Medicine and Health Sciences Commons^™

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 …

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.

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.

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.

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 …

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.

Tumor Epithelial Cell Matrix Metalloproteinase 9 (Mmp-9) Is A Prognostic Marker In Colorectal Cancer, Ds Zuzga, Av Gibbons, P Li, Wj Lubbe, I Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at American Association Cancer Research in 2008

Zuzga D.S., Gibbons A.V., Li P., Lubbe W.J., Chervoneva I., Pitari G.M. “Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer”. In: American Association for Cancer Research Special Conference, Molecular Diagnostics in Cancer Therapeutic Development: Proceedings; 2008 Sept 22-25; Philadelphia, PA. Abstract A40.

Colorectal cancer is the second leading cause of cancer-related mortality indeveloped nations. Mortality from colon cancer largely reflects metastasis, thespread of the disease to distant sites. Early diagnosis of pre-metastatic diseaseand accurate stratification of patients with metastasis is pivotal to decreasemortality rates from colon cancer by effectively …

Topical Application Of Entry Inhibitors As "Virustats" To Prevent Sexual Transmission Of Hiv Infection., Michael M Lederman, Robin Jump, Heather A Pilch-Cooper, Michael Root, Scott F Sieg

Kimmel Cancer Center Faculty Papers

With the continuing march of the AIDS epidemic and little hope for an effective vaccine in the near future, work to develop a topical strategy to prevent HIV infection is increasingly important. This stated, the track record of large scale "microbicide" trials has been disappointing with nonspecific inhibitors either failing to protect women from infection or even increasing HIV acquisition. Newer strategies that target directly the elements needed for viral entry into cells have shown promise in non-human primate models of HIV transmission and as these agents have not yet been broadly introduced in regions of highest HIV prevalence, they …

Left Ventricular Pseudoaneurysm Found By Ct Scan., Hitoshi Hirose, Md, Iwao Matsunaga, Md, Michael D. Strong Iii, Md

Department of Surgery Faculty Papers

A 62-year-old male with a previous coronary artery bypass grafting underwent CT scan for evaluation of left epigastric pain. Findings showed a large left ventricular pseudoaneurysm, which was subsequently confirmed by left ventriculogram. The pseudoaneurysm was successfully repaired surgically.

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 …

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 …

Cell Autonomous Expression Of Inflammatory Genes In Biologically Aged Fibroblasts Associated With Elevated Nf-Kappab Activity., Andres Kriete, Kelli L Mayo, Nirupama Yalamanchili, William Beggs, Patrick Bender, Csaba Kari, Ulrich Rodeck

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years. RESULTS: Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains …

Evidence That The Nijmegen Breakage Syndrome Protein, An Early Sensor Of Double-Strand Dna Breaks (Dsb), Is Involved In Hiv-1 Post-Integration Repair By Recruiting The Ataxia Telangiectasia-Mutated Kinase In A Process Similar To, But Distinct From, Cellular Dsb Repair., Johanna A Smith, Feng-Xiang Wang, Hui Zhang, Kou-Juey Wu, Kevin Jon Williams, René Daniel

Kimmel Cancer Center Faculty Papers

Retroviral transduction involves integrase-dependent linkage of viral and host DNA that leaves an intermediate that requires post-integration repair (PIR). We and others proposed that PIR hijacks the host cell double-strand DNA break (DSB) repair pathways. Nevertheless, the geometry of retroviral DNA integration differs considerably from that of DSB repair and so the precise role of host-cell mechanisms in PIR remains unclear. In the current study, we found that the Nijmegen breakage syndrome 1 protein (NBS1), an early sensor of DSBs, associates with HIV-1 DNA, recruits the ataxia telangiectasia-mutated (ATM) kinase, promotes stable retroviral transduction, mediates efficient integration of viral DNA …

Spinal Cord Stimulation: An Update., Steven Falowski, Amanda Celii, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Spinal cord stimulation has been used in the treatment of many chronic pain disorders since 1967. In this update, the indications for spinal cord stimulation are reviewed with attention to recent publications. A focused review of the literature on abdominal and visceral pain syndromes is also provided. Furthermore, the technology has evolved from the use of monopolar electrodes to complex electrode arrays. Similarly, the power source has changed from a radio frequency-driven system to a rechargeable impulse generator. These topics are covered, along with a short discussion of implant technique. Finally, we include a review of complications of such therapy. …

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

Proteomic Profiling Of Endorepellin Angiostatic Activity On Human Endothelial Cells., Jason J Zoeller, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Endorepellin, the C-terminal domain V of the heparan sulfate proteoglycan perlecan, exhibits powerful and targeted anti-angiogenic activity on endothelial cells. To identify proteins involved with endorepellin anti-angiogenic action, we performed an extensive comparative proteomic analysis between vehicle- and endorepellin-treated human endothelial cells. RESULTS: Proteomic analysis of endorepellin influence on human umbilical vein endothelial cells identified five differentially expressed proteins, three of which (beta-actin, calreticulin, and chaperonin/Hsp60) were down-regulated and two of which (vimentin and the beta subunit of prolyl 4-hydroxylase also known as protein disulfide isomerase) were up-regulated in response to endorepellin treatment-and associated with a fold change (endorepellin/control) …

Enhancing Teaching And Learning: Integrating Technology And Nursing Education, Kellie Smith, Edd, Rn, Elizabeth Elkind, Rnc, Msn, Mba, Phd(C)

College of Nursing Faculty Papers & Presentations

Enhancing teaching and learning: Integrating technology and nursing education. Jefferson School of Nursing Faculty Development Day: Understanding scholarship: The Boyer model and career development. Philadelphia, PA (podium)

15 PowerPoint slides.