Digital Commons Network^™

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in immunocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing the …

Tgfb1 Disrupts The Angiogenic Potential Of Microvascular Endothelial Cells Of The Corpus Luteum., Dulce Maroni, John S. Davis

Journal Articles: Obstetrics & Gynecology

Cyclical formation and regression of the ovarian corpus luteum is required for reproduction. During luteal regression, the microvasculature of the corpus luteum is extensively disrupted. Prostaglandin F2α, a primary signal for luteal regression, induces the expression of transforming growth factor β1 (TGFB1) in the corpus luteum. This study determined the actions of TGFB1 on microvascular endothelial cells isolated from the bovine corpus luteum (CLENDO cells). We hypothesized that TGFB1 participates in the disruption of the microvasculature during luteal regression. TGFB1 activated the canonical SMAD signaling pathway in CLENDO cells. TGFB1 (1 ng/ml) significantly reduced both basal and fetal-calf-serum-stimulated DNA synthesis, …

Identification Of Factors Associated With Good Response To Growth Hormone Therapy In Children With Short Stature: Results From The Answer Program®., Peter A Lee, John Germak, Robert Gut, Naum Khutoryansky, Judith Ross

Department of Pediatrics Faculty Papers

UNLABELLED: ABSTRACT:

OBJECTIVE: To identify factors associated with growth in children on growth hormone (GH) therapy using data from the American Norditropin Studies: Web-enabled Research (ANSWER) Program® registry.

METHODS: GH-naïve children with GH deficiency, multiple pituitary hormone deficiency, idiopathic short stature, Turner syndrome, or a history of small for gestational age were eligible (N = 1,002). Using a longitudinal statistical approach, predictive factors were identified in patients with GHD for change from baseline in height standard deviation score (ΔHSDS) following 2 years of treatment.

RESULTS: Gradual increases in ΔHSDS over time were observed for all diagnostic categories. Significant predictive factors …

Oncogene-Induced Nrf2 Transcription Promotes Ros Detoxification And Tumorigenesis., Gina M. Denicola, Florian A. Karreth, Timothy J. Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, Kenneth H. Yu, Charles J. Yeo, Eric S. Calhoun, Francesca Scrimieri, Jordan M. Winter, Ralph H. Hruban, Christine Iacobuzio-Donahue, Scott E. Kern, Ian A Blair, David A. Tuveson

Department of Surgery Faculty Papers

Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer. Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2. Indeed, somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and increase the constitutive transcription of Nrf2 target genes were recently identified, indicating that enhanced ROS detoxification and additional Nrf2 functions may …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …

Ceacam1 Separates Graft-Versus-Host-Disease From Graft-Versus-Tumor Activity After Experimental Allogeneic Bone Marrow Transplantation., Sydney X Lu, Lucy W Kappel, Anne-Marie Charbonneau-Allard, Renée Atallah, Amanda M Holland, Claire Turbide, Vanessa M Hubbard, Jimmy A Rotolo, Marsinay Smith, David Suh, Christopher King, Uttam K Rao, Nury Yim, Johanne L Bautista, Robert R Jenq, Olaf Penack, Il-Kang Na, Chen Liu, George Murphy, Onder Alpdogan, Richard S Blumberg, Fernando Macian, Kathryn V Holmes, Nicole Beauchemin, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In …

Systematically Controlling For The Influence Of Age, Sex, Hertz And Time Post-Whole-Body Vibration Exposure On Four Measures Of Physical Performance In Community-Dwelling Older Adults: A Randomized Cross-Over Study, Harold L. Merriman, C. Jayne Brahler, Kurt Jackson

Physical Therapy Faculty Publications

Though popular, there is little agreement on what whole-body vibration (WBV) parameters will optimize performance. This study aimed to clarify the effects of age, sex, hertz, and time on four physical function indicators in community-dwelling older adults (N = 32). Participants were exposed to 2 minutes WBV per session at either 2 Hz or 26 Hz, and outcome measures were recorded at 2-, 20-, and 40-minute post-WBV. Timed get-up-and-go and chair sit-and-reach performances improved post-WBV for both sexes, were significantly different between 2 Hz and 26 Hz treatments (P ≤ 0.05), and showed statistically significant interactions between age and gender …

Preventable Lifestyle Risk Factors For Non-Communicable Diseases In The Pakistan Adolescents Schools Study 1 (Pass-1)., Ali Khan Khuwaja, Saleem Khawaja, Komal Motwani, Adeel Khoja, Iqbal Azam Syed, Zafar Fatmi, Badar Sabir Ali, Muhammad Masood Kadir

Department of Medicine

Objectives: The rising burden of preventable risk factors for non-communicable diseases (NCDs) among adolescents is a major public health challenge worldwide. We identified the preventable risk factors for NCDs in adolescents.

Methods: In a school-based study, pre-tested structured questionnaires were completed by 414 adolescents (14 to 17 years) at six schools in three cities in Pakistan. The chi-squared test and adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated in a multinomial logistic regression analysis.

Results: Over 80% of the adolescents had unhealthy diets, and 54% were physically inactive. Most adolescents were exposed to passive smoking, and 14% …

Pakistan Society For Neurology Conference Abstracts

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Psychological And Cognitive Determinants Of Vision Function In Age-Related Macular Degeneration., Barry W. Rovner, Robin J Casten, Robert W Massof, Benjamin E Leiby, William S Tasman

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD.

METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Tumor-Derived Interleukin-10 As A Prognostic Factor In Stage Iii Patients Undergoing Adjuvant Treatment With An Autologous Melanoma Cell Vaccine., Amit Mahipal, Mizue Terai, David Berd, Inna Chervoneva, Kashyap Patel, Michael Mastrangelo, Takami Sato

Department of Medical Oncology Faculty Papers

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP).

METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind …

Department Of Radiology-Annual Executive Summary Report-July 1, 2010 To June 30, 2011, Vijay M. Rao, Md

Department of Radiology Administrative Documents and Reports

90 page Department of Radiology Annual Executive Summary Report, July 1, 2010 to June 30, 2011, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

Tables of Contents:

Department of Radiology

Chairman, Vice Chairmen 1

Divisions and Directors 1

Committees and Chairmen 1

Radiology Department Faculty Rank 2

Faculty with Secondary Appointments 3

Clinical Divisions 4

Radiology Residents and Fellows 5

Department Organizational Chart 6

Department Administration Chart 7

State of the Department 8

Appendix I: Publications Journal Articles 22

Books and Book Chapters 30

Abstracts 33

Appendix II: Formal Scientific Presentations 44

Appendix III: Honors, Editorial Activities, Service to Regional …

The Impact Of A Multimodal Approach To Pre-Emptive Analgesia On Postoperative Pain And Analgesic Requirements For Patients Undergoing Orthopaedic Lower Limb Surgery At The Aga Khan University Hospital, Nairobi: A Single Blind Randomised Controlled Trial, John M. Bugo

Master of Medicine in Anaesthesiology

Study Objective: The aim of this study was to evaluate the postoperative morphine-sparing and pain reducing effects of a preemptive, multimodal, perioperative analgesic regimen incorporating the use of preincisional intrathecal blockade plus parenteral anti-inflammatory agents, in patients undergoing lower limb orthopaedic surgery. Study design: Prospective Single blinded Randomized Controlled Trial. Study setting: The Aga Khan Hospital, Nairobi, Kenya. Methods: 44 ASA physical status 1 and 2 patients undergoing lower limb orthopaedic surgery were randomly allocated into two groups of 22 patients each. Patients in the Intervention group were given a preincisional subarachnoid injection of 15mg hyperbaric Bupivacaine and 25mcg Fentanyl, …

Hepatitis B Vaccination Rate And Determining Factors Amongst Health Care Workers At Aga Khan University Hospital, Nairobi, Herman Ekea

Master of Medicine in Internal Medicine

Aim: To determine Hepatitis B vaccination rate and determining factors for health care workers (HCWs) at AKUHN. Design: Cross sectional analytical study Study subjects and setting: Aga Khan University Hospital-Nairobi, is a 254 bed tertiary hospital, with 815 HCWs with occupational risk of infection with hepatitis B virus (HBV). The hospital has a HCW vaccination policy and vaccine available to HCWs as part of medical scheme Methodology: Two hundred and sixty six (266) eligible HCWs of all cadres were stratified then randomly recruited after giving informed consent. A questionnaire was then administered to assess knowledge, attitude and practice towards HBV …

Prevalence Of Nasal Carriage Of Methicillin-Resistant Staphylococcus Aureus In Healthcare Workers At Aga Khan University Hospital, Nairobi, Geoffrey A. Omuse

Master of Medicine in Clinical Pathology

Objective: To establish the prevalence of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in healthcare workers (HCW) at Aga Khan University Hospital, Nairobi (AKUHN). Background: Healthcare workers are a major reservoir of MRSA and may play a role in the spread of nosocomial MRSA infections. MRSA can cause significant morbidity and mortality. There is both molecular and epidemiological evidence linking HCW to MRSA outbreaks. Method: A cross sectional study conducted between July and December 2010. Nasal swabs were taken from 246 randomly selected HCW from various departments.MRSA was identified using both phenotypic and genotypic methods. Antibiotic susceptibility testing of all …

Beyond Mannequins: A Potpourri Of Enabling Technology For Healthcare Education, Rosalyn P. Scott

Department of Surgery Faculty Publications

No abstract provided.

Psychostimulants As Cognitive Enhancers: The Prefrontal Cortex, Catecholamines And Attention Deficit Hyperactivity Disorder, Craig Berridge, David M. Devilbiss

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention deficit hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically-relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally-activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses …

Sonic Hedgehog Dependent Phosphorylation By Ck1Α And Grk2 Is Required For Ciliary Accumulation And Activation Of Smoothened, Yongbin Chen, Noriaki Sasai, Guoqiang Ma, Tao Yue, Jianhang Jia, James Briscoe, Jin Jiang

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo), but how vertebrate Smo is activated remains poorly understood. In Drosophila, Hh dependent phosphorylation activates Smo. Whether this is also the case in vertebrates is unclear, owing to the marked sequence divergence between vertebrate and Drosophila Smo (dSmo) and the involvement of primary cilia in vertebrate Hh signaling. Here we demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. We demonstrate that …

The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames

PCOM Biomedical Studies Student Scholarship

Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H₂O₂), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO^-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production …

Relationship Of Vitamin D Levels To Blood Pressure In A Biethnic Cohort, Rosario O. Sakamoto

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Serum hydroxyvitamin D [25(OH)D] has been well-accepted as not an ordinary vitamin but a pro-hormone that has many benefits beyond its well-known effects on bone. Cardiovascular risk factors such as hypertension remain a huge health burden and Blacks have been recognized to have higher prevalence of hypertension compared to non-Hispanic Whites. Despite increasing evidence of the benefits of vitamin D on blood pressure control, there is much more to be learned about the relationship of serum 25(OH)D to blood pressure among different ethnicities.

Purpose: The goal of this study was to determine whether vitamin D serum 25(OH)D levels were …

Acute Effects Of A Selective Cannabinoid-2 Receptor Agonist On Neuroinflammation In A Model Of Traumatic Brain Injury., Melanie B Elliott, Ronald F Tuma, Peter S Amenta, Mary F Barbe, Jack I Jallo

Department of Neurosurgery Faculty Papers

Proposed therapeutic strategies for attenuating secondary traumatic brain injury (TBI) include modulation of acute neuroimmune responses. The goal of this study was to examine the acute effects of cannabinoid-2 receptor (CB(2)R) modulation on behavioral deficits, cerebral edema, perivascular substance P, and macrophage/microglial activation in a murine model of TBI. Thirty male C57BL/6 mice underwent sham surgery, or cortical contusion impact injury (CCI). CCI mice received vehicle or the CB(2)R agonist 0-1966 at 1 and 24 h after injury. Performance on the rotarod, forelimb cylinder, and open-field tests were evaluated before and at 48 h after sham or CCI surgery. Cerebral …

Chemical Cardiomyopathies: The Negative Effects Of Medications And Nonprescribed Drugs On The Heart., Vincent M Figueredo

Division of Cardiology Faculty Papers

The heart is a target of injury for many chemical compounds, both medically prescribed and not medically prescribed. Pathophysiologic mechanisms underlying the development of chemical-induced cardiomyopathies vary depending on the inciting agent, including direct toxic effects, neurohormonal activation, altered calcium homeostasis, and oxidative stress. Numerous chemicals and drugs are implicated in cardiomyopathy. This article discusses examples of medication and nonprescribed drug-induced cardiomyopathies and reviews their pathophysiologic mechanisms.

Oral Ingestion Of Hexavalent Chromium Through Drinking Water And Cancer Mortality In An Industrial Area Of Greece - An Ecological Study, Athena Linos, Athanassios Petralias, Costas A. Christophi, Eleni Christoforidou, Paraskevi Kouroutou, Melina Stoltidis, Afroditi Veloudaki, Evangelia Tzala, Konstantinos C. Makris, Margaret R. Karagas

Dartmouth Scholarship

Background: Hexavalent chromium is a known carcinogen when inhaled, but its carcinogenic potential when orally ingested remains controversial. Water contaminated with hexavalent chromium is a worldwide problem, making this a question of significant public health importance.

Methods: We conducted an ecological mortality study within the Oinofita region of Greece, where water has been contaminated with hexavalent chromium. We calculated gender, age, and period standardized mortality ratios (SMRs) for all deaths, cancer deaths, and specific cancer types of Oinofita residents over an 11-year period (1999 - 2009), using the greater prefecture of Voiotia as the standard population.

Results: A total of …

Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab

Gill Heart & Vascular Institute Faculty Publications

The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for …

Download The Full Pdf Of Jefferson Surgical Solutions Spring 2011, Volume 6, Number 1

Jefferson Surgical Solutions

No abstract provided.

News In Brief

Jefferson Surgical Solutions

No abstract provided.

Those Who Give: Making A Difference Now And Down The Road: The Howell Professorship In Pancreatic Cancer Research

Jefferson Surgical Solutions

No abstract provided.

On The Job: Dr. Goldberg Spends Research Year Targeting Breast Cancer

Jefferson Surgical Solutions

No abstract provided.

Beekley’S Combat Experience Informs Research And Protocols At Home And Abroad

Jefferson Surgical Solutions

No abstract provided.