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Full-Text Articles in Medicine and Health Sciences

The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai Jan 2009

The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai

All ETDs from UAB

Several reports have suggested that Mycoplasma pneumoniae (Mp) can contribute importantly to the expression of symptoms in asthmatic human subjects. As a foundation for understanding the interactions between Mp and asthma susceptibility, we first studied the mechanisms by which the host normally eliminated Mp. Mice were inoculated with 4x106 Mp intranasally. Twenty-four hours after inoculation with Mp, subpopulations of CD11b+ macrophages/monocytes had been recruited into the lungs. The clearance of Mp was impaired both in macrophage-depleted and in macrophage-deficient mice. Furthermore, mice deficient in MyD88, a major adaptor for TLR signaling, showed dramatically defective clearance of Mp, associated with reduced …

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Regulation Of B Cell Biology By Fcγ Receptors, Xinrui Li Jan 2009

Regulation Of B Cell Biology By Fcγ Receptors, Xinrui Li

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B cell development, maturation and proliferation are all strictly regulated processes. Disruption of the regulatory network at any step would lead to immune disorders. The regulatory system of B cells can be considered as two layers: a general homeostasis regulation system and a specificity-based control system. General regulation of B cell homeostasis is mastered by BLyS (B Lymphocyte Stimulator) and several other BLyS family cytokines, which serve as a crucial survival factor for which transitional and mature B cells compete. Specificity-based control is achieved via B cell antigen receptors (BCRs), which serve as a determinant of whether an antigen-specific B …

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Late Development Plasticity In The T Helper 17 Lineage, Yun Kyung Lee Jan 2009

Late Development Plasticity In The T Helper 17 Lineage, Yun Kyung Lee

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CD4 T cells are a principal component of the adaptive immune system that is required for the efficient elimination of foreign antigens, but dysregulated CD4 T cells responses may result in autoimmune and chronic inflammatory diseases. The differentiation of effector CD4 T cells is directed by cytokines elicited by pathogendriven innate immune responses. Therefore the coordinated innate and adaptive immune responses provide an efficient system for host protection. Our understanding of distinct differentiated CD4 T cells has recently expanded with the discovery of the Th17 lineage, a new subset of effector CD4 T cells that has been implicated in chronic …

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Structural Studies Of Yeast Mitochondrial Peripheral Membrane Protein Tim44, Ratnakar Josyula Jan 2009

Structural Studies Of Yeast Mitochondrial Peripheral Membrane Protein Tim44, Ratnakar Josyula

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Tim44 is a peripheral membrane protein and a component of the TIM23 translocon on the matrix side. It is well established that Tim44 tethers the presequence associated motor (PAM) complex to the Inner Mitochondrial Membrane (IMM), through its C-Terminal Domain (CTD). This study focuses on understanding the high resolution structure of Tim44 CTD and the molecular basis for its membrane anchoring mechanism. The crystal structure of Tim44 CTD revealed that it exists as a single domain. The N-terminal amphipathic helices A1 and A2 protrude away from the main body of Tim44 CTD. These two flexible helices have been tested for …

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Mouse Model Of Cooley's Anemia, Yongliang Huo Jan 2009

Mouse Model Of Cooley's Anemia, Yongliang Huo

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β thalassemia major or Cooley’s anemia (CA) is a heterogeneous group of inherited disorders characterized by deficient β globin chain production. Newborns with CA are healthy because of the high fetal hemoglobin (HbF) levels present in their red blood cells (RBCs). As HbF levels decline during the first year of life, patients develop severe anemia that necessitates regular blood transfusion to maintain life. CA has been difficult to model in the mouse due to the lack of a fetal hemoglobin equivalent in the mouse. By utilizing a human fetal to adult delayed hemoglobin switching cassette, I hypothesize that a CA …

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Klf4 And Retinoid Receptor Signaling In Cancer, Wen Jiang Jan 2009

Klf4 And Retinoid Receptor Signaling In Cancer, Wen Jiang

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The fight against cancer has generated wide interest in understanding the genetic mechanisms behind the disease. One group of oncogenes – transcription factors – offers many opportunities for treatment or prevention. Among these transcription factors is KLF4, which functions in post-mitotic epithelial cells to promote differentiation. KLF4 has tumorigenic activity in both in vitro and in vivo models. In analyzing transcripts that were induced by KLF4, we noted the induction of multiple nuclear receptors, including retinoid receptors. Retinoids are well-established as chemopreventive agents, but the mechanisms by which they act to prevent cancer remain unclear. Previous studies have shown that …

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Regulation Of Neural Precursor Cell Apoptosis And Proliferation By Glycogen Synthase Kinase-3, Tae-Yeon Eom Jan 2009

Regulation Of Neural Precursor Cell Apoptosis And Proliferation By Glycogen Synthase Kinase-3, Tae-Yeon Eom

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Neurogenesis is a crucial process for development, plasticity, and regenerative capacity of the developing and adult brain. Impairment of neurogenesis has been implicated in the etiology of psychiatric disorders. Although substantial studies have shown that therapeutic interventions enhance neurogenesis, much less is known about what factors impair neurogenesis. Thus, the present work examined if glycogen synthase kinase-3 (GSK3) has a role in impaired neurogenesis, focusing on apoptosis and proliferation of neural precursor cells (NPCs). This investigation found that GSK3 promotes apoptotic signaling in cultured NPCs subjected to two insults, trophic factor withdrawal and genotoxic stress. Both stimuli activated GSK3, Bax, …

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The Effect Of Stearic Acid On Breast Cancer Development And Progression, Lynda Michelle Evans Jan 2009

The Effect Of Stearic Acid On Breast Cancer Development And Progression, Lynda Michelle Evans

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earate is an 18-carbon saturated fatty acid that is found in many foods in the western diet including beef and chocolate. Cell culture studies indicate stearate may have various anti-cancer properties including inhibition of cancer cell proliferation and invasion, morphological changes, and induction of apoptosis. Animal studies have found that dietary stearate delays tumor development and decreases tumor incidence. To date, many of the mechanisms underlying these processes are unclear. In this study, evidence is presented showing stearate induces morphological changes in breast cancer cells. Inhibition of de novo diacylglycerol (DAG) generation and subsequent protein kinase C (PKC) activation inhibits …

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Genome Copy Number Profiles Of African-American And European-American Early-Onset Breast Cancer, Tyesha Latrece Farmer Jan 2009

Genome Copy Number Profiles Of African-American And European-American Early-Onset Breast Cancer, Tyesha Latrece Farmer

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Breast cancer is the second leading cause of cancer related death among women in the United States, surpassed only by lung cancer. It is estimated that over 200,000 women developed breast cancer and more than 40,000 died of the disease in 2008 alone. Although the overall incidence of breast cancer is lower in African-American women, the incidence of early-onset breast cancer is higher than that observed in European-American women. African-American women also have higher mortality rates due to this disease than those observed in their European-American counterparts. Breast cancer exhibits heterogeneity at the molecular, cellular, and clinical levels, and the …

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Impact Of Health Care Coverage And Other Socio-Demographic Variables On The Follow-Up Of Cervical Cancer Screening Among Colombian Women, Isabel Cristina Garces-Palacio Jan 2009

Impact Of Health Care Coverage And Other Socio-Demographic Variables On The Follow-Up Of Cervical Cancer Screening Among Colombian Women, Isabel Cristina Garces-Palacio

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In Colombia, cervical cancer is the most common cancer among women with incidence (36.4/100,000) and mortality rates (18/100,000) much higher than those of the U.S. (7.7 and 2.3 respectively). About 70% of the Colombian population has health care coverage (HCC) through the subsidized regime (SR) which serves the poorest persons and the contributory regime (CR) which serves the working population. Our goal was to determine the role that HCC plays in cervical cancer screening follow-up among Colombian women. A population-based cross-sectional study of 24,717 women between the ages of 18 and 49, using the 2005 Demographic and Health Survey was …

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The Protective Role Of Transglutaminase 2 In Ischemic Stroke, Anthony J. Filiano Jan 2009

The Protective Role Of Transglutaminase 2 In Ischemic Stroke, Anthony J. Filiano

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Stroke is a leading cause of long term disabilities in the US. Currently, administration of thrombolytics is the only approved therapy. Due to the variability, small management time window, and lack of options for effective treatment, there is a clear need for new compounds to alleviate cell death post-stroke. Transglutaminase 2 (TG2) can decrease apoptotic signaling during stroke and lead to increased neuronal survival making it a potential target for therapeutic intervention. TG2, a multifunction enzyme that has both transamidase (TG) and GTPase activities, amongst others, has recently been shown to be upregulated in numerous neurodegenerative conditions, including stroke. In …

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Occupational Stress, Dietary Self-Efficacy, Eating Habits And Body Composition In Police Officers, Rebecca Witten Grizzle Jan 2009

Occupational Stress, Dietary Self-Efficacy, Eating Habits And Body Composition In Police Officers, Rebecca Witten Grizzle

All ETDs from UAB

Obesity is a paramount public health threat in the U.S. as approximately twothirds of the adult population is overweight. Police officers have an even higher prevalence of overweight and obesity and other cardiovascular risk factors. Police officers often attribute their above average cardiovascular disease risk to shift work, jobrelated stress, and poor dietary habits while working. Occupational stress is a major concern among police officers. Therefore, it is important to understand the relationships among occupational stress, obesity, and diet habits. However, few research studies have characterized these relationships in police officers. The specific aims of this study were to determine …

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Comorbidity And Body Mass Index (Bmi) As Predictors Of Survival For African Americans And Caucasians Following Surgery For Adenocarcinoma Of The Colon, Robert B. Hines Jan 2009

Comorbidity And Body Mass Index (Bmi) As Predictors Of Survival For African Americans And Caucasians Following Surgery For Adenocarcinoma Of The Colon, Robert B. Hines

All ETDs from UAB

There is a survival disparity between African Americans and Caucasians having colon cancer. Among the reasons given as possible causes for the increased risk of death in African Americans following a diagnosis of colon cancer are comorbidity and body habitus. The primary question this dissertation sought to answer was whether or not comorbidity and/or BMI could account for any of the increased risk of death seen in African Americans with colon cancer. However, before answering this question, the matter of which comorbidity index to use in assessing the comorbidity burden in this population of colon cancer patients had to be …

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Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng Jan 2009

Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng

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Growth hormone (GH), a 22 kD polypeptide primarily produced in the anterior pituitary gland, is a key regulator of postnatal growth and affects carbohydrate, protein and lipid metabolism. Growth hormone receptor (GHR) is a single membrane-spanning type Ⅰ glycoprotein of the cytokine receptor family and is initially synthesized as a precursor and undergoes carbohydrate processing during transport through the Golgi. It has no intrinsic kinase activity. One molecule of GH binding to predimerized GHR on the cell surface induces the receptor conformational change activating the cytoplasmic domainassociated tyrosine kinase, Janus Kinase 2 (JAK2), which phosphorylates GHR, followed by the activation …

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Erythrocyte Invasion By Plasmodium Falciparum, Matthew L. Jones Jan 2009

Erythrocyte Invasion By Plasmodium Falciparum, Matthew L. Jones

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Malaria poses a severe threat to global public health, with the majority of the world’s population living in malaria-endemic settings. Plasmodium falciparum is a major cause of malaria, and is the predominant cause of fatal malaria. This parasite, like other Plasmodium spp., has a complex life cycle, but causes disease only as a result of a lytic life cycle phase that occurs within the erythrocyte. As development within the erythrocyte is fully responsible for disease pathology, it follows that a detailed molecular understanding of the process of erythrocyte invasion by P. falciparum parasites would allow the development of new and …

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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 Jan 2009

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 …

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The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud Jan 2009

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

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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 …

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Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar Jan 2009

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

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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 …

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Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli Jan 2009

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

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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 …

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The Distinction Between First And Higher-Order Pregnancies Among Low-Income Adolescents, Ann Elizabeth Montgomery Jan 2009

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

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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 …

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Physical Therapy And Chiropractic Use In Survivors Of Childhood Cancer: Impact On Health-Related Quality Of Life, Michele Montgomery Jan 2009

Physical Therapy And Chiropractic Use In Survivors Of Childhood Cancer: Impact On Health-Related Quality Of Life, Michele Montgomery

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The purpose of this study to was examine prevalence of physical therapy (PT) and chiropractic use in survivors of childhood cancer and which factors are associated with the use of these services. In addition, the health-related quality of life (HRQOL) of survivors with musculoskeletal and neurological chronic conditions who reported using either PT or chiropractic was compared to those survivors with the same conditions who did not use either service. This study was a secondary analysis of the Childhood Cancer Survivor Study (CCSS) and included a subset of 9289 survivors who completed both the baseline and 2003 follow-up questionnaires. In …

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Parenting Behaviors And Adolescent Obesity, Kathy Lynne Newman Jan 2009

Parenting Behaviors And Adolescent Obesity, Kathy Lynne Newman

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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 …

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The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson Jan 2009

The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson

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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 …

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Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi Jan 2009

Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi

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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 …

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Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker Jan 2009

Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker

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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 …

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Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck Jan 2009

Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck

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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 …

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A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta Jan 2009

A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta

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The retroviral life cycle is separated into two distinct phases of infection. In the first phase, viral enzymes and proteins allow the virus to establish infection. The virus usurps host machinery in the second stage to produce infectious virus. In both phases of the replication cycle, the envelope (Env) glycoprotein (gp) is a key component of infectivity. Env plays a pivotal role in viral entry, by mediating attachment and facilitating fusion of the viral and cellular membranes, and during assembly, where Env must be incorporated into budding virions in order to produce infectious virions. The Env cytoplasmic domain (CD) interacts …

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Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis Jan 2009

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

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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 …

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Involvement Of Reactive Oxygen Species In The Acute Development Of Insulin Resistance Following Trauma And Hemorrhage, Lidong Zhai Jan 2009

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

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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 …

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Maintaining Healthy Eating Behaviors With Women After A Weight Management Program: A Grounded Theory Approach, Christie Zunker Jan 2009

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

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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 …

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