Medicine and Health Sciences Commons^™

Chronic Ethanol Exposure Sensitizes The Lung In A Mouse Model Of Endotoxemia-Induced Acute Lung Injury : Potential Role Of Plasminogen Activator Inhibitor-1., Lauren G. Poole

Electronic Theses and Dissertations

The goal of this project is to characterize a new mouse model of alcohol-enhanced acute lung injury (ALI) and to determine the role of plasminogen activator inhibitor-1 (PAI-1) in this model. Male mice (WT and PAI-1-/-) were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks; some animals were administered intraperitoneal lipopolysaccharide (LPS) prior to sacrifice. Chronic alcohol feeding enhanced induction of the chemokines MIP-2 and KC (murine IL-8 homologues) after LPS injection in wild type animals. This enhanced chemokine expression did not correlate with enhanced pulmonary neutrophil infiltration, however animals exposed to chronic ethanol showed sustained …

Regulation Of Receptor Tyrosine Kinases By Ubiquilin1., Zimple Kurlawala

Electronic Theses and Dissertations

Receptor Tyrosine Kinases (RTK’s) like EGFR, Insulin Receptor, IGF1R and others mediate growth, proliferation and balance between apoptosis and survival. Dysregulation of RTK activity has been identified in a wide range of cancers and contributes to initiation, progression and metastasis of tumors. Ubiquilins (UBQLN) are fairly novel proteins and are studied mostly in the field of neurodegenerative disorders. Our laboratory recently discovered a link between UBQLN1 function and tumorigenesis. UBQLN1 is lost in about 50% of non-small cell lung cancer (NSCLC) cases. We have identified an interaction between UBQLN1 and IGF1R. Furthermore, UBQLN1 regulates activity of IGF1R and EGFR. Following …

Identifying Hepatocellular Carcinoma (Hcc) Cells With Cancer Stem Cell-Like Properties., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular Carcinoma (HCC) is a challenging condition to treat in the clinic due to its distinct tumor phenotype, aggressive growth, and chemotherapy resistance. Cancer Stem Cells (CSCs) are a poorly differentiated subpopulation of cells within the tumor microenvironment, and role of CSCs in tumor initiation and chemotherapy resistance is not well understood in HCC. In this study, we have successfully identified HCC cells with CSC-like properties that showed resistance to Doxorubicin. Using the established serum free culture techniques, we have enriched CSC-like cells among hepatocellular cancer cells. These enriched cells exhibit all CSC-like properties i.e. self-renewal capability, anchorage independent growth …

The Effect Of Protandim Supplementation On Oxidative Damage And Athletic Performance., Seteena Leigh Ueberschlag

Electronic Theses and Dissertations

A double-blind placebo-controlled trial determined the long term effects of Protandim® supplementation on 5-km running performance, as well as on acute and long-term oxidative damage assessed by serum lipid peroxides (Thiobarbituric acid-reacting substances: TBARS). Thirty-eight subjects were placed into one of two groups: an experimental (675 mg/day Protandim®) or control group (675 mg/day corn starch). 5-km runs were performed at baseline and 88 (SD 4) days post-supplementation with samples taken immediately pre- and 10-min post 5-km run, as well as at rest ∼30 and ∼60 days during the supplementation period. There was ~25% week-to-week coefficient of variation of TBARS at …

Metabolomics Of Transformed Mda-Mb-231 Cell Lines Expressing Different Levels Of Human Arylamine N-Acetyltransferase 1 (Nat1)., Samantha Marie Carlisle

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme that is found in almost all tissues of the body. Expression of NAT1 is commonly elevated in several cancers including breast cancer. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Three MDA-MB-231 breast adenocarcinoma cell lines that stably express wild-type, increased, and decreased levels of human NAT1 have been constructed and characterized for NAT1 mRNA, NAT1 acetylation activity, cell doubling rates, and endogenous acetyl-CoA levels. Differences in polar metabolic profile between these three cell lines were investigated using a comprehensive GC×GC−TOF …

Suramin Protects From Cisplatin-Induced Acute Kidney Injury., Tess Dupre

Electronic Theses and Dissertations

In rodent models, suramin improves recovery following acute kidney injury (AKI). We hypothesized that suramin would be useful in protection against cisplatin-induced AKI. This hypothesis was tested by pre-treating C57BL/6j mice with suramin prior to cisplatin. Our data indicates that suramin protects the kidney from injury by decreasing cisplatininduced decreases in kidney function. Renal histology indicated that suramin significantly protected from cisplatin-induced AKI. Data indicate that suramin pretreatment attenuated mRNA expression of pro-inflammatory cytokines and chemokines following cisplatin treatment, while also decreasing markers of cell stress and cell death. We utilized the same experimental design with 10-month old FVB mice …

The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson

Electronic Theses and Dissertations

Background: The Epidermal Growth Factor Receptor (EGFR) is a 170- kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR responsible for cell growth, proliferation, and tissue homeostasis in epithelial cells; however, the EGFR is overexpressed in many human malignancies including MDA-MB-468 cells, a metastatic breast epithelial cell line. Previous studies have indicated that within the MDA-MB-468 cell line, receptors at the cell surface promote cell growth when activated with Epidermal Growth Factor (EGF) ligand. Activated receptors that are internalized to the endosomes however induce apoptosis. This contrasting response at different cellular …

Searching For Novel Ligands For The Cannabinoid And Related Receptors., Pritesh Prakash Kumar

Electronic Theses and Dissertations

The first purpose of the present dissertation was to apply a high throughput assay to systematically screen a library of food and drug administration (FDA)-approved drugs as potential ligands for the cannabinoid receptor 2 (CB2). A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring changes in intracellular cAMP levels was validated and found to be suitable for testing ligands that may act on CB2. Among the 640 FDA-approved drugs screened, raloxifene, a drug used to treat/prevent post-menopausal osteoporosis, was identified for the first time to be a novel CB2 inverse agonist. The dissertation reporting these results demonstrated that by …

Promoting Differentiation And Survival Of Human C-Kit+ Cardiac Progenitor Cells Ex Vivo., Tareq Al-Maqtari

Electronic Theses and Dissertations

c-kit+ cardiac progenitor cells (CPCs) have recently gained much attention due to the therapeutic effects they exert on cardiac function following their administration into the infarcted heart as evidenced by animal studies and by a recent clinical trial (SCIPIO). However, injecting these cells in the heart is associated with poor differentiation into specialized cardiac cell types and with rapid death of the engrafted cells. With the ultimate goal of advancing cardiac stem cell therapy, we sought to facilitate the differentiation of human CPCs into cardiac cell types (e.g. cardiomyocytes, smooth muscle cells, endothelial cells and cardiac fibroblasts) by overexpressing selected …

Network Participation In Public Health : The Development Of Instruments And Adapted Theory To Predict Stakeholder Participation In A Public Health Network., David Johnson

Electronic Theses and Dissertations

Background: Participation in public health networks is important to achieve the goals of public health. This dissertation addresses a common problem in public health management—of how to measure support and predict participation by individuals and organizations in network level collaboratives—through testing an adapted theory producing a newly developed instrument. Purpose: Community health collaboratives have grown in popularity and in funding opportunities in the past couple decades, but they notoriously fail to achieve measureable results. By adapting theory and relevant instruments to a specific public health network context, factors that enable and inhibit participation are identified. Method: A prospective, theory-driven, sequential …

Beef Cattle Management Systems For Estrus Synchronization And Heifer Development, Hazy Rae Nielson

Department of Animal Science: Dissertations, Theses, and Student Research

Four experiments were conducted to evaluate estrus synchronization and heifer development systems. In the first experiment delaying AI 19 h following GnRH administration in a hybrid estrus detection and time AI protocol was evaluated. Final pregnancy rate was not different among heifers detected in estrus, AI at the time GnRH administration, or delayed AI. The second study compared the effect of melengestrol acetate (MGA) -PG and 14-d controlled internal drug release (CIDR) -PG estrus synchronization protocols on estrus response and pregnancy rates of 311 d old heifers. Final pregnancy rate was similar between CIDR and MGA treatment groups. The objective …

Skmc Student Handbook 2015-2016, Thomas Jefferson University

Jefferson Medical College Administrative Documents and Reports

71 page student handout

Structure-Based Screen Identifies A Potent Small Molecule Inhibitor Of Stat5a/B With Therapeutic Potential For Prostate Cancer And Chronic Myeloid Leukemia., Zhiyong Liao, Lei Gu, Jenny Vergalli, Samanta A. Mariani, Marco De Dominici, Ravi K. Lokareddy, Ayush Dagvadorj, Puranik Purushottamachar, Peter A. Mccue, Edouard J. Trabulsi, Costas D. Lallas, Shilpa Gupta, Elyse Ellsworth, Shauna Blackmon, Adam Ertel, Paolo Fortina, Benjamin E. Leiby, Guanjun Xia, Hallgeir Rui, David T. Hoang, Leonard G Gomella, Gino Cingolani, Vincent Njar, Nagarajan Pattabiraman, Bruno Calabretta, Marja T. Nevalainen

Department of Cancer Biology Faculty Papers

Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic …

Acute Myocardial Infarction And Myocardial Ischemia-Reperfusion Injury: A Comparison, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as …

Expert Clinician To Novice Nurse Educator. Learning From First-Hand Narratives, Jeanne Merkle Sorrell, Pamela Cangelosi

Walden Faculty and Staff Publications

The nurse educator role often looks deceptively simple. Compared to the complexity of bedside care for a patient with multiple comorbidities and hour-by-hour monitoring, watching over students to guide their learning may appear easy. Yet, when experienced nurse clinicians try out this new endeavor for the first time, they often describe themselves as frustrated and uncertain about how to best implement the role. Through years of experience as clinicians, nurses often arrive at a comfort zone where they know what to do for their patients in order to keep them safe and enhance their healing. When moving to the nurse …

Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander

Gill Heart & Vascular Institute Faculty Publications

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.

Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …

Federally Qualified Health Centers’ Capacity And Readiness For Research Collaborations: Implications For Clinical-Academic-Community Partnerships, Heather M. Brandt, Vicki M. Young, Dayna A. Campbell, Seul Ki Choi, Jessica S. Seel, Daniela B. Friedman

Faculty Publications

BACKGROUND: Federally qualified health centers (FQHCs) provide a health care safety net for underserved populations and contribute unique expertise to research that could further enhance quality of patient care. The purpose of this research was to assess interest in, readiness to, and capacity for conducting research in FQHCs in South Carolina (SC). METHODS: A Web-based survey was administered to 20 FQHCs across SC. Fourteen representatives of FQHCs completed the 39-item survey that assessed research experience and interest, partnerships and funding, barriers and benefits to research participation, training and technical assistance needs, and research capacity. RESULTS: FQHCs are interested in conducting …

Nutrinews, Volume 8, August, 2015, Department Of Nutrition And Dietetics, University Of North Florida

NutriNews

This issue features Dementia or B Vitamin Deficiency?, Food Science News, Fruit of the Month Club: Featuring Guava

New Dentist News (August 2015), Ada Committee On The New Dentist

New Dentist News

New Dentist News offers timely information on scientific, social, educational, political and economic developments affecting new dentists. This collection is historical and items may not reflect current standards. For up-to-date information contact the ADA. The New Dentist News was alternately titled ADA Lifeline, 1997-June 2001.

Department Of Surgery Update, August 2015, Wright State University Department Of Surgery

Department of Surgery Updates

A three page newsletter created by the Department of Surgery documenting changes to the department. This issue contains a message from the chair, a list of important dates, committee meetings, scholarly activity and more.

Targeted Ultrasound Of An Indeterminate Breast Lesion On Mammography: When Does It Influence Management?, Saba Sohail, Imrana Masroor, Shaista Afzal

Department of Radiology

Objective: To determine the change over mammographic diagnosis, BI-RADS category and management following targeted ultrasound of an indeterminate lesion seen on mammography and associated factors, if any.
Study design: Descriptive, analytical study.
Place and duration of study: Radiology Department, The Aga Khan University Hospital and Clifton Medical Services, Karachi, from April 2010 to May 2011.
Methodology: Patients referred for targeted breast ultrasound following X-ray mammography were selected regardless of age. Targeted Ultrasound (TUS) was defined as a limited ultrasound of a specific lesion or breast part as indicated by the referring source. Comparison was made between the post mammography and …

Stability Of Isometric Strength Asymmetry And Its Relationship To Sprint And Change-Of-Direction Performance Asymmetry In Division-I Collegiate Athletes, Benjamin H. Gleason

Electronic Theses and Dissertations

The purpose of this dissertation was to evaluate the stability of strength asymmetry over a long-term period (1 year) and investigate the relationship of strength asymmetry to field test performance asymmetry in NCAA division-1 athletes. Isometric mid-thigh pull (IMTP) peak force asymmetry, ground contact time and finish time asymmetries on 10m sprint and 505 agility test performances were also observed. The impact of strength was also investigated in these studies to determine its effect on the magnitude of asymmetry.

In the second study, peak force asymmetry over a one-year period was observed to be a rather volatile quality, with ranges …

Pharmacodynamics Of Folic Acid Receptor Targeted Antiretroviral Nanotherapy In Hiv-1-Infected Humanized Mice., Pavan Puligujja, Mariluz Araínga, Prasanta Dash, Diana L. Palandri, R. Lee Mosley, Santhi Gorantla, Larisa Y Poluektova, Joellyn Mcmillan, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold …

Prevalence Of A Chytrid Pathogen (Batrachochytrium Dendrobatidis) In Eastern Hellbender Salamanders In New York And Pennsylvania, Linxuan Wu

Biology Theses

Amphibian populations are currently declining globally. There are many possible causes for these declines, among which an emerging infectious disease, chytridiomycosis, has been implicated. Chytridiomycosis in the U.S.A. is mainly caused by the Batrachochytrium dendrobatidis. In this study, I used qPCR assays to detect the existence of this pathogen in the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) populations in the Allegheny and Susquehanna River drainages of New York and Pennsylvania. Chytrid is most often tested by using skin swabs, but in this study, tail clips, dorsal skin, blood and eggs were tested as well. Batrachochytrium dendrobatidis was detected …

Communication Between Family Carers And Health Professionals About End-Of-Life Care For Older People In The Acute Hospital Setting: A Qualitative Study, Glenys Caswell, Kristian Pollock, Rowan Harwood, Davina Porock

Publications and Research

Background: This paper focuses on communication between hospital staff and family carers of patients dying on acute hospital wards, with an emphasis on the family carers’ perspective. The age at which people in the UK die is increasing and many continue to die in the acute hospital setting. Concerns have been expressed about poor quality end of life care in hospitals, in particular regarding communication between staff and relatives. This research aimed to understand the factors and processes which affect the quality of care provided to frail older people who are dying in hospital and their family carers.

Methods: The …

Today - August 2015, Loma Linda University Health

TODAY

Inside this issue:

-- Final beam is placed for Loma Linda University Health - San Bernardino in topping-off ceremony
-- Loma Linda University Transplantation Institute leads all of Southern California in liver transplant survival
-- Cancer Center receives UniHealth Foundation grant
-- Innerweave The Wholeness Story
-- Center for Health Disparities holds annual research symposium
-- Off to work . . . one woman's story of retirement
-- Cheng Family Foundation presents $75,000 gift to Loma Linda University Eye Institute for children's intervention program
-- IndyCar racer visits Children's Hospital outpatient clinic
-- Loma Linda University Health reaches out to …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C₁₂ and C₁₄ chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter …

Oncolog, Volume 60, Number 08, August 2015, Stephanie Deming, Bryan Tutt, K. Nair

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New Gene Therapy for Bladder Cancer Shows Promise: A gene therapy that stimulates interferon production within the body may prove to be effective against high-risk, early-stage bladder cancer when standard treatment fails.
• Vaccine Helps T Cells Target Sarcomas, Melanomas and other Tumors: A vaccine that delivers an antigen to dendritic cells, in turn activating killer T cells that can target specific cancers, is the subject of two ongoing clinical trials,
• INBRIEF: Glypican-1 Shows Promise as a Biomarker for Pancreatic Cancer/Stereotactic Ablative Radiation Therapy for Stage I Non-Small Cell Lung Cancer May Offer Survival Benefit
• HOUSE CALL: Prostate Cancer Screening-Who should …

Fusing Heterogeneous Data For Alzheimer's Disease Classification, P. S. Pillai, Tze-Yun Leong

Research Collection School Of Computing and Information Systems

In multi-view learning, multimodal representations of a real world object or situation are integrated to learn its overall picture. Feature sets from distinct data sources carry different, yet complementary, information which, if analysed together, usually yield better insights and more accurate results. Neuro-degenerative disorders such as dementia are characterized by changes in multiple biomarkers. This work combines the features from neuroimaging and cerebrospinal fluid studies to distinguish Alzheimer's disease patients from healthy subjects. We apply statistical data fusion techniques on 101 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We examine whether fusion of biomarkers helps to improve diagnostic …