bluuebunny/crossref_metadata_2025 huggingface dataset:
PHASE TRANSITIONS FOR A ϕ6 MODEL IN (2+1)-DIMENSIONAL CURVED SPACETIME
Authors: JOY MINU , KURIAKOSE V. C.
Published: April 2003

Considering a massive ϕ6 self-interacting scalar field coupled arbitrarily to a (2+1)-dimensional Bianchi type-I spacetime, we evaluate the one-loop effective potential. It is found that ϕ6 potential can be regularized in (2+1)-dimensional curved spacetime. A finite expression for the energy–momentum tensor is obtained for this model. Evaluating the finite temperature effective potential, the temperature dependence of phase transitions is studied. The crucial dependence of the phase transitions on the spacetime curvature and on the coupling to gravity is also studied. The nature of phase transitions for the present model is clarified to be first order. A first-order phase transition proceeds by nucleation of bubbles of broken phase in the background of unbroken phase.
FROM LEXICAL COHESION TO TEXTUAL COHERENCE: A DATA DRIVEN PERSPECTIVE
Authors: HARABAGIU SANDA M.
Published: April 2003

This paper presents research that connects the cohesion structure of a text to the derivation of its coherence structure. Two different algorithms that derive the cohesion structure in the form of lexical paths from large thesauri are illustrated. Their results are correlated with (1) cue phrases of discourse usage and (2) coherence constraints empirically derived. A novel model of coherence structure is devised, based on the data provided by lexical paths from real world texts.
Relationship between lung inflammation, changes in lung function and severity of exposure in victims of the Bhopal tragedy
Authors: Vijayan VK , Sankaran K
Published: April 2003

The world's worst chemical industrial disaster, which occurred at Bhopal on 2-3 December, 1984, resulted in considerable respiratory morbidity in the exposed population. Therefore, a study was planned to evaluate the relationship between lower respiratory tract inflammation, lung function and severity of exposure. Sixty patients exposed to methyl isocyanate and presenting with respiratory symptoms were studied using bronchoalveolar lavage (BAL) 1-7 yrs after the accident. Pulmonary function tests included forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). An index of severity of exposure was derived retrospectively on the basis of the acute symptoms in the victims themselves or the occurrence of death among their family members. Total lung inflammatory cells (p < 0.01) and absolute numbers of macrophages (p = 0.01) and lymphocytes (p < 0.05) increased as severity of exposure increased. FEV1/FVC % (p = 0.05) was also significantly lower as severity of exposure increased. Moderately exposed subjects had significantly lower FEV1/FVC % (p < 0.05) compared to those mildly exposed. In nonsmokers, BAL neutrophils, both percentage and absolute numbers, showed significant negative correlations with FEV1 % predicted (rs = -0.350, p < 0.05; and rs = -0.374, p < 0.01, respectively). Neutrophil percentage was negatively correlated with FEV1/FVC % (rs = -0.378; p < 0.01). Absolute lymphocytes had significant negative correlations with FVC % pred (rs = -0.318; p < 0.05). Macrophages had significant positive correlations with FVC % pred (rs = 0.322; p < 0.05) and FEV1 % pred (rs = 0.433; p < 0.01). Radiographic abnormalities (International Labour Organization (ILO) classification) were associated with decline in FEV1 % pred (p < 0.05). This study suggests that pulmonary function abnormalities occur in gas-exposed subjects as a consequence of an abnormal accumulation of lung inflammatory cells (lymphocytes and neutrophils), and that the intensity of lung inflammation and reduction in pulmonary function are greater in severely exposed subjects. As it has been observed that decline in pulmonary function is associated with radiographic abnormalities, there is a suggestion that injury following toxic gas exposure can lead to irreversible lung damage.
Oxidant-antioxidant imbalance in the experimental interstitial lung disease induced in sheep by visna-maedi virus
Authors: Cottin V , Court-Fortune I , Crevon J , Mornex JF
Published: April 2003

Infection of sheep by visna-maedi virus causes an interstitial pneumonitis similar to that associated with human immunodeficiency virus type-1 (HIV-1). Visna-maedi virus infection of alveolar macrophages leads to their activation. In this study we determined whether an imbalance in oxidant-antioxidant activity may be involved in the pathogenesis of the disease. We investigated the spontaneous and phorbol myristate acetate (PMA)-induced release of hydrogen peroxide (H2O2), and the activities of superoxide dismutase and glutathione peroxidase in alveolar macrophages from lambs experimentally-infected with visna-maedi virus, and in ovine alveolar macrophages infected in vitro. Alveolar macrophages from lambs experimentally-infected in vivo exhibited normal spontaneous H2O2 release and had superoxide dismutase and glutathione peroxidase activities similar to those from control animals. In contrast, after in vitro stimulation with PMA the H2O2 production by macrophages from experimentally-infected lambs was significantly increased. Similarly, spontaneous and PMA-induced H2O2 production by in vitro infected macrophages was significantly increased as compared to controls. In conclusion, the increased capacity of alveolar macrophages infected with the human immunodeficiency virus type-1-related visna-maedi virus to release hydrogen peroxide on stimulation suggests an oxidant-antioxidant imbalance, which may contribute to the pathogenesis of the observed chronic interstitial pneumonitis.
Glucocorticoid resistant asthma: T-lymphocyte steroid metabolism and sensitivity to glucocorticoids and immunosuppressive agents
Authors: Corrigan CJ , Bungre JK , Assoufi B , Cooper AE , Seddon H , Kay AB
Published: April 2003

We have previously shown that T-lymphocytes from clinically glucocorticoid (GC) resistant asthmatics are more refractory to dexamethasone suppression in vitro than those of GC sensitive asthmatics. We wished to extend these observations to compare three GCs used topically for asthma therapy (budesonide, beclomethasone dipropionate and fluticasone 17 alpha-propionate) and three immunosuppressive drugs (cyclosporin A, FK506 (tacrolimus) and mycophenolate mofetil) with dexamethasone for their antiproliferative effects on T-lymphocytes from GC sensitive and resistant asthmatics, and also to compare the rates of steroid metabolism by T-lymphocytes from these patients. Antiproliferative activity of the drugs was measured on peripheral blood T-lymphocytes activated with phytohaemagglutinin (PHA) and anti-CD3 antibody in vitro. The rates of total steroid metabolism and 20 alpha-hydroxylation by T-cell homogenates were measured using radiolabelled progesterone as an established probe substrate. Over a wide concentration range, T-lymphocytes from GC resistant asthmatics were significantly less inhibited by all four GCs as compared with cells from GC sensitive asthmatics. The median inhibitory concentrations (IC50) for inhibition of T-lymphocytes from the GC resistant asthmatics exceeded those likely to be achieved therapeutically by systemic administration (although higher concentrations might in theory be achieved locally in the bronchial mucosa by inhaled administration). In contrast, all three immunosuppressive drugs at putative therapeutic concentrations inhibited T-lymphocytes both from GC sensitive and resistant asthmatics with equivalent potency. The rates of total metabolism and 20 alpha-hydroxylation of steroid by homogenates of T-lymphocytes from GC sensitive and resistant asthmatics were equivalent. Thus, relative GC resistance in T-lymphocytes from GC resistant as compared with sensitive asthmatics is: 1) manifest with GC molecules of variable molecular structure; 2) not accompanied by elevated intracellular metabolism of steroids; and 3) overcome by immunosuppressive drugs which inhibit T-lymphocytes by non-GC-mediated mechanisms. We conclude that current anti-asthma glucocorticoids at therapeutic concentrations are unlikely to be of benefit for the therapy of glucocorticoid resistant asthma, and that other immunosuppressive drugs may have potential as therapeutic agents in these patients.
Abnormal autonomic stress responses in obstructive sleep apnoea are reversed by nasal continuous positive airway pressure
Authors: Veale D , Pepin JL , Wuyam B , Levy PA
Published: April 2003

Obstructive sleep apnoea (OSA) is associated with abnormalities in autonomic stress tests, which are tests of cardiovascular response in the autonomic nervous system (ANS). The level of abnormality has been related to the level of overnight arterial oxygen saturation (Sa,O2). We have studied ANS function pre- and post-treatment with nasal continuous positive airway pressure (nCPAP) in six males with moderately severe or severe OSA (apnoea/hypopnoea index (AHI) median 51 (range 14-74 events.h-1 of sleep). Tests consisted of heart rate responses to Valsalva manoeuvre, deep breathing, and change of posture from lying to standing. In addition, systolic blood pressure (SBP) response to standing and diastolic blood pressure (DBP) response to handgrip were studied. Each abnormal test (compared to published normal values) scored +1.0 and each marginal test result (90-95% confidence interval for normals) scored +0.5. A total score was calculated for the five tests performed in the evening and morning (maximum score 10 per patient). Patients had been receiving treatment for more than 1 year (median 471 (389-624) days) and objective compliance was monitored by a clock counter in the nCPAP machines. Five of six patients had regularly used nCPAP (mean 7.8 h.night-1) and all showed a normalization in ANS test score: pre-nCPAP 2 (1-4.5), post-nCPAP 0.2 (0-0.5) (p < 0.05, Wilcoxon signed rank test). One poorly compliant subject (No. 6; nCPAP 3 h.night-1) had a deterioration in ANS test score: 1 pre-nCPAP to 1.5 post-nCPAP. The improvement in ANS test score in the five compliant patients was positively correlated with an improvement in mean Sa,O2 during sleep posttreatment. We conclude that successful treatment of obstructive sleep apnoea leads to normalization of impaired autonomic stress responses.
Distinct involvement of cAMP-response element-dependent transcriptions in functional and morphological maturation during retinoid-mediated human myeloid differentiation
Authors: Saeki Kumiko , Saeki Koichi , Yuo Akira
Published: April 2003

We evaluated the involvement of cyclic adenosine monophosphate-response element (CRE)-dependent transcriptions in all-trans retinoic acid (ATRA)-induced myeloid differentiation using human monoblastic U937 cells. ATRA treatment caused an increment in the CRE-dependent transcription activity and induced a wide variety of differentiation phenotypes including functional and morphological maturation. Indeed, ATRA treatment induced the expression of CCAAT/enhancer-binding protein β (C/EBPβ), a CRE-dependent transcription factor important in monocytic differentiation, and the inhibition of CRE-enhancer activity by the expression of a dominant-negative CRE-binding protein (dn-CREB) abolished the induction of C/EBPβ. Functional maturation, such as the enhancement of cell adhesion and respiratory burst activity, was dramatically suppressed by the expression of dn-CREB. In addition, the differentiation-dependent induction of an adhesion molecule (CD11b), the phagocyte oxidase required for respiratory burst, and the transcription factor PU.1 responsible for phagocyte oxidase induction were all abolished by dn-CREB. Surprisingly, morphological maturation, including nuclear convolution and ctoplasmic vacuolar formation, was augmented by dn-CREB. Under the same conditions, the differentiation-associated cell-growth arrest was not affected by the expression of dn-CREB. Our results clearly indicate that CRE-driven transcription plays at least three distinct roles during myeloid differentiation: It stimulates functional maturation but suppresses morphological maturation and has no effects on cell-growth arrest.
Immunoregulatory defects in patients with systemic lupus erythematosus in clinical remission
Authors: Crispin J C , Alcocer-Varela J , de Pablo P , Martínez A , Richaud-Patin Y , Alarcón-Segovia D
Published: April 2003

Little is known about the immune system of patients with systemic lupus erythematosus(SLE) during periods of silent disease. To address this issue we analysed lymphoid populations and cytokine productionof mononuclearcells obtained from SLE patients in remission.We studied 43 patients with inactive disease, 10 with active disease and 30 controls. Remission was defined as at least 1 year during which lack of clinical disease activity permitted withdrawal of all treatment. Remission length ranged from 1 to 30 years. Flow cytometry and ELISA were used to study lymphoid populations (CD4, CD8 and CD19) and cytokineproduction(IL-2, 4, 10, 12 and 18). Patientswith short remission periods (up to 15 years) exhibited an increased percentage of B cells; production of IL-2, IL-10 and IL-12 was decreased;productionof IL-18 was increased. Interestingly, patients from groups with long time of inactive disease had corrected most alterations, but had an impaired IL-18 expression. IL-12 production correlated strongly with the length of the remission period (r 0.7565). The immune system of patients with inactive lupus has partially corrected the disturbances present during disease activity.This is accomplishedgradually, sometimes until counter-regulatoryalterationsare developed. This may allow patients to remain without disease activity.
Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model
Authors: Haj-Yahja S , Sherer Y , Blank M , Kaetsu H , Smolinsky A , Shoenfeld Y
Published: April 2003

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipidsyndrome (APS). Mice were immunized with either prothrombin, b2-glycoprotein-I (b2GPI), or b2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibodylevels directed towards their immunizing autoantigens.The groups immunized with b2GPI or b2GPI=prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopeniaand increased fetal resorption rate. All prothrombin-immunized mice as well as most b2GPI=prothrombin-immunized mice developed visible thrombus within the aorta. Some b2GPI immunized mice developed very mild thrombus. None of the CFA=PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or b2GPI=prothrombin is associated with prothromboticactivity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.
Association of homozygous deletion of the Humhv3005 and the VH3-30.3 genes with renal involvement in systemic lupus erythematosus
Authors: Cho Mi-La , Chen Pojen P , Seo Young-Il , Hwang Sue-Yun , Kim Wan-Uk , Min Do-June , Park Sung-Hwan , Cho Chul-Soo
Published: April 2003

To investigate whether deletion of the Humhv3005 and the homologous VH3-30.3 (both share an identical amino acid sequence) genes is associated with susceptibility and/or certain clinical manifestations of systemic lupus erythematosus(SLE), DNA from 108 Korean SLE patients and 102 healthy subjects were analysed for the status of hv3005 gene by polymerase chain reaction-enzyme-linked immunosorbent assay. This method consists of amplification of selected germline VH3 genes with biotinylated primers, efficient capture of amplicons onto streptavidin-coated wells, and quantitative typing of bound VH3 gene with diagnostic oligonucleotides. We found that deletion of the hv3005 gene (including VH3-30.3) was more frequent in SLE patients than in healthy controls (26.9 versus 11.8%, P 0.006, odds ratio 2.75). When clinical features were examined, patients with hv3005 deletion have a higher frequency of lupus nephritis (LN) (75.9 versus 44.3% for those without, P 0.004), and higher activity index [median (range), 6 (2-14) versus 4 (1-16) for those without, P 0.044] when biopsy-provenLN was studied. Collectively, our data suggest that deletion of the hv3005 and the 3-30.3 genes may predispose individual SLE patients to the development of LN.
Estimation of the convection heat transfer coefficient of coolant within the grinding zone
Authors: Jin T , Stephenson D J , Rowe W B
Published: April 2003

The convection heat transfer coefficient of the coolant within the grinding zone has been estimated using hydrodynamic and thermal modelling. The convection coefficient within the grinding zone can be very high, much higher than the values previously reported. The value is determined by the grinding wheel speed and the fluid film thickness within the contact zone. The film thickness in turn can be determined by wheel speed, porosity, grain size, coolant type and flowrate, nozzle size, etc. For deep grinding conditions [creep feed and high-efficiency deep grinding (HEDG)], the upper bound value of fluid film thickness can be easily achieved by a high coolant supply pressure and flowrate. Predicted values of the convection coefficient from hydrodynamic and thermal modelling show good agreement with experimental estimations obtained by matching measured and theoretical grinding temperatures for a wide range of grinding regimes when using a water-based grinding fluid. This includes HEDG and creep feed grinding for large contact lengths and conventional shallow cut grinding for short contact lengths.
Amylopectinosis in Fetal and Neonatal Quarter Horses
Authors: Render J. A. , Common R. S. , Kennedy F. A. , Jones M. Z. , Fyfe J. C.
Published: April 2003

Three Quarter Horses, a stillborn filly (horse No. 1), a female fetus aborted at approximately 6 months of gestation (horse No. 2), and a 1-month-old colt that had been weak at birth (horse No. 3), had myopathy characterized histologically by large spherical or ovoid inclusions in skeletal and cardiac myofibers. Smaller inclusions were also found in brain and spinal cord and in some cells of all other tissues examined. These inclusions were basophilic, red-purple after staining with periodic acid-Schiff (both before and after digestion with diastase), and moderately dark blue after staining with toluidine blue. The inclusions did not react when stained with Congo red. Staining with iodine ranged from pale blue to black. Their ultrastructural appearance varied from amorphous to somewhat filamentous. On the basis of staining characteristics and diastase resistance, we concluded that these inclusions contained amylopectin. A distinctly different kind of inclusion material was also present in skeletal muscle and tongue of horse Nos. 1 and 3. These inclusions were crystalline with a sharply defined ultrastructural periodicity. The crystals were eosinophilic and very dark blue when stained with toluidine blue but did not stain with iodine. Crystals sometimes occurred freely within the myofibers but more often were encased by deposits of amylopectin. This combination of histologic and ultrastructural features characterizes a previously unreported storage disease in fetal and neonatal Quarter Horses, with findings similar to those of glycogen storage disease type IV. We speculate that a severe inherited loss of glycogen brancher enzyme activity may be responsible for these findings. The relation of amylopectinosis to the death of the foals is unknown.
Inflammatory Pseudotumor in a Cat with Cutaneous Mycobacteriosis
Authors: Miller M. A. , Fales W. H. , Mccracken W. S. , O'Bryan M. A. , Jarnagin J. J. , Payeur J. B.
Published: April 2003

A 5-year-old, castrated male, domestic Shorthair Cat had an ulcerated mass with fistulous tracts on the left hind paw. Homogeneous tan tissue diffusely infiltrated the dermis and subcutis of the paw and extended proximally so that, short of amputation, complete excision was not feasible. Biopsy specimens consisted of granulation tissue with marked proliferation of spindle cells. Neutrophils and histiocytic cells were scattered among the spindle cells. The histiocytic cells had abundant foamy or vacuolated cytoplasm, but features of granulomatous inflammation, such as epithelioid macrophages or granuloma formation, were not observed. The initial impression was inflammatory granulation tissue, but the degree of fibroplasia prompted inclusion of fibrosarcoma in the differential diagnosis. Cutaneous mycobacteriosis was diagnosed when numerous acid-fast bacteria were identified with Kinyoun's stain; Mycobacterium avium was subsequently cultured. The cat was euthanatized because of lack of response to enrofloxacin therapy. At necropsy, lesions were localized to the hind limb. Not only is mycobacteriosis an uncommon cause of cutaneous masses in cats, but this case was unusual because of the lack of granuloma formation and the similarity of the mass to a spindle cell tumor.
Mucinous Vacuolar Change of Porcine Urothelium Induced by Regional Embolism or Cryoablation
Authors: Warner T. F. , Nakada S. Y. , y F. T. , Salisbury S. , Chosy S. G. , Moon T. D.
Published: April 2003

Porcine urinary tract epithelium responds to systemic infections with an increase in mucin secretion that has been called “mucinous degeneration.” Here we describe similar changes in calyceal, pelvic, and ureteric urothelium in pig renal tracts 14 days after local embolism and cryoablation (four kidneys) or cryoablation alone (six kidneys). Large mucin-filled vacuoles surrounded by smaller cytoplasmic vesicles were present in the affected urothelium but were rare in calyceal urothelium of normal kidneys. These mucinous vacuolar changes were proportional to the extent of renal necrosis and could be important in the pathologic responses of xenotransplanted pig kidneys.
Dysregulation of β-Catenin is Common in Canine Sporadic Colorectal Tumors
Authors: McEntee M. F. , Brenneman K. A.
Published: April 2003

Human colorectal tumorigenesis is often initiated by APC (adenomatous polyposis coli) or β-catenin (CTNNB1) mutations, which result in dysregulation of β-catenin expression, followed by alterations in E-cadherin and/or p53. We examined 32 canine intestinal tumors for expression and intracellular distribution of β-catenin, E-cadherin, and p53 using immunohistochemistry. β-Catenin in normal mucosal epithelial cells was restricted to lateral cell membranes, but 13/13 (100%) colorectal adenomas had intense cytoplasmic and/or nuclear reactivity. Three of six (50%) colorectal carcinomas, 2/13 (15%) small intestinal carcinomas, and dysplastic cells in 1/2 focal hyperplastic lesions in the small intestine had a similar pattern of staining; remaining tumors had normal membranous β-catenin reactivity. There was a correlation ( P = 0.007) between abnormal β-catenin and E-cadherin staining with 11/13 (85%) colorectal adenomas, 3/6 (50%) colorectal carcinomas, and 3/13 (23%) small intestinal carcinomas showing decreased membranous reactivity compared with normal mucosal epithelium. E-cadherin staining was reduced more often in adenomas than in carcinomas ( P = 0.04). There were two patterns of nuclear p53 staining: >60% of nuclei in 2/26 (8%) carcinomas (one colorectal, one small intestinal) were strongly labeled, whereas three colorectal adenomas and one small intestinal carcinoma had fainter staining in 10-20% of cells. Dysregulation of β-catenin appears to be as important in canine colorectal tumorigenesis as it is in the human disease and could be due to analogous mutations. Malignant progression in canine intestinal tumors does not appear to be dependent on loss of E-cadherin or β-catenin expression or strongly associated with overexpression of nuclear CM1 antibody-reactive p53.
Necrotizing Mycotic Vasculitis with Cerebral Infarction Caused by Aspergillus niger in a Horse with Acute Typhlocolitis
Authors: Tunev S. S. , Ehrhart E. J. , Jensen H. E. , Foreman J. H. , Richter R.-A. , Messick J. B.
Published: April 2003

An 18-year-old Morgan mare was presented to the Veterinary Medical Teaching Hospital, University of Illinois, with a 10-day history of watery diarrhea, depression, and dysphagia. On admission, the animal was severely dehydrated, depressed, and unable to swallow and had no clinical signs of diarrhea. The respiratory and heart rate and body temperature were within normal limits. Following fluid therapy, the mare developed severe watery diarrhea and continued to be depressed, incoordinated, and dysphagic. The animal died on the fourth day after admission and was sent to the Laboratories of Veterinary Diagnostic Medicine for necropsy. Gross postmortem findings were consistent with an acute cerebral infarction in the right cerebral hemisphere, an acute necrotizing typhlocolitis, multifocal petechial and ecchymotic hemorrhages, enlarged and congested pars intermedia of the pituitary gland, and marked bilateral adrenocortical hyperplasia with multifocal areas of necrosis and hemorrhage. Histologic evaluation of the affected brain demonstrated an area of coagulative necrosis of the gray matter, with hemorrhage, vasculitis, and thrombosis. There were many fungal hyphae 3.5–6.0 μm, pale basophilic, septate, and occasionally branching at 45° present in the arterial walls and throughout the necrotic tissue. Immunohistochemical analysis revealed Aspergillus niger as the etiologic agent responsible for the mycotic vasculitis and infarction in the brain. Bacteria culture and immunohistochemical staining of the colon and cecum failed to demonstrate specific pathogens.
Cryptococcus neoformans and Mycobacterium bovis Causing Granulomatous Pneumonia in a Goat
Authors: Gutiérrez M. , Marín J. F. García
Published: April 2003

An adult Blanca-Celtibérica doe originating from a goat herd with a high prevalence of tuberculosis was presented with respiratory signs. At necropsy, this goat had a diffuse and severe mycotic pneumonia associated with the presence of Cryptococcus neoformans concomitant with pulmonary focal caseous nodules from which Mycobacterium bovis was isolated. Microscopically, the mycotic lesion was a granulomatous pneumonia with many large foamy macrophages containing intracellular yeast bodies. The extensive mycotic changes, their granulomatous nature, and the lack of positive response to different immunologic tests for mycobacterial infection suggested an impaired immune status in this animal.
Secretory Carcinoma of the Canine Mammary Gland
Authors: Cassali G. D. , Gobbi H. , Gartner F. , Schmitt F. C.
Published: April 2003

Secretory carcinoma is an uncommon variant of breast cancer, characterized by the presence of intracellular and extracellular eosinophilic secretion. Here, we report the cytologic, histologic, and immunohistochemical findings of a secretory carcinoma diagnosed in the left inguinal mammary gland of a 3-year-old female German Shepherd Dog. The fine-needle aspiration cytology showed numerous large branching sheets of neoplastic cells and isolated cells with cytoplasmic vacuoles. Histologically, the tumor was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. These cells were arranged in solid or tubular structures with lumenal spaces filled with eosinophilic secretion. Immunohistochemical reactions to cytokeratin (CAM 5.2) and α-lactalbumin were strongly positive in all neoplastic cells, and staining for vimentin and S100 protein was negative. The cytomorphologic and immunohistochemical features of this tumor are similar to those seen in tumors in women, hence enabling the diagnosis of a rare case of primary secretory carcinoma of the canine mammary gland.
Immunoliistocliemical Detection of the Enzyme Glutamic Acid Decarboxylase and Hormones of the Islets of Langerhans in Spontaneous Insulin-dependent Diabetes Mellitus in Cattle
Authors: Taniyama H. , Oka S. , Yokota H. , Hirayama K. , Kagawa Y. , Kurosawa T. , Furuoka H. , Ono T.
Published: April 2003

Immunohistochemical expression of glutamic acid decarboxylase (GAD) enzyme was detected in the pancreatic islets of 12 cattle with spontaneous insulin-dependent diabetes mellitus (IDDM). The most characteristic changes were atrophy and decreased number of pancreatic islets, enlarged islets with vacuolated beta cells, and lymphocytic islet adenitis. Atrophied islets were composed of small islet cells without cytoplasmic insulin-positive granules. Immunohistochemically, GAD was not found in the cytoplasm of atrophied islet cells. Furthermore, enlarged islets consisting of islet cells with vacuolated cytoplasm were frequently observed. The cytoplasm of vacuolated cells contained very few GAD- and insulin-positive granules, indicating beta cell destruction. Enlarged islets with mild lymphocytic infiltrates were frequently observed. These findings suggest that islet cells in cattle with IDDM lose their insulin synthesis function and their ability to regulate hormonal secretion of alpha and delta cells.
Oxalate-producing Pulmonary Aspergillosis in an Alpaca
Authors: Muntz F. H. A.
Published: April 2003

An aging lactating alpaca was presented in sternal recumbency. Although bright and alert, she did not respond to symptomatic treatment and was euthanized 5 weeks after initial presentation. Gross postmortem examination revealed purulent material in the pulmonary airways. Histologic examination of the lungs revealed an extensive pyogranulomatous pneumonia with bronchiectasis. There were abundant fungal hyphae and high numbers of associated oxalate crystals, which were presumed to have been produced by the fungus. Low numbers of yeast cells were also present. Microbiological culture of tissues on horse blood agar and Sabouraud's agar identified the fungus to be Aspergillus niger. There was also moderate growth of Candida albicans. Calcium oxalate crystals in cytologic and histologic preparations can suggest an underlying Aspergillus infection. This is the first reported veterinary case of pneumonia due to Aspergillus niger infection and the associated production of oxalate crystals.
Theileriosis in a Missouri Beef Herd Caused by Theileria buffeli
Authors: Stockham S. L. , Kjemtrup A. M. , Conrad P. A. , Schmidt D. A. , Scott M. A. , Robinson T. W. , Tyler J. W. , Johnson G. C. , Carson C. A. , Cuddihee P.
Published: April 2003

A 6-year-old Simmental cow infected with Theileria buffeli had a clinical disease characterized by theilerial parasitemia, macrocytic normochromic anemia with acanthocytosis and spherocytosis, lymphoid hyperplasia (lymphocytosis, edematous lymphadenomegaly), dysproteinemia, evidence of liver disease, and a low serum antibody titer against T. buffeli. The cow was in a herd in which all cattle originated in Missouri; 22/75 (29%) of cattle had a theilerial parasitemia and 26/75 (35%) had titers to T. buffeli of ≥1:160. Classification of the Missouri bovine organism as T. buffeli was based on DNA sequencing and comparison to sequences for T. buffeli and Theileria sp. type A obtained from GenBank. Intraerythrocytic veils and piroplasms were seen during transmission electron microscopy. The organism was successfully transmitted to two splenectomized calves, which developed mild anemias while parasitemic. Blood from the second calf was used as the source of T. buffeli antigen for an indirect immunofluorescence antibody test. Theilerial isolates from a Missouri white-tailed deer were also sequenced and resembled Theileria sp. types F and G and were not consistent with the bovine organism.
In Situ Hybridization for the Detection and Localization of Porcine Epidemic Diarrhea Virus in the Intestinal Tissues from Naturally Infected Piglets
Authors: Kim O. , Chae C.
Published: April 2003

Detection and localization of porcine epidemic diarrhea virus (PEDV) was studied by in situ hybridization with a nonradioactive digoxigenin-labeled probe in formalin-fixed, paraffin-embedded tissues from 10 naturally infected piglets. A 377-base pair cDNA probe for viral RNA encoding the membrane proteins of PEDV cell-culture-adapted strain V215/78 was generated by the reverse transcription polymerase chain reaction. In the retrospective study of pigs from herds with diarrhea, the 10 piglets naturally infected with PEDV had positive signals for PEDV by in situ hybridization. When intestinal tissues were hybridized with the PEDV probe, a strong signal was seen in the villus enterocytes of jejunum and ileum but not in the cecum and colon. Positive cells typically had dark brown reaction products in the cytoplasm. Scattered epithelial cells along the ileal Peyer's patches dome areas contained viral RNA. In one piglet, hybridization signal was also found in the duodenum. PEDV was not demonstrated in tissues outside of the intestinal tract. These findings indicate that jejunal and ileal villus enterocytes are the main target of PEDV replication during epizootic outbreaks of the disease.
Immunohistologic Detection of Estrogen Receptor Alpha in Canine Mammary Tumors: Clinical and Pathologic Associations and Prognostic Significance
Authors: Nieto A. , Peña L. , Pérez-Alenza M. D. , Sánchez M. A. , Flores J. M. , Castaño M.
Published: April 2003

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-α) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3–4 months. ER-α expression was higher in tumors of genitally intact and young bitches ( P < 0.01, P < 0.01) and in animals with regular estrous periods ( P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-α ( P = 0.04). Immunoexpression of ER-α decreased significantly with tumor size ( P = 0.05) and skin ulceration ( P = 0.01). Low levels of ER-α were significantly associated with lymph node involvement ( P < 0.01). Malignant tumors had lower ER-α expression than did benign tumors ( P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-α scores ( P = 0.05) in all tumors. Low ER-α levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up ( P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-α value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-α index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-α in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.
A Subependymal Giant Cell Astrocytoma in a Cat
Authors: Duniho S. , Schulman F. Y. , Morrison A. , Mena H. , Koestner A.
Published: April 2003

A 6-year-old spayed female Domestic Shorthair cat presented with a 1 to 2-month history of blindness and altered behavior. At necropsy, a 1-cm-diameter, firm white mass was found arising from the subependymal region of the right lateral ventricular wall that protruded into and partially filled the lumen. Histologically, there was a well-demarcated, expansile paraventricular neoplasm composed of moderately pleomorphic cells within a richly fibrillar matrix arranged in interlacing streams and perivascular pseudorosette-like patterns. Neoplastic cells varied in morphology from small spindloid cells to larger polygonal cells with eccentric vesicular nuclei to neuronlike cells with vesicular nuclei and prominent nucleoli. The mitotic index was low. Immunohistochemically, neoplastic cells were positive for S-100 protein, glial fibrillary acidic protein, and neuron-specific enolase and negative for neurofilament protein. Ultrastructurally, the cells contained few to abundant bundles of intermediate filaments with variable numbers of mitochondria, endoplasmic reticulum, and ribosomes. These features are characteristic of subependymal giant cell astrocytoma (SEGA) in humans. To our knowledge, this is the first reported case of SEGA in domestic animals.
Vascular Ultrastructure and DNA Fragmentation in Swine Infected with Shiga Toxin-Producing Escherichia coli
Authors: Matise I. , Sirinarumitr T. , Bosworth B. T. , Moon H. W.
Published: April 2003

Shiga toxins (Stx) produced by Escherichia coli cause systemic vascular damage that manifests as edema disease in swine and hemolytic uremic syndrome in humans. In vitro, Stx inhibit protein synthesis and, depending on circumstances, induce necrosis, apoptosis, or both. The mechanism of in vivo Stx-mediated vascular damage is not known. The ability of Stx to cause apoptosis of vasculature in vivo was studied in pigs with edema disease that was produced by oral inoculation with Stx-producing E. coli. Arterioles of ileum and brain were evaluated by terminal dUTP nick-end labeling (TUNEL) assay for DNA fragmentation in myocytes (10 infected pigs, 5 control pigs) and by transmission electron microscopy for ultrastructural changes characteristic of apoptosis (17 infected pigs, 8 control pigs). In comparison with controls, increased numbers of TUNEL-positive arterioles were detected in 6/10 (60%) subclinically affected pigs 14–15 days after inoculation. Ultrastructurally, lesions in myocytes consisted of lysis (necrosis), with cytoplasmic debris and nuclear fragments contained between intact basement membranes. Endothelial cell changes ranged from acute swelling to necrosis and detachment from basement membrane. Subclinically affected pigs (n = 14) tended to have changes predominantly in myocytes, whereas pigs with clinical illness (n = 3) more commonly had changes in endothelial cells. The arteriolar lesions and clinical signs of edema disease are attributed to the effects of Stx on vasculature. Therefore, our findings suggest that the Stx-induced arteriolar lesions seen in this study were primarily necrotic, not apoptotic. We suspect that necrosis was the principal cause of the DNA fragmentation detected.
Rudimentary Hemidesmosome Formation in Congenital Generalized Junctional Epidermolysis Bullosa in the Sprague-Dawley Rat
Authors: Brenneman K. A. , Olivry T. , Dorman D. C.
Published: April 2003

Seven of 14 newborn pups in a litter of Sprague-Dawley rats were found to have generalized detachment of the epidermis, which was thin, wrinkled, and hung in loose folds over distal extremities. Histologic and ultrastructural examination of the skin showed noninflammatory separation of the epidermis from the dermis at the lamina lucida of the basement membrane zone. Ultrastructurally, hemidesmosomes were small and had a rudimentary appearance; keratin tonofilaments in basal keratinocytes were detached from the hemidesmosomes. The skin lesions were consistent with generalized junctional epidermolysis bullosa, which has not previously been reported in the rat. In humans, generalized junctional epidermolysis bullosa is most commonly caused by autosomal recessive inheritance of defective proteins of the hemidesmosomes or anchoring filaments. The specific protein defect involved in the rat lesion was not determined because fresh frozen tissue was not available.
Synovial Sarcoma in an Ayrshire Heifer
Authors: Tremblay C. , Girard C. , Dubreuil P. , Desrochers A. , Lanevschi A.
Published: April 2003

An 8-month-old Ayrshire heifer had a rapidly growing mass in the axillary region of the left thoracic limb. The mass surrounded the distal humerus and entrapped nerves of the brachial plexus, causing an abnormal gait. Histologically, the mass was composed of clusters and cords of round to polygonal cells with scattered, spindle-shaped cells. The neoplastic cells stained positively for vimentin and cytokeratin. No staining was found with S-100 protein, kappa and lambda light chains, or T-cell markers by immunohistochemistry. On electron microscopic evaluation, the cytoplasm of the neoplastic cells contained few organelles, principally rough and smooth endoplasmic reticulum and mitochondria. This synovial sarcoma has histologic and ultrastructural features characteristic of the poorly differentiated subtype of synovial sarcoma in the human classification system.
Multiple Myeloma in Cats: Variable Presentation with Different Immunoglobulin Isotypes in Two Cats
Authors: Bienzle D. , Silverstein D. C. , Chaffin K.
Published: April 2003

Multiple myeloma was diagnosed in two cats with monoclonal hyperglobulinemia, proteinuria, and plasma cell proliferations in bone marrow. An immunoglobulin G-producing myeloma occurred in the vertebral bone marrow of one cat, and twice responded to surgical reduction followed by a combination of local irradiation and chemotherapy. The cat's survival time was approximately 2 years. The other myeloma in a cat that presented with hypercalcemia and renal insufficieny involved visceral organs and produced a biclonal peak due to immunoglobulin A dimer formation on serum electrophoresis. This cat's tumor did not respond to chemotherapy.
Detection of Chelonid Herpesvirus DNA by Nonradioactive in Situ Hybridization in Tissues from Tortoises Suffering from Stomatitis—Rhinitis Complex in Europe and North America
Authors: Teifke J. P. , Löhr C. V. , Marschang R. E. , Osterrieder N. , Posthaus H.
Published: April 2003

Chelonid herpesvirus (ChHV) infection in tortoises associated with stomatitis-rhinitis complex is a severe, mostly epizootic disease characterized by proliferative and diphtheroid-necrotizing glossitis, pharyngitis, rhinitis, and tracheitis, often occurring with pneumonia and encephalitis. The UL5 gene from a German ChHV isolate was used to generate a digoxigenin-labeled 307-base-pair DNA probe by polymerase chain reaction (PCR). ChHV DNA was detected in paraffin-embedded tissues of five naturally infected tortoises (two Afghan tortoises [ Testudo horsfieldii], USA; two Hermann's tortoises [ Testudo hermanni], Switzerland; one T. hermanni, Germany) by means of in situ hybridization (ISH) and PCR. Distribution of ChHV DNA exhibits many characteristics of alphaherpesvirus but also some characteristics of betaherpesvirus infections. The amino acid sequence of a portion of the ChHV UL5 homolog exhibited more than 50% similarity to alphaherpesvirus UL5 proteins. Nuclear hybridization signals were detected in epithelial cells of the lingual mucosa and glands. Furthermore, ChHV DNA was observed in tracheal epithelium, pneumocytes, hepatocytes, the renal tubular epithelium, cerebral glia cells and neurons, and intramural intestinal ganglia. ChHV DNA in endothelial cells of many organs underlines the systemic character of the disease. Importantly, ChHV DNA was detected by ISH in multiple tissues of tortoises originating from different geographic provenances. This indicates a high degree of conservation of the UL5 gene fragment among viruses prevalent in tortoises on different continents. With the described ISH, a molecular biological tool is available for rapid and specific diagnosis of ChHV infections and, more importantly, comparative pathogenetic studies of ChHV isolates from geographically unrelated regions.
Anti-plakin and Desmoglein Autoantibodies in a Dog with Pemphigus Vulgaris
Authors: Olivry T. , Alhaidari Z. , Ghohestani R. F.
Published: April 2003

Paraneoplastic pemphigus was suspected in a 14-year-old Labrador retriever because of mucocutaneous erosions, microscopic suprabasal acantholysis, and keratinocyte apoptosis. In this patient, circulating IgG autoantibodies recognized plakin (envoplakin, periplakin) and desmoglein (desmoglein-1 and −3) antigens. Necropsy, however, failed to confirm the concurrent existence of hematopoietic or solid neoplasia. The diagnosis of pemphigus vulgaris therefore was proposed. This study illustrates that such a combination of clinicopathologic lesions and plakin/desmoglein-specific autoantibodies is not restricted to canine paraneoplastic pemphigus but can also be detected in another form of suprabasal pemphigus.
Cyclooxygenase-2 Expression in Inflammatory Lung Lesions of Nonhuman Primates
Authors: M. Khan K. N. , Stanfield K. , Trajkovic D. , Harris R. K.
Published: April 2003

Mammalian cells contain two related but unique isoforms of cyclooxygenase (COX-1 and COX-2). COX-1 is expressed constitutively in a majority of tissues and is involved in the production of prostaglandins (PGs) that modulate normal physiologic functions. COX-2 is inducible by various stimuli and is involved in the production of PGs that modulate physiologic events in development, cell growth, and inflammation. With the exception of peribronchial glands and chondrocytes of peribronchial cartilage, COX-2 is not detectable in the normal lung of nonhuman primates. We evaluated COX-2 expression by immunohistochemical methods in the inflammatory lesions of two cynomolgus monkeys ( Macaca fascicularis) with acute severe pneumonia. Both monkeys exhibited acute severe bronchopneumonia; histologically, lung lesions were characterized by infiltration of large numbers of neutrophils and fewer macrophages, mild bronchial epithelial hyperplasia, and slight type-2 pneumocyte hyperplasia. In both monkeys, mild to marked COX-2 immunoreactivity was detected within the cytoplasm of macrophages, bronchial epithelial cells, type-2 pneumocytes, and endothelial cells of blood vessels. No COX-2 immunoreactivity was detectable in the neutrophils that constituted >90% of the inflammatory cells. These observations suggest that in acute inflammatory lung lesions in nonhuman primates 1) COX-2 is induced in the bronchial and alveolar epithelial cells, 2) macrophages are the primary inflammatory cells that exhibit COX-2, and 3) neutrophils do not express COX-2.