Doctor of Philosophy, The Ohio State University, 2011, Veterinary Biosciences

Osteoarthritis (OA) is a debilitating disease associated with pain and dysfunction that remains an unresolved and widespread source of symptomatic health problems for many individuals, particularly those 40 years and older. Interleukin-1β (IL-1β) has been cited as a major cytokine involved in OA-related joint degeneration. Recognized as one of the most important mediators of inflammation and host response to infection, increased production of this cytokine has been linked to a wide variety of autoimmune conditions and autoinflammatory disorders. Characterization of its role in primary OA, however, remains elusive and potentially contradictory. Thus, the molecular interactions to explain the relationship between IL-1β and maintenance of healthy articular cartilage have been proposed but are not yet definitively established, and characterization of the function of IL-1β in a spontaneous, in vivo model remains elusive. As such, a primary aim of this study was to provide a comprehensive analysis of the temporal expression and tissue distribution of IL-1β using immunohistochemistry (IHC) throughout initiation and progression of OA in a naturally-occurring animal model. We subsequently elucidated that OA-prone Hartley guinea pig did not demonstrate reduced IL-1β in weight-bearing articular cartilage, synovium, meniscus, or subchondral bone during achievement of adult maturity as in the control guinea pig strain, and that this aberrant expression may correlate to early incidence of OA. As this temporal study provided evidence that IL-1β is a biomarker relevant to the development and progression of OA, and we then performed in vitro and in vivo studies to block and/or reduce the dysregulation of this cytokine's expression such that we could provide evidence of its contribution to premature onset of spontaneous OA. Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques in vitro using a novel adeno-associated viral vector serotype 5 ( (open full item for complete abstract)

Committee: Alicia Bertone DVM PhD (Advisor); Jeffrey Bartlett PhD (Committee Member); Gerard Nuovo MD (Committee Member); Steven Weisbrode VMD PhD (Committee Member) Subjects: Molecular Biology

Doctor of Philosophy, The Ohio State University, 2005, Veterinary Preventive Medicine

Infectious bursal disease virus (IBDV) causes an acute and contagious disease in young chickens from 3-6 weeks of age. Two serotypes of the virus are recognized of which serotype 1 viruses are pathogenic to chickens and are classified into classic, variant, and serotype 2 viruses are nonpathogenic. The disease is controlled by vaccination. In the first part of the study interactions between a mild and a pathogenic strain of IBDV in specific pathogen free (SPF) chickens were studied. Chickens were inoculated with the Bursine-2 vaccine followed by the pathogenic STC strain at various time intervals. Persistence of virus strains was monitored by the reverse transcriptase polymerase chain/restriction fragment length polymorphism (RT-PCR/RFLP), bursa/body weight ratios and histopathological lesion scores. The mild strain interfered with the replication of the pathogenic strain.Currently available ELISA kits were evaluated for their ability to detect antibodies elicited by serotype 1 and serotype 2 viruses. Virus neutralization (VN) test differentiates between antibodies elicited by the two serotypes as well as subtypes of serotype 1 viruses. SPF chickens were inoculated with either serotype 1 STC or serotype 2 OH strain. Sera from these chickens and naturally exposed chickens were tested by five commercial ELISA kits and the VN. The ELISA kits detected antibodies to both serotypes of the virus. Therefore, while determining the antibody profiles of the flocks, the presence of serotype 2 antibodies should be taken into account. Simple and quick diagnostic assays are needed for developing control strategies against IBDV. A differential RT-PCR assay was developed. Two primer sets were designed. Primer set one targeted the segment A of the virus and specifically amplified serotype 2 strains. Primer set 2 targeted the segment B of the virus and amplified the vv strains. These primer sets were validated with 26 different strains maintained in our laboratory. The primer set 2 wa (open full item for complete abstract)

Committee: Yehia Saif (Advisor) Subjects: Biology, Microbiology