bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Be1 and Be2 cells in systemic lupus erythematosus indicates elevated interleukin-10 producing CD5+ B cells
Authors: Kashipaz M R Amel , Huggins M L , Lanyon P , Robins A , Powell R J , Todd I
Published: April 2003

Recent studies indicate that normal B cells can be primed to differentiate into two distinct cytokine- secreting effector subsets, Be1 and Be2. The aim of this study was to analyse, for the first time, Be1 and Be2 cells at the single cell level in SLE patients using the recently developed technique of flow cytometry for intracellular cytokines. Peripheral blood mononuclear cells (PBMC) from SLE patients and age- and sex-matched normal controls were cultured for 24 h in the presence or absence of phorbal myristate acetate and ionomycin (PMA=I) or lipopolysaccharide (LPS). The production of type 1 (IFN-g, IL-2) and type 2 (IL-4, IL-5, IL-6, IL-10, IL-13) cytokines by B cells (and IL-10 production by fractionated CD5+ and CD57 B cells) was investigated using an intracellular cytokine staining technique and flow cytometry. In the absence of PMA=I stimulation, the percentage of B cells from SLE patients was significantly lower than those of normal subjects and significantly more SLE B cells spontaneously produced IL-10 than controls. Moreover, CD5+ B cells from SLE patients were enriched for cells with signs of previous in vivo activation and for high levels of IL-10 production. A significant positive correlation was observed between the percentage of IL-10- and IL-6-producing PMA=I-stimulated B cells in SLE patients, but not in controls. There were no significant differences in the production of other cytokines by B cells of SLE patients and normal subjects. In conclusion, a general alteration of type 1 and type 2 cytokine production by B cells is not observed in SLE patients. The role of B cell cytokines in the pathogenesis of SLE appears to be exerted by elevated secretion of in vivo IL-10, which may play an important role in the immune dysregulation observed in SLE patients. Moreover, the cross regulation of IL-10 and IL-6 is disrupted in SLE patients.
Ecological grinding with chilled air as coolant
Authors: Ramesh K , Yeo S H , Zhong Z W , Huang H
Published: April 2003

Compared with other machining processes, grinding consumes the highest specific energy. Therefore, the use of a water-based coolant is often necessary to overcome thermal damage, to impart better surface integrity and to achieve higher tool life. However, the presence of hazardous chemical additives in the coolant causes environmental problems. As a result, stringent government legislation is being imposed for coolant use and disposal, which could represent up to 7–17 per cent of the total machining cost. This paper reports the development of an ecologically friendly grinding technology that uses chilled air with a biodegradable oil and air mist to replace the conventional water-based coolant. A thermal energy equilibrium model that relates to the grinding energy, heat transfer and internal energy rise was used to discuss the grinding results. This model predicted the maximum material removal for chilled air grinding, which was in agreement with the experiments.
Immunohistochemical Studies of Productive Rhesus Cytomegalovirus Infection in Rhesus Monkeys (Macaca mulatta) Infected with Simian Immunodeficiency Virus
Authors: Kuhn E.-M. , Stolte N. , Mätz-Rensing K. , Mach M. , Stahl-Hennig C. , Hunsmann G. , Kaup F.-J.
Published: April 2003

In humans infected with the human immunodeficiency virus (HIV), clinical disease due to human cytomegalovirus (HCMV) infection is one of the AIDS-defining diseases; HCMV is the most common opportunistic infection found postmortem. Histologically, the typical lesions are characterized by “owl's eye cells.” In rhesus monkeys infected with simian immunodeficiency virus (SIV), comparable lesions are caused by an infection with the rhesus CMV (RhCMV). The aim of this study was to investigate the incidence of productive and latent RhCMV infection in monkeys infected with SIV macaques (SIVmac). Eleven SIVmac-infected rhesus monkeys, which were euthanatized after developing AIDS-like disease, and 11 clinically healthy and uninfected animals comprised the study. The monkeys were screened serologically for RhCMV by western-blot analysis. Immunohistochemistry was performed by an indirect immunoperoxidase technique with a polyclonal rabbit RhCMV-antiserum. Lesions characteristic of RhCMV-associated diseases were detected histologically. All animals were latently RhCMV-infected. Seven of eleven (63.6%) SIV-infected macaques were productively RhCMV infected according to immunohistochemistry. RhCMV antigen was identified in the gastrointestinal tract, the hepatobiliary system, the lungs, and the testicles. Two of these seven animals showed characteristic inflammatory lesions associated with productive infection. Consequently, the CMV prevalence in SIVmac-infected rhesus monkeys and human AIDS patients is comparable.
Oral Malignant Melanoma with Osteoid Formation in a Dog
Authors: Chénier S. , Doré M.
Published: April 2003

Melanomas are the most frequent malignant neoplasms of the oral cavity of dogs. Osteogenic melanoma is a rare variant of melanoma that has been described in humans but not in animals. We describe a case of malignant melanoma with bone production affecting the gingiva of a 12-year-old Miniature Dachshund dog. The tumor was a round, lightly pigmented mass that measured 1 cm in diameter and was hard to cut. Histologically, the tumor was composed of nests and lobules of anaplastic, round, melanin-containing cells supported by a stroma displaying abundant osteoid matrix. Many of the neoplastic melanocytic cells were in close contact with the osteoid trabeculae. Immunohistochemical tests revealed that the neoplastic cells were immunoreactive for S-100 and vimentin and showed no staining with cytokeratin. The animal had a local recurrence of the tumor 3 months after the initial excision. This is the first case of malignant melanoma with osteoid formation reported in animals.
Congenital Fibropapillomatosis in a Piglet
Authors: Vítovec J. , Kursa J. , Kratochvíl P. , Skálová A.
Published: April 2003

We report a case of congenital fibropapillomatosis in the head and neck of a piglet from a swine breeding farm where sporadic cutaneous papillomas of the prepuce and scrotum had previously occurred in several boars. Histologically, the tumor consisted of multiple exophytic, papillary projections composed of branching, densely cellular, fibrovascular stalks covered by hyperplastic keratizing squamous epithelium. Ultra-structural examination failed to reveal viral particles. Cutaneous papillomatosis is rare in swine. To the best of our knowledge, this is the second report of congenital fibropapillomatosis in pigs.
Histology and Tissue Chemistry of Tidemark Separation in Hamsters
Authors: Otterness I. G. , Chang M. , Burkhardt J. E. , Sweeney F. J. , Milici A. J.
Published: April 2003

Adult articular cartilage is divided by the tidemark into a deep calcified layer and a more superficial uncalcified layer. Histologic examination of articular cartilage from the knee joint of golden Syrian hamsters 123 days of age or older revealed defects at the tidemark in the tibia. Defects ranged from small separations of the calcified and uncalcified layers along the tidemark to progressively larger defects apparently formed by dissolution. These larger defects appeared as cavities in the noncalcified cartilage, had smooth rather than rough edges, frequently contained coalesced debris, and often resulted in a bulge in the articular surface. Occasionally, these large defects broke through the articular surface. Defects were not observed in tibial cartilage of younger (<90 days old) hamsters or in femoral cartilage from hamsters of any age. Exercise neither protected against nor increased the severity of the defects. Collagen cross-linking by pyridinoline was examined as a function of age and increased from 1,090 to 3,062 μmoles of pyridinoline/mole of hydroxyproline over the period of 1–9 months of age but was not correlated with defect formation. With increasing age, these focal tidemark defects could lead to osteoarthrosis-like cartilage lesions.
Lysis of Myelocytes in Chickens Infected with Infectious Bursal Disease Virus
Authors: Inoue M. , Fujita A. , Maeda K.
Published: April 2003

In specific-pathogen-free chickens infected with the highly virulent HPS-2 strain or virulent reference GBF-1 strain of infectious bursal disease virus (IBDV), pathologic changes of the bone marrow were investigated. On histologic examination, bone marrow lesions were prominent in the HPS-2 group but only mild in the GBF-1 group. The bone marrow of the HPS-2 group showed severe lysis and depletion of heterophil myelocytes with pyknotic nuclear alteration 2–3 days after inoculation. On examination with an electron microscope, heterophil myelocytes were characterized by shrinkage of the cytoplasm and peripheral condensation of nuclear chromatin. IBDV particles were not detected in altered myelocytes. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method demonstrated a positive reaction in only heterophil myelocytes. In contrast, nucleosomal DNA fragmentation in HPS-2-infected bone marrow cells was indiscernible by agarose gel electrophoresis. These findings indicate that lysis of bone marrow cells is selectively induced in heterophil myelocytes at an early stage after IBDV infection and independent of virus replication.
Recombinant Feline Leukemia Virus (FeLV) Variants Establish a Limited Infection with Altered Cell Tropism in Specific-pathogen-free Cats in the Absence of FeLV Subgroup A Helper Virus
Authors: Bechtel M. K. , Hayes K. A. , Mathes L. E. , Pandey R. , Stromberg P. C. , Roy-Burman P.
Published: April 2003

Feline leukemia virus subgroup B (FeLV-B) is commonly associated with feline lymphosarcoma and arises through recombination between endogenous retroviral elements inherited in the cat genome and corresponding regions of the envelope ( env) gene from FeLV subgroup A (FeLV-A). In vivo infectivity for FeLV-B is thought to be inefficient in the absence of FeLV-A. Proposed FeLV-A helper functions include enhanced replication efficiency, immune evasion, and replication rescue for defective FeLV-B virions. In vitro analysis of the recombinant FeLV-B-like viruses (rFeLVs) employed in this study confirmed these viruses were replication competent prior to their use in an in vivo study without FeLV-A helper virus. Eight specific-pathogenfree kittens were inoculated with the rFeLVs alone. Subsequent hematology and histology results were within normal limits, however, in the absence of detectable viremia, virus expression, or significant seroconversion, rFeLV proviral DNA was detected in bone marrow tissue of 4/4 (100%) cats at 45 weeks postinoculation (pi), indicating these rFeLVs established a limited but persistent infection in the absence of FeLV-A. Altered cell tropism was also noted. Focal infection was seen in T-cell areas of the splenic follicles in 3/4 (75%) rFeLVinfected cats analyzed, while an FeLV-A-infected cat showed focal infection in B-cell areas of the splenic follicles. Nucleotide sequence analysis of the surface glycoprotein portion of the rFeLV env gene amplified from bone marrow tissue collected at 45 weeks pi showed no sequence alterations from the original rFeLV inocula.
Coordinate Expression of Cytokeratins 7 and 20 in Feline and Canine Carcinomas
Authors: Espinosa de Los Monteros A. , Fernández A. , Millán M. Y. , Rodríguez F. , Herráez P. , Martín de Las Mulas J.
Published: April 2003

Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7+/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.
Detection and Localization of Mycoplasma hyopneumoniae DNA in Lungs from Naturally Infected Pigs by In Situ Hybridization Using a Digoxigenin-labeled Probe
Authors: Kwon D. , Chae C.
Published: April 2003

Mycoplasma hyopneumoniae DNA was detected in 20 naturally infected pigs by in situ hybridization using a nonradioactive digoxigenin-labeled DNA probe. A 520-base-pair DNA probe targeting a reiterative sequence of the M. hyopneumoniae genome was generated by the polymerase chain reaction. All 20 pigs infected with M. hyopneumoniae had distinct and positive hybridization signals without background staining. A strong hybridization signal was detected mainly in the luminal surface of bronchial and bronchiolar lining epithelial cells, whereas no hybridization signal was seen in the cytoplasm of bronchial and bronchiolar lining epithelial cells. When hybridization signal was detected in the luminal surface of bronchial and bronchiolar lining epithelial cells, a given bronchus or bronchiole had peribronchiolar lymphoid hyperplastic tissues. Hybridization signals were not seen in the peribronchiolar lymphoid hyperplastic tissues. A less intense signal was detected in the interstitial and alveolar macrophages randomly scattered in the thickened alveolar septa and spaces. Hybridization signal was rarely detected in the type I pneumocytes. The in situ hybridization technique developed in this study was useful for detection of M. hyopneumoniae nucleic acids in tissues taken from naturally infected piglets and may be a valuable technique for studying the pathogenesis of M. hyopneumoniae infection.
Thyroid C-cell Carcinoma with Amyloid in a Red Fox (Vulpes vulpes schrenchki)
Authors: Hirayama K. , Kagawa Y. , Nihtani K. , Taniyama H.
Published: April 2003

An amyloid-producing medullary thyroid carcinoma (MTC) in a red fox ( Vulpes vulpes schrenchki) bred in a zoo was examined using histopathologic and immunohistochemical techniques. The neoplastic cells had an ill-defined cytoplasmic membrane and abundant, finely granular eosinophilic cytoplasm, containing numerous argyrophilic granules. The neoplastic tissues were divided into various sizes by a vascular connective stroma, which was partly fibrovascular with broad areas of hyalinization containing varied amounts of amyloid. Immunohistochemically, neoplastic cells showed reactivity to anti-calcitonin, neuron-specific enolase, somatostatin, and keratin antibodies. However, amyloid in the stroma did not show immunoreactivity to the antibodies used. Histologic and immunohistochemical features of MTC in the present animal were analogous to those of the C-cell carcinoma derived from thyroid C cells (parafollicular cells) reported in humans and dogs.
Nocardia nova Causing Pulmonary Nocardiosis of Black Crakes (Limnocorax flavirostra)
Authors: Bacciarini L. N. , Posthaus H. , Pagan O. , Miserez R.
Published: April 2003

Natural nocardial infection has been reported in many different species including mammals and fish, but reports in birds remain uncommon. Eight juvenile Black Crakes ( Limnocorax flavirostra) died unexpectedly at the Basle Zoo. Necropsy revealed disseminated white, firm nodules, 1–3 mm in diameter, throughout the lung parenchyma. Histologically, the lungs contained multiple, often confluent granulomas with central necrosis. Delicate, gram-positive, 0.5- to 1.0-μ-wide, branching, occasionally beaded, filamentous organisms were visible in necrotic centers. These organisms were acid fast when stained with Fite-Faraco. No histologic lesions were seen in other organs. Nocardia nova was isolated from liver, spleen, kidney, and lung. Granulomatous and necrotizing nocardial pneumonia with agonal septicemia was diagnosed, suggesting an aerogenous infection. To our knowledge, this is the first reported epizootic outbreak of nocardiosis in birds, which is additionally unusual because it was caused by N. nova.
Key Role of Chemokines and Chemokine Receptors in Inflammation, Immunity, Neoplasia, and Infectious Disease
Authors: Rottman J. B.
Published: April 2003

Leukocyte homing is a complex, multistep process involving the coordinated expression of adhesion molecules and certain chemotactic cytokines, termed chemokines. Although chemokines initially burst into the literature as potent inflammatory mediators, it is now clear that they are involved in a variety of processes including lymphocyte maturation, angiogenesis, and tumor growth. Furthermore, a variety of important pathogens manipulate various chemokine/receptor pathways to infect the host and evade the immune system.
In Situ Expression of Intercellular Adhesion Molecule-1 (ICAM-1) mRNA in Calves with Acute Pasteurella haemolytica Pneumonia
Authors: Radi Z. A. , Register K. B. , Lee E.-K. , Kehrli M. E. , Brogden K. A. , Gallup J. M. , Ackermann M. R.
Published: April 2003

The in situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in normal and pneumonic lung tissues of Holstein calves with bovine leukocyte adhesion deficiency (BLAD) was compared with that of age-matched non-BLAD Holstein calves by in situ hybridization. Twenty-four Holstein calves (both BLAD and non-BLAD) were randomly assigned to one of two experimental groups and inoculated intrabronchially with Pasteurella haemolytica or pyrogen-free saline. Lung tissues were collected and fixed in 10% neutral formalin at 2 or 4 hours postinoculation (PI). The expression and distribution of ICAM-1 mRNA in the different cell types of the lung tissue was detected by in situ hybridization with a 307-base-pair bovine ICAM-1 riboprobe. In lungs of both non-BLAD and BLAD saline-inoculated calves, ICAM-1 expression was present in epithelial cells but occurred in <30% of cells in bronchi, bronchioles, and alveoli. ICAM-1 expression in vascular endothelial cells was present in <30% of cells in pulmonary arteries and veins. The expression of ICAM-1 was significantly greater (>60% of cells) in bronchiolar and alveolar epithelial cells and pulmonary endothelial cells of arteries and veins in both BLAD and non-BLAD calves inoculated with P. haemolytica. Bronchiolar epithelium had the highest intensity of mRNA expression and highest percentage of cells that were stained, whereas bronchial epithelium had the lowest intensity and percentage of cells stained. Most alveolar macrophages and neutrophils in infected lungs also expressed ICAM-1. ICAM-1 expression was generally increased in infected BLAD calves at 2 hours PI as compared with non-BLAD calves but not at 4 hours PI. The increased expression of ICAM-1 during acute P. haemolytica pneumonia in calves suggests that ICAM-1 is upregulated and may play a role in leukocyte infiltration. The extent of ICAM-1 expression in P. haemolytica-inoculated calves with BLAD was initially enhanced but otherwise similar to that in non-BLAD calves.
Extragonadal Teratocarcinoma in Chimeric Mice
Authors: Blackshear P. , Mahler J. , Bennett L. M. , McAllister K. A. , Forsythe D. , Davis B. J.
Published: April 2003

Chimeric mice often are created through the genetic manipulation of the mouse embryo in the process of developing animal models of disease. These mice have variable percentages of their somatic and germ cells derived from the donor embryonic stem cells and host blastocysts. In the development of mouse models deficient in the breast cancer susceptibility gene 2 ( Brca2) or the 70-kd heat shock protein ( Hsp70-2), 3–4-week-old chimeras developed single or multiple masses composed of both well-differentiated and poorly differentiated tissues derived from all three germ layers. These cases of extragonadal teratocarcinoma, a rarely reported tumor, may be related to the genetic predisposition of the 129/Ola mouse strain used to generate the embryonic stem cells.
Fatal Measles Virus Infection in Japanese Macaques (Macaca fuscata)
Authors: Choi Y. K. , Simon M. A. , Kim D. Y. , Yoon B. I. , Kwon S. W. , Lee K. W. , Seo I. B. , Kim D. Y.
Published: April 2003

An outbreak of natural measles virus infection occurred in a group of Japanese macaques ( Macaca fuscata). Over a period of 4 months, 12 of 53 Japanese macaques died following a 2-23-day history of anorexia, diarrhea, and dermatitis. The monkeys were kept in outdoor exhibits but had been moved temporarily into indoor caging and then transferred to new outdoor exhibits. Ten monkeys died while they were in temporary caging, and two monkeys died after they were moved to new outdoor exhibits. The diagnoses were made based on the results of histopathology, immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy. Measles virus antigens were detected in the lung, stomach, skin, salivary gland, spleen, and lymph nodes. Tangled, tubular nucleocapsids compatible with paramyxovirus were noted in the lung tissue. As a result of immunosuppression following measles virus infection, various secondary infections including disseminated cytomegalovirus infection, adenoviral and bacterial pneumonia, and Candida albicans-associated gingivitis and esophagitis were noted. The primary infective source or the mode of infection could not be determined in this outbreak, but measles virus may have been transmitted to the monkeys from human visitors while the monkeys were on exhibit.
Collagen Dysplasia (Cutaneous Asthenia) in a Cat
Authors: Sequeira J. L. , Rocha N. S. , Bandarra E. P. , Figueiredo L. M. A. , Eugenio F. R.
Published: April 2003

Hereditary collagen dysplasias comprise a complex group of connective-tissue disorders that result in the reduced tensile strength of affected tissues. These processes are called cutaneous asthenia in the skin of dogs and cats. We report here the case of a crossbred male cat, aged 6 months, that presented with two skin wounds in the region of the right thorax and right iliac tuberosity. The skin of these regions and of the animal's dorsum was hyperextensible, smooth to the touch, and easily torn with minor trauma. Microscopic examination of skin samples revealed reduced dermal connective tissue consisting of shortened and fragmented collagen fibers. Normal fibers were intermingled with altered fibers. Ultrastructural changes in collagen fibers included disorientation of fibrils within the same bundle, marked spacing differences, and variation in the diameter of transverse sections. The fibrils maintained the transverse striations characteristic of normal collagen.
Small Intestinal Adenomatous Polyposis Resulting in Protein-Losing Enteropathy in a Horse
Authors: Patterson-Kane J. C. , Sanchez L. C. , MacKay R. J. , Sundberg J. P. , Homer B. L.
Published: April 2003

A 4-year-old Quarter Horse gelding was presented with a history of weight loss of 6 months duration, along with extensive ventral subcutaneous edema. Clinicopathologic findings included a markedly low serum total protein (2.9 g/dl) and a low packed cell volume (24%). The mucosal surface of the distal jejunum and entire ileum were carpeted with numerous polypoid, papillary, and glandular masses comprised of pseudostratified tall columnar cells and large numbers of interspersed goblet cells. Neoplastic change was diffuse throughout the mucosa of each mass, but abrupt demarcation occurred between neoplastic masses and adjacent mucosa. Immunohistochemical staining for protein of the p53 tumor suppressor gene revealed only occasional cytoplasmic reactivity within polyps and normal mucosa. Nuclear staining for papillomavirus antigens was not observed. Electron microscopic examination revealed features of well-differentiated intestinal epithelial cells, including apical tight junctions and microvilli, desmosomes, and the presence of numerous goblet cells. Microorganisms were not detected. Small intestinal polyposis should be considered as a rare differential diagnosis for protein-losing enteropathy in the horse.
Anthracycline Cardiotoxicity in a Black Rhinoceros (Diceros bicornis)
Authors: Paglia D. E. , Radcliffe R. W.
Published: April 2003

Two weeks before dying of congestive heart failure, a juvenile black rhinoceros ( Diceros bicornis minor) received a single low dose of doxorubicin as part of combination chemotherapy for acute lymphoblastic leukemia. Diffuse hemosiderosis was present at necropsy in a pattern indicative of dietary iron overload, but unique iron-positive degenerative lesions were found in isolated myocardiocytes. Serum analyses revealed hyperferremia, 87% transferrin saturation, and 5- to 10-fold elevations in ferritin concentration, reflecting markedly increased tissue iron stores. Since both toxic and therapeutic effects of anthracyclines are mediated by formation of reactive free radicals via iron-catalyzed reactions, these observations suggest that iron overload may have enhanced myocardial susceptibility to cardiotoxic effects of doxorubicin. Impairments in other myocardial antioxidant defenses, such as deficiencies in catalase and glutathione S-transferase that are known to exist in rhinoceros erythrocytes, may have been underlying factors contributing to an inherent sensitivity of rhinoceros tissues to oxidant-induced injury.
Clinical and Pathologic Features of Oligodendrogliomas in Two Cats
Authors: Dickinson P. J. , Keel M. K. , Higgins R. J. , Koblik P. D. , Lecouteur R. A. , Naydan D. K. , Bollen A. W. , Vernau W.
Published: April 2003

Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.
Distribution of Cells Immunopositive for AM-3K, a Novel Monoclonal Antibody Recognizing Human Macrophages, in Normal and Diseased Tissues of Dogs, Cats, Horses, Cattle, Pigs, and Rabbits
Authors: Yamate J. , Yoshida H. , Tsukamoto Y. , Ide M. , Kuwamura M. , Ohashi F. , Miyamoto T. , Kotani T. , Sakuma S. , Takeya M.
Published: April 2003

The monoclonal antibody AM-3K, which was developed using human pulmonary macrophages as the immunogen, immunocytochemically labels most human macrophages except for blood monocytes and dendritic cell populations. AM-3K also shows cross-reactivity in some animal species. To evaluate the usefulness of AM-3K, the present study investigated the detailed distribution of AM-3K–immunopositive macrophages in normal and diseased tissues of dogs, cats, horses, cattle, pigs, and rabbits. Zamboni's solution-fixed, paraffinembedded sections were the most available for the immunocytochemistry with AM-3K. In all animal species examined, AM-3K labeled most macrophages in splenic red pulp, lymph node sinuses and thymus, and tissue macrophages in the interstitium of various organs and sites such as the kidneys, lungs, heart, pancreas, intestines, and skin. Alveolar macrophages and perivascular microglial cells were also immunoreactive for AM-3K. Interestingly, Kupffer cells of dogs, cats, and horses were labeled for AM-3K, but those of cattle, pigs, and rabbits were not. Furthermore, in tumor tissues and inflammatory lesions such as liver fibrosis and encephalomalacia that were obtained from dogs, infiltrating macrophages were stained with AM-3K, but not all infiltrating macrophages reacted to AM-3K. In addition, only 30–50% of pulmonary and peritoneal macrophages obtained from cats and dogs were reactive for AM-3K. AM-3K did not react with blood monocytes, dendritic cell populations, and osteoclasts. These observations indicate that AM-3K specifically labels most exudate and tissue macrophages in the animal species examined. However, the expression of antigens recognized by AM-3K on macrophages may be dependent on differential maturation stages or different functions evoked by some conditions. AM-3K immunoreaction products were seen on the cytoplasmic membrane of macrophages by immunoelectron microscopy. AM-3K would be useful for detection of macrophage populations in the animal species examined here.
Cellular Proliferative and Telomerase Activity in Canine Mammary Gland Tumors
Authors: Funakoshi Y. , Nakayama H. , Uetsuka K. , Nishimura R. , Sasaki N. , Doi K.
Published: April 2003

In canine mammary tumors, we examined the telomerase activity, proliferative activity by proliferative cell nuclear antigen (PCNA) immunohistochemistry, and percentage of apoptotic cells by the deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The relationship between these measures and histopathologic malignancy was also investigated. PCNA index was highest in malignant tumors (adenocarcinoma: 27.0%; malignant mixed tumor: 15.7%), followed by benign tumors (adenoma: 4.4%; benign mixed tumor: 5.3%), hyperplasia (2.1%), and normal mammary gland (0.9%). In adenoma and adenocarcinoma, papillary and solid types showing higher cellularity tended to have higher PCNA indices than did cystic and tubular types. Although the TUNEL index was <1% in all cases, the relationship between this measure and histopathologic diagnosis showed the same tendency as observed in PCNA immunostaining. Telomerase activity was detectable in all adenomas, benign mixed tumors, and adenocarcinomas examined. In contrast, all normal mammary glands, hyperplasias, and malignant mixed tumors were negative for telomerase. Relative telomerase activity (RTA) of adenocarcinoma (56.5) was significantly higher than that of adenoma (27.8) and benign mixed tumor (33.9), and a significant positive correlation ( P < 0.001) was noted between RTA and PCNA index. No significant correlations were noted between either PCNA or TUNEL index and clinical features such as metastasis and tumor diameter. PCNA index and telomerase activity may be useful markers for judging malignancy of canine mammary tumors.
Virchow's Contributions to Veterinary Medicine: Celebrated Then, Forgotten Now
Authors: Saunders L. Z.
Published: April 2003

In 1858, Rudolf Virchow, the professor of pathology in Berlin University, published the book “Cellular Pathology”. A compendium of his lectures to physicians and medical students, he introduced the use of microscopy for the study of human diseases. To an astonishing extent Rudolf Virchow was helpful to the disciplines of veterinary medicine (and veterinary pathology). Considered a scientific genius in several disciplines, this essay deals exclusively with the devotion of Virchow, a scholarly physician, to the profession of veterinary medicine. He respected veterinary research, supported governmental veterinary education, and provided a role model for the veterinarians who were drafting control legislation of contagious diseases in livestock. Repeatedly, he responded in help when seemingly irretrievable problems arose. Examples of Virchow's activities in the realms of veterinary medicine and pathology are marshalled here to shed light on this pioneer “veterinary pathologist”. In celebration of 50 years of the American College of Veterinary Pathologists in 1999, it is timely to remember that Rudolf Virchow, the father of cellular pathology, also fathered veterinary pathology, whose offsprings in Canada and the U.S.A. (Osler, Clement, Williams, Olafson, Jones 26 ) had enabled them to form and foster the A.C. V.P.
Pathology of Fatal West Nile Virus Infections in Native and Exotic Birds during the 1999 Outbreak in New York City, New York
Authors: Steele K. E. , Linn M. J. , Schoepp R. J. , Komar N. , Geisbert T. W. , Manduca R. M. , Calle P. P. , Raphael B. L. , Clippinger T. L. , Larsen T. , Smith J. , Lanciotti R. S. , Panella N. A. , McNamara T. S.
Published: April 2003

West Nile fever caused fatal disease in humans, horses, and birds in the northeastern United States during 1999. We studied birds from two wildlife facilities in New York City, New York, that died or were euthanatized and were suspected to have West Nile virus infections. Using standard histologic and ultrastructural methods, virus isolation, immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction, we identified West Nile virus as the cause of clinical disease, severe pathologic changes, and death in 27 birds representing eight orders and 14 species. Virus was detected in 23/26 brains (88%), 24/25 hearts (96%), 15/18 spleens (83%), 14/20 livers (70%), 20/20 kidneys (100%), 10/13 adrenals (77%), 13/14 intestines (93%), 10/12 pancreata (83%), 5/12 lungs (42%), and 4/8 ovaries (50%) by one or more methods. Cellular targets included neurons and glial cells in the brain, spinal cord, and peripheral ganglia; myocardial fibers; macrophages and blood monocytes; renal tubular epithelium; adrenal cortical cells; pancreatic acinar cells and islet cells; intestinal crypt epithelium; oocytes; and fibroblasts and smooth muscle cells. Purkinje cells were especially targeted, except in crows and magpies. Gross hemorrhage of the brain, splenomegaly, menin-goencephalitis, and myocarditis were the most prominent lesions. Immunohistochemistry was an efficient and reliable method for identifying infected cases, but the polyclonal antibody cross-reacted with St. Louis encephalitis virus and other flaviviruses. In contrast, the in situ hybridization probe pWNV-E (WN-USAMRIID99) reacted only with West Nile virus. These methods should aid diagnosticians faced with the emergence of West Nile virus in the United States.
Viral Wasting Syndrome of Swine: Experimental Reproduction of Postweaning Multisystemic Wasting Syndrome in Gnotobiotic Swine by Coinfection with Porcine Circovirus 2 and Porcine Parvovirus
Authors: Krakowka S. , Ellis J. A. , Meehan B. , Kennedy S. , McNeilly F. , Allan G.
Published: April 2003

One-day-old gnotobiotic piglets were inoculated intranasally with in vitro passaged porcine circovirus 1 (PCV-1), PCV-2, and porcine parvovirus (PPV) alone or in combination (PCV-1/PCV-2, PCV-1/PPV, and PCV-2/PPV). Piglets were evaluated for 1) the development of porcine postweaning multisystemic wasting syndrome (PMWS), 2) distribution of viral antigens by immunochemistry, and 3) viremia and the presence of viral DNA in nasal and ocular secretions and feces. All single agent-infected piglets and piglets infected with PCV-1/PCV-2 or PCV-1/PPV were clinically asymptomatic. They were transiently viremic and seroconverted to homologous virus(es). At termination of the study on postinfection day (PID) 35, microscopic lesions were restricted to focal inflammatory cell infiltrates in livers and myocardia. One piglet given PCV-1/PPV was PPV viremic for 2 weeks after infection and had lymphangiectasia of the spiral and descending colon associated with granulomatous inflammation. All four PCV-2/PPV-inoculated piglets developed PMWS, characterized by sudden onset of depression and anorexia, icterus, and submucosal edema. One piglet became moribund on PID 27, and the remaining three piglets were euthanatized between PID 27 and PID 30 because of severe disease. Lymph nodes were small and the livers were mottled. Disseminated angiocentric granulomatous inflammation was present in all tissues examined except the brain. Multiple lightly basophilic intracytoplasmic inclusion bodies were identified in macrophages and histiocytes. PCV-2 antigen was widely distributed within macro-phages; PPV antigen was sparse. Hepatocellular necrosis and bile retention were prominent. PCV-2 DNA was identified in ocular, fecal, and nasal secretions. Terminal sera contained antibodies to PPV (4/4) and PCV-2 (3/4). Production of PMWS in gnotobiotic swine appears to require PCV-2 and additional infectious agents such as PPV for full disease expression in gnotobiotic piglets.
Cerebello-Olivary and Lateral (Accessory) Cuneate Degeneration in a Juvenile American Miniature Horse
Authors: Fox J. , Duncan R. , Friday P. , Klein B. , Scarratt W.
Published: April 2003

A 12-month-old American Miniature horse colt was presented to the Virginia Tech Veterinary Teaching Hospital with a 7-month history of progressive ataxia. Physical examination revealed a head intention tremor, base-wide stance, and ataxia. Necropsy findings were confined to the brain. There were bilateral areas of liquefactive necrosis and cavitation corresponding to the dorsal accessory olivary and lateral (accessory) cuneate nuclei. Cerebellar folia of the dorsal vermis were thin. Microscopically, the cerebellar cortex was characterized by patchy areas of Purkinje cell loss with associated variable thinning of the molecular and granule cell layers and astrogliosis. Dorsal accessory olivary and lateral cuneate nuclei were cavitated and had mild glial response around their periphery. Additionally, a focus of necrosis and neuropil vacuolization was found in the right putamen. These findings indicate the presence of a neurodegenerative disorder centered, but not confined to, the cerebellum and its connections in this American Miniature horse colt.
Autoantibodies against the Processed Ectodomain of Collagen XVII (BPAG2, BP180) Define a Canine Homologue of Linear IgA Disease of Humans
Authors: Olivry T. , Dunston S. M. , Fahey M. , Nguyen N. , Marinkovich M. P.
Published: April 2003

Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering dermatosis that affects human children and adults. In contrast to bullous pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen. An immunologic homologue of LAD in humans was identified in two dogs according to the following criteria: 1) erosive, ulcerative, and crusted lesions seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal clefting present in the basement membrane lamina lucida without inflammation or with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd soluble protein LAD-1. The present study establishes unequivocally the existence of a naturally occurring canine model of LAD of humans.
Squamous Cell Carcinoma in an American Bison (Bison bison bison)
Authors: Marder M. Z. , Cummings D. W. , Zegarelli D. J. , Neuschaefer K. , Pulse C. L.
Published: April 2003

The following case report is, to the best of our knowledge, the first documentation of a squamous cell carcinoma in a full-blooded American bison ( Bison bison bison). This female bison developed an ulcerated lesion on the left flank, at the site of a brand, in the summer of her eighth year. In the winter of her ninth year, as the lesion continued to grow, a biopsy was performed, and a diagnosis of squamous cell carcinoma was made. Ultimately, there was metastasis to the liver, a lung, and a prefemoral lymph node.
Malignant Fibrous Histiocytoma (Giant Cell Type) Associated with a Malignant Mixed Tumor in the Salivary Gland of a Dog
Authors: Peérez-Martínez C. , García-Fernández R. A. , Avila L. E. Reyes , Pérez-Pérez V. , González N. , García-Iglesias M. J.
Published: April 2003

A 12-year-old male Boxer dog presented with a 5 X 5 X 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.
Bovine Teat Atresia Associated with Horn Fly (Haematobia irritans irritans (L.))-induced Dermatitis
Authors: Edwards J. F. , Wikse S. E. , Field R. W. , Hoelscher C. C. , Herd D. B.
Published: April 2003

Mammary gland lesions characterized primarily as mammary teat atresia were observed in a Limousin beef cattle herd in eastern Texas. Atresia of multiple teats per mammary gland was reported in firstcalf heifers at the time of calving. Pathogens were not identified in eight mammary glands collected at slaughter. Histology of affected glands demonstrated superficial and deep perivascular inflammation and fibrosing dermatitis of teat and mammary gland skin that resulted in formation of the atretic lesions of glandular tissue. Institution of a horn fly ( Haematobia irritans irritans (L.)) control program using insecticide-impregnated ear tags was associated with elimination of the problem from the herd.
Comparative Immunohistopathology in Pigs Infected with Highly Virulent or Less Virulent Strains of Hog Cholera Virus
Authors: Narita M. , Kawashima K. , Kimura K. , Mikami O. , Shibahara T. , Yamada S. , Sakoda Y.
Published: April 2003

Eight pigs were inoculated subcutaneously with a highly virulent hog cholera virus (HCV) strain ALD. The infected pigs developed severe illness and became moribund on postinoculation day (PID) 7 or PID 10. Histologic lesions were characterized by severe generalized vasculitis, necrosis of lymphocytes, and encephalitis. HCV antigen was detected in crypt tonsilar epithelial cells, macrophages, and reticular endothelial cells of lymphoid tissues. Antigen localization corresponded well with histologic lesions. Five pigs were inoculated with less virulent HCV Kanagawa/74 strain and were euthanatized on PID 30. All five infected pigs recovered from the illness but became stunted. They also had a slight follicular depletion of lymphocytes, histiocytic hyperplasia, and hematopoiesis in the spleen. Less virulent HCV antigen was observed in the tonsils, kidneys, pancreas, adrenal glands, and lungs. Although antigen localization was less associated with histologic lesions, immunoreactivity was stronger than that in the pigs infected with the ALD strain of HCV. An almost complete loss of B lymphocytes was recognized in pigs infected with the ALD strain and was correlated with follicular necrosis in lymphoid tissues. Loss of B lymphocytes was not prominent in the pigs infected with Kanagawa/74 strain. The number of CD4+ and CD8+ T lymphocytes was significantly higher than that in the noninfected control pigs.
Glomerular Lesions in Renal Biopsies of Saimiri Boliviensis (Primate) Examined by Light and Electron Microscopy and Immunohistochemistry
Authors: Borda J. T. , Idiart J. R. , Negrette M. Sanchez
Published: April 2003

In order to determine the existence of glomerular lesions in Saimiri boliviensis, renal biopsies were performed in 20 clinically healthy animals of similar age and both sexes. Biopsies were obtained by laparotomy with a Tru-Cut biopsy needle. Mesangioproliferative glomerulonephritis characterized by an increased number of mesangial cells and increased mesangial matrix was present in 35% of the animals. Proliferative glomerulonephritis characterized by increased numbers of epithelial and endothelial cells with narrowed capillary lumen, and membranous glomerulonephritis characterized by diffuse thickening, wrinkling, and occasional lamellation of basement membranes, were present in 15% of the samples. Ultrastructural features included increased mesangial matrix, fusion of the visceral epithelial foot processes, thickened glomerular basement membranes, and incipient lamellation. Immunohistochemical examination revealed granular deposits of immunoglobulin M in the cytoplasm of mesangial cells and in the mesangial matrix in 50% of the samples.
Granular Cell Lesions in the Distal Female Reproductive Tract of Aged Sprague-Dawley Rats
Authors: Markovits J. E. , Sahota P. S.
Published: April 2003

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with $100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.