@article{sai_nakanishi_scofield_tokarz_linder_cohen_ninomiya-tsuji_2023, title={Aberrantly activated TAK1 links neuroinflammation and neuronal loss in Alzheimer?s disease mouse models}, volume={136}, ISSN={["1477-9137"]}, url={http://dx.doi.org/10.1242/jcs.260102}, DOI={10.1242/jcs.260102}, abstractNote={ABSTRACT}, number={6}, journal={JOURNAL OF CELL SCIENCE}, publisher={The Company of Biologists}, author={Sai, Kazuhito and Nakanishi, Aoi and Scofield, Kimberly M. and Tokarz, Debra A. and Linder, Keith E. and Cohen, Todd J. and Ninomiya-Tsuji, Jun}, year={2023}, month={Mar} } @article{bizikova_linder_anderson_2023, title={Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.12.0573}, abstractNote={Abstract}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bizikova, Petra and Linder, Keith E. and Anderson, Jamie G.}, year={2023}, month={Jun}, pages={S48–S57} } @article{gedon_bizikova_olivry_mendoza-kuznetsova_oberkirchner_robertson_linder_2023, title={Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms}, volume={6}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.13174}, DOI={10.1111/vde.13174}, abstractNote={Abstract}, journal={VETERINARY DERMATOLOGY}, author={Gedon, Natalie Katharina Yvonne and Bizikova, Petra and Olivry, Thierry and Mendoza-Kuznetsova, Ekaterina and Oberkirchner, Ursula and Robertson, James Benjamin and Linder, Keith Emerson}, year={2023}, month={Jun} } @article{phelps_palekar_conley_ferrero_driggers_linder_kullman_reif_sheats_dewitt_et al._2023, title={Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst}, volume={20}, ISSN={["1547-6901"]}, url={https://doi.org/10.1080/1547691X.2023.2176953}, DOI={10.1080/1547691X.2023.2176953}, abstractNote={Abstract Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.}, number={1}, journal={JOURNAL OF IMMUNOTOXICOLOGY}, author={Phelps, Drake W. and Palekar, Anika I. and Conley, Haleigh E. and Ferrero, Giuliano and Driggers, Jacob H. and Linder, Keith E. and Kullman, Seth W. and Reif, David M. and Sheats, M. Katie and DeWitt, Jamie C. and et al.}, year={2023}, month={Dec} } @article{gaudette_ladouceur_troan_whitehurst_dombrowski_lewbart_linder_passingham_christian_schreeg_2023, title={Retrospective analysis of histologic lesions in captive arachnids}, volume={4}, ISSN={["1544-2217"]}, DOI={10.1177/03009858231162948}, abstractNote={Invertebrates, including arachnids, are a common taxon in zoological collections. Invertebrate medicine and pathology are emerging subspecialties, but there is limited reference material or published resources describing histologic lesions in arachnids. Histopathology of 26 captive arachnids (20 spiders and 6 scorpions) from institutional collections was reviewed. Most animals were found dead with limited clinical signs. Tissues evaluated included body wall (cuticle and epidermis), skeletal muscle, book lungs, digestive tract (pharynx, esophagus, sucking stomach, midgut tube, midgut diverticula, and stercoral pocket), central and peripheral nervous system, heart, hemolymph vessels and sinuses, Malpighian tubules, coxal glands, and gonads. Inflammation was frequent (24/26, 92%), and seen in multiple organs (18/24, 75%) with the midgut diverticulum most commonly affected (14/24, 58%) followed by the book lungs (13/24 arachnids, 54%), and body wall (8/24 arachnids, 33%). Inflammation comprised hemocyte accumulation, hemocytic coagula, melanization, and nodulation. Infectious agents, including bacteria (11/26, 42%), fungi (10/26, 38%), and parasites (2/26, 8%), were seen within inflammatory aggregates. Coinfection with multiple infectious agents was common (6/24, 25%). No etiologic agent was identified in 7/24 (29%) cases with inflammatory lesions. Lesions suggestive of decreased nutritional status or increased metabolic rate included midgut diverticula atrophy in 11/26 (42%) animals and skeletal muscle atrophy in 6/26 (23%) animals. Atrophic lesions were seen in combination with infection (8/11, 73%), pregnancy (2/11, 18%), male sex (2/11, 18%), or without other lesions (1/11, 9%). Other suspected contributors to death included dysecdysis-associated trauma (2/26, 8%) and uterine intussusception (1/26, 4%). No animals had neoplasia.}, journal={VETERINARY PATHOLOGY}, author={Gaudette, Chris and LaDouceur, Elise E. B. and Troan, Brigid V. and Whitehurst, Nathan and Dombrowski, Daniel S. and Lewbart, Gregory A. and Linder, Keith E. and Passingham, Kent and Christian, Larry S. and Schreeg, Megan E.}, year={2023}, month={Apr} } @misc{bizikova_olivry_linder_rybnicek_2023, title={Spontaneous autoimmune subepidermal blistering diseases in animals: a comprehensive review}, volume={19}, ISSN={["1746-6148"]}, url={https://doi.org/10.1186/s12917-023-03597-1}, DOI={10.1186/s12917-023-03597-1}, abstractNote={Abstract}, number={1}, journal={BMC VETERINARY RESEARCH}, author={Bizikova, Petra and Olivry, Thierry and Linder, Keith and Rybnicek, Jan}, year={2023}, month={Feb} } @article{schreeg_radkin_haugland_murphy_rushton_linder_2022, title={Ameloblastic carcinoma in horses: case report and literature review}, ISSN={["1943-4936"]}, DOI={10.1177/10406387211068459}, abstractNote={ Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin–vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin–vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin–vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses. }, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Schreeg, Megan E. and Radkin, Megan and Haugland, Jennifer and Murphy, Brian G. and Rushton, Steve and Linder, Keith E.}, year={2022}, month={Jan} } @article{heniff_chen_christiansen_harms_law_legner_linder_2022, title={Cutaneous epitheliotropic lymphosarcoma in a captive white catfish (Ameiurus catus Linnaeus)}, volume={4}, ISSN={["1365-2761"]}, url={https://doi.org/10.1111/jfd.13625}, DOI={10.1111/jfd.13625}, abstractNote={Abstract}, journal={JOURNAL OF FISH DISEASES}, author={Heniff, Ashlyn C. and Chen, Laura R. and Christiansen, Emily F. and Harms, Craig A. and Law, Jerry M. and Legner, Christian and Linder, Keith E.}, year={2022}, month={Apr} } @article{rasche_mozzachio_linder_2022, title={Cutaneous mast cell tumors in 11 miniature pigs: a retrospective study}, ISSN={["1943-4936"]}, DOI={10.1177/10406387221079255}, abstractNote={ Better understanding of mast cell tumors (MCTs) in miniature pigs is needed to guide diagnosis and establish clinical significance. We characterized the gross pathology, histopathology, histochemical staining, and KIT immunoreactivity of cutaneous MCTs in a retrospective descriptive study of 11 miniature pigs ( Sus scrofa domesticus). Tumors were single or multiple papules, small nodules, or plaques. In one pig, lymph nodes and internal organs were affected. Histologically, all MCTs involved the dermis, and some extended to the subcutis (4 of 11) and skeletal muscle (1 of 11). Most tumors were well-demarcated, unencapsulated, nodular or multinodular masses (8 of 11) and fewer were poorly demarcated plaques (3 of 11). Neoplastic cells were often well-differentiated with pale amphophilic-to-eosinophilic faintly granular cytoplasm, occasional binucleation, rare multinucleation, and a low mitotic count (<7 per 10 hpf; 10 of 11). Eosinophils were present in tumors in all cases. Cytoplasmic granules stained most consistently with high-pH (2.5–3) toluidine blue (9 of 10) compared to low-pH (0.5–1) toluidine blue (6 of 9) or Giemsa (7 of 10). KIT immunoreactivity patterns were strong perimembranous (4 of 8), focal perinuclear and stippled cytoplasmic (1 of 8), and diffuse cytoplasmic (3 of 8), and included 1 case that was negative for histochemical stains; hence, KIT is a promising diagnostic marker for MCTs in miniature pigs. }, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Rasche, Brittany L. and Mozzachio, Kristie and Linder, Keith E.}, year={2022}, month={Feb} } @article{banovic_olivry_artlet_rothstein_beco_linek_zabel_peters-kennedy_welle_wilkes_et al._2022, title={Hyperkeratotic erythema multiforme variant in 17 dogs}, volume={12}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.13141}, DOI={10.1111/vde.13141}, abstractNote={Abstract}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Olivry, Thierry and Artlet, Barbara and Rothstein, Emily and Beco, Luc and Linek, Monika and Zabel, Sonja and Peters-Kennedy, Jeanine and Welle, Monika and Wilkes, Rebecca and et al.}, year={2022}, month={Dec} } @article{tham_lanz_linder_2022, title={Localised erythema multiforme-like reaction confined to a region of clipper burn in a dog}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13058}, abstractNote={Localised erythema multiforme (LEM) is only reported to occur in humans and not in domestic species. This case report describes the clinical and histopathological features of LEM‐like reaction in a dog, confined to a region of clipper burn.}, journal={VETERINARY DERMATOLOGY}, author={Tham, Heng L. and Lanz, Otto I and Linder, Keith E.}, year={2022}, month={Jan} } @article{lee_you_taylor-just_linder_atkins_ralph_cruz_bonner_2022, title={Pulmonary exposure of mice to ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX) suppresses the innate immune response to carbon black nanoparticles and stimulates lung cell proliferation}, ISSN={["1091-7691"]}, DOI={10.1080/08958378.2022.2086651}, abstractNote={Abstract Background Per- and polyfluoroalkyl substances (PFAS) have been associated with respiratory diseases in humans, yet the mechanisms through which PFAS cause susceptibility to inhaled agents is unknown. Herein, we investigated the effects of ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), an emerging PFAS, on the pulmonary immune response of mice to carbon black nanoparticles (CBNP). We hypothesized that pulmonary exposure to GenX would increase susceptibility to CBNP through suppression of innate immunity. Methods Male C57BL/6 mice were exposed to vehicle, 4 mg/kg CBNP, 10 mg/kg GenX, or CBNP and GenX by oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) was collected at 1 and 14 days postexposure for cytokines and total protein. Lung tissue was harvested for histopathology, immunohistochemistry (Ki67 and phosphorylated (p)-STAT3), western blotting (p-STAT3 and p-NF-κB), and qRT-PCR for cytokine mRNAs. Results CBNP increased CXCL-1 and neutrophils in BALF at both time points evaluated. However, GenX/CBNP co-exposure reduced CBNP-induced CXCL-1 and neutrophils in BALF. Moreover, CXCL-1, CXCL-2 and IL-1β mRNAs were increased by CBNP in lung tissue but reduced by GenX. Western blotting showed that CBNP induced p-NF-κB in lung tissue, while the GenX/CBNP co-exposed group displayed decreased p-NF-κB. Furthermore, mice exposed to GenX or GenX/CBNP displayed increased numbers of BALF macrophages undergoing mitosis and increased Ki67 immunostaining. This was correlated with increased p-STAT3 by western blotting and immunohistochemistry in lung tissue from mice co-exposed to GenX/CBNP. Conclusions Pulmonary exposure to GenX suppressed CBNP-induced innate immune response in the lungs of mice yet promoted the proliferation of macrophages and lung epithelial cells.}, journal={INHALATION TOXICOLOGY}, author={Lee, Ho Young and You, Dorothy J. and Taylor-Just, Alexia J. and Linder, Keith E. and Atkins, Hannah M. and Ralph, Lauren M. and Cruz, Gabriela and Bonner, James C.}, year={2022}, month={Jun} } @article{bizikova_linder_mamo_2022, title={Trunk-dominant and classic facial pemphigus foliaceus in dogs - comparison of anti-desmocollin-1 and anti-desmoglein-1 autoantibodies and clinical presentations}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13094}, abstractNote={Abstract}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Linder, Keith E. and Mamo, Lisa B.}, year={2022}, month={Jun} } @article{fussell_bizikova_breuhaus_harris_moore_chen_linder_2021, title={Bullous amyloidosis in a horse: first description in veterinary medicine}, volume={6}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12982}, abstractNote={BackgroundBullous amyloidosis is a rare disease in humans that has not been described in a veterinary species in the peer‐reviewed literature. The human disease is characterised by haemorrhagic vesicles and bullae on the skin and mucosae, which form due to amyloid deposition.}, journal={VETERINARY DERMATOLOGY}, author={Fussell, Devin and Bizikova, Petra and Breuhaus, Babetta and Harris, R. Adam and Moore, A. Russell and Chen, Laura and Linder, Keith E.}, year={2021}, month={Jun} } @article{herrmann_linder_meurs_friedenberg_cullen_olby_bizikova_2021, title={Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12972}, DOI={10.1111/vde.12972}, abstractNote={BackgroundJunctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Linder, Keith E. and Meurs, Kathryn M. and Friedenberg, Steven G. and Cullen, Jonah and Olby, Natasha and Bizikova, Petra}, year={2021}, month={Aug}, pages={379-+} } @article{rasche_tucker_linder_harrison_negrao watanabe_2021, title={Case Report: Pulmonary Conidiobolomycosis in a Vietnamese Pot-Bellied Pig}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.799641}, abstractNote={An adult castrated male Vietnamese pot-bellied pig had a 1-week history of acute dyspnea and lethargy. Minimal diagnostic testing was authorized by the owner, resulting in treatment with a third-generation cephalosporin and a non-steroidal anti-inflammatory drug. Partial improvement was observed after a week; however, the pig died 2 weeks after the initial onset of clinical signs. Macroscopically, ~90% of the left lung was effaced by large masses with a caseonecrotic center. Histologic examination revealed eosinophilic granulomas with myriad, intralesional, negatively staining hyphae highlighted by “sleeves” of hypereosinophilic material (Splendore-Hoeppli material). Infection with an oomycete or “zygomycete” (i.e., organisms of the order Entomophthorales or Mucorales) was initially considered. Pan-fungal PCR and sequencing performed on formalin-fixed, paraffin-embedded lung tissue identified Conidiobolus spp., consistent with a diagnosis of primary pulmonary conidiobolomycosis. There are only a few reports of infections with Conidiobolus spp. (and other members of the order Entomophthorales) in swine. Unlike humans and other animal species, conidiobolomycosis in pigs presents more commonly as a primary pulmonary disease rather than rhinofacial or nasopharyngeal disease.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Rasche, Brittany L. and Tucker, Samuel M. and Linder, Keith and Harrison, Tara M. and Negrao Watanabe, Tatiane Terumi}, year={2021}, month={Dec} } @article{sims_nagle_tolbert_anderson_linder_neel_2021, title={Correlation of cytology to histology in a case of canine granulomatous colitis in a Boxer dog}, volume={10}, ISSN={["1939-165X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85117248282&partnerID=MN8TOARS}, DOI={10.1111/vcp.13058}, abstractNote={Abstract}, number={S1}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Sims, Cory S. and Nagle, Jonathan and Tolbert, M. Katherine and Anderson, Katie and Linder, Keith and Neel, Jennifer}, year={2021}, month={Oct} } @article{meuten_moore_donovan_bertram_klopfleisch_foster_smedley_dark_milovancev_stromberg_et al._2021, title={International Guidelines for Veterinary Tumor Pathology: A Call to Action}, ISSN={["1544-2217"]}, DOI={10.1177/03009858211013712}, abstractNote={Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website ( www.vetcancerprotocols.org ), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.}, journal={VETERINARY PATHOLOGY}, author={Meuten, Donald J. and Moore, Frances M. and Donovan, Taryn A. and Bertram, Christof A. and Klopfleisch, Robert and Foster, Robert A. and Smedley, Rebecca C. and Dark, Michael J. and Milovancev, Milan and Stromberg, Paul and et al.}, year={2021}, month={Jul} } @article{mones_schreeg_sommer_linder_lewbart_2021, title={Surgical management and histopathology of wen overgrowth and neoplasia in four oranda goldfish (Carassius auratus)}, volume={9}, ISSN={["2052-6121"]}, DOI={10.1002/vrc2.27}, abstractNote={Abstract}, number={1}, journal={VETERINARY RECORD CASE REPORTS}, author={Mones, Alissa and Schreeg, Megan and Sommer, Samantha and Linder, Keith and Lewbart, Gregory}, year={2021}, month={Mar} } @article{bai_linder_muddiman_2021, title={Three-dimensional (3D) imaging of lipids in skin tissues with infrared matrix-assisted laser desorption electrospray ionization (MALDESI) mass spectrometry}, volume={413}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-020-03105-6}, abstractNote={Three-dimensional (3D) mass spectrometry imaging (MSI) has become a growing frontier as it has the potential to provide a 3D representation of analytes in a label-free, untargeted, and chemically specific manner. The most common 3D MSI is accomplished by the reconstruction of 2D MSI from serial cryosections; however, this presents significant challenges in image alignment and registration. An alternative method would be to sequentially image a sample by consecutive ablation events to create a 3D image. In this study, we describe the use of infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) in ablation-based 3D MSI for analyses of lipids within fresh frozen skin tissue. Depth resolution using different laser energy levels was explored with a confocal laser scanning microscope to establish the imaging parameters for skin. The lowest and highest laser energy level resulted in a depth resolution of 7 μm and 18 μm, respectively. A total of 594 lipids were putatively detected and detailed lipid profiles across different skin layers were revealed in a 56-layer 3D imaging experiment. Correlated with histological information, the skin structure was characterized with differential lipid distributions with a lateral resolution of 50 μm and a z resolution of 7 μm.}, number={10}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Bai, Hongxia and Linder, Keith E. and Muddiman, David C.}, year={2021}, month={Apr}, pages={2793–2801} } @article{alloway_linder_may_rose_delay_bender_tucker_luff_2020, title={A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection}, volume={57}, ISSN={["1544-2217"]}, DOI={10.1177/0300985820908797}, abstractNote={ Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus–2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC. }, number={3}, journal={VETERINARY PATHOLOGY}, author={Alloway, Elizabeth and Linder, Keith and May, Susan and Rose, Trevor and DeLay, Josepha and Bender, Susan and Tucker, Alison and Luff, Jennifer}, year={2020}, month={May}, pages={427–431} } @article{levy_linder_mamo_herrmann_bizikova_2020, title={Cutaneous polyautoimmunity in two unrelated dogs: pemphigus foliaceus and generalized discoid lupus erythematosus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12851}, abstractNote={BackgroundPolyautoimmunity, the concurrent expression of two or more distinct autoimmune diseases (ADs) in a single individual, is a known phenomenon in humans and has been rarely reported in dogs. To the best of the authors’ knowledge, comorbid pemphigus foliaceus (PF) and generalized discoid lupus erythematosus (GDLE) has not been reported in dogs.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Levy, Britt J. and Linder, Keith E. and Mamo, Lisa B. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={325-+} } @article{elliott_linder_nolan_2020, title={Feasibility study evaluating arrhythmogenesis and cardiac damage after heart-base irradiation in mice: A brief communication}, volume={6}, ISSN={["2053-1095"]}, DOI={10.1002/vms3.303}, abstractNote={Abstract}, number={4}, journal={VETERINARY MEDICINE AND SCIENCE}, author={Elliott, James and Linder, Keith and Nolan, Michael W.}, year={2020}, month={Nov}, pages={1009–1016} } @article{eisemann_ashwell_devine_poole_poore_linder_2020, title={Physiological response, function of sweat glands, and hair follicle cycling in cattle in response to fescue toxicosis and hair genotype}, volume={98}, ISSN={0021-8812 1525-3163}, url={http://dx.doi.org/10.1093/jas/skaa013}, DOI={10.1093/jas/skaa013}, abstractNote={Abstract}, number={3}, journal={Journal of Animal Science}, publisher={Oxford University Press (OUP)}, author={Eisemann, J.H. and Ashwell, M.S. and Devine, T.L. and Poole, D.H. and Poore, M.H. and Linder, K.}, year={2020}, month={Mar} } @article{high_linder_mamo_levy_herrmann_bizikova_2020, title={Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12852}, abstractNote={BackgroundHyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to “classic” erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={High, Endya J. and Linder, Keith E. and Mamo, Lisa B. and Levy, Britt J. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={330-+} } @article{you_lee_taylor-just_linder_bonner_2020, title={Sex differences in the acute and subchronic lung inflammatory responses of mice to nickel nanoparticles}, volume={14}, ISSN={["1743-5404"]}, DOI={10.1080/17435390.2020.1808105}, abstractNote={Abstract Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.}, number={8}, journal={NANOTOXICOLOGY}, author={You, Dorothy J. and Lee, Ho Young and Taylor-Just, Alexia J. and Linder, Keith E. and Bonner, James C.}, year={2020}, month={Sep}, pages={1058–1081} } @article{tham_linder_olivry_2019, title={Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review}, volume={15}, ISSN={1746-6148}, url={http://dx.doi.org/10.1186/s12917-019-2003-9}, DOI={10.1186/s12917-019-2003-9}, abstractNote={Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes. In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans. Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.}, number={1}, journal={BMC Veterinary Research}, publisher={Springer Science and Business Media LLC}, author={Tham, Heng L. and Linder, Keith E. and Olivry, Thierry}, year={2019}, month={Jul} } @article{tam_hall_messenger_jima_house_linder_smart_2019, title={C/EBP beta suppresses keratinocyte autonomous type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer}, volume={40}, ISSN={["1460-2180"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85083447649&partnerID=MN8TOARS}, DOI={10.1093/carcin/bgz012}, abstractNote={Abstract}, number={9}, journal={CARCINOGENESIS}, author={Tam, Hann W. and Hall, Jonathan R. and Messenger, Zachary J. and Jima, Dereje D. and House, John S. and Linder, Keith and Smart, Robert C.}, year={2019}, month={Sep}, pages={1099–1109} } @article{levy_linder_olivry_2019, title={The role of oclacitinib in the management of ischaemic dermatopathy in four dogs}, volume={30}, ISBN={1365-3164}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/vde.12743}, DOI={10.1111/vde.12743}, abstractNote={BackgroundIschaemic dermatopathy represents a heterogenous and poorly‐characterized canine syndrome that is often refractory to conventional immunosuppression. Janus‐kinase inhibitors (JAKinibs) are used for the treatment of various human autoimmune diseases, including dermatomyositis. Oclacitinib is a generally well‐tolerated, veterinary‐approved, nonselective JAKinib that has therapeutic potential as an immunosuppressant.}, number={3}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Levy, Britt J. and Linder, Keith E. and Olivry, Thierry}, year={2019}, month={Apr}, pages={201–e63} } @article{southern_neupane_ericson_dencklau_linder_bradley_mckeon_long_breitschwerdt_2018, title={Bartonella henselae in a dog with ear tip vasculitis}, volume={29}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12695}, DOI={10.1111/vde.12695}, abstractNote={BackgroundBartonella henselae, a Gram‐negative, zoonotic, alpha‐proteobacteria has been previously implicated in association with cutaneous vasoproliferative lesions (bacillary angiomatosis), nodular panniculitis and multifocal erythema (erythema multiforme) in dogs.}, number={6}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Southern, Brittany L. and Neupane, Pradeep and Ericson, Marna E. and Dencklau, Jamie C. and Linder, Keith E. and Bradley, Julie M. and McKeon, Gabriel P. and Long, Charles T. and Breitschwerdt, Edward B.}, year={2018}, month={Oct}, pages={537–e180} } @article{linder_bizikova_luff_zhou_yuan_breuhaus_nelson_mackay_2018, title={Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8)}, volume={29}, number={1}, journal={Veterinary Dermatology}, author={Linder, K. E. and Bizikova, P. and Luff, J. and Zhou, D. and Yuan, H. and Breuhaus, B. and Nelson, E. and Mackay, R.}, year={2018} } @article{fukuyama_martel_linder_ehling_ganchingco_baeumer_2018, title={Hypochlorous acid is antipruritic and anti-inflammatory in a mouse model of atopic dermatitis}, volume={48}, ISSN={["1365-2222"]}, DOI={10.1111/cea.13045}, abstractNote={Summary}, number={1}, journal={CLINICAL AND EXPERIMENTAL ALLERGY}, author={Fukuyama, T. and Martel, B. C. and Linder, K. E. and Ehling, S. and Ganchingco, J. R. and Baeumer, W.}, year={2018}, month={Jan}, pages={78–88} } @article{levine_cianciolo_linder_bizikova_birkenheuer_brooks_salous_nordone_bellinger_marr_et al._2017, title={Endothelial alterations in a canine model of immune thrombocytopenia}, volume={30}, ISSN={0953-7104 1369-1635}, url={http://dx.doi.org/10.1080/09537104.2017.1378807}, DOI={10.1080/09537104.2017.1378807}, abstractNote={Abstract Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is poorly understood. Platelets play a role in maintaining endothelial integrity, and variable thrombocytopenia-induced endothelial changes may influence bleeding severity. Platelet-derived endothelial stabilizers and markers of endothelial integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP model, thrombocytopenia would lead to alterations in the endothelial ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker of endothelial injury associated with thrombocytopenia. Thrombocytopenia was induced in healthy dogs with an antiplatelet antibody infusion; control dogs received an isotype control antibody. Cutaneous biopsies were obtained prior to thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on platelet recovery. Cutaneous capillaries were assessed by electron microscopy for vessel thickness, the number of pinocytotic vesicles, the number of large vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought to represent an endothelial membrane reserve that can be used for repair of damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had significantly decreased pinocytotic vesicle numbers compared to control dogs (P = 0.0357) and the increase in plasma vWF from baseline to 24 hours correlated directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This direct correlation between plasma vWF and the number of large vacuoles, representing the vesiculo-vacuolar organelle (VVO), a permeability structure, suggests that circulating vWF could serve as a biomarker for endothelial alterations and potentially a predictor of thrombocytopenic bleeding. Overall, our results indicate that endothelial damage occurs in the canine ITP model and variability in the degree of endothelial damage may account for differences in the bleeding phenotype among patients with ITP.}, number={1}, journal={Platelets}, publisher={Informa UK Limited}, author={LeVine, Dana N. and Cianciolo, Rachel E. and Linder, Keith E. and Bizikova, Petra and Birkenheuer, Adam J. and Brooks, Marjory B. and Salous, Abdelghaffar K. and Nordone, Shila K. and Bellinger, Dwight A. and Marr, Henry and et al.}, year={2017}, month={Nov}, pages={88–97} } @article{draughn_allen_routh_stone_kirker_boegli_schuchman_linder_baynes_james_et al._2017, title={Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections}, volume={11}, journal={Drug Design Development and Therapy}, author={Draughn, G. L. and Allen, C. L. and Routh, P. A. and Stone, M. R. and Kirker, K. R. and Boegli, A. and Schuchman, R. M. and Linder, K. E. and Baynes, R. E. and James, G. and et al.}, year={2017}, pages={153–162} } @article{risselada_linder_griffith_roberts_davidson_zamboni_messenger_2017, title={Pharmacokinetics and toxicity of subcutaneous administration of carboplatin in poloxamer 407 in a rodent model pilot study}, volume={12}, number={10}, journal={PLoS One}, author={Risselada, M. and Linder, K. E. and Griffith, E. and Roberts, B. V. and Davidson, G. and Zamboni, W. C. and Messenger, K. M.}, year={2017} } @article{banovic_linder_uri_rossi_olivry_2016, title={Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases)}, volume={27}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12389}, DOI={10.1111/vde.12389}, abstractNote={BackgroundGeneralized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized.}, number={6}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley-Blackwell}, author={Banovic, Frane and Linder, Keith E. and Uri, Maarja and Rossi, Michael A. and Olivry, Thierry}, year={2016}, month={Dec}, pages={488-+} } @article{olivry_mayhew_paps_linder_peredo_rajpal_hofland_cote-sierra_2016, title={Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions}, volume={136}, ISSN={["1523-1747"]}, url={https://doi.org/10.1016/j.jid.2016.05.117}, DOI={10.1016/j.jid.2016.05.117}, abstractNote={Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease.}, number={10}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, publisher={Elsevier BV}, author={Olivry, Thierry and Mayhew, David and Paps, Judy S. and Linder, Keith E. and Peredo, Carlos and Rajpal, Deepak and Hofland, Hans and Cote-Sierra, Javier}, year={2016}, month={Oct}, pages={1961–1969} } @article{palerme_jones_ward_balakrishnan_linder_breitschwerdt_keene_2016, title={Infective endocarditis in 13 cats}, volume={18}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2016.04.003}, DOI={10.1016/j.jvc.2016.04.003}, abstractNote={To describe the clinical presentation, clinicopathological abnormalities and outcomes of a series of cats diagnosed with infective endocarditis (IE) at two tertiary care referral institutions.Thirteen client-owned cats presenting to the cardiology or emergency services of tertiary referral institutions with a diagnosis of endocarditis based on the modified Duke criteria.Retrospective case series. Medical records were reviewed to extract relevant data. In addition, cases that had cardiac tissue available were evaluated by polymerase chain reaction for the presence of Bartonella DNA.Prevalence of feline IE was 0.007%. Cats with endocarditis tended to be older (median age: 9 years, range: 2-12 years) and no sex or breed was overrepresented. Commonly encountered clinical signs included respiratory distress (n = 5) and locomotor abnormalities of varying severity (n = 5). Echocardiographic examination detected valvular lesions consistent with endocarditis on the aortic (n = 8) or mitral (n = 5) valves. Nine cats were diagnosed with congestive heart failure at the time of endocarditis diagnosis. Overall, prognosis was grave with a median survival time of 31 days.In contrast to dogs, cats with IE typically present with clinical signs consistent with cardiac decompensation and locomotor abnormalities suggestive of either thromboembolic disease or inflammatory arthritis. Given the advanced state of disease when diagnosis typically occurs, prognosis is grave.}, number={3}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Palerme, Jean-Sébastien and Jones, Ashley E. and Ward, Jessica L. and Balakrishnan, Nandhakumar and Linder, Keith E. and Breitschwerdt, Edward B. and Keene, Bruce W.}, year={2016}, month={Sep}, pages={213–225} } @article{doelle_linder_boche_jagannathan_leeb_linek_2016, title={Initial characterization of stiff skin-like syndrome in West Highland white terriers}, volume={27}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12316}, abstractNote={BackgroundStiff skin syndrome and systemic or localized scleroderma are cutaneous disorders characterized by dermal fibrosis and present clinically with induration of the skin, with or without joint, internal organ or vascular involvement.}, number={3}, journal={VETERINARY DERMATOLOGY}, author={Doelle, Maren and Linder, Keith E. and Boche, Janna and Jagannathan, Vidhya and Leeb, Tosso and Linek, Monika}, year={2016}, month={Jun}, pages={210-+} } @article{tham_olivry_linder_bizikova_2016, title={Mucous membrane pemphigoid in dogs: A retrospective study of 16 new cases}, volume={27}, number={5}, journal={Veterinary Dermatology}, author={Tham, H. L. and Olivry, T. and Linder, K. E. and Bizikova, P.}, year={2016}, pages={376-} } @article{alpi_brown_neel_grindem_linder_harper_2016, title={Scanning technology selection impacts acceptability and usefulness of image-rich content}, volume={104}, ISSN={["1536-5050"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84955278757&partnerID=MN8TOARS}, DOI={10.3163/1536-5050.104.1.003}, abstractNote={OBJECTIVE Clinical and research usefulness of articles can depend on image quality. This study addressed whether scans of figures in black and white (B&W), grayscale, or color, or portable document format (PDF) to tagged image file format (TIFF) conversions as provided by interlibrary loan or document delivery were viewed as acceptable or useful by radiologists or pathologists. METHODS Residency coordinators selected eighteen figures from studies from radiology, clinical pathology, and anatomic pathology journals. With original PDF controls, each figure was prepared in three or four experimental conditions: PDF conversion to TIFF, and scans from print in B&W, grayscale, and color. Twelve independent observers indicated whether they could identify the features and whether the image quality was acceptable. They also ranked all the experimental conditions of each figure in terms of usefulness. RESULTS Of 982 assessments of 87 anatomic pathology, 83 clinical pathology, and 77 radiology images, 471 (48%) were unidentifiable. Unidentifiability of originals (4%) and conversions (10%) was low. For scans, unidentifiability ranged from 53% for color, to 74% for grayscale, to 97% for B&W. Of 987 responses about acceptability (n=405), 41% were said to be unacceptable, 97% of B&W, 66% of grayscale, 41% of color, and 1% of conversions. Hypothesized order (original, conversion, color, grayscale, B&W) matched 67% of rankings (n=215). CONCLUSIONS PDF to TIFF conversion provided acceptable content. Color images are rarely useful in grayscale (12%) or B&W (less than 1%). Acceptability of grayscale scans of noncolor originals was 52%. Digital originals are needed for most images. Print images in color or grayscale should be scanned using those modalities.}, number={1}, journal={JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION}, author={Alpi, Kristine M. and Brown, James C., Jr. and Neel, Jennifer A. and Grindem, Carol B. and Linder, Keith E. and Harper, James B.}, year={2016}, month={Jan}, pages={15–23} } @article{bizikova_linder_wofford_mamo_dunston_olivry_2015, title={Canine epidermolysis bullosa acquisita: A retrospective study of 20 cases}, volume={26}, number={6}, journal={Veterinary Dermatology}, author={Bizikova, P. and Linder, K. E. and Wofford, J. A. and Mamo, L. B. and Dunston, S. M. and Olivry, T.}, year={2015}, pages={441-} } @article{pinto_mcmullen_linder_cullen_gilger_2015, title={Clinical, histopathological and immunohistochemical characterization of a novel equine ocular disorder: heterochromic iridocyclitis with secondary keratitis in adult horses}, volume={18}, ISSN={["1463-5224"]}, DOI={10.1111/vop.12234}, abstractNote={Abstract}, number={6}, journal={VETERINARY OPHTHALMOLOGY}, author={Pinto, Nelson I. and McMullen, Richard J., Jr. and Linder, Keith E. and Cullen, John M. and Gilger, Brian C.}, year={2015}, month={Nov}, pages={443–456} } @article{bizikova_moriello_linder_sauber_2015, title={Dinotefuran/pyriproxyfen/permethrin pemphigus-like drug reaction in three dogs}, volume={26}, number={3}, journal={Veterinary Dermatology}, author={Bizikova, P. and Moriello, K. A. and Linder, K. E. and Sauber, L.}, year={2015}, pages={206-} } @article{rossi_messenger_linder_olivry_2015, title={Generalized Canine Discoid Lupus Erythematosus Responsive to Tetracycline and Niacinamide Therapy}, volume={51}, ISSN={["1547-3317"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84943745108&partnerID=MN8TOARS}, DOI={10.5326/jaaha-ms-6116}, abstractNote={Discoid lupus erythematosus (DLE) is a commonly reported canine autoimmune disease that normally presents with a phenotype consisting of erythema, depigmentation, scaling, erosions/ulcers, and scarring over the nasal planum and the proximal dorsal muzzle. Recently, two cases of a generalized variant of this disease have been reported, whose lesions responded to either systemic glucocorticoids or a combination of topical corticosteroids, topical tacrolimus, and the oral antimalarial hydroxychloroquine. The purpose of this report is to describe an 11 yr old shih tzu that presented with skin lesions consisting of multiple annular, erythematous papules and plaques, hyperpigmentation, adherent scaling, and atrophic scars over the caudal dorsum, flanks, craniodorsal thorax, and lateroproximal extremities. A diagnosis of generalized DLE was made based on the clinical presentation, histopathology, laboratory values, and direct immunofluorescence findings. Treatment consisted of oral tetracycline and oral niacinamide, which resulted in complete remission of clinical signs. This is the first documented report of generalized canine DLE responding to the described immunomodulating regimen. Such a combination might therefore be considered as a glucocorticoid and/or antimalarial alternative for the management of generalized DLE.}, number={3}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Rossi, Michael A. and Messenger, Linda M. and Linder, Keith E. and Olivry, Thierry}, year={2015}, pages={171–175} } @article{olivry_rossi_banovic_linder_2015, title={Mucocutaneous lupus erythematosus in dogs (21 cases)}, volume={26}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84955657545&partnerID=MN8TOARS}, DOI={10.1111/vde.12217}, abstractNote={BackgroundThe diagnosis of dogs with chronic juxtamucosal erosive lesions and histopathology typical of cutaneous lupus erythematosus (CLE) is unclear.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Olivry, Thierry and Rossi, Michael A. and Banovic, Frane and Linder, Keith E.}, year={2015}, month={Aug}, pages={256-+} } @article{pultorak_linder_maggi_balakrishnan_breitschwerdt_2015, title={Prevalence of Bartonella spp. in Canine Cutaneous Histiocytoma}, volume={153}, ISSN={0021-9975}, url={http://dx.doi.org/10.1016/j.jcpa.2015.04.001}, DOI={10.1016/j.jcpa.2015.04.001}, abstractNote={Canine cutaneous histiocytoma (CCH) is a common, benign neoplastic proliferation of histiocytes of Langerhans cell origin that often ulcerate, become secondarily infected and regress spontaneously. Bartonella is a fastidious genus of facultative intracellular pathogens that can be transmitted through arthropod bites and epidermal animal scratches and has been identified previously in the cytoplasm of histiocytes within granulomatous lesions and in skin biopsy samples of inflammatory pustules and papules. Based on the established inflammatory and oncogenic properties of Bartonella, we hypothesized that Bartonella spp. DNA could be amplified from CCH more often than from non-lesional skin and bacteria could be localized within skin tumours using indirect immunofluorescence (IIF). Paraffin wax-embedded surgical biopsy samples from dogs with CCH and non-neoplastic skin adjacent to osteosarcomas (control group selected due to wide surgical margins) were retrieved from the archive of the pathology service of North Carolina State University College of Veterinary Medicine. DNA was extracted and regions of the 16S–23S rRNA intergenic transcribed spacer (ITS) region and the pap31 and gltA genes were amplified by polymerase chain reaction (PCR) using Bartonella-specific primers. IIF was performed using a primary Bartonella henselae monoclonal antibody to localize B. henselae in tissues of PCR-positive dogs. Bartonella vinsonii subsp. berkhoffii was amplified from 1/17 (5.8%) control tissues and B. henselae was amplified from 4/29 (13.8%) CCH tissues. The prevalence of B. vinsonii subsp. berkhoffii (P = 0.37) or B. henselae (P = 0.28) did not vary statistically between study groups. B. henselae could be visualized in 2/4 (50.0%) CCH tissues using IIF. Based on this study, Bartonella spp. are unlikely to cause CCH.}, number={1}, journal={Journal of Comparative Pathology}, publisher={Elsevier BV}, author={Pultorak, E.L. and Linder, K. and Maggi, R.G. and Balakrishnan, N. and Breitschwerdt, E.B.}, year={2015}, month={Jul}, pages={14–21} } @article{tham_linder_tucker_maggi_bizikova_2015, title={Protozoal nodular dermatitis and panniculitis in a Rottweiler puppy caused by Caryospora bigenetica}, volume={27}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12271}, DOI={10.1111/vde.12271}, abstractNote={BackgroundCaryospora bigenetica is an intracellular protozoan parasite in snakes and raptors (primary hosts) and rodents (secondary host). Experimental infection has been documented in mice, pigs and goats; natural infection in dogs is rare.}, number={1}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Tham, Heng L. and Linder, Keith E. and Tucker, Alison and Maggi, Ricardo and Bizikova, Petra}, year={2015}, month={Nov}, pages={44–e12} } @article{agler_nielsen_urkasemsin_singleton_tonomura_sigurdsson_tang_linder_arepalli_hernandez_et al._2014, title={Canine hereditary ataxia in Old English Sheepdogs and Gordon Setters is associated with a defect in the autophagy gene encoding RAB24}, volume={10}, number={2}, journal={PLoS Genetics}, author={Agler, C. and Nielsen, D. M. and Urkasemsin, G. and Singleton, A. and Tonomura, N. and Sigurdsson, S. and Tang, R. Q. and Linder, K. and Arepalli, S. and Hernandez, D. and et al.}, year={2014} } @article{banovic_olivry_linder_2014, title={Ciclosporin therapy for canine generalized discoid lupus erythematosus refractory to doxycycline and niacinamide}, volume={25}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911380668&partnerID=MN8TOARS}, DOI={10.1111/vde.12139}, abstractNote={BackgroundGeneralized discoid lupus erythematosus (DLE) is an autoimmune skin disease variant rarely reported in dogs. The antimalarial immunomodulator hydroxychloroquine has been suggested as maintenance therapy for generalized DLE in one dog, but several recurrences were noted in the 1 year follow‐up of that patient.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Olivry, Thierry and Linder, Keith E.}, year={2014}, month={Oct}, pages={483–E79} } @article{banovic_olivry_bazzle_tobias_atlee_zabel_hensel_linder_2014, title={Clinical and Microscopic Characteristics of Canine Toxic Epidermal Necrolysis}, volume={52}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985814537530}, DOI={10.1177/0300985814537530}, abstractNote={ Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation; however, few reports detail the histologic findings. We characterize the clinical features and histologic variations of 3 canine TEN patients. Clinically, irregular erythematous and purpuric macules evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, periocular and perilabial mucocutaneous junctions frequently were affected. Thirteen of 17 biopsies were evaluated. Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was the predominant inflammatory pattern, and intraepidermal lymphocytes, along with fewer histiocytes, were present to some degree in all samples along with lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion development with subsequent variation in progression to coagulation necrosis among patients. Histopathologic changes overlapped with those reported for erythema multiforme, in contrast to traditional histologic descriptions of canine TEN. A specific algorithm for assessment of drug causality in epidermal necrolysis (ALDEN) was applied for each patient; carprofen was associated with a probable score for causality in 1 dog. Clinicians should be encouraged to take multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked epithelium and were not diagnostic. }, number={2}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Banovic, F. and Olivry, T. and Bazzle, L. and Tobias, J. R. and Atlee, B. and Zabel, S. and Hensel, N. and Linder, K. E.}, year={2014}, month={Jun}, pages={321–330} } @article{rossi_balakrishnan_linder_messa_breitschwerdt_2014, title={ConcurrentBartonella henselaeinfection in a dog with panniculitis and owner with ulcerated nodular skin lesions}, volume={26}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12174}, DOI={10.1111/vde.12174}, abstractNote={BackgroundBartonella henselae, a Gram‐negative, zoonotic Alphaproteobacteria that infects erythrocytes, endothelial cells and dendritic cells, has previously been implicated as a cause of panniculitis in dogs and a human.}, number={1}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Rossi, Michael A. and Balakrishnan, Nandhakumar and Linder, Keith E. and Messa, Jacqueline B. and Breitschwerdt, Edward B.}, year={2014}, month={Oct}, pages={60–e22} } @article{bizikova_linder_olivry_2014, title={Fipronil-amitraz-S-methoprene-triggered pemphigus foliaceus in 21 dogs: clinical, histological and immunological characteristics}, volume={25}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12117}, DOI={10.1111/vde.12117}, abstractNote={BackgroundA recently launched topical ectoparasiticide containing fipronil, amitraz and S‐methoprene has been associated with the development of an acantholytic pustular dermatitis similar to that of Promeris‐triggered pemphigus foliaceus (PF).}, number={2}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Bizikova, Petra and Linder, Keith E. and Olivry, Thierry}, year={2014}, month={Mar}, pages={103–e30} } @article{banovic_olivry_linder_tobias_2014, title={Pathology in Practice}, volume={245}, ISSN={["1943-569X"]}, DOI={10.2460/javma.245.11.1237}, number={11}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Banovic, Frane and Olivry, Thierry and Linder, Keith E. and Tobias, Jeremy R.}, year={2014}, month={Dec}, pages={1237–1239} } @article{rowe_mathews_linder_tate_2014, title={The Effect of Photodynamic Therapy on Cisterna Chyli Patency in Rats}, volume={43}, ISSN={["1532-950X"]}, DOI={10.1111/j.1532-950x.2014.12222.x}, abstractNote={ObjectiveTo radiographically and histologically evaluate the effects of photodynamic therapy on the cisterna chyli in rats.}, number={6}, journal={VETERINARY SURGERY}, author={Rowe, Eric A. and Mathews, Kyle G. and Linder, Keith E. and Tate, Lloyd P.}, year={2014}, month={Aug}, pages={642–649} } @article{banovic_linder_boone_jennings_murphy_2013, title={Cat scratch-induced Pasteurella multocida necrotizing cellulitis in a dog}, volume={24}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12038}, DOI={10.1111/vde.12038}, abstractNote={BackgroundIn humans, rapidly developing Pasteurella multocida cellulitis after a cat scratch or bite is a well‐known entity that sometimes progresses to necrotizing fasciitis and can be fatal.}, number={4}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Banovic, Frane and Linder, Keith and Boone, Alison and Jennings, Sam and Murphy, K. Marcia}, year={2013}, month={Jun}, pages={463–e108} } @article{balakrishnan_cherry_linder_pierce_sontakke_hegarty_bradley_maggi_breitschwerdt_2013, title={Experimental infection of dogs with Bartonella henselae and Bartonella vinsonii subsp. berkhoffii}, volume={156}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2013.09.007}, DOI={10.1016/j.vetimm.2013.09.007}, abstractNote={The lack of a suitable infection model remains an important obstacle for the pathophysiological understanding of Bartonella spp. The following pilot study was designed to determine whether cell culture-grown Bartonella henselae SA2 and Bartonella vinsonii subsp. berkhoffii genotype III would cause persistent bacteremia in dogs. Pre-inoculation screening established that two laboratory-raised Golden retrievers were naturally-infected with Bartonella koehlerae. Despite prior infection, one dog each was inoculated subcutaneously with 5 × 10(4)B. henselae (SA2 strain) or 3 × 10(4)B. vinsonii subsp. berkhoffii genotype III. Dogs were bled weekly for serological testing and culture using Bartonella alpha proteobacteria growth medium (BAPGM) diagnostic platform. Dog 1 seroconverted to B. henselae and Dog 2 seroconverted to B. vinsonii subsp. berkhoffii genotype III. Throughout the study period, Bartonella spp. DNA was neither amplified nor isolated in ante-mortem BAPGM enrichment blood cultures. B. henselae SA2 was isolated from a postmortem bone marrow from Dog 1 and B. koehlerae DNA was amplified from postmortem lung from Dog 2 following BAPGM enrichment culture. Limitations include lack of uninfected controls, a potentially suboptimal B. vinsonii subsp. berkhoffii inoculum and a relatively short duration of study. We conclude that following intradermal infection, sequestration of Bartonella spp. in tissues may limit diagnostic detection of these bacteria in dog blood samples.}, number={1-2}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Balakrishnan, Nandhakumar and Cherry, Natalie A. and Linder, Keith E. and Pierce, Eric and Sontakke, Neal and Hegarty, Barbara C. and Bradley, Julie M. and Maggi, Ricardo G. and Breitschwerdt, Edward B.}, year={2013}, month={Nov}, pages={153–158} } @article{breitschwerdt_linder_day_maggi_chomel_kempf_2013, title={Koch's Postulates and the Pathogenesis of Comparative Infectious Disease Causation Associated with Bartonella species}, volume={148}, ISSN={0021-9975}, url={http://dx.doi.org/10.1016/j.jcpa.2012.12.003}, DOI={10.1016/j.jcpa.2012.12.003}, abstractNote={In his homage to Lucretius (‘Georgica’), Vergil is credited with stating: ‘Felix qui potuit rerum cognoscere causas’ (‘Fortunate is he who knows the causes of things’). Based on numerous commentaries and publications it is obvious that clinicians, diagnosticians and biomedical research scientists continue to struggle with disease causation, particularly in the assessment of the pathogenic role of ‘stealth pathogens’ that produce persistent infections in the host. Bartonella species, because of their evolutionary ability to induce persistent intravascular infections, present substantial challenges for researchers attempting to clarify the ability of these stealth bacteria to cause disease. By studying the comparative biological and pathological behaviour of microbes across mammalian genera, researchers might be able more rapidly to advance medical science and, subsequently, patient care by undertaking focused research efforts involving a single mammalian species or by attempting to recapitulate a complex disease in an rodent model. Therefore, in an effort to further assist in the establishment of disease causation by stealth pathogens, we use recent research observations involving the genus Bartonella to propose an additional postulate of comparative infectious disease causation to Koch's postulates.}, number={2-3}, journal={Journal of Comparative Pathology}, publisher={Elsevier BV}, author={Breitschwerdt, E.B. and Linder, K.L. and Day, M.J. and Maggi, R.G. and Chomel, B.B. and Kempf, V.A.J.}, year={2013}, month={Feb}, pages={115–125} } @article{banovic_olivry_linder_tobias_2013, title={Lichenoid psoriasifrom dermatitis}, volume={245}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Banovic, F and Olivry, T and Linder, KE and Tobias, JR}, year={2013}, pages={1237–1239} } @article{asakawa_cullen_linder_2013, title={Necrolytic migratory erythema associated with a glucagon-producing primary hepatic neuroendocrine carcinoma in a cat}, volume={24}, ISSN={["0959-4493"]}, DOI={10.1111/vde.12041}, abstractNote={BackgroundIn humans, necrolytic migratory erythema (NME) is a syndrome with a characteristic skin rash that is associated most often with a pancreatic glucagonoma and is recognized as part of the glucagonoma syndrome. In veterinary medicine, NME (also called as superficial necrolytic dermatitis, hepatocutaneous syndrome or metabolic epidermal necrosis) has been described in dogs in association with chronic liver diseases or, less frequently, glucagonoma, but NME associated with glucagonoma has not previously been reported in cats.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Asakawa, Midori G. and Cullen, John M. and Linder, Keith E.}, year={2013}, month={Aug}, pages={466–E110} } @article{jennings_wise_nickeleit_maes_cianciolo_piero_law_kim_mccalla_breuhaus_et al._2013, title={Polyomavirus-Associated Nephritis in 2 Horses}, volume={50}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985813476063}, DOI={10.1177/0300985813476063}, abstractNote={ Polyomaviruses produce latent and asymptomatic infections in many species, but productive and lytic infections are rare. In immunocompromised humans, polyomaviruses can cause tubulointerstitial nephritis, demyelination, or meningoencephalitis in the central nervous system and interstitial pneumonia. This report describes 2 Standardbred horses with tubular necrosis and tubulointerstitial nephritis associated with productive equine polyomavirus infection that resembles BK polyomavirus nephropathy in immunocompromised humans. }, number={5}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Jennings, S. H. and Wise, A. G. and Nickeleit, V. and Maes, R. K. and Cianciolo, R. E. and Piero, F. Del and Law, J. M. and Kim, Y. and McCalla, A. C. and Breuhaus, B. A. and et al.}, year={2013}, month={Feb}, pages={769–774} } @article{boswell_fogle_linder_copple_2013, title={What Is Your Diagnosis?}, volume={242}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.242.3.311}, DOI={10.2460/javma.242.3.311}, abstractNote={HistoryA 12-year-old Clydesdale gelding was evaluated because of worsening skin lesions of 9 years' duration.Lesions were located distally on all limbs and previously diagnosed as pastern dermatitis.Lesions had not improved with treatments that included bathing, homeopathic remedies, and soaking the distal portion of the limbs in various solutions.Lesions extended proximally from the coronary band to the level of the carpus and tarsus.Areas were affected by severe regional lichenification with scaling, hyperkeratosis, and multifocal to coalescing firm nodules (1.0 to 3.0 cm in diameter), which were occasionally ulcerated.Where thickened skin folded, a purulent exudate and crusting were often present and cutaneous myiasis was a complicating feature.The remainder of findings on clinical examination were unremarkable.To evaluate lymphatic flow, nuclear lymphoscintigraphy of the right thoracic and right pelvic limbs was performed with technetium Tc 99m sulfur colloid.Following a described protocol, 1 the radiopharmaceutical was injected SC proximal to the coronary band at 4 equidistant sites on the lateral aspect of the limb.After injection, lateral, 1-minute static images of the right thoracic and right pelvic limbs were acquired at 0, 5, 15, 30, 60, and 120 minutes (Figure 1).}, number={3}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Boswell, Stacie G. and Fogle, Callie A. and Linder, Keith and Copple, Christina N.}, year={2013}, month={Feb}, pages={311–313} } @article{stowe_anderson_guy_linder_grindem_2012, title={A Case of Enzootic Nasal Adenocarcinoma in a Ewe}, volume={2012}, ISSN={2090-7001 2090-701X}, url={http://dx.doi.org/10.1155/2012/347193}, DOI={10.1155/2012/347193}, abstractNote={An approximately 2-year-old open Suffolk ewe presented to the North Carolina State University College of Veterinary Medicine Veterinary Health Complex for evaluation of a left nasal mass. An ultrasound-guided aspirate and core biopsies were performed. An epithelial neoplasia with mild mixed inflammation (neutrophils and plasma cells) was diagnosed on cytology and confirmed on histopathology. Immunohistochemistry (IHC), reverse transcriptase polymerase chain reaction (RT-PCR), and transmission electron microscopy were also performed. IHC and RT-PCR identified the presence of enzootic nasal tumor virus and confirmed the final diagnosis of enzootic nasal adenocarcinoma.}, journal={Case Reports in Veterinary Medicine}, publisher={Hindawi Limited}, author={Stowe, Devorah Marks and Anderson, Kevin L. and Guy, James S. and Linder, Keith E. and Grindem, Carol B.}, year={2012}, pages={1–4} } @article{beerlage_varanat_linder_maggi_cooley_kempf_breitschwerdt_2012, title={Bartonella vinsonii subsp. berkhoffii and Bartonella henselae as potential causes of proliferative vascular diseases in animals}, volume={201}, ISSN={0300-8584 1432-1831}, url={http://dx.doi.org/10.1007/s00430-012-0234-5}, DOI={10.1007/s00430-012-0234-5}, abstractNote={Bartonella species are highly fastidious, vector borne, zoonotic bacteria that cause persistent intraerythrocytic bacteremia and endotheliotropic infection in reservoir and incidental hosts. Based upon prior in vitro research, three Bartonella sp., B. bacilliformis, B. henselae, and B. quintana can induce proliferation of endothelial cells, and each species has been associated with in vivo formation of vasoproliferative tumors in human patients. In this study, we report the molecular detection of B. vinsonii subsp. berkhoffii, B. henselae, B. koehlerae, or DNA of two of these Bartonella species simultaneously in vasoproliferative hemangiopericytomas from a dog, a horse, and a red wolf and in systemic reactive angioendotheliomatosis lesions from cats and a steer. In addition, we provide documentation that B. vinsonii subsp. berkhoffii infections induce activation of hypoxia inducible factor-1 and production of vascular endothelial growth factor, thereby providing mechanistic evidence as to how these bacteria could contribute to the development of vasoproliferative lesions. Based upon these results, we suggest that a fourth species, B. vinsonii subsp. berkhoffii, should be added to the list of bartonellae that can induce vasoproliferative lesions and that infection with one or more Bartonella sp. may contribute to the pathogenesis of systemic reactive angioendotheliomatosis and hemangiopericytomas in animals.}, number={3}, journal={Medical Microbiology and Immunology}, publisher={Springer Science and Business Media LLC}, author={Beerlage, Christiane and Varanat, Mrudula and Linder, Keith and Maggi, Ricardo G. and Cooley, Jim and Kempf, Volkhard A. J. and Breitschwerdt, Edward B.}, year={2012}, month={Mar}, pages={319–326} } @article{olivry_linder_2012, title={Bilaterally Symmetrical Alopecia With Reticulated Hyperpigmentation}, volume={50}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985812463406}, DOI={10.1177/0300985812463406}, abstractNote={ An adult castrated male Doberman Pinscher was presented with a 6-month history of well-demarcated alopecic patches with reticulated hyperpigmentation and fine peripheral scaling on the axillae, thorax, abdomen, inguinal region, and thighs. The dog later developed hyperthermia, lethargy, apparent joint pain, peripheral lymphadenomegaly, vomiting, and diarrhea. Relevant laboratory tests results included anemia, thrombocytopenia, proteinuria, and an elevated antinuclear antibodies serum titer. Histologically, skin biopsy specimens had a lymphocyte-rich interface dermatitis and interface mural folliculitis ending in follicular destruction. Altogether, these signs were consistent with a unique alopecic variant of chronic cutaneous lupus erythematosus, eventually associated with the development of systemic lupus erythematosus. This rare form of chronic cutaneous lupus needs to be added to the expanding list of lymphocyte-mediated autoimmune alopecias in dogs. }, number={4}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Olivry, T. and Linder, K. E.}, year={2012}, month={Oct}, pages={682–685} } @article{schramme_josson_linder_2012, title={Characterization of the origin and body of the normal equine rear suspensory ligament using ultrasonography, magnetic resonance imaging, and histology}, volume={53}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/j.1740-8261.2011.01922.x}, DOI={10.1111/j.1740-8261.2011.01922.x}, abstractNote={The suspensory ligament is difficult to image accurately, partly because it contains ligamentous fibers, as well as noncollagenous adipose and muscle tissue in the normal horse. Our hypothesis was that magnetic resonance (MR) imaging would be more accurate than ultrasonography in identifying the size of the suspensory ligament and the presence and size of noncollagenous tissues within the ligament. Eleven horses were used for ultrasonographic andMRimaging and histologic evaluation of the rear suspensory ligament. The origin and body of the normal suspensory ligament had a heterogenous appearance onMRimages with two separate islands of mixed signal intensity evident throughout its otherwise hypointense cross‐sectional area. Histologically, there were isolated islands of muscle, adipose, loose connective tissue and dense collagenous partitions, organized in two separate bundles that extended through the full length of the suspensory ligament origin and body to the level of its bifurcation. Comparison ofMRimages with corresponding histologic sections confirmed that islands of heterogenous signal intensity in normal suspensory ligaments correlated well with these bundles. Using ultrasonography, it was impossible to distinguish these islands from surrounding dense collagenous tissue consistently.MRimaging determined the cross‐sectional area of the suspensory ligament more accurately than ultrasonography. Based upon these results,MRimaging is superior to ultrasonography for assessment of the suspensory ligament. The appearance associated with normal ligament anatomy needs to be understood beforeMRsignal variation can be considered as indicative of disease in the suspensory ligament.}, number={3}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Schramme, Michael and Josson, Anne and Linder, Keith}, year={2012}, month={Feb}, pages={318–328} } @article{olivry_linder_wang_bizikova_bernstein_dunston_paps_casal_2012, title={Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs}, volume={7}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0032072}, DOI={10.1371/journal.pone.0032072}, abstractNote={In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children.}, number={2}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Olivry, Thierry and Linder, Keith E. and Wang, Ping and Bizikova, Petra and Bernstein, Joseph A. and Dunston, Stanley M. and Paps, Judy S. and Casal, Margret L.}, editor={Brandner, Johanna M.Editor}, year={2012}, month={Feb}, pages={e32072} } @article{varanat_maggi_linder_breitschwerdt_2012, title={Infection of human brain vascular pericytes (HBVPs) by Bartonella henselae}, volume={202}, ISSN={0300-8584 1432-1831}, url={http://dx.doi.org/10.1007/s00430-012-0279-5}, DOI={10.1007/s00430-012-0279-5}, abstractNote={Angiogenesis is an important physiological and pathological process. Bartonella is the only genus of bacteria known to induce pathological angiogenesis in the mammalian host. Bartonella-induced angiogenesis leads to the formation of vascular tumors including verruga peruana and bacillary angiomatosis. The mechanism of Bartonella-induced angiogenesis is not completely understood. Pericytes, along with endothelial cells, play an important role in physiological angiogenesis, and their role in tumor angiogenesis has been extensively studied. Abnormal signaling between endothelial cells and pericytes contributes to tumor angiogenesis and metastasis; however, the role of pericytes in Bartonella-induced angiogenesis is not known. In this study, after infecting human brain vascular pericytes (HBVPs) with Bartonella henselae, we found that these bacteria were able to invade HBVPs and that bacterial infection resulted in decreased pericyte proliferation and increased pericyte production of vascular endothelial growth factor (VEGF) when compared to the uninfected control cells. In the context of pathological angiogenesis, reduced pericyte coverage, accompanied by increased VEGF production, may promote endothelial cell proliferation and the formation of new vessels.}, number={2}, journal={Medical Microbiology and Immunology}, publisher={Springer Science and Business Media LLC}, author={Varanat, Mrudula and Maggi, Ricardo G. and Linder, Keith E. and Breitschwerdt, Edward B.}, year={2012}, month={Nov}, pages={143–151} } @article{monteiro-riviere_linder_inman_saathoff_xia_riviere_2012, title={LACK OF HYDROXYLATED FULLERENE TOXICITY AFTER INTRAVENOUS ADMINISTRATION TO FEMALE SPRAGUE-DAWLEY RATS}, volume={75}, ISSN={["1087-2620"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000303594100001&KeyUID=WOS:000303594100001}, DOI={10.1080/15287394.2012.670894}, abstractNote={Hydroxylated fullerenes (C60OHx) or fullerols are water-soluble carbon nanoparticles that have been explored for potential therapeutic applications. This study assesses acute in vivo tolerance in 8-wk-old female Sprague-Dawley rats to intravenous (iv) administration of 10 mg/kg of well-characterized C60(OH)30. Complete histopathology and clinical chemistries are assessed at 8, 24, and 48 h after dosing. Minor histopathology changes are seen, primarily in one animal. No clinically significant chemistry changes were observed after treatment. These experiments suggest that this fullerol was well tolerated after iv administration to rats.}, number={7}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Monteiro-Riviere, Nancy A. and Linder, Keith E. and Inman, Alfred O. and Saathoff, John G. and Xia, Xin-Rui and Riviere, Jim E.}, year={2012}, pages={367–373} } @article{urkasemsin_linder_bell_lahunta_olby_2012, title={Mapping of Purkinje Neuron Loss and Polyglucosan Body Accumulation in Hereditary Cerebellar Degeneration in Scottish Terriers}, volume={49}, ISSN={["1544-2217"]}, DOI={10.1177/0300985811412622}, abstractNote={ A hereditary cerebellar degenerative disorder has emerged in Scottish Terriers. The aims of this study were to describe and quantify polyglucosan body accumulation and quantify Purkinje neurons in the cerebellum of affected and control dogs. The brains of 6 affected Scottish Terriers ranging in age from 8 to 15 years and 8 age-matched control dogs were examined histopathologically. Counts of Purkinje neurons and polyglucosan bodies were performed in control and affected dogs on cerebellar sections stained with periodic acid–Schiff. Affected dogs showed a significant loss of Purkinje neurons compared with control dogs (vermis: P < .0001; hemisphere: P = .0104). The degeneration was significantly more pronounced dorsally than ventrally ( P < .0001). There were significantly more polyglucosan bodies in the ventral half of the vermis when compared with the dorsal half ( P < .0001) in affected dogs. In addition, there were more polyglucosan bodies in the ventral half of the vermis in affected dogs than in control dogs ( P = .0005). Polyglucosan bodies in all affected dogs stained positively with toluidine blue and alcian blue. Immunohistochemically, polyglucosan bodies in affected dogs were positive for neurofilament 200 kD and ubiquitin and negative for glial fibrillary acidic protein, synaptophysin, neurospecific enolase, vimentin, and S100; the bodies were negative for all antigens in control dogs. Ultrastructurally, polyglucosan bodies in 1 affected dog were non–membrane-bound, amorphous structures with a dense core. This study demonstrates significant Purkinje cell loss and increased polyglucosan bodies in the cerebellum of affected Scottish Terriers. }, number={5}, journal={VETERINARY PATHOLOGY}, author={Urkasemsin, G. and Linder, K. E. and Bell, J. S. and Lahunta, A. and Olby, N. J.}, year={2012}, month={Sep}, pages={852–859} } @article{stevens_linder_2012, title={Pathology in Practice}, volume={241}, ISSN={["1943-569X"]}, DOI={10.2460/javma.241.5.567}, abstractNote={A 7-month-old sexually intact male domestic longhair cat was evaluated because of unusual skin lesions affecting both ears.The cat had been relinquished by its owner to a county animal shelter.No medical history was available. Clinical and Gross FindingsOn physical examination, the cat was in good body condition with abnormalities limited to both external ear canals and pinnae.The cat had locally extensive crusted and hyperkeratotic proliferative plaques that filled the external and vertical ear canals and extended onto 35% to 50% of the proximal concave portions of both pinnae.Le-}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Stevens, Brenda J. and Linder, Keith E.}, year={2012}, month={Sep}, pages={567–569} } @article{stevens_linder_2012, title={Proliferative and necrotizing otitis externa}, volume={241}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Stevens, BJ and Linder, KE}, year={2012}, month={Sep}, pages={567–569} } @article{oberkirchner_linder_olivry_2012, title={Successful treatment of a novel generalized variant of canine discoid lupus erythematosus with oral hydroxychloroquine}, volume={23}, ISSN={["0959-4493"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84855339558&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2011.00994.x}, abstractNote={Abstract}, number={1}, journal={VETERINARY DERMATOLOGY}, author={Oberkirchner, Ursula and Linder, Keith E. and Olivry, Thierry}, year={2012}, month={Feb}, pages={65–E16} } @article{chanoit_mathews_keene_small_linder_2012, title={Surgical treatment of a pulmonary artery vascular hamartoma in a dog}, volume={240}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.240.7.858}, DOI={10.2460/javma.240.7.858}, abstractNote={Abstract}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Chanoit, Guillaume and Mathews, Kyle G. and Keene, Bruce W. and Small, Merrilee T. and Linder, Keith}, year={2012}, month={Apr}, pages={858–862} } @article{thrall_maccarini_stauffer_macfall_hauck_snyder_case_linder_lan_mccall_et al._2012, title={Thermal dose fractionation affects tumour physiological response}, volume={28}, ISSN={["0265-6736"]}, DOI={10.3109/02656736.2012.689087}, abstractNote={Purpose: It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in one versus three to four fractions per week, over 5 weeks. Materials and methods: Canine sarcomas were randomised to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumour response was based on changes in tumour volume, oxygenation, water diffusion quantified using MRI, and a panel of histological and immunohistochemical end points. Results: There was a greater reduction in tumour volume and water diffusion at the end of therapy in tumours receiving one hyperthermia fraction per week. There was a weak but significant association between improved tumour oxygenation 24 h after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF-1α and CA-IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA-IX. There were no significant changes in interstitial fluid pressure, VEGF, vWF, apoptosis or necrosis as a function of treatment group or temperature. Conclusions: We did not identify an advantage to a three to four per week hyperthermia prescription, and response data pointed to a one per week prescription being superior.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, Donald E. and Maccarini, Paolo and Stauffer, Paul and Macfall, James and Hauck, Marlene and Snyder, Stacey and Case, Beth and Linder, Keith and Lan, Lan and Mccall, Linda and et al.}, year={2012}, pages={431–440} } @article{wood_breitschwerdt_nordone_linder_gookin_2012, title={Uropathogenic E. coli Promote a Paracellular Urothelial Barrier Defect Characterized by Altered Tight Junction Integrity, Epithelial Cell Sloughing and Cytokine Release}, volume={147}, ISSN={0021-9975}, url={http://dx.doi.org/10.1016/j.jcpa.2011.09.005}, DOI={10.1016/j.jcpa.2011.09.005}, abstractNote={The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequelae of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute uropathogenic E. coli infection in vitro using intact canine bladder mucosa mounted in Ussing chambers to determine whether infection induces primarily a transcellular or paracellular permeability defect. The Ussing chamber sustains tissue viability while physically separating submucosal and lumen influences, so this model is ideal for quantitative measurement of transepithelial electrical resistance (TER) to assess alterations of urothelial barrier function. Using this model, changes in both tissue ultrastructure and TER indicated that uropathogenic E. coli infection promotes a paracellular permeability defect associated with the failure of umbrella cell tight junction formation and umbrella cell sloughing. In addition, bacterial interaction with the urothelium promoted secretion of cytokines from the urinary bladder with bioactivity capable of modulating epithelial barrier function including tumour necrosis factor-α, interleukin (IL)-6 and IL-15. IL-15 secretion by the infected bladder mucosa is a novel finding and, because IL-15 plays key roles in reconstitution of tight junction function in damaged intestine, this study points to a potential role for IL-15 in UTI-induced urothelial injury.}, number={1}, journal={Journal of Comparative Pathology}, publisher={Elsevier BV}, author={Wood, M.W. and Breitschwerdt, E.B. and Nordone, S.K. and Linder, K.E. and Gookin, J.L.}, year={2012}, month={Jul}, pages={11–19} } @article{stringer_de voe_linder_troan_mccalla-martin_loomis_2012, title={VESICULOBULLOUS SKIN REACTION TEMPORALLY RELATED TO FIROCOXIB TREATMENT IN A WHITE RHINOCEROS (CERATOTHERIUM SIMUM)}, volume={43}, ISSN={["1042-7260"]}, DOI={10.1638/2011-0128.1}, abstractNote={Abstract:  A 40 yr-old female white rhinoceros (Ceratotherium simum) suffered from chronic nail-bed abscesses. Due to worsening of clinical signs, the animal's nonsteroidal anti-inflammatory treatment was switched to firocoxib. Approximately 7 days after this change, the animal developed multifocal vesicles and bullae along the lateral aspects of the thorax and abdomen, the dorsum, and the proximal limbs. Cytology and culture did not identify an infectious etiology. Histologically, the lesions consisted of a severe, subacute vesiculobullous dermatitis with intraepidermal to subepidermal clefting with areas of individual keratinocyte necrosis and minor neutrophilic epidermal infiltrates. These findings are similar to those seen in some drug reactions in people; therefore an adverse drug reaction to the firocoxib was suspected.}, number={1}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Stringer, Elizabeth M. and De Voe, Ryan S. and Linder, Keith and Troan, Brigid and McCalla-Martin, Amy and Loomis, Michael R.}, year={2012}, month={Mar}, pages={186–189} } @article{olivry_linder_paps_bizikova_dunston_donne_mondoulet_2012, title={Validation of a novel epicutaneous delivery system for patch testing of house dust mite-hypersensitive dogs}, volume={23}, number={6}, journal={Veterinary Dermatology}, author={Olivry, T. and Linder, K. E. and Paps, J. S. and Bizikova, P. and Dunston, S. and Donne, N. and Mondoulet, L.}, year={2012} } @article{foster_chinnadurai_nutt_pandiri_linder_alley_smith_2011, title={Congenital peritoneopericardial diaphragmatic hernia in an alpaca}, volume={89}, ISSN={0005-0423}, url={http://dx.doi.org/10.1111/j.1751-0813.2010.00661.x}, DOI={10.1111/j.1751-0813.2010.00661.x}, abstractNote={An adult alpaca was presented because of abdominal pain and was diagnosed with an intestinal obstruction. The putative diagnosis at surgery was an intestinal obstruction caused by peritonitis and intra‐abdominal adhesions. The cause of the inflammation was not determined at that time. The alpaca died soon after surgery from post‐surgical complications and a peritoneopericardial diaphragmatic hernia that was not diagnosed until necropsy.}, number={1-2}, journal={Australian Veterinary Journal}, publisher={Wiley}, author={Foster, DM and Chinnadurai, SK and Nutt, JN and Pandiri, A and Linder, KE and Alley, ML and Smith, GW}, year={2011}, month={Jan}, pages={51–54} } @article{snyder_linder_hedan_hauck_2011, title={Establishment and Characterization of a Canine Soft Tissue Sarcoma Cell Line}, volume={48}, ISSN={["1544-2217"]}, DOI={10.1177/0300985810383871}, abstractNote={Stringently controlled in vitro experiments are a necessary part of translational research. Cell lines are useful for exploring the underlying biology of cancer. Very few canine soft tissue sarcoma cell lines exist. This report describes the establishment of a new canine soft tissue sarcoma cell line (MBSa1) derived from a high-grade, metastatic neurofibrosarcoma. The primary tumor tissue was obtained from a 12-year-old neutered male German Shepherd Dog and was maintained in tissue culture for a minimum of 20 passages over 7 months. MBSa1 was injected into athymic mice to determine tumorigenicity. Five million cells were injected into the subcutis of the right flank of athymic nude mice. Nine of the 10 mice grew tumors 1 cm or larger within 8 weeks of cell injection. The large number of in vitro passages coupled with solid tumor formation in athymic nude mice demonstrates that MBSa1 has been immortalized and is tumorigenic.}, number={2}, journal={VETERINARY PATHOLOGY}, author={Snyder, S. A. and Linder, K. and Hedan, B. and Hauck, M. L.}, year={2011}, month={Mar}, pages={482–485} } @article{varanat_broadhurst_linder_maggi_breitschwerdt_2011, title={Identification of Bartonella henselae in 2 Cats With Pyogranulomatous Myocarditis and Diaphragmatic Myositis}, volume={49}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985811404709}, DOI={10.1177/0300985811404709}, abstractNote={ Most cats infected with Bartonella henselae remain outwardly healthy carriers for years; however, self-limiting fever, transient anemia, neurologic dysfunction, lymphadenopathy, reproductive disorders, aortic valvular endocarditis, and neutrophilic myocarditis have been described in experimentally or naturally infected cats. Two cats in a North Carolina shelter died with pyogranulomatous myocarditis and diaphragmatic myositis. Bacteria were visualized in the lesions by Warthin-Starry silver impregnation and by B. henselae immunohistochemistry. B. henselae DNA was amplified and sequenced from the heart of 1 cat and from multiple tissue samples, including heart and diaphragm, from the second cat. This study supports a potential association between B. henselae and what has been historically described as “transmissible myocarditis and diaphragmitis” of undetermined cause in cats. }, number={4}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Varanat, M. and Broadhurst, J. and Linder, K. E. and Maggi, R. G. and Breitschwerdt, E. B.}, year={2011}, month={Apr}, pages={608–611} } @article{bizikova_linder_olivry_2011, title={Immunomapping of desmosomal and nondesmosomal adhesion molecules in healthy canine footpad, haired skin and buccal mucosal epithelia: comparison with canine pemphigus foliaceus serum immunoglobulin G staining patterns}, volume={22}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952335927&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2010.00924.x}, abstractNote={Abstract}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Linder, Keith E. and Olivry, Thierry}, year={2011}, month={Apr}, pages={132–142} } @article{oberkirchner_linder_dunston_bizikova_olivry_2011, title={Metaflumizone-amitraz (Promeris)-associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug-triggered pemphigus foliaceus}, volume={22}, ISSN={["0959-4493"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80052525616&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2011.00974.x}, abstractNote={Abstract}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Oberkirchner, Ursula and Linder, Keith E. and Dunston, Stan and Bizikova, Petra and Olivry, Thierry}, year={2011}, month={Oct}, pages={436–448} } @article{varanat_maggi_linder_breitschwerdt_2011, title={Molecular Prevalence of Bartonella, Babesia, and Hemotropic Mycoplasma sp. in Dogs with Splenic Disease}, volume={25}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/j.1939-1676.2011.00811.x}, DOI={10.1111/j.1939-1676.2011.00811.x}, abstractNote={BackgroundAmong diseases that cause splenomegaly in dogs, lymphoid nodular hyperplasia (LNH), splenic hemangiosarcoma (HSA), and fibrohistiocytic nodules (FHN) are common diagnoses. The spleen plays an important role in the immunologic control or elimination of vector‐transmitted, blood‐borne pathogens, includingBartonellasp.,Babesiasp., and hemotropicMycoplasmasp.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Varanat, M. and Maggi, R.G. and Linder, K.E. and Breitschwerdt, E.B.}, year={2011}, month={Oct}, pages={1284–1291} } @article{oberkirchner_linder_olivry_2011, title={Recognizing and treating ProMeris-triggered pemphigus foliaceus in dogs}, volume={106}, number={6}, journal={Veterinary Medicine}, author={Oberkirchner, U and Linder, K and Olivry, T}, year={2011}, pages={284} } @article{house_zhu_ranjan_linder_smart_2010, title={C/EBP alpha and C/EBP beta Are Required for Sebocyte Differentiation and Stratified Squamous Differentiation in Adult Mouse Skin}, volume={5}, ISSN={["1932-6203"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952118221&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0009837}, abstractNote={C/EBPα and C/EBPβ are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPα and C/EBPβ in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPα or C/EBPβ alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPα and C/EBPβ in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPα and C/EBPβ in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPα and C/EBPβ are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.}, number={3}, journal={PLOS ONE}, author={House, John S. and Zhu, Songyun and Ranjan, Rakesh and Linder, Keith and Smart, Robert C.}, year={2010}, month={Mar} } @article{bizikova_linder_paps_olivry_2010, title={Effect of a novel topical diester glucocorticoid spray on immediate- and late-phase cutaneous allergic reactions in Maltese-beagle atopic dogs: a placebo-controlled study}, volume={21}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/j.1365-3164.2009.00782.x}, DOI={10.1111/j.1365-3164.2009.00782.x}, abstractNote={The inhibitory effect of 0.0584% hydrocortisone aceponate spray on immediate- and late-phase skin reactions and the duration of inhibition after medication withdrawal were studied in 10 Maltese-beagle atopic dogs. All subjects were sprayed on axillary and inguinal regions and on one randomly chosen side of the thorax once daily for 14 (phase 1) or 7 days (phase 2). Intradermal injections (IDT) of histamine and anticanine IgE antiserum were performed bilaterally on the thorax before, 7 and 14 days after treatment. During phase 2, IDT was performed once weekly for 5 weeks. Each IDT was evaluated by an investigator blinded to the site of active treatment. Skin biopsies of 24-h anti-IgE-associated late-phase reactions were collected from both thoracic sides before and 14 days after treatment to determine the number of inflammatory cells and dermal thickness. Phase 1: Histamine and anti-IgE-induced global wheal scores at treated sites were significantly lower after 7 and 14 days with negative reactions present in >90% of dogs. Late-phase reactions at both sides were also significantly decreased compared with that at baseline, and this was associated with reduced inflammatory cell influx. Moreover, a significant decrease in dermal thickness was recorded at treated sides after 14 days. Phase 2: Histamine reactions became positive at untreated sides in all dogs 2 weeks after treatment. In conclusion, the 0.0584% hydrocortisone aceponate spray significantly decreased immediate- and late-phase IDT reactions, and prolonged application caused skin atrophy at treated sites. A 2-week withdrawal period prior to IDT is proposed.}, number={1}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Bizikova, Petra and Linder, Keith E. and Paps, Judy and Olivry, Thierry}, year={2010}, month={Feb}, pages={71–80} } @article{urkasemsin_linder_bell_lahunta_olby_2010, title={Hereditary Cerebellar Degeneration in Scottish Terriers}, volume={24}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2010.0499.x}, abstractNote={BACKGROUND Hereditary cerebellar degeneration is described in several dog breeds. This heterogeneous group of diseases causes cerebellar ataxia associated with cerebellar cortical degeneration. OBJECTIVE To report the clinical and histopathological features, and describe the mode of inheritance of hereditary cerebellar degeneration in Scottish Terriers. ANIMALS Sixty-two affected dogs recruited through the Scottish Terrier Club of America. MATERIALS AND METHODS Prospective, observational study: Owners of affected dogs were contacted for a description of clinical signs, age of onset, and disease progression. Medical records, videotapes of gait, and brain imaging were evaluated. When possible, necropsy was performed and the brain examined histopathologically. Prevalence of the disease was estimated and a pedigree analysis was performed to determine mode of inheritance. RESULTS Gait abnormalities were noted in the 1st year of life in 76% of dogs, and progressed slowly; only 1 of 27 dogs dead at time of writing was euthanized because of cerebellar degeneration. Clinical signs included wide based stance, dysmetria, intention tremor, and difficulty negotiating stairs and running. Cerebellar atrophy was detected on magnetic resonance imaging. On histopathological examination, there was segmental loss of Purkinje neurons, thinning of molecular and granular layers, and polyglucosan bodies in the molecular layer. Prevalence of disease was estimated at 1 in 1,335 American Kennel Club registered Scottish Terriers. Genetic analysis results are consistent with an autosomal recessive mode of inheritance. CONCLUSION AND CLINICAL IMPORTANCE A hereditary cerebellar degenerative disorder with a relatively mild phenotype has emerged in the Scottish Terrier. Genetic studies are needed.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Urkasemsin, G. and Linder, K. E. and Bell, J. S. and Lahunta, A. and Olby, N. J.}, year={2010}, pages={565–570} } @article{kim_chiera_linder_trempus_smart_horowitz_2010, title={Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound- and Carcinogen-Induced Tumorigenesis}, volume={70}, ISSN={["1538-7445"]}, DOI={10.1158/0008-5472.can-10-1213}, abstractNote={Abstract}, number={21}, journal={CANCER RESEARCH}, author={Kim, Tae-Hyung and Chiera, Shannon L. and Linder, Keith E. and Trempus, Carol S. and Smart, Robert C. and Horowitz, Jonathan M.}, year={2010}, month={Nov}, pages={8507–8516} } @article{oberkirchner_linder_zadrozny_olivry_2010, title={Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide}, volume={21}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77956458558&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2009.00876.x}, abstractNote={Abstract}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Oberkirchner, Ursula and Linder, Keith E. and Zadrozny, Leah and Olivry, Thierry}, year={2010}, month={Oct}, pages={510–516} } @article{liles_linder_cain_pease_2010, title={ULTRASONOGRAPHY OF HISTOLOGICALLY NORMAL PARATHYROID GLANDS AND THYROID LOBULES IN NORMOCALCEMIC DOGS}, volume={51}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2010.01686.x}, abstractNote={The purpose of this study is to characterize the sonographic appearance of canine parathyroid glands using high-resolution ultrasonography. Ten cadaver dogs were studied after euthanasia for reasons not relating to the parathyroid. The cervical region was examined using a 13-5 MHz linear transducer in right and left recumbency. Ultrasonographic features of the parathyroid and thyroid glands were compared with the gross and histopathologic findings. Thirty-five structures were identified sonographically as parathyroid glands but only 26 of 35 glands (74% positive predictive value) were proven to be normal parathyroid glands histopathologically. Of the nine false positives, five (14%) were proven to be lobular thyroid tissue. The remaining four (11%) structures were visible grossly or found histopathologically. There were no statistical differences between ultrasonographic and gross measurements of the parathyroid glands. The average size as seen sonographically was 3.3 x 2.2 x 1.7 mm and the average gross size was 3.7 x 2.6 x 1.6 mm (length, width, height). The average size of the thyroid lobules assessed sonographically was 2.3 x1.6 x 0.8 mm (length, width, height). Normal parathyroid glands can be identified using high-resolution ultrasonography. But some thyroid lobules will be misinterpreted as parathyroid glands; this will result in false positives when identifying parathyroid glands with ultrasonography.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Liles, Sofija R. and Linder, Keith E. and Cain, Brandon and Pease, Anthony P.}, year={2010}, pages={447–452} } @article{mccalla-martin_chen_linder_estrada_piedrahita_2010, title={Varying phenotypes in swine versus murine transgenic models constitutively expressing the same human Sonic hedgehog transcriptional activator, K5-HGLI2ΔN}, volume={19}, ISSN={0962-8819 1573-9368}, url={http://dx.doi.org/10.1007/s11248-010-9362-0}, DOI={10.1007/s11248-010-9362-0}, abstractNote={This study was undertaken to characterize the effects of constitutive expression of the hedgehog transcriptional activator, Gli2, in porcine skin. The keratinocyte-specific human transgene, K5-hGli2 Delta N, was used to produce transgenic porcine lines via somatic cell nuclear transfer techniques. In mice, K5-hGli2 Delta N induces epithelial downgrowths resembling basal cell carcinomas. Our porcine model also developed these basal cell carcinoma-like lesions, however gross tumor development was not appreciated. In contrast to the murine model, diffuse epidermal changes as well as susceptibility to cutaneous infections were seen in the swine model. Histologic analysis of transgenic piglets revealed generalized epidermal changes including: epidermal hyperplasia (acanthosis), elongated rete ridges, parakeratotic hyperkeratosis, epidermal neutrophilic infiltration, capillary loop dilation and hypogranulosis. By 2 weeks of age, the transgenic piglets developed erythematic and edematous lesions at high contact epidermal areas and extensor surfaces of distal limb joints. Despite antibiotic treatment, these lesions progressed to a deep bacterial pyoderma and pigs died or were euthanized within weeks of birth. Non-transgenic littermates were phenotypically normal by gross and histological analysis. In summary, constitutive expression of the human hGli2 Delta N in keratinocytes, results in cutaneous changes that have not been reported in the K5-hGli2 Delta N murine model. These findings indicate a need for a multiple species animal model approach in order to better understand the role of Gli2 in mammalian skin.}, number={5}, journal={Transgenic Research}, publisher={Springer Science and Business Media LLC}, author={McCalla-Martin, Amy C. and Chen, Xiaoxin and Linder, Keith E. and Estrada, Jose L. and Piedrahita, Jorge A.}, year={2010}, month={Jan}, pages={869–887} } @article{tuttle_maclean_linder_cullen_wolfe_loomis_2009, title={ACQUIRED ARTERIOVENOUS FISTULA IN A GRIZZLY BEAR (URSUS ARCTOS HORRIBILIS)}, volume={40}, ISSN={["1042-7260"]}, DOI={10.1638/2007-0030.1}, abstractNote={Abstract A captive adult male grizzly bear (Ursus arctos horribilis) was evaluated due to multifocal wounds of the skin and subcutaneous tissues sustained as a result of trauma from another grizzly bear. On presentation, one lesion that was located in the perineal region seemed to be a deep puncture with purple tissue protruding from it. This perineal wound did not heal in the same manner or rate as did the other wounds. Twenty-five days after initial detection, substantial active hemorrhage from the lesion occurred and necessitated anesthesia for examination of the bear. The entire lesion was surgically excised, which later proved curative. An acquired arteriovenous fistula was diagnosed via histopathology. Arteriovenous fistulas can develop after traumatic injury and should be considered as a potential complication in bears with nonhealing wounds.}, number={1}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Tuttle, Allison D. and MacLean, Robert A. and Linder, Keith and Cullen, John M. and Wolfe, Barbara A. and Loomis, Michael}, year={2009}, month={Mar}, pages={193–195} } @article{mathews_linder_davidson_goldman_papich_2009, title={Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs}, volume={70}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.70.5.640}, abstractNote={Abstract}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Mathews, Kyle G. and Linder, Keith E. and Davidson, Gigi S. and Goldman, Rebecca B. and Papich, Mark G.}, year={2009}, month={May}, pages={640–647} } @article{bizikova_linder_suter_van wettere_olivry_2009, title={Canine cutaneous epitheliotropic T-cell lymphoma with vesiculobullous lesions resembling human bullous mycosis fungoides}, volume={20}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/j.1365-3164.2009.00760.x}, DOI={10.1111/j.1365-3164.2009.00760.x}, abstractNote={Abstract}, number={4}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Bizikova, Petra and Linder, Keith E. and Suter, Steven E. and Van Wettere, Arnaud J. and Olivry, Thierry}, year={2009}, month={Aug}, pages={281–288} } @article{varanat_maggi_linder_horton_breitschwerdt_2009, title={Cross-contamination in the Molecular Detection of Bartonella from Paraffin-embedded Tissues}, volume={46}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1354/vp.08-VP-0259-B-BC}, DOI={10.1354/vp.08-VP-0259-B-BC}, abstractNote={ The genus Bartonella comprises a group of gram-negative, fastidious bacteria. Because of diagnostic limitations of culture and serologic testing, polymerase chain reaction (PCR) has become a powerful tool for the detection of Bartonella spp. in blood and tissue samples. However, because many wild and domestic animals harbor Bartonella spp., transfer of Bartonella DNA during sample collection or histologic processing could result in false-positive PCR test results. In this study, we describe evidence of Bartonella DNA dissemination and transfer in the necropsy room and during the subsequent processing of formalin-fixed paraffin-embedded tissues. Bartonella DNA was amplified from different areas of the necropsy room, from the liquid paraffin in the tissue processor, and from different parts of the microtome. Unless stringent procedures are established and followed to avoid cross-contamination, the molecular detection of Bartonella spp. from tissue samples obtained at necropsy or processed in a multispecies histopathology laboratory will not be reliable. }, number={5}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Varanat, M. and Maggi, R. G. and Linder, K. E. and Horton, S. and Breitschwerdt, E. B.}, year={2009}, month={May}, pages={940–944} } @article{olivry_linder_2009, title={Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases}, volume={20}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-73149118226&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2009.00821.x}, abstractNote={Abstract}, number={5-6}, journal={VETERINARY DERMATOLOGY}, author={Olivry, Thierry and Linder, Keith E.}, year={2009}, pages={313–326} } @article{mitsui_mathews_linder_kruse_roe_2009, title={Effects of fascial abrasion, fasciotomy, and fascial excision on cutaneous wound healing in cats}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.4.532}, DOI={10.2460/ajvr.70.4.532}, abstractNote={Abstract}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Mitsui, Akiko and Mathews, Kyle G. and Linder, Keith E. and Kruse, Meghan A. and Roe, Simon C.}, year={2009}, month={Apr}, pages={532–538} } @article{breitschwerdt_maggi_varanat_linder_weinberg_2009, title={Isolation of Bartonella vinsonii subsp. berkhoffii Genotype II from a Boy with Epithelioid Hemangioendothelioma and a Dog with Hemangiopericytoma}, volume={47}, ISSN={0095-1137}, url={http://dx.doi.org/10.1128/JCM.00069-09}, DOI={10.1128/JCM.00069-09}, abstractNote={ABSTRACT}, number={6}, journal={Journal of Clinical Microbiology}, publisher={American Society for Microbiology}, author={Breitschwerdt, E. B. and Maggi, R. G. and Varanat, M. and Linder, K. E. and Weinberg, G.}, year={2009}, month={Apr}, pages={1957–1960} } @article{santoro_pease_linder_olivry_2009, title={Post-traumatic peripheral arteriovenous fistula manifesting as digital haemorrhages in a cat: diagnosis with contrast-enhanced 3D CT imaging}, volume={20}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-65649086814&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2009.00754.x}, abstractNote={Abstract}, number={3}, journal={VETERINARY DERMATOLOGY}, author={Santoro, Domenico and Pease, Anthony and Linder, Keith E. and Olivry, Thierry}, year={2009}, month={Jun}, pages={206–213} } @article{varanat_travis_lee_maggi_bissett_linder_breitschwerdt_2009, title={Recurrent Osteomyelitis in a Cat due to Infection with Bartonella vinsonii subsp. berkhoffii Genotype II}, volume={23}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2009.0372.x}, DOI={10.1111/j.1939-1676.2009.0372.x}, abstractNote={A 4-year-old spayed-female Domestic Shorthair cat, obtained from a shelter as a kitten, was examined in May 2007 because of an intermittent lameness. Rectal temperature was 102°F. The cat weighed 3.3 kg. There was a focal, nonpainful, 2.5-cm-diameter firm swelling at the medial aspect of the left metatarsal region. Radiographs of the left rear leg identified lysis of the distal aspect of the 1st metatarsal bone and adjacent soft tissue swelling. Thoracic radiographs were unremarkable. Neoplasia was suspected and digital amputation was elected. Preanesthetic blood tests identified thrombocytopenia (25,000/μL; reference range, 200,000–500,000) with an adequate estimated platelet count because of clumping, mild lymphopenia (1,071 lymphocytes/μL; reference range, 1,200–8,000), mild hyperglobulinemia (5.4 g/dL; reference range, 2.3–5.3), and negative FIV and FeLV ELISA test results. The neutrophil count was 4,725/μL (reference range, 2,500–8,500) with no bands or neutrophil toxicity. Urinalysis was unremarkable. At surgery, the left medial metatarsophalangeal joint was disarticulated and the digit was removed. Histopathologic evaluation identified a mixed inflammatory response, characterized by a large number of well-differentiated plasma cells, macrophages with erythrophagocytosis and focal aggregates of neutrophils. Pyogranulomatous osteomyelitis was diagnosed. Plasma cell numbers were sufficiently high that plasma cell neoplasia was considered a plausible differential diagnosis. Fungal, acid-fast, and silver stains did not identify infectious agents. Culture of the amputated tissue was not performed. Two weeks postoperatively, an ulcer formed at the surgical site and was accompanied by moderate muscle atrophy. The distal limb became necrotic from the surgical site to the mid-tibia, which was accompanied by severe atrophy of the left rear leg to the level of the stifle and a loss of distal deep pain, which required mid femoral amputation. At no time had the cat traumatized the original incision. Despite necrosis, there was minimal to no purulent discharge and the cat never appeared overtly uncomfortable, despite rapid deterioration in the limb. In November 2007, the cat was examined because of lethargy. The cat was thrombocytopenic (97,000/μL; reference range, 175,000–600,000) and neutropenic (1,064/μL; reference range, 2,500–8,500). Urinalysis identified proteinuria and neutrophils suggestive of a urinary tract infection and the cat was treated with amoxicillin-clavulanate 62.5 mg PO q12h for 7 days. Urine culture was not performed. In February 2008, diffuse distal swelling and lameness developed in the left front leg. Radiographs identified mild soft tissue swelling and mild degenerative joint disease. The cat was treated with meloxicam 0.45 mg PO q24h for 3 days, then q72h to alleviate pain and swelling. Despite this treatment, the cat remained intermittently lame. Swelling and lameness of the left front leg again were documented by physical examination in May 2008, at which time the swelling had become firmer and more localized over the left carpus. There also was thickening of the right carpal region, which was firmer and less pliable than the left carpal region. Radiographs identified osteolysis of the left radial carpal bone with concurrent periosteal reaction. There was also cortical expansion of the right 5th metacarpal bone. Although serum globulin concentration was within reference range, serum protein electrophoresis documented polyclonal gammopathy associated with increased gamma globulins (2.54 g/dL; reference range, 0.5–1.90). By June 2008, the cat had persistent decreased weight bearing on the left thoracic limb. The left carpus was swollen and painful, and the distal limb had developed a valgus deformity. The right thoracic leg was also painful during carpal palpation and range of motion manipulations, but the owner reported no lameness or pain at home. The lateral phalanges of the right thoracic limb were swollen and firm. The cat was sedated with 0.15 mg dexmeditomidine IM. Radiographs of the left and right thoracic limbs, chest, and right pelvic limb were obtained. Cytology samples were also obtained from the lesions in the left and right thoracic limbs by fine needle aspiration. Radiographs documented an ovoid expansile lesion of the right 5th metacarpal bone, characterized by extensive and irregular osteoproliferation, marked cortical bone destruction, and moderate thickening of the soft tissues lateral to the metacarpal lesion (Fig 1). Severe osteolysis of left radial carpal bone was also present, as well as irregular periosteal proliferation involving all left carpal bones and the proximal aspects of all left metacarpal bones. Moderate left carpal joint effusion was also noted. The radiographic findings of polyostotic osteolysis and irregular osteoproliferation in a patient of this age were consistent with multifocal osteomyelitis of either bacterial or fungal etiology. Given the presence of left carpal joint effusion and involvement of the left carpal bones, septic arthritis of the left carpal joint was considered likely. Soft tissue swelling adjacent to the right 5th metacarpal bone was thought to represent cellulitis. Other aggressive bone lesions (ie, primary or metastatic osseous neoplasia) were considered less likely. Right pelvic limb and thoracic radiographs were within normal limits. (A) Dorsopalmar radiograph of the right pes. Note the aggressive expansile lesion of the right 5th metacarpal bone and adjacent soft tissue swelling (white arrow). (B) Dorsopalmar radiograph of the left pes. Note the severe osteolysis of the radial carpal bone (large white arrow), osteoproliferation of the carpal and metacarpal bones (small white arrow), and carpal joint effusion (white arrowhead). Cytology from the left carpal lesion identified erythrophagocytosis, nontoxic neutrophils, epithelioid, and multinucleated cells thought to be osteoclasts, scattered plasmacytoid osteoblasts, and numerous benign plasma cells. Organisms were not seen, including lack of viral, anaplasma, or ehrlichial inclusions. The cytology results and clinical information supported chronic neutrophilic and plasmacytic osteomyelitis. Based on cellular appearance and the duration of the disease process, plasma cells were reported to be reactive rather than neoplastic, but myeloma could not be excluded from the differential diagnosis. The cat was treated with tramadol hydrochloride 12.5 mg PO q12h while the owner decided whether to pursue additional diagnostic testing. In August 2008 the cat was sedated with a combination of 80 mg ketamine, 0.16 mg dexmedetomidine, and 0.27 mg buprenorphine IM. Radiographs showed moderate progression of the osseous lesions identified in June. Blood was obtained for a CBC and serum biochemical profile. With the exception of mild thrombocytopenia (193,000/μL; reference range, 200,000–500,000) potentially associated with platelet clumping, CBC findings were within reference ranges and the neutrophil count was 5,355/μL (reference range, 2,500–8,500). Serum biochemical abnormalities included hypercalcemia (11.6 mg/dL; reference range, 8.2–10.8) and hyperglobulinemia (6.0 g/dL; reference range, 2.3–5.3). Fungal serology for aspergillosis, blastomycosis, coccidiomycosis, and histoplasmosis was negative and repeat FIV and FeLV test results were negative. A bone marrow aspiration sample, obtained to further assess the possibility of a plasma cell myeloma, was unremarkable. Aerobic culture of the bone marrow aspirate yielded mild growth of Salmonella enterica subsp. enterica, which was considered a potential sample collection contaminant. Mycoplasma and fungal cultures of the bone marrow aspirate were negative. Aerobic, anaerobic, fungal, and Mycoplasma cultures of joint fluid, aspirated from the left carpal-metacarpal joint were negative for growth. An aseptically obtained jugular blood sample, submitted to the Vector Borne Diseases Diagnostic Laboratory, NCSU-CVM, was cultured in BAPGM (Bartonella alpha proteobacteria growth medium).1 Although awaiting test results, the cat was treated with 20 mg PO q12h and azithromycin 20 mg PO q48h for presumptive intracellular bacterial infection. Bartonella spp. PCR following direct extraction from the blood sample was negative. After a 7-day incubation period, Bartonella vinsonii subsp. berkhoffii genotype II DNA was PCR amplified and sequenced from the BAPGM enrichment blood culture.1Bartonella henselae DNA and DNA from a healthy dog served as positive and negative controls, respectively. Subculture onto an agar plate did not result in bacterial growth. By IFA testing, B. vinsonii subsp. berkhoffii and B. henselae antibody titers were 1 : 128 and 1 : 64, respectively. The cat was treated for bartonellosis for 3 months with azithromycin 36 mg (10 mg/kg) PO q48h and concurrently with amoxicillin-clavulanate 62.5 mg PO q12h for 2 months for possible infection with S. enterica. During this time period, the owner reported a progressive increase in weight bearing on the left forelimb and decreased pain when walking, and meloxicam and tramadol were discontinued. In February 2009, repeated BAPGM blood culture failed to detect B. vinsonii subsp. berkhoffii DNA or growth of bacteria. B. vinsonii subsp. berkhoffii and B. henselae antibody titers were negative. The cat continued to be less painful, but both the left and right carpi were grossly larger than in November 2008. Radiographs showed continued progression of the previously described thoracic limb lesions. Radiographs of the right pelvic limb and thorax remained within normal limits. Azithromycin was discontinued once blood culture results became available. Reculture was recommended, but not performed 1 month after cessation of antibiotics. As of June 2009, the cat was healthy, was walking without pain, and had not received additional antibiotics or pain medications. After successful blood culture detection of B. vinsonii subsp. berkhoffii in August 2008, the original formalin-fixed, paraffin-embedded left medial metatarsal osteomyelitis lesion, was sent to the Intracellular Pathogens Research Laboratory to determine if the cat was infected with B. vinsonii subsp. berkhoffii at the time of digital amputation. B. vinsonii subsp. berkhoffii genotype II DNA again was amplified and sequenced from the original lesion. B. vinsonii subsp. berkhoffii genotype I was isolated for the 1st time in 1993 from a dog with shifting leg lameness, epistaxis, recent-onset seizures, and endocarditis.2 Subsequently, 3 additional genotypes (designated II–IV), all of which have been implicated as a cause of endocarditis in dogs, were described based upon sequence differences in the Bartonella 16S-23S intergenic spacer region and the pap31 gene.3,4 In pet dogs, both seroprevalence studies and blood culture isolation results indicate infrequent exposure to or active infection with any of the 4 B. vinsonii subsp. berkhoffii genotypes, whereas exposure is more frequent in rural and working dogs, and in coyotes and feral dog populations.1,3,5,6 On a comparative medical basis, dogs and humans infected with Bartonella spp. can develop similar disease manifestations, including endocarditis, granulomatous lymphadenitis, granulomatous hepatitis, bacillary angiomatosis, peliosis hepatis, seizures, and arthritis.5,6 Although seemingly well-adapted on an evolutionary basis to induce persistent infection in canine reservoir hosts (eg, coyotes), B. vinsonii subsp. berkhoffii has only rarely been isolated from pet dogs, foxes, or humans.2,3 To our knowledge, this case report describes the 1st isolation of B. vinsonii subsp. berkhoffii from a cat and the 1st association of a Bartonella spp. with osteomyelitis in any animal other than a human being. B. henselae and Bartonella clarridgeiae are transmitted among cats by Ctenocephalides felis.5,7 Healthy cats are considered reservoir hosts for these 2 Bartonella spp. and are generally nonclinical carriers of these intravascular bacteria.5,7 In various study populations throughout the world, B. henselae bacteremia has been reported in 8–56% of healthy cats whereas prevalence of B. clarridgeiae bacteremia generally is much lower.7 Although disease associated with B. henselae and B. clarridgeiae is not commonly recognized in cats, other non–reservoir-adapted Bartonella spp., such as B. vinsonii subsp. berkhoffii, for which dogs are the only known reservoir hosts,3–5 may be pathogenic when transmitted to cats. In humans, musculoskeletal manifestations, including osteomyelitis, have been reported as a complication of cat scratch disease (CSD), caused by B. henselae. In a study by Maman et al,8 about 10% of CSD patients developed chronic musculoskeletal complications including myalgia, arthritis, osteomyelitis, and neuralgia. There are also case reports of B. henselae-associated osteomyelitis, most often in children, at times, not accompanied by fever or lymphadenopathy.9,10 Non–host-adapted Bartonella spp. are more likely to be associated with development of pathology, for example B. henselae osteomyelitis in people and B. vinsonii subsp. berkhoffii osteomyelitis in this cat. Because B. vinsonii subsp. berkhoffii genotype II was PCR amplified and sequenced from an enrichment blood culture obtained 15 months after digital amputation and then was retrospectively amplified and sequenced from the paraffin block produced at the time of initial surgery, it is likely that this organism caused persistent bacteremia, recurrent osteomyelitis, and arthritis in this cat. Recently, we described Bartonella spp. DNA carryover when processing necropsy and biopsy tissue samples, which represents a potentially unique problem for the molecular diagnosis of bartonellosis in veterinary medicine.11 In this cat, recurrent disease accompanied by repeated sequencing of an infrequently detected subspecies and defined genotype makes DNA carryover less likely. In addition, special precautions were taken in our laboratory when sampling paraffin blocks to minimize this possibility. Whether infection with B. vinsonii subsp. berkhoffii after digital amputation contributed to postoperative necrosis and what appeared to be ischemic atrophy of the left rear leg could not be determined because tissues from the amputated leg were not submitted for histopathology. Current recommendations for the treatment of Bartonella musculoskeletal infections are based predominantly on empirical data. Although reinfection cannot be ruled out, it seems likely that B. vinsonii subsp. berkhoffii was not immunologically or therapeutically eliminated after digital and rear leg amputations in this cat. BAPGM enrichment cultures of blood and joint fluid recently were used to document failure of azithromycin or marbofloxacin to eliminate B. henselae and B. vinsonii subsp. berkhoffii from a dog that progressed from nonerosive to erosive polyarthritis.12 Resistance to macrolide antibiotics has been reported for B. henselae,13 but additional studies are required to determine if B. vinsonii subsp. berkhoffii can also develop macrolide resistance. In addition to osteomyelitis, clinical and radiographic findings in this cat suggested chronic, progressive polyarthritis, which also was reported in 3 dogs that were seroreactive to B. vinsonii subsp. berkhoffii antigens.14 As reported in this cat, clinical improvement occurred in these dogs in conjunction with antimicrobial therapy and was accompanied by a rapid decrease in B. vinsonii subsp. berkhoffii antibodies.14 In humans with B. henselae osteomyelitis, prognosis is good with patients being treated for a median duration of 32 days with mono, dual, or triple antibiotic therapy.9 Bartonella sp. are highly fastidious organisms that can be difficult or impossible to isolate by conventional blood culture or to detect by PCR amplification after direct extraction of DNA from patient samples.1,15 These diagnostic limitations are especially applicable when attempting to document infection with a Bartonella spp. in a nonreservoir host.16,17 In conjunction with efforts to enhance the sensitivity of PCR for detection of Bartonella-specific DNA sequences, we have recently incorporated pre-enrichment culture of aseptically obtained diagnostic samples (blood, cerebrospinal, aqueous, and joint fluids and effusions) using a liquid insect cell culture-based medium (BAPGM) before PCR testing.8 Combining pre-enrichment culture with PCR amplification has substantially improved diagnostic sensitivity when testing samples from dogs and humans infected with novel Bartonella species.18 Historically, because B. henselae and B. clarridgeiae could be readily isolated from cat blood after an incubation period of a few weeks in a high CO2 incubator, our laboratory did not initially recommend the use of BAPGM when culturing cat blood samples. As illustrated by this cat, direct PCR from blood was negative, suggesting that an enrichment culture approach may be necessary to diagnose infection with non–reservoir-adapted Bartonella spp. in cats, as has been shown for dogs and human patients.1,4,16,17 In addition, PCR amplification of B. vinsonii subsp. berkhoffii DNA only after enrichment culture supports the presence of viable bacteria in the blood sample, because the initial PCR-negative blood sample was diluted 1 part blood to 10 parts BAPGM before incubation for 7 days. Various Bartonella spp. are transmitted among reservoir hosts by fleas, lice, sand flies, keds, and possibly biting flies and ticks.19 Transmission to non–reservoir-adapted hosts can occur via an arthropod bite or a scratch or bite by a carrier animal. The mode of B. vinsonii subsp. berkhoffii transmission to this cat is unknown. B. vinsonii subsp. berkhoffii DNA has been amplified and sequenced from saliva obtained from healthy dogs, and dogs have been implicated in the direct transmission of B. henselae to humans.20 Therefore, dog bite transmission could have been a source of infection for this cat. Although there is clinical and epidemiological evidence to support B. vinsonii subsp. berkhoffii transmission by Rhipicephalus sanguineus, tick transmission has not been proven.19 In recent years, Bartonella spp. have been associated with a wide spectrum of inflammatory lesions in dogs and human patients, including endocarditis, encephalitis, meningitis, granulomatous hepatitis, splenitis, and necrotizing granulomatous lymphadenitis.6,21,22 Classically these facultative, intracellular bacteria induce a B-cell–associated granulomatous reaction, characterized by numerous histiocytes, plasmacytoid monocytes, small lymphocytes, multinucleated giant cells, and plasma cells intermingled with monocytoid B-cells.23 Granulomatous inflammation, accompanied by an unusually large number of plasma cells and hyperglobulinemia, was most likely related to B. vinsonii subsp. berkhoffii infection in this cat. Importantly, 2 pathologists thought plasma cell tumor was a diagnostic consideration. Fever and leukocytosis were not associated with polyarthritis and osteomyelitis in this cat. Thrombocytopenia and neutropenia have been reported in dogs and humans infected with Bartonella spp.24 Although osteomyelitis may have caused hypercalcemia, endogenous production of active vitamin D may have contributed, as reported in twins with CSD.25 Additional studies are needed to determine the frequency of B. vinsonii subsp. berkhoffii infection in cats. Based on this case report, Bartonella spp. infection should be considered in the differential diagnosis of osteomyelitis, hypercalcemia, hyperglobulinemia, and thrombocytopenia in cats. This study was supported by the State of North Carolina and in part through graduate student stipend or salary support provided by Bayer Animal Health and IDEXX Laboratories.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Varanat, M. and Travis, A. and Lee, W. and Maggi, R.G. and Bissett, S.A. and Linder, K.E. and Breitschwerdt, E.B.}, year={2009}, month={Nov}, pages={1273–1277} } @article{van wettere_linder_suter_olby_2009, title={Solitary Intracerebral Plasmacytoma in a Dog: Microscopic, Immunohistochemical, and Molecular Features}, volume={46}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1354/vp.08-VP-0012-V-BC}, DOI={10.1354/vp.08-VP-0012-V-BC}, abstractNote={ A primary intracerebral plasmacytoma was identified in a 7-year-old spayed female Boston Terrier. Grossly, a well-demarcated, 2 cm in diameter, roughly spherical tumor was in the rostral aspect of the left cerebral hemisphere. Histologically, the neoplasm was composed of sheets of round cells with distinct plasmacytoid features and marked anisocytosis and anisokaryosis. Cells were positive for vimentin, CD18, CD79a, and lambda light-chain, and negative for kappa light chain, cytokeratin, lysozyme, glial fibrillary acidic protein, and S100 protein. Clonally rearranged B-cell antigen receptor genes were detected by PARR (polymerase chain reaction for antigen receptor rearrangements), confirming clonal proliferation of B lymphocytes. Although primary solitary intracerebral plasmacytoma is rare in dogs and other species, it should be included in the differential diagnosis for central nervous system round-cell neoplasms. Clonality testing can be utilized to support the histological diagnosis of this neoplasm type. }, number={5}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Van Wettere, A. J. and Linder, K. E. and Suter, S. E. and Olby, N. J.}, year={2009}, month={May}, pages={949–951} } @article{thomas_duke_wang_breen_higgins_linder_ellis_langford_dickinson_olby_et al._2009, title={‘Putting our heads together’: insights into genomic conservation between human and canine intracranial tumors}, volume={94}, ISSN={0167-594X 1573-7373}, url={http://dx.doi.org/10.1007/s11060-009-9877-5}, DOI={10.1007/s11060-009-9877-5}, abstractNote={Numerous attributes render the domestic dog a highly pertinent model for cancer-associated gene discovery. We performed microarray-based comparative genomic hybridization analysis of 60 spontaneous canine intracranial tumors to examine the degree to which dog and human patients exhibit aberrations of ancestrally related chromosome regions, consistent with a shared pathogenesis. Canine gliomas and meningiomas both demonstrated chromosome copy number aberrations (CNAs) that share evolutionarily conserved synteny with those previously reported in their human counterpart. Interestingly, however, genomic imbalances orthologous to some of the hallmark aberrations of human intracranial tumors, including chromosome 22/NF2 deletions in meningiomas and chromosome 1p/19q deletions in oligodendrogliomas, were not major events in the dog. Furthermore, and perhaps most significantly, we identified highly recurrent CNAs in canine intracranial tumors for which the human orthologue has been reported previously at low frequency but which have not, thus far, been associated intimately with the pathogenesis of the tumor. The presence of orthologous CNAs in canine and human intracranial cancers is strongly suggestive of their biological significance in tumor development and/or progression. Moreover, the limited genetic heterogenity within purebred dog populations, coupled with the contrasting organization of the dog and human karyotypes, offers tremendous opportunities for refining evolutionarily conserved regions of tumor-associated genomic imbalance that may harbor novel candidate genes involved in their pathogenesis. A comparative approach to the study of canine and human intracranial tumors may therefore provide new insights into their genetic etiology, towards development of more sophisticated molecular subclassification and tailored therapies in both species.}, number={3}, journal={Journal of Neuro-Oncology}, publisher={Springer Science and Business Media LLC}, author={Thomas, Rachael and Duke, Shannon E. and Wang, Huixia J. and Breen, Tessa E. and Higgins, Robert J. and Linder, Keith E. and Ellis, Peter and Langford, Cordelia F. and Dickinson, Peter J. and Olby, Natasha J. and et al.}, year={2009}, month={Mar}, pages={333–349} } @article{hardie_linder_pease_2008, title={Aural Cholesteatoma in Twenty Dogs}, volume={37}, ISSN={["1532-950X"]}, DOI={10.1111/j.1532-950X.2008.00455.x}, abstractNote={Objective—To determine the clinical course in dogs with aural cholesteatoma.}, number={8}, journal={VETERINARY SURGERY}, author={Hardie, Elizabeth M. and Linder, Keith E. and Pease, Anthony P.}, year={2008}, month={Dec}, pages={763–770} } @article{chinnadurai_brown_van wettere_tuttle_fatzinger_linder_harms_2008, title={MORTALITIES ASSOCIATED WITH SEPSIS, PARASITISM, AND DISSEMINATED ROUND CELL NEOPLASIA IN YELLOW-LIPPED SEA KRAITS (LATICAUDA COLUBRINA)}, volume={39}, ISSN={["1937-2825"]}, DOI={10.1638/2008-0018.1}, abstractNote={Abstract This case series describes multiple mortalities associated with sepsis, neoplasia, and endoparasitism in yellow-lipped sea kraits (Laticauda colubrina) at an exhibit aquarium. Over a 2-yr period, the facility kept 42 L. colubrina, of which 38 died and 19 were suitable for necropsy and histopathology. The common clinical syndrome seen in these animals consisted of partial to compete anorexia, increased time spent “hauled-out” on land, intermittent regurgitation, chronic lethargy, and weight loss. Few animals died without premonitory signs. Nutritional support and treatment for presumptive parasitism and sepsis were unsuccessful. The mortality seen in this collection of sea kraits could be placed into three groups; one group of animals (n = 9) died of sepsis secondary to necrotizing enteritis or pneumonia; one group (n = 6) remained apparently healthy for over 1 yr and then died with multifocal granulomas and sepsis; and the last group (n = 3) died as a result of multicentric lymphoid neoplasia with secondary sepsis. The unifying factor in the majority of these cases is the presence of septicemia as the proximate cause of death. Based on the clinical picture, it is presumed that an immunosuppressive event, such as transport, captivity stress, or possible concurrent viral infection, resulted in a septic event and death.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Chinnadurai, Sathya K. and Brown, Danielle L. and Van Wettere, Arnaud and Tuttle, Allison D. and Fatzinger, Michael H. and Linder, Keith E. and Harms, Craig A.}, year={2008}, month={Dec}, pages={626–630} } @article{ranck_linder_haber_meuten_2008, title={Primary intimal aortic angiosarcoma in a dog}, volume={45}, ISSN={["0300-9858"]}, DOI={10.1354/vp.45-3-361}, abstractNote={ A primary intimal aortic angiosarcoma was diagnosed in a 4-year-old, spayed female German Shepherd that presented for complications of thromboembolic disease because of infarcts in multiple organs. On gross examination, aneurysmal dilatation of the aorta was associated with a friable, necrotic mass attached to the endothelial surface, which partially occluded the aortic lumen. On histologic examination, plump neoplastic spindle cells formed a plaque-like mass arising from the intima that merged with a large accumulation of fibrin and necrotic debris, and projected into the lumen. Neoplastic cells invaded periaortic vessels and were seen in some infarct-associated thromboemboli. Tumor cells expressed vimentin and CD31, with infrequent, patchy staining with factor VIII-related antigen; tumor cells were negative for cytokeratin and smooth-muscle actin. Aortic angiosarcoma is a rare malignancy in humans. This is the first description of a primary intimal aortic angiosarcoma in a dog, with immunohistochemical evidence of endothelial origin. }, number={3}, journal={VETERINARY PATHOLOGY}, author={Ranck, R. S. and Linder, K. E. and Haber, M. D. and Meuten, D. J.}, year={2008}, month={May}, pages={361–364} } @article{chinnadurai_van wettere_linder_harms_devoe_2008, title={Secondary amyloidosis and renal failure in a captive California sea lion (Zalophus californianus)}, volume={39}, ISSN={["1937-2825"]}, DOI={10.1638/2007-0096R.1}, abstractNote={Abstract A 16-yr-old, captive-born, female California sea lion (Zalophus californianus) was evaluated for intermittent lethargy, partial anorexia, and polydipsia of 2 wk duration. The animal was immobilized for physical examination. It was in thin body condition, with multifocal mucosal ulcerations over the caudal and ventral tongue. Blood was collected for hematology, serum chemistry, and leptospirosis serology. Serum chemistry revealed severe azotemia, mild hyperglycemia, and severe hyperphosphatemia. The animal went into cardiac arrest during recovery from anesthesia and died. On histopathology, abundant amorphous, finely fibrillar, eosinophilic material was deposited in the kidneys, and smaller amounts of the same material were found in the splenic and pancreatic vessels; these findings are consistent with systemic secondary amyloidosis. The animal also had chronic nephritis, which, coupled with renal amyloidosis, resulted in renal failure and death. Systemic amyloidosis should be considered as an additional differential diagnosis for renal failure in California sea lions.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Chinnadurai, Sathya K. and Van Wettere, Arnaud and Linder, Keith E. and Harms, Craig A. and DeVoe, Ryan S.}, year={2008}, month={Jun}, pages={274–278} } @article{mackillop_thrall_ranck_linder_munana_2007, title={Imaging diagnosis-synchronous primary brain tumors in a dog}, volume={48}, ISSN={["1058-8183"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35448932842&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2007.00294.x}, abstractNote={Four-year-old, neutered male, Bassett Hound. The dog was referred for progressive neurologic dysfunction of approximately 1 month. He would occasionally circle to the right and had developed behavior changes. Two weeks before evaluation the dog began drifting to the left when ambulating and would fall over after shaking his head. Signs of vestibular disequilibrium progressed to falling and rolling to the left. There was mild dehydration (<5%), markedly depressed mentation, and moderate vestibular ataxia with a tendency to stumble to the left. When supported, the dog would circle aimlessly to the right. Menace response was absent in the left eye. Vertical and occasional beats of horizontal nystagmus with a fast-phase to the right were noted in both eyes upon neck extension. Postural reactions were decreased in the left thoracic and pelvic limbs and dysmetric in the right thoracic and pelvic limbs. Neuroanantomic localization was multifocal: right forebrain and caudal fossa. A solitary caudal fossa mass with secondary obstructive hydrocephalus was also considered. Vestibular signs were thought to be consistent with a right-sided paradoxical central vestibular lesion although multifocal cerebellovestibular disease could not be excluded. The differential diagnosis included meningoencephalitis, neoplasia, brain abscess or congenital anomaly. Magnetic resonance (MR) imaging of the brain was performed using a 1.5 T magnet. Two anatomically distant brain masses with disparate features were identified (1, 3). T2-weighted transverse spin echo magnetic resonance image (4000/91) of a cerebellar primitive neuroectodermal tumor. The tumor is mildly T2 hyperintense with a large cystic region in the right dorsolateral aspect. That the hyperintense region is cystic is based on its hypointense appearance in fluid-attenuated inversion recovery images (not shown). T2-weighted transverse spin echo magnetic resonance image (4000/91) of the pilocytic astrocytoma in the right thalamus. Note the ill-defined mass effect, moderate T2-intensity, and peritumoral edema tracking along cerebral white matter (arrow). The first was an approximately 1.5–2.0 cm, mildly T2-hyperintense, ill defined, partially cystic, mass in the right cerebellar hemisphere that was causing mild compression of the brainstem (Fig. 1). In a T2*-weighted gradient echo sequence there were multiple susceptibility artifacts consistent with intralesional hemorrhage (Fig. 2). There was faint, wispy contrast enhancement of this mass. The mass caused overcrowding of the caudal fossa, and faint T2-hyperintensity was present in the cervical spinal cord at the C2 level, consistent with syringohydromyelia. T2*-weighted transverse gradient echo magnetic resonance image (875/26/20°), of the cerebellar primitive neuroectodermal tumor. This image was acquired 5 mm rostral to the image in Fig. 1. There are multiple signal voids (arrow head) representing susceptibility artifact from intratumoral hemorrhage. There was a second similarly sized mass located in the right, ventral aspect of the thalamus at the level of the sella turcica with extension into the right frontal lobe. The imaging characteristics of this mass were different from the cerebellar mass as it had greater T2 intensity, marked adjacent T2 hyperintensity consistent with vasogenic edema, and no evidence of intralesional hemorrahge (Fig. 3). Following contrast medium administration there was faint enhancement of the forebrain mass itself, as well as wispy peripheral enhancement suggestive of peripheral neovascularization. The different imaging characteristics of these masses suggested disparate etiologies. The characteristics of the cerebellar mass suggested it might be associated with a vascular event with resultant necrosis and hemorrhage while the features of the forebrain mass were more consistent with a glial tumor. However, the imaging features were not specific and other etiologies for these lesions included metastatic neoplasia, inflammatory disease or multifocal primary brain tumors. Following MR imaging mannitol was administered intravenously and CSF was collected from the cerebellomedullary cistern. CSF analysis was within the normal reference range. Progressive neurological signs prompted a CT-guided brain biopsy. In CT images, the forebrain mass did not contrast enhance and there was a subtle hypoattenuating focus within the mass, consistent with edema. The cerebellar mass was hyperattenuating relative to adjacent neuropil and contained a central hypoattenuating focus consistent with cystic fluid, necrosis, or chronic hemorrhage. Samples of the forebrain mass were obtained with a core biopsy needle using CT guidance and submitted for stat frozen section histologic assessment. Despite sampling from the apparent epicenter of the mass, the biopsy was interpreted as mild gliosis without evidence of inflammation or neoplasia. The dog failed to adequately ventilate following anesthesia and was euthanized based on the poor prognosis for recovery. The right cerebral hemisphere was swollen with moderate subdural hemorrhage. The caudal aspect of the cerebellum was herniated into the fourth ventricle and compressed the associated segment of brain stem, which had moderate patchy hemorrhage. There was no evidence of transtentorial brain herniation. Following transverse sectioning of the brain, a poorly defined, slightly expansile pale mass, with fine stippling was centered in the right thalamus. There was a more discrete, spheroid mass in the cerebellum that was mottled dark brown-red and effaced approximately 70% of the right hemisphere. Microscopically, the forebrain mass was composed of elongated fascicles of slender spindle cells with a fibrillary cytoplasm and thin oval nuclei (Fig. 4A). This mass had diffuse, strong immunoreactivity for glial fibrillary acidic protein (GFAP) and mild to moderate regional immunoreactivity for vimentin but staining was negative for cytokeratin, neuron-specific enolase (NSE), neurofilament, and synaptophysin. The histological diagnosis was astrocytoma with pilocytic features. Photomicrographs of two primary brain tumors in a dog. (A) Thalamus, astrocytoma with pilocytic features composed of discrete fascicles of long slender spindle cells with hyperchromatic elongated nuclei and pale abundant fibrillary cytoplasm. (B) Cerebellum, primitive neuroectodermal tumor, consistent with medullobastoma, formed by sheets of densely packed round to angular small cells with scant cytoplasm and round nuclei. Hematoxylin and eosin, 200 × . The cerebellar mass was distinctly different from the forebrain mass, being composed of dense sheets of small, round to angular cells, with hyperchromatic round nuclei (Fig. 4B). Scattered tumor cells had increased amounts of eosinophilic cytoplasm. Occasionally small cells arranged in rosette-like aggregates. Pyknotic debris was scattered throughout the mass, and there were multiple foci of hemorrhage. Small patchy areas of neoplastic cells exhibited mild immunoreactivity for vimentin but cells lacked specific staining for cytokeratin, GFAP, NSE, neurofilament, synaptophysin, CD3 or CD79a. Individual cells distributed throughout the mass stained for GFAP and were consistent with reactive astrocytes. Morphology supported a primitive neuroectodermal tumor (PNET) in the cerebellum, consistent with a medulloblastoma. We conclude that our patient developed two independent synchronous brain tumors. Multifocal brain lesions may occur from inflammatory, neoplastic, vascular, metabolic, or degenerative etiologies. Cerebrospinal fluid analysis is often used to distinguish inflammatory disease from tumors, although some tumors may be associated with pleocytosis. A multifocal distribution of intracranial masses is suggestive of metastatic neoplasia; however, multiple primary brain tumors or a combination of primary and secondary brain tumors should be considered when brain masses have disparate MR imaging characteristics, as seen here. Multiple intracranial tumors are found in humans with brain metastasis but may also be found with certain heritable neurocutaneous syndromes (syn. phakomatoses) such as neurofibromatosis types 1 and 2 (NF1 and NF2).1,2 For example, people with NF1 are prone to optic nerve gliomas and/or juvenile pilocytic astrocytomas whereas NF2 is associated with either bilateral vestibulocochlear nerve (acoustic) schwannomas or an acoustic schwannoma and another primary brain tumor.2 In one study in dogs, 39/170 (23%) of dogs with a primary brain tumor had at least one other unrelated tumor.3 Interestingly, six of 170 (3.5%) had a second unrelated intracranial neoplasm. In most of these animals (4/6) the second tumor was a pituitary adenoma, although one dog had a meningioma and an astrocytoma. In contrast, multiple menginiomas may be found in as many as 17% of cats with meningioma.4 We found two reports of multiple histologically distinct brain tumors in dogs; one dog had an oligodendroglioma and a meningioma while the other had an oligodendroglioma and metastatic mammary carcinoma.1,5 Both patients were Boxer dogs, a breed predisposed to glioma.1 Multiple histologically distinct brain tumors are a rare occurrence in people without phakomatosis or exposure to ionizing radiation.6,7 Anatomically distant brain tumors, such as in our dog, may reflect coincidental tumorigenesis; alternatively, a genetic abnormality or exposure to a carcinogen may predispose to multifocal neoplasia. It has been speculated that adjacent or collision tumors may result from neoplastic transformation of peritumoral tissue because of chronic inflammation.6 In many instances of multifocal primary intracranial neoplasia, the second tumor is an incidental finding. Therapy is initially directed at the symptomatic tumor unless both tumors can be removed through the same surgical approach.7 Primary brain tumors usually occur in older dogs.8 There are, however, a number of reports of astrocytomas in young dogs such as this animal and gliomas are one of the most common malignancies in children.9 On MR imaging, canine astrocytomas are usually ill-defined intraparenchymal space-occupying masses that are hyperintense on T2-weighted images and hypointense on T1-weighted images.10 Astrocytomas may be associated with mild to marked peritumoral edema and as in this dog extensive peritumoral edema may obscure tumor boundaries. Astrocytomas have variable enhancement patterns but are often heterogenous.10 In our dog, faint contrast enhancement and extensive peritumoral edema made biopsy of the mass difficult and samples were mostly composed of rarefied neuropil with reactive gliosis. Primitive neuroectodermal tumors are rare and thought to arise from neoplastic transformation of embryonal neuroectoderm. The World Health Organization (WHO) for classification of nervous system tumors in domestic animals defines PNET as a generic term for brain tumors that are histologically indistinguishable from medulloblastoma—which is the common term used for this tumor type in the cerebellum.11 MR imaging and CT characteristics of the cerebellar tumor in this dog support the diagnosis of medulloblastoma. PNETs are primarily found in adult dogs (range 3–10 years old) but there are reports of medulloblastoma in dogs ≤2 years of age.12 In our dog, lack of association with the ventricular system argues against another primitive neoplasm, such as an anaplastic ependymal tumor. Medulloblastoma and pilocytic astrocytoma are the two most common brain tumors in children and the simultaneous occurrence of both tumors in this relatively young dog is extremely unusual.2,13 Medulloblastoma is a malignant embryonal tumor that is thought to be derived from either the external germinal layer of the cerebellum or subependymal matrix cells.14 On MR imaging, human medulloblastomas are predominantly isointense to grey matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences and hypointense or isointense to grey matter on T1-weighted sequences. Though in our dog the cerebellar tumor was not T2-isointense to brain, its T2-intensity was lower than the forebrain astrocytoma. In people, it is not uncommon for there to be regions of heterogeneity in medulloblastomas because of tumor hemorrhage, necrosis, or cavitation.2,15 Contrast enhancement is usually mild to moderate. One reported canine medulloblastoma had similar MR imaging characteristics to the cerebellar tumor in our dog.12 Complete neuraxial MR imaging has been recommended in the presurgical evaluation of people with suspected medulloblastoma because intrathecal or drop metastasis may be found in approximately 40% of patients.15 Diffusion-weighted imaging (DWI) is used in people to help distinguish PNETs from other brain tumors. DWI has historically been used in the diagnosis of stroke because of its capacity to identify the restricted movement of water protons, a characteristic feature of acute stroke. Of 12 human PNETs, including nine medulloblastomas, tumors were characterized as having restricted water diffusion.15 Medulloblastomas are densely cellular and have a high nuclear:cytoplasmic ratio which may restrict the motion of both extra- and intracellular water protons.15 These same tumor characteristics are thought to be the reason that medulloblastomas are hyperattenuating on CT images and predominantly isointense on T2-weighted and FLAIR sequences.2 In our dog, the combination of a densely cellular neoplasm along with intratumoral hemorrhage may explain the hyperattenuation on CT images. Although uncommon, multiple histologically distinct intracranial tumors should be considered in dogs that have multifocal brain masses with disparate MR imaging characteristics. A heterogeneous, slightly T2 hyperintense cerebellar mass lesion should raise the index of suspicion for a medulloblastoma. The authors would like to thank Drs. Talmage Brown, Brian Summers, Tom Van Winkle, Jim Cooley, and Jon Patterson for their histopathologic review of tissue from this dog.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={MacKillop, Edward and Thrall, Donald E. and Ranck, Rose S. and Linder, Keith E. and Munana, Karen R.}, year={2007}, pages={550–553} } @article{mackillop_olby_linder_brown_2007, title={Intramedullary cavernous malformation of the spinal cord in two dogs}, volume={44}, ISSN={["1544-2217"]}, DOI={10.1354/vp.44-4-528}, abstractNote={ Intramedullary cavernous malformations (CVMs) of the spinal cord were diagnosed in 2 adult dogs that presented for paraparesis. An intramedullary spinal cord lesion was identified on a myelogram in the first dog, and expansion of the vertebral canal was evident on radiographs in the second. Extensive intraparenchymal hemorrhage was found on gross postmortem examination in both dogs, and a distinct lobulated intramedullary mass was evident in the second dog. Microscopically, both lesions were composed of dilated, thin-walled vascular channels with little-to-no intervening neural parenchyma. Both dogs had evidence of channel thrombosis along with perilesional hemorrhage and hemosiderin accumulation. The second dog had additional degenerative changes, including thickened fibrous channel walls with hyalinization, foci of mineralization, and occasional tongues of entrapped gliotic neuropil. CVMs appear to be an uncommon cause of both acute and chronic spinal cord disease in the dog. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Mackillop, E. and Olby, N. J. and Linder, K. E. and Brown, T. T.}, year={2007}, month={Jul}, pages={528–532} } @article{snyder_linder_neel_2007, title={Malignant peripheral nerve sheath tumor in a hamster}, volume={46}, number={6}, journal={Journal of the American Association for Laboratory Animal Science}, author={Snyder, L. A. and Linder, K. E. and Neel, J. A.}, year={2007}, pages={55–57} } @article{tuttle_frederico_linder_gunkel_remick_redding_2007, title={Pathological fracture of the ulna due to osteosarcoma in an Arabian camel (Camelus dromedarius)}, volume={161}, ISSN={["0042-4900"]}, DOI={10.1136/vr.161.1.30}, abstractNote={OSTEOSARCOMA, a malignant mesenchymal neoplasia originating within bone, occurs only rarely in large animal species (Cotchin 1960, 1977, Pascoe and Summers 1981, Pool 1998). The long bones are the primary site for osteosarcoma in small animals, while in large animals the common sites are generally the skull and mandible (Thorpe and Graham 1934, Pospischil and others 1982, Livesey and Wilkie 1986, Steinberg and George 1989, Plumlee and others 1993, Pool 1998, Perez-Martinez and others 1999), although osteosarcomas have been reported to affect the pelvis, vertebrae, ribs and, rarely, the appendicular skeleton in domestic ruminants and equine species (Heimann 1975, Rosenberger 1975, Livesey and Wilkie 1986, Zaruby and others 1993, Wan and others 1994, Nelson and Baker 1998, Jenner and others 2003). This short communication describes a case of pathological fracture secondary to osteosarcoma in an Arabian camel (Camelus dromedarius). A seven-year-old intact female Arabian camel was presented to the North Carolina State University’s College of Veterinary Medicine Veterinary Teaching Hospital for evaluation of a left forelimb lameness of three days’ duration. The camel was found at pasture with an acute, non-weight-bearing lameness on the left forelimb, which was swollen in the radiohumeral region. Treatment with butorphanol (0·06 mg/kg orally every 24 hours), diazepam (0·02 mg/kg orally every 24 hours), and a single oral dose of 1·1 mg/kg flunixin meglumine had been administered by the referring veterinarian. The camel had calved eight months previously, and had given birth to one other calf before that, but had no other significant medical history. Upon arrival, the camel was quiet and dull, with a normal rectal temperature (37·7°C, reference range 36·4 to 42°C), tachycardia (88 bpm, reference range 40 to 50 bpm) and tachypnoea (28 breaths/minute, reference range 5 to 12 breaths/minute). Auscultation of the heart and lungs revealed no audible abnormalities. The faeces were soft, and adequate borborygmi were audible in all four abdominal quadrants. The body condition score was 4/9. Severe lameness (grade 4/5) was apparent in the left forelimb, with moderate swelling around the left elbow. Radiographs of the left radiohumeral joint revealed a cranially displaced oblique articular fracture involving the proximal ulna. The fracture line extended from the trochlear notch to the caudal surface of the ulna distal to the olecranon. Slight radiolucencies were noted in the bone at the cranial edge of the fracture (Figs 1, 2). Cranial displacement of the distal radius and ulna had resulted in subluxation of the radiohumeral joint. A complete blood count revealed mild anaemia (packed-cell volume 21 per cent, reference range 24 to 42 per cent) and a regenerative neutrophilia (white blood cell count 19·8 x 103 cells/μl [reference range 2·9 x 103 to 9·7 x 103 cells/μl]; absolute numbers of bands 0·2 x 103 cells/μl [the presence of any bands is considered abnormal]). A serum chemistry panel revealed mildly elevated levels of globulin (46 g/l, reference range 28 to 44 g/l) and gamma glutyltransferase (39·0 iu/l, reference range 0 to 20 iu/l), Veterinary Record (2007) 161, 30-33}, number={1}, journal={VETERINARY RECORD}, author={Tuttle, A. D. and Frederico, L. and Linder, K. and Gunkel, C. and Remick, A. and Redding, R.}, year={2007}, month={Jul}, pages={30–33} } @article{cannon_linder_brizuela_harvey_2006, title={Marked swelling with coalescing ecchymoses of the lower mandible in a Xenopus laevis frog}, volume={35}, ISSN={["1548-4475"]}, DOI={10.1038/laban0506-19}, number={5}, journal={LAB ANIMAL}, author={Cannon, Coralie Zegre and Linder, Keith and Brizuela, Brenda J. and Harvey, Stephen B.}, year={2006}, month={May}, pages={19–22} } @article{tarigo_linder_neel_harvey_remick_grindem_2006, title={What is your diagnosis? Reluctant to dive: coelomic effusion in a frog}, volume={35}, ISSN={["0275-6382"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33750693063&partnerID=MN8TOARS}, DOI={10.1111/j.1939-165X.2006.tb00145.x}, abstractNote={Abstract An adult female, albino South African Clawed frog (Xenopus laevis) from a research colony at the Biological Resources Facility of the College of Agriculture and Life Sciences at North Carolina State University (NCSU) was presented with depression, lethargy, loss of diving reflex, and a distended abdomen. Cytologic examination of coelomic effusion fluid at the NCSU veterinary teaching hospital revealed a mixed population of inflammatory cells, including heterophils and a predominance of large mononuclear cells (macrophages) that often contained intracytoplasmic, negatively‐stained, rod‐shaped to filamentous organisms consistent with Mycobacterium sp. Ziehl‐Neelsen stain revealed bright pink to red, acid‐fast organisms with a beaded appearance. Histopathologic findings in tissues obtained at necropsy included marked, multifocal to coalescing, heterophilic, granulomatous and fibrinous coelomitis as well as severe multifocal heterophilic and granulomatous hepatitis, interstitial pneumonia and sinusitis/rhinitis. Slender gram‐positive, acid‐fast bacterial rods were identified in sections of coelomic pleura, kidneys, nasal cavities, spleen, liver, and pulmonary interstitium, indicative of systemic mycobacteriosis. Based on mycobacterial culture, the organism was identified as M marinum complex. Mycobacteria are variably gram‐positive, often acid‐fast, small rods that are ubiquitous in aquatic environments. The clinical and pathologic spectrum of disease in amphibians depends on host and pathogen status. Xenopus sp and several other frogs are good models for studying the pathogenesis of M tuberculosis infection. In addition to culture, polymerase chain reaction assays may be used for definitive identification of the organisms; accurate speciation may require further genetic investigation.}, number={3}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Tarigo, Jaime and Linder, Keith and Neel, Jennifer and Harvey, Stephen and Remick, Amera and Grindem, Carol}, year={2006}, month={Sep}, pages={341–344} } @article{govett_harms_linder_marsh_wyneken_2004, title={Effect of four different suture materials on the surgical wound healing of loggerhead sea turtles, Caretta caretta}, volume={14}, ISBN={1529-9651}, DOI={10.5818/1529-9651.14.4.6}, abstractNote={ABSTRACT The tissue reaction to four suture materials placed in the skin of juvenile loggerhead sea turtles, Caretta caretta, was evaluated both grossly and histologically. Chromic gut, polyglyconate, polyglactin 910, and poliglecaprone 25 were used in 258 turtles to close a wound produced at the time of laparoscopic sex determination. Gross tissue reactions were graded in 68 turtles at one week, and in the remaining 190 turtles at two weeks following surgery. Gross observations (eversion formation, holding of sutures, epibiont [organisms growing on suture site] present and crusts) were graded from one to three with one being mild and three being most severe. Gross observation scores did not differ among suture types. Crust scores were significantly greater for chromic gut and for polyglactin than for poliglecaprone 25 and polyglyconate. At the suture site, 32% of the turtles had an eversion in the incision ranging in size from 0.25 to 10 mm2 [mean 2.02 (+/− 1.95) mm2]. Eversion size did not vary signific...}, number={4}, journal={Journal of Herpetological Medicine and Surgery}, author={Govett, P. D. and Harms, Craig and Linder, K. E. and Marsh, J. C. and Wyneken, J.}, year={2004}, pages={6} } @article{mozzachio_linder_dixon_2004, title={Uterine smooth muscle tumors in potbellied pigs (Sus scrofa) resemble human fibroids: A potential animal model}, volume={32}, ISSN={["1533-1601"]}, DOI={10.1080/01926230490440880}, abstractNote={ Uterine leiomyomas, commonly termed fibroids, clinically affect approximately 25% of women of reproductive age in the United States, with a subclinical incidence as high as 77%. The pathogenesis of fibroid formation remains poorly understood, due in large part to the lack of a suitable animal model. This retrospective study characterizes the clinical, gross, and histopathologic features of similar, spontaneously occurring uterine tumors in potbellied pigs. Medical records available through a local Potbellied Pig Spay/Neuter Program, pig sanctuaries, and the Duchess Fund database were reviewed for evidence of reproductive disease or surgery. One-hundred and six female potbellied pigs were evaluated and uterine neoplasia was identified in 17 animals; tissues were available for 13 of these. Uterine leiomyoma was diagnosed in 11 of 13 cases, leiomyosarcoma in 1 of 13 cases, and undifferentiated sarcoma in 1 case. Pigs presented with clinical signs including abdominal distension or vaginal bleeding or were subclinical and identified during ovariohysterectomy. Tumors ranged from microscopic to 45 kg, were often multiple, and primarily involved the uterine horns. Hematoxylin and eosin and trichrome-stained sections were evaluated for morphological features of human and animal leiomyomas; immunohistochemistry to detect smooth muscle actin was also performed. The cellular pattern/morphology and variable degree of fibroplasia of the leiomyomas were similar to that reported for human fibroids. These results support further investigation of uterine leiomyomas in potbellied pigs as a potentially valuable animal model for studying human fibroids. }, number={4}, journal={TOXICOLOGIC PATHOLOGY}, author={Mozzachio, K and Linder, K and Dixon, D}, year={2004}, pages={402–407} } @inbook{linder_2003, place={Boston, MA}, title={The skin xenograft mouse model in veterinary dermatology research modeling canine demodicosis}, volume={4}, booktitle={Advances in Veterinary Dermatology}, publisher={Blackwell Science}, author={Linder, K.}, editor={Thoday, K and Foil, C and Bond, R and Linder, K and Parker, W and Kunkle, G and Yager, JEditors}, year={2003} } @article{spirito_charlesworth_ortonne_meneguzzi_linder_baird_2002, title={Animal Models for Skin Blistering Conditions: Absence of Laminin 5 Causes Hereditary Junctional Mechanobullous Disease in the Belgian Horse}, volume={119}, ISSN={0022-202X}, url={http://dx.doi.org/10.1046/j.1523-1747.2002.01852.x}, DOI={10.1046/j.1523-1747.2002.01852.x}, abstractNote={Recent achievements in the genetic correction of keratinocytes isolated from patients with junctional epidermolysis bullosa have paved the way to a gene therapy approach for the disease. Because gene therapy protocols require preclinical validation in animals, we have characterized spontaneous animal models of junctional epidermolysis bullosa. In this study we have elucidated the genetic basis of the hereditary junctional mechanobullous disease in the Belgian horse, a condition characterized by blistering of the skin and mouth epithelia, and exungulation (loss of the hoof). Immunofluorescence analysis associated the condition to the absent expression of the gamma2 chain of laminin 5 and designated Lamc2 as the candidate gene. Comparative analysis of the nucleotide sequence of the full-length gamma2 cDNA isolated by reverse transcription polymerase chain reaction amplification of total RNA purified from the epithelium of a junctional epidermolysis bullosa foal and a healthy control disclosed a homozygous basepair insertion (1368insC) in the affected animal. Mutation 1368insC results in a downstream premature termination codon and is predicted to cause absent expression of the laminin gamma2 polypeptide. Our results also show that: (i) the horse junctional epidermolysis bullosa genetically corresponds to the severe Herlitz form of junctional epidermolysis bullosa in man; (ii) the amino acid sequence and structure of the horse laminin gamma2 chain are virtually identical to the human counterpart; (iii) the moderate eruption of skin blisters in the affected animals with respect to the human Herlitz junctional epidermolysis bullosa patients correlates with the protection provided by hair. Our observations suggest that the affected foals are a convenient source of epithelial cells from tissues that cannot be obtained from human junctional epidermolysis bullosa patients, and imply that hairless strains of animals with recessive skin disorders would be the best models for in vivo gene therapy approaches to skin blistering diseases.}, number={3}, journal={Journal of Investigative Dermatology}, publisher={Elsevier BV}, author={Spirito, Flavia and Charlesworth, Alexandra and Ortonne, Jean-Paul and Meneguzzi, Guerrino and Linder, Keith and Baird, John}, year={2002}, month={Sep}, pages={684–691} } @article{croy_linder_yager_2001, title={Primer for non-immunologists on immune-deficient mice and their applications in research}, volume={45}, number={4}, journal={Comparative Medicine}, author={Croy, B. and Linder, K. and Yager, J.}, year={2001}, pages={300–313} } @article{linder_2001, title={Skin biopsy site selection in small animal dermatology with an introduction to histologic pattern-analysis of inflammatory skin lesions}, volume={16}, ISSN={["1096-2867"]}, DOI={10.1053/svms.2001.27595}, abstractNote={The skin biopsy is an invaluable diagnostic tool in veterinary dermatology. Biopsy site selection and interpretation of the biopsy report significantly influence the value of this procedure for diagnosing inflammatory skin diseases and are discussed in this article. Skin diseases often present with several different recognizable lesions that change significantly during their evolution. Individual lesions are typically heterogenous--some areas are diagnostic and some are not. Understanding which skin lesions to biopsy, and when and where to sample them, can significantly improve the value of information collected. To increase the information returned to clinicians for a biopsy, veterinary dermatopathologists have adopted the pattern-analysis method of classifying inflammatory skin lesions. This approach is based on recognizing morphologically distinct inflammatory patterns in skin biopsies and their association with particular sets of diseases. A basic knowledge of the pattern-analysis method is essential for maximizing the interpretation of skin biopsy reports.}, number={4}, journal={CLINICAL TECHNIQUES IN SMALL ANIMAL PRACTICE}, author={Linder, KE}, year={2001}, month={Nov}, pages={207–213} } @article{bröjer_parsons_linder_peregrine_dobson_2000, title={Halicephalobus gingivalis encephalomyelitis in a horse}, volume={41}, number={7}, journal={Canadian Veterinary Journal}, author={Bröjer, J and Parsons, D and Linder, K and Peregrine, A and Dobson, H}, year={2000}, month={Jul}, pages={559–561} } @article{white_linder_schultheiss_scott_garnett_taylor_best_walder_rosenkrantz_yaeger_2000, title={Sebaceous adenitis in four domestic rabbits (Oryctatagus cuniculus)}, volume={11}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1046/j.1365-3164.2000.00144.x}, DOI={10.1046/j.1365-3164.2000.00144.x}, abstractNote={Four domestic rabbits were presented with a history of nonpruritic scale. Multiple skin biopsies revealed findings compatible with sebaceous adenitis as reported in other species: inflammation directed at the sebaceous gland, and/or an absence of sebaceous glands, a perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, hyperkeratosis, follicular keratosis, follicular dystrophy, perifollicular fibrosis, and a mural infiltrative lymphocytic folliculitis. Histological changes not consistent with sebaceous adenitis in other species were interface dermatitis and interface folliculitis with single cell necrosis and basal cell hydropic degeneration.}, number={1}, journal={Veterinary Dermatology}, publisher={Wiley}, author={White, Stephen D. and Linder, Keith E. and Schultheiss, Patricia and Scott, Kathryn V. and Garnett, Page and Taylor and Best and Walder, Emily J. and Rosenkrantz, Wayne and Yaeger, Julie A.}, year={2000}, month={Mar}, pages={53–60} } @article{bowker_van wulfen_springer_linder_1998, title={Functional anatomy of the cartilage of the distal phalanx and digital cushion in the equine foot and a hemodynamic flow hypothesis of energy dissipation}, volume={59}, number={8}, journal={American Journal of Veterinary Research}, author={Bowker, R. and Van Wulfen, K. and Springer, S. and Linder, K.}, year={1998}, month={Aug}, pages={961–968} } @article{anderson_linder_peregrine_1998, title={Halicephalobus gingivalis (Stefanski, 1954) from a fatal infection in a horse in Ontario, Canada with comments on the validity of H. deletrix and a review of the genus}, volume={5}, ISSN={1252-607X 1776-1042}, url={http://dx.doi.org/10.1051/parasite/1998053255}, DOI={10.1051/parasite/1998053255}, abstractNote={Although the original description given by Stefanski (1954) was satisfactory, Anderson & Bemrick (1965), in describing H. deletrix (= Micronema deletrix), claimed Stefanski's description was "inadequate" and the species a "species inquirenda". Thus, infections in horses and humans have been assigned to H. deletrix. We believe the species reported in horses and humans is H. gingivalis and that H. deletrix is its synonym. H. gingivalis is separated herein from forms found free-living. The genital tract in the advanced fourth stage of H. gingivalis is didelphic and amphidelphic and terminal ends of the horns are reflected, the anterior one ventrally, the posterior one dorsally. In the adult parthenogen the latter forms a short ovary, whereas most of the anterior horn forms a combined uterus-oviduct as a receptacle for a single large egg which is laid in the 2-cell or multi-cell stage. Eggs in the 2-cell stage embryonated to larvae in 17 hours at 28 degrees C but did not hatch until an additional 24 hours. First-stage larvae were unusually large and variable in length (136-199 microns x = 168). Inactive third-stage larvae were 180-240 microns (x = 203) in length. The possible route of infection in horses and humans is briefly discussed.}, number={3}, journal={Parasite}, publisher={EDP Sciences}, author={Anderson, R. and Linder, K. and Peregrine, A.}, year={1998}, month={Sep}, pages={255–261} } @article{bowker_linder_wulfen_sonea_1997, title={Anatomy of the distal interphalangeal joint of the mature horse: relationships with navicular suspensory ligaments, sensory nerves and neurovascular bundle}, volume={29}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/j.2042-3306.1997.tb01654.x}, DOI={10.1111/j.2042-3306.1997.tb01654.x}, abstractNote={Summary}, number={2}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Bowker, R. M. and Linder, K. and Wulfen, Kimberly K. and Sonea, Ioana M.}, year={1997}, month={Mar}, pages={126–135} } @article{bowker_linder_van wulfen_perry_ocello_1996, title={Verteilung eines in das Hufgelenk und in die Bursa podotrochlearis injizierten Lokalanästhetikums: eine experimentelle Studie = Distributions of local anesthetics injected into the distal interphalangeal joint and podotrochlear bursa: an experimental study}, volume={12}, DOI={10.21836/PEM19960454}, number={4}, journal={Pferdeheilkunde}, author={Bowker, R. and Linder, K. and van Wulfen, K. and Perry, R. and Ocello, P.}, year={1996}, pages={609–612} } @article{dunstan_linder_1995, title={Mammals, other than man, do not have follicular bulges: implications for the bulge-activation hypothesis}, volume={1}, ISSN={1078-4454}, journal={Dermatopathology, practical & conceptual : dermatology, pathology}, author={Dunstan, R and Linder, K}, year={1995}, pages={155–162} } @article{bowker_under_sonea_holland_1995, title={Sensory innervation of the navicular bone and bursa in the foal}, volume={27}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/j.2042-3306.1995.tb03034.x}, DOI={10.1111/j.2042-3306.1995.tb03034.x}, abstractNote={Summary}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Bowker, R. M. and Under, K. and Sonea, I. M. and Holland, R. E.}, year={1995}, month={Jan}, pages={60–65} } @article{bowker_rockershouser_linder_vex_sonea_caron_1994, title={A silver-impregnation and immunocytochemical study of innervation of the distal sesamoid bone and its suspensory ligaments in the horse}, volume={26}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/j.2042-3306.1994.tb04372.x}, DOI={10.1111/j.2042-3306.1994.tb04372.x}, abstractNote={Summary}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Bowker, R. M. and Rockershouser, Sara J. and Linder, K. and Vex, Kelly B. and Sonea, Ioana M. and Caron, J. P.}, year={1994}, month={May}, pages={212–219} } @article{bowker_brewer_vex_guida_linder_sonea_stinson_1993, title={Sensory receptors in the equine foot}, volume={54}, number={11}, journal={American Journal of Veterinary Research}, author={Bowker, R. and Brewer, A. and Vex, K. and Guida, L. and Linder, K. and Sonea, I. and Stinson, A.}, year={1993}, pages={1840–1844} } @inbook{carey_laurikainen_ptok_reinke_linder_nair_marcelo_1992, title={Culture Conditions Affect Expression of the α6β4 Integrin Associated with Aggressive Behavior in Head and Neck Cancer}, ISBN={9781461365365 9781461534686}, ISSN={0065-2598}, url={http://dx.doi.org/10.1007/978-1-4615-3468-6_10}, DOI={10.1007/978-1-4615-3468-6_10}, abstractNote={Prevention of disease has always been more effective than treatment. Sanitation practices and vaccines have eliminated many of the most dreaded and lethal diseases of man and domestic animals. Cancer, a devastating disease caused by unregulated growth of genetically altered cells, is as daunting a challenge today as smallpox was in Edward Jenner’s time two centuries ago. Fortunately, we are on the threshold of a new era in biology. We can now examine growth-regulatory mechanisms at the cellular and molecular levels, and we can begin to apply what we learn in new clinical and experimental systems.}, booktitle={Advances in Experimental Medicine and Biology}, publisher={Springer US}, author={Carey, Thomas E. and Laurikainen, Leena and Ptok, Angelika and Reinke, Timothy and Linder, Keith and Nair, Thankam S. and Marcelo, Cynthia}, year={1992}, pages={69–79} }