Medicine and Health Sciences Commons^™

Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde

All ETDs from UAB

The purpose of this investigation was to determine if 30 days of continuous contact lens wear produces a different ocular inflammatory response compared to 30 days of daily wear of Bausch & Lomb® PureVisionTM silicone hydrogel contact lenses. Eighty-five individuals wore these lenses for 30 days continuously in one eye and daily in the contralateral eye. Relative concentrations of 27 cytokines were measured in tear samples collected from the subjects using cytometric bead-based assays. Clinical tests were also conducted to correlate changes in cytokine levels to changes in clinical profiles. This study contributes to a greater understanding of the impact …

Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya

All ETDs from UAB

Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, …

Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee

All ETDs from UAB

Pharmacogenetics has proven to be an invaluable tool in predicting variability in drug response; however, there are numerous incidences where genetics cannot fully explain interindividual drug variability. Other factors, such as the epigenetic mechanism of DNA methylation, may offer an alternate explanation. Therefore, this dissertation focuses on both genetic and epigenetic regulation in order to gain a better understanding of the molecular basis behind drug response variability. Initial investigations focused on the antineoplastic agent 5-Fluorouracil (5-FU), which can produce severe toxicity in patients with deficiency in dihydropyrimidine dehydrogenase (DPD). Genotypic studies have identified >32 sequence variants in the DPYD gene; …

Parental Attitudes Of Human Papillomavirus Vaccination Of Adolescent Girls In Alabama, Allison G. Litton

All ETDs from UAB

Human papillomavirus is the most common sexually transmitted infection in the United States. This study examined racial and socio-demographic differences between African Americans and non-Hispanic Whites in Alabama regarding HPV vaccine acceptability. This cross sectional study employed a statewide survey of Alabama parents using a random digit dial phone method conducted through the Survey Research Unit at UAB. Participants were female caregivers of adolescent girls between the ages of 10-14 years. The final sample size was 403. Analyses included descriptive statistics, cross tabulations and odds ratios to assess race/ethnicity and other subgroup differences and logistic regression of intention to vaccinate …

Regulation Of Vh Replacement In Human Immature B Cells By B Cell Receptor (Bcr) - Mediated Signaling, Jing Liu

All ETDs from UAB

VH replacement occurs through RAG-mediated secondary recombination to change unwanted IgH genes. In this dissertation, I focused on studying the molecular mechanism that regulates VH replacement in human immature B cells. In part I, our results show that VH replacement is regulated by B cell antigen receptor (BCR) mediated signaling. Using the human EU12 mHC+ cells as an experimental model system, crosslinking BCR with F(ab')2 anti-IgM antibodies results in BCR internalization, cell proliferation arrest, and induction of VH replacement. Pretreatment of human EU12 mHC+ cells with the protein tyrosine kinase inhibitor Genistein, Syk kinase inhibitors, and a Src kinase inhibitor …

Counterregulatory Roles Of Transforming Growth Factor (Tgf)-Beta And Atrial Natriuretic Peptide (Anp) In Pressure Overload-Induced Cardiac Remodeling And Fibrosis, Jason Anthony Lucas

All ETDs from UAB

Pressure overload stress (eg. hypertension or aortic stenosis) results in excessive cardiac fibrosis, changes in left ventricular (LV) geometry, and disruption of LV contractility, ultimately leading to heart failure. We hypothesize that transforming growth factor-beta (TGF-beta), a pro fibrogenic factor, and atrial natriuretic peptide (ANP), an anti fibrogenic factor, interact directly in a counterregulatory manner to balance the production of extracellular matrix (ECM) under pressure overload induced cardiac stress or hypoxia-induced pulmonary vascular adaptation. In this report, we examine structural and functional responses of the intact heart to pressure overload stress in vivo. We then utilize isolated rat pulmonary artery …

Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther

All ETDs from UAB

Maintenance of immune homeostasis involves a balance between T cell effector responses to antigen stimulus and reciprocal downregulation of this response through peripheral tolerance mechanisms. Upon exposure to pathogen, cytokine production and signaling serve to tightly coordinate cell-mediated clearance of antigen followed by contraction of the immune response. Interkeukin-2 (IL-2) is a type I family cytokine critical for expansion of activated T cells in vitro and enhancement of T cell memory responses in vivo. Deficiency of IL-2 in vivo also revealed a critical role for IL-2 in immune tolerance through the maintenance of T regulatory cell populations (Treg) in peripheral …

The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud

All ETDs from UAB

An understanding of the molecular mechanisms involved in the generation of protective antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design. The heavy chain third complementarity-determining region (HCDR3) of an antibody molecule is at the center of its antigen-binding site and plays a determinative role in antigen recognition. The goal of this dissertation was to investigate the role of HCDR3 diversity and composition on the antibody response to the polysaccharide α 1→3 Dextran (DEX). In the first study, we investigated the role of TdT, a DNA polymerase that plays a major role in generating …

Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar

All ETDs from UAB

Na-Coupled Bicarbonate Transporters (NCBTs) are members of the bicarbonate transporter superfamily that play important roles in regulating intracellular pH (pHi) and extracellular pH (pHo) in the central nervous system. Electrogenic Na/bicarbonate Cotransporter 1 (NBCe1) is an NCBT that is expressed in different mammalian tissues including the brain. NBCe1 has three splice variants - NBCe1-A, -B and -C - that differ in the amino and carboxy termini. We have first performed a systematic characterization of the localization profiles of the three NBCe1 splice variants at mRNA and protein levels in rat brain. In these studies, we have used anti-sense probes and …

Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli

All ETDs from UAB

Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the …

The Distinction Between First And Higher-Order Pregnancies Among Low-Income Adolescents, Ann Elizabeth Montgomery

All ETDs from UAB

Rapid repeat pregnancy is defined as having a subsequent pregnancy within 2 years of the first. In the United States, approximately 30-50% of adolescent mothers will experience a repeat pregnancy within 12 to 24 months of the first birth (Sangalang, Barth, & Painter, 2006; Coard, Nitz, & Felice, 2000). The negative implications of adolescents having a first birth--most notably in the areas of "health, career, and economic conditions" (Khalili, 2005, p. 19)--are compounded when a second pregnancy occurs (Key, Barbosa, & Owens, 2001). This exploratory study addressed one of the primary gaps in the literature related to rapid repeat adolescent …

Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros

All ETDs from UAB

Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution of …

Fmic Annual Report 2009​ | English, French Medical Institute For Mothers And Children

French Medical Institute for Mothers and Children (FMIC) Archives

No abstract provided.

The Antecedents And Consequences Of The Niche Approach To Healthcare Delivery, Lejon Poole

All ETDs from UAB

ABSTRACT OBJECTIVE: Niche hospitals represent a growing segment in the health care industry. A niche strategy is an approach that focuses on a narrow market segment that its resources and capabilities can exploit (Porter, 1980; Powers and Khan, 2004). The purpose of the proposed study was to provide an understanding of the antecedents and consequences of the niche approach to healthcare delivery. The interaction of the niche strategy and the physician-owner as a unique bundle of resources was also examined. The subsequent model tested the relationships among generic strategies, market effects, firm effects, and financial performance. RESEARCH DESIGN AND METHODS: …

Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle

All ETDs from UAB

Cystic fibrosis (CF) is a lethal genetic disorder leading to pulmonary decline and premature death. The gene responsible for CF, the cystic fibrosis transmembrane conductance regulator (CFTR), serves as a chloride and bicarbonate channel situated at the apical cell surface of epithelia. The discovery of small molecules that augment channel gating of mutant CFTR (so-called `potentiators') represents a major theme of CF research, and offers hope for new therapeutic interventions. High-throughput screening (HTS) provides a means to test millions of agents in an unbiased manner for CFTR potentiating properties. New agents identified by HTS have undergone extensive pre-clinical and clinical …

The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes

All ETDs from UAB

Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because …

Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis

All ETDs from UAB

Neuroinflammation and Fragile X syndrome (FXS) are two particularly devastating neurologic conditions for which no adequate treatment exists and much is still unknown about the underlying cellular and molecular processes. Neuroinflammation contributes to the pathogenesis of many neurologic and psychiatric disorders, thus treatment of the underlying inflammation has broad implications. FXS is the most common cause of inherited intellectual and developmental delay and one of the few known genetic causes of autism. Neuroinflammation and FXS have potential links with glycogen synthase kinase-3 (GSK3) and its inhibitor, lithium. Therefore, the overall goal of this research was to examine the role of …

Involvement Of Reactive Oxygen Species In The Acute Development Of Insulin Resistance Following Trauma And Hemorrhage, Lidong Zhai

All ETDs from UAB

Hyperglycemia develops in the intensive care unit in many patients following injury, infection and critical illness. However, little is known about the mechanism of acute development of insulin resistance that causes this hyperglycemia, even though reducing or normalizing the elevated glucose levels has become a major therapeutic target in many ICUs. Using rodent models of injury, acute hepatic insulin resistance occurs within minutes and continues for at least several hours even following fluid resuscitation. We have previously reported that TNF-alpha; is necessary for the hepatic insulin resistance in the rat following resuscitation. However, whether TNF-alpha; plays a role in the …

Maintaining Healthy Eating Behaviors With Women After A Weight Management Program: A Grounded Theory Approach, Christie Zunker

All ETDs from UAB

The purpose of this qualitative study was to explore the process of how women maintain their weight and continue healthy eating behaviors after completing a weight management program, which emphasized low-energy density foods. This is important since many women regain weight after participating in weight management programs. Theoretical sampling strategies guided participant recruitment. Inclusion criteria were: self-reported African American or Caucasian women aged 30 and older who lost > 5% of their body weight during their participation in the EatRight weight management program at least one year ago or longer. Height and weight was measured. Participants that remained > 5% below their …

Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck

All ETDs from UAB

Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …

Diffusion Pathways Through The Outer Membrane Of Mycobacteria, Olga Danilchanka

All ETDs from UAB

The extraordinary capacity of Mycobacterium tuberculosis (Mtb) to adapt to environmental changes during infection contributes to its success as a pathogen. While the unique outer membrane (OM) of mycobacteria functions as a permeability barrier for toxic molecules, uptake of nutrients is required to sustain viability of Mtb. Whereas hydrophobic molecules can diffuse through membranes, uptake of small hydrophilic compounds is mediated by water-filled channels, porins. For example, Msp-like porins of M. smegmatis (Ms) were shown to be required for uptake of hydrophilic beta-lactam antibiotics, which are also known to diffuse through porins in gram-negative bacteria. Because the structure of the …

Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton

All ETDs from UAB

Three reasons to review accumulating data in clinical trials include: ethical issues, financial concerns and administrative concerns. Interim analysis is a good way to monitor accumulating data in clinical trials. Interim analysis allows for the possibility that a study may be terminated early; that is, if the currently observed data convincingly favor the null or the alternative hypothesis then the study ends early. In addition, many clinical trials are conducted to compare a treatment group to a standard group on multiple endpoints. Combining interim analyses with multiple endpoints allows for more information to be provided from the trial than either …

Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder

All ETDs from UAB

Members of the Fc receptor-like (FCRL) family are cell-surface proteins with ancient conservation, distinct lymphocyte expression patterns, and tyrosine-based signaling capa-bilities that imply a fundamental role for them in modulating immune responses. Though they share many features with the Fc receptors (FCR) for IgG and IgE, FCRLs have not been found to bind immunoglobulin. In these studies, we sought to characterize the cellu-lar expression pattern, binding partner, and function of a recently identified FCRL family member, human FCRL6. By developing specific monoclonal antibodies (mAbs) we determined that FCRL6 is dis-tinctly expressed by cytotoxic lymphocytes, namely NK cells, CD8+ T cells, …

Shunt Failure In Children With Hydrocephalus: Impact Of Sociodemographic Predictors On Time To Medical Evaluation For Shunt Failure And The Economic Burden Associated With Shunt Failure, Chevis Nacole Shannon

All ETDs from UAB

Ventriculo-peritoneal shunts continue to be the standard surgical procedure for treating children diagnosed with hydrocephalus, regardless of etiology. The failure of these shunts can cause acute medical problems for the child requiring immediate medical care. It is known that hydrocephalus directly impacts a child's health status, educational abilities, developmental opportunities and emotional well being. An important gap in the current literature is the examination in a homogenous patient population of the impact of sociodemographic factors on the management of shunt failure and the economic burden on the family. The objective of this dissertation research study was to better understand shunt …

Parenting Behaviors And Adolescent Obesity, Kathy Lynne Newman

All ETDs from UAB

PARENTING BEHAVIORS AND EARLY ADOLESCENT OBESITY KATHY NEWMAN SCHOOL OF NURSING ABSTRACT The incidence of adolescent obesity has more than tripled in the past 30 years with the rate increasing from 5% to 17%. Approximately 17.0% of adolescents in the United States are obese with 4% being categorized as morbidly obese. Obesity disproportionately affects minority adolescent groups. Previous studies have examined relationships between parental behaviors and adolescent health risk behaviors, but few studies have compared these relationships across different racial/ethnic groups. The purpose of this study was to examine the relationships between parental nurturance, parental involvement, family cohesion, and early …

Injury Prevention For High School Female Cross-Country Athletes, Jason Brumitt

Faculty Publications - College of Physical Therapy

Female athletes are at greater risk for certain injuries and conditions than are their male counterparts due to unique anatomic, physiologic, and psychological factors.1-4 Injury to the female high school student athlete may significantly impact her physical and mental well-being, disrupt the athlete’s family life with medical appointments, and affect her team’s success.5 Athletic trainers and therapists (ATs) should consider these injury risk factors when developing injury prevention programs for female student athletes.

Rationale And Design Of A Trial Of Angiotensin-Converting Enzyme Inhibition In Infants With Single Ventricle., Daphne T. Hsu, Seema Mital, Chitra Ravishankar, Renee Margossian, Jennifer S. Li, Lynn A. Sleeper, Richard V. Williams, Jami C. Levine, Brian W. Mccrindle, Andrew M. Atz, Darlene Servedio, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

METHODS: The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

RESULTS: A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to …

Review Of Cancer Among Indigenous Peoples, Sasha Stumpers, Neil Thomson

Research outputs pre 2011

This review provides a comprehensive synthesis of population-level cancer statistics and other key information for Aboriginal and Torres Strait Islander people alongside comparative figures for non-Indigenous Australians. It includes general information on the extent of cancer, including: incidence, hospitalisation and mortality. The review also provides information on the extent of cancer for specific cancers: lung, cervical, breast, prostate, liver, pancreatic and colorectal (bowel). Finally, the review discusses issues surrounding Aboriginal and Torres Strait Islander people’s use of cancer services.

Prolonged Monitoring After Decelerations On Outpatient Non-Stress Tests: How Long Is Enough?, P. Koduri, Md, M. Giraldo, Md, V. Berghella, Md, S. P. Chauhan, Md

Department of Obstetrics and Gynecology Faculty Papers

Objective: To determine the appropriate duration of prolonged monitoring following decelerations noted on outpatient non-stress test (NST).

Conclusion: Prolonged monitoring beyond 120 min is not associated with increased rate of delivery secondary to NRFS or worse neonatal outcome measured by the 5 minute Apgar score. Monitoring after a deceleration on outpatient NST may be limited to less than 120 minutes. Larger studies are needed to confirm this finding.

Does 17 Alpha-Hydroxyprogesterone Caproate Decrease The Rate Of Preterm Birth In Women With An Ultrasound-Indicated Cerclage?, T. J. Rafael, D. Mackeen, V. Berghella

Department of Obstetrics and Gynecology Faculty Papers

Objective: To estimate whether the use of 17 alpha-hydroxyprogesterone caproate (17P) in women with an ultrasound-indicated cerclage (UIC) reduces the rate of preterm birth (PTB).

Conclusions: Among women with a prior spontaneous PTB and current UIC for CL<25mm, 17P did not reduce the rate of PTB <35 weeks.