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Articles 31 - 60 of 94
Full-Text Articles in Medicine and Health Sciences
Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda
All ETDs from UAB
Glioblastoma multiforme (GBM) is the most lethal form of primary brain neoplasm with average patient survival between 9 and 15 months even with the most aggressive treatment modalities. Unfortunately, this poor outcome has not appreciably changed in the past 50 years emphasizing the lack of traditional `trial and error' methods in identifying an efficacious treatment for GBM. Pharmacogenomics is greatly impacting cancer research through the development of personalized medicine and rationally designed treatment paradigms for the development of more efficacious and less toxic treatment modalities. The main objective of this research was to utilize a pharmacogenomic approach to identify new …
Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton
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 …
Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde
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
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
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; …
Structural And Functional Studies On Heat Shock Protein Hsp40-Hdj1 And Golgi Er Trafficking Protein Get3, Junbin Hu
All ETDs from UAB
Molecular chaperones are a large group of proteins that bind and stabilize nascent polypeptides and facilitate protein folding. One major function of chaperones is to bind hydrophobic segments of nascent polypeptides to prevent them from aggregating. How chaperone Hsp40 recognizes and interacts with polypeptides and cooperates with chaperone Hsp70 is a fundamental question. The crystal structure of the putative peptide-binding fragment of Hdj1, a human member of the type II Hsp40 family was determined, suggesting the domain I of Hsp40 may possess significant flexibility which is important for Hsp40 to regulate the size of the cleft. The flexibility may be …
The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins
The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins
All ETDs from UAB
Bisphenol A (BPA) is a synthetically made compound used to produce a myriad of consumer goods. Recent studies have shown BPA to leach from these products in appreciable amounts, resulting in nearly ubiquitous exposure. In this study, we assessed whether chronic administration to a range of low concentrations of BPA could accelerate spontaneously developing mammary cancer using a transgenic model that over-expresses wild type ErbB2/neu transgene (MMTV-erbB2). MMTV-erbB2 mice were provided drinking water containing 0 (control), 2.5 (BPA 2.5), 25 (BPA 25), 250 (BPA 250), or 2500 (BPA 2500) µg BPA/L from eight weeks of age until sacrifice. This range …
Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan
Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan
All ETDs from UAB
Malaria causes an estimated 1-3 million deaths each year, with the majority of deaths being a result of infection with Plasmodium falciparum. No commercially available vaccine currently exists, but multiple subunit-based vaccines are in development including one based on the promising vaccine candidate P. falciparum Merozoite Surface Protein-3 (PfMSP3). PfMSP3 varies in sequence between P. falciparum isolates, but all variation is restricted to the N-terminal domain. This observation has lead to the development of a PfMSP3-based vaccine comprised solely of the highly conserved, yet poorly immunogenic, C-terminal domain. The rationale for supporting the C-terminal domain relies entirely on its conserved …
A System Genetics Analysis Of Energy Metabolism Traits In Drosophila Melanogaster, Patricia Paola Jumbo-Lucioni
A System Genetics Analysis Of Energy Metabolism Traits In Drosophila Melanogaster, Patricia Paola Jumbo-Lucioni
All ETDs from UAB
Obesity is emerging as a global public health problem and it has shown to precede and predict the development of type 2 diabetes, a complex disease that has also reached epidemic proportions in the US and worldwide. Despite that obesity-related traits are highly heritable, the genetic basis underlying their natural variation and the loci playing pleiotropic roles among organismal traits have not been fully elucidated. The overall goals of these present studies were: to shed light on the architecture of the genetic co-expression networks regulating variations in obesity-related traits, elucidate the extent to which they are regulated by pleiotropic loci, …
Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle
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 …
Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri
Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri
All ETDs from UAB
Acid Sensing Ion Channel 1 is one of the many proteins in the Epithelial Sodium Channel/Degenerin family. The proteins in this family interact to form cation channels with unique biophysical properties and can all be inhibited by the small molecule amiloride. Their expression in many different cell types underlies their involvement in a large variety of physiological and pathophysiological processes. ASIC-1 containing channels, specifically, are an important therapeutic target for ischemic stroke, nociception, the invasiveness of glioblastoma cells, and many other processes including anxiety and memory formation. Of the members of the ENaC/Deg family, chicken ASIC-1 is the only protein …
Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena
Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena
All ETDs from UAB
Rapid bone loss occurs during prolonged periods of weightlessness experienced by astronauts during spaceflights which leads to osteopenia and increased fracture risk upon return to earth. Spaceflight studies have shown that the bone loss occurs as a result of both a decrease in bone formation and an increase in bone resorption, however, the molecular mechanisms still need to be elucidated. Previous studies from our laboratory and other groups have indicated that modeled microgravity leads to inhibition of osteoblastogenesis and a stimulation of adipogenesis of human mesenchymal stem cells in osteogenic medium which is most likely mediated by a decrease in …
Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka
Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka
All ETDs from UAB
Mitochondria are responsible for most of the energy produced in human tissues, and this is dependent on the reduction of oxygen (O2) to water by the mitochondrial respiratory chain. Defects in mitochondrial energy production are now recognized to be involved in diabetes, cancer, cardiovascular disease, and other pathologies. To date, studies of these defects have employed quantification of O2 consumption in isolated, purified mitochondria. By using this strategy however, the cellular context, role of glycolysis, and normal regulation of mitochondrial function by metabolite availability are lost. Thus, an understanding of how mitochondria function and respond to stimuli in an intact …
Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang
Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang
All ETDs from UAB
Embryonic stem (ES) cells are pluripotent and, therefore, can differentiate into most if not all somatic cell types. Because of this characteristic, ES cells have great potential for medical therapies. Since the first cloned mammal, Dolly the sheep, was published in 1996 (1), several groups have successfully cloned other animals by the same nuclear transfer method (2). Isogenic ES cell lines can also be established from donor cells by the same technique (3). However, to date there has been no report of successful derivation of human ES cells by nuclear transfer. Based on the cell fusion (4) and nuclear transfer …
The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng
The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng
All ETDs from UAB
Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …
Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish
Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish
All ETDs from UAB
Current research suggests that up to 75% of American women have engaged in vaginal douching during their lives. Prevalence of the behavior is disproportionately high among minority women (especially African American) and women of low SES. Two bodies of research present conflicting results regarding the benefits or risks to reproductive health that are posed by vaginal douching, although the majority of research on this topic suggests that douching is associated with negative health outcomes. Although studies have suggested prevalence rates, behavioral correlates, and biological associations of vaginal douching, very few studies have used behavioral theory when examining the practice. The …
The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson
The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson
All ETDs from UAB
Glioblastoma (GBM) is an incurable tumor of the central nervous system (CNS). Over the past 50 years, little progress has made in improving the quality of life and median lifespans of patients who are diagnosed with this devastating disease. However, new insights into the aberrant signaling pathways at the root of GBM pathology are providing new targets for next generation cancer therapies. Two signaling pathways that are commonly upregulated in GBM are NF-kappaB and STAT3. Importantly, tumor models in which NF-kappaB and STAT3 signaling are inhibited have demonstrated the importance of these pathways to GBM growth and proliferation. Therefore, better …
Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi
Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi
All ETDs from UAB
Worldwide 15-40% of adolescents practice Disordered Eating Behavior (DEB). This study examined DEB development and the role of 1) shared familial factors among sibling pairs; and 2) non-shared familial experiences among discordant sibling pairs adjusted for individual and shared familial factors. The "National Longitudinal Study of Adolescent Health" data on 3274 adolescents were analyzed. The sample contained: twins (n=952), full siblings (n=1434), half siblings (n=418), and biologically not-related siblings (n=470). Multivariable regression analysis examined familial factors associated with DEB in the overall sample and sibling pair types. Adolescents engaging in DEB (~16%) were more likely to be white females with …
Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker
Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker
All ETDs from UAB
Astrocytes and microglia are specialized glial cells of the Central Nervous System (CNS) that modulate neural activity and regulate immunological and inflammatory events. These cells perform their functions, in part, through the secretion of soluble mediators such as cytokines and chemokines. However, in response to the same neurological insult or inflammatory stimuli, the responses of these cells can vary greatly. This notion of differential responses was examined in our studies using Oncostatin M (OSM). OSM is a member of the IL-6 family of cytokines, which can be produced by microglia, astrocytes, neurons, and infiltrating leukocytes in the CNS, and is …
Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck
Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck
All ETDs from UAB
Unlike antigen-specific alpha beta-T cells, gamma delta-T cells can recognize and lyse cancerous cells rapidly upon encounter in a manner that does not require the recognition of tumor-specific antigens. Given the well-documented capacity of gamma delta-T cells to innately kill malignant cells, efforts are now underway to exploit the antitumor properties of gamma delta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gamma delta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively-transferred gamma delta-T cells would be employed therapeutically against breast …
Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis
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
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
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 …
Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn
Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn
All ETDs from UAB
Calreticulin (CRT), classically known for its chaperone functions in the endoplasmic reticulum and as a calcium regulator, also is found on the cell surface and in the extracellular matrix. It is involved in many cellular processes including signaling, adhesion, migration, apoptotic cell clearance, gene regulation, and production of a fibronectin matrix. CRT has been suggested to play a role in wound healing and fibrosis. Therefore, these studies investigated the role of CRT in collagen production, an important extracellular matrix molecule in wounding and fibrosis. We demonstrated that CRT regulates collagen through transcription, secretion, and processing. We also investigated the role …
Protein Trafficking And 4.1r Relocalization In Plamodium Falciparum-Infected Erythrocytes, Lindsay A. Parish
Protein Trafficking And 4.1r Relocalization In Plamodium Falciparum-Infected Erythrocytes, Lindsay A. Parish
All ETDs from UAB
Malaria is a mosquito-borne infectious disease that is caused by parasites in the genus Plasmodium. There are four species of malaria that routinely infect humans, but it is P. falciparum that is responsible for the majority of the severe and fatal cases of malaria. P. falciparum has a complex life cycle involving a mosquito vector and intracellular stages in both hepatocytes and erythrocytes; however, it is only the intraerythrocytic stages that are the cause of the pathology associated with malaria. This pathology is largely due to the ability of infected erythrocytes to cytoadhere to host microvasculature. After invasion, the parasite …
Predictors Of Self-Reported Health Status In Occupationally And Environmentally Exposed Individuals, Christie Shelton
Predictors Of Self-Reported Health Status In Occupationally And Environmentally Exposed Individuals, Christie Shelton
All ETDs from UAB
Every year, over 3.5 billion pounds of industrial toxins and one to two billions pounds of environmental toxins are deliberately released into the environment. Although exposures have been shown to have an adverse effect on the health of the individuals, the effect of these exposures on the self-reported health status of individuals who have been environmentally and occupationally exposed to these toxins is still unclear. The purposes of this study were to: 1) identify the best subset of predictors of self-reported health status in current/former farmers and manufacturing workers from the set of age, sex, race, blood pressure, cholesterol measures, …
The Relationship Of Sexual Empowerment And Sexual Pressure To Condom Use Of Young Adult African American And Caucasian Women, Carrie Ann Long
The Relationship Of Sexual Empowerment And Sexual Pressure To Condom Use Of Young Adult African American And Caucasian Women, Carrie Ann Long
All ETDs from UAB
Introduction: HIV knowledge, high self-esteem, condom self-efficacy, positive attitudes toward condom use, and condom negotiation skills have been associated with decreased HIV risk behavior among women, but have not been examined within a framework of empowerment for sexual risk. Sexual pressure, inclusive of both coercive and noncoercive pressures to engage in unwanted or unprotected sex, has also not been studied in association with sexual empowerment as a framework or as a potential moderator between sexual empowerment and condom use among women of different racial groups. Study Purpose: 1) To explore the relationship between sexual empowerment and condom use; 2) to …
Pathological Modification Of Tau Induce Toxicity And Facilitate Cell Death, Tori A. Matthews
Pathological Modification Of Tau Induce Toxicity And Facilitate Cell Death, Tori A. Matthews
All ETDs from UAB
eimer’s disease (AD) is a progressive neurodegenerative disorder characterized by two major pathophysiological hallmarks, beta-amyloid (A��) plaques and tau tangles. In AD and other tau associated neurodegenerative disorders, termed tauopathies, a critical role in promoting neuronal degeneration has been demonstrated for hyperphosphorylated forms of tau. Recent findings suggest that cleavage of tau in the carboxyl-terminal region (Asp421) may also promote deleterious effects of tau on neuronal health. In the first half of my study, the relationship between Asp421 cleaved tau and a common AD associated stressor (endoplasmic reticulum [ER] stress) was investigated using an inducible cortical neuronal model. Cells expressing …
Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith
Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith
All ETDs from UAB
The Drosophila Bone Morphogenetic Protein (BMP) Glass bottom boat (Gbb) is a ligand for the BMP type II receptor, Wishful thinking (Wit). Mutations in either of these proteins impair synaptic growth at the neuromuscular junction (NMJ). Gbb is a retrograde signal (from target to innervating neuron) that is essential for proper NMJ development and function. Tissue-specific rescue of pathway mutants and immunolocalization experiments indicate that the receptor-ligand interaction occurs at the NMJ, and results in the nuclear accumulation of the phosphorylated form of the transcription factor Mad, indicating that retrograde transport along the axon is critical for pathway activation. We …
Substitute Costs: A Method For Determining Ecological Service Values In Stormwater Management, Steven B. Mckinney
Substitute Costs: A Method For Determining Ecological Service Values In Stormwater Management, Steven B. Mckinney
All ETDs from UAB
Many alternatives exist for estimating the value of the natural environment. These approaches have been developed over the past 40 to 50 years and began principally because of increasing awareness that economic development had an associated cost in environmental degradation. Environmental economics provides some of the tools necessary to aid in balancing economic growth with the environmental impacts created by this growth and to do so through evaluating policy. Using environmental economics as a mechanism for policy assessment allows the evaluation of potential gains from specific courses of economic growth and of the trade-offs in environmental services that may be …