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Articles 1861 - 1890 of 2525

Full-Text Articles in Medicine and Health Sciences

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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Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith Jan 2009

Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith

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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 …

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The Relationship Of Sexual Empowerment And Sexual Pressure To Condom Use Of Young Adult African American And Caucasian Women, Carrie Ann Long Jan 2009

The Relationship Of Sexual Empowerment And Sexual Pressure To Condom Use Of Young Adult African American And Caucasian Women, Carrie Ann Long

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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 …

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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

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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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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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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

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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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The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng Jan 2009

The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng

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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 …

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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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Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck Jan 2009

Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck

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Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …

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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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Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder Jan 2009

Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder

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Members of the Fc receptor-like (FCRL) family are cell-surface proteins with ancient conservation, distinct lymphocyte expression patterns, and tyrosine-based signaling capa-bilities that imply a fundamental role for them in modulating immune responses. Though they share many features with the Fc receptors (FCR) for IgG and IgE, FCRLs have not been found to bind immunoglobulin. In these studies, we sought to characterize the cellu-lar expression pattern, binding partner, and function of a recently identified FCRL family member, human FCRL6. By developing specific monoclonal antibodies (mAbs) we determined that FCRL6 is dis-tinctly expressed by cytotoxic lymphocytes, namely NK cells, CD8+ T cells, …

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Shunt Failure In Children With Hydrocephalus: Impact Of Sociodemographic Predictors On Time To Medical Evaluation For Shunt Failure And The Economic Burden Associated With Shunt Failure, Chevis Nacole Shannon Jan 2009

Shunt Failure In Children With Hydrocephalus: Impact Of Sociodemographic Predictors On Time To Medical Evaluation For Shunt Failure And The Economic Burden Associated With Shunt Failure, Chevis Nacole Shannon

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Ventriculo-peritoneal shunts continue to be the standard surgical procedure for treating children diagnosed with hydrocephalus, regardless of etiology. The failure of these shunts can cause acute medical problems for the child requiring immediate medical care. It is known that hydrocephalus directly impacts a child's health status, educational abilities, developmental opportunities and emotional well being. An important gap in the current literature is the examination in a homogenous patient population of the impact of sociodemographic factors on the management of shunt failure and the economic burden on the family. The objective of this dissertation research study was to better understand shunt …

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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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Characterizing The Role Of Primary Cilia In The Hair Follicle And Skin, Jonathan Merle Lehman Jan 2009

Characterizing The Role Of Primary Cilia In The Hair Follicle And Skin, Jonathan Merle Lehman

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Primary cilia have been established as a nearly ubiquitous microtubule based signaling organelle, yet their function in many organs, including the hair and skin, is unknown. We hypothesized that the primary cilium would play vital roles in the hair follicle and skin based on the cilium's well characterized interactions with the Shh and Wnt developmental signaling pathways. This dissertation describes our efforts to determine the localization of the primary cilia in the murine hair follicle and assess the function of this organelle in the hair and skin. We used confocal immunofluorescence microscopy to virtually section the entire hair follicle and …

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Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton Jan 2009

Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton

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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 …

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Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan Jan 2009

Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan

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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 …

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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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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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Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya Jan 2009

Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya

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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, …

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Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee Jan 2009

Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee

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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; …

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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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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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Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros Jan 2009

Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros

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Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution 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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The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins Jan 2009

The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins

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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 …

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Structural And Functional Studies On Heat Shock Protein Hsp40-Hdj1 And Golgi Er Trafficking Protein Get3, Junbin Hu Jan 2009

Structural And Functional Studies On Heat Shock Protein Hsp40-Hdj1 And Golgi Er Trafficking Protein Get3, Junbin Hu

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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 …

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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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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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