Medicine and Health Sciences Commons^™

Inducible Heat Shock Protein 70 Enhances Human Papillomavirus Type 31 Genome Replication, Viral Capsid Protein Nuclear Localization And Progeny Virion Morphogenesis In Human Keratinocytes, Hebin Song

Biomedical Sciences ETDs

Human papillomaviruses (HPVs) are small, non-enveloped double stranded DNA viruses that demonstrate a strict species and cell type tropism for human epithelial cells. The association between high-risk HPV types and cervical cancer is well established. Additionally, HPVs have been implicated as causes in development of several other epithelial cancer types. Increasing data indicate heat shock proteins (HSPs) including inducible HSP70 (HSP70i) are involved in the replicative cycles of different viruses including adenoviruses, polyomaviruses (PyV), and some RNA viruses. Cell-free system studies implicate HSP70i in HPV11 genome replication with E1 and E2 proteins, and there is evidence that HSP70 is involved …

Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith

Theses and Dissertations

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …

Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney

Theses and Dissertations

The chemokine receptor CCR5 has been implicated in the pathogenesis of prostate cancer. A novel natural product, anibamine, was isolated and found to be a micromolar inhibitor of the receptor. Anibamine was used as a new anti-prostate cancer lead compound. To discover the pharmacophore, analogs of anibamine were designed using the “deconstruction-reconstruction-elaboration” approach and synthesized. The establishment of a stereoselective route to only one isomer was explored, to increase yield and eliminate elaborate purification procedures. Analogs were found to have anti-prostate cancer activity at levels higher than the parent compound. The molecular modeling studies of the deconstructed analogs indicate that …

Teaching A School-Based Aac Team To Support The Communication Skills Of A Student Who Requires Aac, Amy Thatcher

Speech and Hearing Sciences ETDs

Many children of all ages are in need of augmentative and alternative communication (AAC). Adult communication partners in the school setting typically interact differently with children who use AAC than they do with others. In prior studies, an eight-step instructional program designed to teach adult communication partners to facilitate the communication skills of students who use AAC has been used within an individual instructional format. The eight-step instructional model used to teach these adults has been shown to be effective; however, research is required to establish the efficacy of this program when providing instruction to adult communication partners within group …

Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez

Theses and Dissertations

The neisserial transferrin binding proteins (Tbps) comprise a bipartite system for iron acquisition from human transferrin. TbpA is a TonB-dependent outer membrane protein that forms the pore for iron internalization. TbpB is a surface-exposed lipoprotein that makes the iron-uptake process more efficient. Previous studies have shown that the genes encoding these proteins are arranged in a bicistronic operon, with the tbpB gene located upstream of tbpA. The operon is under the control of the ferric uptake regulator (Fur) protein. However, promoter elements necessary for the regulation of the operon have not been experimentally defined. In this study, putative regulatory motifs …

Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia

Theses and Dissertations

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task …

Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah

Theses and Dissertations

Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.

Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins

Theses and Dissertations

This thesis investigates two separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1). To address how the H493R mutation elicits the specific pathologies of SCAN1 and to further elucidate the role of TDP1 in processing DNA end modifications, we generated a Tdp1 knockout mouse and characterized their behavior and specific repair deficiencies in extracts of embryonic fibroblasts …

Denitration In Colonic Smooth Muscle, Seemab Malick

Theses and Dissertations

Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that …

Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones

Theses and Dissertations

The primary aims of this study were to examine acquired genetic and epigenetic changes that occur in individuals with increasing age and to determine how these changes are influenced by genetic/environmental factors. Acquired genetic changes were assessed by determining the frequency and chromosomal contents of spontaneously occurring micronuclei in identical and fraternal twins. A total of 115 individuals (48 twin pairs and 19 singletons) were evaluated, ranging in age from 7 to 85 years. As expected, micronuclei frequencies, which are indicative of genomic damage, significantly increased with age (p<0.0001, r=0.446). The majority of micronuclei (32%) contained sex chromosomes and the frequency of sex chromosome-bearing micronuclei significantly increased with age (p<0.0001). The frequency of autosome-containing micronuclei was not significantly influenced by age or gender. However, some autosomes were seen more (chromosomes 4, 8, and 9) or less (chromosomes 17 and 22) frequently than expected by chance (p<0.05). An evaluation of the numerical contents of the sex chromosome-containing micronuclei and their corresponding binucleates showed that the majority of the binucleates had an abnormal chromosomal complement (either hypodiploid or hyperdiploid), with the subset of binucleates having a normal chromosomal complement decreasing with age for both the Y chromosome in males and the X chromosome in females. Model fitting, implemented in Mx, showed the variation in the frequency of micronuclei to be best explained by either additive genetic and unique environmental components, or common and unique environmental factors. Specific environmental exposures and health conditions that were shown to influence micronuclei frequencies, included: multivitamins, leafy green vegetables, fruit, vitamin E supplements, arthritis, heart disease, allergies, and alcohol. To assess acquired epigenetic changes, global methylation profiles of two identical twin pairs were compared and found to differ, indicating that individuals do develop alterations in their methylation profiles with age. Furthermore, the twin pair having a significant difference in their micronuclei frequencies and environmental exposures had more differences in their methylation pattern compared to the twin pair whose micronuclei frequencies and environmental factors did not differ. Overall, genetic and epigenetic changes were shown to occur with age and to be influenced by genetic and lifestyle factors.

Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman

Theses and Dissertations

There is conflicting data on the effects of statins on cerebral vasospasm and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. In this retrospective cohort study, patients were divided into those who received pravastatin (PRAV group) 40mg/d and those who did not (NP group). Data were analyzed using multivariate logistic regression. Eighty-one patients met inclusion criteria. There was a statistically significant decreased in the incidence of vasospasm in the PRAV group; however, this association did not retain significance after adjusting for WFNS, race, elevated WBC, and clipping (59% PRAV vs. 88% NP, p=0.08). There was no statistically significant difference in …

Gender And Ovarian Hormone Effects On The Relative Contribution Of Chromaticity To Brightness, Brian Keith Foutch

Dissertations

PURPOSE: The chromatic contribution to brightness perception was compared in males and females. METHODS: Direct brightness matching (DBM) and heterochromatic flicker photometry (HFP) were used to measure relative luminous efficiency, and DBM/HFP ratios were predicted to be higher for females than males on repeated measures and for each "primary" color. No gender differences were predicted in DBM or HFP measures. Within-females effects of estradiol (E2) and progesterone (PG) levels, contraceptive use, and menstrual cycle phase were also investigated. It was expected that E2 would directly predict DBM/HFP ratios and that PG would antagonize that relationship. Based on that prediction, DBM/HFP …

Trudi Schoop: Passing On Her Legacy, Jeff Gilbert

Creative Arts Therapies Theses

The purpose of this thesis project was to create a documentary style recording of a panel of dance/movement therapy professionals talking about their work with, or study of, noted dance/movement therapy pioneer Trudi Schoop at a workshop during the 2009 American Dance Therapy Association (ADTA) Conference. My research questions for the panel and its audience were: “What were the qualities about Trudi Schoop that so many people appreciated about her (what was that light)?” “What did she do to cultivate those qualities?” and “How did she pass that on to others?” (Results in Appendix C).

The audience was invited to …

The Effect Of All-Trans Retinoic Acid And Fatty Acids On Mcf-7 Breast Cancer Cell Progression, David A. Brown

Master's Theses

Vitamin A metabolites and retinoids may slow the progression of breast cancer and elicit anti-neoplastic properties similar to those of omega-3 fatty acids. Studies using animal models show a decrease in the incidence, growth and metastisis of mammary tumors in the presence of specific fatty acids. This effect is also seen with use of retinoids, specifically all-trans retinoic acid (AtRA). Thus, fatty acids may also alter retinoid homeostasis in mammary carcinoma cells (MCF-7s). The potential for inter/co dependency among fatty acids and retinoids is considerable, and here it has been hypothesized that a decrease in cancer progression will occur in …

Contextual Factors Influencing The Acute Care Registered Nurse's Response To Clinical Alarms, Kathleen Mary Stacy Phd

Dissertations

Nurses are faced with a multitude of clinical alarms on a daily basis. There is an inherent expectation that upon hearing an alarm the nurse will immediately respond to assess the situation and initiate appropriate action to correct the problem. Yet this does not always occur. Issues with alarm responsiveness can pose a serious threat to patient safety. The purpose of this qualitative study was to develop a broader understanding of the contextual factors that influenced the acute care nurse's response to clinical alarms. This study used an interpretive phenomenological methodology to study the lived experiences of the nurses who …

Bactericidal Effects Of Low Temperature Atmospheric Pressure Plasma On Porphyromonas Gingivalis, Arwa Mahasneh

Dental Hygiene Theses & Dissertations

Purpose: The biomedical application of low temperature atmospheric pressure plasma (LTAPP) is a collaborative interest for engineering, medical, dental and biological researchers. This laboratory study tested whether LTAPP can limit growth of Porphyromonas gingivalis, a periodontal pathogen strongly associated with periodontal disease, disease progression, and refractory periodontitis. Methods: After extensive pilot trials, the study consisted of 24 agar plate samples of P. gingivalis- 20 samples were exposed to LTAPP at 5, 7, 9 and 10 minutes and 4 control samples were exposed to helium gas only. Immediately after exposures, the samples were incubated anaerobically for 72 hour at …

The Role Of Human Endogenous Retroviruses In Renal Cell Carcinoma, Michele D. Tisdale

Biological Sciences Theses & Dissertations

Human endogenous retroviruses make up approximately 8-9% of the human genome. A number of expressed HERVs, those that are actively transcribing, have been associated with various cancers. Suppression mechanisms that control HERV expression often fail or become more permissive in tissues where expression should be restricted. Previous studies have identified HERV expression in breast cancer tissues, whereas normal tissue HERV expression remained suppressed. In addition, studies of DNA hypermethylation have correlated with the ability to contribute to cancer development. Hypermethylation of several tumor suppressor genes occurs frequently in cancers and alterations in promoter regions could contribute to the development of …

Ekg Tracking For Augmented Standardized Patient Virtual Pathology Stethoscope Heart Auscultation, Sujith Surendran

Electrical & Computer Engineering Theses & Dissertations

In recent years, a lot of research has focused on improving the clinical skills of medical students and medical practitioners using standardized patients. Standardized patients (SP's) are used by the medical students and physicians in place of mannequins for a more realistic experience. SP's are real people trained to simulate specific illnesses and conditions to a high degree of accuracy which makes it difficult for the medical students to distinguish them from real patients. This research will enhance the capabilities of the standardized patients by providing a non-invasive, natural, harmless and realistic appearing tracking method for placing virtual pathologies using …

Oncology Nurses' Perceptions Of Self-Compassion: A Pilot Study, Miriam R. Lindell

Theses and Graduate Projects

Oncology nurses face extraordinary stressors in their work. If this stress becomes prolonged, these nurses are at risk for burnout and compassion fatigue. One effective way for nurses to manage stress is to care for themselves, body, mind, and spirit. The concept of self-compassion reflects a meaningful approach to self-care. This pilot study explored the perception'of self-compassion by hospital based oncology nurses. A convenience sample of 37 oncology nurses was surveyed using four demographic questions and the Self-Compassion Scale by Kristin Neff. The results demonstrated positive correlation between years of nursing experience and years of oncology nursing experience with common …

Transformational Nursing Simulation: Bringing Life To Inanimate Objects For The Purpose Of Educating And Re-Igniting Passion, Pamela A. Torkkola

Theses and Graduate Projects

A transformational nursing simulation program that incorporates a holistic approach in caring for the caregiver is the focus for a Master's Field Project paper. As an alternative to the construction of a generic nursing simulation center that is limited to the education of knowledge and skills, a larger vision centered in Margaret Newman's nursing theory, Health as Expanding Consciousness is proposed. Business models, an incremental approach and practical suggestions are offered in support of healthcare organizations working toward a Center for Nursing Arts and Sciences in times of economic challenge.

Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen

Theses and Dissertations

Understanding the genetic foundations of schizophrenia and the resultant symptom manifestations is an important step as we work toward development of new prevention and treatment strategies. This work has sought better understanding of this disease through use of three subject cohorts and two studies using simulated data exploring features of complex disease. First, we probed the symptoms of schizophrenia in subjects of African and European ancestry drawn from the Genetic Association Information Network (GAIN) schizophrenia study and found significant differences between groups, particularly in affective symptoms. The genetic basis of symptom variation was then explored in a selection of candidate …

Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti

Theses and Dissertations

Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …

Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat

Theses and Dissertations

Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin …

Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow

Theses and Dissertations

Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …

Shoulder Rehabilitation For The Injured Overhead-Throwing Athlete, Joshua M. Raskoff

Recreation, Parks, and Tourism Administration

Baseball incorporates the violent motion of throwing as a main act of physical exertion. The shoulder joint is vulnerable to injury during this movement. The overall purpose of this study was to produce a rehabilitation program for injured overhead-throwing athletes and have it evaluated by healthcare professionals. A paper and pen style questionnaire was sent through the mail to a network of professionals in California. Eighteen of the 20 questionnaires were returned. The quantitative feedback of the Likert scale questions indicated that the program was effective and usable while the qualitative feedback indicated the opposite. The additional comments allowed experts …

Profiles Of Drug Endangered Children: Investigation In A Clinical Sample, Imanie Samanmali Wijayaratne

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the increase in children born prenatally exposed to methamphetamine, little is known about the cognitive and neuropsychological outcomes of these children. Research specific to prenatal-methamphetamine exposure is extremely limited and has been primarily restricted to rat studies. This research combined with the few studies examining children prenatally exposed to methamphetamine suggests that methamphetamine-exposure is associated with various cognitive and neuropsychological delays and is impacted by both biological and environmental factors. Given the scarcity of research in this area, the current study used archival data from a psychological assessment clinic to (1) describe the frequency of prenatal methamphetamine-exposure cases, (2) …

Observer Reliability Of Cephalometric Landmark Identification On 3-D Mr Images, Michael S. Pollack

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Cephalometric analysis is a cornerstone of orthodontic diagnosis, yet much information is lost when 3-dimensional structures are assessed with 2-dimensional methods. CBCT offers 3-dimensional imaging but at the cost of higher levels of ionizing radiation. Magnetic resonance imaging provides 3-dimensional imaging without ionizing radiation and additionally imparts visualization of soft tissue structures. Prior to employing MR images for cephalometric analysis, reliability of landmark identification must be assessed. The purpose of this study was to evaluate intra- and interobserver reliability in 3-dimensional landmark identification using MR images.

Materials and Methods: Fifteen cranial MR images (3.0 T, MP-RAGE) from subjects between …

Using Cone Beam Computed Tomography To Identify A Prediction Model For Obstructive Sleep Apnea, Jodi Parker

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Obstructive Sleep Apnea (OSA) patients have increased risk of morbidity and mortality. Early diagnosis may reduce morbidity and mortality. Prediction of OSA from imaging may help to identify OSA patients earlier in life. CBCT can be used for OSA diagnostic imaging due to its three-dimensional (3D) visualization of the upper airway and craniofacial complex. Magnification associated with conventional 2D radiography is eliminated with CBCT, and radiation to the patient is significantly less than previous modalities used to measure craniofacial & airway measurements associated with OSA. During a CBCT scan, the patient's image is taken supine, rather than the upright …

Effects Of Functional Appliances On The Tmj And Mandibular Length Of Skeletal Class Ii Patients: A Cone Beam Computed Tomography Study, David C. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Functional appliances have been efficiently used in the treatment of Class II malocclusions caused by retrognathic mandibles. Cone beam computed tomography has enabled us to make more accurate linear measurements by eliminating superimposition of other structures and to analyze skeletal anatomic detail in all three planes of space. This retrospective study evaluated the osseous changes in the temporomandibular joint (TMJ) and length of the mandible in skeletal Class II malocclusion patients treated with the fixed functional appliances and compared measurements with Class I malocclusion patients treated with orthodontic mechanics that did not alter skeletal relationships.

Materials and Methods: Twelve …

Influence Of Stainless Steel Orthodontic Brackets On Magnetic Resonance Imaging, Christian James Hoybjerg

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Magnetic resonance imaging (MRI) machines provide 2D as well as 3D images that are excellent in contrasting soft-tissue in the maxillofacial region and are void of ionizing radiation. The drawbacks include the lack of depiction of cortical bony detail and image degradation caused by substances in the scanned area. Specifically, in the orthodontic field stainless steel brackets cause more distortion of MR images then any other bracket material. It is unknown what type of stainless steel alloy causes the most MRI distortion. The purpose of this study is to evaluate the degree of craniofacial MR distortion caused by various …