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1. Epigenetic clock and methylation studies in cats

Author

Raj, Ken, Szladovits, Balazs, Haghani, Amin, Zoller, Joseph A, Li, Caesar Z, Black, Pete, Maddox, Dewey, Robeck, Todd R, and Horvath, Steve

Subjects
Aging, Human Genome, Biotechnology, Genetics, Generic health relevance, Animals, Biomarkers, Cats, DNA Methylation, Epigenesis, Genetic, Epigenomics, Mice, Cat, Development, Epigenetic clock, DNA methylation
Abstract

Human DNA methylation profiles have been used successfully to develop highly accurate biomarkers of aging ("epigenetic clocks"). Although these human epigenetic clocks are not immediately applicable to all species of the animal kingdom, the principles underpinning them appear to be conserved even in animals that are evolutionarily far removed from humans. This is exemplified by recent development of epigenetic clocks for mice and other mammalian species. Here, we describe epigenetic clocks for the domestic cat (Felis catus), based on methylation profiles of CpGs with flanking DNA sequences that are highly conserved between multiple mammalian species. Methylation levels of these CpGs are measured using a custom-designed Infinium array (HorvathMammalMethylChip40). From these, we present 3 epigenetic clocks for cats; of which, one applies only to blood samples from cats, while the remaining two dual-species human-cat clocks apply both to cats and humans. We demonstrate that these domestic cat clocks also lead to high age correlations in cheetahs, tigers, and lions. It is expected that these epigenetic clocks for cats possess the potential to be further developed for monitoring feline health as well as being used for identifying and validating anti-aging interventions.

Published
2021

3. Session 7: Oncology

Author

Williams, David, primary, Johnson, Geoff, additional, Allan, Frederik, additional, Mosca, Andrea, additional, Dobson, Jane, additional, Brewer, David, additional, Bacon, Nicholas, additional, Macfarlane, Michael, additional, Cerda, Estela Ciriano, additional, Marrington, Mary, additional, Grant, Jessica, additional, Frezoulis, Petros, additional, Harper, Aaron, additional, Berman, Katherine, additional, Green, Jodie, additional, Gramer, Irina, additional, Guillen, Alexandra, additional, Henriques, Tiago, additional, Dunning, Mark, additional, Henry, Perrine, additional, Price, Phoebe Pickard, additional, Stell, Anneliese, additional, O'Neil, Dan, additional, Church, David B, additional, Brodbelt, David, additional, Russak, Onne-Marju, additional, Berlato, Davide, additional, Sharman, Mellora, additional, Verganti, Sara, additional, Schiavo, Luca, additional, Giuliano, Antonio, additional, Williams, Tim, additional, Trewin, Isla, additional, Szladovits, Balazs, additional, Suarez-Bonnet, Alejandro, additional, Koll, Sarah, additional, Stewart, Sarah, additional, Yale, Andrew, additional, Priestnall, Simon, additional, Pittaway, Rachel, additional, and Taylor, Angela, additional

Published
2021
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4. DNA methylation networks underlying mammalian traits

Author

Haghani, Amin, primary, Li, Caesar Z., additional, Robeck, Todd R., additional, Zhang, Joshua, additional, Lu, Ake T., additional, Ablaeva, Julia, additional, Acosta-Rodríguez, Victoria A., additional, Adams, Danielle M., additional, Alagaili, Abdulaziz N., additional, Almunia, Javier, additional, Aloysius, Ajoy, additional, Amor, Nabil M.S., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Banks, Gareth, additional, Belov, Katherine, additional, Bennett, Nigel C., additional, Black, Peter, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Carter, Gerald, additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chakrabarti, Lisa, additional, Chatzistamou, Ioulia, additional, Chavez, Andreas S., additional, Chen, Hao, additional, Cheng, Kaiyang, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, Cook, Joseph A., additional, Cooper, Lisa N., additional, Cossette, Marie-Laurence, additional, Day, Joanna, additional, DeYoung, Joseph, additional, Dirocco, Stacy, additional, Dold, Christopher, additional, Dunnum, Jonathan L., additional, Ehmke, Erin E., additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Erbay, Ebru, additional, Erlacher-Reid, Claire, additional, Faulkes, Chris G., additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gerber, Livia, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Grant, Matthew J, additional, Green, Carla B., additional, Hanson, M. Bradley, additional, Hart, Daniel W., additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Huang, Taosheng, additional, Izpisua Belmonte, Juan Carlos, additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Krützen, Michael, additional, Kwon, Soo Bin, additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaître, Jean-François, additional, Levine, Andrew J., additional, Li, Xinmin, additional, Li, Cun, additional, Lim, Andrea R., additional, Lin, David T. S., additional, Lindemann, Dana M., additional, Liphardt, Schuyler W., additional, Little, Thomas J., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, McClure, Matthew, additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Munshi-South, Jason, additional, Murphy, William J., additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Nyamsuren, Batsaikhan, additional, O’Brien, Justine K., additional, Ginn, Perrie O’Tierney, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Osborn, Steve, additional, Ostrander, Elaine A., additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pedersen, Amy B., additional, Pellegrini, Matteo, additional, Peters, Katharina J., additional, Petersen, Jessica L., additional, Pietersen, Darren W., additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Poganik, Jesse R., additional, Prado, Natalia A., additional, Reddy, Pradeep, additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schmitt, Todd, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shafer, Aaron B.A., additional, Shindyapina, Anastasia V., additional, Simmons, Melanie, additional, Singh, Kavita, additional, Sinha, Ishani, additional, Slone, Jesse, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Staggs, Lydia, additional, Stedman, Nancy, additional, Steinman, Karen J., additional, Stewart, Donald T, additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takahashi, Joseph S., additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Thompson, Michael J., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Villar, Diego, additional, Vinters, Harry V., additional, Vu, Ha, additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yan, Qi, additional, Yao, Mingjia, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Yang, additional, Zhao, Peng, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Gorbunova, Vera, additional, Yang, X. William, additional, Raj, Ken, additional, and Horvath, Steve, additional

Published
2023
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7. Clinical and clinicopathological features and outcomes of cats with suspected dietary induced pancytopenia

Author

Glanemann, Barbara, primary, Humm, Karen, additional, Abreu, Mariana, additional, Aspinall, Sophie, additional, Buckeridge, David, additional, Carveth, Hope, additional, Darcy, Hannah, additional, Florey, Jessica, additional, Frowde, Polly, additional, Gajanayake, Isuru, additional, Green, Kate, additional, Holmes, Emma, additional, Hrovat, Alenka, additional, Jasensky, Anne‐Katherine, additional, Jones, Bryn A, additional, Lantzaki, Vasiliki, additional, Lo, Eve JY, additional, MacDonald, Kirsty, additional, O'Brien, Kevin, additional, Suárez‐Bonnet, Alejandro, additional, Van den Steen, Nele, additional, Szladovits, Balazs, additional, Willems, Annelies, additional, and Wilson, Helen, additional

Published
2023
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13. Epigenetic predictors of maximum lifespan and other life history traits in mammals

Author

Li, Caesar Z., primary, Haghani, Amin, additional, Robeck, Todd R., additional, Villar, Diego, additional, Lu, Ake T., additional, Zhang, Joshua, additional, Faulkes, Chris G., additional, Vu, Ha, additional, Ablaeva, Julia, additional, Adams, Danielle M., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Belov, Katherine, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chatzistamou, Ioulia, additional, Chen, Hao, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, DeYoung, Joseph, additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Hanson, M. Bradley, additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaitre, Jean-Francois, additional, Levine, Andrew J., additional, Li, Cun, additional, Li, Xinmin, additional, Lin, David TS, additional, Lindemann, Dana M., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Ostrander, Elaine A., additional, O'Tierney Ginn, Perrie, additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pellegrini, Matteo, additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Prado, Natalia A., additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shindyapina, Anastasia V., additional, Singh, Kavita, additional, Sinha, Ishani, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Steinman, Karen J., additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Vinters, Harry V., additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yang, X. William, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Peng, additional, Zhao, Yang, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Raj, Ken, additional, Gorbunova, Vera, additional, and Horvath, Steve, additional

Published
2021
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16. SYSTEMATIC EVALUATION OF 106 LABORATORY REFERENCE DATA ARTICLES FROM NONDOMESTIC SPECIES PUBLISHED FROM 2014 TO 2016: ASSESSING COMPLIANCE WITH REFERENCE INTERVAL GUIDELINES

Author

Moore, A Russell, primary, Camus, Melinda S., additional, Harr, Kendal, additional, Kjelgaard-Hansen, Mads, additional, Korchia, Jeremie, additional, Jeffery, Unity, additional, Paltrinieri, Saverio, additional, Pratt, Suzanne M., additional, and Szladovits, Balazs, additional

Published
2020
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21. Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation

Author

Wu, Ying, primary, Chang, Yu-Mei, additional, Polton, Gerry, additional, Stell, Anneliese J., additional, Szladovits, Balazs, additional, Macfarlane, Michael, additional, Peters, Laureen M., additional, Priestnall, Simon L., additional, Bacon, Nicholas J., additional, Kow, Kelvin, additional, Stewart, Sarah, additional, Sharma, Eshita, additional, Goulart, Michelle R., additional, Gribben, John, additional, Xia, Dong, additional, and Garden, Oliver A., additional

Published
2020
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23. Evaluation of concurrent analysis of cerebrospinal fluid samples collected from the cerebellomedullary cistern and lumbar subarachnoid space for the diagnosis of steroid-responsive meningitis arteritis in dogs

Author

Carletti, Beatrice E., primary, De Decker, Steven, additional, Rose, Jeremy, additional, Sanchez-Masian, Daniel, additional, Bersan, Erika, additional, Cooper, Camilla, additional, Szladovits, Balazs, additional, Walmsley, Gemma, additional, and Gonçalves, Rita, additional

Published
2019
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27. ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats

Author

Garden, Oliver A., primary, Kidd, Linda, additional, Mexas, Angela M., additional, Chang, Yu‐Mei, additional, Jeffery, Unity, additional, Blois, Shauna L., additional, Fogle, Jonathan E., additional, MacNeill, Amy L., additional, Lubas, George, additional, Birkenheuer, Adam, additional, Buoncompagni, Simona, additional, Dandrieux, Julien R. S., additional, Di Loria, Antonio, additional, Fellman, Claire L., additional, Glanemann, Barbara, additional, Goggs, Robert, additional, Granick, Jennifer L., additional, LeVine, Dana N., additional, Sharp, Claire R., additional, Smith‐Carr, Saralyn, additional, Swann, James W., additional, and Szladovits, Balazs, additional

Published
2019
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31. Breed predispositions, clinical findings, and prognostic factors for death in dogs with nonregenerative immune‐mediated anemia.

Author

Woolhead, Vanessa L., Szladovits, Balazs, Chan, Antonia, Swann, James W., and Glanemann, Barbara

Subjects
*PROGNOSIS, *ANEMIA, *DOG breeds, *BONE marrow, *HOSPITAL records, *LOGISTIC regression analysis, *DOGS, *LIKELIHOOD ratio tests
Abstract

Background: Breed predispositions, survival, and prognostic factors have not been evaluated in dogs with nonregenerative immune‐mediated anemia (nrIMA). Hypothesis/Objectives: To describe clinicopathologic variables, evaluate their associations with survival, and determine breed predispositions for dogs with nrIMA. Animals Fifty‐nine client‐owned dogs with nrIMA. Methods: Referral hospital records were reviewed retrospectively for dogs with primary nrIMA (PCV ≤30%, corrected reticulocyte percentage (CR%) ≤1.0, bone marrow sampling with evidence of immune‐mediated destruction, and underlying causes excluded). Breed predispositions were evaluated by calculation of odds ratios in a case control study; prognostic factors by logistic regression in a cohort study. Results: Fifty‐nine dogs with nrIMA had a median PCV of 12% (interquartile range [IQR]: 10%‐17%) and CR% 0.1 (0%‐0.2%). At least ≥1 ACVIM IMHA diagnostic criteria were met by 35 dogs (59%). Whippets, Lurchers, and miniature Dachshunds were predisposed to nrIMA. Median survival time was 277 days (IQR: 37‐1925), with 3‐ and 12‐month survival rates 61% and 43%, respectively. Erythroid regeneration and remission were achieved by 88% and 62% of dogs, respectively. Corrected reticulocyte percentage >0.2 was associated with improved survival. Conclusion and Clinical Importance: Although there is overlap of clinical features between dogs with IMHA and nrIMA, the prognosis for those with nrIMA depends predominantly on the severity of reticulocytopenia. [ABSTRACT FROM AUTHOR]

Published
2021
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37. Comparison of medical and/or surgical management of 23 cats with intracranial empyema or abscessation.

Author

Martin, Sophie, Drees, Randi, Szladovits, Balazs, and Beltran, Elsa

Abstract

Objectives: Feline intracranial abscessation or empyema is infrequently reported in the veterinary literature. To date, the largest study is based on a population of 19 cats with otogenic infection. The aim of this study was to review a larger population of cats with intracranial empyema from multiple aetiologies and document their signalment, imaging findings, treatment protocols (including medical and/or surgical management) and to compare outcomes. Methods: Cases presenting to a single referral centre over a 10 year period with compatible history, neurological signs and imaging findings consistent with intracranial abscessation and empyema were reviewed retrospectively. Results: Twenty-three cats met the inclusion criteria. Advanced imaging (CT and/or MRI) was performed in 22/23 cats; one case was diagnosed via ultrasound. Ten cases underwent medical and surgical management combined, 10 underwent solely medical management and three were euthanased at the time of diagnosis. Short-term outcome showed that 90% of surgically managed and 80% of medically managed cats were alive at 48 h post-diagnosis. Long-term survival showed that surgically managed cases and medically managed cases had a median survival time of 730 days (range 1–3802 days) and 183 days (range 1–1216 days), respectively. No statistical significance in short- or long-term survival (P >0.05) was found between medically and surgically managed groups. Conclusions and relevance: Feline intracranial abscessation and empyema are uncommon conditions that have historically been treated with combined surgical and medical management. This study documents that, in some cases, intracranial abscessation and empyema can also be successfully treated with medical management alone. [ABSTRACT FROM AUTHOR]

Published
2019
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38. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma

Author

Pinheiro, Dammy, Chang, Yu-Mei, Bryant, Hannah, Szladovits, Balazs, Dalessandri, Tim, Davison, Lucy J., Yallop, Elizabeth, Mills, Emily, Leo, Chiara, Lara, Ana, Stell, Anneliese, Polton, Gerry, Garden, Oliver A., Davison, Lucy [0000-0002-1920-0817], and Apollo - University of Cambridge Repository

Subjects
Male, lcsh:Medicine, Pathology and Laboratory Medicine, T-Lymphocytes, Regulatory, White Blood Cells, Animal Cells, Basic Cancer Research, Tumor Microenvironment, Dog Diseases, Small Animals, lcsh:Science, Immune Response, Non-Hodgkin lymphoma, T Cells, Forkhead Transcription Factors, Hematology, Prognosis, Veterinary Diagnostics, Oncology, Research Design, Lymphomas, Female, Cellular Types, Veterinary Pathology, Research Article, Tumor Immunology, Veterinary Medicine, Clinical Pathology, Lymphoma, B-Cell, Clinical Research Design, Immune Cells, Animal Types, CD8 Antigens, Immunology, Genes, MHC Class II, Research and Analysis Methods, Veterinary Immunology, Immunophenotyping, Ikaros Transcription Factor, Dogs, Diagnostic Medicine, Cancer Detection and Diagnosis, Animals, Small Animal Care, Animal Models of Disease, Medicine and health sciences, Blood Cells, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Disease Models, Animal, Hematologic cancers and related disorders, Animal Studies, Veterinary Oncology, Clinical Immunology, Veterinary Science, lcsh:Q
Abstract

The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

Published
2014

41. Pathology in Practice

Author

Stock, Graham J., primary, Feltrer, Yedra, additional, Flach, Edmund J., additional, and Szladovits, Balazs, additional

Published
2013
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46. Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma.

Author

Pinheiro, Dammy, Chang, Yu-Mei, Bryant, Hannah, Szladovits, Balazs, Dalessandri, Tim, Davison, Lucy J., Yallop, Elizabeth, Mills, Emily, Leo, Chiara, Lara, Ana, Stell, Anneliese, Polton, Gerry, and Garden, Oliver A.

Subjects
LYMPHOMAS, DISSECTION, ANIMAL models in research, CARCINOGENESIS, IMMUNE response, T cells, B cell lymphoma, DOG diseases, PROGNOSIS
Abstract

The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms. [ABSTRACT FROM AUTHOR]

Published
2014
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47. Hepatozoon canisin three imported dogs: a new tickborne disease reaching the United Kingdom

Author

Attipa, Charalampos, Maguire, David, Solano‐Gallego, Laia, Szladovits, Balazs, Barker, Emily N, Farr, Alison, Baneth, Gad, and Tasker, Séverine

Abstract

An increasing number of non‐endemic vectorborne pathogens have been described in dogs imported to the UK in the past two decades. Recently, an outbreak of canine babesiosis in south‐east England has raised veterinary awareness with regard to the impact of such diseases on the UK canine population. Canine hepatozoonosis, caused by Hepatozoon canisand transmitted by the ingestion of Rhipicephalus sanguineusticks, is widespread in the Mediterranean basin. Herein we describe the first three molecularly confirmed clinical cases of canine hepatozoonosis in dogs imported into the UK. Veterinarians in the UK should be aware of H canisas a potential infection in imported dogs, especially in the face of the expanding distribution of R sanguineusticks in Europe.

Published
2018
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48. Research Paper Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs.

Author

Dodam, John R., Cohn, Leah A., Durham, Harris E., and Szladovits, Balazs

Subjects
*SELEGILINE, *PLACEBOS, *CARDIOPULMONARY system, *VETERINARY therapeutics, *BLOOD pressure measurement, *LABORATORY dogs
Abstract

To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. Prospective randomized experimental study. Twenty-eight adult, random source, hound dogs weighing 21–33 kg. Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED ( n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY ( n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT ( n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg−1 PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 µg m−2), OXY (0.1 mg kg−1) or BUT (0.4 mg kg−1) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO2 were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO2. BUT decreased level of consciousness and resistance to restraint. Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs. [ABSTRACT FROM AUTHOR]

Published
2004
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49. Spherocytosis as an indicator of fragmentation injury in dogs with splenic torsion.

Author

Beeston D, Szladovits B, and Cortellini S

Subjects
Animals, Dogs, Male, Female, Dog Diseases diagnosis, Torsion Abnormality veterinary, Splenic Diseases veterinary
Abstract

Objective: To describe the presentation, diagnosis, and treatment of 4 cases of splenic torsion with associated spherocytosis., Animals: 4 client-owned dogs with spherocytosis and splenic torsion., Clinical Presentation: Each dog presented with nonspecific clinical signs, and 3 out of 4 dogs were anemic on presentation., Results: The diagnosis of splenic torsion was made with abdominal ultrasound or CT and confirmed during exploratory laparotomy. Spherocytosis was described as occasional (patient 1), rare (patient 2), and low number (patients 3 and 4). Two dogs survived to hospital discharge, and 2 dogs died following cardiorespiratory arrest., Clinical Relevance: Spherocytosis has not previously been reported in cases of splenic torsion, and identification of spherocytes on blood film evaluation warrants further investigation. The cause of spherocytosis in splenic torsion remains unknown but may be associated with microangiopathic fragmentation injury.

Published
2024
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50. Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat.

Author

Heaps LA, Scudder CJ, Lipscomb VJ, Steinbach SM, Priestnall SL, Martineau H, Szladovits B, Fowkes RC, and Garden OA

Abstract

Case Summary: A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat's clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value., Relevance and Novel Information: Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats., Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2017
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