or neoplastic adrenocortical lesions were present in 4/6 (66%) ferrets; 1/6 (17%) ferrets had previously been clinically diagnosed with adrenal gland-associated endocrinopathy. The remaining ferret had previously had the right adrenal gland removed, but the reason for the removal is unknown. Based upon the histologic findings in these six ferrets, there appears to be an association between proliferative adrenal lesions and cystic prostatitis in domestic ferrets.
Primary Central Nervous System T-cell Lymphoma in a Cat
Authors: Fondevila D. , Vilafranca M. , Pumarola M.
Published: January 2010

A 5-year-old intact male Persian cat was presented with progressive neurologic deficits, hyperesthesia, hyperreflexia, ataxia, and intention tremors, which resulted in death. Serologic tests for feline leukemia virus and feline immunodeficiency virus infection were negative. Neurohistologic examination revealed the presence of pleomorphic cellular infiltrates in cerebral leptomeninges and around parenchymal vessels. The majority of infiltrating cells were uniformly immunostained using an antiserum directed against T cells. Immunohistochemical examination of paraffin-embedded brain sections for the antigens of canine distemper virus, herpesvirus, Borna virus, and Toxoplasma gondii were negative. Histologic and immunohistochemical studies revealed a primary central nervous system T-cell lymphoma affecting the brain.
A Belief-Behavior Gap? Exploring Religiosity and Sexual Activity Among High School Seniors
Authors: Cobb Leonard Kathleen , Scott-Jones Diane
Published: January 2010

Religiosity, sexual activity, and contraception were examined via questionnaires and interviews in a diverse sample of 118 high school seniors. The majority reported religion to be important; importance and frequency ratings declined from private (e.g., prayer) to public (e.g., group activities) components of religion. Most were sexually active and used contraception. Nearly half acknowledged religious teachings on sexual activity, and one third believed premarital sex is proscribed. Religiosity items were negatively correlated with approval of sexual activity in hypothetical relationship scenarios, but religiosity was not related to self-reported sexual activity or contraceptive use. Participants emphasized relationships and physical health, not religious proscriptions, in their standards for sexual activity. Older adolescents may believe sexual activity is acceptable in committed romantic relationships.