bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphologic Characterization of Castor Oil-induced Colitis in Ponies
Authors: Johnson C. M. , Cullen J. M. , Roberts M. C.
Published: March 2010

Ten ponies (160-250 kg, ages 17 months to 20 years) developed severe diarrhea within 24 hours of castor oil administration (2.5 ml/kg orally). The diarrhea was most severe between 24 and 48 hours post-dosing and subsided by 72 hours. Ponies were euthanatized at 24, 48, and 72 hours post-dosing and intestine was evaluated histologically and ultrastructurally. Twenty-four hours after dosing, the mucosa of the cecum and ventral colon had extensive superficial epithelial erosion and neutrophil infiltration. In the ileum, the epithelium of villous tips was separated from the lamina propria. Scanning electron microscopic examination of the cecal mucosa revealed that basement membranes were exposed in most areas except within necks of crypts. Ultrastructurally, changes in superficial enterocytes of the cecum and ventral colon were characterized by loss of microvilli, distortion of the cytoplasmic terminal web, expansion of the cytoplasmic matrix with formation of precipitates, and widening of intercellular spaces between junctional complexes. Enterocytes located within necks of crypts were flattened along the basement membrane and extended to margins of erosions. Venules within the superficial lamina propria were occluded by fibrin thrombi. Erosions in the cecum and ventral colon of ponies examined 48 hours after treatment were less extensive than those of ponies examined at 24 hours. At 48 hours post-dosing, basement membranes adjacent to crypts were covered by cuboidal enterocytes characterized ultrastructurally by sparse, irregularly shaped microvilli located on broad cytoplasmic protrusions and by numerous free ribosomes. These features indicated that immature enterocytes had migrated from crypts to resurface the eroded mucosa. By 72 hours post-dosing, the entire mucosa was covered by columnar epithelium, although cells were shorter and had decreased density of microvilli than cells of control animals. A single dose of castor oil consistently produced transient diarrhea associated with neutrophilic inflammation and mucosal erosion in the cecum and ventral colon. Resolution of diarrhea occurred shortly after epithelial restitution.
Rhabdomyosarcomas in Young Pigs in a Swine Breeding Farm: A Morphologic and Immunohistochemical Study
Authors: Vos J. H. , Borst G. H. A. , de las Mulas J. Martin , Ramaekers F. C. S. , van Mil F. N. , Molenbeek R. F. , Ivanyi D. , van den Ingh T. S. G. A. M.
Published: March 2010

Within a 6-month-period, solitary or multiple tumors were observed in 25 young pigs in their first weeks of life in a swine breeding farm. The herd comprised approximately 100 animals, and affected pigs were observed in several litters. The number of affected littermates varied from one to three. Five animals, all from different litters and with a total of 11 tumors, were studied. Histologically the tumors were classified as undifferentiated sarcomas. Electron microscopic examination of the tumors ( n = 3) revealed myogenic differentiation, characterized by the presence of numerous cytoplasmic filaments with longitudinal densities and cytoplasmic dense bodies. Immunohistochemically, all 11 tumors were labeled by vimentin and desmin antibodies. Two tumors from which frozen material was available were additionally labeled by a titin antibody but did not show immunoreactivity with antibodies directed against myosin and α-sarcomeric actin. The tumors were finally diagnosed as undifferentiated rhabdomyosarcomas. The high incidence of these tumors within a short period of time in multiple young animals in different litters indicates a common causative event. The clinical history suggests a genetic cause.
Palpebral Amelanotic Melanomas in F344 Rats
Authors: Yoshitomi K. , Boorman G. A.
Published: March 2010

Spontaneous amelanotic melanomas in the eyelids of F344 rats were found in one of 1/926 (0.11 %) male and 5/925 (0.54%) female F344 rats that were used as control and treated animals in five different carcinogenicity studies conducted by the National Toxicology Program (Research Triangle Park, NC). These melanomas were grossly recognized as single, tan or white, well-circumscribed masses of the right or left eyelid. These melanomas primarily occurred in the dermis of the skin of the eyelids and consisted of poorly differentiated spindle cells characteristically arranged in interlacing fascicles. Rarely, epithelioid tumor cells were also observed, and these tumor cells showed a negative histochemical reaction for melanin. The epidermis and dermal–epidermal junction were usually uninvolved. The diagnosis of amelanotic melanoma could only be established by electron microscopic examination. The most striking ultrastructural feature of the tumor cells was a large number of intracytoplasmic premelanosomes (stage II melanosomes without melanin), which nearly filled the cytoplasm of most tumor cells. Giant premelanosomes and melanophagosomes were also seen. The tumor cells did not possess the ultrastructural features characteristic of Schwann cells (thin, long cell processes and pericytoplasmic basal laminae). The histologic and ultrastructural features of these palpebral tumors were similar to those of cutaneous amelanotic melanomas of the pinna in F344 rats.
A Clinicopathologic, Histologic, and Immunohistochemical Study of Mixed Germ Cell-Stromal Tumors of the Testis in 16 Dogs
Authors: Patnaik A. K. , Mostofi F. K.
Published: March 2010

In a review of 262 neoplasms in 225 dogs, 18 tumors in 16 dogs were mixed germ cell–stromal tumors containing intimately admixed germ cells and Sertoli cells in tubular structures of various sizes. Seven of the 18 neoplasms were predominantly composed of germ cells, and 11 were predominantly composed of Sertoli cells. In 15 neoplasms, the germ cells were more anaplastic than the Sertoli cells, and in three neoplasms, both cell types were anaplastic. Five of the seven mixed-cell tumors with predominantly germ cells had germ cells infiltrating the adjoining tissues. Immunocytochemical studies of all 18 mixed-cell tumors, testes from five clinically normal dogs, six seminomas, and six Sertoli cell tumors revealed that neuron specific enolase (NSE) and vimentin were useful in demonstrating the dual population of the mixed cell tumors by differential staining of the germ cells and Sertoli cells. Half of the tumors stained differentially with desmin. In the normal testes, seminomas, and Sertoli cell tumors, parallel staining of germ cells and Sertoli cells by NSE and vimentin was seen, but only the appropriate tissues stained with desmin. The mixed-cell tumors in this study had morphologic features in common with mixed germ cell–sex cord stromal tumors and gonadoblastomas of human beings; clinically, they had more in common with the former. These mixed cell tumors in dogs should be classified separately.
Islet Amyloid Polypeptide: A Review of Its Biology and Potential Roles in the Pathogenesis of Diabetes Mellitus
Authors: O'Brien T. D. , Butler P. C. , Westermark P. , Johnson K. H.
Published: March 2010

Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic β-cells and is co-packaged with insulin in the β-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the β-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretogogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)–89 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20–29 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical/chemical damage to β-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of β-cells and/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin-dependent diabetes mellitus and NIDDM is currently unknown.
The Immunocytochemistry of Cytokeratin in Fish Tissues
Authors: Bunton T. E.
Published: March 2010

An increasing interest in fish species as sentinels of environmental pollution and in carcinogenesis research has led to the identification of diagnostically challenging neoplasms of uncertain cellular origin and the need for additional diagnostic methods. To determine the potential of using commercially available antibodies to intermediate filament proteins on paraffin-embedded fish tissues for immunocytochemistry in tumor diagnosis, the application of three antikeratin antibodies to normal adult tissues from two fish species was assessed. Multiple tissues from 12–14-in, striped bass ( Morone saxtills) and 6-month-old medaka ( Oryzias latipes) of both sexes were fixed in Bouin's or formalin fixatives. Formalin-fixed neoplasms from several mammalian species, including cat, dog, hedgehog ( Atelerix albiventris, Erinaceus europaeus), rhesus macaque ( Macaca mulatta), and sloth bear ( Melursus ursinus), were also used as positive controls. Using a strepavidin horseradish peroxidase method on paraffin-embedded tissues, the broad spectrum antibodies AE1/AE3 (Boehringer Mannheim, Indianapolis, IN) and MAK-6 (Triton Biosciences, Alameda, CA), which recognize most of the 19 human cytokeratins, and CAM 5.2 (Becton Dickinson, Mountain View, CA), which recognizes cytoker-atins present in human liver, were used as primary antibodies. Epithelia from skin, gills, cornea, bile ducts, renal tubules, gastrointestinal tract, and thymus were strongly positive with AE1/AE3 and MAK-6 in striped bass, but nonepithelial tissues such as bone and muscle were negative. Skin, gills, cornea, and portions of the gastrointestinal tract were strongly positive in medaka with the same antibodies, whereas bile duct, renal, and intestinal epithelia were less so. Tissue digestion improved the intensity of staining, and fixation with Bouin's fixative improved results somewhat compared with formalin fixation. Although CAM 5.2 elicited positive reactions in mammalian hepatocytes and biliary, intestinal, and renal epithelia, all tissues from either fish were negative despite manipulations of conditions such as strength of primary antibody concentration and duration of tissue digestion. Although variations in results among mammals and fish and between the two fish species may indicate differences in tissue cytokeratin immunogenicity, biochemistry, or content, the broad crossreactivity seen suggests good potential for the use of diagnostic immunocytochemistry in fish carcinogenesis research.
Analysis of DNA Aneuploidy and c-myc Oncoprotein Content of Canine Plasma Cell Tumors Using Flow Cytometry
Authors: Frazier K. S. , Hines M. E. , Hurvitz A. I. , Robinson P. G. , Herron A. J.
Published: March 2010

To derive a method for determining malignant potential of plasma cell tumors, a retrospective analysis of the DNA ploidy and relative p62c-myc oncoprotein content using bivariate flow cytometry was performed on 23 formalin-fixed, paraffin-embedded tissues from 23 dogs. The samples included one tissue each from 17 males and six females 2 to 16 years of age (mean = 7.5 years). Twelve breeds were represented, including three Cocker Spaniels, three Golden Retrievers, and five of mixed breed. Ten of the samples were histologically classified as malignant-plasma cell tumors, and ten specimens were classified as benign. Three samples of plasmacytic inflammation, from two Cocker Spaniels and one Shih Tsu, were included as controls. The ploidy and relative c-myc content data obtained were compared with the histologic grade. A significant difference in ploidy was found between benign and malignant tumors (P ≤ 0.05). Five of nine malignant plasma cell tumors were aneuploid; the remainder were diploid (4/9) or tetraploid (1/9). Only one of the benign plasmacytomas was aneuploid (1/10), whereas six were diploid (6/10), and three were tetraploid (3/10). All of the controls were diploid (3/32). When relative amounts of p62c-myc from malignant and benign tumors were compared by flow cytometry, a greater significant difference was established (P ≤ 0.01) than by using aneuploidy alone. Relative values of p62c-myc content ranged from 219 to 553 units in 8/10 malignant plasma cell tumors and from 86 to 392 units in 3/10 benign plasmacytomas. The remainder of the neoplasms (2/10 malignant and 7/10 benign) lacked measurable values of p62c-myc above background fluorescence concentrations. Two atypical cutaneous plasmacytomas with later metastasis were included in the study. The results indicate that simultaneous analysis of ploidy and relative p62c-myc concentration can be used as an aid in assessment of malignant potential in canine plasma cell tumors.
Nursing Disease in Mink: Clinical and Postmortem Findings
Authors: Schneider R. R. , Hunter D. B.
Published: March 2010

One hundred fifty lactating mink on one ranch in southern Ontario were monitored over the lactation period in 1989 for evidence of clinical disease, and serial blood samples were collected for biochemical analysis. Antemortem blood samples were collected and necropsies performed on the 17 females that developed nursing disease and on 17 controls matched to the same stage of lactation and on ten nonlactating controls. Twenty-two additional nursing disease cases were selected from seven ranches in the following year and processed similarly. The clinical signs typically observed in affected females were sudden onset lethargy and anorexia followed by dehydration, ataxia, and a reluctance to move. The major clinical-pathologic findings were a marked increase in serum osmolality and total protein, urea nitrogen, creatinine, phosphorus, glucose, and potassium concentrations and a decrease in sodium and chloride concentration. In addition, the animals were acidotic, there was a reduction in the urine specific gravity, and the hemogram was consistent with a stress response. Emaciation and dehydration were the only pathologic changes consistently present in cases of nursing discase and not in controls. In almost all cases, bacteria were not cultured from the liver, spleen, and mammary gland, but Campylobacter jejuni was cultured from the intestinal contents of 15/17 affected mink and 2/5 controls. Aleutian disease virus antibody was not present in any of the affected mink, Lipid vacuoles in hepatocytes and renal tubular epithelium, hypertrophy of cells in the adrenal cortex, and pulmonary congestion and atelectasis were present in both diseased females and controls, as were various sporadic inflammatory lesions. Nursing disease may result from energy depletion due to lactation. All lactating females are affected by this process: clinical disease reflects the terminal physiologic decompensation of the most susceptible individuals.
Cervico-pectoral Ectopia Cordis in Two Holstein Calves
Authors: Hiraga T. , Abe M. , Iwasa K. , Takehana K. , Tanigaki A.
Published: March 2010

Two Holstein calves affected with cervico-pectoral ectopia cordis, a male (No. 1) delivered stillborn and a female (No. 2) died 1 hour after birth, were examined macroscopically and radiographically to assess the severity and elucidate the teratogenesis of the anomaly. The heart of one calf was covered by the intact pericardium and skin and displaced to the caudalmost portion of the ventrocervical region, just cranial to an enlarged thoracic inlet. The cranial vena cava and the vena azygos were duplicated. The sternum was bilaterally divided into two parts fused only at the xyphoid process and was semicircular. The heart of the other calf, covered solely by the pericardium, was exposed ventrally from an oval opening in the body wall just cranial to a defective Y-shaped sternum. In both calves, the arterial branching pattern from the aortic arch was intermediate between the patterns of the dog and pig, and in each case a single pulmonary vein emptied into the left atrium. Pronounced or slight torticollis, cleft palate, and abnormalities in the urogenital system were also found. From an embryological perspective, cervical and pectoral ectopia cordis have a common pathogenesis; the cervical type occurs at a slightly earlier fetal stage than the pectoral type.
Clinical and Histologic Characterization of Cutaneous Reactions to Stings of the Imported Fire Ant (Solenopsis invicta) in Dogs
Authors: Rakich P. M. , Latimer K. S. , Mispagel M. E. , Steffens W. L.
Published: March 2010

Four adult dogs received experimentally controlled stings in the dorsolateral abdominal skin by imported fire ants ( Solenopsis invicta). The sites were examined grossly 15 minutes and at 1, 2, 3, 4, 5, 6, 24, 48, and 72 hours and histologically 15 minutes and 6, 24, 48, and 72 hours after stinging. The initial gross lesions at 15 minutes were swelling and erythema, and the microscopic changes were vascular congestion and superficial dermal edema. By 6 hours, the lesions consisted of bright erythematous pruritic papules characterized microscopically by a band of full thickness dermal necrosis and inflammation. By 24 hours and continuing to the end of the study at 72 hours, the sites appeared completely normal grossly. Biopsies taken 24, 48, and 72 hours after stings contained microscopic changes similar to those present at 6 hours after stings. These histologic changes are unlike those described for human beings stung by imported fire ants. In human beings, fire ant stings are characterized histologically by an initial superficial vesicle that evolves into a sterile pustule.
A Retrospective Study of Multicentric Bovine Renal Cell Tumors
Authors: Kelley L. C. , Crowell W. A. , Puette M. , Langheinrich K. A. , Self A. D.
Published: March 2010

Tissues from twenty mature cows with primary renal cell tumors were submitted over an 11-year period because of gross lesions detected during routine slaughter and inspection. Tumors visualized grossly were multiple and bilateral in seven cattle, multiple within one kidney in four cattle, and solitary in nine cattle. The tumors were primarily cortical, yellow-orange to tan, proliferative, well circumscribed, and extended above the capsular surface of the kidney. Tumors were microscopically multiple even when grossly described as solitary lesions, except in one cow. Twelve tumors (60%) were microscopically multiple in one kidney, seven tumors (35%) were multiple and bilateral, and only one cow (5%) exhibited extrarenal metastasis. Tumors from nineteen cows were composed of eosinophilic granular epithelial cells; tumors from one cow were clear cell type. Each tumor contained several histologic patterns. Corpora amylacea, proteinaceous secretions, and hemosiderin were characteristic findings in bovine renal cell carcinoma. All 20 cows with renal cell tumors exhibited positive immunoreactivity to uromodulin (Tamm-Horsfall protein).
Cystic Urogenital Anomalies in Ferrets (Mustela putorius furo)
Authors: Li X. , Fox J. G. , Erdman S. E. , Lipman N. S. , Murphy J. C.
Published: March 2010

Single or multiple semispherical to bilobulated fluid-filled cystic structures of variable size were observed on the dorsal aspects of the urinary bladder of four male and two female ferrets ( Mustela putorius furo). All ferrets had been neutered. On physical examination, the cysts were palpated as caudal abdominal masses. Three of the six ferrets presented with dysuria, and two ferrets had signs compatible with endocrine dysfunction. Adrenal cortical hyperplasia or neoplasia were observed in all of the five ferrets examined. Sex hormones assayed in one of the six ferrets revealed elevated levels of serum estrodiol. The posterior aspect of the cysts was located on and/or attached to the trigone or neck of the bladder, with variable intraluminal communication with the bladder and/or the urethra. The anterior aspect of the cysts projected dorsally or dorsocranially into the caudal abdomen. The cysts were thin walled and contained urinelike fluid ( n = 5) or viscous yellow fluid ( n = 1). Histologically, the cyst walls were composed of three layers, epithelium, muscle, and serosa, with fibrovascular stroma between layers. The epithelium consisted of simple to stratified transitional, columnar, or squamous epithelial cells. The muscular layer consisted of intermittent bundles and/or single to double layers of continuous to discontinuous smooth muscle. The serosal layer consisted of loose fibrous stroma covered by flattened mesothelial cells. The cystic anomalies in these ferrets were most likely derived from the urogenital glands/ducts or other remnants.
Gastric Infarction in Cynomolgus Monkeys (Macaca fascicularis)
Authors: Fikes J. D. , O'Sullivan M. G. , Bain F. T. , Jayo M. J. , Harber E. S. , Carlson C. S.
Published: March 2010

Five cases of gastric infarction were observed in adolescent or adult cynomolgus monkeys ( Macaca fascicularis) over a 20-month period. Gastric infarcts were encountered as striking and unexpected findings at necropsy. Gross and microscopic findings included gastric necrosis, hemorrhage, and edema that involved large areas of the fundus and pylorus. A consistent finding was the presence of thrombi in the gastric microvasculature, particularly in the venous system. All animals had acute clinical episodes with substantial tissue damage resulting from a variety of causes, including trauma, pancreatitis, necrotizing cystitis, and intestinal intussusception. In addition, three animals had microvascular thrombosis in nongastric tissues. Our findings suggest that cynomolgus monkeys may be predisposed to developing gastric infarction under conditions of severe systemic insult that predispose to disseminated intravascular coagulation.
Immunohistochemical Diagnosis of Systemic Bovine Zygomycosis by Murine Monoclonal Antibodies
Authors: Jensen H. E. , Aalbæk B. , Lind P. , Krogh H. V.
Published: March 2010

Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with homologous antigens in an enzyme-linked immunosorbent assay were subsequently screened for reactivity with homologous fungi in immunohistochemical techniques. All four Mabs raised against the WF of A. arrhizus failed to react on tissues. However, four of the Mabs raised against the WSSA of R. arrhizus (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) revealed a high homologous reactivity on tissues and the cross-reactivity of these were subsequently evaluated on tissues containing other members of the family Mucoraceae and other unrelated fungi. On tissues and on immunoblots all four Mabs reacted identically and specifically with members of the family Mucoraceae, i.e., Absidia corymbifera, R. arrhizus, and Rhizomucor pusillus. The Mabs were all isotyped as IgM antibodies, were nonprecipitating, and reacted with homologous antigens with molecular masses from 14 to 110 kDa. With WSSA from A. corymbifera and R. pusillus the four Mabs were bound to antigens from 14 to 52 kDa and from 20 to 28 kDa, respectively. The diagnosis of 145 bovine lesions obtained by one of the specific Mabs (Mab-WSSA-RA-1) were compared to results obtained by heterologously absorbed polyclonal antibodies. In most lesions ( n = 140 [∼ 97%]) the Mab and the polyclonal antibodies reacted in a similar pattern, i.e., positively for zygomycosis in 89 lesions, negatively in 41 aspergillosis lesions, and negatively in 10 undiagnosed lesions. Hyphae within two of four lesions in lymph nodes, which were not stained by the polyclonal antibodies, reacted with the specific Mab. However, in another three lesions of lymph nodes stained by the polyclonal antibodies no reactivity was seen with the Mab-WSSA-RA-1. The immunoreactivity of the Mabs (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) raised against WSSA of R. arrhizus justify their application for the in situ diagnosis of systemic bovine zygomycosis.
Apoptosis and CD4+ Lymphocyte Depletion Following Feline Immunodeficiency Virus Infection of a T-lymphocyte Cell Line
Authors: Johnson C. M. , Benson N. A. , Papadi G. P.
Published: March 2010

An interleukin-2-dependent feline T-lymphocyte cell line (FCD4-D), of which 65% of cells express CD4, was inoculated with the NCSU-1 isolate of feline immunodeficiency virus (FIVNCSU-1) and subsequently monitored for percentage of viable cells, percentage of apoptotic cells, percentage of CD4-expressing cells, and virus production. A decrease in viability from 91% to 12% over an 11-day postinoculation period was associated with an increase in the percentage of cells with nuclear morphology suggestive of apoptosis from < 5% to 97% based on ethidium bromide and acridine orange fluorescence. These changes were associated with a 24% reduction in the percentage of viable CD4-expressing cells at 7 days postinoculation. The relative amount of low-molecular-weight nuclear DNA was greater in FIV-infected cultures than in uninfected cultures from day 7 to day 15 postinoculation. This DNA was characterized by cleavage into fragments differing in size by approximately 180 base pairs. Ultrastructurally, nuclear chromatin and cytoplasm were condensed into discrete electron-dense bodies, and cell membrane projections were lost. Syncytia were occasionally present in FIV-inoculated cultures. Cytologic changes were associated with a logarithmic rise in Mg++-dependent reverse transcriptase levels in culture supernatants on days 4-7 postinoculation. Supplementation of FIV-inoculated culture medium with 1 mM ZnCl2 enhanced viability, decreased the percentage of cells undergoing apoptosis, and prevented the loss of CD4+ lymphocytes at 7 days postinoculation. These data suggest that feline CD4+ lymphocytes die by apoptosis following in vitro infection with FIVNCSU-1. The feline/FIV model may be a suitable system to investigate the mechanisms of lentivirus-associated CD4+ lymphocyte depletion in vivo.
p53 Tumor Suppressor Protein Overexpression in Osteogenic Tumors of Dogs
Authors: Sagartz J. E. , Bodley W. L. , Gamblin R. M. , Couto C. G. , Tierney L. A. , Capen C. C.
Published: March 2010

Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression correlate with highly aggressive tumor behavior.
Histologic Classification and Immunophenotype of Lymphosarcomas in Cats with Naturally and Experimentally Acquired Feline Immunodeficiency Virus Infections
Authors: Callanan J. J. , Jones B. A. , Irvine J. , Willett B. J. , McCandlish I. A. P. , Jarrett O.
Published: March 2010

Lymphosarcoma (malignant lymphoma) is the commonest hematopoietic tumor in the cat. Many cases are associated with feline leukemia virus (FeLV) infection, but epidemiologic and experimental data suggest that feline immunodeficiency virus (FIV) may also have a role in lymphomagenesis. In this paper, we describe the clinical presentation, histologic classification, and immunophenotype of lymphosarcoma in eight domestic cats with natural or experimental FIV infections. The tumors were often of unusual distribution, with the majority of cases conforming to the least common anatomic classification of “miscellaneous.” Histopathologic and immunophenotypic analysis using a panel of anti-cat and cross-reactive anti-human monoclonal and polyclonal antibodies identified seven of these tumors as high-grade B cell lymphomas of the centroblastic or immunoblastic subtypes. The remaining case was a T-cell tumor associated with a concurrent FeLV infection. Our findings, together with the results of an analysis of FIV proviral DNA in these tumors, indicate that the B-cell lymphosarcomas were comparable to those observed in human and simian immunodeficiency virus infections and that the role of FIV in lymphomagenesis is indirect and related to the potential for malignant transformation during polyclonal B cell activation.
Morphometric and Histopathologic Analysis of Lymphoid Depletion in Murine Spleens Following Infection withBrucella abortusstrains 2308 or RB51 or an htrA Deletion Mutant
Authors: Palmer M. V. , Cheville N. F. , Tatum F. M.
Published: March 2010

BALB/C mice were inoculated intraperitoneally with suspensions of Brucella abortus strains 2308 or RB51 or an htrA mutant. Spleens were examined on postinoculation day (PID) 2, 4, 7, 10, 15, 21, 30, and 60. Brucellae were cultured in high numbers from the spleens of mice infected with strains 2308 or htrA through PID 60; however, mice infected with strain RB51 cleared the infection between PID 30 and PID 60. Histopathologic changes in spleens from 2308-infected mice were characterized by marked accumulations of macrophages, which expanded marginal zones beginning as early as PID 7 and persisting through PID 60. Morphometric analysis showed a decrease in splenic white pulp in 2308-infected mice at PID 10, which correlated with the peak of bacterial infection. Although this decrease was significant ( P < 0.05) when compared with values at the previous (PID 7) and the following (PID 15) time periods, it was not significantly different from white pulp values noted at PID 2 or PID 4 or the values for control spleens. Spleens from RB51-infected mice showed only mild to moderate accumulations of macrophages in marginal zone areas during the peak of RB51 infection (PID 7-10). Morphometric analysis of RB51-infected spleens showed a decrease in white pulp area, which coincided with peak bacterial numbers. However, this decrease was not significant ( P > 0.05). Spleens from mice infected with the htrA mutant showed moderate to marked accumulations of macrophages in marginal zone areas, which persisted through PID 60. Multifocal necrosis in lymphoid follicles as early as PID 4 was seen in both htrA and 2308 infection. Morphometric analysis of htrA-infected spleens revealed no significant decrease in white pulp and no obvious correlation with bacterial numbers in the spleen. These results suggest that virulent B. abortus does not induce lymphoid depletion significantly below those values seen in noninfected mice; thus, the possible role of lymphoid depletion in the pathogenesis of brucellosis remains questionable.
Comparative Effects of Bluetongue Virus Infection of Ovine and Bovine Endothelial Cells
Authors: Russell H. , O'Toole D. T. , Bardsley K. , Davis W. C. , Ellis J. A.
Published: March 2010

Bluetongue virus (BTV) infection results in disparate clinical syndromes among ruminant species. An in vitro model system of BTV/target cell interaction was developed using umbilical vein endothelial cells (EC) from fetal lambs and calves. These cells had microscopic, ultrastructural, and immunocytochemical features typical of EC. BTV infection in these cells was examined using virus binding assays, plaque assays, a whole-cell enzyme-linked immunosorbent assay, flow cytometry, electron microscopy, and a bioassay for interferon activity. EC from both species supported cytopathic BTV infections. Ovine EC bound more BTV initially and produced more virus over time, whereas bovine EC underwent more rapid lysis subsequent to infection. An ultrastructural comparison of BTV-infected ovine and bovine EC, grown as differentiated capillary-like cords on a laminin-rich matrix or as monolayers, revealed no significant interspecies differences in viral morphogenesis between 1 minute and 24 hours after infection. The intracellular distribution of BTV nonstructural protein 1, which localized to virus inclusion bodies and tubules, was identical for ovine and bovine endothelial cells. Ovine and bovine EC produced a soluble mediator of interferon activity in response to BTV infection; however, ovine EC produced higher levels of interferon activity at lower levels of infection. These findings indicate differences in BTV-EC interaction that may contribute to the pathogenesis of the severe inflammatory disease that is characteristic of clinical bluetongue disease in sheep.
Effect of Substrate on Indirect Immunofluorescence Test for Canine Pemphigus Foliaceus
Authors: Iwasaki T. , Shimizu M. , Obata H. , Ogata M. , Nagata M. , Yanai T. , Kitagawa H. , Sasaki Y.
Published: March 2010

The effect of substrate on indirect immunofluorescence (IIF) tests for the detection of circulating autoantibodies was studied by examining sera from 14 canine pemphigus foliaceus patients, six sera with non-pemphigus dermatoses and ten normal dog sera against five different substrates from three species. These substrates included bovine esophagus, bovine nose, bovine tongue, monkey esophagus, and canine nose skin. Nine out of 14 (64.3%) sera from patients with canine pemphigus foliaceus showed intercellular space staining by indirect immunofluorescence using bovine esophagus as substrate. However, sera from nonpemphigus dermatoses and normal dog did not react with bovine esophagus. In other substrates, only bovine tongue showed 1/8 (12.5%) positive reaction at the intercellular space by sera from canine pemphigus foliaceus. Dog nose skin showed the intercellular space staining against ten of ten (100%) normal dog serum. Monkey esophagus showed the fluorescent deposit at the intercellular space in four of nine (44.4%) of pemphigus foliacues dog sera, however, four of ten (40%) of normal dog sera revealed nonspecific intercellular staining. These results indicate that the sensitivity and the specifity of IIF test in canine pemphigus foliaceus depend on the substrate. The best substrate for detecting circulating autoantibody in canine pemphigus foliaceus patients among five different substrates was bovine esophagus because of its sensitivy and high specifity. The diagnosis of canine pemphigus foliaceus should be made on the basis of a combination of clinical signs, histopathology, direct immunofluorescence, and the detection of circulating autoantibody.
Distribution of Bluetongue Virus in Tissues of Experimentally Infected Pregnant Dogs as Determined by In Situ Hybridization
Authors: Brown C. C. , Rhyan J. C. , Grubman M. J. , Wilbur L. A.
Published: March 2010

Six female dogs (four pregnant and two nonpregnant) were inoculated with bluetongue virus (BTV), serotype 11. Pregnant animals and one nonpregnant dog received 5.5-6.3 log10of cell culture-adapted virus. The other nonpregnant dog received a modified live vaccine contaminated with bluetongue virus. The nonpregnant animals never became clinically ill and were euthanatized 35 days post-inoculation. Three of the four pregnant dogs aborted, and all four died or were euthanatized 5-10 days post-inoculation. The predominant pathologic feature in the adults was severe pulmonary edema. Various tissues from the bitches and fetuses were examined by in situ hybridization using a digoxigenin-labeled probe corresponding to the nonstructural protein-1 gene of BTV-17. By this technique, viral nucleic acid was detected predominantly in endothelial cells of lung of all four dogs, with lesser amounts in capillaries of uterus, spleen, and kidney in some of the dogs. In two adult dogs, bluetongue viral nucleic acid was detected in mononuclear cells of the periarteriolar lymphoid sheaths of spleen. There was minimal staining of capillaries in placentae in three of the five fetuses examined. There was no viral nucleic acid detected in any of the other fetal tissues.
Coinfection of a Bearded Dragon,Pogona vitticeps, with Adenovirus- and Dependovirus-like Viruses
Authors: Jacobson E. R. , Kopit W. , Kennedy F. A. , Funk R. S.
Published: March 2010

Four neonate bearded dragons, Pogona vitticeps, from two collections became ill and died. Multiple tissues were collected and processed for light microscopy. In hematoxylin and eosin-stained sections of liver of one lizard, numerous basophilic intranuclear inclusions were observed. In three lizards, intranuclear inclusions were primarily seen within enterocytes in the small intestine. A portion of paraffin-embedded liver of one lizard and small intestine of a second lizard were removed, deparaffinized, and examined by electron microscopy. For the most part, inclusions in the liver consisted of nonenveloped viral particles 60-66 nm in diameter. Smaller nonenveloped virions 15-17 nm in diameter were occasionally seen in association with these particles. In the intestine, inclusions consisted only of 60-70 nm particles. Based on morphology and location, the larger particles were consistent with an adenovirus. Based on size and presence within nuclei of host cells coinfected with the adenovirus-like virus, the smaller viral agent was consistent with members of the genus Dependovirus.
Lysosomal Storage Disease in an Emu (Dromaius novaehollandiae)
Authors: Rim D. Y. , Cho D. Y. , Taylor H. W.
Published: March 2010

Lysosomal storage disease involving the brain, spinal cord, liver, and spleen was discovered in a 6-month-old male emu ( Dromaius novaehollandiae). The diagnosis was based on light and electron microscopic studies and histochemical staining characteristics. This is the first case of lysosomal storage disease reported in a ratite.
Immunohistochemical Characterization of Hemangiopericytomas and Other Spindle Cell Tumors in the Dog
Authors: Pérez J. , Bautista M. J. , Rollón E. , Lara F. Chacón-M. de , Carrasco L. , Mulas J. Martín de las
Published: March 2010

The immunohistochemical expression of muscle actin has been studied in 45 canine hemangiopericytomas (CHP) using a monoclonal antibody (HHF35) and formalin-fixed, paraffin-embedded specimens. The distribution of vimentin, desmin, cytokeratins, lysozyme, factor VIII-related antigen, S-100 protein, and glial fibrillary acidic protein was studied both in CHP and in some canine soft-tissue neoplasms (seven fibrosarcomas, seven benign schwannomas, seven benign fibrous histiocytomas, and six leiomyosarcomas) used as controls for differential diagnosis. All CHP and control tumors expressed vimentin. Twenty-three CHP expressed muscle actin, whereas all control tumors analyzed were muscle actin-negative, with the exception of leiomyosarcomas. Among muscle actin- and vimentin-positive CHP, one case could be reclassified as leiomyosarcoma because it was desmin-positive, two cases expressed lysozyme, and nine cases expressed S-100 protein. Among muscle actin-negative and vimentin-positive CHP, seven expressed S-100 protein. In addition, S-100 protein was detected in five schwannomas. All CHP and control tumors analyzed were negative for cytokeratins, factor VIII-related antigen, and glial fibrillary acidic protein. Our results support the hypothesis of a pericytic origin of CHP, and suggest that muscle actin, desmin, vimentin, and lysozyme could be useful for the differential diagnosis of canine spindle cell tumors, but not all these neoplasms can be identified with these tumor tissue markers.
Histopathological Changes in the Upper Respiratory Tract of F344 Rats Following Infection with a Rat-adapted Influenza Virus
Authors: Ibanes J. D. , Morgan K. T. , Burleson G. R.
Published: March 2010

The present study determined the morphogenesis of upper respiratory tract disease in rats following infection with a rat-adapted influenza virus. Sixty-eight 60-day-old, male F344 rats were infected by intranasal inoculation and necropsied at days 1, 2, 4, 7, 14, and 28 post-inoculation (PI). Responses to infection were studied by routine light microscopy for histopathologic changes and immunocytochemistry for localization of viral antigen. Severe infection-induced changes involved the respiratory epithelium and underlying lamina propria, and the nasal-associated lymphoid tissue, with minimal involvement of the transitional epithelium. The lesions were most severe on the septum and the medial aspect of the nasoturbinates. Viral antigen, located in the respiratory epithelium of affected regions at days 1 and 2 PI, was associated with neutrophilic infiltration and epithelial necrosis and erosion. At day 4 PI, an infiltrate of lymphocytes, macrophages, and fewer neutrophils was present, often accompanied by epithelial regeneration. Changes in the nasal-associated lymphoid tissue were evaluated using morphometric analysis and consisted of hyperplasia (days 4 to 7 PI) followed by progressive involution (days 14 to 28 PI). Mild lesions associated with foci of viral antigen were also observed in the nasal olfactory epithelium on days 1, 2, and 4 PI. The changes observed in the present study indicate the potential value of rat-adapted influenza virus infection as a model of human influenza.
Cerebral Infarction in Two Cynomolgus Macaques (Macaca fascicularis) with Hypernatremia
Authors: Harber E. S. , O'Sullivan M. G. , Jayo M. J. , Carlson C. S.
Published: March 2010

Hypernatremia resulting in neurologic symptoms ranging from lethargy to coma, and with underlying lesions of cerebral hemorrhage and thrombosis, has been reported in human beings. Herein we report two cases of cerebral infarction with venous thrombosis in cynomolgus monkeys. Both animals were severely hypernatremic because of water deprivation, with serum sodium levels of 185 and 193 meq/liter, respectively. At necropsy, there were bilateral multiple hemorrhagic and malacic areas visible on the surface of the cerebrum and extending into the parenchyma, primarily involving the occipital lobes. These lesions were interpreted microscopically as infarcts because, in addition to hemorrhage and necrosis, multiple thrombi were present in small and medium-sized veins of gray matter and meninges. The pathogenesis of hypernatremia-induced cerebral lesions is believed to involve cellular dehydration that caused shrinkage of the brain. Because the vasculature of the brain is tightly adherent to the skull, this shrinkage results in tearing of blood vessels, with consequent hemorrhage and thrombosis.
Malignant Epithelioid Schwannoma Affecting the Trigeminal Nerve of a Dog
Authors: Pumarola M. , Añor S. , Borràs D. , Ferrer I.
Published: March 2010

A malignant epithelioid schwannoma was diagnosed affecting the trigeminal nerve of an 11-year-old dog. Neurologic abnormalities included an altered mental status, ataxia, left head tilt, postural reaction deficits of all four limbs, a pronounced left masticatory muscle atrophy, and absent left facial sensation. Histologically, a densely arranged epithelioid population with a very high mitotic index was surrounded by a spindle-shaped cell proliferation characteristic of schwannomas. Both cell populations stained positively for vimentin, but only spindle cells were occassionally positive for S-100 protein. The histologic and immunohistochemical features of this tumor were consistent with those found in human epithelioid schwannomas.
Malignant Intracranial Teratoma in a Juvenile Wistar Rat
Authors: Reindel J. , Bobrowski W. , Gough A. , Anderson J.
Published: March 2010

An intracranial malignant teratoma was identified in a 91-day-old male Wistar rat manifesting central nervous system-related clinical signs. This tumor occupied the right midbrain and portions of the right caudal cerebrum and cranioventral cerebellum. Microscopically, the tumor contained intermingled cartilage, bone (with medullary hematopoietic tissue), fibrous connective tissue, skeletal muscle, fat, pseudostratified ciliated epithelium, stratified squamous epithelium, serous and mucoserous glands, and neural tissue with ependymal and choroid plexus epithelia. Poorly differentiated cells with primitive cartilaginous matrix were present throughout the lining of lateral ventricles, in the aqueduct of Sylvius, and in meninges overlying normal cerebellar tissue indicating tumor metastasis occurred via cerebrospinal fluid. This neoplasm was not identified in extracranial sites and hence was considered a primary intracranial malignant teratoma with metastases via cerebrospinal fluid.
Leishmania Infection of Canine Skin Fibroblasts In Vivo
Authors: Rodríguez J. Hervás , Mozos E. , Méndez A. , Pérez J. , Gómez-Villamandos J. C.
Published: March 2010

In this paper we describe two cases of naturally occurring leishmaniasis in dogs in which Leishmania sp. amastigotes are found within the cytoplasm of fibroblasts. The infected cells were identified histologically, immunohistochemically, and ultrastructurally as fibroblasts. This is the first report of leishmaniasis in any species in which amastigotes were identified in vivo within fibroblasts.