Medicine and Health Sciences Commons^™

Tetraspanin Cd9: Contributions To Cancer Cell And Vascular Cell Phenotypes From The Sixth Man, Michael James Herr Ii

Theses and Dissertations (ETD)

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate …

The Relationship Between Health Literacy And Health Outcomes: A Mixed-Methods Study Of African-American Adult Patients With Asthma, Courtnee Erin Melton

Theses and Dissertations (ETD)

Introduction: Asthma affects 24.6 million people in the United States, and AfricanAmericans share a disproportionate burden of the disease. African-Americans have a higher prevalence of asthma, worse asthma control, higher hospitalization rates, and higher asthma mortality rates African-Americans are also more likely to have low health literacy. Low health literacy has been linked to increased use of emergency care, increased hospitalization, decreased use of preventive services, poorer medication adherence, poorer interpretation of prescription labels, nutrition labels, and health messages, and poorer health outcomes. Consequently, health literacy is one of the modifiable individual factors that contributes to asthma disparities among African-Americans. …

Development And Application Of A Biorobotic Simulation Of Stance Phase Gait To Study Foot And Ankle Kinematics, Kelly N. Salb

Theses and Dissertations (ETD)

Ankle instantaneous axis of rotation (IAR) measurements represent a more complete parameter for characterizing joint motion. However, few studies have implemented this measurement to study normal, injured, or pathological foot-ankle biomechanics. Additionally, while load is suggested to play a major role in ankle biomechanics, including influences on articular surfaces, bony motion, and formation of the arches, studies concerning the effects of joint loading are limited.

A novel testing protocol was developed to simulate in vivo mechanics of the foot-ankle complex during early stance phase gait in a human cadaveric model. Two studies were conducted. The first study was to assess …

Cost Of Illness Study Of Anxiety Disorders For The Ambulatory Adult Population Of The United States, Elaheh Shirneshan

Theses and Dissertations (ETD)

Background: Anxiety disorders are the most common psychiatric illness in the United States. However, economic burdens of this category of mental illnesses have not been well studied yet. The objective of this study was to estimate the societal cost of anxiety disorders for the ambulatory adult population of the U.S.

Data and Method: Data was collected from the 2009 and 2010 Medical Expenditure Panel Survey (MEPS), Bureau of Labor Statistics (BLS), and National Vital Statistics System (NVSS). Cost components included in the analyses were direct medical costs (i.e. cost for inpatient visits, outpatient visits, emergency room visits, office-based visits, prescription …

Adenylyl Cyclase 2 Selectively Regulates Il-6 Expression In Human Bronchial Smooth Muscle Cells, Amy Sue Bogard

Theses and Dissertations (ETD)

Adenylyl cyclase (AC) catalyzes the formation of the ubiquitous second messenger cAMP. AC isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions, and most cells express multiple isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses. Overexpression of individual isoforms had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes in human bronchial smooth muscle cells (BSMC) and human embryonic kidney cells (HEK-293). Most notable, in BSMC overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production …

Development And Characterization Of A Recombinant Vesicular Stomatitis Virus (Rvsv) For The Treatment Of Glioblastoma, Erika A. Dillard

Theses and Dissertations (ETD)

Background: Over the past 30 years, little has changed in the treatment modalities and prognosis of patients suffering from Glioblastoma multiforme (GBM), the most common and by far the most devastating adult primary malignant brain tumor. Conventional therapies provide only a marginal increase in survival of GBM patients, post-diagnosis. Therefore, more novel means of treating GBM are needed to increase long-term survival and quality of life for those affected. Replication competent oncolytic viruses (OVs) have recently emerged as a possible option for treatment of high-grade gliomas. Particularly, recombinant vesicular stomatitis virus (rVSV), an enveloped, negative strand RNA virus, has shown …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Regulation Of Secretory Phospholipase A2 By Thyroid Hormone, Pragya Sharma

Theses and Dissertations (ETD)

Rationale: Low grade inflammation has been correlated with elevated risk of hepatic steatosis and atherosclerosis. Secretory phospholipase A2 group IIA (PLA2g2a) enhances the progression of several chronic inflammatory diseases including arthritis and atherosclerosis. The potential linkage of hypothyroidism with inflammation led us to examine the modulation of sPLA2 expression by thyroid hormone (T3) in liver.

Objective: Most of the studies of phospholipase A2 group IIA (PLA2g2a) have been conducted with macrophages and vascular smooth muscle cells with regard to atherosclerosis. The liver is one of the major contributors to the total pool of extracellular PLA2g2a. The aim of the present …

Determinants Of Upper Genital Tract Complications In A Chlamydial Urogenital Mouse Model, Enitra N. Jones

Theses and Dissertations (ETD)

Genital Chlamydia trachomatis infection is a major public health concern. Chlamydia is the most commonly reported infection in the United States and the most common bacterial sexually transmitted infection worldwide. Unrecognized infection endangers female reproductive health by serious complications such as Pelvic Inflammatory Disease, ectopic pregnancy, and involuntary infertility. Widespread Chlamydia control programs were implemented more than two decades ago to improve women's reproductive health but, despite initial success, the number of chlamydial infections reported have increased.

One of the hypotheses put forth to explain increased chlamydial reporting suggests that a longterm caveat of control initiatives is interference with the …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Developmental Characterization Of The Choroid Plexus In Sialidosis (Neu1 Deficient) Mice, Danielle Lee Helton

Theses and Dissertations (ETD)

The lysosomal sialidase Neuraminidase-1 (Neu1) initiates the hydrolysis of sialoglycoconjugates by cleaving their terminal sialic acid residues. Neu1 creates a complex with the carboxypeptidase protective protein/cathepsin A (PPCA), which is necessary for its catalytic activation and its transport to the lysosomal compartment. In humans, a primary deficiency of this enzyme leads to a pediatric, catastrophic, neurodegenerative lysosomal storage disorder called sialidosis. Mice deficient in Neu1 exemplify the early-onset severe form of sialidosis. Our laboratory has recently discovered that loss of Neu1 exacerbates the process of lysosomal exocytosis (LyEXO) in various cell types by influencing the sialic acid content of lysosomal …

Full-Gestational Exposure To Nicotine And Ethanol Results In Long-Term Dysregulation In The Ventral Tegmental Area, Emily Elizabeth Roguski

Theses and Dissertations (ETD)

Nicotine is considered a gateway drug for other drugs of abuse. The majority of smokers that begin smoking in adolescence, continue into adulthood. Multiple factors have been linked with smoking initiation, including maternal smoking. Drug exposure during pregnancy has long been suspected to exert deleterious effects on the fetal brain. Concurrent use of smoking and drinking alcohol throughout pregnancy is an all too frequent occurrence in the human population especially in disadvantaged and younger women.

The present study investigated the potential contributing factors for the enhanced nicotine selfadministration as seen in offspring with gestational exposure to nicotine and ethanol (Nic+EtOH).* …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.

Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek

Theses and Dissertations (ETD)

Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …

Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock

Theses and Dissertations (ETD)

Hypoxia is a hallmark of most solid tumors. In response to hypoxic stress tumor cells adapt by regulating survival, metabolism and angiogenesis. The heterodimeric HypoxiaInducible Factor (HIF) transcription factors are the master regulators of this response. HIFs play key roles in many critical aspects of cancer biology including angiogenesis, stem cell maintenance, metabolic reprogramming, invasion, metastasis and resistance to radiation therapy and chemotherapy. Overexpression of HIF-1α and HIF-2α has been documented in multiple human cancers and HIF-1 protein is over-expressed in ~30% of primary breast tumors and ~70% of metastases, which independently correlates with poor prognosis and decreased survival in …

Nkg2d Ligands In Cancer, Neha Das Gupta

Theses and Dissertations (ETD)

NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …

Toll-Like Receptors 2 And 9 Are Important For Innate Immune Cell Activation And Recruitment In Hypersensitivity Pneumonitis, Kelly J. Andrews

Theses and Dissertations (ETD)

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of environmental antigens. The disease is characterized by alveolitis and granuloma formation; however, some patients develop chronic HP (CHP), a restrictive lung disease characterized by fibrosis. Previous studies revealed that neutrophils are recruited into the lung via a MyD88- dependent pathway and regulate disease severity through cytokine production. Toll-like receptors (TLRs) 2 and 9 recognize conserved molecular patterns present in bacteria, and signal through the adaptor molecule MyD88. The goal of my project is to investigate the role of TLRs 2 and 9 in the pathogenesis of HP …

In Vitro Manual Therapy And Biorobotic Simulation Of Glenohumeral Joint Mobilization Techniques, Hunter Johnson Smith

Theses and Dissertations (ETD)

Physical therapists (PT) employ mobilization techniques for restoring range of motion to joints. Few studies have attempted to quantify the biomechanics of manual therapy on the glenohumeral (GH) joint. The objectives of this study were to develop an in vitro protocol to determine the biomechanical effects of joint mobilization on the GH joint, and to then simulate these mobilizations in the University of Tennessee Health Science Center (UTHSC) Joint Implant Biomechanics Laboratory’s Robotic Testing Platform (RTP).

The GH joint is an incredibly shallow socket joint. This gives the joint an unusually large range of motion (ROM) compared to other ball …

Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora

Theses and Dissertations (ETD)

Macromolecular complexes of cystic fibrosis transmembrane conductance regulator (CFTR) comprise of network of proteins that can regulate cAMP-/cGMP-activated CFTR chloride channel function. We report the physical and functional coupling of CFTR with nitric oxide (NO) producing enzyme-inducible nitric oxide synthase (iNOS) at the apical plasma membrane in inflammatory bowel disease (IBD). The complex formation requires the scaffolding protein Na+ /H+ exchanger regulatory factor 2 (NHERF2). We demonstrate that iNOS is overexpressed at or near the apical plasma membrane of gut epithelial cells in IBD and, through the stimulation of the NO-cGMP pathway, generates compartmentalized cGMP underneath the plasma membrane. This …

Analysis Of Community-Based Accumulation Of Home Medications (Caches) Found At Death Scenes In Davidson County, Tennessee, Carrie E. Plummer

Theses and Dissertations (ETD)

Introduction: Stockpiling of unused medications by community-dwelling individuals results in Community-based ACcumulation of Home mEdicationS (CACHES). CACHES place the individual, health care and justice system, and ecosystem at risk for adverse outcomes including: a) diversion of prescription medications by friends and family, b) pediatric poisonings, c) adverse drug events, d) increased criminal justice system costs related to prescription drug abuse, e) increased health care costs, and f) pollution of local water supplies via improper medication disposal. This study explores the relationship among individual risk factors (gender, race, age, comorbid conditions), geographical location, health care risk factors (number of prescribers and …

The Protumorigenic Role Of Caspase-8 In Neuroblastoma, Devin Drew Twitchell

Theses and Dissertations (ETD)

Neuroblastoma (NB), the most common extracranial solid tumor in children, accounts for 15% of cancer-related deaths in pediatric patients. Caspase-8 (casp8), a proapoptotic protein, is silenced in approximately, 50-70% of neuroblastoma patient samples. Loss of casp8 has been suggested to increase NB metastasis and correlated, in some studies, with advanced-stage NB. Furthermore, decreased casp8 expression may facilitate neuroblastoma tumorigenesis by protecting cells from cell death mediated by either integrins or chemotherapeutics. Paradoxically, casp8 expression is maintained in 30-50% of NB patient samples giving rise to the possibility that casp8 may provide selective advantages for NB tumorigenesis. Caspase-8 is shown to …

A Series Of Pharmaceutical Technology Concepts Applied To Pediatric Formulations, Hao Lou

Theses and Dissertations (ETD)

Pediatric formulations have received great attention from regulatory agencies in the United States and Europe. Since solid dosage forms such as tablets and capsules will not be able to improve pediatric patients’ compliance, customized pediatric formulations are needed. In response, formulators in the pharmaceutical industry have made significant effort into developing various pediatric formulations. However, developing satisfactory pediatric formulations is a process that is guided by case by case basis. The objective of this current study was to apply the scientific pharmaceutical technology concepts into developing modern pediatric formulations. We have shown that the drug delivery design will be affected …

Gene Therapy And Stem Cell Therapy To Improve The Outcome Of Human Islet Transplantation, Hao Wu

Theses and Dissertations (ETD)

Since its first introduction in 1990s, the Edmonton Protocol for human islet transplantation has helped more than 500 patients with type 1 diabetes worldwide and met great success from bench to bedside. The Edmonton Protocol involves isolating islets from a cadaveric donor pancreas by enzymatic digestion and infusing into the patient's portal vein. Each recipient usually receives islets from two or three donors for an optimal outcome and is dosed with two immunosuppressive drugs, sirolimus and tacrolimus and a monoclonal antibody drug daclizumab to prevent the graft rejection. However, despite the administration of immunosuppressive drugs and the recent improvement in …

Changes In Pharyngeal Airway Dimensions Due To Mara Treatment In Class Ii Malocclusions, James K. Dillehay

Theses and Dissertations (ETD)

Orthodontic treatment effects on the pharyngeal airway have recently become a hot topic in the field of orthodontics. Current literature has shown facial skeletal morphology to be correlated with pharyngeal airway shape and volume. This study used CBCT imaging to identify what, if any, effects two different treatment modalities for correcting Class II malocclusions have on the pharyngeal airway volume. This retrospective study consisted of two groups of Class II patients: 38 patients (15 females, 23 males) treated with the MARA and an Edgewise appliance and 32 patients treated with an Edgewise appliance and Class II elastics. Both pre and …

Treatment Effects Of The Mandibular Anterior Repositioning Appliance (Mara) And Conventional Orthodontic Mechanics On Temporomandibular Joint Morphology: A Comparison Using Cone Beam Computed Tomography, Brenton E. Glassell

Theses and Dissertations (ETD)

Introduction: An ongoing debate exists in orthodontics about the amount of condylefossa remodeling and growth seen in Class II patients using functional appliance therapy. Some clinicians and researchers have found that that the use of functional appliances increases the amount of condylar growth and subsequent Class II skeletal correction; others believe that the mandible has a preset amount of growth and that conventional orthodontics will result in a similar amount of condylar growth to functional appliance therapy. Purpose: The aim of this study was to compare condylar remodeling in functional appliance treatment using the mandibular anterior repositioning appliance (MARA) to …

Effects Of Noise On Cognitive Function During Dual Tasks Across Normally Aging Adults, Jennine Harvey

Theses and Dissertations (ETD)

This study expands upon methods used to investigate cognition and speech perception which have been limited by lack of (a) pre-screening of cognitive function in participants, (b) reporting visual or auditory accuracy and reaction time measures across experimental conditions that examine reaction times, and (c) comprehensive test battery that includes performance across multiple levels of dual task paradigms (DTPs). This study aims to examine group performance on dual tasks (DT) increasing in cognitive (task difficulty) and perceptual load (noise) with age. Participants were divided into two groups based upon age. Group 1 consisted of 14 listeners (Female=11) who were 40-59 …

Virologic Factors Contributing To The Genetic Diversification Of Influenza Viruses Circulating In North American Swine, Thomas Paul Fabrizio Ii

Theses and Dissertations (ETD)

The purpose of this study was to determine mechanisms of reassortment of swine influenza viruses and determine if certain reassortant gene combinations can drive evolution and host adaptation in the context of the triple reassortant internal gene (TRIG) cassette. The TRIG contains a unique combination of a human polymerase basic 1 (PB1) gene with avian polymerase basic 2 (PB2) and polymerase acidic (PA) genes. The remaining internal genes, nucleoprotein (NP), matrix (M), and non-structural (NS) are of swine origin. This differs considerably from classical swine lineage viruses which are drifted variants of the 1918 pandemic with all swine origin genes. …

Functional Study Of Hemogen Knockout Mouse Model, Peng Gao

Theses and Dissertations (ETD)

Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …

In Vitro And In Vivo Characterization Of The Infection Efficiency Of A Modified Retrovirus Envelope Glycoprotein For Targeting Gene Transduction, Robin L. Krueger

Theses and Dissertations (ETD)

Attributes of both the viral glycoprotein and its cellular receptor play key roles in determining the outcome of infection. This body of work endeavors to illustrate how these two components influence the efficiency of virus infection in in vitro and in vivo systems with an emphasis on characterizing the transduction capacity of a novel entry-targeting glycoprotein. In previous work, the Moloney murine leukemia virus (MLV) envelope glycoprotein (Env) was modified to generate the Sst-RBS glycoprotein. This glycoprotein was created by replacing the wild type (WT) receptor binding site (RBS), located on the surface subunit (SU) of the Env, with the …

Bone Properties Of Recombinant Inbred Line - Bxd Mouse, Yueying Angela Zhang

Theses and Dissertations (ETD)

Osteoporosis is identified by reduced bone mass, decreased bone quality and altered bone micro-architecture. These traits are quantitative and also highly regulated by genetic and environmental factors. As a powerful tool for collaborative analysis of quantitative traits and gene function, BXD recombinant inbred (RI) lines mice have been used to identify genetic effects for bone density.

For the first time, we investigated the bone properties of BXD RI mice by analyzing femur and tibia and compared their phenotypes of different compartments. In this study, microcomputed tomography (µCT) provided an accurate measurement on characterizing bone quality and bone architecture ex-vivo; three-point …