Medicine and Health Sciences Commons^™

Focal Adhesion Kinase, A Major Regulator Of Oligodendrocyte Morphological Maturation And Myelination, Audrey Lafrenaye

Theses and Dissertations

The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system. During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the myelin sheath. However, the exact regulatory circuits involved in the signaling events that occur between the ECM and oligodendrocytes are currently not fully understood. Therefore, in this dissertation we investigated the role of a known integrator of cell-ECM signaling, namely, focal adhesion kinase (FAK), …

Exploring The Mechanism Of Alginate Acetylation In Pseudomonas Aeruginosa, Janice Paletta

Theses and Dissertations

The opportunistic pathogen P. aeruginosa is the leading cause of morbidity and mortality in cystic fibrosis patients. During chronic infection of the cystic fibrosis lung, P. aeruginosa undergoes conversion to a mucoid phenotype, constitutively producing the exopolysaccharide alginate, composed of the uronic acids D-mannuronate and L-guluronate. This alginate production contributes significantly to virulence in the cystic fibrosis lung. Evidence suggests that the acetylation state of the mannuronate component of the alginate influences the ability of components of the immune system to phagocytose the organism. To garner new and relevant information regarding the mechanism of alginate acetylation in Pseudomonas aeruginosa, a …

A Survey Of The Usage Of Topical Anesthesia Among Dentist, Lawrence Shults

Theses and Dissertations

Purpose: The purposes of this study were four-fold: 1) to determine the types and effectiveness of various topical anesthetics being used among dentists currently treating children, 2) to determine the types of procedures for which topical anesthetics are being used among children, 3) to understand the awareness and use of a relatively newer compounded topical gel Oraqix (Dentsply Caulk) among children, 4) to understand the adverse reactions to topical anesthesia that are seen among children. Methods: A cross sectional survey was designed, regarding the type, procedural use, effectiveness, and adverse reactions noted among children to various topical anesthetics. The survey …

Mechanisms Associated With Aging And Age-Related Disease In Drosophila, Melanie Jones

Theses and Dissertations

Aging is an intrinsic process that is independent of obvious disease. In contrast to normal aging, age-related diseases are conditions that typically manifest at advanced ages, are associated with explicit pathology and cause disability and premature death. We used Drosophila as a model to investigate the molecular-genetic mechanisms associated with aging and age-related disease. Age-related locomotor impairment (ARLI) is a serious condition for the elderly and greatly impacts their quality of life. Toward identifying genes and mechanisms that influence ARLI, we performed a forward genetic screen using Drosophila mutants. This screen identified a loss of function mutant in PDK1, a …

Oral Health Status Of Children In The Child Health Investment Partnership (Chip) Program, Latrice Foster

Theses and Dissertations

Purpose: The purpose of this study is to describe children’s dental disease status and functional health literacy of families enrolled in the Child Health Investment Partnership program in Roanoke Valley. Methods: This was a prospective cohort study of children (n=166) enrolled in the Child Health Investment Partnership of Roanoke Valley, Virginia (CHIP). The parents of the 166 children completed the Life Skills Progression (LSP) survey at enrollment between September 2004 and September 2008 to assess their functional health literacy levels. Their LSP scores were used to determine their subsequent health care literacy (HCL), personal health literacy (PHL), and dental-child utilization …

Identification Of Loci Contributing To The Smith-Magenis Syndrome-Like Phenotype And Molecular Evaluation Of The Retinoic Acid Induced 1 Gene, Stephen Williams

Theses and Dissertations

Smith-Magenis syndrome (SMS) is a multiple congenital abnormalities intellectual disability syndrome that results from a deletion of chromosome 17p11.2 or mutation of the retinoic acid inducted one gene (RAI1). SMS is characterized by a multitude of phenotypic features including craniofacial defects, short stature, obesity, intellectual disability, self-abusive behavior, sleep disturbance and behavioral abnormalities. Interestingly, although SMS is a clearly defined syndrome with a known molecular change at its foundation, ~40% of all candidate cases sent to the Elsea lab for evaluation do not have a mutation or deletion of RAI1. We hypothesize that at least one other locus must be …

Characterization Of Adherence, Cytotoxicity And Biofilm Formation By Gardnerella Vaginalis, Jennifer Patterson

Theses and Dissertations

Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder in women of childbearing age. BV is of major clinical importance due to its ability to significantly affect pregnancy outcome and enhance the transmission and acquisition of HIV. BV is characterized by a dramatic shift in the vaginal microflora; in most BV cases, the predominant bacterial species is Gardnerella vaginalis. It has been demonstrated that G. vaginalis forms an adherent biofilm on the vaginal epithelium of women with BV. Furthemore, evidence suggests that the high rate of recurrence associated with BV is related to incomplete eradication of the biofilm. The …

Characterization Of The Staphylococcus Aureus Immunodominant Surface Antigen B, Isab, Nicole Lawrence

Theses and Dissertations

Staphylococcus aureus is a significant cause of morbidity and mortality world-wide. This opportunistic pathogen is capable of causing several severe diseases that are exacerbated by its diverse and widespread antibiotic resistance profile. Therefore it is necessary to identify novel therapeutic targets to effectively treat S. aureus disease. Lorenz et al first described the Immunodominant Surface Antigen B, IsaB, because it was 1 of 4 unique proteins immunogenic during septicemia and not colonization, suggesting that IsaB may be a virulence factor and a possible novel therapeutic target. Interestingly, IsaB has no homology to proteins of known function and appears to be …

Genetic Variations Of Cyp2b6 Enzyme And The Response To Meperidine In Oral Sedation, Heath Whitfield

Theses and Dissertations

Purpose: The purpose of this study was to determine the relationship of the CYP2B6 genotype to the clinical response to meperidine in pediatric dental patients. Methods: Forty-nine patients, ASA I/ II, 41–101 months old, received an oral sedative regimen containing meperidine for dental treatment. The North Carolina Behavior Rating Scale (NCBRS) and Overall Effectiveness of Sedation Scale (OESS) were used to assess their behavior and sedation outcome. Saliva DNA samples were genotyped by PCR-RFLP. Results: We found the following genotype distributions: homozygous wild-type 1*1 (n = 19, 39%), heterozygous 1*6 (n = 25, 51%), and homozygous variant 6*6 (n = …

The Effects Of Motivational Interviewing In Pregnancy On Knowledge And Retention Of Infant Oral Health Information, Andrew Zima

Theses and Dissertations

THE EFFECTS OF MOTIVATIONAL INTERVIEWING IN PREGNANCY ON KNOWLEDGE AND RETENTION OF INFANT ORAL HEALTH INFORMATION By Andrew D. Zima, Jr., B.S., M.S., D.D.S. A thesis submitted in partial fulfillment of the requirements for the degree of Masters of Science in Dentistry at Virginia Commonwealth University. Virginia Commonwealth University, 2010 Major Director: Tegwyn H. Brickhouse, D.D.S., Ph.D Associate Professor, Department of Pediatric Dentistry Purpose: The purpose was to examine the effect of motivational counseling in pregnancy with readiness and acceptance of infant oral health information. Methods: The study used a prospective cohort design to examine the effect of prenatal education …

Differential Roles Of The Two Major Endocannabinoid Hydrolyzing Enzymes In Cannabinoid Receptor Tolerance And Somatic Withdrawal, Joel Schlosburg

Theses and Dissertations

While there is currently active debate over possible therapeutic applications of marijuana and cannabis-based compounds, consistently their primary drawbacks have been the psychoactive properties, dependence, and abuse potential. Prolonged administration of ∆9-tetrahydrocannabinol (THC), the primary psychoactive constituent in marijuana, demonstrates both tolerance and physical withdrawal in both preclinical and clinical studies. Repeated THC administration also produces CB1 receptor adaptations in the form of reduced activation of receptors, along with a downregulation of membrane surface receptors, in many brain regions involved in THC-associated behaviors. The increased need for drug to maintain therapeutic effects, and a withdrawal syndrome following discontinuation of use, …

Proteasome-Dependent Entry Of Herpes Simplex Virus, Mark Delboy

Theses and Dissertations

Herpes simplex virus entry into cells is a multistep process that engages the host cell machinery. The proteasome is a large, ATP-dependent, multisubunit protease that plays a critical role in the maintenance of cell homeostasis. A battery of assays were used to demonstrate that proteasome inhibitors blocked an early step in herpes simplex virus entry that occurred after capsid penetration into the cytosol but prior to capsid arrival at the nuclear periphery. Proteasome-dependent viral entry was not reliant on host or viral protein synthesis. MG132, a peptide aldehyde that competitively inhibits the degradative activity of the proteasome, had a reversible …

Sensitivity Analysis – The Effects Of Glasgow Outcome Scale Misclassification On Traumatic Brain Injury Clinical Trials, Juan Lu

Theses and Dissertations

I. EFFECTS OF GLASGOW OUTCOME SCALE MISCLASSIFICATION ON TRAUMATIC BRAIN INJURY CLINICAL TRIALS The Glasgow Outcome Scale (GOS) is the primary endpoint for efficacy analysis of clinical trials in traumatic brain injury (TBI). Accurate and consistent assessment of outcome after TBI is essential to the evaluation of treatment results, particularly in the context of multicenter studies and trials. The inconsistent measurement or interobserver variation on GOS outcome, or for that matter, on any outcome scales, may adversely affect the sensitivity to detect treatment effects in clinical trial. The objective of this study is to examine effects of nondifferential misclassification of …

The Influence Of Organizational Culture On The Existence Of Systems Employed To Improve Quality Of Care In Medical Office Practices, Donna Dugan

Theses and Dissertations

A frequently cited reason for poor quality of care in the ambulatory care setting is the lack of optimally designed systems to address care for those with preventive or chronic care needs. Organizational theory suggests that culture plays an important role in the shaping of these types of programs. The purpose of this cross-sectional study is to understand through descriptive and regression analysis of secondary data, the relationship between the existence of cultural characteristics such as collegiality, quality emphasis and autonomy, and the systems employed to improve quality of care within primary care practices. The study uses an integrated theoretical …

Modulation Of Cocaine-Like Behavioural Activity By Serotonin Uptake Inhibition Relative To The Effects Of The Novel And Selective Dopamine Transporter Inhibitor, D-84, Angela Batman

Theses and Dissertations

Cocaine dependence is a major health concern worldwide, but despite this high rate of abuse there are currently no approved therapies for cocaine dependence. Replacement pharmacotherapies are one possible approach for treating cocaine dependence, and identification of such therapeutics for cocaine abuse is the long-term goal of this research. Cocaine binds to, and inhibits uptake at the dopamine (DAT), serotonergic (SERT) and noradrenaline (NET) uptake transporters, but studies have shown that cocaine produces its strong behavioural and positive reinforcing effects through inhibition of the DAT. To this end a great number of diverse, non-selective DAT-inhibiting compounds have been investigated as …

The Clinical Utility Of Molecular Typing Of Multiply-Resistant Pseudomonas Aeruginosa In Children With Cystic Fibrosis, Ruth Ann Luna

Theses and Dissertations

Chronic infection with P. aeruginosa is expected in patients with cystic fibrosis (CF), but the ability to delay, prevent, or better manage infection with multiply-resistant P. aeruginosa (MRPA) can potentially increase quality of life and extend survival. The Texas Children’s Hospital CF Care Center has identified an endemic MRPA strain (dominant clone), and this study aimed to identify risk factors for acquisition of the clone as well as determine differences in patient outcome associated with subsequent infection with the clone. The study included 71 patients with CF with documented MRPA infection. Designation of patients as members of the dominant clone …

Perifosine, A Novel Akt Inhibitor Induces Apoptosis, Cell Cycle Arrest And Has A Chemo-Sensitizing Effect In Medulloblastoma Cell Lines, Anil Kumar

Theses and Dissertations

Primary central nervous system (CNS) tumors are the most common solid tumors found in children. While surgery and radiotherapy still remain the standard treatment modalities in pediatric brain tumors, chemotherapy also has an important part in the management of these tumors. However, most of the available chemotherapeutic drugs have suboptimal effectiveness. Deregulation of various pro-apoptotic and anti-apoptotic pathways has been cited as a major mechanism underlying this drug resistance. The role of various serine threonine kinases, including Akt kinases, in promoting drug resistance is being extensively studied in various cancers. A complete understanding of the molecular mechanisms that underlie drug …

The Influences Of Matrix Metalloproteinase-1 Expression On Glioblastoma Pathology, Nicholas Pullen

Theses and Dissertations

Glioblastoma multiforme (GBM) is an aggressive central nervous system (CNS) cancer characterized by enhanced tumor cell motility, pernicious invasion into the normal brain, extensive tumor-induced angiogenesis, and adaptive resistance to current therapeutic paradigms. One of the difficulties associated with GBM is the ability of the tumor cells to infiltrate normal CNS tissue. Neurosurgeons can remove the primary tumor mass, but peripheral cells that are inaccessible will ultimately result in a secondary lesion that can lead to death. The matrix metalloproteinases (MMP) are well known for their abilities to facilitate processes of cellular motility and invasion through their clearance of extracellular …

Recapitulating Osteoblastogenesis With Electrospun Fibrinogen Nanofibers And Adipose Stem Cells And Electrospinning Adipose Tissue-Derived Basement Membrane, Michael Francis

Theses and Dissertations

To repair, replace, or regenerate damaged or diseased tissue has been a long-standing, albeit elusive, goal in medical research. Here, we characterize patient-derivable mesenchymal stem cell types, termed adipose-derived stem cells (ASCs). These cells, which can be derived from liposuction fat and lipoaspirate saline, are sources for patient-derivable extracellular matrix (ECM), fibrinogen (Fg) and adipose tissue extracellular matrix, and may prove useful for synthesizing new bone tissue analogues in vitro. Traditionally and rapidly isolated ASCs were thoroughly characterized as multipotent, having osteogenic, adipogenic, and chondrogenic differentiation potential, and they exhibited comparable proliferative lifespans. These ASCs also shared an indistinguishable immunophenotype …

Regulation Of Telomerase Expression In Stem Cell Reprogramming, Patrick Sachs

Theses and Dissertations

A great need exists for an abundant, easily accessible source of patient-specific cells that will function for use in regenerative medicine. One promising source is the adult stem cell derived from adipose tissue (ASCs). Isolated from waste lipoaspiration, these cells could serve as a readily available source for the regeneration of damaged tissues. To further define the biology of ASCs, we have isolated multiple cell strains from different adipose tissue sources, indicating wide-spread distribution in the body. We find that a widely used set of cell surface markers fail to distinguish ASCs from normal fibroblasts. However, our ASC isolations are …

The Effect Of Implicit Stereotypes On The Physical Performance In Older Adults, Gabriele R. Moriello

Theses and Dissertations

The purpose of this study was to explore how stereotypes affect physical performance in older adults. A multigroup pretest post test design was utilized to determine whether implicit activation of positive or negative stereotypes has an effect on physical performance. Ninety six community dwelling older adults 65 years of age or older were included in the sample. Participants were randomly assigned to one of three groups: exposure to positive stereotypes of aging, exposure to negative stereotypes of aging, or a control condition. In order to simulate how older adults are exposed to stereotypes in real world settings, participants were primed …

Schizophrenia Gene Networks And Pathways And Their Applications For Novel Candidate Gene Selection, Jingchun Sun, Peilin Jia, Ayman H. Fanous, Edwin Van Den Oord, Xiangning Chen, Brien P. Riley, Richard L. Amdur, Kenneth S. Kendler, Zhongming Zhao

Psychiatry Publications

Background

Schizophrenia (SZ) is a heritable, complex mental disorder. We have seen limited success in finding causal genes for schizophrenia from numerous conventional studies. Protein interaction network and pathway-based analysis may provide us an alternative and effective approach to investigating the molecular mechanisms of schizophrenia.

Methodology/Principal Findings

We selected a list of schizophrenia candidate genes (SZGenes) using a multi-dimensional evidence-based approach. The global network properties of proteins encoded by these SZGenes were explored in the context of the human protein interactome while local network properties were investigated by comparing SZ-specific and cancer-specific networks that were extracted from the human interactome. …

Metabolic Oscillations In Pancreatic Islets Depend On The Intracellular Ca2+ Level But Not Ca2+ Oscillations, Matthew J. Merrins, Bernard Fendler, Min Zhang, Arthur Sherman, Richard Bertram, Leslie S. Satin

Pharmacology and Toxicology Publications

Abstract

Plasma insulin is pulsatile and reflects oscillatory insulin secretion from pancreatic islets. Although both islet Ca²⁺ and metabolism oscillate, there is disagreement over their interrelationship, and whether they can be dissociated. In some models of islet oscillations, Ca²⁺ must oscillate for metabolic oscillations to occur, whereas in others metabolic oscillations can occur without Ca²⁺ oscillations. We used NAD(P)H fluorescence to assay oscillatory metabolism in mouse islets stimulated by 11.1 mM glucose. After abolishing Ca²⁺ oscillations with 200 μM diazoxide, we observed that oscillations in NAD(P)H persisted in 34% of islets (n = 101). …

A Transposon In Comt Generates Mrna Variants And Causes Widespread Expression And Behavioral Differences Among Mice, Zhengsheng Li, Megan K. Mulligan, Xusheng Wang, Michael F. Miles, Lu Lu, Robert W. Williams

Pharmacology and Toxicology Publications

Background

Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits.

Methodology/Principal Findings

We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 …

Ethnicity And Health Disparities In Alcohol Research, Karen G. Chartier, Raul Caetano

Social Work Publications

Recent advances in alcohol research continue to build our understanding of alcohol consumption and related consequences for U.S. ethnic minority groups. National surveys show variations across ethnicities in drinking, alcohol use disorders, alcohol problems, and treatment use. Higher rates of high-risk drinking among ethnic minorities are reported for Native Americans and Hispanics, although within-ethnic group differences (e.g., gender, age-group, and other subpopulations) also are evident for ethnicities. Whites and Native Americans have a greater risk for alcohol use disorders relative to other ethnic groups. However, once alcohol dependence occurs, Blacks and Hispanics experience higher rates than Whites of recurrent or …

Pooled Protein Immunization For Identification Of Cell Surface Antigens In Streptococcus Sanguinis, Xiuchun Ge, Todd Kitten, Cindy L. Munro, Daniel H. Conrad, Ping Xu

Philips Institute for Oral Health Research Publications

Background

Available bacterial genomes provide opportunities for screening vaccines by reverse vaccinology. Efficient identification of surface antigens is required to reduce time and animal cost in this technology. We developed an approach to identify surface antigens rapidly inStreptococcus sanguinis, a common infective endocarditis causative species.

Methods and Findings

We applied bioinformatics for antigen prediction and pooled antigens for immunization. Forty-seven surface-exposed proteins including 28 lipoproteins and 19 cell wall-anchored proteins were chosen based on computer algorithms and comparative genomic analyses. Eight proteins among these candidates and 2 other proteins were pooled together to immunize rabbits. The antiserum reacted …

Transcriptomic Analysis Of The Venom Gland Of The Red-Headed Krait (Bungarus Flaviceps) Using Expressed Sequence Tags, Ang Swee Siang, Robin Doley, Freek J. Vonk, R. Manjunatha Kini

Biochemistry and Molecular Biology Publications

Background

The Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genus Bungarus have been well characterized, a detailed compositional analysis of B. flaviceps is currently lacking.

Results

Here, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of a B. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of β-bungarotoxin), phospholipase A …

Increased Interleukin-6 Activity Associated With Painful Chemotherapy-Induced Peripheral Neuropathy In Women After Breast Cancer Treatment, Angela R. Starkweather

School of Nursing Publications

Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, ) or did not experience CIPN symptoms (Comparison group, ). CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R) compared to women without CIPN symptoms ( for both). In addition, soluble gp130, which blocks the IL-6/sIL-6R …

Rifaximin Treatment In Hepatic Encephalopathy, Nathan M. Bass, Kevin D. Mullen, Arun J. Sanyal, Fred Poordad, Guy Neff, Carroll B. Leevy, Samuel Sigal, Muhammad Y. Sheikh, Kimberly Beavers, Todd Frederick, Lewis Teperman, Donald Hillebrand, Shirley Huang, Kunal Merchant, Audrey Shaw, Enoch Bortey, William P. Forbes

Internal Medicine Publications

Background

Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established.

Methods

In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode …

Pioglitazone, Vitamin E, Or Placebo For Nonalcoholic Steatohepatitis, Arun J. Sanyal, Naga Chalasani, Kris V. Kowdley, Arthur Mccollough, Anna Mae Diehl, Nathan M. Bass, Brent A. Neuschwander-Tetri, Joel E. Lavine, James Tonascia, Aynur Unalp, Mark Van Natta, Jeanne Clark, Elizabeth M. Brunt, David E. Kleiner, Jay H. Hoofnagle, Patricia R. Robuck

Internal Medicine Publications

Background

Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease.

Methods

We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary …