Digital Commons Network^™

Neprilysin: An Enzyme Candidate To Prevent Alzheimer's Disease, Salim Sabri El-Amouri

MUSC Theses and Dissertations

Alzheimer's disease is named after Alois Alzheimer, the German psychiatrist and neuropathologist who identified it in 1907. Alzheimer's disease (AD) is the most common form of dementia and accounts for at least half of all dementias (Owen et al., 1994). The disease moved from eighth to seventh place among the leading causes of death in 2004, with 65,829 deaths in the United States (Minifio et al., 2006). In an attempt to solve the mystery of this disease, scientists have discovered brain changes in people with AD that lead to dementia. Nerve cells die in areas of the brain that are …

Dual-Hit Hypothesis For Dopamine Neurodegeneration And Motor Dysfunction, Heather Anne Boger

MUSC Theses and Dissertations

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Studies have shown that GDNF levels decrease in the substantia nigra (SN) and striatum during normal aging and in patients with Parkinson's disease. Furthermore, exogenous GDNF infusion protects DA neurons against injury induced by 6-hydroxydopamine, MPTP, and methamphetamine (METH). A heterozygous mouse model was created to assess whether a chronic reduction in this neurotrophic factor impacts motor function and the nigrostriatal DA system during the aging process. In this dissertation, two models of dopaminergic loss and motor dysfunction were characterized. …

Stromal Haze, Myofibroblasts, And Surface Irregularity After Prk, Marcelo V. Netto, Rajiv R. Mohan, Sunilima Sinha, Ajay Sharma, William Dupps, Steven E. Wilson

Pharmacy Faculty Articles and Research

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze.

Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups[.]

Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr …

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Lin, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …

Efficacy And Safety Of The Six-Dose Regimen Of Artemether-Lumefantrine In Pediatrics With Uncomplicated Plasmodium Falciparum Malaria: A Pooled Analysis Of Individual Patient Data, M. Makanga, Zul Premji, C. Falade, J. Karbwang, E.A. Mueller, K. Andriano, P. Hunt, P.I. De Palacios

Pathology, East Africa

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene.

Statins And The Vasculopathy Of Systemic Sclerosis: Potential Therapeutic Agents?, Chris T. Derk, Sergio A. Jimenez

Department of Medicine Faculty Papers

It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation …

Effect Of Prophylactic And Therapeutic Mitomycin C On Corneal Apoptosis, Cellular Proliferation, Haze, And Long-Term Keratocyte Density In Rabbits, Marcelo V. Netto, Rajiv R. Mohan, Sunilima Sinha, Ajay Sharma, Pankaj C. Gupta, Steven E. Wilson

Pharmacy Faculty Articles and Research

PURPOSE—To determine the mechanism through which topical mitomycin C prevents and treats corneal haze after photorefractive keratectomy (PRK) and to examine the effects of dosage and duration of exposure.

METHODS—In 224 New Zealand rabbits, −9.0 diopter PRK with mitomycin C or balanced salt solution was performed. Haze level was graded at the slit-lamp. Rabbits were sacrificed at 4 hours, 24 hours, 4 weeks, or 6 months after surgery and immunohistochemistry was performed with TUNEL assay, Ki67 and α-SMA.

RESULTS—TUNEL-positive apoptotic cells marginally increased in all mitomycin C groups whereas Ki67-positive mitotic cells decreased significantly following mitomycin C application. A greater …

Functional Redistribution Of Hippocampal Cannabinoid Cb1 Receptors In The Rat Pilocarpine Model Of Acquired Epilepsy, Katherine Winslow Falenski

Theses and Dissertations

Cannabinoids, such as the marijuana derivative Δ9-THC, are known to have CBl receptor-mediated anticonvulsant effects in several animal models of seizures and epilepsy, including the rat pilocarpine model of acquired epilepsy. However, the distribution of CBl receptor expression and function in brains of epileptic rats has not been characterized. Therefore, this dissertation was initiated to evaluate the effect of epileptogenesis on the distribution and function of the endogenous CBI receptor system in the rat pilocarpine model, a well-established model of acquired temporal lobe epilepsy. Using immunohistochemistry, we demonstrated that chronically epileptic rats exhibit a unique, long-term, and specific redistribution of …

Analyse De L'Evolution De La Pratique De L'Excision Au Burkina Faso: L'Environment Institutionel, Politique Et Programmatique De La Lutte Contre La Pratique De L'Excision, Nafissatou J. Diop, Zakari Congo, Aina Ouedraogo, Alphosine Sawadogo, Lydia Saloucou, Ida Tamini

Reproductive Health

La présente analyse du projet Frontiers du Population Council fait un tour historique des événements majeurs de la lutte contre la pratique de l’excision au Burkina Faso avant d’aborder les conventions internationales auxquelles le pays a adhéré ainsi que les textes nationaux adoptés en ce qui concerne les droits de l’homme, spécifiquement le droit des femmes et des enfants. Elle analyse également l’application de la loi à travers l’évolution des cas de condamnation depuis l’adoption de la loi. Enfin, elle s’intéressera à quelques programmes d’intervention mis en place en identifiant les acquis et les limites. Ce travail fait partie d’une …

Effect Of A Paediatric Incentive Spacer And Reinforcement Of Inhalation Technique Training In Preschool Children, Jasminka Murdzoska

Theses : Honours

Incorrect inhaled drug delivery technique is a common problem in paediatric asthma [1-4]. Previously, device technique training has been shown to significantly improve inhaler skills, using subjective methods, namely check-list analysis [5-8]. However, more objective measures are needed to examine more comprehensively the effect of training in preschool children and parents. Resistance to regular asthma therapy is also a frequent problem when attempting to treat young children. Reasoning with young children can be very difficult and parents often have to struggle with their child to achieve compliance [2]. The Funhaler spacer (FH) (Funhaler™; InfaMed, Australia) has been developed in an …

Paired-Pulse Depression At Photoreceptor Synapses., Katalin Rabl, Lucia Cadetti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to …

Development Of An Audio Visual Tool For Medical Training At Kennedy Space Center, Rimawi, Nidal El

Browse all Theses and Dissertations

As part of an effort to improve efficiency of space-flight medical support at Kennedy Space Center, a training video was created to replace a series of lectures given before a launch or landing of the Space Shuttle. The video was designed to familiarize volunteer physicians from around the country with the specific emergency response protocols for a Space Shuttle launch or landing emergency at Kennedy Space Center. The methods used were consistent with standard film making techniques as outlined in several film making texts. The Production was divided into three phases; A pre-production phase wherein the research, screenwriting and production …

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen, Eric A. Weaver, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao, Zhongjing Lu

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide …

3,3′-Diindolylmethane And Paclitaxel Act Synergistically To Promote Apoptosis In Her2/Neu Human Breast Cancer Cells, Kandace P. Mcguire, N. Ngoubilly, M. Neavyn, Susan Lanza-Jacoby

Department of Surgery Faculty Papers

Background. HER2/neu positive breast tumors are difficult to treat. About 25 to 30% of invasive breast tumors overexpress the HER2/neu oncogene. These tumors are aggressive and become resistant to chemotherapeutic drugs. 3,3′-diindolylmethane (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, has been found to have anti-cancer properties in both humans and animals. DIM has been shown to induce cell cycle arrest and apoptosis in animal breast cancer models. Because HER2/neu overexpression confers resistance to paclitaxel, and DIM has anti-tumor effects, we hypothesized that DIM will enhance the cytotoxic effects of paclitaxel, a common …

The Earliest Dipodomyine Heteromyid In North America And The Phylogenetic Relationships Of Geomorph Rodent, Steven J Norris

Faculty, Staff and Student Publications

The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne agent of Lyme disease, has been characterized by two different approaches using mass spectrometry, providing a launching point for future studies on the dramatic changes in protein expression that occur during transmission of the bacterium between ticks and mammals.

Cisplatin Nephrotoxicity And Hydration Protocols, Ahmed Usman, Heeranand Keswani, Suresh Nagdev,, Ghulam H, Tehseen Khursheed,, Anis Malik,, Kasif Jafferi

Department of Medicine

Objective : Ahmed Usman, Heeranand Keswani, Suresh Nagdev, Ghulam Haider, Tehseen Khursheed, Anis Malik, Kasif Jafferi To evaluate the nephrotoxicity of cisplatiri in cancer patients, using different protocols of hydration.

Study Design : Randomized controlled trial.

Patients & Methods : This study was conducted between 1st June to 30th November 2004. Ninetynine patients with normal renal function were enrolled in the study and randomly assigned into the 3 study groups, each group having 33patients. In group 1 hydration was done with saline (2 liter) alone, in group 2 with saline (2 liter) and furosemide (40mg) and in group 3 with …

Understanding The Nature Of Surgical Excellence Using A Competency Modeling Approach, Hope S. Hanner-Bailey

Psychology Theses & Dissertations

Currently, a thorough description of the knowledge, skills, abilities, and other personal characteristics (KSAOs) that distinguish an exceptional surgeon does not exist. This knowledge is pertinent to the development of selection, training, and performance assessment methods that can be used to develop high performing surgeons. Expert surgeons from around the country were recruited to participate in an interview to discuss the KSAOs (i.e., the competencies) needed to be exceptional in the field. A smaller number of novice surgeons were also interviewed. The expert interview data were distilled into a competency model that consists of ten competencies and patterns within the …

Construction Of Improved Temperature-Sensitive And Mobilizable Vectors And Their Use For Constructing Mutations In The Adhesin-Encoding Acm Gene Of Poorly Transformable Clinical Enterococcus Faecium Strains, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator …

Chronic Exposure To Mdma (Ecstasy) Elicits Behavioral Sensitization In Rats But Fails To Induce Cross-Sensitization To Other Psychostimulants, Gunjan M Modi, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA.

METHODS: The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 …

Dose-Response Characteristics Of Methylphenidate On Locomotor Behavior And On Sensory Evoked Potentials Recorded From The Vta, Nac, And Pfc In Freely Behaving Rats, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).

METHODS: The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto …

Orally Delivered, Plant-Produced Tat Protein Primes Mice For A Challenge Dna Vaccine Expressing Tat, A V. Karasev, S Foulke, C Wellens, I Zwierzynski, R Baldwin, H Koprowski, M S. Reitz Jr

Department of Microbiology and Immunology Faculty Papers

Oral Presentation.

Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …

Vital Pulp Therapy With Mineral Trioxide Aggregate: An Outcomes Study, Heather H. Lauer

Loma Linda University Electronic Theses, Dissertations & Projects

Mineral trioxide aggregate (MTA) is used in a variety of endodontic procedures. MTA is proven to provide good marginal adaption to dentin, to be biocompatible, and to stimulate dentin bridge formation through animal studies. These properties make MTA a potentially useful material to be used in vital pulp therapy. Clinical data on the use of MTA as a vital pulp medicament is sparse. The purpose of this study was to evaluate the clinical outcome of vital pulp therapy using MTA as the pulp medicament. Inclusion criteria for patient selection for recall was based on pulp treatment necessary from carious pulp …

Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert

Loma Linda University Electronic Theses, Dissertations & Projects

With an incidence approaching 1/4000 live births and as high as 60% in low birth weight infants, cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute mortality and chronic disability in newborns. Herein, we tested the hypothesis that following a hypoxic-ischemic insult hyperbaric oxygen (HBO) treatment can restore high energy metabolite levels in the affected regions of the brain and through this increase in energy levels ameliorate the spread of cell death following the insult. We also investigated if an additional mechanism by which HBO affords its neuroprotection is by altering the expression of the …

Ricketts And Steiner Analysis Using Newtom 3g™ Scout Images, James I. Gibson Iii

Loma Linda University Electronic Theses, Dissertations & Projects

NewTom 3G™ scout images have the general appearance of traditional lateral cephalometric radiographs. The purpose of this research was to determine if Ricketts and Steiner analyses could be accomplished on NewTom 3G™ scout images.

This was a retrospective study comparing the use of NewTom 3G™ scans in DICOM (Digital Imaging and Communications in Medicine) format to scout images from 25 consecutive patients of the Loma Linda University School of Dentistry Department of Orthodontics, three of these patients did not meet the inclusion criteria. The DICOM images were used to create controls. The controls and scout images were digitized using QuickCeph™. …

Stability Of The Miniscrew-Bone Interface: Reverse Torque Values In Rabbits, Daniel John Drye

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Miniscrews are used in orthodontics as practical temporary anchorage devices (TAD's). The purpose of this animal study was to measure reverse torque values for Absoanchor 1.2 mm and Micerium 1.5mm miniscrews at 0, 2, and 12 weeks under loaded and unloaded conditions.

Methods: Ninety-six miniscrews were placed in the femora of twelve rabbits and allowed to heal for either two or twelve weeks. Half of the fixtures were loaded immediately with NiTi open coil springs producing a force of 150-200g and the other half served as unloaded controls. For each of the healing times, two and twelve weeks, …

Role Of Rapid Urease Test And Histopathology In The Diagnosis Of Helicobacter Pylori Infection In A Developing Country, Javed Yakoob, Wasim Jafri, Shahab Abid, Zaigham Abbas, Saeed Hamid, Muhammad Islam, Kashif Anis, Hasnain Ali Shah, Hizbullah Shaikh

Section of Gastroenterology

Background

The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.

Methods

One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard …

Encephalopathy Caused By Bartonella Henselae Following Cat Scratch, Joseph L. Yozviak Do, Facp, John Margraf Md, Marcelo Gareca Md

Department of Medicine

No abstract provided.

The Influence Of Concurrent Cognitive Tasks On Postural Sway In Children, Yvette Blanchard, Shannon Carey, Jocelyn Coffey, Alison Cohen, Trisha Harris, Stephanie Michlik, Geraldine Pellecchia

All PTHMS Faculty Publications

Purpose: The purpose of this study was to examine the influence of concurrent tasks on postural sway in children.

Methods: Nineteen fourth-grade students, while standing on a balance platform, were asked to stand still, count backward, and read second-grade level sentences. The AMTI Accusway System was used to calculate the length of center of pressure path (LCOP), sway range (SR), and variability (SV) in mediolateral (ML) and anteroposterior (AP) directions of sway.

Results: Analysis of variance revealed a main effect of cognitive task condition for SR-AP, SR-ML, SV-AP, and SV-ML. Post hoc comparisons revealed lower values of those four dependent …

Dermatophyte Growth And Degradation Of Human Stratum Corneum In Vitro (Pathogenesis Of Dermatophytosis)., Azam J. Samdani

Department of Medicine

Background: This study was carried out to determine growth of dermatophytes using human stratum corneum in vitro and the degrading effect of Keratinases (Proteinases) on stratum corneum for a complete understanding of the host parasite relationship.

Method: Trichophyton rubrum isolates derived from patients with tinea cruris infections were obtained from the Department of Medical Microbiology, University Hospital of Wales, U.K. Human stratum corneum sterilized with ethylene oxide was used as a nitrogen source in agar culture medium plates.

Result: Fungal growth took place in plates which contained human stratum corneum particles while there was no growth in the plates without …