Medicine and Health Sciences Commons^™

Cns Recruitment Of Cd8+ T Lymphocytes Specific For A Peripheral Virus Infection Triggers Neuropathogenesis During Polymicrobial Challenge., Christine M Matullo, Kevin J O'Regan, Mark Curtis, Glenn F Rall

Department of Microbiology and Immunology Faculty Papers

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with …

Mutant Tdp-43 In Motor Neurons Promotes The Onset And Progression Of Als In Rats, Cao Huang, Jianbin Tong, Fangfang Bi, Hongxia Zhou, Xu-Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. …

A Meta-Analysis Of Array-Cgh Studies Implicates Antiviral Immunity Pathways In The Development Of Hepatocellular Carcinoma., Xu Guo, Yanna Ba, Xi Ma, Jiaze An, Yukui Shang, Qichao Huang, Hushan Yang, Zhinan Chen, Jinliang Xing

Kimmel Cancer Center Faculty Papers

BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.

METHODS: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.

RESULTS: Eighty …

Race/Ethnicity, Gender, Weight Status, And Colorectal Cancer Screening., Heather Bittner Fagan, Ronald E Myers, Constantine Daskalakis, Randa Sifri, Arch G Mainous, Richard Wender

Department of Medical Oncology Faculty Papers

Background. The literature on colorectal cancer (CRC) screening is contradictory regarding the impact of weight status on CRC screening. This study was intended to determine if CRC screening rates among 2005 National Health Interview Survey (NHIS) respondent racial/ethnic and gender subgroups were influenced by weight status. Methods. Univariable and multivariable logistic regression analyses were performed to determine if CRC screening use differed significantly among obese, overweight, and normal-weight individuals in race/ethnic and gender subgroups. Results. Multivariable analyses showed that CRC screening rates did not differ significantly for individuals within these subgroups who were obese or overweight as compared to their …

Wnt Signaling Exerts An Antiproliferative Effect On Adult Cardiac Progenitor Cells Through Igfbp3., Angelos Oikonomopoulos, Konstantina-Ioanna Sereti, Frank Conyers, Michael Bauer, Annette Liao, Jian Guan, Dylan Crapps, Jung-Kyu Han, Hanhua Dong, Ahmad F Bayomy, Gabriel C Fine, Karen Westerman, Travis L Biechele, Randall T Moon, Thomas Force, Ronglih Liao

Center for Translational Medicine Faculty Papers

RATIONALE: Recent work in animal models and humans has demonstrated the presence of organ-specific progenitor cells required for the regenerative capacity of the adult heart. In response to tissue injury, progenitor cells differentiate into specialized cells, while their numbers are maintained through mechanisms of self-renewal. The molecular cues that dictate the self-renewal of adult progenitor cells in the heart, however, remain unclear.

OBJECTIVE: We investigate the role of canonical Wnt signaling on adult cardiac side population (CSP) cells under physiological and disease conditions.

METHODS AND RESULTS: CSP cells isolated from C57BL/6J mice were used to study the effects of canonical …

Urolithiasis Location And Size And The Association With Microhematuria And Stone-Related Symptoms., Costas D Lallas, Xiaolong S Liu, Allen N Chiura, Akhil K Das, Demetrius H Bagley

Department of Urology Faculty Papers

PURPOSE: To conduct a study to assess the association between calculus location and size and the incidence of both microhematuria and symptoms of urolithiasis in a urology office environment.

PATIENTS AND METHODS: After Institutional Review Board approval, a prospective study was conducted with data from 100 consecutive patients who presented to our office with documented urolithiasis. The location (caliceal, pelvic, or ureteral) and size (

RESULTS: A total of 111 stones were found in the study population resulting in a 45.9% incidence of microhematuria. In patients with renal pelvic and ureteral stones, 67.6% demonstrated microhematuria vs 36.4% with caliceal stones, …

An Evaluation Of Neuroplasticity And Behavior After Deep Brain Stimulation Of The Nucleus Accumbens In An Animal Model Of Depression., Steven M Falowski, Ashwini Sharan, Beverly A S Reyes, Carl Sikkema, Patricia Szot, Elisabeth J Van Bockstaele

Department of Neurosurgery Faculty Papers

BACKGROUND: Recent interest has demonstrated the nucleus accumbens (NAcc) as a potential target for the treatment of depression with deep brain stimulation (DBS).

OBJECTIVE: To demonstrate that DBS of the NAcc is an effective treatment modality for depression and that chemical and structural changes associated with these behavioral changes are markers of neuroplasticity.

METHODS: A deep brain stimulator was placed in the NAcc of male Wistar-Kyoto rats. Groups were divided into sham (no stimulation), intermittent (3 h/d for 2 weeks), or continuous (constant stimulation for 2 weeks). Exploratory and anxietylike behaviors were evaluated with the open-field test before and after …

Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …

B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …

Prevalence And Risk Of Polypharmacy Among The Elderly In An Outpatient Setting: A Retrospective Cohort Study In The Emilia-Romagna Region, Italy, S. Lane Slabaugh, Vittorio Maio, Megan Templin, Safiya Abouzaid

College of Population Health Faculty Papers

Background: Polypharmacy, the simultaneous taking of many medications, has been well documented and is a topic of much concern for those looking to improve the quality of care for the elderly. Elderly patients often develop complicated and multi-factorial health states that require extensive pharmacotherapy, leaving this population at risk for exposure to drug-drug interactions and other adverse events. Previous literature supports an association between an increase in the rate of adverse events as the number of drugs taken by a patient increases.

Objective: We sought to evaluate the prevalence of polypharmacy, and to determine patient characteristics that are predictive of …

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Current And Future Directions In Frailty Research., Anita Mohandas, Joanne Reifsnyder, Mimi Jacobs, Tim Fox

College of Population Health Faculty Papers

The concept of frailty has been evolving dramatically for the past 30 years. Through its evolution, a variety of single and multidimensional models have been used to describe frailty. This article reviews the current literature related to the defining dimensions of frailty and identifies the gaps in the literature requiring additional research. A detailed literature review was performed to identify key dimensions and models currently being used to define frailty, classify interventions that have been developed to reverse frailty, and identify potential areas for future research within this field. Despite the large body of research defining the dimensions of frailty, …

Vaccine-Preventable Diseases And Foreign-Born Populations, Marc Altshuler, Md, Giang Nguyen, Md

Department of Family & Community Medicine Faculty Papers

Foreign-born individuals account for over 12% of the U.S. population, according to the most recent census data. Since many vaccine-preventable outbreaks in the U.S. have been correlated with disease importation, Congress has mandated vaccinations for numerous immigrant populations. It is essential for primary care physicians to be knowledgeable on the unique immunization-related needs of foreign-born individuals, to recognize some of the cultural and linguistic challenges that immigrants have accessing healthcare, and remember to use each medical encounter as an opportunity to provide necessary vaccinations.

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Value-Added Services Of Hospital-Based Radiology Groups, Vijay M. Rao, Md

Department of Radiology Faculty Papers

Presentation at 97th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA).

Summary of presentation.

16 slides.

We Can Do It Together: Par1/Par2 Heterodimer Signaling In Vsmcs., Rafal Pawlinski, Michael Holinstat

Department of Medicine Faculty Papers

In this issue, Sevigny and colleagues demonstrate that a protease-activated receptor 1 (PAR1)-PAR2 heterodimer regulates vascular smooth muscle cell (VSMC) hyperplasia following vascular injury ¹. PARs belong to a family of G-protein coupled receptors that are proteolytically activated by a variety of proteases ^{2, 3}. Cleavage of PARs results in intracellular signaling mediated by activation of various G proteins including G_12/13, G_q, and G_i ^{2, 4-6}. The PAR family consists of 4 members, PAR1-PAR4, with PARs 1, 3, and 4 being primarily activated by thrombin, while PAR2 is activated by trypsin and …

Epitope Characterization Of Sero-Specific Monoclonal Antibody To Clostridium Botulinum Neurotoxin Type A., Cindi R Corbett, Erin Ballegeer, Kelly A Weedmark, M D Elias, Fetweh H Al-Saleem, Denise M Ancharski, Lance L Simpson, Jody D Berry

Department of Medicine Faculty Papers

Botulinum neurotoxins (BoNTs) are extremely potent toxins that can contaminate foods and are a public health concern. Anti-BoNT antibodies have been described that are capable of detecting BoNTs; however there still exists a need for accurate and sensitive detection capabilities for BoNTs. Herein, we describe the characterization of a panel of eight monoclonal antibodies (MAbs) generated to the non-toxic receptor-binding domain of BoNT/A (H(C)50/A) developed using a high-throughput screening approach. In two independent hybridoma fusions, two groups of four IgG MAbs were developed against recombinant H(C)50/A. Of these eight, only a single MAb, F90G5-3, bound to the whole BoNT/A protein …

The Evolution Of Cauterization: From The Hot Iron To The Bovie., Michelle F. Deleon, Ms, Charles J. Yeo, Md, Pinckney Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

The Bovie electrocautery has become a fundamental tool of modern-day surgery, particularly for its integral role in hemostasis, yet despite this landmark invention and its widespread use, there is very little said about the man behind the machine: William T. Bovie. It would be thousands of years from the inception of cautery in medicine until the birth of Dr. Bovie and his device. However, his work in biophysics and collaboration with Dr. Harvey Cushing would revolutionize surgical practice in the early 20th century and forever ingrain his name into the field of surgery.

Hand Problems Among Endourologists., Kelly A Healy, Raymond W Pak, Ryan C Cleary, Arturo Colon-Herdman, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Endourology has evolved rapidly for the management of both benign and malignant disease of the upper urinary tract. Limited data exist, however, on the occupational hazards posed by complex endourologic procedures. The aim of this study was to determine the prevalence and possible causes of hand problems among endourologists who routinely perform flexible ureteroscopy compared with controls.

MATERIALS AND METHODS: An online computer survey targeted members of the Endourological Society and psychiatrists in academic and community settings. A total of 600 endourologists and 578 psychiatrists were contacted by e-mail. Invited physicians were queried regarding their practice settings …

Promoting Your Institutional Repository On And Off Campus, Daniel G. Kipnis, Msi

Academic Commons and Scott Memorial Library Staff Papers and Presentations

Webinar presentation for Association for Library Collections and Technical Services.

Navigating The Digital Divide: A Teaching-Learning Initiative With The Ipad2, Beth Ann Swan, Kathryn Shaffer, Kellie Smith, Anthony J. Frisby, Mary Hanson-Zalot

College of Nursing Faculty Papers & Presentations

Background/ Rationale: It has been established that Interprofessional Education (IPE) offers a solution to foster teamwork and improve patient care and should be implemented early in professional role development. Thomas Jefferson University has been providing IPE to interprofessional healthcare students for over 5 years. A long term strategic goal was identified to “create innovative learning environments that support interprofessional education including state-of-the-art technologies”. In actualizing this goal, the curriculum was enhanced with technology supported collaborative learning techniques to assist in group processing and reflection. Combining traditional IPE activities with technology supported components incorporated the advantages of both delivery methods, …

Molecular Diagnostics In Periprosthetic Joint Infection., Javad Parvizi, Lesley Walinchus, Bahar Adeli

Department of Orthopaedic Surgery Faculty Papers

Periprosthetic joint infection (PJI) is a significant and costly challenge to the orthopedic community. The lack of a gold standard for diagnosis remains the biggest obstacle in the detection and subsequent treatment of PJI. Molecular markers in the serum and joint fluid aspirate hold immense promise to enhance the development of a firm diagnostic criterion. The primary goal is one marker with high sensitivity and specificity. Here, we review our current research efforts in the field of molecular markers: C-reactive protein, erythrocyte sedimentation rate, white blood cells, and leukocyte esterase. Each marker has been studied to determine its sensitivity, specificity, …

Implications Of Observation-Fact Modifiers To I2b2 Ontologies, Jack W. London, Devjani Chatterjee

Kimmel Cancer Center Faculty Papers

Biomedical translational research can be facilitated by integrating clinical and research data. In particular, study cohort identification and hypothesis generation is enabled by the mining of integrated clinical observations and research resources. The "informatics for integrating biology and the bedside, " or i2b2, framework is widely used for this biomedical data mining. The i2b2 "star schema" data model using entity-attribute-value (EA V) formatted concepts is a very efficient strategy for querying large amounts of data. However, until the most recent i2b2 release, the utility of the platform was somewhat constrained by the limitations on being able to express "facts about …

Effect Of Protein Kinase C Delta (Pkc-Δ) Inhibition On The Transcriptome Of Normal And Systemic Sclerosis Human Dermal Fibroblasts In Vitro., Peter J Wermuth, Sankar Addya, Sergio A Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Previous studies demonstrated that protein kinase C- δ (PKC-δ) inhibition with the selective inhibitor, rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-δ to regulate collagen production in fibroblasts, we examined the effects of PKC-δ inhibition on the transcriptome of normal and SSc human dermal fibroblasts. Normal and SSc human dermal fibroblasts were incubated with rottlerin (5 …

Use Of The Anterolateral Thigh In Cranio-Orbitofacial Reconstruction., William J Parkes, Howard Krein, Ryan Heffelfinger, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Objective. To detail the clinical outcomes of a series of patients having undergone free flap reconstruction of the orbit and periorbita and highlight the anterolateral thigh (ALT) as a workhorse for addressing defects in this region. Methods. A review of 47 patients who underwent free flap reconstruction for orbital or periorbital defects between September 2006 and May 2011 was performed. Data reviewed included demographics, defect characteristics, free flap used, additional reconstructive techniques employed, length of stay, complications, and follow-up. The ALT subset of the case series was the focus of the data reviewed for this paper. Selected cases were described …

Clinical Care Plan: Interdisciplinary Course (Ccpic), Marcia Levinson, Pt, Phd, Mft, Amy M Egras, Pharm.D, Bcps, E. Adel Herge, Otd, Otr/L, Kathryn Shaffer, Rn, Msn

Department of Physical Therapy Faculty Papers

Background/Rationale:

Interprofessional collaborative practice significantly improves patient outcomes, reduces mortality and enhances quality-of-life.

Person-focused care demands collaboration among professions in a team approach to address multiple issues including illness, prevention, and health promotion activities.

Key elements of successful implementation of interprofessional education supported by Clinical Care Plan, Interprofessional Course (CCPIC):

-Increasing knowledge of the roles, responsibilities, and competencies of multiple health professions.

-Collaborating in teams

-Recognizing the patient as the expert

-Communicating effectively

Course Statistics:

-176 students from various disciplines completed course (2008-2011).

Disciplines include:

-Medicine, Nursing, Occupational Therapy, Physical Therapy, Pharmacy

The Characteristics Of Borrelia Hermsii Infection In Human Hematopoeitic Stem Cell-Engrafted Mice Mirror Those Of Human Relapsing Fever, Raja Vuyyuru, Hongqi Liu, Tim Manser, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fevers in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans.

Innate And Adaptive Immunity To The Nematode Strongyloides Stercoralis In A Mouse Model., Sandra Bonne-Annee, Jessica A. Hess, David Abraham

Department of Microbiology and Immunology Faculty Papers

Mice have been used to the study the mechanisms of protective innate and adaptive immunity to larval Strongyloides stercoralis. During primary infection, neutrophils and eosinophils are attracted by parasite components and kill the larvae by release of granule products. Eosinophils also function as antigen-presenting cells for the induction of a Th2 response. B cells produce both IgM and IgG that collaborate with neutrophils to kill worms in the adaptive immune response. Vaccine studies have identified a recombinant diagnostic antigen that induced high levels of immunity to infection with S. stercoralis in mice. These studies demonstrate that there are redundancies in …

Second Floor Pilot For Group Learning Tools, Aisr, Education Services

Library Posters

Poster promoting collaborative learning tools including whiteboards and Teamspot.

Macrophages And Neutrophils From Humans And Mice Kill Larval Strongyloides Stercoralis During Innate Immunity, Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess Ligas, David Abraham, Phd

Department of Microbiology and Immunology Faculty Papers

The parasitic nematode Strongyloides stercoralis (Ss) infects 30-100 million people worldwide, yet little is known about the immune response in humans. Previous studies on innate immunity to Ss in mice have demonstrated a role for eosinophils, neutrophils (PMN) and complement activation in the protective immune response.