Digital Commons Network^™

A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon

Department of Cancer Biology Faculty Papers

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …

Fli-1 In B Cell Proliferation And Systemic Lupus Erythematosus, Sarah Gail Bradshaw

MUSC Theses and Dissertations

PBMC from patients with SLE and splenic lymphocytes from murine models of SLE demonstrate increased expression of the ETS transcription factor Fli-1. Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease. These findings suggest investigation of the role of Fli-1 in SLE may elucidate etiology of the disease and potential therapies. The MRL/lpr mouse is a model of SLE exhibiting increased lymphocytic expression of Fli-1. Reduction of Fli-1 expression by heterozygousity at the Fli-1 locus (Fli1+/-) results in decreased auto- and alloantibodies, proteinuria, and renal pathology; and drastically decreased mortality. Disruption of the C-terminal transactivation domain (Fli1ΔCTA/ΔCTA) reduces …

Moving Forward: Tackling Stigma In A Tanzanian Community, Laura Nyblade, Kerry Macquarrie, Gideon Kwesigabo, Aparna Jain, Lusajo Kajula, Fausta Philip, William Henerico Tibesigwa, Jessie K. Mbwambo

HIV and AIDS

The International Center for Research on Women, the Muhimbili University College of the Health Sciences, the Population Council, and Family Health International conducted an evaluation of a community-based effort to reduce stigma surrounding HIV infections in a peri-urban community in Tanzania. Results presented a mixed, but hopeful, picture for a way forward in tackling stigma at the community level. Tackling stigma requires that the individuals tasked with doing this undergo personal change. Programs can start by focusing stigma-reduction efforts on a smaller, more manageable geographical area and adding specific anti-stigma components to their portfolio of activities. Engaging community opinion leaders …

If You Build It, Will They Come? Kenya Healthy Start Pediatric Hiv Study: A Diagnostic Study Investigating Barriers To Hiv Treatment And Care Among Children, Karusa Kiragu, Katie D. Schenk, Julie Murugi, Avina Sarna

HIV and AIDS

In Kenya the proportion of eligible HIV-positive children receiving ART treatment is only 11 percent. This study explored and documented possible barriers in the community to accessing pediatric HIV testing and treatment, to guide the development of new interventions to encourage uptake. The study identified barriers such as cost, use of traditional healers, low knowledge of treatment options, attitudinal barriers, stigma, unique treatment issues, and dissatisfaction with available services. Additionally, healthcare workers missed opportunities to provide services and cited numerous service-side challenges. The study recommends prioritizing community awareness, mobile clinics, strengthening capacity of healthcare workers, supporting family-based HIV testing, and …

Evaluation Of A Simple Intervention To Increase Self- Efficacy For Independent Exercise In Cardiac Rehabilitation Participants, Sherry A. Barkley

Electronic Theses and Dissertations

Purpose: While benefits of exercise after a cardiac event are well documented, participation in and adherence to cardiac rehabilitation (CR) programs is often low. The purpose of this study was to test the effectiveness of a self- efficacy coaching intervention (SCI): a simple theory-based behavioral intervention to increase self-efficacy for independent exercise as well as independent exercise behavior in CR patients. It was hypothesized that persons receiving the SCI treatment (T) would have higher levels of self-efficacy for exercise and greater participation in independent exercise than participants in an attention control (C) group.
Methods: People referred to a hospitalbased CR …

Rabies Prevalence Among And New Distribution Records Of Arkansas Bats, D. Blake Sasse, David A. Saugey

Journal of the Arkansas Academy of Science

No abstract provided.

A Comprehensive Analysis Of The Naturally Occurring Polymorphisms In Hiv-1 Vpr: Potential Impact On Ctl Epitopes., Alagarsamy Srinivasan, Velpandi Ayyavoo, Sundarasamy Mahalingam, Aarthi Kannan, Anne Boyd, Debduti Datta, Vaniambadi S Kalyanaraman, Anthony Cristillo, Ronald G Collman, Nelly Morellet, Bassel E Sawaya, Ramachandran Murali

Department of Microbiology and Immunology Faculty Papers

The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates …

One-Year Treatment With Mometasone Furoate In Chronic Obstructive Pulmonary Disease, Peter M.A. Calverley, Stephen I. Rennard, Harold S. Nelson, Jill P. Karpel, Eduardo H. Abbate, Paul Stryszak, Heribert Staudinger

Journal Articles: Pulmonary & Critical Care Med

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse …

Has The Hiv Epidemic Peaked?, John Bongaarts, Thomas Buettner, Gerhard Heilig, Francois Pelletier

Poverty, Gender, and Youth

This working paper reviews the highly diverse regional and country patterns of HIV epidemics and discusses possible causes of the geographic variation in epidemic sizes. The main finding of this analysis is that the HIV epidemic reached a major turning point over the past decade. The peak years of HIV incidence rates are past for all regions, and the peaks of prevalence rates are mostly in the past except in Eastern Europe, where it is expected to peak in 2008. But owing in part to the life-prolonging effect of antiretroviral therapy and to sustained population growth, the absolute number of …

Sexual Behavior And Sti/Hiv Status Among Adolescents In Rural Malawi: An Evaluation Of The Effect Of Interview Mode On Reporting, Barbara Mensch, Paul C. Hewett, Richard Gregory, Stephane Helleringer

Poverty, Gender, and Youth

This paper presents the results from an interview-mode experiment conducted by the Population Council with unmarried young women in rural southern Malawi. To collect data on sexual behavior and the dynamics of HIV transmission, respondents were randomly assigned to either an audio computer-assisted self-interview (ACASI) or a conventional face-to-face (FTF) interview. Clear evidence indicates that the mode of interviewing and probing concerning various sexual partnerships affects respondents’ reporting of their sexual activity, yet the results are not always in accordance with expectations. Reporting for “ever had sex” and “sex with a boyfriend” is higher in the FTF mode, whereas, when …

Autoimmune-Induced Preferential Depletion Of Myelin-Associated Glycoprotein (Mag) Is Genetically Regulated In Relapsing Eae (B6 × Sjl) F1 Mice, Dusanka S. Skundric, Rujuan Dai, Vaagn L. Zakarian, Weili Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Experimental autoimmune encephalomyelitis (EAE) is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS). Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG), as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions. …

Hiv-1 Tat Protein Alter The Tight Junction Integrity And Function Of Retinal Pigment Epithelium: An In Vitro Study., Ling Bai, Zhenping Zhang, Hui Zhang, Xiumei Li, Qiurong Yu, Haotian Lin, Wenhui Yang

Department of Medicine Faculty Papers

BACKGROUND: How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE). METHODS: A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells …

Barriers To Breast Cancer Prevention, Detection And Treatment Among Middle Eastern Women, Senida Husic

Mahurin Honors College Capstone Experience/Thesis Projects

Many have heard of breast cancer and how it has become one of the top caused of death in the United States. but how many know of the impact it has on other parts of the world, the developed and developing countries? Accourding to the World Health Organization (WHO), 13% of all deaths in the world are due to cancer and it is predicted to increase in the upcoming decades. In the Arab World, particularly in the Eastern Mediterranean Region, 70% of women who discovered in late stages in the Unted States. The reseach focused on identifying whether the barriers …

The Potential For Sustainability Of Malaria In Pregnancy Initiatives In East And Southern Africa: Kenya And Malawi, Washington Onyango-Ouma, Sam Agatre Okuonzi, Doreen Ali, Harriet Birungi, Annie Mwangi

Reproductive Health

This study assesses the sustainability of initiatives to improve maternal and child health survival by preventing and treating illness from malaria, and documents best practices for promoting sustainability and lessons for replication in countries where malaria is endemic. The study applied the Child Survival Sustainability Assessment framework to initiatives in Kenya and Malawi to analyze progress toward sustainability, including not only a biomedical perspective but also the human, social, and organizational processes that influence sustainability of health projects. The report concludes that Malaria in Pregnancy (MIP) interventions were sustained within and beyond the project districts in both countries. Furthermore, both …

Sexual And Reproductive Health Needs Of Adolescents Perinatally Infected With Hiv In Uganda, Harriet Birungi, John Frank Mugisha, Juliana K. Nyombi, Francis Obare, Humphres Evelia, Hannington Nyinkavu

Reproductive Health

In Uganda, HIV/AIDS treatment, care and support programs are still organized around either adult or pediatric care and fail to adequately address the needs of adolescents, specifically perinatally-infected adolescents. This study, implemented jointly by the Population Council's Frontiers in Reproductive Health (FRONTIERS) program and the AIDS Support Organization (TASO), aimed to better understand the reproductive health and sexuality of this population group, and to identify anxieties or fears they have around entering social stages of adulthood. This study confirms that wide programmatic gaps exist in addressing the sexual and reproductive health needs of young people perinatally infected with HIV who …

Situation Analysis Of The Integration Of Family Planning Services In Postpartum, Postabortion And Prevention Of Mother To Child Transmission Programs In Nicaragua, Freddy Solis, Ana Del Carmen Rojas, Gadea Adilia, M. Estela Rivero-Fuentes, Ricardo Vernon

Reproductive Health

Between September 2005 and April 2007, FRONTIERS and Alva, a Nicaraguan consulting firm, conducted a situation analysis of the provision and use of contraceptive services in postpartum, postabortion and prevention of mother-to-child transmission of HIV (PMTCT) programs. The project‘s objective was to assess the degree to which contraceptive services were linked to postpartum, postabortion and PMTCT services and if this allowed the programs to meet the contraceptive needs of their clients. The project proposes recommendations for improving the quality of these programs.

An Efficient Algorithm For Biomarker Identification, Jiang Li, Rick Mckenzie, Lisa Cazares, Richard Drake, John Semmens

Electrical & Computer Engineering Faculty Publications

No abstract provided.

Three Dimensional Echocardiography In Congenital Heart Defects., Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

Three dimensional echocardiography (3DE) is a new, rapidly evolving modality for cardiac imaging. Important technological advances have heralded an era where practical 3DE scanning is becoming a mainstream modality. We review the modes of 3DE that can be used. The literature has been reviewed for articles that examine the applicability of 3DE to congenital heart defects to visualize anatomy in a spectrum of defects ranging from atrioventricular septal defects to mitral valve abnormalities and Ebstein's anomaly. The use of 3DE color flow to obtain echocardiographic angiograms is illustrated. The state of the science in quantitating right and left ventricular volumetrics …

Spatio-Temporal Analysis Of The Relationship Between Wnv Dissemination And Environmental Variables In Indianapolis, Usa., Hua Liu, Qihao Weng, David Gaines

Political Science & Geography Faculty Publications

Background: This study developed a multi-temporal analysis on the relationship between West Nile Virus (WNV) dissemination and environmental variables by using an integrated approach of remote sensing, GIS, and statistical techniques. WNV mosquito cases in seven months (April-October) of the six years (2002–2007) were collected in Indianapolis, USA. Epidemic curves were plotted to identify the temporal outbreaks of WNV. Spatial-temporal analysis and k-mean cluster analysis were further applied to determine the high-risk areas. Finally, the relationship between environmental variables and WNV outbreaks were examined by using Discriminant Analysis.

Results: The results show that the WNV epidemic curve reached its peak …

Novel Functions Of Acyl-Coa Thioesterases And Acyltransferases As Auxiliary Enzymes In Peroxisomal Lipid Metabolism., Mary Hunt, Stefan Alexson

Articles

Peroxisomes are single membrane bound organelles present in almost all eukaryotic cells, and to date have been shown to contain approximately 60 identified enzymes involved in various metabolic pathways, including the oxidation of a variety of lipids. These lipids include very long-chain fatty acids, methyl branched fatty acids, prostaglandins, bile acid precursors, and xenobiotics that are either β-oxidized or α-oxidized in peroxisomes. The recent identification of several acyl-CoA thioesterases and acyltransferases in peroxisomes has revealed their various functions in acting as auxiliary enzymes in α- and β-oxidation in this organelle. To date, 9 functional acyl-CoA thioesterases and acyltransferases have been …

Stem Cells: The Dawn Of A New Era For Huntington’S Disease Research, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Direct Inhibition Of Cdk9 Blocks Hiv-1 Replication Without Preventing T Cell Activation In Primary Human Peripheral Blood Lymphocytes, Dominic Salerno, Muneer G Hasham, Renee Marshall Demarest, Judit Garriga, Alexander Y Tsygankov, Xavier Graña

Rowan-Virtua School of Osteopathic Medicine Departmental Research

HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in transformed cells is very sensitive to direct CDK9 inhibition. Thus, CDK9 could be a potential target for anti-HIV-1 therapy. A clearer understanding of the requirements for CDK9 activity in primary human T cells is needed to assess whether the CDK9-dependent step in HIV-1 transcription can be targeted clinically. We have investigated the effects …

Uncovering P53 Mutations And Abnormal Gene Expression In Pediatric Adrenocortical Cancer, Alina Nico West

Theses and Dissertations (ETD)

Pediatric adrenocortical cancer is extremely rare and often fatal (approximately 0.3-0.4 cases per million worldwide; 50% 5-year survival). The incidence of pediatric adrenocortical cancer in southern Brazil is 10-15 times higher than the worldwide incidence. Due to the rarity of adrenocortical cancer, especially in children, underlying gene dysregulation and mechanisms of tumorigenesis of the adrenal gland are very poorly described in the literature. However, it is well-known that the tumor suppressor p53, which is mutated in over 50% of all human cancers, is commonly mutated in pediatric adrenocortical cancer. In addition, evidence strongly suggests that if a child has adrenocortical …

Effectiveness Of An Evidence-Based Curriculum Module In Nursing Schools: Targeting Safe Patient Handling And Movement, Nancy Menzel, Audrey L. Nelson, Thomas R. Waters, Nancy Hughes, Pamela C. Hagan, Gail Powell-Cope, Viviam Thompson

Nursing Faculty Research

Nursing schools in the United States have not been teaching evidence-based practices for safe patient handling, putting their graduates at risk for musculoskeletal disorders (MSDs). The specific aim of this study was to translate research related to safe patient handling into the curricula of nursing schools and evaluate the impact on nurse educators and students' intentions to use safe patient handling techniques. Nurse educators at 26 nursing schools received curricular materials and training; nursing students received the evidence-based curriculum module. There were three control sites. Questionnaires were used to collect data on knowledge, attitudes, and beliefs about safe patient handling …

Humanized Chimeric Receptors In The Therapy Of Multiple Sclerosis, Ioana Moisini

Theses and Dissertations (ETD)

The role of autoreactive, antigen-specific T-cells in the development of autoimmunity has long been documented. T-cells expressing chimeric receptors are specifically redirected against such cells and have been proven to suppress autoimmune encephalomyelitis, the murine model of multiple sclerosis. We here demonstrate the ability of humanized chimeric receptors to suppress experimental autoimmune encephalomyelitis (EAE) in a humanized mouse model by redirecting T lymphocytes against autoreactive T-cells. The receptors were synthesized by linking the 84-102 epitope of human myelin basic protein (MBP) to the extracellular and transmembrane domains of the beta chain of human major histocompatibility complex (MHC) class II molecule …

The Glossina Proteolytic Lectin (Gpl) Gene Is Expressed Only In Members Of Glossina Species, M. W. Burugu, B. N. Mbatia, E. O. Osir, E. U. Kenya, L. U. Abubakar

All Peer-Reviewed Publications

Differentiation of bloodstream-form trypanosomes into procyclics in tsetse flies (Diptera: Glossinidae) is a crucial step in the establishment of midgut infections. A number of factors have been implicated in the transformation process, including enzymes and lectins or lectin-like molecules. Recently, Glossina proteolytic lectin (Gpl) gene, which encodes a protein with both lectin and trypsin activities has been shown to stimulate transformation of bloodstream-form trypanosomes into procyclics in vitro. Using RT-PCR, we show that the induction of Gpl gene expression by blood meal occurs only in Glossina fuscipes fuscipes Newstead, Glossina austeni Newstead, Glossina pallidipes Austen, and not in the Anopheles …

The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner

Theses and Dissertations (ETD)

High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with high-risk disease did not respond to the putatively effective topotecan systemic exposure. These children represent a subset …

The Cystic Fibrosis Transmembrane Conductance Regulator: Regulation By Hsp-90, Kevin Marrs

Theses and Dissertations (ETD)

The hypothesis of this project is that a functionally relevant association exists between CFTR and Hsp90. In testing this hypothesis, (a) the association of CFTR and Hsp90 is confirmed via crosslinking and immunoprecipitation of CFTR from stably transfected HEK-293 cells, electrophoretic separation of cross-linked proteins, and protein identification via SDS-PAGE, western blotting, and mass spectrometry. Also, this hypothesis is tested by (b) functionally assessing the effect of Hsp90 on CFTR function via Ussing chamber analysis, two-electrode voltage clamp analysis, preliminary in vivoanimal studies, and protein phosphorylation. The HEK-293 Flag-CFTR cells used in this study allows for a high degree …

Cardiopulmonary Predicators Of Dysfunctional Ventilator Weaning Response After Coronary Artery Bypass Graft, Annapoorna Mary

Theses and Dissertations (ETD)

Although the majority of coronary artery bypass graft (CABG) surgery patients are extubated within 6 to 8 hours following surgery, 20% to 40% of patients remain intubated 12 hours after surgery due to dysfunctional ventilator weaning response (DVWR). DVWR associated with increased morbidity and mortality (30% to 43%) following CABG surgery. Finding significant antecedence to predict DVWR could help to identify and prevent the complications from DVWR after CABG surgery. Literature review revealed that there is an association between cardiopulmonary indicators (CPI) and DVWR after CABG surgery. Cardiopulmonary indicators are the selected hemodynamic parameters that have an association with DVWR. …

Transcriptional Control Of Vascular Smooth Muscle Cell Proliferation By Peroxisome Proliferator-Activated Receptor-Γ: Therapeutic Implications For Cardiovascular Diseases, Florence Gizard, Dennis Bruemmer

Internal Medicine Faculty Publications

Proliferation of vascular smooth muscle cells (SMCs) is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD), used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARgamma is prominently upregulated during neointima formation …