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Articles 1891 - 1920 of 2525

Full-Text Articles in Medicine and Health Sciences

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 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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Targeting Angiogenesis With Plasminogen Kringle 5, Braden Cox Mcfarland Jan 2009

Targeting Angiogenesis With Plasminogen Kringle 5, Braden Cox Mcfarland

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The recombinant fifth kringle domain of plasminogen (rK5) has been shown to induce apoptosis of dermal microvessel endothelial cells (MvEC), and this pro-apoptotic effect required rK5 binding to cell surface glucose-regulated protein 78 (GRP78). GRP78 is a member of the heat shock protein family and under certain conditions is expressed on the cell surface. I am interested in identifying new anti-angiogenic therapy for glioblastoma tumors. The efficacy of certain anti-angiogenic therapy can be improved when combined with radiation, and radiation is a standard therapy for glioblastoma tumors; therefore, I investigated the pro-apoptotic effect of rK5 combined with radiation on primary …

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Comparisons Between Behavioral And Electrophysiological Measures Of Visual Function In Rodent Models Of Retinal Degeneration, Glen R. Rubin Jan 2009

Comparisons Between Behavioral And Electrophysiological Measures Of Visual Function In Rodent Models Of Retinal Degeneration, Glen R. Rubin

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The critical flicker frequency (CFF) is the lowest frequency for which a flickering light appears steady. Measuring CFF indicates rod- and cone-driven function relative to light intensity. CFF can be measured by both electroretinogram (ERG) and behavior. We measured CFF in several rodent models of retinal degeneration in order to better characterize retinal degeneration and understand the functional implications of electrophysiological changes. We measured ERG CFF in RCS dystrophic (RCS-p+) and wild type (WT) rats at PN23, PN44, and PN64. ERG CFF data in RCS rats show significant early degeneration of the rods followed by cones. CFF was significantly lower …

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Substitute Costs: A Method For Determining Ecological Service Values In Stormwater Management, Steven B. Mckinney Jan 2009

Substitute Costs: A Method For Determining Ecological Service Values In Stormwater Management, Steven B. Mckinney

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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 …

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Predictors Of Self-Reported Health Status In Occupationally And Environmentally Exposed Individuals, Christie Shelton Jan 2009

Predictors Of Self-Reported Health Status In Occupationally And Environmentally Exposed Individuals, Christie Shelton

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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, …

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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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Protein Trafficking And 4.1r Relocalization In Plamodium Falciparum-Infected Erythrocytes, Lindsay A. Parish Jan 2009

Protein Trafficking And 4.1r Relocalization In Plamodium Falciparum-Infected Erythrocytes, Lindsay A. Parish

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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 …

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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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Mouse Modeling Of Pancreatic Ductal Adenocarcinoma (Pdac); Search For Early Diagnostic Markers And Therapeutic Targets, Kyoko Kojima Jan 2009

Mouse Modeling Of Pancreatic Ductal Adenocarcinoma (Pdac); Search For Early Diagnostic Markers And Therapeutic Targets, Kyoko Kojima

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PDAC is a highly malignant neoplasm that carries a very poor prognosis. PDAC development is a multistage transformation process that involves multiple genetic alterations that include activation of EGFR/HER2 and KRAS, and loss-of-function mutations in INK4A/ARF, p53 and SMAD4. In recent years, several genetically engineered mouse models that accurately recapitulate human pancreatic neoplasia have been developed. Histological characterizations of those models have revealed possible roles for the mutated RAS, INK4a/ARF and p53 in pancreatic tumorigenesis. However, the role of SMAD4 mutation, which is associated with late stages of tumor progression, has yet to be explored. Additionally, those models that would …

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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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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

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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

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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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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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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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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

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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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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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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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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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