@article{schreeg_evans_allen_lewis_luckring_evola_richard_piner_thompson_adin_et al._2019, title={Cardiac Leiomyosarcoma in a Cat Presenting for Bilateral Renal Neoplasia}, volume={168}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2019.02.005}, abstractNote={A 10-year-old neutered female domestic longhair cat was presented to a tertiary care veterinary hospital for evaluation of a right renal mass that was identified incidentally on abdominal radiographs and classified further as a sarcoma based on fine needle aspiration cytology. Further diagnostic workup, including ultrasound and cytology, identified a sarcoma in the left kidney. After approximately 1 month of conservative medical management, the clinical condition deteriorated and the cat was humanely destroyed. Post-mortem examination confirmed bilateral renal masses with multifocal infarction and extensive necrosis, and further identified a large mass at the apex of the heart as well as multiple pulmonary nodules. Microscopical examination of the masses identified a population of poorly-differentiated neoplastic spindle cells, consistent with sarcoma. Immunohistochemically, the neoplastic cells expressed smooth muscle actin and muscle-specific actin, but were negative for myoglobin and factor VIII. Phosphotungstic acid–haematoxylin staining was unable to identify cross-striations in the neoplastic cells. Based on these results and the pattern of lesion distribution, the cat was diagnosed with cardiac leiomyosarcoma with pulmonary and bilateral renal metastasis.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Schreeg, M. E. and Evans, B. J. and Allen, J. and Lewis, M. C. and Luckring, E. and Evola, M. and Richard, D. K. and Piner, K. and Thompson, E. M. and Adin, D. B. and et al.}, year={2019}, month={Apr}, pages={19–24} } @article{jones_adin_thompson_robertson_rivas_2019, title={Computed Tomography for the Diagnosis and Characterization of Dermoid Sinuses in Two Dogs}, volume={55}, ISSN={["1547-3317"]}, DOI={10.5326/JAAHA-MS-6891}, abstractNote={ABSTRACT A 6 mo old male castrated bloodhound–Rhodesian ridgeback mix (case 1) presented for a mass suspected to be a dermoid sinus in the thoracolumbar region, and a 2.5 yr old male castrated Rhodesian ridgeback (case 2) presented for a mass suspected to be a dorsal cervical dermoid sinus. Both dogs underwent single-phase contrast computed tomography (CT) to characterize the extent of the dermoid sinus prior to surgical excision. Soft tissue and bony abnormalities of the vertebral spine associated with the dermoid sinuses were confirmed in both dogs prior to surgery, demonstrating communication with the dura of the spinal cord. Surgical exploration and excision of the dermoid sinus was performed in each dog, including partial laminectomy. Both cases had resolution of the sinus and an uncomplicated recovery. These cases show that single-phase contrast CT was accurate in characterizing the extent of the dermoid sinus without adjunctive tests or more invasive diagnostics. Single-phase contrast CT should be considered as a preoperative method to characterize the extent of dermoid sinuses, avoiding the risks associated with myelography or fistulography and the expense of MRI. This is also the first report of a dermoid sinus in the thoracolumbar region and the first in a bloodhound and Rhodesian ridgeback mix.}, number={4}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Jones, Susan and Adin, Christopher and Thompson, Elizabeth and Robertson, Ian and Rivas, Rudy}, year={2019} } @article{thompson_robe_roe_cole_2019, title={Influence of wire configuration on resistance to fragment distraction of tension bands placed in a greater trochanteric osteotomy model}, volume={49}, ISBN={1532-950X}, url={https://doi.org/10.1111/vsu.13350}, DOI={10.1111/vsu.13350}, abstractNote={AbstractObjectiveTo determine the influence of wiring configurations on initial tension and resistance to tensile loads in tension band constructs without the contributions of Kirschner‐wire stabilization.Study designExperimental study.Sample populationA solid brass femur model manufactured on the basis of computed tomography of a normal right femur of a 30‐kg dog modified by transection of the greater trochanter and placement of two pins that did not cross the simulated osteotomy.MethodsFour tension band configurations were applied to the metal trochanteric osteotomy model: figure‐of‐eight with one twist (OT), figure‐of‐eight with two twists (TT), dual interlocking single loop, and double loop (DL). Configurations were tested under both monotonic loading (n = 8 per configuration) and incremental cyclic loading (n = 8 per configuration). Initial tension after tying, residual tension remaining after each cycle, and failure load at 2 mm of displacement (considered equivalent to clinical failure) were compared between configurations.ResultsThe initial tension and the load to 2 mm of displacement were lower for OT wires compared with TT wires. The DL was the strongest and most stable configuration, generating 2.3 to 3.5 times greater initial tension, maintaining a greater percentage of residual tension under incremental cyclic loads, and resisting 2.0 to 2.4 times greater load before failure at 2 mm. Failure load was highly correlated with initial tension.ConclusionWire configurations reaching greater initial tension, such as the DL, allowed constructs to resist higher tensile loads.Clinical impactWire configurations allowing higher initial tension may be warranted when tension bands are expected to sustain high tensile loads.}, number={4}, journal={VETERINARY SURGERY}, publisher={Wiley}, author={Thompson, Elizabeth and Robe, Amir K. and Roe, Simon C. and Cole, Jacqueline H.}, year={2019}, pages={710–718} } @article{thompson_sollinger_opara_adin_2018, title={Selective Osmotic Shock for Islet Isolation in the Cadaveric Canine Pancreas}, volume={27}, ISSN={["1555-3892"]}, DOI={10.1177/0963689717752947}, abstractNote={ Currently, islet isolation is performed using harsh collagenases that cause nonspecific injury to both islets and exocrine tissue, negatively affecting the outcome of cell transplantation. We evaluated a novel islet isolation protocol utilizing high concentrations of glucose to cause selective osmotic shock (SOS). Islets have a membrane glucose transporter that allows adaptation to changes in glucose concentrations while exocrine tissue can be selectively destroyed by these osmolar shifts. Canine pancreata were obtained within 15 min after euthanasia from animals ( n = 6) euthanized for reasons unrelated to this study. Each pancreas was divided into 4 segments that were randomized to receive 300 mOsm glucose for 20 min (group 1), 600 mOsm for 20 min (group 2), 300 mOsm for 40 min (group 3), or 600 mOsm for 40 min (group 4). Islet yield, purity, and viability were compared between groups. Mean ± standard error of the mean islet yield for groups 1 to 4 was 428 ± 159, 560 ± 257, 878 ± 443, and 990 ± 394 islet equivalents per gram, respectively. Purity ranged from 37% to 45% without the use of density gradient centrifugation and was not significantly different between groups. Islet cell viability was excellent overall (89%) and did not differ between treatment protocol. Islet function was best in groups treated with 300 mOsm of glucose (stimulation index [SI] = 3.3), suggesting that the lower concentration of glucose may be preferred for use in canine islet isolation. SOS provides a widely available means for researchers to isolate canine islets for use in islet transplantation or in studies of canine islet physiology. }, number={3}, journal={CELL TRANSPLANTATION}, author={Thompson, Elizabeth M. and Sollinger, Jennifer L. and Opara, Emmanuel C. and Adin, Christopher A.}, year={2018}, month={Mar}, pages={542–550} } @article{miller_akaronu_thompson_hood_fogle_2014, title={Modulating DNA Methylation in Activated CD8+ T Cells Inhibits Regulatory T Cell–Induced Binding of Foxp3 to the CD8+ T Cell IL-2 Promoter}, volume={194}, ISSN={0022-1767 1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.1401762}, DOI={10.4049/jimmunol.1401762}, abstractNote={Abstract We have previously demonstrated that CD4+CD25+ regulatory T cells (Tregs) activated during the course of feline immunodeficiency virus (FIV) infection suppress CD8+ CTL function in a TGF-β–dependent fashion, inhibiting IFN-γ and IL-2 production and inducing G1 cell-cycle arrest. In this article, we describe the molecular events occurring at the IL-2 promoter leading to suppression of IL-2 production. These experiments demonstrate that Foxp3 induced by lentivirus-activated Tregs in the CD8+ target cells binds to the IL-2 promoter, actively repressing IL-2 transcription. We further demonstrate that the chronic activation of CD8+ T cells during FIV infection results in chromatin remodeling at the IL-2 promoter, specifically, demethylation of CpG residues. These DNA modifications occur during active transcription and translation of IL-2; however, these changes render the IL-2 promoter permissive to Foxp3-induced transcriptional repression. These data help explain, in part, the seemingly paradoxical observations that CD8+ T cells displaying an activation phenotype exhibit altered antiviral function. Further, we demonstrate that blocking demethylation of CpG residues at the IL-2 promoter inhibits Foxp3 binding, suggesting a potential mechanism for rescue and/or reactivation of CD8+ T cells. Using the FIV model for lentiviral persistence, these studies provide a framework for understanding how immune activation combined with Treg-mediated suppression may affect CD8+ T cell IL-2 transcription, maturation, and antiviral function.}, number={3}, journal={The Journal of Immunology}, publisher={The American Association of Immunologists}, author={Miller, Michelle M. and Akaronu, Nnenna and Thompson, Elizabeth M. and Hood, Sylvia F. and Fogle, Jonathan E.}, year={2014}, month={Dec}, pages={990–998} } @article{meyer_bauer_letang_brighton_thompson_simmen_bonner_jaspers_2014, title={Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers}, volume={306}, ISSN={["1522-1504"]}, DOI={10.1152/ajplung.00290.2013}, abstractNote={A hallmark of cigarette smoking is a shift in the protease/antiprotease balance, in favor of protease activity. However, it has recently been shown that smokers have increased expression of a key antiprotease, secretory leukoprotease inhibitor (SLPI), yet the mechanisms involved in SLPI transcriptional regulation and functional activity of SLPI remain unclear. We examined SLPI mRNA and protein secretion in differentiated nasal epithelial cells (NECs) and nasal lavage fluid (NLF) from nonsmokers and smokers and demonstrated that SLPI expression is increased in NECs and NLF from smokers. Transcriptional regulation of SLPI expression was confirmed using SLPI promoter reporter assays followed by chromatin immunoprecipitation. The role of STAT1 in regulating SLPI expression was further elucidated using WT and stat1−/−mice. Our data demonstrate that STAT1 regulates SLPI transcription in epithelial cells and slpi protein in the lungs of mice. Additionally, we reveal that NECs from smokers have increased STAT1 mRNA/protein expression. Finally, we demonstrate that SLPI contained in the nasal mucosa of smokers is proteolytically cleaved but retains functional activity against neutrophil elastase. These results demonstrate that smoking enhances expression of SLPI in NECs in vitro and in vivo, and that this response is regulated by STAT1. In addition, despite posttranslational cleavage of SLPI, antiprotease activity against neutrophil elastase is enhanced in smokers. Together, our findings show that SLPI regulation and activity is altered in the nasal mucosa of smokers, which could have broad implications in the context of respiratory inflammation and infection.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY}, author={Meyer, Megan and Bauer, Rebecca N. and Letang, Blanche D. and Brighton, Luisa and Thompson, Elizabeth and Simmen, Rosalia C. M. and Bonner, James and Jaspers, Ilona}, year={2014}, month={Feb}, pages={L269–L276} } @article{miller_thompson_suter_fogle_2013, title={CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of Feline Immunodeficiency Virus infection}, volume={152}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2012.12.005}, DOI={10.1016/j.vetimm.2012.12.005}, abstractNote={Acute lentiviral infection is characterized by early CD8+ cytotoxic T cell (CTL) activity and a subsequent decline in plasma viremia. However, CD8+ lymphocytes fail to eliminate the virus and a progressive T cell immune dysfunction develops during the course of chronic lentiviral infection. To further define this CD8+ immune dysfunction we utilized PARR (PCR for antigen receptor rearrangements), a technique which measures clonally expanded lymphocyte populations by comparison of highly conserved T cell receptor (TCR) regions to identify the prevalence of clonal CD8+ T cells following FIV infection. We then compared phenotype, mRNA profiles, CD8+ proliferation and plasma viremia during acute and chronic infection for PARR positive (PARR+) and PARR negative (PARR−) Feline Immunodeficiency Virus (FIV) infected cats. We demonstrated that approximately forty percent of the FIV+ cats examined exhibit CD8+ clonality compared to none of the FIV− control cats. There were no phenotypic differences between PARR+ and PARR− CD8+ lymphocytes from FIV+ cats but retrospective analysis of plasma viremia over the course of infection revealed a delayed peak in plasma viremia and a decline in lymphocyte counts were observed in the PARR+ group during acute infection. CD8+ lymphocytes isolated from chronically infected PARR− cats exhibited significantly higher mRNA expression of IFN-γ and IL-2 following mitogenic stimulation when compared to PARR+ CD8+ lymphocytes. These data suggest that clonal CD8+ expansion may be related to impaired control of acute viremia and less effective CD8+ anti-viral function. Using PARR to assess changes in CD8+ clonality during the progression from acute to chronic FIV infection may help to better characterize the factors which contribute to CD8+ anergy and lentiviral persistence.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Miller, Michelle M. and Thompson, Elizabeth M. and Suter, Steven E. and Fogle, Jonathan E.}, year={2013}, month={Apr}, pages={200–208} }