Cell and Developmental Biology Commons^™

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed using …

The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller

Student Publications & Research

CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Natural And Exogenous Genome Editing In Wiskott-Aldrich Syndrome Patient Cells, Tamara J. Laskowski

Dissertations and Theses (Open Access)

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease characterized by thrombocytopenia, recurrent infections and increased autoimmunity. This disease is caused by mutations in the WAS gene (WAS) which encodes for the WAS protein (WASp), exclusively expressed in hematopoietic cells and required for proper platelet production and lymphoid cell function. Approximately 11% of patients with WAS exhibit a phenomenon called Somatic Revertant Mosaicism which is characterized by the presence of lymphocytes which naturally revert back to normal phenotype by restoring WASp expression. To date, the mechanisms of this naturally-occurring gene therapy remains poorly understood, and the full extent …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso

Dissertations and Theses (Open Access)

T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR⁺ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, …

Cd8Α Dendritic Cells Drive Establishment Of Hsv-1 Latency, Kevin R. Mott, Sariah J. Allen, Mandana Zandian, Bindu Konda, Behrooz G. Sharifi, Clinton Jones, Steven L. Wechsler, Terrence Town, Homayon Ghiasi

School of Veterinary and Biomedical Sciences: Faculty Publications

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wildtype (WT) C57BL/6 versus CD8α^‒/‒ (lack functional CD8 T cells and CD8α⁺ DCs), CD8β^‒/‒ (have functional CD8α⁺ T cells and CD8α⁺ DCs), and β2m^‒/‒ (lack functional CD8 T cells but have CD8α^{+ …}

Overexpression Of Thioredoxin Binding Protein (Tbp-2) Increases Oxidation Sensitivity And Apoptosis In Human Lens Epithelial Cells, Yibo Yu, Kuiyi Xing, Rilwan Badamas, Charles A. Kuszynski, Hongli Wuand, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioredoxin (Trx) is an important redox regulator with cytosolic Trx1 and mitochondrial Trx2 isozymes. Trx has multi-physiological functions in cells and its bioavailability is negatively controlled through active site binding to a specific thioredoxin binding protein (TBP-2). This paper describes the delicate balance between TBP-2 and Trx, and the effect of overexpression of TBP-2 in the human lens epithelial cells. Cells overexpressing TBP-2 (TBP-2 OE) showed a 7- fold increase of TBP-2, and a nearly 40% suppression of Trx activity but no change in Trx expression. The TBP-2 OE cells grew slower and their population decreased to 30% by day …

Evaluation Of Novel Oral Vaccine Candidates And Validation Of A Caprine Model Of Johne’S Disease, Murray E. Hines Ii, Sue E. Turnquist, Marcia R.S. Ilha, Sreekumari Rajeev, Arthur L. Jones, Lisa Whittington, John P. Bannantine, Raul G. Barletta, Yrjö T. Gröhn, Robab Katani, Adel M. Talaat, Lingling Li, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne’s disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease go at challenge model. …

Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor

Graduate School of Biomedical Sciences Theses and Dissertations

Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of …

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are …

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces cerevisiae expressing …

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Dens Agenesis And Cervical Vertebral Malformation In A Labrador Retriever Puppy, Elisa Salas, Henry E. Cerny, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Cervical vertebral malformations can cause acute or progressive pain, paralysis, and potentially death. Herein we present a case report of dens agenesis; cervical vertebral malformations of C1, C2, C6, and C7; subluxation of C1 and C2 and C4 and C5; and associated degenerative myelopathy in a 5-month-old female Labrador Retriever puppy. We additionally review current knowledge regarding pathogenesis and treatment.

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

Novel Gammaherpesvirus Functions 1 Encoded By Bovine Herpesvirus (Bovine Lymphotropic Virus), J. Jia, G. Delhon, E. R. Tulman, D. G. Diel, Fernando A. Osorio, X. Wen, G. F. Kutish, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a

macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique, 141 kilobase pair L

DNA region predicted to encode 77 genes. BoHV-6 encoded in variable genomic regions a novel complement of genes relative to other characterized macaviruses, likely contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, …

Evaluating The Clinical And Physiological Effects Of Long Term Ultraviolet B Radiation On Guinea Pigs (Cavia Porcellus), Megan K. Watson, Adam W. Stern, Amber L. Labelle, Stephen Joslyn, Timonthy M. Fan, Katie Leister, Micah Kohles, Kemba Marshall, Mark A. Mitchell

School of Veterinary and Biomedical Sciences: Faculty Publications

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B …

Experimental Infection Of Pregnant Goats With Bovine Viral Diarrhea Virus (Bvdv) 1 Or 2, Thomas Passler, Kay P. Riddell, Misty A. Edmondson, Manuel F. Chamorro, John D. Neill, Bruce W. Brodersen, Heather L. Walz, Patricia K. Galik, Yijing Zhang, Paul H. Walz

School of Veterinary and Biomedical Sciences: Faculty Publications

Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. BVDV infections of goats commonly result in reproductive disease, but viable PI goats are rare. Using 2 BVDV isolates, previously demonstrated to cause PI cattle and white-tailed deer, this study evaluated the outcome of experimental infection of pregnant goats. Pregnant goats (5 goats/group) were intranasally inoculated with BVDV 1b AU526 (group 1) or BVDV 2 …

Glutaredoxin-2 Is Required To Control Oxidative Phosphorylation In Cardiac Muscle By Mediating Deglutathionylation Reactions, Mary-Ellen Harper, Ryan J. Mailloux, Jian Ying Xuan, Skye Mcbride, Wael Maharsy, Stephanie Thorn, Chet E. Holterman, Christopher R.J. Kennedy, Peter Rippstein, Robert Dekemp, Jean Da Silva, Mona Nemer, Marjorie Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2−/−) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered …

Altered Entrainment To The Day/Night Cycle Attenuates The Daily Rise In Circulating Corticosterone In The Mouse, Patricia J. Sollars, Michael J. Weiser, Andrea E. Kudwa, Jayne R. Bramley, Malcolm D. Ogilvie, Robert L. Spencer, Robert J. Handa, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT_1B receptors, decreasing responsiveness to light. Consequently, 5-HT_1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light:dark cycle (T …

Sumoylation Differentially Regulates Sp1 To Control Cell Differentiation, Lili Gong, Wei-Ke Ji, Xiao-Hui Hu, Wen-Feng Hu, Xiang-Cheng Tang, Zhao-Xia Huang, Ling Li, Mugen Liu, Shi-Hua Xiang, Erxi Wu, Zachary Woodward, Yi-Zhi Liu, Quan Dong Nguyen, David Wan-Cheng Li

School of Veterinary and Biomedical Sciences: Faculty Publications

The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 …

Protective Humoral Immune Response Induced By An Inactivated Porcine Reproductive And Respiratory Syndrome Virus Expressing The Hypo-Glycosylated Glycoprotein 5, Jung-Ah Lee, Byungjoon Kim, Fernando A. Osorio, Asit K. Pattnaik, Nak-Hyung Lee, Sang-Won Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses to the swine industry worldwide. Although inactivated and live vaccines are commercially available for the control of PRRS, both types of vaccine have not always proven successful in terms of generating a protective immune response, particularly in the case of inactivated vaccines. In this study, we tested whether an inactivated vaccine could induce a humoral immune response to PRRS during a homologous challenge. Amino acid substitutions were introduced into glycoprotein (GP) 5 of the FL12 strain of the PRRS virus (PRRSV) using site-directed mutagenesis with a pFL12 infectious clone. The …

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Moraxella Spp. Isolated From Field Outbreaks Of Infectious Bovine Keratoconjunctivitis: A Retrospective Study Of Case Submissions From 2010 To 2013, John Dustin Loy, Bruce W. Brodersen

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is the most costly eye disease of cattle. The principal etiologic agent of IBK is the Gram-negative bacterium Moraxella bovis. However, there have been reports of IBK outbreaks associated with Moraxella bovoculi. A retrospective study of IBK diagnostic cases submitted from July 1, 2010, through October 31, 2013, was conducted. Included in the study were 1,042 Moraxella isolates from 1,538 swabs of lacrimal secretions collected from 282 herds from 30 U.S. states. Moraxella isolates were identified to the species level and were composed of M. bovoculi (701 isolates), M. bovis …

In Situ Detection Of Autoreactive Cd4 T Cells In Brain And Heart Using Major Histocompatibility Complex Class Ii Dextramers, Chandirasegaran Massilamany, Arunakumar Gangaplara, Ting Jia, Christian Elowsky, Qingsheng Li, You Zhou, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

This report demonstrates the use of major histocompatibility complex (MHC) class II dextramers for detection of autoreactive CD4 T cells in situ in myelin proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in SJL mice and cardiac myosin heavy chain-α (Myhc) 334-352-induced experimental autoimmune myocarditis (EAM) in A/J mice. Two sets of cocktails of dextramer reagents were used, where dextramers+ cells were analyzed by laser scanning confocal microscope (LSCM): EAE, IAs/PLP 139-151 dextramers (specific)/anti- CD4 and IAs/Theiler’s murine encephalomyelitis virus (TMEV) 70-86 dextramers (control)/anti-CD4; and EAM, IAk/Myhc 334-352 dextramers/ anti-CD4 and IAk/bovine ribonuclease (RNase) 43-56 dextramers (control)/anti-CD4. LSCM analysis of …

Generation Of Calves Persistently Infected With Hobi-Like Pestivirus And Comparison Of Methods For Detection Of These Persistent Infections, F. V. Bauermann, S. M. Falkenberg, B. Vander Ley, N. Decaro, Bruce W. Brodersen, A. Harmon, B. Hessman, E. F. Flores, J. F. Ridpath

School of Veterinary and Biomedical Sciences: Faculty Publications

The identification and elimination of persistently infected (PI) cattle are the most effective measures for controlling bovine pestiviruses, including bovine viral diarrhea virus (BVDV) and the emerging HoBi-like viruses. Here, colostrum-deprived calves persistently infected with HoBi-like pestivirus (HoBi-like PI calves) were generated and sampled (serum, buffy coat, and ear notches) on the day of birth (DOB) and weekly for 5 consecutive weeks. The samples were subjected to diagnostic tests for BVDV—two reverse transcriptase PCR (RT-PCR) assays, two commercial real-time RT quantitative PCR (RT-qPCR), two antigen capture enzyme-linked immunosorbent assays (ACE), and immunohistochemistry (IHC)—and to HoBi-like virus-specific RT-PCR and RT-qPCR assays. …

Generation And Screening Of A Comprehensive Mycobacterium Avium Subsp. Paratuberculosis Transposon Mutant Bank, Govardhan Rathnaiah, Elise A. Lamont, N. Beth Harris, Robert J. Fenton, Denise K. Zinniel, Xiaofei Liu, Josh Sotos, Zhengyu Feng, Ayala Livneh-Kol, Nahum Y. Shpigel, Charles J. Czuprynski, Srinand Sreevatsan, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s Disease in ruminants. This enteritis has significant economic impact and world wide distribution. Vaccination is one of the most cost effective infectious disease control measures. Unfortunately, current vaccines reduce clinical disease and shedding, but are of limited efficacy and do not provide long-term protective immunity. Several strategies have been followed to mine the MAP genome for virulence determinants that could be applied to vaccine and diagnostic assay developent. In this study, a comprehensive mutant bank of 13,536 MAP K-10 Tn5367 mutants (P>95% )was constructed and screened in …

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

School of Veterinary and Biomedical Sciences: Faculty 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 …

Intricacies Of Cardiac Damage In Coxsackievirus B3 Infection: Implications For Therapy, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of …