Medicine and Health Sciences Commons^™

Regulation Of Cell Death By Transfer Rna., Ya-Ming Hou, Xiaolu Yang

Department of Biochemistry and Molecular Biology Faculty Papers

SIGNIFICANCE: Both transfer RNA (tRNA) and cytochrome c are essential molecules for the survival of cells. tRNA decodes mRNA codons into amino-acid-building blocks in protein in all organisms, whereas cytochrome c functions in the electron transport chain that powers ATP synthesis in mitochondrion-containing eukaryotes. Additionally, in vertebrates, cytochrome c that is released from mitochondria is a potent inducer of apoptosis, activating apoptotic proteins (caspases) in the cytoplasm to dismantle cells. A better understanding of both tRNA and cytochrome c is essential for an insight into the regulation of cell life and death.

RECENT ADVANCES: A recent study showed that the …

Intracellular Reprogramming Of Expression, Glycosylation, And Function Of A Plant-Derived Antiviral Therapeutic Monoclonal Antibody., Jeong-Hwan Lee, Da-Young Park, Kyung-Jin Lee, Young-Kwan Kim, Yang-Kang So, Jae-Sung Ryu, Seung-Han Oh, Yeon-Soo Han, Kinarm Ko, Young-Kug Choo, Sung-Joo Park, Robert Brodzik, Kyoung-Ki Lee, Doo-Byoung Oh, Kyung-A Hwang, Hilary Koprowski, Yong Seong Lee, Kisung Ko

Department of Cancer Biology Faculty Papers

Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar …

Oncogenes And Inflammation Rewire Host Energy Metabolism In The Tumor Microenvironment: Ras And Nfκb Target Stromal Mct4., Ubaldo E. Martinez-Outshoorn, Md, Joseph Curry, Md, Ying-Hui Ko, Md, Zhao Lin, Md, Madalina Tuluc, Md, David Cognetti, Md, Ruth Birbe, Md, Edmund A. Pribitkin, Md, Alessandro Bombonati, Richard Pestell, Md, Anthony Howell, Federica Sotgia, Michael P. Lisanti, Md

Kimmel Cancer Center Faculty Papers

Here, we developed a model system to evaluate the metabolic effects of oncogene(s) on the host microenvironment. A matched set of "normal" and oncogenically transformed epithelial cell lines were co-cultured with human fibroblasts, to determine the "bystander" effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis. In addition, expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer cells was sufficient to induce the metabolic reprogramming of cancer-associated fibroblasts toward glycolysis, via oxidative stress. Evidence for "metabolic symbiosis" between oxidative cancer cells …

Hdl-C: Does It Matter? An Update On Novel Hdl-Directed Pharmaco-Therapeutic Strategies., Ramprasad Gadi, Aman Amanullah, Vincent M. Figueredo

Division of Cardiology Faculty Papers

It has long been recognized that elevated levels of low-density lipoprotein cholesterol (LDL-C) increase the risk of cardiovascular disease (CHD) and that pharmacologic therapy to decrease LDL-C significantly reduces cardiovascular events. Despite the effectiveness of statins for CHD risk reduction, even optimal LDL-lowering therapy alone fails to avert 60% to 70% of CHD cases. A low plasma concentration of high-density lipoprotein cholesterol (HDL-C) is also associated with increased risk of CHD. However, the convincing epidemiologic data linking HDL cholesterol (HDL-C) to CHD risk in an inverse correlation has not yet translated into clinical trial evidence supporting linearity between HDL-C increases …

Beginner's Guide To Colorectal Cancer Research, Kayla M. Walker

Summer Training Program in Cancer Immunotherapy

Introduction

For a while now obesity has been a health care concern for people all over the world. In the many years that obesity research has been conducted, various things have been taken into consideration including diet, exercise and medical history. In relatively recent years, researchers have expanded their definition of physical activity levels to include both the amounts of occupational physical activity and leisure time activity that a person partakes in.

The 2002 census occupation system assigned a 4 digit Metabolic equivalent (MET) to 509 separate occupations. These codes are particularly helpful for statistics agencies that need to collect …

Adverse Childhood Experiences, Disability And Health-Risk Behaviors, Sophia Miryam Schussler-Fiorenza Rose Md, Phd

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Jefferson And Japan: Working Together To Advance Best Practices In Healthcare Education And Research, Yumiko Radi

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Orthopaedics And Ipads: The Future Of Resident Education?, Nathan Tiedeken Md, John A. Handal Md, Solomon P. Samuel D.Eng.

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Jefferson Hosts American Public Health Association Student Assembly's Strategic Planning Meeting, Alex Bryan

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Health Reform Upate: The Road To Implementing State-Run, Partnered, And Federally Facilitated Exchanges, Anne Mainardi Md, Shira Yun Md

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Prophylactic Vs. Therapeutic: Dna Vaccine To Metastatic Colorectal Cancer Using Molecular Marker Guanylyl Cyclase-C, Anmol Khurana, Msii

Summer Training Program in Cancer Immunotherapy

The role of heat-stable enterotoxin receptor guanylyl cyclase C (GCC) is well known for its aberrant chloride conductance in the intestinal epithelium in response to bacterial infection. Recently, its use as a molecular marker to detect metastatic colon cancer has grown, as has its use as oral hormone therapy for tumor suppression. This study investigates the preliminary stages of a DNA dendritic cell-based vaccine development specific to targeting guanylyl cyclase in systemic tissues. Construction of the plasmid as well as its transduction to Class I MHC molecules in antigen-presenting dendritic cells is examined. Future exploration includes a comparative assessment of …

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …

The Conception Of Gcc- Specific Chimeric Antigen Receptors, Raven Smith-Parris

Summer Training Program in Cancer Immunotherapy

Colorectal Cancer is an aggressive disease that claims the lives of both men and women every year. It is the second leading cause of cancer-related death in the U.S. The overwhelming mortality rate it amasses begs for the discovery of alternative forms of treatment. The nature of cancer requires immunotherapeutic approach that is tumor specific in nature. Adoptive T-cell therapy is an alternative that satisfies these conditions. Guanylyl Cyclase C is a receptor found on the luminal side of the gut that is tissue-specific for the intestinal epithelium. Further, its expression is maintained throughout colorectal tumorigenesis making in an excellent …

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …

Scott Memorial Library Information Flyer Fall 2013-2014, Education Services

The AC's Research Support Newsletter (Formerly AISR Connections)

Scott Memorial Library information flyer for Fall 2013.

Aisr Connections (Fall 2013-2014), Education Services

The AC's Research Support Newsletter (Formerly AISR Connections)

AISR Connections highlighting new services and happenings at the Scott Memorial Library at Thomas Jefferson University.

The Effectiveness Of The Learning To Breathe Program On Adolescent Emotion Regulation, Stacie M. Metz, Jennifer L. Frank, Diane K. Reibel, Todd Cantrell, Richard Sanders, Patricia C. Broderick

Marcus Institute of Integrative Health Faculty Papers

This study assessed the effectiveness of a mindfulness-based program, Learning to BREATHE, on adolescent emotion regulation. Participants included 216 regular education public high school students with pretest and posttest data participating in the program or instruction-as-usual comparison condition. Program participants reported statistically lower levels of perceived stress and psychosomatic complaints and higher levels of efficacy in affective regulation. Program participants also evidenced statistically larger gains in emotion regulation skills including emotional awareness, access to regulation strategies, and emotional clarity. These findings provide promising evidence of the effectiveness of Learning to BREATHE on the development of key social-emotional learning skills.

A Statement On Vemurafenib-Resistant Melanoma., Edward J Hartsough, A E Aplin

Department of Cancer Biology Faculty Papers

Despite recent advancements in the treatment of late-stage mutant BRAF (V600E/K) melanomas, a major hurdle continues to be acquired resistance to BRAF inhibitors such as vemurafenib. The mechanisms for resistance have proven to be heterogeneous, emphasizing the need to use broad therapeutic approaches. In this issue, the study "Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas" by Liu et al. proposes that signal transducer and activator of transcription 3 (STAT3)-paired box 3 (PAX3) signaling may be a mechanism that is used by melanomas to resist RAF inhibitors.

Poor Positive Predictive Value Of Mcconnell’S Sign On Transthoracic Echocardiography For The Diagnosis Of Acute Pulmonary Embolism, Urvashi Vaid, Md, Ms, Esme Singer, Md, Gregary D. Marhefka, Md, Walter K. Kraft, Md, Michael Baram, Md, Fccm

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Abstract: Background: Acute pulmonary embolism (PE) is a life-threatening condition. Making a definitive diagnosis with radiologic studies may delay therapy or be unsafe for the patient. Echocardiography is readily available and can suggest PE by demonstrating right ventricular (RV) dysfunction. McConnell’s sign on echocardiogram (ECHO-CG) (RV dysfunction with characteristic sparing of the apex) has been reported to have high sensitivity and specificity for the diagnosis of acute PE. It is hypothesized that McConnell’s sign on ECHO-CG in patients hospitalized with suspected acute PE would have a high positive predictive value (PPV).

Methods: Data, from 2005 to 2010, were retrospectively collected …

Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo., Aine M Duffy, Michael J Schaner, Jeannie Chin, Helen E Scharfman

Department of Neuroscience Faculty Papers

Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. …

Metabolic Syndrome Increases Risk For Pulmonary Embolism After Hip And Knee Arthroplasty., Boris Mraovic, Md, Brian R Hipszer, Md, Richard H. Epstein, Md, Javad Parvizi, Md, Edward C Pequignot, Md, Inna Chervoneva, Md, Jeffrey Joseph, Md

Department of Anesthesiology Faculty Papers

AIM: To investigate whether patients with metabolic syndrome (MetS) undergoing total hip or knee replacement have an increased risk for pulmonary embolism (PE).

METHODS: We studied patients undergoing total hip or total knee replacement from January 2001 to April 2006. The diagnosis of PE was based on a positive finding with a chest CT or a lung scan. Components of MetS were defined as 1) BMI≥30 kg/m(2) , 2) non-fasting preadmission glucose ≥11.1 mmol/L or diagnosis of diabetes, 3) hypertension, and 4) dyslipidemia. MetS was diagnosed if at least three of these components were present.

RESULTS: Of 7282 patients, 107 …

Improving Function In Age-Related Macular Degeneration: A Randomized Clinical Trial., Barry W. Rovner, Robin J Casten, Mark T Hegel, Robert W Massof, Benjamin E. Leiby, Allen C. Ho, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects).

PARTICIPANTS: Patients with AMD (n = 241) attending retina practices.

INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment.

MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life …

A Multicenter, Prospective, Randomized Comparison Of A Novel Signal Transmission Capsule Endoscope To An Existing Capsule Endoscope., Eric H Choi, Klaus Mergener, Carol Semrad, Laurel Fisher, David R Cave, Milan Dodig, Carol Burke, Jonathan A Leighton, David Kastenberg, Peter Simpson, James Sul, Kanishka Bhattacharya, Roger Charles, Lauren Gerson, Luke Weber, Glenn Eisen, Warren Reidel, John J Vargo, Jamile Wakim-Fleming, Simon K Lo

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission.

OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB).

DESIGN: Prospective, multicenter, comparative study.

SETTING: Six academic hospitals.

PATIENTS: A total of 105 patients with OGIB.

INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion.

MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination.

RESULTS: Data analysis resulted in …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

Cancer Metabolism: New Validated Targets For Drug Discovery., Federica Sotgia, Ubaldo E. Martinez-Outshoorn, Md, Michael P. Lisanti

Kimmel Cancer Center Faculty Papers

Recent studies in cancer metabolism directly implicate catabolic fibroblasts as a new rich source of i) energy and ii) biomass, for the growth and survival of anabolic cancer cells. Conversely, anabolic cancer cells upregulate oxidative mitochondrial metabolism, to take advantage of the abundant fibroblast fuel supply. This simple model of "metabolic-symbiosis" has now been independently validated in several different types of human cancers, including breast, ovarian, and prostate tumors. Biomarkers of metabolic-symbiosis are excellent predictors of tumor recurrence, metastasis, and drug resistance, as well as poor patient survival. New pre-clinical models of metabolic-symbiosis have been generated and they genetically validate …

Body Mri Artifacts In Clinical Practice: A Physicist's And Radiologist's Perspective., Martin J Graves, Donald Mitchell

Department of Radiology Faculty Papers

The high information content of MRI exams brings with it unintended effects, which we call artifacts. The purpose of this review is to promote understanding of these artifacts, so they can be prevented or properly interpreted to optimize diagnostic effectiveness. We begin by addressing static magnetic field uniformity, which is essential for many techniques, such as fat saturation. Eddy currents, resulting from imperfect gradient pulses, are especially problematic for new techniques that depend on high performance gradient switching. Nonuniformity of the transmit radiofrequency system constitutes another source of artifacts, which are increasingly important as magnetic field strength increases. Defects in …

The Efficacy Of Allergen Immunotherapy With Cat Dander In Reducing Symptoms In Clinical Practice., Aerik A Williams, John R Cohn, Shirley M Fung, Patricia Padams

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Background. Allergy to cat dander is a common form of allergic disease. Allergen immunotherapy has been demonstrated to be effective in decreasing allergic symptoms. Objectives. To examine outcomes in allergic asthmatic patients on cat immunotherapy (CIT) compared to allergic asthmatics on traditional immunotherapy (IT) without cat sensitivity. Methods. A retrospective review identified allergic asthmatics on CIT for at least three years. An equal number of allergic asthmatics on IT were identified for comparison. Outcomes investigated include measurements of risk of asthma exacerbation. Results. Thirty-five patients were identified in each group. There were no differences in the CIT group versus the …

Assessment Of Subacromial Space And Its Relationship With Scapular Upward Rotation In College Baseball Players., Stephen John Thomas, Charles Buz Swanik, Thomas W Kaminski, Jill S Higginson, Kathleen A Swanik, Levon N Nazarian

Department of Radiology Faculty Papers

CONTEXT: Subacromial impingement is a common injury in baseball players and has been linked to a reduction in the subacromial space. In addition, it has been suggested that decreases in scapular upward rotation will lead to decreases in the subacromial space and ultimately impingement syndrome.

OBJECTIVE: The objective of this study was to evaluate the relationship between acromiohumeral distance and scapular upward rotation in healthy college baseball players.

DESIGN: Posttest-only study design.

SETTING: Controlled laboratory setting.

PARTICIPANTS: 24 healthy college baseball players. Intervention: Participants were measured for all dependent variables at preseason.

MAIN OUTCOME MEASURES: Acromiohumeral distance at rest and …

Failure Patterns In Resected Pancreas Adenocarcinoma: Lack Of Predicted Benefit To Smad4 Expression., Jordan M. Winter, Laura H. Tang, David S. Klimstra, Weiguo Liu, Irena Linkov, Murray F. Brennan, Michael I. DʼAngelica, Ronald P. Dematteo, Yuman Fong, William R. Jarnagin, Eileen M. OʼReilly, Peter J. Allen

Department of Surgery Faculty Papers

OBJECTIVE: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).

BACKGROUND: SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.

METHODS: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 >months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes …

Association Between Obesity And Infarct Size: Insight Into The Obesity Paradox., Beatriz Cepeda-Valery, Md, Leandro Slipczuk, Md, Vincent M. Figueredo, M.D., Gregg S. Pressman, D Lynn Morris, Md, Carl J Lavie, Md, Abel Romero-Corral, Md

Division of Cardiology Faculty Papers

Abstract:

Background: In patients with coronary heart disease, being overweight or obese is associated with better outcomes, a phenomenon known as the 'obesity paradox'. Despite the high prevalence of obesity in the United Sates, its effects on infarct size are largely unexplored.

Methods: Prospective cross-sectional study of 102 consecutive patients admitted with acute myocardial infarction (MI). Standardized forms were used to collect data on body mass index (BMI), waist circumference (WC), cardiovascular risk factors, and medications. Peak troponin I and creatinine phosphokinase (CPK) were used to estimate infarct size. Epicardial and pericardial fat were measured by echocardiography. We used univariate …