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Fibulin-2 Is Dispensable For Mouse Development And Elastic Fiber Formation, Francois-Xavier Sicot, Takeshi Tsuda, Dessislava Markova, John Klement, Machiko Arita, Rui-Zhu Zhang, Te-Cheng Pan, Robert P. Mecham, David E. Birk, Mon-Li Chu

Department of Dermatology and Cutaneous Biology Faculty Papers

Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin family, of which two members have been shown to play essential roles in elastic fiber formation during development. Fibulin-2 interacts with two major constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and localizes to elastic fibers in many tissues in vivo. The protein is prominently expressed during morphogenesis of the heart and aortic arch vessels and at early stages of cartilage development. To examine its role in vivo, we generated mice that do not express the fibulin-2 gene (Fbln2) through homologous recombination of embryonic stem cells. Unexpectedly, the …

Trk: A Neuromodulator Of Age-Specific Behavioral And Neurochemical Responses To Cocaine In Mice., Michelle Niculescu, Shane A Perrine, Jonathan S Miller, Michelle E Ehrlich, Ellen M Unterwald

Farber Institute for Neuroscience Faculty Papers

Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadolescent, and adult male CD-1 mice were exposed to cocaine (20 mg/kg) for 7 d. The rewarding effects of cocaine were assessed, as were the response to a Trk antagonist and the regulation of dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32). Cocaine was rewarding in both periadolescent and adult mice using a conditioned place preference procedure. In contrast, postweanling mice …

Dilated Cisternae Chyli. A Sign Of Uncompensated Cirrhosis At Mr Imaging, Sachit K. Verma, Donald G. Mitchell, Diane Bergin, Yulia Lakhman, Amy Austin, Manisha Verma, David Assis, Steven K. Herrine, Laurence Parker

Department of Radiology Faculty Papers

Background: To retrospectively determine the frequency of dilated cisterna chyli (CC) on MR images in patients with cirrhosis, and to assess its value as a simple diagnostic imaging sign of uncompensated cirrhosis.

Methods: Study population included 257 patients (149 with pathologically proved cirrhosis and 108 control subjects without history of chronic liver diseases) who had 1.5T MR imaging. Cirrhosis patients were divided into compensated and uncompensated groups. Three independent observers qualitatively evaluated visibility of CC 2mm or greater in transverse diameter, identified as a tubular structure with fluid signal intensity (SI). CC diameters greater than 6 mm were defined as …

Diverse Antidepressants Increase Cdp-Diacylglycerol Production And Phosphatidylinositide Resynthesis In Depression-Relevant Regions Of The Rat Brain, Kimberly R. Tyeryar, Habiba O.U. Vongtau, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

BACKGROUND: Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we …

Mlk Day 2008

Diversity Programs

Calendar of event in Honor of Dr. Martin Luther King, Jr. Day, January 2008.

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

Alternate Cyclin D1 Mrna Splicing Modulates P27Klp1 Binding And Cell Migration, Zhiping Li, Chenguang Wang, Xuanmao Jiao, Sanjay Katiyar, Mathew C. Casimiro, George C. Prendergast, Michael J. Powell, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27^KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties …

The Clinical Efficacy Of Reflexology In Nursing Home Residents With Dementia, Nancy A. Hodgson

Selected Works of Nancy Hodgson, PhD

No abstract provided.

Book Review: Drugs During Pregnancy And Lactation: Treatment Options And Risk Assessment, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Environmental Causes Of Human Congenital Malformations: The Physician's Role In Dealing With These Complex Clinical Problems Caused By Environmental And Genetic Factors., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Bio-Monitoring The Elimination Of Folic Acid-Preventable Spina Bifida And Anencephaly, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Department Of Radiology-Annual Executive Summary Report-July 1, 2007 To June 30, 2008, Vijay M. Rao M.D.

Department of Radiology Administrative Documents and Reports

79 page Department of Radiology Annual Executive Summary Report, July 1, 2007 to June 30, 2008, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

2008 Clinic Yearbook, Christopher Yingling

Sidney Kimmel Medical College Yearbooks

The Clinic is the yearbook of the Sidney Kimmel Medical College (formerly Jefferson Medical College) at Thomas Jefferson University.

Palliative Care In Nursing Homes: A Comparison Of High And Low-Level Providers, Nancy A. Hodgson

Selected Works of Nancy Hodgson, PhD

No abstract provided.

Guest Perspective - Dr. Robert L. Brent, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Expressions Of Asia 2008

Diversity Programs

Lectures, cultural events, and Asian cuisine during Expressions of Asia, January 2008.

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 …

Targeting Nf-Kappab: A Promising Molecular Therapy In Inflammatory Arthritis., Jorge A. Roman-Blas, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The nuclear factor-kappa B family of transcription factors is intimately involved in the regulation of the inflammatory responses that play a fundamental role in the damage of articular tissues. Thus, many studies have examined the important contributions of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases and their pharmacologic modulation. Currently available therapeutic agents including nonsteroidal anti-inflammatory drugs, corticosteroids, nutraceuticals, and disease-modifying antirheumatic drugs, as well as novel specific small-molecule inhibitors have been employed. In addition, promising nucleic acid-based strategies have shown encouraging results. However, further research will be needed before NF-kappaB-aimed strategies become an …

Molecular Ablation Of Tgf-Beta Signaling Pathways By Tyrosine Kinase Inhibition: The Coming Of A Promising New Era In The Treatment Of Tissue Fibrosis, Joel Rosenbloom, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

No abstract provided.

Navigating Distance Learning Technologies Using Team Teaching, Jennifer Bellot, Anthony J. Frisby, Lori Lauver, Mary L. Manning, Beth A. Swan, Ksenia Zukowsky, Mary Powell, Margaret M. West, Alexis Marsella

Selected Works of Jennifer Bellot

In 2004, the American Association of Colleges of Nursing (AACN) adopted the position to move the current level of preparation necessary for advanced practice nurse (APN) roles from the master's degree to the doctoral level. AACN also called for educating APNs and other nurses seeking top leadership and clinical roles in Doctor of Nursing Practice (DNP) Programs.

In September 2007, the Jefferson School of Nursing welcomed its first cohort of 18 DNP students. Students represented a wide variety of practice specialties including acute care, primary care, healthcare administration, population health, education and industry. Twenty students comprise the second cohort entering …

Hiv-1 Tat And Aids-Associated Cancer: Targeting The Cellular Anti-Cancer Barrier?, Giuseppe Nunnari, Johanna A Smith, René Daniel

Department of Medicine Faculty Papers

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced …

Distinguishing Post-Treatment Changes From Recurrent Disease In Cholangiocarcinoma: A Case Report., Timothy N Showalter, A Omer Nawaz, Frederick M Fellin, Pramila R Anne, Ernest L Rosato, Adam P Dicker

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Three-dimensional techniques for radiotherapy have expanded possibilities for partial volume liver radiotherapy. Characteristic, transient radiographic changes can occur in the absence of clinical radiation-induced liver disease after hepatic radiotherapy and must be distinguished from local recurrence. CASE PRESENTATION: In this report, we describe computed tomography changes after chemoradiotherapy for cholangiocarcinoma as an example of collaboration to determine the clinical significance of the radiographic finding. CONCLUSION: Because of improved three-dimensional, conformal radiotherapy techniques, consultation across disciplines may be necessary to interpret post-treatment imaging findings.

Upa Is Upregulated By High Dose Celecoxib In Women At Increased Risk Of Developing Breast Cancer., Wenyi Qin, Weizhu Zhu, John E Hewett, George Rottinghaus, Yin-Chieh Chen, John T Flynn, Beth Kliethermes, Ferdinando Mannello, Edward R Sauter

Department of Physiology Faculty Papers

BACKGROUND: While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E2 expression in nipple aspirate fluid (NAF) and uPA and PGE2 expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk.

METHODS: NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking …

Inhibition Of Oncogene-Induced Inflammatory Chemokines Using A Farnesyltransferase Inhibitor., Katharine C Degeorge, Brent R Degeorge, James S Testa, Jay L Rothstein

Department of Microbiology and Immunology Faculty Papers

ABSTRACT: BACKGROUND: Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can …

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 …

Sevoflurane Enhances Ethanol-Induced Cardiac Preconditioning Through Modulation Of Protein Kinase C, Mitochondrial Katp Channels, And Nitric Oxide Synthase, In Guinea Pig Hearts., Kazuhiro Kaneda, Masami Miyamae, Shingo Sugioka, Chika Okusa, Yoshitaka Inamura, Naochika Domae, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND: Volatile anesthetics and regular ethanol consumption induce cardioprotection mimicking ischemic preconditioning. We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial K(ATP) channels attenuated this enhanced cardioprotection. The effects of regular ethanol consumption on expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase were determined. METHODS: Isolated perfused guinea pig hearts underwent 30-min global ischemia and 120-min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 wk. Anesthetic preconditioning was elicited by 10-min exposure to sevoflurane (1 minimum alveolar anesthetic concentration; 2%) in ethanol …

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 …

Bone Stress Injury Of The Ankle In Professional Ballet Dancers Seen On Mri., Ilan Elias, Adam C Zoga, Steven M Raikin, Judith R Peterson, Marcus P Besser, William B Morrison, Mark E Schweitzer

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Ballet dancers have been shown to have a relatively high incidence of stress fractures of the foot and ankle. It was our objective to examine MR imaging patterns of bone marrow edema (BME) in the ankles of high performance professional ballet dancers, to evaluate clinical relevance. METHODS: MR Imaging was performed on 12 ankles of 11 active professional ballet dancers (6 female, 5 male; mean age 24 years, range 19 to 32). Individuals were imaged on a 0.2 T or 1.5 T MRI units. Images were evaluated by two musculoskeletal radiologists and one orthopaedic surgeon in consensus for location …

Eosinophilic Fasciitis: Demographics, Disease Pattern And Response To Treatment: Report Of 12 Cases And Review Of The Literature, Lindsay Bischoff, Chris T. Derk

Department of Medicine Faculty Papers

BACKGROUND:
Eosinophilic fasciitis is a rare scleroderma-like illness. The clinical spectrum of the disease has evolved since its initial description.

METHODS:
We identified all patients diagnosed with eosinophilic fasciitis over the past 10 years at our scleroderma clinic. Demographics, disease pattern, serologies, tissue pathology and reponse to treatment were all recorded.

RESULTS:
Twelve patients with eosinophilic fasciitis were identified in our clinic over the past 10 years. The mean age at diagnosis was 49.8 +/- 9.8 years, with nine female and three male patients. The first symptoms were noticed at an average of 8.8 +/- 6.1 months before diagnosis. The …

Management Of The Neck In Differentiated Thyroid Cancer, David M. Cognetti, Edmund A. Pribitkin, William M. Keane

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Differentiated thyroid cancer is characterized by an excellent long-term prognosis, which unlike other head and neck carcinomas, is not influenced definitively by regional lymph node metastasis. The relative rarity of the disease, together with its tendency for delayed metastasis and its low mortality, makes a prospective randomized trial comparing treatment outcomes difficult. As a result, the effect of cervical lymph node metastases on survival is unclear, making meaningful recommendations for their management somewhat subjective. This article discusses guidelines for the management of the neck in differentiated.