Veterinary Physiology Commons^™

Investigation Into Cardiacmyhc-Α 334–352-Specific Tcr Transgenic Mice Reveals A Role For Cytotoxic Cd4 T Cells In The Development Of Cardiac Autoimmunity, Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah B. Gurumurthy, Raymond A. Sobel, Jay Reddy

Jay Reddy Publications

Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334–352 and found that Myhc-α-specific TCRs were expressed in both CD4⁺ and CD8⁺ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At the fourth …

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Taejoon Won, Hannah M. Kalinoski, Megan K. Wood, David M. Hughes, Camille M. Jaime, Paul Delgado, Monica V. Talor, Ninaad Lasrado, Jay Reddy, Daniela Čiháková

Jay Reddy Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …

Establishing Hematology And Serum Chemistry Reference Intervals For Wild Hawaiian Monk Seals (Neomonachus Schauinslandi), Angela C. Kaufman, Stacie J. Robinson, Dori L. Borjesson, Michelle Barbieri, Charles L. Littnan

United States Department of Commerce: Staff Publications

Hematology and serum chemistry reference intervals have been previously established for the endangered Hawaiian monk seal (Neomonachus schauinslandi) as an imperative measure for health assessments. Monitoring the health of the wild population depends upon reference intervals that are context specific; hence we developed reference intervals from fresh samples, as opposed to frozen, from wild monk seals. This study builds on the number of parameters from previous efforts by using samples collected between 2004 and 2015 from wild monk seals. Blood samples were analyzed by a single veterinary diagnostic laboratory within 24 hr of collection from apparently healthy, wild …

Endocrine And Metabolic Effects Of Consuming Sugar-Sweetened Beverages: Preclinical And Clinical Studies", Peter Havel

Science Seminar Series

Peter J. Havel of the School of Veterinary Medicine at UC Davis will speak on his research on Endocrine and Metabolic Effects of Consuming Sugar-Sweetened Beverages: Preclinical and clinical studies at this Science Seminar Series lecture.

Whole Genomic Sequence Analysis Of Bacillus Infantis: Defining The Genetic Blueprint Of Strain Nrrl B-14911, An Emerging Cardiopathogenic Microbe, Chandirasegara Massilamany, Akram Mohammed, John Dustin Loy, Tanya Purvis, Bharathi Krishnan, Rakesh H. Basavalingappa, Christy M. Kelley, Chittibabu Guda, Raúl G. Barletta, Etsuko N. Moriyama, Timothy P.L. Smith, Jay Reddy

Jay Reddy Publications

Background: We recently reported the identification of Bacillus sp. NRRL B-14911 that induces heart autoimmunity by generating cardiac-reactive T cells through molecular mimicry. This marine bacterium was originally isolated from the Gulf of Mexico, but no associations with human diseases were reported. Therefore, to characterize its biological and medical significance, we sought to determine and analyze the complete genome sequence of Bacillus sp. NRRL B-14911.

Results: Based on the phylogenetic analysis of 16S ribosomal RNA (rRNA) genes, sequence analysis of the 16S-23S rDNA intergenic transcribed spacers, phenotypic microarray, and matrix-assisted laser desorption ionization time-offlight mass spectrometry, we propose that this …

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse, Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

Jay Reddy Publications

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

Gender Differences In Cns Autoimmunity Induced By Mimicry Epitope For Plp 139–151 In Sjl Mice, Chandirasegara Massilamany, Sivasubramani Thulasingam, David Steffen, Jay Reddy

Jay Reddy Publications

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83–95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139–151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83–95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific …