bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic and Histochemical Changes in Articular Cartilages of Immature Beagle Dogs Dosed with Difloxacin, a Fluoroquinolone
Authors: Burkhardt J. E. , Hill M. A. , Carlton W. W. , Kesterson J. W.
Published: March 2010

The histologic and histochemical features of quinolone-induced arthropathy were studied using 14 skeletally immature Beagle dogs (3 to 4 months old) dosed orally with difloxacin at 300 mg/kg body weight once daily for 1, 2, 5, or 7 days. A placebo was given to eight other age-matched Beagle dogs that served as controls. A scoring technique that included lesion size and histologic features was used to determine the progression of lesions. Articular-epiphyseal cartilage complexes on the femoral and humeral heads and tibial tarsal bone were identified as predilection sites. Within predilection sites on femoral and humeral heads, lesions developed in specific areas. Lesions appeared within 2 days of the onset of treatment, and lesion scores increased with time. Grossly, the lesions were raised, fluid-filled vesicles on the articular surface. Histologic changes included vesicle formation with loss of proteoglycan, clumping of unmasked collagen, and degeneration and necrosis of chondrocytes. In lesions with higher scores, chondrocytes were often in clusters or they were undergoing metaplasia toward spindle-shaped cells. Although dissolution of matrix and necrosis of chondrocytes were typical of all lesions, smaller lesions had histologically normal chondrocytes adjacent to small vesicles. In sections stained with toluidine blue, proteoglycan was aggregated with collagen fibrils or was absent from the matrix adjacent to vesicles. Unique features, such as biomechanical forces, may predispose specific areas of articular cartilage to develop lesions.
Spongy Degeneration of White Matter in the Central Nervous System of Silver Foxes (Vulpes vulpes)
Authors: Hagen G. , Bjerkås I.
Published: March 2010

A disorder of central nervous white matter in Norwegian-bred silver foxes is described from the case histories of 21 clinically affected foxes. The main presenting sign of this disorder was caudal limb ataxia, which appeared between 2½ and 4 months of age and progressed over the next 4-8 weeks. Only four affected foxes were allowed to live beyond this period, but they showed moderate to marked improvement.

Light microscopic examination of specimens from 16 affected foxes necropsied between 3½ and 6½ months of age revealed lesions that were restricted to the white matter of brain and spinal cord. The lesions were characterized by a symmetrical spongy change with vacuoles of varying sizes and included significant myelin deficiency. There was a relative preservation of axons and nerve cells and no significant inflammation or vascular reaction. An astrocytic hypertrophy was usually associated with the spongy change.

Ultrastructural examination of central nervous tissue from two, perfusion-fixed, 6-month-old foxes showed intramyelin vacuoles resulting from splitting of the myelin lamellae at the intraperiod line and was interpreted as indicating myelin edema. Expanded extracellular spaces and watery astrocytic processes also contributed to the vacuolar appearance. Astrocytic processes in affected areas were hypertrophic and contained abundant filaments.

Although the 16 silver foxes had severe clinical signs, their lesions had features in common with the juvenile form of Canavan's disease in children and a spongy degeneration reported in Labrador Retrievers; however, the clinical course in the foxes was not uniformly progressive.
Hemogram Changes in Lactating Dairy Cows Given Human Recombinant Granulocyte Colony Stimulating Factor (r-MethuG-CSF)
Authors: Cullor J. S. , Fairley N. , Smith W. L. , Wood S. L. , Dellinger J. D. , Inokuma M. S. , Souza L. M.
Published: March 2010

As a prelude to mammary gland challenge experiments, this investigation was implemented to assess the hematologic changes in lactating dairy cattle induced by two dosage regimes of human recombinant colony stimulating factor (Hr-GCSF). This study documents the capability of the human recombinant colony stimulating factor to produce hematologic changes in both a time and dose dependent manner when administered to the adult lactating bovine. A screening dose of 1 μg/kg of Hr-GCSF administered to three study subjects produced a three- to four-fold increase in peripheral blood mature neutrophil counts ( P < 0.043) by day 12 of the trial. The priming dose treatment group of four lactating cows (3 μg/kg of Hr-GCSF) exhibited a three- to five-fold increase in peripheral blood mature neutrophil counts ( P < 0.05) and two- to three-fold increases in white blood cell counts by day 5 of the trial. Hematologic examinations of the control group ( n = 4; no Hr-GCSF administration) did not detect significant changes in their neutrophil counts over baseline values. The milk somatic cell counts did not statistically shift over baseline values in any of the control or Hr-GCSF treatment groups. When attempting to alter the course of infectious disease processes, potential applications of colony stimulating factors provide interesting speculations about new therapeutic modalities.
Age-related Changes in the Prostate and Testes of the Beagle Dog
Authors: Lowseth L. A. , Gerlach R. F. , Gillett N. A. , Muggenburg B. A.
Published: March 2010

Age-related changes in the histologic morphology of the Beagle dog prostate have been used as a model for similar changes that occur in human beings. Previous studies of the aging changes in Beagle dogs have been limited to animals less than 10 years of age. In this study, the prostate, testes, and serum testosterone levels were evaluated in healthy Beagle dogs that were grouped by age to provide five groups of dogs that ranged from 3 to 14 years of age. Tissue sections from the prostate and testes were examined qualitatively and quantitatively by light microscopy. All animals 6 years of age and older had histologic characteristics of complex benign prostatic hyperplasia. A mean statistically significant increase in prostatic weight with increased age was noted (mean value 1.08 ± 0.22 g/kg body weight at 3 years of age, increasing to 2.64 ± 0.37 g/kg body weight at 14 years of age). Morphometric analysis of the prostatic tissue suggested that similar to the change observed in human males, the increase in size was primarily due to an increase in the absolute volume of interstitial tissues (mean value 2.8 ± 1.1 cm3 at 3 years of age, increasing to 7.4 ± 1.3 cm3 at 14 years of age). The epithelial component did not contribute to the increase noted, with the exception that the percentage of glandular lumen did increase with age, indicating progressive cystic dilatation of the glands. Stereologic analysis of the testes showed a decrease in the relative percentage of germ cells with increasing age (mean value 58.5 ± 2.3% at 3 years of age, decreasing to 45.2 ± 4.0% at 14 years of age). No distinct age-related trend was detected in serum testosterone concentrations. These findings indicate that the progression of benign prostatic hyperplasia occurs throughout the entire life span of the dog; an association with changes in the testes was not identified.
Lectin Histochemistry on Squamous Metaplasia in Different Epithelial Tumors of Dogs
Authors: Castagnaro M. , Canese M. G.
Published: March 2010

Biotinylated lectins and avidin-biotin-peroxidase complex were used to study the correlation between cellular glycoconjugates' expression and squamous maturation in normal canine skin and in various epithelial neoplasms. Normal skin tissue was obtained from five, male, random-source dogs, 5 to 7 years old. The tumors tested, selected from the files of our Department, were fifteen squamous cell carcinomas from different tissue origin, five hepatoid perianal gland adenocarcinomas with squamous metaplasia, and fourteen solid mammary carcinomas with and without histologic evidence of squamous metaplasia. Except for mammary gland carcinomas, all tumors had been surgically excised from male dogs. Intermediate filament aggregation of twelve solid mammary gland carcinomas were studied electron microscopically. The basal and the lower spinous cells in normal skin and the less differentiated cells in squamous cell carcinomas stained moderately with Griffonia simplicifolia agglutin-I. Spinous and granular cell layers stained strongly with Phytolacca americana mitogen and Arachis hypogaea agglutinin. Both lectins stained well-differentiated cells in squamous cell carcinomas. The electron microscopic study carried out in solid carcinomas of mammary glands revealed some relationship between the presence of intracytoplasmic tonofibrils and the binding of Griffonia simplicifolia glutinin-I and Phytolacca americana mitogen to the tumors tested.

Our results suggest that the glycosylation pattern occurring during normal keratinocyte differentiation is conserved in squamous cell carcinomas and that Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen may represent useful tools in distinguishing poorly differentiated squamous cell carcinomas from other poorly differentiated mammary epithelial tumors.
Follicle Associated Epithelium of the Gut Associated Lymphoid Tissue of Cattle
Authors: Parsons K. R. , Bland A. P. , Hall G. A.
Published: March 2010

The morphology of the gut-associated lymphoid tissue of the small and large intestine in three gnotobiotic calves was examined by scanning and transmission electron microscopy, and the distribution of specialized membranous cells present in the follicle associated epithelium was defined. Isolated follicles remaining in the ileum of a cow after involution of the continuous Peyer's patch were examined by scanning electron microscopy. The presence of membrane-bound particles, reported to be exclusively associated with the continuous Peyer's patch, was investigated in other gut-associated tissue of the small and large intestine of the calf.

The presence of two types of follicle associated epithelium in the small intestine of the calf was confirmed, and the follicle associated epithelium of the large intestine proved to be a homogeneous population of specialized membranous cells, similar to that of the continuous Peyer's patch of the small intestine. In the discrete Peyer's patches, some specialized membranous cells were completely hidden by adjacent enterocytes and could only be identified by cytoplasmic extensions into the intestinal lumen. In the proximal part of the continuous Peyer's patch, a transitional zone was detected where the follicle associated epithelium of some domed villi was composed of a homogeneous population of specialized membranous cells, while the epithelium covering other domed villi consisted of a mixture of absorptive and specialized membranous cells, usually only found in the discrete Peyer's patches. Membrane-bound particles were observed associated with gut-associated lymphoid tissue in the small and large intestine.
Ultrastructural Studies of the Lung of Turkeys (Meleagris gallopavo) Inoculated Intratracheally withEscherichia coli
Authors: Ackermann M. R. , Cheville N. F.
Published: March 2010

To test the hypothesis that walls of air capillaries are a site for Escherichia coli to pass the air-blood barrier, fimbriated and nonfimbriated strains of E. coli were inoculated intratracheally into 18-day-old turkeys. Venous blood was cultured, and turkeys were necropsied from 0.5 to 8 hours post-inoculation. Lungs were processed for histopathology and electron microscopy. E. coli 078 was identified ultrastructurally using rabbit anti-lipopolysaccharide antibody and protein A-colloidal gold. All birds developed bacteremia; there was no significant difference between groups given fimbriated or nonfimbriated bacteria. Bacteria adhered to the plasma membrane of air capillary epithelial cells and were seen within vacuoles of portions of these cells that lined the fornices of air capillaries. Bacteria were also seen in the basement membrane at the basal surface of air capillary epithelial cells and, rarely, in vacuoles of subjacent endothelial cells. Infected granular and nongranular cells that lined air atria were necrotic 4 hours post-inoculation. Bacteria were within the overlying trilaminar substance and between reticular fibers of the interstitial stroma and pleura at 30 minutes postinfection and thereafter. Thus, the pulmonary air capillaries are a site for entrance of E. coli into the pulmonary blood capillaries, but fimbriae play little or no role in passage across the air-blood barrier.
Gross, Histologic, Cytochemical, and Immunocytochemical Study of Medullary Thyroid Carcinoma in Sixteen Dogs
Authors: Patnaik A. K. , Lieberman P. H.
Published: March 2010

The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 ( n = 13), S-100 protein ( n = 5), neuron specific enolase ( n = 14), synaptophysin ( n = 11), calcitonin ( n = 16), somatostatin ( n = 4), gastrin ( n = 7), and serotonin ( n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.
Colonization of the Pharyngeal Tonsil and Respiratory Tract of the Gnotobiotic Pig by a Toxigenic Strain ofPasteurella multocidaType D
Authors: Ackermann M. R. , Cheville N. F. , Gallagher J. E.
Published: March 2010

Seven-day-old gnotobiotic pigs were inoculated intranasally with Pasteurella multocida and euthanatized 2, 5, 9, and 14 days after inoculation. Tissues from the oropharynx and respiratory tract of pigs were cultured quantitatively and analyzed microscopically. Pigs remained afebrile and alert, except one that died of acute fibrinopurulent pneumonia. Pasteurella multocida was isolated in greatest numbers from the pharyngeal tonsils, but only in low numbers from turbinate, trachea, lung, spleen, and liver. Significant histologic changes were limited to the tonsil. Infected pigs developed mild tonsillitis with lymphocytic hyperplasia, and accumulation of cell debris and bacteria in crypts. Capsular antigens of P. multocida, identified on tissue sections with rabbit anti-capsular polysaccharide antibody and immunocytochemical reagents, were confined to the crypt lumen. Ultrastructurally, bacteria were free within crypt material or within phagosomes of macrophages or neutrophils. In a second experiment, 5-day-old pigs were infected with Streptococcus suis type 2, followed by toxigenic Pasteurella multocida at 7 days of age; one pig died of streptococcal septicemia. Pigs developed a mild tonsillitis, and both bacteria were cultured from the tonsillar crypts for up to 14 days after infection. These studies show that a toxigenic strain of Pasteurella multocida, which is a causative agent of atrophic rhinitis, can colonize the tonsil and respiratory tract of gnotobiotic pigs for up to 14 days. In addition, colonization can occur concurrently with Streptococcus suis type 2.
Ultrastructural Features of Lesions in Bronchiolar Epithelium in Induced Respiratory Syncytial Virus Pneumonia of Calves
Authors: Bryson D. G. , Platten M. F. , McConnell S. , McNulty M. S.
Published: March 2010

Ultrastructural changes were observed in bronchioles in acute and repair stages of respiratory syncytial virus pneumonia induced in eight young calves (calf Nos. 1–8) using a bovine strain of respiratory syncytial virus. Five of the calves were Friesians and three were Hereford x Friesians and all were male. Tissues from three mock-infected control calves (two Friesian, one Hereford x Friesian) were also examined. Calves were from 3 to 6 days old at the time of first inoculation, with the exception of calf No. 8, which was 2 weeks old. In the acute stage of the induced pneumonia, evidence of respiratory syncytial virus replication and release was demonstrable in both ciliated and non-ciliated bronchiolar epithelial cells, with the virus-releasing process most obvious at 4 and 5 days after infection. Respiratory syncytial virus infection of bronchiolar epithelium was associated with various changes, including hypertrophy, hyperplasia, and formation of syncytia. Necrosis of epithelial cell structures usually appeared to be preceded by their desquamation from bronchiolar walls. Respiratory syncytial virus infection resulted in considerable damage to the bronchiolar ciliary apparatus. Such damage was seen as early as 1 day post-infection and was still obvious at 10 days post-infection. Neutrophils were closely associated with respiratory syncytial virus infected epithelial cells and evidence of neutrophil fusion with infected epithelial cells was seen. These observations suggest that neutrophils may be involved in killing respiratory syncytial virus infected cells and that neutrophils might play an important role in early antiviral defense against respiratory syncytial virus at a time when antibody levels are low and other cellular defenses are not fully in play. Bronchiolar repair was evident from 6 days after infection and was well advanced at 10 and 13 days after infection.
Pathogenesis of Venezuelan Equine Encephalitis Virus Infection in Mice and Hamsters
Authors: Jackson A. C. , SenGupta S. K. , Smith J. F.
Published: March 2010

The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice ( n = 24, 6 to 8 weeks old) and hamsters ( n = 9, 90–110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extrancural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extrancural disease before major central nervous system disease developed.
A Histomorphologic and Immunohistochemical Study of Chordoma in Twenty Ferrets (Mustela putorius furo)
Authors: Dunn D. G. , Harris R. K. , Meis J. M. , Sweet D. E.
Published: March 2010

The histomorphologic and immunohistochemical features of chordoma in 20 ferrets were evaluated. The mean age was 3.4 years, and, in the cases for which sex was known, females ( n = 10) outnumbered males ( n = 5) two to one. All 20 tumors occurred on the tip of the tail. Nineteen of 20 tumors (95%) were composed of three tissue components, often arranged concentrically with lobules of physaliferous cells at the periphery, trabecular bone in the center, and cartilage in between. The bone often contained marrow and hematopoietic cells. One tumor lacked chondromatous or osseous tissue. Immunohistochemical results were consistent with previous studies of chordoma. All 20 tumors (100%) were positive for keratin and vimentin intermediate filaments; 15 (75%) were positive for S-100 protein; and 17 (85%) were positive for neuron specific enolase. This neoplasm shares morphologic and immunohistochemical features with “classic,” as well as chon-droid chordoma, of human beings, making it a potential animal model.
Pathology of Enzootic Intranasal Tumor in Thirty-eight Goats
Authors: De las Heras M. , Garcia de Jalon J. A. , Sharp J. M.
Published: March 2010

Intranasal tumors were studied in 38 goats ranging from 7 months to 8 years of age of both Murciana-Granadina and crossed breeds. Tumors were diagnosed in eight herds. Clinically, the affected goats showed a copious seromucous nasal discharge, ocular protusion, and skull deformations. The tumors originated from the ethmoid region. They involved one or both nasal cavities, although most were bilateral (26/38). The tumors were generally accompanied by inflammatory polyps. The histologic patterns were very similar in all cases, and the tumors were classified as low grade adenocarcinomas of the nasal glands. Histochemical, immunohistochemical, and ultrastructural studies suggested that the serous glands of nasal mucosa were the probable origin of the neoplastic cells. Budding and extracellular retrovirus-like particles were observed ultra-structurally in 6/8 tumors. The similarities between these caprine tumors and nasal tumors in sheep and the etiologic role of the retrovirus are discussed.
The Effects ofEscherichia coliand its Endotoxin on Amyloidogenesis in Ducks
Authors: Ling Y. S. , Mao H. P. , Zhong A. C. , Guo Y. C.
Published: March 2010

To compare the effects of two inocula on the induction of amyloidosis in normal and thymectomized ducks, 180 normal and 50 thymectomized ducks were injected intravenously weekly for up to 16 weeks with either crude endotoxin or crude whole cell extract of a virulent strain of Escherichia coli (O78), and another 60 ducks were injected with normal saline as study control. During the first 5 weekly injections, the initial doses of inducing agents were the smallest and then adjusted upward to the maximum study doses (1 or 2 mg/bird of crude endotoxin and 15-18 × 108bacteria/bird of crude whole cell extract), which were then maintained over the course of the study. The incidence of amyloid deposition were: 50.00% (25/50) for thymectomized ducks that received 1 mg/bird/week of crude endotoxin, 61.67% (37/60) for intact ducks that received 15 × 108-18 × 108bacteria (crude whole cell extract)/bird/week, 53.33% (32/60) for intact ducks received 2 mg/bird/week of crude endotoxin, and 63.33% (38/60) for intact ducks received 1 mg/bird/week of crude endotoxin. The results suggest that crude whole cell extract and crude endotoxin induced amyloidosis in ducks at similar rates and that, in ducks, thymectomy has no appreciable effect on the occurrence of amyloidosis.
A Comparative Study of Natural Killer Cell Activity, Lymphoproliferation, and Cell Phenotypes in Nonhuman Primates
Authors: Rappocciolo G. , Allan J. S. , Eichberg J. W. , Chanh T. C.
Published: March 2010

Three different species of nonhuman primates (baboons [ Papio hamadryas], rhesus monkeys [ Macaca mulatta], and African green monkeys [ Cercopithecus aethiops]) were evaluated for their natural killer cell activity, and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin, and pokeweed mitogen) and to react with a panel of mouse monocional antibodies directed against human leukocyte surface antigens. Rhesus monkeys displayed the highest natural killer cell cytotoxic activity (185.7 ± 33 lytic units) compared with those of baboons (83.8 ± 19 lytic units) and of African green monkeys from West Africa (39.08 ± 8 lytic units) and from the Caribbean basin (37.9 ± 9 lytic units). No correlation was observed between the natural killer cell cytotoxic activity and the percentage of CD 16′ natural killer cells among the three species studied. High spontaneous proliferative capacity was observed in African green monkeys obtained from West Africa compared with those of the other species studied. Although no significant differences were noted in T and B cell mitogen-induced in vitro proliferation, baboon mononuclear cells were less responsive to concanavalin A (stimulation index of 16 ± 3 [ x ± standard error of mean]) than to phytohemagglutinin (stimulation index of 47 ± 12). However, rhesus and African green monkey cells proliferated more efficiently in response to concanavalin A. Unlike in human beings where the ratio between helper-inducer (CD4 +) and cytotoxic-suppressor (CD8 +) T-lymphocytes is generally > 1, the CD4 +/ CD8 + ratios in baboons and rhesus and African green monkeys were 0.58, 0.69, and 0.35, respectively. Basic information on normal immune functions in these primates is important because of their increased use as experimental animal models for the study of human diseases such as acquired immunodeficiency syndrome (AIDS).
Hepatic Storage of Glycosaminoglycans in Feline and Canine Models of Mucopolysaccharidoses I, VI, and VII
Authors: Haskins M. E. , Otis E. J. , Hayden J. E. , Jezyk P. F. , Stramm L.
Published: March 2010

Livers from normal cats and dogs, cats with mucopolysaccharidoses (MPS) I and VI, and dogs with MPS VII were analyzed biochemically and morphometrically to determine the lysosomal storage of glycosaminoglycans (GAG) in these animal models of human genetic disease. Analyses were performed on liver samples from seven normal cats ranging in age from 13 weeks to 15 months; six MPS I-affected cats ranging in age from 10 weeks to 26 months; four MPS VI-affected cats ranging in age from 9 months to 32 months; four normal dogs ranging in age from 1 month to 47 months; and three MPS VII-affected dogs, 5 days, 11 days, and 14 months of age. All of the animals were from the breeding colony at the University of Pennsylvania School of Veterinary Medicine and were maintained in accordance with national standards for the care and use of laboratory animals. Each GAG subclass was quantitated, and total GAG concentration was determined. Liver from cats with MPS I had the highest total GAG concentration (5.7 times that of the control), followed by liver from dogs with MPS VII (1.8 times) and cats with MPS VI (1.5 times). These data were very closely correlated ( R2 = 0.982) with the results of the morphometric analyses of hepatocyte and Kupffer cell vacuolation associated with lysosomal storage and support the validity of both methods. This is particularly important for the quantification of total and individual GAG concentrations in tissue preparations. The values obtained should prove useful in future assessments of therapeutic regimes, such as enzyme replacement, bone marrow transplantation, and gene therapy, for these genetic diseases.
Neuropathologic Findings of Bromethalin Toxicosis in the Cat
Authors: Dorman D. C. , Zachary J. F. , Buck W. B.
Published: March 2010

Ten random source male domestic shorthair cats, 2 to 6 years old and 3.0–4.4 kg body weight, were each given a single oral dose (1.5 mg/kg) of bromethalin (cat Nos. 1–5) or bait vehicle carrier (cat Nos. 6–10). Bromethalin-dosed cats developed a toxic syndrome characterized by ataxia, focal motor seizures, vocalization, decerebrate posture, decreased conscious proprioception, recumbency, depression, and semicoma. Bromethalin-dosed cats were euthanatized if seizure activity or hindlimb paralysis developed. Survival times were 48 hours (cat No. 1), 89 hours (cat No. 2), 90 hours (cat No. 3), and 97 hours (cat No. 4). Control cats (cat Nos. 6–10) and one bromethalin-dosed cat (cat No. 5) were euthanatized on day 20 after dosing. Spongy change (edema—characterized by the formation of vacuoles in extracellular spaces and myelin lamellae), hypertrophied fibrous astrocytes, and hypertrophied oligodendrocytes were observed in the white matter of the cerebrum, cerebellum, brain stem, spinal cord, and optic nerve of all bromethalin-dosed cats. Spongy change occasionally extended into contiguous cerebellar Purkinje cell layer and cerebral cortical gray matter. The severity of lesions varied among cats but was most pronounced in cat No. 5 (480 hours after dosing). A leukocytic inflammatory response, gitter cell (macrophage) response, or axonal degeneration was not observed in the vacuolated areas. Ultrastructural findings included separation of myelin lamellae at the interperiod lines with the formation of intramyelinic vacuoles (intramyelinic edema), rupture and coalescence of intramyelinic vacuoles into larger extracellular spaces (spongy change), and pronounced cytosolic edema of astrocytes and oligoden-droglial cells.
Classification of 1,198 Cases of Bovine Lymphoma Using the National Cancer Institute Working Formulation for Human Non-Hodgkin's Lymphomas
Authors: Vernau W. , Valli V. E. O. , Dukes T. W. , Jacobs R. M. , Shoukri M. , Heeney J. L.
Published: March 2010

A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 × oil immersion field, 175 μm in diameter) of enzootic lymphomas (3.72 ± 0.06, mean ± standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 ± 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma.
Correlations between Presence of Spontaneous Lesions of the Pituitary (Adenohypophysis) and Plasma Prolactin Concentration in Aged Wistar Rats
Authors: van Nesselrooij J. H. J. , Kuper C. F. , Bosland M. C.
Published: March 2010

The predictive value of elevated plasma prolactin concentrations for the presence of spontaneous pituitary lesions was studied in 40 male and 38 female Wistar (Cpb:WU) rats, all 30 months old. The pituitaries were examined light microscopically and stained for prolactin using immunohistochemical methods. Plasma prolactin concentrations were measured by radioimmunoassay. Pituitary lesions were classified on the basis of their morphology in hematoxylin and eosin-stained sections as foci of hypertrophic or hyperplastic cells and hemorrhagic, pleomorphic, or spongiocytic adenomas; no carcinomas were found. There were significantly ( P = 0.001) more female than male rats with pituitary adenomas (58% females, 33% males) or without any pituitary lesions (21% females, 5% males); however, there were less female (21%) than male rats (63%) with foci of hyperplastic and/or hypertrophic cells but no adenomas in the pituitary ( P = 0.001). Elevation of plasma prolactin concentration above the upper 99th percentile value in age-matched rats without lesions was predictive, but not conclusively, of the presence of pituitary hemorrhagic adenomas in both sexes. It was, however, not predictive of the presence of foci of hypertrophic or hyperplastic cells. Elevation of plasma prolactin concentration above 10 ng/ml in male and 60 ng/ml in female rats was conclusive for the presence of hemorrhagic adenomas. Using multivariate analysis, significant positive correlations ( P < 0.01) were found between plasma prolactin concentration and presence and size of hemorrhagic adenomas and their prolactin staining intensity (correlation coefficients between 0.392 and 0.652). Foci of hyperplastic cells stained positively for prolactin, whereas hypertrophic cell foci and pleomorphic and spongiocytic adenomas did not stain for prolactin. There were no correlations (coefficients of less than ± 0.189) between plasma prolactin concentration and the presence of hypertrophic or hyperplastic cell foci and pleomorphic or spongiocytic adenomas in the pituitary. The morphologic criteria developed to distinguish spontaneous hypertrophic, hyperplastic, and neoplastic lesions of the rat pituitary corresponded well with their prolactin immunoreactivity and/or ability to elevate plasma prolactin concentration. These criteria constitute a biologically meaningful classification system for these rat pituitary lesions.
Correlation between Histologic Diagnosis Mean Nucleolar Organizer Region Count and Prognosis in Canine Mammary Tumors
Authors: Bostock D. E. , Moriarty J. , Crocker J.
Published: March 2010

In this study, surgically excised mammary tumors from 98 bitches were graded histologically, and the grade was compared with the mean nucleolar organizer region (NOR) count in silver-stained paraffin-embedded sections. Histologically benign tumors, papillary adenocarcinomas, and intraductal carcinomas showed relatively little variation; the mean count for each category was between three and four NOR per nucleus. There was, however, a significant increase in the NOR counts in tubular and solid carcinomas. This increase was most pronounced for tumors that showed evidence of infiltration into the surrounding connective tissues. The mean NOR count for noninfiltrative carcinomas was 5.1, and that for invasive carcinomas was 7.3 ( P < 0.03). The mean NOR count for individual carcinomas ranged from 2.0 to 12.3, and a significant correlation was found between an increased NOR count and tumor-related death during the first post-surgical year. The 39 bitches in which the tumor had an NOR count less than 8.0 had a generally favorable prognosis; only six (15%) died as a result of the original neoplasm. In contrast, 18/21 dogs (85%) with a carcinoma having an NOR count greater than 8.0 died from the tumor during the first post-surgical year. A similar, although less pronounced result was obtained specifically for invasive carcinomas, in which 3/12 (25%) tumors with an NOR count less than 6.0 resulted in the death of the host, compared with 17/20 (85%) that had an NOR count greater than 6. By using this technique, it is possible to identify a subgroup of bitches with invasive mammary carcinomas that have a very poor prognosis following apparently adequate surgical ablation of the primary tumor.
Immunohistochemical Localization of Matrix Proteins in the Femoral Joint Cartilage of Growing Commercial Pigs
Authors: Ekman S. , Heinegård D.
Published: March 2010

The immunocytochemical localization of several matrix macromolecules, including collagen type II and proteoglycans, in the distal femoral articular-epiphyseal cartilage complex of 15 commercial pigs between the age of 6 and 18 weeks was studied. Early osteochondrotic lesions, i.e., chondronecrosis in the resting region of the growth cartilage, as well as extensions of necrotic cartilage into the subchondral bone, were present in all animals, except those 6 weeks old. A battery of antibodies were used for identification of macromolecules in the matrix at different stages of the disease. Chondrocyte involvement in the process could be studied by identifying the sequence of alterations in matrix macromolecules as the lesion developed. The immunostaining for aggrecan (large aggregating proteoglycans), cartilage oligomeric matrix protein, fibronectin, collagen type II, fibromodulin, and biglycan was more prominent in the areas of chondronecrosis, extending into the subchondral bone, than in the normal resting region. This altered pattern of matrix macromolecules resembled that of the matrix of the proliferative chondrocytes and suggests that the chondrocyte maturation had stopped in the proliferative zone. The matrix in the areas of chondronecrosis in the resting region resembled that in the normal resting region. Thus the chondronecrosis appears to have preceded alterations of the matrix composition. The antibody reactivity pattern was, however, altered in the matrix of the clustered chondrocytes in areas of chondronecrosis. Staining in these regions suggested a more prominent appearance of fibronectin and collagen type II than in the normal matrix of the resting region. These changes are suggestive of attempt to repair. The chondronecrotic areas restricted to the resting region have a matrix that is different from the matrix of the abnormal cartilage extending into the subchondral bone, which resembled the matrix of the proliferative region. Hence the osteochondrotic lesion may not start in the resting region, instead the maturation of chondrocytes seems to stop in the proliferative zone, which would result in impaired bone formation.
Thrombosis of the Portal Vein in Eleven Dogs
Authors: Van Winkle T. J. , Bruce E.
Published: March 2010

Case records from the small animal necropsy service of the University of Pennsylvania (Philadelphia, PA) from January 1981 through August 1990 were searched for reports of animals with grossly visible portal vein thrombi. Eleven dogs identified from their case materials as having portal vein thrombosis were used for this study. The age of the dogs ranged from 2 to 13 years, and there were five spayed females and six males—four intact and two castrated. Seven breeds were represented (Lhasa Apso, German Wire haired Pointer, Shetland Sheepdog, Dalmatian, Irish Wolfhound, Old English Sheepdog, and Siberian Husky), and the remaining four cases were identified as mixed breeds. The weight of the dogs ranged from 7.7 to 50 kg, and most of them were considered overweight. Dogs with microthrombi and tumor emboli in the portal vein were excluded. No age, sex, or breed predisposition was found. Thrombi were also detected in the pulmonary arteries in five of the dogs and both the pulmonary arteries and aorta in one dog. The portal thrombi extended into the mesenteric veins in three dogs, resulting in infarction of the jejunum. One of these dogs and two other dogs had chronic occlusion of the portal vein, with the formation of secondary portosystemic shunts. Conditions also present in dogs with portal vein thrombi included pancreatic necrosis (four dogs), peritonitis (two dogs), distant neoplasia (three dogs), and therapy with steroids (ten dogs).
Bovine Myocardial Epithelial Inclusions
Authors: Baker D. C. , Schmidt S. P. , Langheinrich K. A. , Cannon L. , Smart R. A.
Published: March 2010

Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis.
Bronchoalveolar Eosinophilic Cells in a Canine Model of Asthma: Two Distinctive Populations
Authors: Baldwin F. , Becker A. B.
Published: March 2010

In a canine model of asthma, the identity and relationships of two types of cells with eosinophilic granules found in bronchoalveolar lavage (BAL) were investigated. Five female and three male newborn mongrel dogs were sensitized by intraperitoneal injection of 500 μg ragweed in 30 mg aluminum hydroxide repeated weekly for 8 weeks and then biweekly until 16 weeks of age. Three female and two male littermate controls received 30 mg aluminum hydroxide. From 4 months of age, dogs received six breaths of wet-nebulized ragweed solution through an endotracheal tube bimonthly. Bronchoalveolar lavage was performed 2 months or more after the last exposure to ragweed and was repeated 5 hours after ragweed inhalation. Dogs studied were 15 to 38 months of age. Eosinophilic cell populations were determined in BAL and peripheral blood; cells were examined by light and electron microscopy. Two eosinophilic cell types were in BAL: an eosinophil and an atypical cell with globule leukocyte characteristics. Specific microgranules, a constant feature of eosinophils, were prominent in the atypical cell and suggest a relationship to the eosinophil granulocyte series for the atypical cell and cells identified by others as globule leukocytes. In ragweed sensitized animals, there were more eosinophilic cells in BAL fluid and more eosinophils in peripheral blood. There was a proportional increase in BAL eosinophils 5 hours after ragweed inhalation and a corresponding decline in peripheral blood eosinophils. There was no increase in numbers of eosinophils in the sensitized animals; eosinophil and atypical cell numbers in littermate controls were unchanged.
Histologic Characterization of Hepatic Carcinogenesis in Transgenic Mice Expressing SV40 T-antigens
Authors: Cullen J. M. , Sandgren E. P. , Brinster R. L. , Maronpot R. R.
Published: March 2010

The development of hepatic neoplasms was histologically characterized in transgenic mice that expressed an albumin enhancer-promotor/SV40 T-antigen fusion gene. At least five transgenic and three control mice were examined at monthly intervals over a 3-month period. At 1 month of age, five transgenic mice (two male, three female) and three controls (one male, two female) were examined. Five transgenic mice (two male, three female) and three controls (one male, two female) were examined at 2 months of age. Fourteen transgenic mice (12 male, two female) and three controls (two male, one female) were examined at 3 months of age. At 1 month of age, liver-to-body weight ratios of transgenic mice were increased nearly twofold as compared with controls. Histologically, livers from transgenic mice were characterized by dysplastic hepatocytes with marked variation in nucleus and cell size. At 2 months of age, livers from transgenic mice were 2.5 times larger than control livers and contained numerous 1–5-mm cystic spaces. Transgenic livers also contained multiple eosinophilic, basophilic, and clear foci, as well as cystic, hyperplastic bile ducts and biliary adenomas. At 3 months of age, transgenic livers were enlarged over eightfold as compared with controls and contained numerous cysts and solid masses up to 2 cm in diameter. Trabecular, glandular, and anaplastic hepatocellular carcinomas, as well as benign and malignant biliary neoplasms, were diagnosed. No metastasis was observed. Subcutaneous trabecular hepatocellular carcinomas developed in two of three syngeneic mice that had received transplants of a solid hepatic neoplasm, confirming the neoplastic behavior of these tumors. These experiments, in which viral oncogene expression is targeted to all hepatocytes, support the multistage hypothesis of tumor development and illustrate the similarities in morphologic response of liver to a variety of carcinogenic insults.
Leptospirosis in Equine Fetuses, Stillborn Foals, and Placentas
Authors: Poonacha K. B. , Donahue J. M. , Giles R. C. , Hong C. B. , Petrites-Murphy M. B. , Smith B. J. , Swerczek T. W. , Tramontin R. R. , Tuttle P. A.
Published: March 2010

Leptospirosis was diagnosed in 51 equine fetuses and 16 stillborn foals with gestational ages from 3½ to 11 months. Diagnosis was based on one or more of the following: positive fetal antibody titer, positive fluorescent antibody test, demonstration of spirochetes in kidney and/or placental sections stained by the Warthin-Starry technique, high leptospiral titers in aborting mares, or isolation of Leptospira spp. from fetal organs. Gross lesions were observed in 80.3% of the fetuses, stillborn foals, and placentas. Gross placental lesions included nodular cystic allantoic masses, edema, areas of necrosis of the chorion, and necrotic mucoid exudate coating the chorion. The liver (23 cases) was enlarged, mottled, and pale to yellow. The kidneys (seven cases) were swollen and edematous with pale white radiating streaks in cortex and medulla. Microscopic lesions were observed in 96% of fetuses, stillborn foals, and placentas. Placental lesions consisted of thrombosis, vasculitis, mixed inflammatory cell infiltration of the stroma and villi, cystic adenomatous hyperplasia of allantoic epithelium, and villous necrosis and calcification. Fetal lesions included hepatocellular dissociation, mixed leukocytic infiltration of the portal triads, giant cell hepatopathy, suppurative and nonsuppurative nephritis, pulmonary hemorrhages, pneumonia, and myocarditis. Spirochetes were demonstrated with the Warthin-Starry stain in the allantochorion and/or kidney of 69 of the 71 cases. Using the direct fluorescent antibody technique, 56/60 cases tested positively for leptospires. Leptospires were isolated from fetal tissues in 20/42 cases. Sixteen of the isolates were identified by restriction enzyme analysis as Leptospira interrogans serogroup Pomona serovar kennewicki; case Nos. 36 and 41 were serovar grippotyphosa. The other two isolates were not identified. Microagglutination titers against leptospires were demonstrated in the body fluid of 47/67 cases tested and titers ranged from 1:50 to greater than 1:1,638,400 against Leptospira interrogans serovars pomona, grippotyphosa, copenhageni, hardjo, canicola, and bratislava. Sixty-two of 71 aborting mares tested had titers ranging from 200 to greater than 3,276,800. Leptospiral antibody titers in the body fluid and gross and histopathologic lesions did not differ with age, breed, or sex or between fetuses and stillborn foals.