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Full-Text Articles in Medicine and Health Sciences

Brachytherapy Seed And Applicator Localization Via Iterative Forward Projection Matching Algorithm Using Digital X-Ray Projections, Damodar Pokhrel Oct 2010

Brachytherapy Seed And Applicator Localization Via Iterative Forward Projection Matching Algorithm Using Digital X-Ray Projections, Damodar Pokhrel

Theses and Dissertations

Interstitial and intracavitary brachytherapy plays an essential role in management of several malignancies. However, the achievable accuracy of brachytherapy treatment for prostate and cervical cancer is limited due to the lack of intraoperative planning and adaptive replanning. A major problem in implementing TRUS-based intraoperative planning is an inability of TRUS to accurately localize individual seed poses (positions and orientations) relative to the prostate volume during or after the implantation. For the locally advanced cervical cancer patient, manual drawing of the source positions on orthogonal films can not localize the full 3D intracavitary brachytherapy (ICB) applicator geometry. A new iterative forward …


Utilization Patterns And Economic Impact Of Iv Iron And Erythropoiesis Stimulating Agents In Chronic Kidney Disease Patients: A Multi-Hospital Study, Avani Joshi Oct 2010

Utilization Patterns And Economic Impact Of Iv Iron And Erythropoiesis Stimulating Agents In Chronic Kidney Disease Patients: A Multi-Hospital Study, Avani Joshi

Theses and Dissertations

Background: Chronic kidney disease (CKD) affects approximately 20 million Americans and is the cause of significant morbidity and mortality. Anemia, common in CKD, develops early in the disease process. It contributes to increased risk of cardiovascular disease, hospitalization, mortality, and diminishes health-related quality of life. Intravenous iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in CKD. The utilization patterns of IV iron and ESA, and their impact on hospital costs and length of stay merits investigation. Objectives: There were five general objectives of this investigation. The rate and extent of utilization of IV iron in anemic CKD …


Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart Sep 2010

Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart

Theses and Dissertations

Since its discovery, it was appreciated that the antifolate pemetrexed had multiple targets within folate metabolism. This laboratory was instrumental in showing that pemetrexed elicited its primary action as a thymidylate synthase inhibitor. Unusual for an antifolate, pemetrexed showed significant clinical activity against malignant pleural mesothelioma and non-small cell lung cancer. Accordingly, the FDA recently issued first-line approvals for pemetrexed in these diseases, leading us to question whether the effects of pemetrexed on other folate-dependent targets could explain this atypical clinical activity of the drug. Studies in this dissertation showed that in addition to thymidylate synthase inhibition, pemetrexed was also …


B Cell Adam10 Activity Is Increased By Kainate Receptor Activation: Potential Role Of This Pathway In Th2 Immunity And Cancer, Jamie Sturgill Sep 2010

B Cell Adam10 Activity Is Increased By Kainate Receptor Activation: Potential Role Of This Pathway In Th2 Immunity And Cancer, Jamie Sturgill

Theses and Dissertations

CD23 has long been appreciated to be a natural, negative regulator of IgE synthesis. This understanding is due in part to animal models in which CD23 deficient or CD23 transgenic animals display exacerbated or reduced IgE levels respectively. Interestingly, CD23 is susceptible to proteolytic cleavage from the cell surface. When this occurs, CD23 loses its regulatory capability and the solubilized form can lead to pro-inflammatory events through its cytokinergic activity on macrophages. Thus, targeting this specific cleavage would be beneficial to the control of allergic disease by stabilizing CD23 at the cell surface. Inhibitor studies performed by our group as …


The Influence Of Language Production, Comprehension, And Pragmatic Judgment On Prosocial Behavior In Children With Language Impairment, Nicole Yvette Weber Sep 2010

The Influence Of Language Production, Comprehension, And Pragmatic Judgment On Prosocial Behavior In Children With Language Impairment, Nicole Yvette Weber

Theses and Dissertations

The purpose of this study was to examine the relationship between language skills and prosocial behavior in 37 children with language impairment (LI) and 37 typically developing peers matched for age (ranging from 6;11 to 11;1 years). The influence of gender on this relationship was also considered. Three different subtests of the Comprehensive Assessment of Spoken Language (Carrow-Woolfolk, 1999) were used to evaluate language ability in the areas of language comprehension, language production and pragmatic judgment skills. The Teacher Behavior Rating Scale (C. H. Hart & Robinson, 1996) was used to evaluate prosocial behavior. The current study replicated previous research …


Mechanisms Of Rotator Cuff Disease: Alterations Of Scapular Kinematics On Subacromial Space, Amee Seitz Aug 2010

Mechanisms Of Rotator Cuff Disease: Alterations Of Scapular Kinematics On Subacromial Space, Amee Seitz

Theses and Dissertations

Rotator cuff disease is multi-factored and has been attributed to both intrinsic and extrinsic factors. Extrinsic factors contribute to compression of the rotator cuff tendons. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. Subacromial impingement is related to factors that encroach upon the subacromial space, while internal impingement affects the articular side of the tendons adjacent to glenoid. While the mechanisms of impingement are varied, further research is necessary to improve treatment and patient outcomes. Chapter 2 is a thorough review of literature on the mechanisms of …


Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar Aug 2010

Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar

Theses and Dissertations

This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed …


Samoan Speech Audiometry: Developing Word Recognition Materials For Native Speakers Of Samoan, Emma Lilian Kruger Aug 2010

Samoan Speech Audiometry: Developing Word Recognition Materials For Native Speakers Of Samoan, Emma Lilian Kruger

Theses and Dissertations

Hearing can be evaluated through the presentation of tones or speech. Speech audiometry determines an individual's speech recognition threshold and word recognition score. Traditionally these materials were developed using familiar, frequently used, monosyllabic words. Currently, there are various types of word recognition materials including those which use word lists, short half-lists, and materials which use sentences level stimuli with competing noise. Word recognition materials were first developed in Standard American English; today, materials are now readily available in many other languages. When possible, word recognition materials are developed digitally to standardize their presentation. Currently, no recorded word recognition materials are …


Adam10 Is A Critical Regulator Of B Cell Development, Antibody Production, And Myeloid-Derived Suppressor Cell Expansion: Effects Of B Cell-Specific Adam10 Deletion And Overexpression In Vivo., David Gibb Aug 2010

Adam10 Is A Critical Regulator Of B Cell Development, Antibody Production, And Myeloid-Derived Suppressor Cell Expansion: Effects Of B Cell-Specific Adam10 Deletion And Overexpression In Vivo., David Gibb

Theses and Dissertations

Proteolytic processing of transmembrane receptors and ligands can have dramatic effects on cell signaling and subsequent cellular responses. Previous studies demonstrated that a disintegrin and metalloproteinase 10 (ADAM10) may cleave numerous B cell-expressed receptors, including the low affinity IgE receptor (CD23). However, lethality of ADAM10-deficient embryos has limited examination of these cleavage events in lymphocytes. To investigate their role in B cell development and function, we generated B cell-specific ADAM10 knockout mice. Intriguingly, deletion prevented development of the entire marginal zone B cell (MZB) lineage. Further analysis revealed that ADAM10 is required for S2 cleavage of the Notch2 receptor and …


Brain Mapping Of The Mismatch Negativity And The P300 Response In Speech And Nonspeech Stimulus Processing, Skylee Simmons Neff Aug 2010

Brain Mapping Of The Mismatch Negativity And The P300 Response In Speech And Nonspeech Stimulus Processing, Skylee Simmons Neff

Theses and Dissertations

Previous studies have found that behavioral and P300 responses to speech are influenced by linguistic cues in the stimuli. Research has found conflicting data regarding the influence of phonemic characteristics of stimuli in the mismatch negativity (MMN) response. The current investigation is a replication of the study designed by Tampas et al. (2005), which studied the effects of linguistic cues on the MMN response. This current study was designed to determine whether the MMN response is influenced by phonetic or purely acoustic stimuli, and to expand our knowledge of the scalp distribution of processing responses to within- and across-category speech …


Adherence To The American College Of Surgeons (Acs) Recommendation On Double Gloving, Hand Free Zone And Blunt Suture Needle Use Among Surgeon Ranks, Akbar Nassiry Aug 2010

Adherence To The American College Of Surgeons (Acs) Recommendation On Double Gloving, Hand Free Zone And Blunt Suture Needle Use Among Surgeon Ranks, Akbar Nassiry

Theses and Dissertations

Background: The American College of Surgeons guidelines suggest the use of intact gloves, double gloving, hands-free zone technique to pass sharp instruments, and blunt tip suture needles to protect patients, as well as the surgical team. This study estimates the extent to which these guidelines are followed in a large academic health system. Methods: Over a two-month period in the spring of 2010, 320 general surgical attendings, subspecialty surgical attendings, and surgical resident physicians practicing at a large academic health system, were approached during or after surgical conferences to participate in a cross-sectional study. Nearly 1/3rd completed an anonymous and …


Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen Aug 2010

Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen

Theses and Dissertations

CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not …


Environmental Responses Of Two-Component Systems In Streptococcus Sanguinis, Jenishkumar Patel Aug 2010

Environmental Responses Of Two-Component Systems In Streptococcus Sanguinis, Jenishkumar Patel

Theses and Dissertations

The gram-positive bacterium Streptococcus sanguinis is a member of human indigenous oral microbialflora and has long been recognized as a key player in the bacterial colonization of the mouth. S. sanguinis is also the most common viridians streptococcal species implicated in infective endocarditis. Although many studies have focused on two-component systems in closely related Streptococcus species such as S. mutans, S. pneumoniae and S. gordonii; the mechanism of the response regulator in S. sanguinis is still unknown. The ability of S. sanguinis to adapt and thrive in hostile environments suggests this bacterium is capable of sensing and responding to various …


Volumetric Growth Model Of Human Medulloblastoma In The Nude Mouse Cerebellum, Thomas Gavigan Aug 2010

Volumetric Growth Model Of Human Medulloblastoma In The Nude Mouse Cerebellum, Thomas Gavigan

Theses and Dissertations

Medulloblastoma is the most common brain tumor in children, accounting for 10-20% of primary central nervous system (CNS) neoplasms and approximately 40% of all posterior fossa tumors. It is a highly invasive embryonal neuroepithelial tumor that typically arises in the cerebellar vermis and has a tendency to disseminate throughout the CNS early in its course. The molecular mechanisms of the disease largely remain uncharacterized, as the clinical treatment is still associated with mortality and severe side effects. The development of a clinically relevant in vivo model is important not only to further understand the disease but also to provide a …


Factors Affecting Gingival Excess, Altered Passive Eruption And Recession In The Mandibular Anterior And Premolar Sites, William Bohlen Aug 2010

Factors Affecting Gingival Excess, Altered Passive Eruption And Recession In The Mandibular Anterior And Premolar Sites, William Bohlen

Theses and Dissertations

Abstract FACTORS AFFECTING GINGIVAL EXCESS, ALTERED PASSIVE ERUPTION AND RECESSION IN THE MANDIBULAR ANTERIOR AND PREMOLAR SITES By William F Bohlen, D.M.D. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University. Virginia Commonwealth University, 2010 Major Director: Thomas Waldrop, DDS, MS Program director, Department of Periodontics, Virginia Commonwealth University AIM: The aim of this study was to determine the factors affecting gingival excess, altered passive eruption and recession. METHODS: 100 subjects were examined clinically and models of their mandible were fabricated. Demographic, periodontal and cast measurements were …


Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis Aug 2010

Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis

Theses and Dissertations

Krüppel-like factors (KLFs) are a family of 3 Cys2/His2 zinc finger transcription factors with a diverse set of roles in cellular differentiation, cell cycle regulation, tumor suppression, erythropoiesis, angiogenesis, and other processes. During embryonic development, KLF2 has a role in vessel maturation. Adult conditional KLF4 knockout mouse embryos have thickened arterial intima follow vascular injury. Breeding KLF2+/- and KLF4+/- mice resulted in the generation of KLF2/KLF4 double knockout (DKO) embryos. KLF2/KLF4 DKO embryos died by E10.5 with cranial bleeding. Using immunohistochemistry, embryo whole-mounts were examined for differences in gross vascularization between wild-type (WT), KLF2-/- and KLF2/KLF4 (DKO embryonic day 9.5 …


Novel Roles For Reelin In Retinogeniculate Targeting, Cheryl Haner Aug 2010

Novel Roles For Reelin In Retinogeniculate Targeting, Cheryl Haner

Theses and Dissertations

In the developing visual system, the axon of a pre-synaptic cell must be guided to a post-synaptic partner. Retinal ganglion cells (RGCs) in the eye are an excellent model to study this process. Multiple classes exist that respond to specific types of light input, and these project to different destinations in the brain that process distinct types of information. The RGC axons that navigate to the lateral geniculate nucleus (LGN) do so in a class-specific manner. Axons from RGCs that mediate non-image forming functions innervate the ventral LGN (vLGN) and the intergeniculate leaflet (IGL). Axons from RGCs that process image-forming …


Assessing Economic And Hrql Burden Of Food Allergy And Anaphylaxis In The U.S., Dipen Patel Jul 2010

Assessing Economic And Hrql Burden Of Food Allergy And Anaphylaxis In The U.S., Dipen Patel

Theses and Dissertations

Background: Food allergy, an abnormal immunologic response to food protein, has an estimated prevalence of 6% in young children and 3.7% in adults in the U.S. The only proven therapy for food allergy is strict elimination of the offending allergens. As a result, caregivers and patients could experience constant anxiety and stress that affects their quality of life. Additionally, food allergy can lead to significant economic impact on the health care system, since severe reactions often lead to ED visits and hospitalizations. Objectives: The first major objective was to determine the economic burden of Food Allergy and Anaphylaxis (FAA) patients …


Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal Jul 2010

Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal

Theses and Dissertations

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …


The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji Jul 2010

The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji

Theses and Dissertations

Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. …


Membrane-Bound Matrix Metalloproteinases Influence Reactive Synaptogenesis Following Traumatic Brain Injury, Kelly Warren Jul 2010

Membrane-Bound Matrix Metalloproteinases Influence Reactive Synaptogenesis Following Traumatic Brain Injury, Kelly Warren

Theses and Dissertations

Traumatic brain injury (TBI) produces axonal damage and deafferentation, triggering injury-induced synaptogenesis, a process influenced by matrix metalloproteinases (MMP) and their substrates. Here we report results of studies examining the expression and potential role of two membrane-bound MMPs, membrane-type 5-MMP (MT5-MMP) and a disintegrin and metalloproteinase-10 (ADAM-10), along with their common synaptic substrate N-cadherin, during the period of reactive synaptogenesis. Protein and mRNA expression of MT5-MMP, ADAM-10 and N-cadherin were compared in two TBI models, one exhibiting adaptive plasticity (unilateral entorhinal cortex lesion; UEC) and the other maladaptive plasticity (fluid percussion injury + bilateral EC lesions; TBI+BEC), targeting 2, 7, …


The Relationship Among Maternal Infant Bonding, Spirituality, And Maternal Perception Of Childbirth Experience, Linda Bennington Jul 2010

The Relationship Among Maternal Infant Bonding, Spirituality, And Maternal Perception Of Childbirth Experience, Linda Bennington

Theses and Dissertations

The beginning of life is an intense experience for both mother and baby and sets the foundation for future interactions. Researchers have theorized that maternal infant bonding begins prenatally and continues on through the postnatal period. Mṻller (1996) examined that process to determine if prenatal bonding was related to postnatal bonding and discovered that there was only a modest correlation between the two. This led to speculation as to what variables, besides prenatal bonding, could influence postnatal bonding. Klaus & Kennell (1976) noted the detrimental effects of a lack of bonding in terms of abuse and attachment disorders and emphasized …


Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda Jul 2010

Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda

Theses and Dissertations

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of …


Role Of Pyridoxine 5'-Phosphate Oxidase In Metabolism And Transfer Of Pyridoxal 5'-Phosphate, Sayali Karve Jul 2010

Role Of Pyridoxine 5'-Phosphate Oxidase In Metabolism And Transfer Of Pyridoxal 5'-Phosphate, Sayali Karve

Theses and Dissertations

Deficiency of vitamin B6 due to mutations in key B6 metabolizing enzymes is suspected to contribute to several pathologies. Vitamin B6 in its active form, pyridoxal 5’-phosphate (PLP) is a cofactor for over 140 known B6 requiring (or PLP-dependent) enzymes, that serve vital roles in many biochemical reactions. There are three primary vitamin B6 forms, pyridoxine (PN), pyridoxamine (PM) and pyridoxal (PL) which are phosphorylated to pyridoxine 5’-phosphate (PNP), pyridoxamine 5’-phosphate (PMP) and PLP respectively. Pyridoxal kinase (PLK) and pyridoxine 5’-phosphate oxidase (PNPO) are the key enzymes involved in both salvage and de novo pathways of PLP biosynthesis. Mutations in …


The Effect Of Anticholinergic Burden On Functional Outcomes In Patients With Moderate To Severe Alzheimer’S Disease, Sheetal Dharia Jul 2010

The Effect Of Anticholinergic Burden On Functional Outcomes In Patients With Moderate To Severe Alzheimer’S Disease, Sheetal Dharia

Theses and Dissertations

Background: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by a progressive loss of memory, judgment, and thinking in older adults. The current treatment is cholinesterase inhibitors, which increase acetylcholine at the synapse. Medications with anticholinergic (AC) activity are given for a variety reasons including for the treatment of comorbid conditions or side effects of cholinesterase inhibitors (ChEIs). These drugs inhibit acetylcholine in the brain. Studies have shown the detrimental outcomes of using AC medications with ChEIs in older adults. Moreover, older patients take more medications and have an increased risk of developing AC toxicity …


The Development And Use Of A Geographic Information System For Evaluating The Association Between Pesticide Exposure And Prostate Cancer, Kristen Wells Jul 2010

The Development And Use Of A Geographic Information System For Evaluating The Association Between Pesticide Exposure And Prostate Cancer, Kristen Wells

Theses and Dissertations

Abstract 1 – A Geographic Information System for Evaluating Residential Pesticide Exposure and Prostate Cancer Incidence Agricultural pesticide exposure is hypothesized to be a risk factor for prostate cancer, and such exposures are of particular concern for men living in farming communities where large-scale pesticide applications occur. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006, and county and census tract level age-adjusted incidence rates were calculated. Historical crop-specific land use records and pesticide sales data for the state of Iowa during 1990 were integrated into a geographic information system …


The Transcriptional Regulation Of Hla-E By Interferon-Gamma In Tumor Cells, Quintesia Grant Jul 2010

The Transcriptional Regulation Of Hla-E By Interferon-Gamma In Tumor Cells, Quintesia Grant

Theses and Dissertations

The human Class Ib gene, HLA-E inhibits both Natural Killer Cells and a subset of CD8+ cytotoxic T lymphocytes by engaging the CD94/NKG2A inhibitory receptor. IFN-γ induces the expression of HLA-E as well as Class Ia molecules, which are required for the killing of target cells. Since HLA-E has negative effects on immune killing of target cells, we have sought to identify locus specific mechanisms of IFN-γ induction in order to identify molecular targets for selective activation of Class Ia genes, but not HLA-E. We have previously identified a unique upstream IFN-γ response region in the HLA-E promoter and showed …


Pyridoxal Kinase: Its Role In Vitamin B6 Metabolism, Jigarkumar Desai Jul 2010

Pyridoxal Kinase: Its Role In Vitamin B6 Metabolism, Jigarkumar Desai

Theses and Dissertations

Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two vitamin B6 salvage enzymes involved in metabolism of the primary inactive vitamin B6 (pyridoxal, pyridoxine and pyridoxamine) into the active cofactor form, pyridoxal 5’-phosphate (PLP). PLP, arguably the most important vitamin, is required by numerous vitamin B6 (PLP-dependent) enzymes as a co-factor. These enzymes serve vital roles in the metabolism of glucose, lipids, amino acids, heme, DNA/RNA and many neurotransmitters. High levels of vitamin B6 are linked to neurotoxicity, due to the non-specific interactions of PLP with non-B6 proteins. This problem is controlled, in part, by maintaining …


The Mechanism Of Obesity In Rai1+/- Mice, Kristie Schmidt Jul 2010

The Mechanism Of Obesity In Rai1+/- Mice, Kristie Schmidt

Theses and Dissertations

Smith-Magenis syndrome (SMS) is a genetic disorder caused by a deletion or mutation of the retinoic acid induced 1 (RAI1) gene on chromosome 17p11.2 that results in haploinsufficiency. SMS patients with a deletion account for 90% of the cases, while the other 10% have a mutation in RAI1. The syndrome is characterized by cognitive impairment, craniofacial abnormalities, sleep disturbances, developmental delay, obesity, and behavioral phenotypes. SMS is thought to affect 1:25,000 live births, although due to similar infantile phenotypes with Down syndrome and Prader-Willi syndrome, SMS may be mis- or under-diagnosed. In a study of 54 children, it was shown …


Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers Jul 2010

Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers

Theses and Dissertations

Previous studies from this and other laboratories have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to promote both autophagy and apoptosis in breast tumor cells, as well as interfering with endothelial cell function and potentially disrupting tumor vasculature. The current work was designed to investigate the interaction between JG-03-14 and cell culture models of colon carcinoma and melanoma, specifically HCT116 human colon carcinoma cells and B16F10 murine melanoma cells. In both cases, JG-03-14 promoted death in the bulk of the treated population. FACS analysis, DAPI and TUNEL staining …