Medicine and Health Sciences Commons^™

Maternal Gestational Glucose Concentration And Offspring Body Composition, Insulin Sensitivity, And Ss-Cell Function, Nikki C. Bush

All ETDs from UAB

Background: Evidence suggests that intrauterine exposure to elevated glucose concentrations may be a mediating factor in prenatal programming of offspring disease risk. However, studies examining the effects of maternal glucose concentration on measures of body composition, insulin sensitivity, and ß-cell response in prepubertal children are limited. Therefore, the objective of this study was to determine the associations of maternal glucose concentration with children's fat mass, insulin sensitivity, and ß-cell response using robust and physiologic measures. Methods: Participants were 40 children aged 5-10 years. Children's insulin sensitivity index (SI) and measures of basal, static, dynamic, and total ß-cell response were determined …

Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter

All ETDs from UAB

Human papillomaviruses (HPVs) are small, double-stranded deoxyribonucleic acid (DNA) tumor viruses capable of establishing persistent infections in the epithelia. After infecting actively-dividing basal cells, the papillomavirus (PV) genome is main-tained as extrachromosomal nuclear plasmids. It is largely unknown how the viral ge-nome is maintained in actively-dividing cells. Our lab demonstrated that several HPV genotypes appear to employ a distinct strategy to facilitate partitioning of HPV DNA into daughter cells during mitosis. Association of the HPV-11 origin of replication (ori)-binding protein E2 with the mitotic apparatus via cellular adapter proteins is thought to mediate equal partitioning of HPV genomes into daughter …

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …

Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen

All ETDs from UAB

Mammalian antimicrobial peptides, including cathelicidins and defensins, play an important role in host defense via direct antimicrobial activity as well as immune regula-tion. The cathelin-related antimicrobial peptide (mCRAMP) is the only identified mouse cathelicidin and the orthologue of human LL-37. We show that all mouse B cell subsets, including follicular, marginal zone, B1a, and B1b cells, as well as CD4+ and CD8+ T cells produce mCRAMP directly ex vivo. In addition, mCRAMP-deficient B cells produced less IgG1 antibody in vitro in response to CD40L or LPS plus IL-4 when compared to WT B cells. The addition of recombinant mCRAMP at …

Diversity, Commonality, And Stability Of Mutans Streptococci In High Caries Risk Children, Kyounga Cheon

All ETDs from UAB

Mutans streptococci (MS), Streptococcus mutans and Streptococcus sobrinus are associated with the initiation of dental caries in humans. Initially, a single S. mutans genotype has been shown to colonize primary molars soon after eruption. More genotypes can be acquired with age and further dental development. Current methods used to genotype isolates from an individual have not systematically determined the minimum number required to demonstrate an individual's genetic diversity. The purpose of this study was to determine the optimum number of oral isolates of MS (i.e., from plaque samples) to genotype in order to demonstrate diversity. This study also initiated a …

The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark

All ETDs from UAB

Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …

Examining The Association Between Body Mass Index And Weight Related Quality Of Life In Black And White Women, Tiffany Lashaun Cox

All ETDs from UAB

Obesity not only increases risk for morbidity/mortality, but also impacts the quality of life of obese individuals. In the United States, black women have the highest prevalence of obesity of any other group with approximately 80% of black women over age 20 having a body mass index (BMI) ≥ 25 kg/m2. We aimed to examine the association between weight and quality of life in this high risk population and compare it to weight-related quality of life in white women using the Impact of Weight on Quality of Life (IWQOL)-Lite questionnaire. Data for 343 women were analyzed (172 black, 171 white). …

The Effects Of Weight Reduction On Obesity-Related Cancer Biomarkers And In Vitro Cancer Cell Growth, Maria Azrad

All ETDs from UAB

Obesity increases the risk for breast and endometrial cancers while weight loss reduces the risk for these cancers. One aim of this dissertation was to determine the effects of weight loss from an overweight state [body mass index (BMI) 27-30] to a normal weight state on several obesity-related cancer biomarkers in African-American (AA) and European-American (EA) premenopausal women. We also sought to determine whether the method of weight loss, caloric restriction alone (CR) or combined with exercise resulted in similar changes in cancer biomarkers. The biomarkers of interest were urinary estrogen metabolites, and serum adiponectin, leptin, insulin-like growth factor (IGF)-1, …

Regulation Of The Acid-Sensing Ion Channel 1 By Protein Kinase C And Matriptase, Edlira Bashari

All ETDs from UAB

Acid-sensing ion channel 1 (ASIC1) is a member of the Epithelial Na+ channel/ Degenerin (ENaC/Deg) family of ion channels. Like the other members of this family, it is sensitive to the diuretic amiloride. It was previously shown that both normal astrocytes and glioma cells express ASIC1 and some ENaC subunits. However, only high-grade glioma cells exhibit an inward Na+ current that is sensitive to amiloride and to psalmotoxin 1 (PcTX-1), a specific blocker of ASIC1. Amiloride, PcTX-1, and the knockdown of ASIC1 reduce glioma cell migration. The exact composition of the amiloride-sensitive channel and the molecular mechanisms that regulate its …

The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley

All ETDs from UAB

Transforming growth factor-beta (TGF-beta) negatively regulates mammary gland development and requires Wnt5a to exert some of these effects on mammary gland development. Wnt5a is a non-canonical signaling Wnt that is expressed in all stages of mammary gland development except lactation. Using slow release pellets containing Wnt5a, as well as Wnt5a null tissue, we previously showed that Wnt5a also acts to limit mammary development. Initial studies revealed a potential role for TGF-beta and Wnt5a in regulating mammary gland progenitor cells, indicating they may act to regulate the stem and progenitor cell population. In order to study the role of Wnt5a on …

Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle

All ETDs from UAB

Low density Lipoprotein receptor Related 6 (LRP6) functions as an essential co-receptor for Wnt/Beat;-catenin signaling as pathway activation, reflected by cytosolic Beta-catenin stabilization and TCF/LEF-1 transactivation, requires Glycogen Synthase Kinase 3Beta(GSK3Beta)-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane anchored LRP6 intracellular domain. Additionally, LRP6 undergoes a proteolytic cleavage event resulting in the formation of a soluble LRP6 intracellular domain (LRP6-ICD). LRP6-ICD can function within the Wnt/Beta-catenin pathway by interacting with GSK3Beta and attenuating the phosphorylation of GSK3Beta substrates such as cytosolic Beta-catenin as well as stimulate TCF/LEF-1 activity. However, LRP6-ICD's role(s) within the Wnt/Beta-catenin pathway and the mechanism(s) that …

Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty

All ETDs from UAB

Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …

Evaluations Of Clinical Signs Currently And Not Currently Used In Syndromic Case Management (Scm) Of Reproductive Tract Infections (Rtis) Among Pregnant Women In Jamaica, Gelen Receno Del Rosario

All ETDs from UAB

Reproductive tract infections include sexually transmitted infections, endogenous infections caused by overgrowth of organisms that can be present in the genital tract of a healthy woman, and iatrogenic infections. In Jamaica, women in the reproductive age group of 15-44 years old accounts for 95% of all RTIs. RTIs among Jamaican women of reproductive age can seriously impact the health of the women and their children. The advent of HIV/AIDS has had a significant impact on increasing awareness of the effect of STIs. Health care organizations have reacted with great commit-ment to STI prevention and treatment as a significant factor in …

Sense Of Community Among Adolescents Participating In The Mobile Youth Survey: A Measurement Study, Randolph Stacer Devereaux

All ETDs from UAB

A measurement study was conducted to evaluate 11 items representing the latent variable labeled "sense of community" (SOC) employed by investigators of the Mobile Youth Survey (MYS). In previous research the 11 items representing the concept of SOC have been combined to form a composite variable, assuming that the concept was best represented by a single factor (e.g., Bolland, Bryant, Lian, McCallum, Vazsonyi & Barth, 2007). However, no systematic analysis has been conducted to determine the psychometric properties of the 11-item composite variable. The objects of the present study are a) to determine the component structure of the items used …

Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers

All ETDs from UAB

A number of steps in breast cancer progression and metastasis are regulated by redox signaling pathways. Electrophilic lipids such as 15-deoxy-delta12,14-Prostaglandin J2 (15d-PGJ2) are mediators of redox signaling pathways because of their ability to modify critical cysteine residues (thiols) in redox-sensitive proteins. In this thesis, we examine the effect of lipid electrophiles such as 15d-PGJ2 and others on redox signaling pathways in breast cancer. Furthermore, we develop new strategies to regulate cancer cell behavior in response to lipid electrophiles using three strategies: 1) through organelle-specific targeting of electrophiles 2) by exploiting the concentration-dependence of effects of electrophiles, and 3) utilizing …

The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan

All ETDs from UAB

Alzheimer Disease (AD) is pathologically characterized by the appearance of senile plaques composed of ß-amyloid and neurofibrillary tangles composed of the microtubule-associated protein tau. During the development of AD pathology, tau is hyperphosphorylated and aberrantly cleaved, both of which potentially contribute to its pathogenic and fibrillogenic nature. The accumulative nature of these post-translational products, and their contribution to tau pathology, has led to a great deal of study regarding mechanisms for both the maintenance of tau stability and degradation. The first part of this study reviews the developments regarding the contribution of phosphorylated tau to different physiological and pathological processes. …

Characterization Of The Oligosaccharides Of B. Anthracis Exosporium, Shengli Dong

All ETDs from UAB

Fatal systemic anthrax is caused by exposure to spores of Bacillus anthracis. The outermost layer of the B. anthracis spore is called the exosporium. It consists of a paracrystalline basal layer and an external hair-like nap. The filaments of the hair-like nap are primarily composed of the glycoprotein BclA. Our previous studies showed that a 715-Da tetrasaccharide and a 324-Da disaccharide are attached to BclA through GalNAc. We named the novel nonreducing terminal sugar of the 715-Da tetrasaccharide anthrose. We subsequently proposed a plausible anthrose biosynthetic pathway and identified a gene cluster of four continuous genes that appeared to encode …

Familial Clustering Of Cancer In Two Tertiary Care Hospitals In Nairobi, Kenya, G. W. Kiarie, N. O. Abinya, M. D. Joshi, G. N. Lule, G. Z. Mutuma

Internal Medicine, East Africa

Objective: To describe the occurrence of cancers in families of individuals diagnosed cancer.

Design: Cross-sectional descriptive study.

Setting: Outpatient cancer clinics at Kenyatta National Hospital (KNH) and Radiotherapy Clinic at Nairobi Hospital.

Subjects: Patients with a tissue histological or cytological diagnosis of cancer.

Main outcome measures: A reported family history of cancer.

Results: A total number of 485 cancer patients were recruited, 382, from KNH and 103 from Nairobi Hospital. These index cases had 45 different types of cancer, with the most common being breast and uterine-cervical malignancies. Prevalence of family history of cancer was found to be 18.8% and …

Self-Blood Pressure Monitoring, Stage Of Change, Medication Adherence, Self-Efficacy And Blood Pressure Control In Hypertensive Workers, Tonya Lynn Breaux-Shropshire

All ETDs from UAB

ABSTRACT According to the World Health Organization, hypertension is the leading cause of death in the world and it is one of the primary reasons patients seek health care. Prior to 2010, uncontrolled blood pressure (BP) rates were approximately 18%, despite the fact that prescribed medical treatment is available to adequately control patients' BP. It has been established that medication adherence is a major factor in controlling BP, and self-BP monitoring is highly recommended by the national guideline to improve blood pressure control. However, information related to assessing hypertensive patients' readiness to engage in health care treatment and self-monitoring is …

Association Between Birth Outcomes And Aflatoxin B1-Biomarker Levels Among Pregnant Women In Kumasi, Ghana, Faisal Mohammed Barbas Shuaib

All ETDs from UAB

Aflatoxins are fungal metabolites that contaminate staple food crops in many developing countries. Although studies have linked these toxins to adverse health outcomes, few studies have investigated the association between birth outcomes and aflatoxin B1-lysine adduct levels among pregnant women. The objective of this dissertation was to investigate the association between birth outcomes and aflatoxin B1- lysine adduct levels among pregnant women in Kumasi, Ghana. In a cross-sectional study of 755 pregnant women, Aflatoxin B1-lysine adduct (AF-ALB) levels were determined by High Performance Liquid Chromatography. AF-ALB associations were assessed as both continuous and categorical values. Analysis of variance (ANOVA) was …

Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella

All ETDs from UAB

The cataract is a common ailment affecting the aged population. It appears over time and affects the quality of one’s life by the eventual loss of vision. Currently, there is no effective strategy to prevent or treatment to reverse the development of a cataract. As well, there is no consensus on one particular mechanism or sequence of events that contributes to its formation. In order to better understand the possible etiology of the cataract, it is necessary to define the biochemical changes that occur to lens proteins as one ages, as these are the key players in the prevention of …

Methods For Estimating Mediation Effect In Survival Analysis: Does Weight Loss Mediate The Undernutrition-Mortality Relationship In The Older Adults?, Yanhui Sun

All ETDs from UAB

The influence of undernutrition on mortality and other adverse outcomes through the mechanism of unintentional weight loss in older adults is often assumed, but the analytic methods to test these mediation mechanisms are not well-developed, and the need for methodological advances in this area motivated this program of research. We first examined the test-retest reliability and predictive validity of self-reported caloric intake as a measure of undernutrition. Acceptable reliability was observed, consistent with previous reports, but the evidence for predictive validity was inconsistent and self-reported caloric intake deficiency was not found to be related to observed weight loss. We then …

Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun

All ETDs from UAB

Curcumin, a pleiotropic polyphenol derived from turmeric plants Curcuma Longa with rhizome, exhibits strong evidence as an anti-inflammation, anti-oxidant and anti-cancer reagent both in vitro and in vivo. Due to its low stability and systemic bioavailability, a large amount of curcumin has to be administrated to achieve therapeutic effects both in animal and in human. The major effort to overcome this barrier is making by encapsulation of curcumin into nanoparticles such as polymers and liposomes; some promising data have demonstrated the effectiveness of such method. Exosomes are vesicle-like nanoparticles secreted by living cells. Exosomes contain both cell surface molecules and …

Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin

All ETDs from UAB

DNA replication and cytokinesis are two important parts of the cell division process. Our studies address different aspects of both of these processes and potential links between them. One of the best approaches for studying DNA replication in eukaryotes has been an analysis in cell free in vitro systems. The existing cell free replication systems for Drosophila are relatively ineffective. In the first part of this work, we have developed an optimized in vitro system to study DNA replication using early egg extracts of Drosophila. Our studies indicate that this system proves to be an extremely useful tool for a …

Oral Lesions As Clinical Markers For Antiretroviral Therapy Failure In Hiv Patients, Irene M. Tamí-Maury

All ETDs from UAB

The true nature of the association of oral lesions (OL) and gold standards of HIV progression, CD4+ T cell counts (CD4) and HIV-1 RNA viral load (VL), is not completely clear, especially when patients are on antiretroviral therapy (ART). Our aim was to assess the association between OL and virologic failure among HIV/AIDS patients on ART. We conducted a retrospective study of 744 HIV patients who entered care between 2000 and 2006 at the UAB 1917 Clinic. Data was collected for 2 years after enrollment. Prevalence of OL was 35.8%. Oropharyngeal candidiasis (OPC) was the most prevalent OL (74.9%). Among …

Structural And Functional Study Of P58(Ipk), Jiahui Tao

All ETDs from UAB

P58(IPK) is an endoplasmic reticulum (ER)-resident protein which is upregulated during unfolded protein response (UPR). In stressed cells, P58(IPK) functions to restore protein folding equilibrium in ER by suppressing protein aggregation and promoting protein folding. P58(IPK) associates with the unfolded protein via its N-terminal TPR domain and presents it to BiP (binding immunoglobulin protein) for subsequent folding. P58(IPK) belongs to the Hsp40 family. Collectively, P58(IPK) is a stress-inducible ER-resident molecular chaperone. In this dissertation, we report the crystal structure of P58(IPK) TPR domain to 2.5 Å resolution. In the crystal structure, the 43-kDa TPR domain consists of nine tandemly linked …

Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian

All ETDs from UAB

Macrophages play a critical role in the initiation and progression of atherosclerosis by producing pro-inflammatory mediators and transforming into lipid-laden foam cells. The prevention of lipid accumulation and inflammation in macrophage foam cells, therefore, represents a promising target for effective therapy for atherosclerosis. Adiponectin is a circulating cytokine primarily expressed and secreted by adipocytes, and is downregulated in obesity-linked diseases including type 2 diabetes, coronary artery disease and hypertension. In oxidized low-density lipoprotein (oxLDL)-induced human THP-1 macrophage foam cells, adiponectin suppresses lipid accumulation through decreasing lipid uptake and increasing high-density lipoprotein (HDL)-mediated lipid efflux. The potential mechanisms that adiponectin utilizes …

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

All ETDs from UAB

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …

Investigation Of The Cese Framework For Viscous Flows, Balaji Shankar Venkatachari

All ETDs from UAB

A transient viscous solver has been developed based on the novel space-time conser-vation element solution element (CESE) framework. Till date, the numerical accuracy of the CESE framework in modeling inviscid flow problems has been well documented, while very little work has been done in regards to modeling transient viscous flows. In this work, an attempt to fill that gap in literature was carried out by rigorously investigat-ing the numerical accuracy and computational performance of the CESE framework in simulating such flows. The study aims at gaining a deeper understanding on the numeri-cal accuracy and dissipation characteristics of the CESE framework, …

Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi

All ETDs from UAB

The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric …