Medicine and Health Sciences Commons^™

Intracellular Bacteria Encode Inhibitory Snare-Like Proteins., Fabienne Paumet, Jordan Wesolowski, Alejandro Garcia-Diaz, Cedric Delevoye, Nathalie Aulner, Howard A Shuman, Agathe Subtil, James E Rothman

Department of Microbiology and Immunology Faculty Papers

Pathogens use diverse molecular machines to penetrate host cells and manipulate intracellular vesicular trafficking. Viruses employ glycoproteins, functionally and structurally similar to the SNARE proteins, to induce eukaryotic membrane fusion. Intracellular pathogens, on the other hand, need to block fusion of their infectious phagosomes with various endocytic compartments to escape from the degradative pathway. The molecular details concerning the mechanisms underlying this process are lacking. Using both an in vitro liposome fusion assay and a cellular assay, we showed that SNARE-like bacterial proteins block membrane fusion in eukaryotic cells by directly inhibiting SNARE-mediated membrane fusion. More specifically, we showed that …

Jefferson Alumni Bulletin – Volume 58, Number 3, Fall 2009

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 58, Number 3, Fall 2009 Dean’s Message, page 2 Findings--Researchers Counter Allergy to Plavix with Steroids and Antihistamines, page 4 Why in the World Would You Go into Medicine Today?, page 6 Philadelphia 1918: The Flu Pandemic Hits Home, page 14 New Movie Underscores Healthcare Conflicts, page 20 Faculty Profile: Vincenzo Berghella, MD ’90, page 22 On Campus, page 24 Class Notes, page 28 Looking at Scholarships from Both Sides, page 36 Alumni Giving, page 38 In Memoriam, page 50 By the Numbers, page 53

N-Glycosylation Status Of E-Cadherin Controls Cytoskeletal Dynamics Through The Organization Of Distinct Β-Catenin- And Γ-Catenin-Containing Ajs., Basem T Jamal, Mihai Nita-Lazar, Zhennan Gao, Bakr Amin, Janice Walker, Maria A Kukuruzinska

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

N-glycosylation of E-cadherin has been shown to inhibit cell-cell adhesion. Specifically, our recent studies have provided evidence that the reduction of E-cadherin N-glycosylation promoted the recruitment of stabilizing components, vinculin and serine/threonine protein phosphatase 2A (PP2A), to adherens junctions (AJs) and enhanced the association of AJs with the actin cytoskeleton. Here, we examined the details of how N-glycosylation of E-cadherin affected the molecular organization of AJs and their cytoskeletal interactions. Using the hypoglycosylated E-cadherin variant, V13, we show that V13/β-catenin complexes preferentially interacted with PP2A and with the microtubule motor protein dynein. This correlated with dephosphorylation of the microtubule-associated protein …

Utilization Of Dantrolene In Stiff-Person Syndrome: A Case Report, John M. Vasudevan, Md, S. Kamal Fetouh, Md,, Nethra S. Ankam, Md, Adam L. Schreiber, Do, Ma

Department of Rehabilitation Medicine Faculty Papers

Setting: University hospital-based acute rehabilitation.

Patient: 75-year-old woman with Stiff-Person Syndrome (SPS) with a recent fall and Colles fracture.

Case Description: Four months prior to admission, the patient was diagnosed with SPS, negative for anti-GAD antibodies. Diagnosis was based on a 3-year history of progressive rigidity leading to frequent falls and fractures. Anxiety and fear of falling limited her mobility, and she sustained a sacral pressure ulcer during acute hospitalization. On admission, history was remarkable for unsteady gait and muscle cramps exacerbated when startled or excited. Examination was remarkable for rigidity in her axial and limb muscles. She presented …

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Early And Late Treatment Of Migraine With Dhe Ns (Migranal®), Meryl Latsko, Md, Mph, Stephen D. Silberstein, Md

Department of Jefferson Headache Center Papers and Presentations

To examine the use of DHE NS (Migranal®) in the early and late treatment of migraine in subjects with a history of cutaneous allodynia.

Transverse Myelitis In Pregnancy: A Case Report, Brian P. Mcdonald, Do, Nethra S. Ankam, Md

Department of Rehabilitation Medicine Faculty Papers

Objective: Describe the clinical course and treatment of a patient with paraplegia secondary to transverse myelitis during her pregnancy.

Setting: Acute Inpatient Rehabilitation Unit, University Hospital.

Participant: 36 year old Caucasian woman at 18 weeks gestation.

Interventions: Provided education and training on basic childcare tasks at a wheelchair level, and on how to obtain wheelchair accessible baby furniture. Provided availability of a peer who sustained a spinal cord injury prior to pregnancy. Maintained a close working relationship with maternal fetal health department regarding management of nausea and pain management, and educated team members about the possibility of autonomic …

Frovatriptan As Preemptive Treatment For Fasting-Induced Migraine, Meryl Latsko, Md, Mph, Stephen D. Silberstein, Md

Department of Jefferson Headache Center Papers and Presentations

To examine frovatriptan's efficacy as preemptive treatment for fasting-induced migraine.

Dronedarone., Chinmay Patel, Gan-Xin Yan, Peter R Kowey

Department of Medical Genetics Faculty Papers

Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. …

Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …

Jefferson Alumni Bulletin – Volume 58, Number 2, Summer 2009

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 58, Number 2, Summer 2009

Dean’s Message, page 2

Findings, Biomaker Predicts Disease Recurrence in Colorectal Cancer, page 4

Service Lines: Guiding Patients Through the Maze, page 6

University’s Emphasis on Interdisciplinary Care Fuels Growth, page 12

Mütter Turns 150 with New Take on the Old, page 16

On Campus, page 18

Graduation 2009, page 22

Class Notes, page 24

In Memoriam, page 30

By The Numbers, page 33

Nerve Injection Of Viral Vectors Efficiently Transfers Transgenes Into Motor Neurons And Delivers Rnai Therapy Against Als., Rui Wu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Chunyan Liu, Maria Castro, Zuoshang Xu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

RNA interference (RNAi) mediates sequence-specific gene silencing, which can be harnessed to silencing disease-causing genes for therapy. Particularly suitable diseases are those caused by dominant, gain-of-function type of gene mutations. In these diseases, the mutant gene generates a mutant protein or RNA product, which possesses toxic properties that harm cells. By silencing the mutant gene, the toxicity can be lessened because the amount of the toxic product is lowered in cells. In this report, we tested RNAi therapy in a mouse model for amyotrophic lateral sclerosis (ALS), which causes motor neuron degeneration, paralysis, and death. We used a transgenic model …

Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.

METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.

RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher …

Intravenous Inoculation Of A Bat-Associated Rabies Virus Causes Lethal Encephalopathy In Mice Through Invasion Of The Brain Via Neurosecretory Hypothalamic Fibers., Mirjam A R Preuss, Marie-Luise Faber, Gene S Tan, Michael Bette, Bernhard Dietzschold, Eberhard Weihe, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

The majority of rabies virus (RV) infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown …

Interaction With Lc8 Is Required For Pak1 Nuclear Import And Is Indispensable For Zebrafish Development., Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, Jonathan Chernoff, Ulrich Rodeck, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import …

A Novel Codon Insert In Protease Of Clade B Hiv Type 1., Parris S Jordan, Art Poon, Joseph Eron, Kathleen Squires, Caroline Ignacio, Douglas D Richman, Davey M Smith

Division of Infectious Diseases and Environmental Medicine Faculty Papers

A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69.

Jefferson Alumni Bulletin – Volume 58, Number 1, Spring 2009

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 58, Number 1, Spring 2009

JMC’s New Dean, page 2

Findings- Researchers Use Toxin Gene to “Kill Cancer Cells”, page 4

Restrictions, Hospitalists, PA s: Dramatic Changes in Education, page 6

Scholarship Dinner, page 13

Breaking Ground with Team-Based Education, page 14

On Campus, page 18

Class Notes, page 24

In Memoriam, page 28

By The Numbers, page 29

Y27632, A Rho-Activated Kinase Inhibitor, Normalizes Dysregulation In Alpha1-Adrenergic Receptor-Induced Contraction Of Lyon Hypertensive Rat Artery Smooth Muscle., Maria Regina Freitas, Masumi Eto, Jason A Kirkbride, Christa Schott, Jean Sassard, Jean-Claude Stoclet

Department of Molecular Physiology and Biophysics Faculty Papers

RhoA-activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the alpha1-adrenergic receptor agonist-induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca(2+)-depletion and pre-treatment with phenylephrine (PE), smooth muscle contraction was induced by serial additions of CaCl(2). In LH SMA Ca(2+) permeated cells to a lesser extent as compared with LN SMA, while CaCl(2)-induced contraction of LH …

Positional Information Generated By Spatially Distributed Signaling Cascades., Javier Muñoz-García, Zoltan Neufeld, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile …

Piel- Manual De Enseñanza Para El Paciente Y La Familia Sobre Lesiones De La Médula Espinal, Thomas Jefferson University Hospital And Magee Rehabilitation

Manual de Lesión de la Médula Espinal (Español)

Introducción a la función de la piel

La piel es una parte fundamental del cuerpo y tiene muchas funciones necesarias:

• La piel lo protege del medio ambiente. Cuando la piel está intacta, existe una barrera contra las bacterias y las lesiones a los órganos que se encuentran en el interior del organismo. Evita que la luz solar en exceso o los químicos nocivos penetren en el organismo.

• La piel lo ayuda a mantenerse caliente o fresco. Las glándulas sudoríparas producen sudor y lo refrescan al evaporar el sudor de la piel.

• Las terminaciones nerviosas de la piel …

Download Full Pdf Issue-Jefferson Translations, Vol. 4, No. 1, Winter 2009

Jefferson Translations

This issue includes the announcement of a prestigious $11.6M grant to study heart failure, a recap of the Center for Translational Medicine's 4th Annual Symposium, an update on hematology research in blood clots, a visit with Dr. Cheung the Nephrology Chief, faculty news, and the Leon Peris award winner.

Introduction-Spinal Cord Injury Manual, Thomas Jefferson University Hospital And Magee Rehabilitation

Spinal Cord Injury Manual (English)

About this Manual:

This Spinal Cord Injury Manual is designed for use by the person with a spinal cord injury or dysfunction and his or her family. It is a guide to provide information on the many aspects of spinal cord injury and dysfunction. This handbook will help you and your family prepare for discharge from our comprehensive rehabilitation program and supplement lifelong learning about spinal cord injury and dysfunction. The handbook is divided into topic sections and bound in loose-leaf form so that a member of the health care team may use each section in addition to teaching and …

Activities Of Daily Living-Spinal Cord Injury Manual, Thomas Jefferson University Hospital And Magee Rehabilitation

Spinal Cord Injury Manual (English)

Introduction

Activities of daily living (ADL) include eating, drinking, functional bathing, grooming, dressing and toileting. Also included are functional transfers, EADL (Electronic Aids for Daily Living) and home management.

As soon as it is appropriate, you will be encouraged to perform as many of your own ADLs as you can. You may need to learn new techniques, use assistive devices to compensate for decreased muscle strength and range of motion or to compensate for decreased endurance.

ADL training will begin when your therapist determines that you have enough strength, balance and skill to do these tasks. You may practice these …

Psychosocial Issues-Spinal Cord Injury Manual, Thomas Jefferson University Hospital And Magee Rehabilitation

Spinal Cord Injury Manual (English)

Introduction

A sudden trauma like a spinal cord injury will have a significant impact on you and the people close to you. You may see parts of your life change a great deal. Other parts of your life may not change at all. Regardless of the extent of your injury and disability, being hurt and having a disruption to your life may present unexpected problems or changes. This chapter provides information about services that are available at Thomas Jefferson University Hospital, Magee Rehabilitation Hospital and in the community to provide assistance.

Coping with a Spinal Cord Injury

After a spinal …

Bladder-Spinal Cord Injury Manual, Thomas Jefferson University Hospital And Magee Rehabilitation

Spinal Cord Injury Manual (English)

Introduction

Your bladder and urinary system play a very important part in keeping you healthy by acting like a “filter” and getting rid of the waste products from food and fluid that you have eaten and absorbed. After you have had a spinal cord injury, you often lose your ability to control urination. You may not be able to feel that your bladder is full, and if you can feel it, you may not be able to empty it.

It is important to note here that the changes that occur in your bladder will be unique to you. Although there …

Sexuality-Spinal Cord Injury Manual, Thomas Jefferson University Hospital And Magee Rehabilitation

Spinal Cord Injury Manual (English)

Introduction

In this section, you will learn how spinal cord impairments can affect the way that you feel about yourself as a man or woman as well as how spinal cord impairments can affect the way that you function sexually. Information on sexuality, sexual functioning, birth control, erectile dysfunction and having a baby may be important to you today, or these issues may be something that you choose to put away and think about at another time. In either case, this information is just a starting point. Feel free to ask questions and share your concerns and thoughts with the …

Terapia Recreativa- Manual De Enseñanza Para El Paciente Y La Familia Sobre Lesiones De La Médula Espinal, Thomas Jefferson University Hospital And Magee Rehabilitation

Manual de Lesión de la Médula Espinal (Español)

Introducción

Su tiempo libre y la forma en que usa ese tiempo pueden ser una fuente de satisfacción, disfrute y realización personal. Usted probablemente tenga muchas preguntas sobre el efecto de su lesión en la capacidad de participar en sus actividades y deportes favoritos. Existe terapia recreativa disponible para ayudarlo a responder todas las preguntas e inquietudes y a planificar un estilo de vida para el tiempo libre que le resulte satisfactorio.

¿Qué es la terapia recreativa?

La terapia recreativa es una forma de tratamiento que utiliza actividades recreativas para trabajar sobre sus objetivos de rehabilitación. Mediante la utilización de …

Glosario Principal- Manual De Enseñanza Para El Paciente Y La Familia Sobre Lesiones De La Médula Espinal, Thomas Jefferson University Hospital And Magee Rehabilitation

Manual de Lesión de la Médula Espinal (Español)

Glosario principal para Manual de enseñanza para el paciente y la familia sobre lesiones de la médula espinal,

(29 páginas,458Kb)

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link Newsletter, Vol. 5, Iss. 1, Winter 2009

Public Health Link

This issue includes a spotlight on alumnae—Meghan Gannon, along with recaps of the Oxfam Hunger banquet, SAPHE Students Participate in AIDS Walk Philly, the Annual APHA: Public Health Without Borders conference and program announcements.

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …