Medical Sciences Commons^™

Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey

All ETDs from UAB

Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and currently, no medical therapy exists to treat this condition. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests mitochondrially- produced reactive oxygen species play a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained …

Usp16 And Histone H2a Deubiquitination In Mouse Embryonic Stem Cell Function, Wei Yang

All ETDs from UAB

In eukaryotic cells, genomic DNA is packaged into a chromatin structure by association with histone and non-histone proteins. Posttranslational modifications of histones play important roles in the regulation of chromatin structure and function. Ubiquitination of histone H2A (ubH2A) represents a predominate modification, occurring on ~10% of total cellular H2A. While H2A ubiquitination is primarily conferred by Polycomb Repressive Complex 1 (PRC1), H2A deubiquitination has been attributed to multiple H2A deubiquitinases. Our laboratory previously reported the purification and functional characterization of a H2A-specific deubiquitinase, USP16 (initially named as Ubp-M) in human cells. However, whether USP16 represents a general and important regulator …

Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou

All ETDs from UAB

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678 and rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the ß2 integrin Mac-1. The purpose of this work was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1. Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in …

Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman

All ETDs from UAB

Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …

Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts

All ETDs from UAB

Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control …

Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy

All ETDs from UAB

Despite the body's ability to repair bone fractures under normal circumstances, up to 10% of the 7.9 million fractures suffered in the United States each year do not achieve bony union. Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis are known to work in concert to control many stages of this process, but when one is impaired it leads to failure of bone healing, referred to as a nonunion. Such nonunion fractures often result from critical-size defects that will not completely heal over the natural lifetime of the animal. Based on this …

Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day

All ETDs from UAB

Traumatic brain injury (TBI) affects millions of persons per year, potentially leading to permanent disability or death, and exacts a staggering financial toll. Despite the severity of this public health problem, there are no clinically proven pharmacotherapeutics available that effectively attenuate the secondary neurochemically-mediated damage that follows the initial biomechanical insult. In addition, the heterogeneous nature of TBI and complexity of secondary injury cascades suggest that a polytherapeutic approach could be a powerful strategy with which to simultaneously target more than one deleterious pathway. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of …

Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft

All ETDs from UAB

Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …

Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft

All ETDs from UAB

Type 1 Diabetes (T1D) is defined as the selective immune destruction of insulin producing beta cells within the islet. A new emphasis has been put on the role of the gastrointestinal (GI) tract in T1D; however, there is much more to learn about this relationship. Distinct differences have been observed in the intestinal permeability, barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared to healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are commonly used to models to study T1D in humans. Most murine studies …

Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall

All ETDs from UAB

may be advantageous for increasing seasonal and yearly variability in sex ratios.

The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers

All ETDs from UAB

In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …

Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher

All ETDs from UAB

Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and …

The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher

All ETDs from UAB

temperatures were near pivotal. The second chapter addresses the effects of fluctuating

Protein O-Glcnac Modification In Diabetic Vascular Calcification, Jack Heath

All ETDs from UAB

Vascular calcification is prevalent in patients of diabetes mellitus, which represents an independent risk factor that positively correlated with morbidity and mortality in these patients. Vascular calcification is now recognized as a cell-regulated process of osteogenic differentiation of vascular smooth muscle cells (VSMC) in response to stress, such as hyperglycemia and oxidative stress. Both hyperglycemia and oxidative stress have been shown to induce protein modification by O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation), which is also elevated in diabetes. The present studies aimed to determine the effects of protein O-GlcNAcylation on vascular calcification in diabetes, and uncover the underlying molecular mechanisms. With the …

Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven

All ETDs from UAB

The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition …

Effect Of Protons On The Biology Of Human Gliomas, Avinash Vinayak Honasoge

All ETDs from UAB

Gliomas are the most common and most deadly primary brain cancer. Patient outcome for the most malignant variety, the World Health Organization (WHO) Type IV glioblastoma multiforme (GBM), has stagnated over the last several decades - the best combination treatment of surgical resection, radiation, and chemotherapy results in median survival of just over a year. To escape treatment, GBM must multiply and migrate in a confined brain environment. Both of these aspects of tumor cell invasion rely on the cell's ability to volume regulate; cell division involves a stage called "pre-mitotic condensation" in which the cells shrink immediately prior to …

Copper Homeostasis In Mycobacteria, Jennifer L. Rowland

All ETDs from UAB

Mycobacterium tuberculosis, the causative agent on tuberculosis in humans, is a globally important pathogen. In 2013, nearly 1.2 million people died from tuberculosis. Drug treatments and effective vaccines are lacking for this pathogen. A better understanding of the basic physiology of M. tuberculosis is required to improve disease outcomes. Upon inhalation into the lungs, M. tuberculosis is taken up by macrophages, in a process called phagocytosis, which normally destroys invading bacteria. As the phagosome inside the macrophage matures, bactericidal mechanisms are activated including: lowering pH, and introducing reactive oxygen and nitrogen species and hydrolytic enzymes to degrade bacterial cell walls. …

Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons

All ETDs from UAB

Rhodopsin is a prototypical G-protein coupled receptor whose biological function has been well worked out, yet little is known about the mechanism by which it is so efficiently transported to the rod outer segment (ROS) after synthesis. If rhodopsin is not efficiently transported to the ROS, rod cells will apoptose leading to cone cell apoptosis as well which results in the blinding disease retinitis pigmentosa. Work has begun to elucidate proteins responsible for transporting rhodopsin to the ROS using Xenopus laevis as a model since the photoreceptors of this amphibian are large and transgenic animals are relatively easy to prepare. …

Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti

All ETDs from UAB

The incidence of new cases of skin cancer, which includes non-melanoma epithelial tumors and melanoma, has increased dramatically over the last few decades. Approximately 75% of all skin cancer-related deaths is due to melanoma, which is one of the most aggressive and difficult cancers to treat. The initiating events and mechanisms that influence melanoma development are not fully known, due in part to a paucity of animal models amenable to identifying new oncogenic mutations, and investigating mechanisms of immunosurveillance. Transgenic mouse models often harbor an activating mutation in a known oncogene in all somatic cells, and its widespread expression from …

Gender Differences In High Sensitivity C - Reactive Protein And Self-Reported Muscle Strengthening Activity Among U.S. Adults, Michael R. Richardson

UNF Graduate Theses and Dissertations

Objectives: We sought to examine the gender differences between C - reactive protein (CRP) and muscle strengthening activity (MSA) in U.S. adults (≥20 years of age)

Background: Elevated levels of CRP have been shown to be associated with an increase in risk of cardiovascular disease (CVD). Studies analyzing the relationship between physical activity (PA) and CRP by gender have produced mixed results.

Methods: The sample (n=9,135) included participants in the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Three categories of reported MSA participation were created: no MSA (referent group), some MSA (≥1 to/wk), and meeting the …

Meta-Analysis Of Herbal Cannabis Therapy For Chronic Pain, Michael J. Seneca

UNF Graduate Theses and Dissertations

Since the first so-called “medical marijuana” legislation was passed in California in 1996, a total of twenty states and the District of Columbia have passed laws permitting limited use of cannabis. Despite the changes in state laws, cannabis remains illegal for any purpose under federal law. Changes in state laws have coincided with a renewed interest in the substance for the treatment of a variety of conditions. There has been a significant increase in published data over the past twenty years examining the efficacy of cannabis as an appetite stimulant, antiemetic agent, and analgesic adjuvant. The purpose of this meta-analysis …

Nonnutritive Sweetener And Weight Management: A Potential Paradox In Modern Dieting, Katharine Mary Wright

UNF Graduate Theses and Dissertations

Obesity is a serious health concern in modern society. One way to reduce caloric intake is with nonnutritive sweeteners (NNS). However, recent research suggests they may be compounding the obesity problem. Nonnutritive sweeteners have been linked to increased body mass in a few studies and may be a barrier to effective weight management for some individuals.

Under the framework of the health belief model, the research question was: Does this pattern of NNS-BMI covariance exist in young adults at the University of North Florida and, if so, are there other dietary or activity differences that might partially explain this relationship? …

Monitoring Brown Fat Metabolic Activity Using Microwave Radiometry: Antenna Design And Frequency Selection, Dario B. Rodrigues, Paul R. Stauffer, Paolo F. Maccarini

Department of Radiation Oncology Faculty Papers

This paper describes the use of microwave radiometry for monitoring brown fat metabolism (mBAT). The radiometric frequency band and receive antenna were optimized for coupling to 2-6 ml BAT depots in the supraclavicular region. Radiometric signal variations induced by higher metabolic activity resulting from a cold stimulus were calculated with electromagnetic and thermal simulations in a segmented computational model of the human neck including BAT. A 2.5 cm dia. log spiral antenna was selected as optimum using a 500 MHz bandwidth and center frequency 2.75 GHz. Results suggest sufficient sensitivity to track subsurface temperature variations during long term mBAT monitoring …

The Impact Of Implementing A Sudden Infant Death Syndrome Education Package In Jordan, Shereen Hamadneh

Theses: Doctorates and Masters

Background: Sudden Infant Death Syndrome (SIDS) is a problem worldwide. In North Jordan, SIDS rate was high as 1.32 per 1,000 live births and contributed 6% to the infant mortality rate (Bataineh, Shawagfeh, & Twalbeh, 2008). However, SIDS risk factors are preventable and can be reduced by improving knowledge and changing relevant behaviours of parents and healthcare providers (American Academy of Pediatrics, 2013; American SIDS Institute, 2011; Bataineh, Hussein Shawagfeh, & Twalbeh, 2008; Bredemeyer, 2004; Grazel, Phalen, & Polomano, 2010b; Moon, Oden, & Grady, 2004; NICHD, 2010). Still educating Jordanians about SIDS has not been a national health policy priority. …

Homebirth In Wa: Why Women Make This Choice, Colleen Ball

Theses: Doctorates and Masters

Background: Homebirths in Western Australia (WA) account for approximately 0.8% of all births. Two consecutive reports from the Perinatal and Infant Mortality Monitoring Committee found increased rates of perinatal mortality in homebirths and recommended a prospective cohort study to assess mortality and morbidity outcomes for women with planned home births in WA. The Homebirth in WA Study, of which this thesis is a component, has been funded by a directed research grant.

Aim: The aim of this study was to explore the specific reasons why women in WA choose homebirth. Research on homebirths is focused on perinatal outcomes and …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

Self-Medication With Antibiotics Among Non-Medical University Students Of Karachi: A Cross-Sectional Study, Syed Jawad Shah, Hamna Ahmad, Rija Binte Rehan, Sidra Najeeb, Mirrah Mumtaz, Muhammad Hashim Jilani, Muhammad Sharoz Rabbani, Muhammad Zakariya Alam, Saba Farooq, M Masood Kadir

Community Health Sciences

Background: The prevalence of self -medication with antibiotics is quite high in developing countries as opposed to developed countries. Antibiotics are often taken erroneously for certain ailments, without having the appropriate knowledge of their use. This carries potential risks for the individual as well as the community, in form of several side effects such as antibiotic resistance. Therefore the prevalence of self-medicated antibiotics in developing countries needs to be studied.Methods: A descriptive cross-sectional study was carried out at six different non-medical universities of Karachi. 431 students were included in the study. Data was collected using self-administered questionnaires and analyzed using …

Effects Of Cpla-2 On The Migration And Proliferation Of Human Vascular Smooth Muscle Cells And The 2-D Migratory Patterns Of Tropomyosin In Femoral And Abdominal Aorta Tissue, Jaimeson Thomas Powell

Theses and Dissertations

Abstract 1: Platelet derived growth factor BB (PDGF BB) has an important influence on smooth muscle cell proliferation in restenosis and atherosclerosis. Our understanding of different signal transduction pathways involved in the response of smooth muscle cells to PDGF BB is potentially significant for understanding and manipulating these processes. Prior studies have demonstrated a crucial activation of cytosolic phospholipase A2 (cPLA2) in smooth muscle cells to PDGF BB with the production of arachidonic acid and prostaglandin E2. In these studies we investigated the role for another PLA2, calcium-independent PLA2 (iPLA2) in comparison to cPLA2 on smooth muscle cell migration and …

The Role Of Microrna In Staphylococcal Enterotoxin B-Induced Inflammation And Acute Lung Injury, Roshni Rao

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a potent activator of the Vβ8+T-cells leading to the proliferation of nearly 30% of the T-cell pool. As a consequence, excessive amounts of cytokine mediators are released leading to extensive tissue damage and sometimes toxic shock and death. Due to the ease with which SEB can be aerosolized anddisseminated, it is considered a biological weapon. In the current study, we investigated the pro-inflammatory effects of SEB in two mouse models of acute inflammatory lung injury. Specifically, while inflammatory cues are known to elicit changes in key transcriptional factors and gene expression, we explored for the …

An Evolutionary Perspective On Infectious And Chronic Disease, John Eberth

Theses and Dissertations

The integration of evolutionary biology with traditional medicine can elucidate novel mechanisms of contemporary disease. Whereas the goal of traditional medicine is to treat and cure the proximate causes, evolutionary biology aims to understand the driving forces behind why humans are susceptible to disease. To form the basis of this hypothesis we postulate that modern man's current genetic information was programmed at a time, and in an environment, that is not relevant to today's human populations. The discordance between these genes of our ancestors and the environment of contemporary humans is thought to be a major reason for the increase …