bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus-related graft cirrhosis
Authors: Berenguer Marina , Prieto Martín , Palau Antonio , Rayón José M. , Carrasco Domingo , Juan Fernando San , López-Labrador F-Xavier , Moreno Rosalba , Mir José , Berenguer Joaquín
Published: April 2003

An increase in the number of hepatitis C virus (HCV)-infected transplant recipients at need for repeated liver transplantation is anticipated. To date, there is a certain reluctance to accept these patients because of an increased organ shortage, early reports suggesting a poor outcome, and uncertainty regarding the natural history of recurrent hepatitis C in the second graft. The aim of this study is to determine the outcome of patients undergoing retransplantation for HCV-related graft cirrhosis. Of 49 transplant recipients with HCV-related allograft cirrhosis, 31 patients developed decompensation with criteria for retransplantation. Thirteen patients were denied this option. Of the 18 patients accepted, 6 patients died while on the waiting list (5 patients died of graft cirrhosis at a median of 3.2 months of listing), and 12 patients have undergone retransplantation (median, 10 months since HCV cirrhosis). After retransplantation, 8 patients (67%) died at a median of 8 months, and 4 patients (33%) remain alive after 1.9 years of follow-up. Causes and times of death from retransplantation were: surgical complications, n = 3 (perioperative period) HCV cirrhosis of the second graft, n = 2 (at 9 and 54 months) fibrosing cholestatic hepatitis, n = 1 (at 2 years) lymphoproliferative disorder, n = 1 (at 7 months) and endocarditis, n = 1 (at 3.5 years, with underlying cirrhosis). Of the 4 patients alive, fibrosis stages in the last biopsy specimens are stage 1 (n = 1), stage 3 (n = 1), and stage 4 or cirrhosis (n = 1; one patient has not undergone biopsy), despite antiviral therapy. The outcome of retransplantation for HCV cirrhosis of the first graft is very poor because of multiple complications. The severity of recurrent HCV disease in the second graft seems to be related to that observed in the first graft.
NEURAL NETWORKS IN THE RECOGNITION OF MACHINE PRINTED ARABIC CHARACTERS
Authors: BOUSLAMA FAOUZI
Published: April 2003

The objective of this study is to analyze and compare three different recognition approaches to machine printed Arabic characters. The first approach is a template matching and a correlation technique where an input character is compared to a standard set of stored prototype images. The second and the third approaches are based on feature analysis and matching. The features in the second approach are extracted from the horizontal and vertical projections of the images of characters. The third approach is a structural approach where the features are extracted from the geometry of the segments that make a character. In all approaches, the same neural network structure, feedforward with the back propagation learning algorithm, is used for classification. A centering and scaling normalization preprocessing stage precedes the feature extraction process and is used to achieve a size and a position invariant recognition system. The study focuses on the 28 basic Arabic characters of the Cairo font. The performance of the recognition algorithms in each approach is evaluated and the results are compared.
Hematopoietic stem cells: can old cells learn new tricks?
Authors: Ho Anthony D , Punzel Michael
Published: April 2003

Since the establishment of cell lines derived from human embryonic stem (ES) cells, it has been speculated that out of such “raw material,” we could some day produce all sorts of replacement parts for the human body. Human pluripotent stem cells can be isolated from embryonic, fetal, or adult tissues. Enormous self-renewal capacity and developmental potential are the characteristics of ES cells. Somatic stem cells, especially those derived from hematopoietic tissues, have also been reported to exhibit developmental potential heretofore not considered possible. The initial evidences for the plasticity potential of somatic stem cells were so encouraging that the opponents of ES cell research used them as arguments for restricting ES cell research. In the past months, however, critical issues have been raised challenging the validity and the interpretation of the initial data. Whereas hematopoietic stem-cell therapy has been a clinical reality for almost 40 years, there is still a long way to go in basic research before novel therapy strategies with stem cells as replacement for other organ systems can be established. Given the present status, we should keep all options open for research in ES cells and adult stem cells to appreciate the complexity of their differentiation pathways and the relative merits of various types of stem cells for regenerative medicine.
Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and Gαi proteins and enhances engraftment of competitive, repopulating stem cells
Authors: Broxmeyer Hal E , Kohli Lisa , Kim Chang H , Lee Younghee , Mantel Charlie , Cooper Scott , Hangoc Giao , Shaheen Montaser , Li Xiaxin , Clapp D Wade
Published: April 2003

Stromal cell-derived factor-1 (SDF-1/CXCL12) enhances survival of myeloid progenitor cells. The two main questions addressed by us were whether these effects on the progenitors were direct-acting and if SDF-1/CXCL12 enhanced engrafting capability of competitive, repopulating mouse stem cells subjected to short-term ex vivo culture with other growth factors. SDF-1/CXCL12 had survival-enhancing/antiapoptosis effects on human bone marrow (BM) and cord blood (CB) and mouse BM colony-forming units (CFU)-granulocyte macrophage, burst-forming units-erythroid, and CFU-granulocyte-erythroid-macrophage-megakaryocyte with similar dose responses. The survival effects were direct-acting, as assessed on colony formation by single isolated human BM and CB CD34+++ cells. Effects were mediated through CXCR4 and Gαi proteins. Moreover, SDF-1/CXCL12 greatly enhanced the engrafting capability of mouse long-term, marrow-competitive, repopulating stem cells cultured ex vivo with interleukin-6 and steel factor for 48 h. These results extend information on the survival effects mediated through the SDF-1/CXCL12–CXCR4 axis and may be of relevance for ex vivo expansion and gene-transduction procedures.
Monocyte and macrophage functions in M-CSF-deficient op/op mice during experimental leishmaniasis
Authors: Schönlau Frank , Schlesiger Christian , Ehrehen Jan , Grabbe Stephan , Sorg Clemens , Sunderkötter Cord
Published: April 2003

Mice with a naturally occurring Csfmop/Csfmop (op/op) gene mutation lack functional macrophage-colony stimulating factor (M-CSF) and are deficient of M-CSF-derived macrophages. They are severely monocytopenic, and their remaining M-CSF-independent macrophages were shown to differ in differentiation and distinct functions when compared with phenotypicaly normal mice of the same background. It is not known if osteopetrosis mice (op/op mice) are able to mount a specific immune response against intracellular pathogens, as this would require complex effector functions by macrophages. We therefore investigated the ability of op/op mice and their M-CSF-independent macrophages to combat infection with Leishmania major. op/op mice retained the ability to resist an infection with L. major by mounting a T helper cell type 1 cell response, eliminating parasites and resolving the lesions. Macrophages from op/op mice were able to sufficiently perform effector functions in vitro, such as phagocytosis, production of leishmanicidal nitric oxide (NO), killing of parasites, and release of interleukin (IL)-12. There were quantitative differences, as M-CSF-derived macrophages from hematopoietic organs of control mice showed significantly higher rates of phagocytosis and higher NO release after stimulation with lipopolysaccharides than corresponding macrophages from op/op mice. In contrast, when peritoneally elicited macrophages were used, those from op/op mice revealed a stronger response than those from control mice with regard to release of NO or IL-12. These differences suggest that M-CSF-independent maturation of op/op monocytes subsequent to their release from hematopoietic tissue exerts influence on their effector functions. However, M-CSF or M-CSF-derived macrophages are not necessary for an effective immune response against L. major.
Case-based generation of adaptive product manuals
Authors: Pham D T , Setchi R M
Published: April 2003

This paper presents an intelligent hypermedia product support system developed for the needs of a truck manufacturer that enables formalization of and learning from experience. Case-based reasoning (CBR) is employed to interpret a user's request for information, construct a new solution and adapt it to the user and his/her task. The proposed approach is illustrated with a case study that describes context-sensitive retrieval of hypermedia documents contained within an intelligent product manual.
Computer-based modelling of thermal distortions in turning
Authors: Sukaylo V A , Krukovsky P G , Kaldos A , Lierath F , Kundrak J , Emmer T
Published: April 2003

It is well established that in metal removal processes almost all the energy used for the process is transformed into heat, thus affecting the tool life and the accuracy of the workpiece. The primary heat source is the deformation work and friction in the contact zone between the workpiece and the tool, which cause the temperature to increase. In order to control the temperature increase, cutting fluids are used to reduce friction and to remove the heat from the work zone. A finite element method based computer model was developed for the simulation of thermal deformation in multipass turning when different cooling conditions were applied. This paper presents novel theoretical and experimental solutions to establish model parameters in order to ensure adequacy of the model to the real heat transfer process in turning. This new inverse problem solution (IPS) technique was applied to obtain the heat generated by the cutting process and the heat transfer coefficients from the workpiece to still air and the air-oil or air-water cooling mixture. The predicted results for workpiece temperature field and workpiece accuracy are in good agreement with the measured data.
Expression of Surfactant Protein mRNA in Normal and Neoplastic Lung of B6C3F1 Mice as Demonstrated by In Situ Hybridization
Authors: Pilling A. M. , Mifsud N. A. M. , Jones S. A. , Endersby-Wood H. J. , Turton J. A.
Published: April 2003

The localization of surfactant protein (SP), A, B, C, and D mRNAs was examined in B6C3F1 mice in the normal lung, and in a range of spontaneous proliferative lung lesions using nonisotopic in situ hybridization (ISH). The aim was to develop diagnostic markers, and if possible, throw further light on the histogenesis of these lesions. Tissues from 21 animals were examined, the lesions studied were: 4 alveolar epithelial hyperplasias, 12 alveolar/bronchiolar (A/B) adenomas, and 5 A/B carcinomas. Lung metastases of hepatocellular carcinoma (HCC) were used as controls. In the nonneoplastic lung, staining for SP A, B, and C mRNA was observed in normal and hyperplastic type II cells but not in the bronchiolar epithelium. SP mRN As were present in all lung tumors, with SPs A, B, and C being coexpressed in 10/12 (83%) of adenomas and 4/5 (80%) of carcinomas in both solid and tubulopapillary areas. No signals for SP D mRNA were noted in normal or neoplastic lung. Additionally, no staining for any SP transcript was observed in the HCC metastases examined. In summary, ISH for SP A, B, or C mRNA was a helpful aid in the diagnosis of proliferative lesions of the murine lung, enabling differentiation from hepatocellular metastases. Furthermore, this work provides strong support for the proposal that spontaneous lung tumors in B6C3F1 mice are of alveolar, not bronchiolar origin, and consistently show type II cell differentiation. We suggest that such tumors should be referred to as alveolar adenomas and carcinomas.
Pathogenesis of Newcastle Disease in Chickens Experimentally Infected with Viruses of Different Virulence
Authors: Brown C. , King D. J. , Seal B. S.
Published: April 2003

Groups of 4-week-old White Rock chickens were inoculated intraconjunctivally with nine isolates of Newcastle disease virus representing all pathotypes. Birds were monitored clinically and euthanatized sequentially, with collection of tissues for histopathologic examination and in situ hybridization using an antisense digoxigenin-labeled riboprobe corresponding to the sequence of the gene coding for the matrix protein. Disease was most severe with velogenic viscerotropic pathotypes and was characterized by acute systemic illness with extensive necrosis of lymphoid areas in the spleen and intestine. Viral nucleic acid was detected in multiple tissues but most prominently in macrophages associated with lymphoid tissue. Velogenic neurotropic isolates caused central nervous system disease despite minimal amounts of viral nucleic acid detected in neural tissue. Mesogenic and lentogenic pathotypes caused no overt disease; however, viral nucleic acid was present in myocardium and air sac epithelium following infection with these isolates. Compromise of air sac and myocardium may predispose mesogen- and lentogen-infected chickens to secondary infection and/or decreased meat and egg production.
Neurotoxicity of 1,3,5-Trinitrobenzene (TNB): Immunohistochemical Study of Cerebrovascular Permeability
Authors: Chandra A. M. S. , Campbell G. A. , Reddy G. , Qualls C. W.
Published: April 2003

1,3,5-Trinitrobenzene (TNB) is a soil and water contaminant at certain military installations. Encephalopathy in rats given 10 daily oral doses of TNB has been reported. The lesion was bilaterally symmetric vacuolation and microcavitation in the cerebellar roof nuclei, vestibular nuclei, olivary nuclei, and inferior colliculi. The contribution of the blood-brain barrier (BBB) in the genesis of these lesions remains uncertain. One of the main goals of the present work was to evaluate the functional state of the BBB. Male Fischer 344 rats (five rats/group) were euthanatized after four, five, six, seven, eight, or 10 daily doses of TNB (71 mg/kg). A different set of rats (five rats/group) was allowed to recover for 10 or 30 days after receiving 10 doses of TNB. Integrity of the BBB was assessed by immunohistochemical staining for extrav-asated plasma albumin on paraffin-embedded sections. Rats euthanatized after four to eight doses had no lesions, and albumin extravasation in the susceptible regions of the brain was minimal. Rats receiving 10 daily doses of TNB had bilaterally symmetric vacuolation and microcavitation in the cerebellar nuclei, vestibular nuclei, and inferior colliculi in association with multifocal, often confluent foci of extravasated albumin in susceptible nuclei. Albumin was present in vascular walls, extracellular space, and neurons. Immunoreactivity in neurons was of two types: cytoplasmic staining representing pinocytic uptake and homogenous staining of the entire neuron (nucleus and cytoplasm) due to uncontrolled albumin leakage through the damaged cell membrane. In rats allowed to recover for 10 days, the microcavitated foci were infiltrated by glial and gitter cells. Albumin immunoreactivity was present as extracellular granular debris, and neuronal staining (for albumin) was mild. In rats allowed to recover for 30 days, immunoreactivity to albumin was not seen. This study demonstrates that TNB-mediated tissue damage is accompanied by breakdown of the BBB. The presence of vacuolation and associated extravasated serum proteins in TNB-treated rats is an indication of vasogenic brain edema, which appears to be a critical event in TNB toxicity. Additional studies are needed to determine the reason for selective regional vulnerability and brain microvasculature susceptibility to TNB.
Detection of an Autoantibody from Pug Dogs with Necrotizing Encephalitis (Pug Dog Encephalitis)
Authors: Uchida K. , Hasegawa T. , Ikeda M. , Yamaguchi R. , Tateyama S.
Published: April 2003

An autoantibody against canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum of two Pug dogs (Nos. 1 and 2) by indirect immunofluorescence assay (IFA). Dog No. 1, a 2-year-old male, exhibited severe depression, ataxia, and generalized seizures and died 2 months after the onset of symptoms. Dog No. 2, a 9-month-old male, exhibited severe generalized seizures and died 17 months after the onset of symptoms. Histopathologic examination revealed a moderate to severe multifocal accumulation of lymphocytes, plasma cells, and a few neutrophils in both the gray and white matter of the cerebrum in dog No. 1. In dog No. 2, the cellular infiltrates were mild, but there was a severe, diffuse, and multifocal necrosis in the cerebral cortex with prominent astrocytosis. With the aid of IFA using fluorescein isothiocyanate-labeled antidog IgG goat serum and a confocal imaging system, specific reactions for glial cells were detected in the CSF of these Pug dogs but not in six canine control CSF samples. Double-labeling IFA using CSF from these Pug dogs and a rabbit antiserum against glial fibrillary acidic protein (GFAP) revealed that the autoantibody recognized GFAP-positive astrocytes and their cytoplasmic projections. By immunoblot analysis, the autoantibody from CSF of these Pug dogs recognized two common positive bands at 58 and 54 kd, which corresponded to the molecular mass of human GFAP. The role of this autoantibody for astrocytes is not yet clear. However, if the presence of the autoantibody is a specific feature of Pug dog encephalitis, it will be a useful clinical diagnostic marker and a key to the pathogenesis of this unique canine neurologic disease.
Demonstration of Tritrichomonas foetus in the External Genitalia and of Specific Antibodies in Preputial Secretions of Naturally Infected Bulls
Authors: Rhyan J. C. , Wilson K. L. , Wagner B. , Anderson M. L. , Bondurant R. H. , Burgess D. E. , Mutwiri G. K. , Corbeil L. B.
Published: April 2003

Portions of penis and prepuce were collected from 24 bulls with current or recent Tritrichomonas foetus infection. Epididymides were collected from seven of the bulls, and seminal vesicles and prostate were collected from four. Following immunohistochemical staining with two monoclonal antibodies (34.7C4.4 and TF1.15) prepared against T. foetus surface antigens, trichomonads were identified in sections from 15 of the bulls. Organisms were most often located in penile crypts in the midshaft and caudal regions and less often in preputial crypts. Trichomonads were not observed in sections from other genitalia or in subepithelial tissue. T. foetus antigen, however, was present in the cytoplasm of some epithelial cells and the cytoplasm of some mononuclear cells in subepithelial lymphoid aggregates and follicles. Preputial smegma was collected from 16 T. foetus-infected bulls and from 16 control bulls with negative T. foetus cultures. Preputial antibody levels to TF1.17, a surface antigen of T. foetus, were determined by an enzyme-linked immunosorbent assay. Preputial secretions from infected bulls contained specific antibody of each isotype and subisotype tested. IgG1 responses were the greatest, IgM and IgA responses were approximately equal, and IgG2 responses were low. Each isotype and subisotype response in infected bulls was significantly greater than that in the controls. These results confirm previous speculation concerning anatomical sites of infection and suggest that parasite antigen can be taken up and processed locally, resulting in deposition of specific IgG1, IgG2, IgA, and IgM antibodies in the preputial cavity.
Splenic Myeloid Metaplasia, Histiocytosis, and Hypersplenism in the Dog (65 Cases)
Authors: Spangler W. L. , Kass P. H.
Published: April 2003

Splenectomy specimens from 65 dogs with severe, diffuse, sustained, and progressive splenomegaly were examined. The clinical signs, hematology, and serum chemistry values in for the dogs were not useful diagnostic features. Microscopic changes in the spleens were distinctive and consisted of 1) myeloid metaplasia, 2) histiocytosis, 3) erythrophagocytosis, and 4) thrombosis with segmental infarction. Ultrastructural features suggested proliferative changes in the splenic reticular cells and macrophages (reticular meshwork) that described a continuum from reactive changes associated with immunologic damage of erythrocytes to neoplastic proliferation of histiocytic components. Thirty percent of the dogs survived 12 months. Approximately one half (53%) of the dogs with complete postmortem evaluations showed multiorgan involvement with a tissue distribution and cell morphology consistent with histiocytic neoplasia. For the remaining dogs (47%), only splenic pathology was consistently present, and a specific cause of death was often not evident. Distinctive histologic changes in the splenic tissues—including mitotic activity, erythrophagocytosis, giant cell formation, thrombosis/infarction, and the proportion and distribution of histiocytic and hematopoietic cells—were statistically evaluated for prognostic relevance. The presence of giant cells was the only reliable prognostic feature, and that was indicative of a fatal outcome. These descriptive changes of myeloid metaplasia in the canine spleen are compared with the human clinical and pathologic syndromes of 1) agnogenic myeloid metaplasia, 2) hemophagocytic syndromes, and 3) hypersplenism. These diseases in humans produce histopathologic changes in the spleen that are similar to those observed in the canine splenic tissue we examined in this study.
Dermal Intravascular Leiomyosarcoma in a Cat
Authors: Jacobsen M. C. , Valentine B. A.
Published: April 2003

A 10-year-old female spayed domestic shorthaired cat presented with a subcutaneous tumor between the first and second phalanges of the left hind foot. Six months after excision, a similar tumor occurred on the medial aspect of the third phalanx of the same limb. Histologically, both tumors consisted of solid masses of spindle and round cells, many of which grew within endothelial-lined vessels. Tumor cells stained positively for smooth muscle actin and vimentin, but were negative for cytokeratin, S-100, desmin, synaptophysin, factor VIII-related antigen, and neuron-specific enolase. The diagnosis was dermal intravascular leiomyosarcoma.
Immunohistochemical and Clinical Evaluation of p53 in Canine Cutaneous Mast Cell Tumors
Authors: Jaffe M. H. , Hosgood G. , Taylor H. W. , Kerwin S. C. , Hedlund C. S. , Lopez M. K. , Davidson J. R. , Miller D. M. , Paranjpe M.
Published: April 2003

One hundred twenty-six cutaneous mast cell tumors obtained by excisional biopsy from 106 dogs were evaluated using immunohistochemical staining for the presence of p53 protein. A standard avidin–biotin immunohistochemical protocol was used incorporating a polyclonal antibody of rabbit origin (CM-1) as the primary antibody. Histopathologic grading of tumors was performed on hemotoxylin and eosin–stained samples. There was a significant difference in the percentage of cells staining positive for p53 for the histopathologic grades ( P = 0.0005). Grade III tumors had a significantly greater p53 content than did grade I or II tumors ( P < 0.05). Clinical data obtained retrospectively was available for 54 dogs. Tumor recurred in 19 of 54 (35.2%) dogs. Twenty-nine dogs died by the end of the study; 9 of 29 (31.0%) died of mast cell tumor disease. Histopathologic grade showed a significant negative association with survival time. Both clinical stage and histopathologic grade showed a significant negative association with time to recurrence. The percentage of cells staining positive for p53 did not significantly improve the forward analysis. Immunohistochemical detection of p53 did not appear useful in characterizing the clinical association between cutaneous mast cell tumor cellular features and survival time or time to tumor recurrence in dogs.
Experimental Infection of Ponies with Borrelia burgdorferi by Exposure to Ixodid Ticks
Authors: Chang Y.-F. , Novosol V. , McDonough S. P. , Chang C.-F. , Jacobson R. H. , Divers T. , Quimby F. W. , Shin S. , Lein D. H.
Published: April 2003

Seven specific-pathogen-free (SPF) ponies, 1–5 years old, were exposed to Borrelia burgdorferi–infected adult ticks while being treated with dexamethasone over 5 consecutive days. One SPF pony (pony No. 178) was first exposed to laboratory-reared nymphs without B. burgdorferi infection and 3 weeks later was exposed to B. burgdorferi–infected adult ticks with concurrent dexamethasone treatment for 5 consecutive days. Four uninfected ponies treated with dexamethasone, exposed to laboratory-reared ticks without B. burgdorferi infection served as uninfected controls. Clinical signs, bacteriologic culture, polymerase chain reaction (PCR) for bacterial DNA, immunologic responses, and gross lesions and histopathologic changes were investigated during the experiment or at necropsy 9 months after tick exposure. In all of the seven challenged ponies, infection with B. burgdorferi was detected from monthly skin biopsies and various tissues at postmortem examination by culture and by PCR. However, pony No. 178 exposed to laboratory-reared nymphs (without B. burgdorferi infection) and challenged with B. burgdorferi–infected adult ticks 2 months later did not develop a B. burgdorferi infection. All of the infected ponies seroconverted. Control ponies and pony No. 178 were negative by culture, PCR, and serology. Except for skin lesions, we failed to induce any significant histopathologic changes in this study. This is the first report of successful tick-induced experimental infection in ponies by exposure to B. burgdorferi–infected ticks. This Lyme disease model will be very useful to evaluate efficacy of vaccines against the Lyme agent and the effect of antibiotic therapy on horses infected with B. burgdorferi.
Systemic κAL Amyloidosis Associated with Bovine Leukocyte Adhesion Deficiency
Authors: Taniyama H. , Yamamoto S. , Sako T. , Hirayama K. , Higuchi H. , Nagahata H.
Published: April 2003

Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein–Friesian cow with systemic κAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine κ-light chain and reacted weakly against bovine λ-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin κ-light chains of precursor protein in cattle.
Subcutaneous Atypical Mycobacteriosis in Captive Tiger Quolls (Dasyurus maculatus)
Authors: Raymond J. T. , Tell L. , Bush M. , Nichols D. K. , Schulman F. Y. , Montali R. J.
Published: April 2003

From July 1989 to October 1998, 9/37 (24%) adult captive tiger quolls ( Dasyurus maculatus) were diagnosed with atypical mycobacterial infection involving the subcutis and skin. Females were more often affected than males (seven females, two males). Grossly, lesions presented as focal thickenings, plaques, and abscesses within the subcutis, often with fistulous tracts. The subcutis and skin overlying cervical and thoracic regions were the primary sites of infection. Cytology of subcutaneous impression smears from all nine affected tiger quolls revealed pyogranulomatous inflammation admixed with several acid-fast bacilli. Histologically, all tiger quolls had nodular to diffuse pyogranulomatous panniculitis and cellulitis. Small numbers of acid-fast bacilli were noted histologically in 7/9 (78%) animals. Skin cultures from seven tiger quolls were positive for one or more different Runyon group IV mycobacteria. The disease described in these tiger quolls is similar to subcutaneous atypical mycobacteriosis of humans and domestic animals.
C-Cell Carcinoma (Medullary Thyroid Carcinoma) Associated with Multiple Endocrine Neoplasms in a Ferret (Mustela putorius)
Authors: Fox J. G. , Dangler C. A. , Snyder S. B. , Richard M. J. , Thilsted J. P.
Published: April 2003

A firm, infiltrative mass was found in the thyroid region of an adult castrated male ferret (Mustela putorius) presenting with vague signs of weight loss, minor inappetence, and decreased activity. Efforts to surgically excise the tissue were unsuccessful, and the animal was euthanatized. Gross and histopathologic evaluation revealed multiple endocrine neoplasms, including C-cell carcinoma, adrenocortical adenoma, pheochromocytoma, and endocrine tumor of the pancreas. This is the first descriptive account of a C-cell carcinoma, also known as medullary thyroid carcinoma, in a ferret, although other endocrine neoplasms in this species have been reported with some frequency. These findings mimic features observed in human multiple endocrine neoplasia syndromes.
Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation
Authors: Frazier K. S. , Paredes A. , Dube P. , Styer E.
Published: April 2003

Connective tissue growth factor (CTGF) has been shown to mediate many actions of transforming growth factor-beta (TGF-β) in the fibrotic response in several diseases. We compared expression of CTGF, TGF-β, platelet-derived growth factor (PDGF), TNF-α, and interleukin-1 (IL-1) by in situ hybridization in Sprague-Dawley rats euthanized at 0, 2, 4, and 8 weeks after 5/6 nephrectomy using the rat remnant kidney model of renal failure. Collagen was evaluated by trichrome stains, immunohistochemistry, and electron microscopy. We compared expression patterns to cells undergoing metaplasia. Tubular epithelial regeneration and transdifferentiation to myofibroblasts were assessed morphologically and by proliferating cell nuclear antigen, smooth muscle actin, desmin, and vimentin immunohistochemistry. CTGF expression was minimal in controls, mild at 2 weeks and marked by 4 to 8 weeks in interstitial fibroblasts, coinciding with damage, regeneration, and fibrosis. TGF-β expression was increased in many cell types at 2 weeks, increased further by 4 weeks, then remained constant. PDGF-B messenger RNA was found in many stromal cells at 2–4 weeks, but expression decreased at 8 weeks. No significant IL-1 or TNF-α staining was detected. We conclude that CTGF and interacting factors are associated with development or progression of chronic interstitial fibrosis. Proximity of CTGF, TGF-β, and PDGF mRNA expression to regenerative epithelial cells and those transdifferentiating to myofibroblasts suggests that growth factors may modulate renal tubular epithelial differentiation.
Marginal Siderosis and Degenerative Myelopathy: a Manifestation of Chronic Subarachnoid Hemorrhage in a Horse with a Myxopapillary Ependymoma
Authors: Huxtable C. R. , de Lahunta A. , Summers B. A. , Divers T.
Published: April 2003

Marginal siderosis is recognized in humans as an uncommon clinicopathologic entity characterized by degeneration of neural tissue at the surface of the brain and spinal cord, in association with the accumulation of hemosiderin, and resulting from chronic subarachnoid hemorrhage. The sources of hemorrhage are various and include neoplasms, malformations, cysts, and vasculopathy. Marginal siderosis of the spinal cord due to a myxopapillary ependymoma was diagnosed in a 19-year-old Dutch Warm Blood horse with clinical signs of myelopathy. There is only one previous report of marginal siderosis in the veterinary literature, also in a horse with clinical myelopathy.
Histopathology of Experimental Plague in Cats
Authors: Watson R. P. , Blanchard T. W. , Mense M. G. , Gasper P. W.
Published: April 2003

Formalin-fixed paraffin-embedded archival tissues of seven adult cats of both sexes that died after being experimentally infected with Yersinia pestis were examined light microscopically to characterize the lesions. The cats were exposed in two groups using two routes of infection: ingestion of Y. pestis-infected rodent or a subcutaneous injection of Y. pestis to simulate a flea bite. Immunohistochemistry was performed on tissues from all organ systems from a representative cat from each group to determine the distribution of Y. pestis bacilli during infection. In all seven cats, bubonic plague lesions were seen. The lesions of pneumonic plague were present in two cats. Septicemic plague was confirmed in all seven cats by bacteriologic culture. Aggregations of bacteria were seen in lymphoid tissue in all cats and in lung tissues from the two cats with pneumonic plague. The most consistent histologic finding was necrosuppurative inflammation in the lymph nodes. Invariably, Y. pestis bacteria were present in large numbers at affected sites. Orally infected cats had more numerous lesions in the lymph nodes of the head and neck regions. These experimentally induced cases of feline plague document that cats are unique among carnivores in exhibiting bubonic, pneumonic, and septicemic plague following exposure to Y. pestis. The lesions of the orally infected cats were consistent with those previously described for naturally occurring Y. pestis infections in cats and corroborate the contention that cats most commonly contract plague by eating Y. pestis-infected rodents and not via flea bite. The histopathology of Y. pestis disease in these cats is comparable to that described for human plague.
Symptomatic Granular Cell Tumor Involving the Pituitary Gland in a Dog: A Case Report and Review of the Literature
Authors: Barnhart K. F. , Edwards J. F. , Storts R. W.
Published: April 2003

A granular cell tumor involving the pituitary gland, optic chiasm and ventral pyriform lobes was discovered in a 12-year-old Labrador Retriever. Clinical signs included acute blindness, seizures, ataxia, weakness, and behavioral changes. The diagnosis was established by histopathologic and ultrastructural examination of neoplastic tissues collected at necropsy. Granular cell tumors involving the central nervous system are well documented in humans but rarely have been described in dogs. The location of the neoplasm and the clinical symptoms seen in this dog closely parallel those of a rare syndrome in humans commonly described as symptomatic parasellar or pituitary granular cell tumors. The cell of origin for these tumors is still highly debated, and attempts to characterize human granular cell tumors through immunohistochemistry have produced conflicting results. An immunohistochemical profile of this neoplasm revealed focal positive staining for vimentin with a lack of staining for neuron-specific enolase, glial fibrillary acidic protein, S-100, and synaptophysin. All neoplastic cells were strongly positive with the periodic acid-Schiff reaction.
Bilateral Focal Cerebral Angiomatosis Associated with Nervous Signs in a Cat
Authors: Kipar A. , Hetzel U. , Armien A. G. , Baumgärtner W.
Published: April 2003

A case of cerebral angiomatosis in a cat was associated with neurologic signs characterized by clusters of severe generalized seizures. Bilaterally in the gray matter, most prominent in the cingulate gyrus, there was focal accumulation of garlandlike arrangements of blood vessels. Vessels exhibited activated, hypertrophic endothelial cells and thickening and progressive dystrophic mineralization of the basement membrane, with complete luminal obstruction of some affected vessels. Thickening of the basement membrane was due to accumulation of endothelium-derived proteins such as laminin and von Willebrand factor. Furthermore, moderate diffuse astrogliosis was observed. Findings indicate an idiopathic angiomatosis, with clinical signs possibly due to ischemia resulting from narrowing or complete obliteration of vessel lumina. Changes represent a unique endothelial cell-derived lesion within the brain not previously described in humans or domestic animals.
Hamster Polyomavirus Infection in a Pet Syrian Hamster (Mesocricetus auratus)
Authors: Simmons J. H. , Riley L. K. , Franklin C. L. , Besch-Williford C. L.
Published: April 2003

An approximately 8-week-old pet Syrian hamster (Mesocricetus auratus) with a 1-week history of dyspnea, hyporexia, and ataxia was submitted for necropsy. On gross examination, the hamster had multiple abdominal adhesions and enlargement of the mesenteric lymph node. Histologic evaluation revealed multicentric lymphoma of the liver, jejunum, mesenteric lymph node, testicular fat pad, and epididymis. Based on the hamster's age and the type and distribution of the lymphoma, a presumptive diagnosis of hamster polyomavirus- induced lymphoma was made. A specific polymerase chain reaction (PCR) was developed, which confirmed the diagnosis. An in situ PCR demonstrated hamster polyomavirus DNA within lymphocytes of the multicentric lymphoma and renal tubular epithelial cells and within clusters of enterocytes in the jejunum. These data are consistent with environmental dissemination of hamster polyomavirus virions through the renal tubular epithelium and into the urine and with fecal shedding of hamster polyomavirus virions; however, additional studies will be needed to confirm these observations.
Heterophil Function and Resistance to Staphylococcal Challenge in Broiler Chickens Naturally Infected with Avian Leukosis Virus Subgroup J
Authors: Stedman N. L. , Brown T. P. , Brooks R. L. , Bounous D. I.
Published: April 2003

Avian leukosis virus subgroup J has a high tropism for myeloid lineage cells and frequently induces neoplastic transformation of myelocytes. The impact of congenital avian leukosis virus subgroup J infection on the function of circulating heterophils and susceptibility to staphylococcal infection was investigated. Six-week-old broiler chickens negative for exogenous avian leukosis viruses or congenitally infected with avian leukosis virus subgroup J were inoculated intravenously with 106 colony-forming units of Staphylococcus aureus, and pre- and postinoculation heterophil function was assessed. All chickens developed a leukocytosis with heterophilia after inoculation, but total leukocyte and heterophil counts were significantly higher in leukosis-negative chickens than in virus-infected chickens. Tenosynovitis was more severe in leukosisnegative chickens, and 2/10 (20%) of the virus-infected chickens had no histologic evidence of tenosynovitis. Osteomyelitis in the tibiotarsus or tarsometatarsus developed in 5/10 (50%) of the chickens in each group. S. aureus was recovered from the hock joint of 6/10 (60%) of the chickens in each group. Heterophils from all chickens exhibited similar phagocytic ability pre- and postinoculation. Heterophils from virus-infected chickens exhibited less bactericidal ability preinoculation than did heterophils from leukosis-negative chickens. However, postinoculation bactericidal ability was similar in both groups. Avian leukosis virus subgroup J provirus was present in heterophils isolated from congenitally infected chickens. Heterophils isolated from broiler chickens congenitally infected with avian leukosis virus subgroup J exhibit no significant functional deficits, and infected and uninfected chickens exhibit similar susceptibility to staphylococcal infection.
Experimental Reproduction of Severe Disease in CD/CD Pigs Concurrently Infected with Type 2 Porcine Circovirus and Porcine Reproductive and Respiratory Syndrome Virus
Authors: Harms P. A. , Sorden S. D. , Halbur P. G. , Bolin S. R. , Lager K. M. , Morozov I. , Paul P. S.
Published: April 2003

Three-week-old cesarean-derived colostrum-deprived (CD/CD) pigs were inoculated with porcine circovirus type 2 (PCV2, n = 19), porcine reproductive and respiratory syndrome virus (PRRSV, n = 13), concurrent PCV2 and PRRSV (PCV2/PRRSV, n = 17), or a sham inoculum ( n = 12) to compare the independent and combined effects of these agents. Necropsies were performed at 7, 10, 14, 21, 35, and 49 days postinoculation (dpi) or when pigs became moribund. By 10 dpi, PCV2/PRRSV-inoculated pigs had severe dyspnea, lethargy, and occasional icterus; after 10 dpi, mortality in this group was 10/11 (91%), and all PCV2/ PRRSV-inoculated pigs were dead by 20 dpi. PCV2-inoculated pigs developed lethargy and sporadic icterus, and 8/19 (42%) developed exudative epidermitis; mortality was 5/19 (26%). PRRSV-inoculated pigs developed dyspnea and mild lethargy that resolved by 28 dpi. Microscopic lesions consistent with postweaning multisystemic wasting syndrome (PMWS) were present in both PCV2- and PCV2/PRRSV-inoculated pigs and included lymphoid depletion, necrotizing hepatitis, mild necrotizing bronchiolitis, and infiltrates of macrophages that occasionally contained basophilic intracytoplasmic inclusion bodies in lymphoid and other tissues. PCV2/ PRRSV-inoculated pigs also had severe proliferative interstitial pneumonia and more consistent hepatic lesions. The most severe lesions contained the greatest number of PCV2 antigen–containing cells. PRRSV-inoculated pigs had moderate proliferative interstitial pneumonia but did not develop bronchiolar or hepatic lesions or lymphoid depletion. All groups remained seronegative to porcine parvovirus. The results indicate that 1) PCV2 coinfection increases the severity of PRRSV-induced interstitial pneumonia in CD/CD pigs and 2) PCV2 but not PRRSV induces the lymphoid depletion, granulomatous inflammation, and necrotizing hepatitis characteristic of PMWS.
Haemophilus somnus Isolated from a Urachal Abscess in a Calf
Authors: Starost M. F.
Published: April 2003

A urachal abscess was diagnosed in a 2-month-old, crossbred heifer that was presented for a distended abdomen and clinical signs of choking. Cultures of the mucopurulent exudate, obtained from within the mass on necropsy, yielded Haemophilus somnus. This is the first known documented report of H. somnus isolated from a urachal abscess.
Piloleiomyosarcoma in Seven Ferrets
Authors: Rickman B. H. , Craig L. E. , Goldschmidt M. H.
Published: April 2003

In each of seven ferrets ( Mustela putorius furo) with leiomyosarcoma, a single dermal mass was identified and biopsied. Each mass consisted of a well-demarcated but nonencapsulated proliferation of large spindle- to strap-shaped cells arranged in interwoven bundles. The cells resembled the smooth muscle cells of the adjacent arrector pili muscles, but with marked nuclear pleomorphism. Immunohistochemical staining for smooth muscle actin, desmin, and vimentin was positive and staining for myoglobin and cytokeratin was negative. Follow-up on three of the ferrets indicates that the prognosis is good following complete surgical excision.
Mixed Germ Cell Tumor in the Eye of a Dog
Authors: Patterson-Kane J. C. , Schulman F. Y. , Santiago N. , Mckinney L. , Davis C. J.
Published: April 2003

A 3-year-old female neutered Staffordshire Bull Terrier presented with a mixed germ cell tumor involving the base of the iris and the ciliary body of the right eye. The tumor mass was composed primarily of packeted vacuolated, polygonal (hepatoid) cells and small round cells; epithelial cells lining tubuloacinar structures were a less prominent component. The hepatoid and round cells stained positively for alpha-fetoprotein and cytokeratin. The epithelial cells stained positively for cytokeratin only, and some contained cytoplasmic mucin droplets. The polygonal cells were interpreted as a hepatoid variant of yolk sac tumor, and the epithelial cells were considered a teratomatous component. Trabeculae of bone were observed within the mass and may have been metaplastic or a teratomatous element. Extragonadal germ cell tumors are rare in dogs and have previously been reported only in the suprasellar region. This is the first report of this tumor type in the eye of a nonhuman species.
Localization of Swine Influenza Virus in Naturally Infected Pigs
Authors: Jung T. , Choi C. , Chae C.
Published: April 2003

Swine influenza virus (SIV) RNA and antigen were detected in 15 naturally infected pigs by in situ hybridization using a nonradioactive digoxigenin-labeled cDNA probe and by immunohistochemistry using an influenza virus H1N1-specific monoclonal antibody. A 582-base pair cDNA probe for viral RNA encoding the nucleocapsid protein of SIV type A H1N1 strain was generated by the reverse transcription polymerase chain reaction. In situ hybridization and immunohistochemistry gave similar results for serial sections from each of 15 lung samples. Positive cells typically exhibited a dark brown (in situ hybridization) or red (immunohistochemistry) reaction product in the nucleus and cytoplasm without background staining. A strong positive signal for both in situ hybridization and immunohistochemistry was detected mainly in the bronchial and bronchiolar epithelial cells. A less intense signal was detected in the interstitial and alveolar macrophages. Simultaneous detection of hybridization and immunohistochemical signals on serial sections provided evidence that SIV had replicated in positive cells. The in situ hybridization technique developed in this study was useful for the detection of SIV RNA in tissues taken from naturally infected pigs and may be a valuable technique for studying the pathogenesis of SIV infection.
Expression of Nitric Oxide Synthase 2 and Tumor Necrosis Factor α in Swine Naturally Infected with Actinobacillus pleuropneumoniae
Authors: Cho W.-S. , Chae C.
Published: April 2003

Nitric oxide synthase 2 (NOS2) and tumor necrosis factor α (TNF-α) were detected and localized in 15 pigs with naturally occurring pleuropneumonia by use of in situ hybridization with a nonradioactive digoxigenin-labeled cDNA probe. Two cDNA probes 491 and 219 base pairs for NOS2 and TNF-α, respectively, were generated by reverse transcription polymerase chain reaction. All 15 pigs infected with Actinobacillus pleuropneumoniae had distinct positive hybridization signals for NOS2 and TNF-α. Strong hybridization signals for both NOS2 and TNF-α were evident in degenerate alveolar leukocytes bordering zones of coagulative necrosis and in alveolar spaces. NOS2 nucleic acids were detected in neutrophils and macrophages. In situ hybridization of serial sections of lung tissue revealed numerous cells positive for NOS2 and TNF-α, suggesting that NOS2 and TNF-α expression may play a role in the pathophysiology of pleuropneumonia.
Early Platelet Aggregation as a Cause of Thrombocytopenia in Classical Swine Fever
Authors: Bautista M. J. , Ruiz-villamor E. , Salguero F. J. , Sánchez-Cordón P. J. , Carrasco L. , Gómez-Villamandos J. C.
Published: April 2003

Twenty pigs were inoculated with a virulent classical swine fever virus isolate to determine the mechanism responsible for thrombocytopenia using histopathologic, ultrastructural, and immunohistochemical (detection of viral antigens gp55 and FVIII-rag) techniques. In animals euthanatized at 2, 4, and 6 days postinoculation (dpi), clusters of granular material staining positive for FVIII-rag were observed in splenic cords, the marginal zone, hepatic sinusoids, and the perisinusoidal space. Moreover, numerous macrophages in these areas were swollen and displayed an intensely positive granular and cytoplasmic reaction. Cell alterations indicative of platelet activation and secretory and phagocytic activation of resident macrophages were also observed in these sites at 2 and 4 dpi. These results suggest that the thrombocytopenia observed in pigs is caused in the first instance by massive activation and subsequent phagocytosis of platelets secondary to the release of platelet-activating factors by activated macrophages.