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2009

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Articles 4081 - 4110 of 4384

Full-Text Articles in Medicine and Health Sciences

Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng Jan 2009

Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng

All ETDs from UAB

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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The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan Jan 2009

The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan

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VH replacement occurs through RAG-mediated secondary recombination between an upstream VH gene and an existing VHDJH joint. In the first part of this dissertation, we focused on the potential regulation of VH replacement in the human B lineage EU12 cells muHC+ population, which underwent spontaneous VH replacement during in vitro culture. We cloned one of the dominant IgH genes, A19H, expressed in the EU12 muHC+ cells, and generated recombinant antibodies. We found that these recombinant antibodies recognize SM antigens. The anti-SM reactivity of A19H can not be efficiently neutralized by a randomly selected group of fourteen IgL chains from healthy …

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Polysaccharide Specific B Cells: A Study Of Their Development And Function, Jeremy B. Foote Jan 2009

Polysaccharide Specific B Cells: A Study Of Their Development And Function, Jeremy B. Foote

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Polysaccharides are important structural components of bacterial capsule and cell walls. Polysaccharide-specific antibodies are an important component of serologic memory capable of protecting against infection by pathogenic microorganisms. An understanding of the biology and function of polysaccharide specific B cells is necessary for formulation of vaccines designed to induce polysaccharide specific memory and long-lived antibody production. The goal of this dissertation was to examine the development of naïve DEX-specific B cells and examine their capacity to generate memory and long-lived plasma cells in response to polysaccharide α 1→3-dextran (DEX), which is expressed by the opportunistic pathogens Enterobacter cloacae, Histoplasma capsulatum …

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Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele Jan 2009

Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele

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Insulin and insulin-like growth factor-1 (IGF-1) are evolutionarily conserved hormonal signaling pathways with structurally similar ligands and receptors. Recent stu-dies suggest that that insulin and IGF-1 exert distinct as well as overlapping functions to regulate different aspects of skeletal development. A major problem in distinguishing the actions of insulin and IGF-1 is the fact that the receptors are co-expressed in many cell types and each ligand is able to cross-activate the other ligands' receptor. To distinguish direct skeletal actions of insulin from that of IGF-1, we have conditionally disrupted each receptor in vitro and in vivo specifically in osteoblasts. Studies …

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Patterns Of Differential Mrna And Protein Expression During Minus Lens Compensation And Recovery In Tree Shrew Sclera, Hong Gao Jan 2009

Patterns Of Differential Mrna And Protein Expression During Minus Lens Compensation And Recovery In Tree Shrew Sclera, Hong Gao

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During the juvenile period of human development, an emmetropization mechanism uses visual signals to precisely guide the axial length elongation rate of the eyes to the optical power to keep the images in sharp focus. However, almost a third of the U.S. population develops axial myopia, in which the eye is elongated relative to the focal plane. The aims of the study were to examine 27 genes and 6 proteins in tree shrew sclera for potential differential expression patterns during minus lens compensation and dur-ing recovery. The study hypothesized that, in response to hyperopia produced by a -5 D lens, …

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The Role Of Transforming Growth Factor Beta-1 In Bone Remodeling, Yi Tang Jan 2009

The Role Of Transforming Growth Factor Beta-1 In Bone Remodeling, Yi Tang

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Bone remodeling depends on the precise coordination of bone resorption by the osteoclasts and bone formation by the osteoblasts. It is proposed that osteoclastic bone resorption releases factors to initiate bone formation, thereby, coupling the bone resorption and formation. Mesenchymal stem cells (MSCs) are progenitors of osteoblasts. Recruitment of MSCs in response to osteoclastic bone resorption may be an initial step for bone formation during bone remodeling process. Therefore, we have established an in vitro osteoclastic bone resorption system. Bone resorption condition medium have been tested to identify the factor inducing the migration of human bone marrow mesechymal stem cells …

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Regulation Of The Human Heme Oxygenase-1 Gene By Nitro-Linoleic Acid, Macienne M. Wright Jan 2009

Regulation Of The Human Heme Oxygenase-1 Gene By Nitro-Linoleic Acid, Macienne M. Wright

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Nitro-fatty acids (NO-FA) exert anti-inflammatory effects in the vasculature. Heme oxygenase-1 (HO-1) degrades heme into iron, biliverdin, and carbon monoxide and is up-regulated as an adaptive and protective response to inflammatory processes. This dissertation examined whether nitro-linoleic acid (LNO2) induced HO-1 gene expression and evaluated the molecular mechanism of induction in human aortic endothelial (HAEC), human embryonic kidney 293 (HEK 293) and mouse embryonic fibroblast (MEF) cells. LNO2 induced HO-1 mRNA and protein in HAEC at the level of transcription. NO scavenging by carboxy-PTIO partially reversed LNO2–mediated induction of HO-1, suggesting that LNO2 acts via NO-dependent and NO-independent mechanisms of …

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Protective Mechanisms Of Apoa-I Mimetic Peptide Action In Sepsis-Induced Tissue Injury, Zhenghao Zhang Jan 2009

Protective Mechanisms Of Apoa-I Mimetic Peptide Action In Sepsis-Induced Tissue Injury, Zhenghao Zhang

All ETDs from UAB

Sepsis is among the top ten causes of death in the US, and it is associated with severe inflammatory tissue damage and organ dysfunction. Reduced plasma high density lipoprotein (HDL) is associated with increased mortality in septic patients. Since raising plasma apolipoprotein (apo) A-I and HDL may reduce sepsis complications, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in two animal models of sepsis, and explored the possible mechanisms. In endotoxemic rats, inflammatory mediators were significantly induced while blood pressure was significantly reduced by 6hr. The impaired arterial response to vasoconstrictors was related to …

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Molecular Characterization Of Neural Apoptosis, Ken C. Walls Jan 2009

Molecular Characterization Of Neural Apoptosis, Ken C. Walls

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Neural cell death plays a critical role in normal nervous system development and dysregulated neural stem cell death contributes to brain malformation, tumorgenesis, and possibly, neurodegenerative disease. The two major forms of cell death in the nervous system are apoptotic and autophagic. Altered clearance of proteins may lead to neuronal dysfunction and neuron loss via apoptotic and/or autophagic pathways. The research presented here examined the molecular regulation of the autophagic and apoptotic pathways in vivo and in vitro by using models of lysosome dysfunction and hypoxia. In vivo investigation of lysosome dysfunction-induced death utilized the cathepsin D (CD)-deficient mouse model. …

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The Relationships Among Satisfaction With Social Support, Perceived Stress, And Coping On Quality Of Life And Survival At 5 To 10 Years After Heart Transplantation, Connie White-Williams Jan 2009

The Relationships Among Satisfaction With Social Support, Perceived Stress, And Coping On Quality Of Life And Survival At 5 To 10 Years After Heart Transplantation, Connie White-Williams

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Introduction: Detailed information regarding satisfaction with social support and its relationship with quality of life (QOL) and survival 5 to 10 years (yrs) after heart transplantation (HT) is unknown. The purpose of this study was to examine the relationships among satisfaction with social support perceived stress, and coping with QOL and survival of patients (pts) who were 5 to 10 years post heart transplantation. Methods: This study was a retrospective outcome analysis from data collected from two existing data sets: The HT QOL Study and the Cardiac Transplant Research Database (CTRD). Institutional Review Board approval was obtained. Data on 555 …

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Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams Jan 2009

Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams

All ETDs from UAB

Cilia are evolutionarily conserved, membrane-bound, microtubule-based organelles found on a diverse array of cell types in eukaryotic organisms. Inherited diseases of cilia protein dysfunction include Nephronophthisis (NPHP), Joubert Syndrome (JBTS), Meckel-Gruber Syndrome (MKS), and Bardet-Biedl Syndrome (BBS). Important insight in the basic cell biological functions of BBS and NPHP proteins has been gained from analysis in the nematode Caenorhabditis elegans. My goal in this dissertation was to model MKS protein function in cilia biology utilizing the powerful genetic malleability of C. elegans. mks-1 and mks-3, the C. elegans homologs of two MKS-associated proteins in humans, were selected for this analysis. …

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The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams Jan 2009

The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams

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Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; …

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Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang Jan 2009

Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang

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Adenovirus (Ad) is the most commonly used viral vector in gene therapy applications to date for a broad range of diseases. Although Ad-based viral vectors have many advantages in a variety of gene therapy designs, the commonly used adenoviral vectors have several key shortcomings. Those shortcomings include (1) inefficient transduction in cell types devoid of Ad’s native receptors and the incapability of gene delivery to targets behind physical barriers; (2) restricted accessibility to the central nerve system due to the existence of the blood-brain barrier (BBB); (3) lack of a useful strategy and platform to generate multi-functionality displaying Ad vectors …

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Oxidation Of Mercury During Selective Catalytic Reduction Of Nitric Oxide, Giang Tong Jan 2009

Oxidation Of Mercury During Selective Catalytic Reduction Of Nitric Oxide, Giang Tong

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A promising method for mercury removal from the gaseous products of coal combustion is the catalytic oxidation of elemental mercury to water-soluble mercuric chloride during selective catalytic reduction of NOx by ammonia, followed by removal of the oxidized mercury during wet flue gas desulfurization. Measurements of the mercury species distribution and sulfate formation at the outlet of a 310 mm long square cell monolithic V2O5-WO3/TiO2 commercial SCR catalyst showed the following trends: (1) Mercury oxidation was highly sensitive to HCl at the low levels characteristic of Powder River Basin subbituminous coals (0-5 ppmv). (2) Mercury oxidation was inhibited by NH3, …

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Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon Jan 2009

Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon

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Oxidative stress plays a critical role in pathogenesis of atherosclerosis. However, the effect of oxidative stress-induced molecular signaling in development of vascular calcification, a feature of advanced atherosclerosis, has not been defined. Osteogenic differentiation of vascular smooth muscle cells (VSMC) is critical in development of vascular calcification. We determined hydrogen peroxide (H2O2)-induced oxidative stress promoted a phenotypic switch of mouse primary VSMC from contractile to osteogenic phenotype. This effect was associated with increased expression and transactivity of Runx2, a key transcription factor for osteogenic differentiation. Inhibition of Runx2 using short hairpin RNA blocked oxidative stress-induced VSMC calcification. By contrast, adenovirus-mediated …

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Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang Jan 2009

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 …

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Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish Jan 2009

Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish

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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 …

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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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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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Parenting Practices And Desire For A Child Among Mothers Living With Hiv, Natalie De La Cruz Jan 2009

Parenting Practices And Desire For A Child Among Mothers Living With Hiv, Natalie De La Cruz

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One-quarter of adults living with HIV/AIDS in the US are women, most of whom are facing decisions regarding their reproductive future. Despite clear challenges and complexities facing HIV-positive women, most research suggests that they maintain strong desires and intentions for motherhood. This research explores the correlates of desire for another child, with a specific emphasis on examining the relationship between current parenting experiences and future childbearing desires, among a predominantly black sample of HIV-positive women (n=96) participating in the Making Our Mothers Stronger (MOMS) Project. Predictors of contraceptive use and consistency between contraceptive practices and fertility desires are also explored …

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Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka Jan 2009

Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka

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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 …

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The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley Jan 2009

The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley

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THE EFFECTS OF P-GLYCOPROTEIN DEFICIENCY ON INTESTINAL INTEGRITY AND HOMEOSTASIS ELIZABETH M. STALEY MICROBIOLOGY ABSTRACT P-glycoprotein (P-gp) is an ATP-binding transmembrane pump associated with substrate extrusion in cells of epithelial and hematopoietic lineage. Polymorphisms in multidrug resistance genes (MDR), which encode this protein, are associated with development of inflammatory bowel disease in patient subsets. Furthermore, FVB/N animals deficient in P-gp expression develop spontaneous colitis. Disease in FVB.mdr1a-/- animals is reported to be the result of P-gp deficiencies in intestinal epithelial cells. We developed a neonatal model of bone marrow reconstitution to accurately evaluate the contribution of P-gp deficiencies in either …

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Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton Jan 2009

Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton

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GENETIC COMPLEXITY AND POPULATION DIVERSITY OF PLASMODIUM FALCIPARUM IN THE PERUVIAN AMAZON PATRICK LEE SUTTON MICROBIOLOGY GRADUATE PROGRAM ABSTRACT Characterizing the genetic complexity of immunologically relevant proteins, expressed during the life cycle of P. falciparum, is essential for identifying and advancing potential vaccine candidates. The current malaria immunity paradigm is rooted in high transmission studies which have investigated the impact of high genetic diversity on the development of humoral responses. Given the dynamic nature of malaria parasites, especially their ability to acclimate to change, it is likely that regions of low transmission do not share the same malaria immunity paradigm …

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Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne Jan 2009

Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne

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Thrombospondin-1 (TSP1) is a multifunctional matricellular protein released by platelets in response to injury and secreted by cells under stress. TSP1 is cleaved into functional N- and C-terminal domain fragments, which have paradoxical actions with respect to angiogenesis, cell survival, and cell adhesion. Wound healing studies by others demonstrated that TSP1 knockout mice have delayed rates of wound closure, which was attributed to actions of the C-terminal domain. We wished to investigate the specific role of the N-terminal domain in tissue remodeling. Previously, we established that a sequence (aa 17-35) in the N-terminal domain of TSP1 induces focal adhesion disassembly, …

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The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul Jan 2009

The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul

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The secretory pathway within a cell consists of series of membrane compartments connected by shuttling secretory vesicles containing cargo that travel from endoplasmic reticulum (ER) though ER-to-Golgi intermediate compartment (ERGIC), the Golgi apparatus, and endosomal compartment to the plasma membrane (PM). The Golgi specific brefeldin A (BFA)-resistant factor 1 GBF1 has been identified as an important factor involved in traffic between ER and Golgi and within the Golgi apparatus. GBF1 belongs to a family of guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP on small GTPases, ADP-ribosylation factors (ARFs). The exchange of the nucleotide activates …

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Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal Jan 2009

Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal

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Hematopoiesis is a highly regulated process directed by the microenvironment or niche in the bone marrow and the transcription factors those signals activate. Gene knockout experiments have identified critical cytokine signals and transcription factors required for promoting the differentiation of a hematopoietic stem cell to a B cell, but the regulatory mechanisms have yet to be fully elucidated. In early B cell development, a transcriptional hierarchy exists wherein E2A proteins activate early B-cell factor (Ebf1), which in turn activates expression of the B cell commitment factor, Pax5. In our studies, we use IL-7 receptor alpha chain (IL-7Rα) knockout animals that …

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Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn Jan 2009

Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn

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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 …

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Marginal Zone B-Cell Precursors As Cellular Agents For Type I Ifn Promoted Antigen Transport, John Hsien Wang Jan 2009

Marginal Zone B-Cell Precursors As Cellular Agents For Type I Ifn Promoted Antigen Transport, John Hsien Wang

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Type I IFN is a known pro-inflammatory cytokine that is associated with the development of systemic lupus erythematosus (SLE). At the level of B-cell regulation, current literature primarily attributes the formation of autoantibodies at the post-germinal center stage when type I IFN is known to promote plasmablast differentiation. However, our findings here point to a type I IFN effect at the pre-germinal stage. Type I IFN promotes T-dependent antibody response, activation-induced cytidine deaminase (AID) expression, germinal center formation, all of which are processes before the onset of plasmablast differentiation. We have determined a subset of splenic transitional B-cells, that is …

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A Novel & Efficient Method To Produce High Titers Of Infectious Hpv In Organotypic Cultures Of Primary Human Keratinocytes, Hsu-Kun Wang Jan 2009

A Novel & Efficient Method To Produce High Titers Of Infectious Hpv In Organotypic Cultures Of Primary Human Keratinocytes, Hsu-Kun Wang

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Infections by the high-risk human papillomavirus type 18 (HPV-18) or type 16 (HPV-16) can lead to cancers of the anogenital tract. Because the propagation of HPVs is restricted to differentiated human squamous epithelia, experimental studies of the productive program are conducted in organotypic cultures. The current methods are of low efficiency and time consuming and have relied on immortalized epithelial cell lines that do not support efficient viral DNA amplification or virion production, compromising HPV genetic analyses and obscuring normal virus-host cell interactions. I used Cre-loxP site-specific recombination to develop a relatively simple, fast and highly efficient system to produce …

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