Medicine and Health Sciences Commons^™

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 …

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 …

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.

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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. …

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 …