bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs
Authors: Vana G. , Meingassner J. G.
Published: April 2003

Many preclinical studies in investigative dermatology are performed preferably in pigs because pig skin is more similar to human skin than is rodent skin. A frequently used model is allergic contact dermatitis (ACD); however, this T-cell—mediated skin condition so far is not well characterized in pigs. The present study is aimed at the evaluation of morphologic and immunohistochemical features of experimentally induced acute ACD in Göttingen minipigs using 2,4-dinitrofluorobenzene (DNFB) as a hapten. Eight minipigs were sensitized with 10% DNFB and challenged 2 weeks later at different sites with 1% DNFB. In addition to clinical examinations, cutaneous blood flow was quantified by laser Doppler velocimetry (Periflux PF3). These examinations were performed before challenge and 8, 24, 48, and 72 hours after challenge. Skin biopsies were taken at the same time points, fixed, sectioned, and stained with Giemsa for histologic evaluation, or with mouse anti-swine monoclonal antibodies (CD1, CD2, CD4, CD5, CD8, CD25, CD45, MHCII) and with one mouse anti-human monoclonal antibody (CD62E) cross-reacting with swine for immunohistochemical evaluation. Positively stained cells were counted per square millimeter of epidermis and dermis by using a video image analyzing system (Videoplan Kontron). Erythema and cutaneous blood flow peaked at 24 hours. The major epidermal changes most pronounced at 48 hours were acanthosis, spongiosis, intracellular edema, exocytosis, and abscesses mainly containing neutrophils and mononuclear cells (MNC). Perivascular infiltrates of MNC as well as neutrophils and eosinophils were the most significant dermal changes, with peak levels at 24–48 hours. In biopsies taken before challenge, CD1+ dendritic cells were found in similar numbers and locations as MHCII+ cells in the epidermis. In the epidermis the maximum CD1+ cell decrease occurred at 24 hours whereas in the dermis the maximum increase in CD1+ stained cells was seen at 72 hours. The dermal infiltrate (CD2+, CD5+, CD25+, and CD45+) was most dense at 48 hours. Between 8 and 48 hours more CD4+ were present than CD8+ cells, whereas at 72 hours CD4+ and CD8+ cells were similar in numbers. These findings closely resemble changes in human ACD. Therefore, DNFB-induced ACD in Göttingen minipigs is considered to be an appropriate animal model to study immunopathologic mechanisms and pharmacologic intervention.
Spontaneously Occurring Hepatocellular Neoplasia in Adolescent Cynomolgus Monkeys (Macaca fascicularis)
Authors: Reindel J. F. , Walsh K. M. , Toy K. A. , Bobrowski W. F.
Published: April 2003

Spontaneous hepatic neoplasms were identified in two adolescent (<5 years of age) male cynomolgus monkeys ( Macaca fascicularis). Monkey No. 1 had a solitary hepatocellular carcinoma (HCC). Monkey No. 2 had multiple discrete tumors consisting of several poorly circumscribed HCCs and a mixed hepatocholangiocellular carcinoma (MHC). Metastases were not evident in either monkey. Histochemical and immunohistochemical stains were used to assess phenotypic alterations in the tumors. Many or most neoplastic hepatocytes (NHs) of both monkeys stained positive for low-molecular-weight cytokeratin (LMWCK), cytokeratin (CK) 8, and CK 18. In monkey No. 1, small aggregates of NHs were positive for carcinoembryonic antigen (CEA), glutathione S-transferase- pi (GST), and α-fetoprotein (AFP), but NHs were uniformly negative for CK 7. NHs in monkey No. 2 were negative for CEA and AFP but were multifocally positive for GST and CK 7. Broad-spectrum cytokeratin (BSCK), high-molecular-weight cytokeratin (HMWCK), and CK 19 did not react with NHs of either animal. Neoplastic cells forming ductlike structures in the MHC of monkey No. 2 stained with LMWCK, CK 7, CK8, CK 18, BSCK, and GST but not with HMWCK or CK 19. Tumors in both monkeys had enhanced pericellular fibronectin staining. Nonneoplastic parenchyma of both monkeys contained multiple discrete foci of cellular alteration and scattered aggregates of hepatocytes with strong cytoplasmic staining for fibronectin. Staining patterns of these tumors demonstrate immunophenotypic heterogeneity of the neoplastic cells within individual tumors and variability among tumors. This information may serve as a useful reference for others encountering similar lesions in primates.
Retrospective Study of Porcine Circovirus 2 Infection in Japan: Seven Cases in 1989
Authors: Mori M. , Sato K. , Akachi S. , Asahi S. , Taniguchi S. , Narita M.
Published: April 2003

Retrospectively, we demonstrated that seven pigs necropsied in 1989 had characteristic porcine circovirus 2 (PCV-2) lymphoid tissue lesions of severe lymphoid depletion, syncytial giant cell formation, and intracytoplasmic inclusion bodies in macrophages. Immunohistochemically, PCV-2 antigen was detected in these tissues and the distribution of positive staining corresponded to the distribution of inclusion bodies. Electron microscopy demonstrated viral particles compatible with porcine PCV-2. Therefore, the disease occurred in Japan as early as 1989.
Congenital Hepatic Fibrosis and Cystic Bile Duct Formation in Swiss Freiberger Horses
Authors: Haechler S. , G. A. M. Van den Ingh T. S. , Rogivue C. , Ehrensperger F. , Welle M.
Published: April 2003

Congenital hepatic fibrosis with autosomal recessive or dominant inheritance has been described in humans, cats, piglets, and dogs. In horses, only two cases of congenital hepatic fibrosis have been previously reported. This retrospective study of records from the Institute for Animal Pathology, University of Berne, identified 30 foals with liver lesions compatible with congenital hepatic fibrosis. Anamnestic data revealed clinical signs of severe liver injury in most affected animals. Pathologic examination showed severely enlarged, firm livers with thin-walled cysts. Histologically, the livers showed diffuse porto-portal bridging fibrosis with many small, irregularly formed and sometimes cystic bile ducts. All foals belonged to the Swiss Freiberger breed. Pedigree analysis revealed that the diseased animals could be traced back to one stallion. These results strongly suggest that congenital hepatic fibrosis in Swiss Freiberger horses is a recessively inherited autosomal genetic defect.
Fatal Nonneurological EHV-1 Infection in a Yearling Filly
Authors: Del Piero F. , Wilkins P. A. , Timoney P. J. , Kadushin J. , Vogelbacker H. , Lee J. W. , Berkowitz S. J. , D. La Perle K. M.
Published: April 2003

A case of fatal nonneurological equine herpesvirus 1 (EHV-1) infection in a yearling filly is described. Gross lesions included extensive pulmonary edema, prominent laryngeal lymphoid follicles, and congestion and edema of the dorsal third ventricle choroid plexus. Histologically, there was vasculitis, hemorrhage, and edema in the lungs and dorsal third ventricle choroid plexus as well as mild intestinal crypt necrosis with occasional intranuclear inclusion bodies. The perivascular and vascular inflammatory infiltrates were comprised mainly of T lymphocytes and macrophages. EHV-1 antigen was identified within the nucleus and cytoplasm of endothelial cells, dendritic-like cells of the pharyngeal lymphoid follicles, pharyngeal glandular epithelium, crypt enterocytes, and monocytes. Attempted virus isolation was negative. Weak seroconversion for EHV-1 was observed. Herpesvirus-like particles were identified within pharyngeal endothelial cells by transmission electron microscopy. Polymerase chain reaction amplified 369 and 188 base-pair fragments specific for EHV-1. The scarcity of pathognomonic viral inclusions and lesions in this case suggests that this disease may not be recognized, particularly in situations when ancillary laboratory procedures are limited.
Hepatitis and Staging of Hepatic Damage in Pigs Naturally Infected with Porcine Circovirus Type 2
Authors: Rosell C. , Segalés J. , Domingo M.
Published: April 2003

A total of 100 liver samples from pigs with postweaning multisystemic wasting syndrome (PMWS) were studied. All livers were evaluated microscopically and were staged based on the severity and localization of lesions. Presence of porcine circovirus type 2 (PCV-2) was evaluated using an in situ hybridization technique. Eighty-eight of 100 livers (88%) had a variable degree of lymphohistiocytic hepatitis, with apoptotic bodies, disorganization of hepatic plates, and/or perilobular fibrosis. Twelve pigs did not have microscopic liver lesions. Four stages of hepatic damage were established based on intensity and distribution of the lesions. Viral nucleic acid was detected in 70 of 100 livers (70%). Target cells for PCV-2 infection included Kupffer cells, hepatocytes, and inflammatory infiltrates. According to distribution of PCV-2 nucleic acid, four basic labeling patterns were identified. This study shows that liver damage is a frequent microscopic finding in cases of PMWS and hepatocytes are a target cell for PCV-2 infection and replication. Therefore, PCV-2 should be considered a new hepatitis-inducing viral agent in pigs.
Necrotizing Meningoencephalitis Associated with Cortical Hippocampal Hamartia in a Pekingese Dog
Authors: Cantile C. , Chianini F. , Arispici M. , Fatzer R.
Published: April 2003

A 4-year-old male Pekingese dog was referred to the clinic with a history of recurrent seizures and progressive abnormal gait and behavior, which did not respond to treatment. At necropsy, a large cortical defect in the right temporo-parietal cortex, malacia of subcortical white matter, right basal nuclei, and capsula interna, as well as abnormalities of the right hippocampus were observed. Histological examination of the brain revealed moderate to severe nonsuppurative meningoencephalitis in the left cerebral hemisphere and extensive infarction-like lesions with milder inflammation in the right hemisphere. In the right hippocampus, the pyramidal cells were arranged in a gyrus-like pattern and intermingled with gemistocytic and fibrillary astrocytes. The histopathological features of the inflammatory lesions were consistent with necrotizing meningoencephalitis and resembled those described in so-called Pug dog encephalitis. The hippocampal changes were interpreted as dysplasia (monolateral hippocampal cortical hamartia), unrelated to clinical signs and necrotizing inflammatory lesions.
Demonstration of Akabane Virus Antigen Using Immunohistochemistry in Naturally Infected Newborn Calves
Authors: Noda Y. , Yokoyama H. , Katsuki T. , Kurashige S. , Uchinuno Y. , Narita M.
Published: April 2003

Eight newborn calves showing ataxia were necropsied and examined histologically. Six of seven cerebrospinal fluid samples collected from these animals had neutralizing antibody for Akabane virus (AKV). All examined calves had nonsuppurative encephalomyelitis, localized mainly in the midbrain and spinal cord. Corresponding to the encephalitic lesion, AKV antigen was demonstrated in neuroglial cells in the brain stem and neuronal cells in the ventral horn of the spinal cord. This is the first study to demonstrate AKV antigen by immunohistochemistry in naturally infected newborn calves.
Diffuse Leptomeningeal Malignant Histiocytosis in the Brain and Spinal Cord of a Tibetan Terrier
Authors: Uchida K. , Morozumi M. , Yamaguchi R. , Tateyama S.
Published: April 2003

An 8-year-old male Tibetan Terrier showed prolonged astasia, complete paralysis, ticlike signs, and seizure and died 2 months after the onset of symptoms. Histopathologically, there was moderate to severe infiltration of pleomorphic histiocytic mononuclear cells bilaterally in the basiarachnoidal and ventricular areas of the brain. The spinal dura mater, arachnoidal space, and leptomeninges were also affected by infiltrative proliferation of these mononuclear cells. The infiltrating cells had the morphologic characteristics of histiocytes but exhibited moderate pleomorphism and atypia, with abundant mitotic figures. With immunohistochemistry and lectin histochemistry, most of the infiltrating cells were positive for lysozyme and lectin RCA-1 and negative for glial fibrillary acid protein, suggesting that they were of monocytic/histiocytic-origin. Positive proliferating cell nuclear antigen immunostaining demonstrated that most nuclei of the histiocytic cells were in the S phase of the cell cycle, consistent with a proliferating population of cells. Based on these findings, the case was diagnosed as diffuse leptomeningeal malignant histiocytosis.
Septicemia and Peritonitis Due to Actinobacillus equuli Infection in an Adult Horse
Authors: Patterson-Kane J. C. , Donahue J. M. , Harrison L. R.
Published: April 2003

Actinobacillus equuli is a rare cause of peritonitis in adult horses. Septicemia and peritonitis due to A. equuli were diagnosed at necropsy in an 8-year-old Saddlebred mare. The origin of the infection was not known; however, small necrotic colonic mucosal lesions presumed to have been caused by phenylbutazone treatment may have allowed bacterial invasion. A good response to antimicrobial treatment has been documented in the small numbers of previously reported acute cases of peritonitis. Because it is potentially treatable, it is important for pathologists and clinicians to identify horses with A. equuli peritonitis.
Naturally Occurring Spirochetes in the Colonic Mucosa of Raccoons (Procyon lotor)
Authors: Hamir A. N. , Trott D. , Palmer M. , Stasko J.
Published: April 2003

The large intestines of 21 raccoons ( Procyon lotor; 11 wild caught, 10 laboratory confined) were examined for the presence of intestinal spirochetes. Light microscopy of sections stained with hematoxylin and eosin and Warthin-Starry stain showed the presence of spiral shaped organisms deep within the lumina of intestinal glands at the ileocolonic junction of 16 raccoons (76% prevalence). All laboratory-confined, grouphoused raccoons harbored the organisms, but only 6/11 (55% prevalence) live-trapped raccoons were positive for these spirochetes. The organisms were free in the glandular lumina, and there were no microscopic lesions. Two types of spirochetes were identified in the colonic glands: a slender spirochete 10-13 μm in length, 0.3 mm in diameter, and possessing long, thin tapered ends and a larger, regularly waved spiral organism (0.5 μm in diameter). The slender spirochete did not resemble any of the known spirochete genera and failed to grow on medium used to propagate oral treponemes and members of the genus Brachyspira.
Pulmonary Expression of Tumor Necrosis Factor Alpha, Interleukin-1 Beta, and Interleukin-8 in the Acute Phase of Bovine Pneumonic Pasteurellosis
Authors: Malazdrewich C. , Ames T. R. , Abrahamsen M. S. , Maheswaran S. K.
Published: April 2003

Inflammatory cytokines are suspected to contribute to the pathogenesis of bovine pneumonic pasteurellosis (BPP) through neutrophil recruitment, leukocyte activation, and the induction of a broad array of soluble inflammatory mediators. An in vivo experimental model of BPP was used to characterize the pulmonary expression kinetics of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) genes and proteins during the acute phase of disease development. Cytokine expression in bronchoalveolar lavage (BAL) fluid, BAL cells, and pneumonic lung parenchyma was quantitated by northern blot analysis, enzyme-linked immunosorbent assay (ELISA), and in situ hybridization at 2, 4, 8, 16, and 24 hours after endobronchial inoculation of Pasteurella (Mannheimia) haemolytica. Expression of TNFα, IL-1β, and IL-8 was significantly increased in the airways and lung lesions of infected calves as compared with mock-infected controls. Although kinetic patterns varied, peak levels of cytokine mRNA occurred within 8 hours postinfection (PI), and peak cytokine concentrations occurred within 16 hours PI. In all samples, IL-8 was expressed to the greatest extent and TNFα was least expressed. Expression of TNFα was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1β and IL-8 in the first 4 hours; bronchial and bronchiolar epithelial cells were also significant sources of IL-8 during this period. By 8 hours PI, neutrophils were the dominant source of both IL-1β and IL-8. These findings demonstrate a spatial and temporal association between pulmonary expression of inflammatory cytokines and acute lung pathology, supporting the hypothesis that cytokines contribute to inflammatory lung injury in BPP.
Spontaneous Eosinophilic Granulated Round Cell Tumors in Rats
Authors: Nagatani M. , Nakamura A. , Yamaguchi Y. , Aikawa T. , Tamura K.
Published: April 2003

Morphologic and histochemical characteristics were noted for three spontaneous tumors with eosinophilic cytoplasmic granules that occurred in aged Fischer 344 rats. Macroscopic lesions were widely distributed in the body, mainly involving the intra-abdominal adipose tissue, pancreas, and mesenterium. These lesions were generally hard swellings with nodular and sclerosing areas. Bloody ascites was a concomitant finding. Histologically, the tumor cells were round, from 9 to 30 μm in diameter with one or two round to oval nuclei, and characterized by eosinophilic granules (0.5–2.0 μm) that stained definitely to weakly positive with the periodic acid-Schiff reaction and demonstrated no metachromasia with toluidine blue stain. Furthermore, the granules were characterized by a positive reaction with lectin histochemistry for concanavalin A (Con A), wheat germ agglutinin (WGA), phaseolus vulgaris agglutinin (PHA-E4), lens culinaris agglutinin (LCA), and recinus communis agglutinin (RCA-I) in all tumors and for ulex europaeus agglutinin (UEA-I), peanut agglutinin (PNA), and soybean agglutinin (SBA) in one tumor. Positive reactions for anti-rat mast cell protease II and CD8 were not demonstrated immunohistochemically. Abundant glycogen was noted in the large tumor cells from one rat. With electron microscopy, the cytoplasmic granules were identified as electron-dense homogenous bodies bounded by a single unit membrane. These characteristics are similar to those of granulated metrial gland cells, but further study is needed to clarify the cell of origin for these tumors.
Immunohistopathologic Demonstration of Pleuropneumonia Associated with Morganella morganii in a Piglet
Authors: Ono M. , Namimatsu T. , Ohsumi T. , Mori M. , Okada M. , Tamura K.
Published: April 2003

Serofibrinous pleuropneumonia in a piglet was examined microbiologically and immunohistopathologically. Large numbers of Morganella morganii were isolated from the pneumonic lesion, but no other pathogens were identified. A large amount of M. morganii antigen was demonstrated, and its distribution was closely associated with the histologic lesion. This finding suggests that pleuropneumonia in piglets might be caused by M. morganii.
Hepatic Failure and Hemochromatosis of Salers and Salers-cross Cattle
Authors: O'Toole D. , Kelly E. J. , McAllister M. M. , Layton A. W. , Norrdin R. W. , Russell W. C. , Saeb-Parsy K. , Walker A. P.
Published: April 2003

Hemochromatosis is rare in domestic mammals. Five clinical cases and one preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross cattle. Clinical disease developed between 9 and 22 months of age. Animals were healthy until weaning but then lost weight, developed rough hair coats, and lost incisor teeth. In two animals, hemochromatosis was identified by liver biopsy, biochemical evidence of hepatic injury, and/or elevated transferrin saturation values. At necropsy, carcasses were thin, with firm dark brown livers and lymph nodes, soft bones, and brown-colored small bowel. The principal histologic changes were hepatocellular siderosis and periportal, bridging, and perivenular fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic iron concentrations in clinically affected cattle were 1,500–10,500 μg/g wet weight (reference range for cattle = <300 μg/g). Ultrastructurally, the heaviest intrahepatic deposition was in hepatocytes, which contained large intracytoplasmic siderosomes. Iron deposition in bone was associated with osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees of five of six affected cattle; no pedigree was available for the remaining animal. Four dams of five affected animals were phenotypically normal and had histologically normal livers. Test mating of four cows to the ancestral bull resulted in a female calf that developed clinicopathologic and histologic evidence of preclinical hemochromatosis by 40 days of age. It was not possible to establish the pattern of inheritance because of the small number of pedigrees from affected cattle.
Expression of S100a, Vimentin, NSE, and Melan A/MART-1 in Seven Canine Melanoma Cell Lines and Twenty-nine Retrospective Cases of Canine Melanoma
Authors: Koenig A. , Wojcieszyn J. , Weeks B. R. , Modiano J. F.
Published: April 2003

We evaluated the expression of vimentin, S100a, and Melan A/MART-1 (melanoma antigen recognized by T cells 1) in seven cell lines established independently from dogs with canine melanoma. We also compared routine immunostaining of 29 clinical specimens from melanoma cases using vimentin, S100a, and neuron-specific enolase (NSE) with staining for Melan A/MART-1 as part of a diagnostic panel. All the cell lines were positive for expression of vimentin and S-100a. MelanA/MART-1 expression was seen consistently in only two of the seven cell lines. Staining for Melan A/MART-1 was most intense near areas of heavy melanin pigmentation. All except one of the clinical specimens were positive for vimentin. S100a was expressed in the majority of both pigmented (15/20, 75%) and amelanotic (8/9, 88.8%) tumors. Seventeen of 29 (58.6%) tumors were positive for NSE. Melan A/MART-1 was expressed in 18/29 (62%) tumors, including 90% of pigmented tumors, but in no amelanotic tumors. Intensity of Melan A/MART-1 staining correlated positively with biologic behavior, with seven malignant tumors showing negative to weak staining and 10 benign tumors showing moderate to strong staining. Three malignant tumors showed moderate to intense staining for Melan A/ MART-1. Our results suggest that expression of Melan A/MART-1 may be unstable in cultured cell lines. Assessment of both S100a and Melan A/MART-1 expression is useful to confirm a diagnosis of canine melanoma, and Melan A/MART-1 may be especially informative regarding the biologic behavior of these tumors.
Atypical Membranoproliferative Glomerulonephritis in a Cat
Authors: Inoue K. , Kami-ie J. , Ohtake S. , Wakui S. , Machida S. , Shirota K.
Published: April 2003

Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals.
CD1-The Pathology Perspective
Authors: Rhind S. M.
Published: April 2003

CD1 molecules are a family of cell surface-associated glycoproteins now recognized as having a role in antigen presentation. These glycoproteins are distinct from yet have some similarities to classical major histocompatibility complex class I and class II molecules. The role of these molecules has been studied in detail over recent years, with an explosion of interest following the demonstration that they can present nonprotein antigens to certain subpopulations of T cells. The purpose of this paper is to provide an overview of current knowledge of the function of the CD1 family with specific emphasis on the potential role in the pathogenesis of certain diseases. Although much of the current research in this field has inevitably concentrated on mice and humans, this work also has potential significance for veterinary species.
Streptozocin-induced Pancreatic Islet Destruction in Beef Cows
Authors: Higdon H. L. , Parnell P. G. , Hill J. E. , Spitzer J. C.
Published: April 2003

Streptozocin (STZ) induces diabetes mellitus in sheep and pigs. To test the effect of STZ in cattle, cows were given 75–150 mg STZ per kilogram of body weight. Cows receiving 150 mg/kg required euthanasia within 24 hours after infusion because of the severe systemic effects of STZ. Seven cows receiving doses of ≤100 mg/kg had mild to marked decrease in islet immunoreactivity for insulin and in pancreatic islet density and mild to severe tubulointerstitial nephritis. Two cows receiving 75 and 85 mg/kg STZ regained their ability to produce insulin and return blood glucose to basal levels. One cow given 100 mg/kg STZ developed insulin insufficiency consistent with type I diabetes mellitus. These findings demonstrate the susceptibility of the bovine pancreas to STZ; however, severe systemic complications were encountered. Alternative dosages and methodologies should be considered in future attempts to induce diabetes in cattle using STZ.
Increased Pulmonary Activation of Nuclear Factor-κB (NF-κB) in Foals Inoculated with Rhodococcus equi is Associated with Increased Expression of Inflammatory Cytokines
Authors: Uhl E. W. , Giguère S. , Jack T. J. , Hodge T.
Published: April 2003

Previous studies revealed that foals inoculated with virulent Rhodococcus equi had significantly higher pulmonary levels of interleukin-1β, interleukin-12 p40, interferon-γ, and tumor necrosis factor-α mRNA compared to foals inoculated with an avirulent plasmid-cured derivative. The purpose of this study was to determine if the increases in cytokine expression were associated with increased pulmonary activation of nuclear factor-kappa;B (NF-kappa;B). Electrophoretic mobility shift assays were performed on pulmonary nuclear protein extracted from foals treated with phosphate-buffered saline, or inoculated with either virulent or avirulent R. equi. NF-kappa;B activation was increased in the nuclear extracts from foals inoculated with virulent R. equi at 14 days after inoculation when increased cytokine expression was also observed. Southwestern histochemistry revealed activated NF-kappa;B in multinucleated giant cells that often contained bacteria. These results indicate that the cytokine response to R. equi is at least partially mediated by NF-kappa;B activation.
Canine T-cell Lymphomas: A Morphological, Immunological, and Clinical Study of 46 New Cases
Authors: Fournel-Fleury C. , Ponce F. , Felman P. , Blavier A. , Bonnefont C. , Chabanne L. , Marchal T. , Cadore J. L. , Goy-Thollot I. , Ledieu D. , Ghernati I. , Magnol J. P.
Published: April 2003

The aim of this study is to report 46 new cases of canine T-cell lymphomas among a series of 140 lymphomas studied by immunophenotyping (incidence 32.8%). According to the updated Kiel classification adapted to the canine species, 13 were classified as low-grade and 33 as high-grade lymphomas. Among the low-grade lymphomas, five were small clear-cell lymphomas, three were pleomorphic small-cell lymphomas, and five mycosis fungoides. Among the high-grade cases, there were 11 pleomorphic mixed-, small-, and largecell lymphomas, 6 pleomorphic large-cell lymphomas, 11 lymphoblastic lymphomas, and 5 unclassifiable highgrade plasmacytoid lymphomas. The cytohistologic features were highly suggestive of a T-cell phenotype on the basis of cell morphology (irregular nuclei and clear cytoplasms) (30/46 cases), a T-cell zone pattern, and the presence of hyperplastic postcapillary venules (22/46 cases). All 46 cases were CD3+ CD79a-, and among 34 cases investigated for CD4 and CD8 expression, 13 were CD4+CD8-, 13 were CD8+CD4-, and 8 were CD4CD8 double positive or double negative. The pleomorphic mixed lymphomas were mainly CD4+CD8- (6/7) and the lymphoblastic lymphomas were double positive or double negative (6/8). The main clinical, hematologic, and biochemical features were generalized (28/46) or regional lymphadenopathy (16/46), hepatosplenomegaly (15/46), extranodal involvement (11/46), mediastinal mass (9/46), and leukemia (8/46), which were mainly present in cases of lymphoblastic lymphomas and hypercalcemia (16/46).
Metastatic Lymphangiosarcoma in a Horse
Authors: Sanchez B. , Nieto A. , de Leon M. A. Ruiz , Rodríguez J. , Flores J.
Published: April 2003

A lymphangiosarcoma with metastases was found in a horse that presented with respiratory distress and edema in the ventral thorax and abdomen. The necropsy revealed diffuse edema in the subcutaneous connective tissue. Mediastinal, mesenteric, iliac, and renal lymph nodes were enlarged and white with soft, yellowish necrotic areas. Histologic examination revealed numerous channels and disorganized vessels lined by large polyhedral, polymorphic cells. Tumor metastases were observed in the spleen, lungs, and kidneys. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for factor VIII, vimentin, and keratin. Laminin was scarce, and collagen IV staining was negative, consistent with a discontinuous or absent basement membrane.
Experimental Rodent Models of Brainstem Tumors
Authors: Wu Q. , Tyler B. , Sukay L. , Rhines L. , Dimeco F. , Clatterbuck R. E. , Guarnieri M. , Carson B. S.
Published: April 2003

Despite recent advances in surgical technology, resection is not an option for many brainstem tumors. Experimental models have played essential roles in examining new approaches to therapy. The objective of the present study was to generate models by determining coordinates for safe inoculation into the brainstem of mice and rats, and to establish whether the implantation of heterotopic cells would create reproducible survival curves. Morbidity and survival studies were used to map stereotactic coordinates allowing successful inoculation of tumor cells. Survival studies were used to investigate the time course of tumor growth. Tumor location was examined by light microscopy and magnetic resonance imaging. Mice survived injections of 2 μL of saline at interaural, lateral, and depth coordinates of −2.5, 1.0, and 3.5 mm and −1.5, 1.0, and 3.5 mm. Rats survived injections at interaural, lateral, and depth coordinates of −2.0, 2.0, and 7.0 mm and −3.0, 0, and 7.0 mm. Median survival of mice challenged with 5 × 105 EMT6 and 104 B16 tumor cells was 11 and 10 days, respectively. Median survival for rats challenged with 104 9L and F98 cells was 14 and 13 days, respectively. The present study demonstrates a feasible approach to preparing models of brainstem tumors. Limitations of these models are discussed.
Lesion Development in White-tailed Deer (Odocoileus virginianus) Experimentally Infected with Mycobacterium bovis
Authors: Palmer M. V. , Waters W. R. , Whipple D. L.
Published: April 2003

The recent discovery of tuberculosis in free-living white-tailed deer in northeastern Michigan underscores the need for increased understanding of the pathogenesis of tuberculosis in wildlife species. To investigate lesion development in white-tailed deer, 32 deer were experimentally infected by intratonsilar instillation of 300 colony-forming units of Mycobacterium bovis. Three deer each were euthanatized and examined at days 15, 28, 42, and 56 after inoculation, and five deer each were euthanatized and examined at days 89, 180, 262, and 328 after inoculation. Microscopic lesions first were seen in the medial retropharyngeal lymph node and lung 28 and 42 days after inoculation, respectively. Lung lesions were present in 12 (38%) of 32 deer, involving 23 lung lobes. Left caudal and right middle and caudal lobes were involved in 17 (74%) of the 23 affected lung lobes. Lesions in the medial retropharyngeal lymph node first appeared as granulomas composed of aggregates of macrophages and Langhans-type giant cells. Some early granulomas contained centrally located neutrophils. As granulomas developed, neutrophils were replaced with a central zone of caseous necrosis that first showed signs of mineralization 42 days after inoculation. Granulomas increased in size as the zone of caseous necrosis expanded. Peripheral fibrosis, first seen at 56 days after inoculation, progressed to only a thin fibrous capsule by 328 days after inoculation. By the termination of the study, the central necrotic core of the granuloma contained abundant liquefied necrotic material and grossly resembled an abscess. Although tuberculous lesions in white-tailed deer follow a developmental pattern similar to that in cattle, fibrosis is less pronounced and the advanced lesions may liquefy, a change seldom reported in cattle. An understanding of lesion development will aid in the identification of the spectrum of disease that may be seen in this important wildlife reservoir of tuberculosis.
Ataxia and Disequilibrium in Domestic Ducks (Anas platyrhynchos f. dom.) with Intracranial Lipomas
Authors: Bartels T. , Krautwald-Junghanns M.-E. , Portmann S. , Gille U. , Brinkmeier J. , Kummerfeld N.
Published: April 2003

Four birds in a flock of 125 purebred Crested ducks ( Anas platyrhynchos f. dom.) had cerebellar signs of unknown etiology. They had radiographically evident perforations of various sizes in the parietooccipital calvaria. Gross necropsy of euthanatized ducks revealed yellow intracranial masses in the brain of each. Histologically, these masses were intracranial lipomas consisting of univacuolated fatty tissue separated into lobules by strands of connective tissue. The masses had caused serious deformation of the rostral part of the cerebellum, leading to a nearly complete flattening of cerebellar folia, and were interpreted as the cause for the central nervous clinical signs observed. These intracranial lipomas were similar to those previously reported in other animals and humans.
Expression of Vascular Endothelial Growth Factor in Canine Mammary Tumors
Authors: Restucci B. , Papparella S. , Maiolino P. , De Vico G.
Published: April 2003

Vascular endothelial growth factor (VEGF) is a dimeric protein that stimulates angiogenesis in vitro and in vivo by inducing endothelial cell proliferation and migration. In this immunohistochemical study, VEGF-immunolabeled cells were counted in a series of 10 benign and 40 malignant canine mammary tumors. The morphologic pattern of VEGF positivity (intensity of immunolabeling and VEGF granule size and distribution) was also evaluated. A low number of cells weakly positive for VEGF with few and small granules polarized to the luminal pole was detected in benign neoplasms. In contrast, in malignancies a high number of VEGF-positive cells had strong immunolabeling, often with large granules found diffusely in the cytoplasm. This level of immunolabeling was more pronounced in the less differentiated, more malignant phenotypes (grade 3). Macrophages, which can synthesize VEGF, were strongly positive. Stromal and myoepithelial cells were negative. VEGF data were correlated statistically with intratumoral microvessel density (number of newly formed microvessels) and both measures were greater in less differentiated malignant neoplasms, demonstrating that angiogenesis and malignancy increase together. VEGF appears to be a powerful angiogenic factor in canine mammary tumors.
Nephrogenic Rest in a Crl:CD (SD)IGS BR Rat
Authors: Jackson C. B. , Kirkpatrick J. B.
Published: April 2003

A nephrogenic rest was found in the kidney of an 11-week-old male Crl:CD (SD)IGS BR rat. Histologically, the rest was within the renal cortical interstitium and consisted of glomeruloid structures (primitive glomeruli) and inconsistently distinct basophilic tubules lined by a single layer of cuboidal to columnar cells and variably bordered by blastemal cells. Nephrogenic rests have not been reported previously in this rat strain.
Glomus Tumor in the Digit of a Cat
Authors: Uchida K. , Yamaguchi R. , Tateyama S.
Published: April 2003

A solitary mass approximately 1.5 X 2 cm located on the outer side of the third digit of the left forepaw of a 7-year-old male cross-breed cat was examined pathologically. The excised tumor mass was hard and white and located within the deep dermis and subcutis. Histopathologically, the mass consisted of a mixed population of small round epithelioid cells arranged in ribbon- or cordlike structures and spindle-shaped cells forming loose irregular bundles in a mucinous stroma. The epithelioid cells were often arranged around small blood vessels. Neoplastic cells were intensely positive for vimentin and alpha smooth muscle actin and negative for keratin, desmin, S-100 protein, and neuron-specific enolase. Based on these pathologic features, the tumor was diagnosed as a glomus tumor, a neoplasm not previously reported in cats and extremely rare in animals.
Reactivation of a Trypanosoma cruzi Infection in a Rhesus Monkey (Macaca mulatta) Experimentally Infected with SIV
Authors: Kunz E. , Mätz-Rensing K. , Stolte N. , Hamilton P. B. , Kaup F.-J.
Published: April 2003

Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected. Analysis of the small subunit rRNA gene of the trypanosome identified the protozoan as T. cruzi.
Spontaneous Basaloid Adenomas of the Mammary Gland in Four Dogs: Clinicopathologic and Immunohistochemical Features
Authors: de las Mulas J. Martín , Ordás J. , Millán M. Y. , de los Monteros A. Espinosa , Reymundo C.
Published: April 2003

Spontaneous basaloid adenomas occurred in four out of 354 dogs with mammary tumors. Affected dogs were pure-bred, intact females between 6 and 8 years of age. Three dogs were nuliparous, two had pseudopregnancies, and none had received contraceptive steroids. The tumors were multiple (three cases) or unique, less than 1 cm in diameter, well delineated, and composed of uniform cords and clusters of monomorphic epithelial cells with focal signs of squamous or glandular differentiation. A basal cell immunophenotype (cytokeratins 5 and 14 positive) without either glandular epithelial (cytokeratins 8, 18, and 19 negative) or myoepithelial (calponin negative) differentiation was observed in the majority of tumor cells. No recurrence or metastasis was recorded after follow-up periods between 3 and 24 months. In spite of the hormone-dependent nature of this tumor in female Beagles given experimental contraceptive steroids, spontaneous basaloid adenomas lacked estrogen receptor alpha and progesterone receptors.
Vasculitis in a Dog Resembling Isolated Angiitis of the Central Nervous System in Humans
Authors: Sasaki M. , Pool R. , Summers B. A.
Published: April 2003

An 11-year-old dog succumbed to a seizure disorder of 18 days duration. At necropsy, an area of hemorrhage and discolored parenchyma was identified in the left pyriform lobe of the brain. Microscopic examination revealed a localized, necrotizing vasculitis with associated cerebral necrosis. Vasculitis was not present in other organs. This presentation is consistent with isolated central nervous system (CNS) angiitis, a rare form of vasculitis in humans.
Immunohistochemical Study of Retinol-binding Protein in Livers of Polar Bears (Thalarctos maritimus)
Authors: Heier A. , Gröne A. , Völlm J. , Kübber-Heiss A. , Bacciarini L. N.
Published: April 2003

Liver tumors of unknown cause have frequently been described in polar bears. Concurrent decrease of vitamin A levels and chronic liver disease are associated with hepatic carcinogenesis in humans. More than 90% of the body's vitamin A is stored in the liver, where it is bound to an intracellular retinol-binding protein (RBP). Therefore, in this retrospective study, RBP was assessed by immunohistochemistry in liver sections of 11 polar bears. Two of these polar bears had hepatocellular carcinoma, four showed other chronic liver changes, and five had normal livers. In normal livers, the cytoplasm stained diffusely positive with intensely staining cytoplasmic granules. RBP staining was evaluated and the abundance of diffuse cytoplasmic staining and intracytoplasmic large granules was determined. All cases with pathologic liver changes had markedly decreased staining intensities for RBP compared with normal livers. The findings of this study suggest that in polar bears, as in humans, vitamin A metabolism may play a role in hepatic carcinogenesis.
Brodifacoum Toxicosis in Two Neonatal Puppies
Authors: Munday J. S. , Thompson L. J.
Published: April 2003

Eight out of a litter of 13 puppies were either born dead or died within 48 hours of birth. Three puppies that died shortly after birth were necropsied. Two puppies had hemorrhage in the thoracic and peritoneal cavities, intestinal serosa, and meninges. The third puppy was smaller than the other two puppies but did not have detectable hemorrhage. Brodifacoum, a second-generation coumarin anticoagulant, was detected in livers from the two puppies with hemorrhage. The dam did not have clinical signs of coagulopathy before or subsequent to whelping. The owners were confident that the dog had not been exposed to rodenticide for at least 4 weeks before whelping. A presumptive diagnosis of in utero brodifacoum toxicity was made. To the authors' knowledge this is the first time a second-generation coumarin anticoagulant has been detected in the liver of a newborn animal. This case is also unique because the dam was unaffected, suggesting that fetuses are more susceptible to brodifacoum toxicity than adult animals.
High‐Temperature Erosion and Corrosion Measurement of Thermally Sprayed Materials
Authors: Cha S.C. , Wölpert P.
Published: April 2003

Thermally‐sprayed surface coatings are a preferred means of protection for highly stressed steel parts against mechanical erosion (like in heat exchanger tubes of power plants) or chemical corrosion (like e.g., in the interior of waste incinerators) at elevated temperature. The authors compare the properties of several coating materials with respect to their stability at 530–640 °C. The Figure shows a freshly‐sprayed and a corroded surface of the Co‐based alloy T800.
Cover Picture: [Cd16In64S134]44−: 31‐Å Tetrahedron with a Large Cavity (Angew. Chem. Int. Ed. 16/2003)
Authors: Li Hailian , Kim Jaheon , O'Keeffe Michael , Yaghi Omar M.
Published: April 2003

It begins with a single InS4 tetrahedron (blue), then, in the hierarchical structure of the [Cd16In64S134]44− ion, comes a supertetrahedron of these tetrahedra, a supertetrahedron of supertetrahedra (a super‐supertetrahedron, extra Cd atoms in white), and finally a supertetrahedron of super‐supertetrahedra. The yellow sphere marks a huge cavity and the Sierpinski tetrahedron the next level of the hierarchy. For more details see the Communication by O. M. Yaghi et al. on page 1819 ff.
Homelessness: integrating international perspectives
Authors: Christian Julie
Published: April 2003

This article, the issue introduction, discusses the background issues effecting the conceptualization and debate surrounding research on homelessness in the US and Europe, focussing largely on the UK. It considers the themes to be developed in this special issue, and examines how psychology together with other disciplines such as sociology, geography and policy studies can be complementary in meeting the challenges of researching, evaluating and understanding the issues. This article also begins to discuss how these divergent approaches can strengthen both the evidence bases on homelessness, and explore some of the lessons that can be learned from different perspectives, a theme raised throughout this issue. Copyright © 2003 John Wiley & Sons, Ltd.
Paget‐Schroëtter syndrome: What to do?
Authors: Sevestre Marie‐Antoinette , Kalka Christoph , Irwin William T. , Ahari Heideh K. , Schainfeld Robert M.
Published: April 2003

Paget‐Schroëtter syndrome, or primary thrombotic occlusion of the axillary‐subclavian vein, is diagnosed in a 42‐year‐old man subsequently treated with thrombolysis and anticoagulation. Treatment strategies, including early and delayed surgical options, are discussed to determine the best risk/benefit ratio. Cathet Cardiovasc Intervent 2003;59:71–76. © 2003 Wiley‐Liss, Inc.
Experimentelle Untersuchung und Modellierung der katalytischen Sulfit/Hydrogensulfit‐Oxidation mit O2
Authors: Kracker‐Semler G. , Marr R. , Siebenhofer M.
Published: April 2003

No abstracts.
The Synthesis of Fused Ring Systems Utilising the Intramolecular Addition of Alkenyl Radicals to Furans
Authors: Demircan Aydin , Parsons Philip J.
Published: April 2003

Studies on the intramolecular addition of alkenyl radicals to furans are reported. The alkenyl radicals undergo a 5‐exo‐trig addition to furans and the resulting spirocyclic intermediate can fragment to give substituted cyclopentene rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Stratified cost‐effectiveness analysis: a framework for establishing efficient limited use criteria
Authors: Coyle Douglas , Buxton Martin J. , O'Brien Bernie J.
Published: April 2003

The cost‐effectiveness of new health care technologies is conditional upon who receives what therapy and under what circumstances. Understanding this heterogeneity in cost‐effectiveness, health care payers often limit reimbursement of therapies to a more restrictive sub‐group of patients than that indicated in a product's licensing. Such limits may be based upon clinical or demographic criteria that are prognostic of costs, outcomes or both. However, there is little guidance on how to estimate and interpret stratified cost‐effectiveness analysis. In this paper we present a framework for estimating the benefits from stratification that permits consideration of both the opportunity cost resulting from a lack of adherence with criteria and the efficiency loss associated with incorporating equity concerns. Copyright © 2003 John Wiley & Sons, Ltd.
On the transferability of hydration‐parametrized continuum electrostatics models to solvated binding calculations
Authors: Rankin Kathryn N. , Sulea Traian , Purisima Enrico O.
Published: April 2003

Using molecular mechanics force field partial atomic charges, we show the nonuniqueness of the parametrization of continuum electrostatics models with respect to solute atomic radii and interior dielectric constant based on hydration (vacuum‐to‐water transfer) free energy data available for small molecules. Moreover, parameter sets that are optimal and equivalent for hydration free energy calculations lead to large variations of calculated absolute and relative electrostatic binding free energies. Hence, parametrization of solvation effects based on hydration data, although a necessary condition, is not sufficient to guarantee its transferability to the calculation of binding free energies in solution. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 954–962, 2003