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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.

Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the …

Temporal And Functional Profile Of The Transcriptional Regulatory Network In The Early Regenerative Response To Partial Hepatectomy In The Rat., Egle Juskeviciute, Rajanikanth Vadigepalli, Jan B Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The goal of these studies was to characterize the transcriptional network regulating changes in gene expression in the remnant liver of the rat after 70% partial hepatectomy (PHx) during the early phase response including the transition of hepatocytes from the quiescent (G0) state and the onset of the G1 phase of the cell cycle. RESULTS: The transcriptome of remnant livers was monitored at 1, 2, 4, and 6 hours after PHx using cDNA microarrays. Differentially regulated genes were grouped into six clusters according their temporal expression profiles. Promoter regions of genes in these clusters were examined for shared transcription …

Elucidating A Normal Function Of Huntingtin By Functional And Microarray Analysis Of Huntingtin-Null Mouse Embryonic Fibroblasts., Hua Zhang, Sudipto Das, Quan-Zhen Li, Ioannis Dragatsis, Joyce Repa, Scott Zeitlin, György Hajnóczky, Ilya Bezprozvanny

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The polyglutamine expansion in huntingtin (Htt) protein is a cause of Huntington's disease (HD). Htt is an essential gene as deletion of the mouse Htt gene homolog (Hdh) is embryonic lethal in mice. Therefore, in addition to elucidating the mechanisms responsible for polyQ-mediated pathology, it is also important to understand the normal function of Htt protein for both basic biology and for HD. RESULTS: To systematically search for a mouse Htt function, we took advantage of the Hdh +/- and Hdh-floxed mice and generated four mouse embryonic fibroblast (MEF) cells lines which contain a single copy of the Hdh …

Prolonged Hemophagocytic Lymphohistiocytosis Syndrome As An Initial Presentation Of Hodgkin Lymphoma: A Case Report., Kathryn Chan, Eric Behling, David S Strayer, William S Kocher, Scott K Dessain

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Hemophagocytic lymphohistiocytosis is an immune-mediated syndrome that typically has a rapidly progressive course that can result in pancytopenia, coagulopathy, multi-system organ failure and death. CASE PRESENTATION: A 57-year-old Caucasian woman was referred in fulminant hemophagocytic lymphohistiocytosis, with fever, pancytopenia, splenomegaly, mental status changes and respiratory failure. She was found to have stage IV classical Hodgkin lymphoma, in addition to Epstein-Barr virus and cytomegalovirus viremia. Her presentation was preceded by a 3-year prodrome consisting of cytopenia and fever that were partially controlled by steroids and azathioprine. CONCLUSION: Fulminant hemophagocytic lymphohistiocytosis may follow a prodromal phase that possesses features suggestive of …

Continuous Source Of Care Among Young Underserved Children: Associated Characteristics And Use Of Recommended Parenting Practices., Esther K Chung, Leny Mathew, Kelly F Mccollum, Irma T Elo, Jennifer F Culhane

Department of Pediatrics Faculty Papers

OBJECTIVES: The aim of this study was to 1) assess sociodemographic and health characteristics associated with having a continuous source of care (CSOC) among young children and 2) determine the relationship between having a CSOC and use of parenting practices.

METHODS: We conducted a prospective, community-based survey of women receiving prenatal care at Philadelphia community health centers. We conducted surveys at the first prenatal visit and at a mean age +/- standard deviation of 3 +/-1, 11 +/- 1, and 24 +/- 2 months postpartum, obtaining information on sociodemographic and health characteristics, child's health care provider, and 6 parenting practices. …

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.

Magnetic Resonance Imaging Findings In Bipartite Medial Cuneiform - A Potential Pitfall In Diagnosis Of Midfoot Injuries: A Case Series., Ilan Elias, Sachin Dheer, Adam C Zoga, Steven M Raikin, William B Morrison

Department of Radiology Faculty Papers

INTRODUCTION: The bipartite medial cuneiform is an uncommon developmental osseous variant in the midfoot. To our knowledge, Magnetic Resonance Imaging (MRI) characteristics of a non-symptomatic bipartite medial cuneiform have not been described in the orthopaedic literature. It is important for orthopaedic foot and ankle surgeons, musculoskeletal radiologists, and for podiatrists to identify this osseous variant as it may be mistakenly diagnosed as a fracture or not recognized as a source of non-traumatic or traumatic foot pain, which may sometimes even require surgical treatment. CASE PRESENTATIONS: In this report, we describe the characteristics of three cases of bipartite medial cuneiform on …

Jefferson Alumni Bulletin – Volume 57, Number 1, Winter 2008

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 57, Number 1, Winter 2008

Dean’s Column: Maintaining the Momentum; Page 2

Findings: Brain Implant May Detect and Stop Epilepsy Seizures, Effects of Vitamin C on Non-Hodgkin’s Lymphoma; Page 4

On Campus; Page 6

Getting to the Heart of the Matter; Page 9

Thank you, Dr. Nasca; Page 18

The Jeffersonian Magazine; Page 22

Class Notes; Page 24

In Memoriam; Page 28

By The Numbers: Heart Rate; Page 29

A Construct With Fluorescent Indicators For Conditional Expression Of Mirna., Linghua Qiu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Zuoshang Xu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transgenic RNAi holds promise as a simple, low-cost, and fast method for reverse genetics in mammals. It may be particularly useful for producing animal models for hypomorphic gene function. Inducible RNAi that permits spatially and temporally controllable gene silencing in vivo will enhance the power of transgenic RNAi approach. Furthermore, because microRNA (miRNA) targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals. RESULTS: We sought to optimally express a miRNA simultaneously with a fluorescent marker. We compared two construct designs. One expressed …

Off-Label Psychopharmacologic Prescribing For Children: History Supports Close Clinical Monitoring., Julie M Zito, Albert T Derivan, Christopher J Kratochvil, Daniel J Safer, Joerg M Fegert, Laurence L Greenhill

Department of Psychiatry and Human Behavior Faculty Papers

The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring.

Annual Report, 2006-2007, David B. Nash

College of Population Health Annual Reports

No abstract provided.

Healing The Health Care System: Summaries From The Department Of Health Policy Summer Seminar, David B. Nash, Nora Dowd Eisenhower, Rosemarie Greco, Deborah C. Meiris

College of Population Health Faculty Papers

Editorial Introduction:
The disease management field continues to evolve. The range of chronic diseases treated has expanded to include such conditions as obesity and pain management, and the care continuum now encompasses wellness, prevention, and population health. One population that is an ideal candidate for our collective efforts is that of older adults. Global and national population projections reveal the impending staggering increase in the age 65+ cohort, which will cause a sharp increase in the demand for health care and other services due to such age-related issues as multiple chronic conditions, falls, and depression.

To begin to address these …

The "Crossroads" And Beyond, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Report On The U.S. Summit: "Chronic Care At The Crossroads: Exploring Solutions For Chronic Care Management", Janice L. Clarke

College of Population Health Faculty Papers

On Tuesday, July 17, 2007 in Washington, DC, Intel Corporation assembled a group of the nation’s most respected health leaders to discuss the issues surrounding chronic care and an aging population and explore solutions to these highly complex and increasingly urgent challenges for the US health care system. The highlevel summit, hosted by Intel Chairman Craig Barrett, was held in the auditorium of the National Museum for Women in the Arts and attended, either in person or via the simultaneous webcast, by presidents, chairmen, and executive directors of influential organizations including the National Business Coalition on Health, the National Medical …

Mice Deficient In Involucrin, Envoplakin, And Periplakin Have A Defective Epidermal Barrier., Lisa M Sevilla, Rachida Nachat, Karen R Groot, John F Klement, Jouni Uitto, Philippe Djian, Arto Määttä, Fiona M Watt

Department of Dermatology and Cutaneous Biology Faculty Papers

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective …

Acetylation In Nuclear Receptor Signaling And The Role Of Sirtuins, Chenguang Wang, Michael J. Powell, Vladimir M. Popov, Richard G. Pestell

Department of Cancer Biology Faculty Papers

It has been known since the early 1970s that nuclear receptor complexes bind DNA in association with co-regulatory proteins. Characterization of these nuclear receptor coregulators has revealed diverse enzymatic activities which temporally and spatially coordinate nuclear receptor activity within the context of local chromatin in response to diverse hormone signals. Chromatin modifying proteins, which dictate the higher order chromatin structure in which DNA is packaged, in turn orchestrate orderly recruitment of nuclear receptor complexes. Modifications of histones include acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, ADP ribosylation, deimination and proline isomerization (1). At this time, we understand how a subset of these …

How Does Quality Enter Into Health Care Purchasing Decisions?, Neil I. Goldfarb, Vittorio Maio, Chureen T. Carter, Laura Pizzi, David B. Nash

College of Population Health Faculty Papers

A number of employers, business consortia, and public purchasers are promoting "value-based purchasing" as a way to improve the quality of patient care. Some purchasers are using publicly available information on health plan and provider performance to make their health plan and provider choices, while others are using their market power to drive improvements in patient care and safety. This article examines six key strategies used by purchasers.

Editorial Board

Jefferson Journal of Psychiatry

No abstract provided.

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Evidence-B(I)Ased Medicine: Limitations And Non-Superstition-Based Alternatives, Joshua S. Green M.D., Ph.D. (Pgy4)

Jefferson Journal of Psychiatry

The Evidence-Based Medicine (EBM) movement crystallized in the early 1990's at McMaster University in Canada. The movement originally challenged practitioners to validate their treatments based on reasoning and clinical studies rather than personal authority. In this essay, I will argue that, contrary to this wholesome intention, EBM is authoritarian in spirit and actually constricts discourse about how to make clinical decisions.

Diphenhydramine-Dependence Resulting From Self-Medication Of Antipsychotic- Induced Extrapyramidal Symptoms, Faisal S. Shaikh M.B.B.S., Ann M. Mortimer M.D.

Jefferson Journal of Psychiatry

Antipsychotic-induced extrapyramidal symptoms should be recognised and adequately treated. We report an unusual complication of not doing so: a patient’s self-medicating to control these symptoms, which produced diphenhydramine-dependence.

Dissociative-Like Spells In A Child With Neurofibromatosis (Type 1), Gregory M. Singleton M.D. (Pgy2), Ann M. Lagges Ph.D., Karen G. Meighen M.D.

Jefferson Journal of Psychiatry

Neurofibromatosis, type 1, (NF1) is a common neurocutaneous disorder of childhood. Little is known about the psychiatric aspects of the condition. We present the case of a 10-year-old male with NF1 and complex spells. For two years he had been experiencing self-limited paroxysms of auditory and visual hallucination, assaultiveness, excited undressing, and amnesia. The spells have been refractory to multiple treatments, including antipsychotic medication. The question remains whether this episodic amnestic disorder is comorbid with NF1 or is caused by it.