Digital Commons Network^™

Cell Surface B2m-Free Human Leukocyte Antigen (Hla) Monomers And Dimers: Are They Neo-Hla Class And Proto-Hla?, Mepur H. Ravindranath, Narendranath M. Ravindranath, Senthamil R. Selvan, Fatiha El Hilali, Carly J. Amato-Menker, Edward J. Filippone

Division of Nephrology Faculty Papers

Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, …

Long-Term Outcomes Of Bevacizumab And Chemoradiation For Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial, Nancy Y. Lee, Jonathan Harris, John Kim, Adam Garden, James Mechalakos, David G. Pfister, Anthony T.C. Chan, Kenneth Hu, A. Dimitrios Colevas, Steven Frank, George Shenouda, Voichita Bar-Ad, John N. Waldron, Paul M. Harari, Adam Raben, Pedro Torres-Saavedra, Quynh-Thu Le

Department of Radiation Oncology Faculty Papers

IMPORTANCE: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

OBJECTIVE: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. …

A Taxonomy Of Childhood Pedal Cyclist Injuries From Latent Class Analysis: Associations With Factors Pertinent To Prevention, Joseph Piatt

Department of Neurosurgery Faculty Papers

Background: Studies of pedal cyclist injuries have largely focused on individual injury categories, but every region of the cyclist's body is exposed to potential trauma. Real-world injury patterns can be complex, and isolated injuries to one body part are uncommon among casualties requiring hospitalization. Latent class analysis (LCA) may identify important patterns in heterogeneous samples of qualitative data.

Methods: Data were taken from the Trauma Quality Improvement Program of the American College of Surgeons for 2017. Inclusion criteria were age 18 years or less and an external cause of injury code for pedal cyclist. Injuries were characterized by Abbreviated Injury …

Unexpected Brain Imaging Findings In Patients With Seizures, Boulenouar Mesraoua, Matthias Koepp, Bernhard Schuknecht, Dirk Deleu, Hassan J Al Hail, Gayane Melikyan, Lubna Elsheikh, A A Asadi-Pooya

Department of Neurology Faculty Papers

New imaging technologies have advanced our ability to localize the epileptogenic zone in patients with epilepsy. As a result of the constant improvement of the image quality, magnetic resonance imaging (MRI) has become the most important ancillary tool in the management of patients with epilepsy. Magnetic resonance imaging for the evaluation of patients with epilepsy should be done using a special temporal lobe protocol and read by physicians experienced with the findings in patients with epilepsy. On the other hand, in the healthy populations, incidental structural brain abnormalities have been reported in 18% of people. Incidental, subtle, or unexpected structural …

Comorbidities In Aging Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with …

Use Of Caudal Epidural Catheter In A Child With Cerebral Palsy With Prior Posterior Spine (T1-Sacrum) Fusion., Divya Dixit, Mary C. Theroux, Kirk W. Dabney, Freeman Miller

Department of Anesthesiology Faculty Papers

No abstract provided.

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …

Novel Actions Of Next-Generation Taxanes Benefit Advanced Stages Of Prostate Cancer., Renée De Leeuw, Lisa D. Berman-Booty, Matthew J. Schiewer, Stephen J Ciment, Robert Den, Adam P. Dicker, William Kelly, Edouard J. Trabulsi, Costas D. Lallas, Leonard G. Gomella, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.

EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro …

Exploration And Confirmation Of The Latent Variable Structure Of The Jefferson Scale Of Empathy., Mohammadreza Hojat, Marianna Lanoue

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: To reaffirm the underlying components of the JSE by using exploratory factor analysis (EFA), and to confirm its latent variable structure by using confirmatory factor analysis (CFA).

METHODS: Research participants included 2,612 medical students who entered Jefferson Medical College between 2002 and 2012. This sample was divided into two groups: Matriculants between 2002 and 2007 (n=1,380) and be-tween 2008 and 2012 (n=1,232). Data for 2002-2007 matriculants were subjected to EFA (principal component factor extraction), and data for matriculants of 2008-2012 were used for CFA (structural equation modeling, and root mean square error for approximation.

RESULTS: The EFA resulted in …

Induction Of Autophagy Restores The Loss Of Sevoflurane Cardiac Preconditioning Seen With Prolonged Ischemic Insult., Mayumi Shiomi, Masami Miyamae, Genzou Takemura, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Shizuka Koshinuma, Yoshihiro Momota, Toshiaki Minami, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 …

Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd

Department of Cancer Biology Faculty Papers

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …

Equivalence Of Students' Scores On Timed And Untimed Anatomy Practical Examinations., Guiyan Zhang, Bruce Fenderson, Richard R Schmidt, J J. Veloski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Untimed examinations are popular with students because there is a perception that first impressions may be incorrect, and that difficult questions require more time for reflection. In this report, we tested the hypothesis that timed anatomy practical examinations are inherently more difficult than untimed examinations. Students in the Doctor of Physical Therapy program at Thomas Jefferson University were assessed on their understanding of anatomic relationships using multiple-choice questions. For the class of 2012 (n = 46), students were allowed to circulate freely among 40 testing stations during the 40-minute testing session. For the class of 2013 (n = 46), students …

Severe Stress Switches Crf Action In The Nucleus Accumbens From Appetitive To Aversive., Julia C Lemos, Matthew J Wanat, Jeffrey S Smith, Beverly A S Reyes, Nick G Hollon, Elisabeth J Van Bockstaele, Charles Chavkin, Paul E M Phillips

Farber Institute for Neuroscience Faculty Papers

Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. …

Periprosthetic Joint Infection: Are Patients With Multiple Prosthetic Joints At Risk?, S Mehdi Jafari, David S Casper, Camilo Restrepo, Benjamin Zmistowski, Javad Parvizi, Peter F Sharkey

Rothman Institute Faculty Papers

Patients who present with a periprosthetic joint infection in a single joint may have multiple prosthetic joints. The risk of these patients developing a subsequent infection in another prosthetic joint is unknown. Our purposes were (1) to identify the risk of developing a subsequent infection in another prosthetic joint and (2) to describe the time span and organism profile to the second prosthetic infection. We retrospectively identified 55 patients with periprosthetic joint infection who had another prosthetic joint in place at the time of presentation. Of the 55 patients, 11 (20%) developed a periprosthetic joint infection in a second joint. …

Direct Evidence For Inhibition Of Mitochondrial Permeability Transition Pore Opening By Sevoflurane Preconditioning In Cardiomyocytes: Comparison With Cyclosporine A., Anna Onishi, Masami Miyamae, Kazuhiro Kaneda, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Diverticular And Aneurysmal Structures Of The Left Ventricle In Adults: Report Of A Case Within The Context Of A Literature Review., Premraj Makkuni, Morris N Kotler, Vincent M. Figueredo

Department of Medical Genetics Faculty Papers

Left ventricular outpouchings are increasingly detected on cardiovascular imaging. Herein, we describe the case of a 45-year-old man who underwent noncardiac preoperative imaging and was found to have an asymptomatic left ventricular outpouching. The patient underwent successful surgical repair of the structure. When left ventricular outpouchings are detected, the main differential diagnoses are pseudoaneurysm, aneurysm, and diverticulum. The outcomes for these conditions differ substantially, and accurate diagnosis can be crucial in making clinical decisions. We review the relevant medical literature, outline the natural history of these left ventricular abnormalities, and discuss options in regard to their management.

Sour Ageusia In Two Individuals Implicates Ion Channels Of The Asic And Pkd Families In Human Sour Taste Perception At The Anterior Tongue., Taufiqul Huque, Beverly J Cowart, Luba Dankulich-Nagrudny, Edmund A Pribitkin, Douglas L Bayley, Andrew I Spielman, Roy S Feldman, Scott A Mackler, Joseph G Brand

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli.

METHODS AND FINDINGS: Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, …

The Devil Is In The Third Year: A Longitudinal Study Of Erosion Of Empathy In Medical School., Mohammadreza Hojat, Michael J. Vergare, Kaye Maxwell, George Brainard, Steven K. Herrine, Gerald A. Isenberg, John Veloski, Joseph S. Gonnella

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: This longitudinal study was designed to examine changes in medical students' empathy during medical school and to determine when the most significant changes occur.

METHOD: Four hundred fifty-six students who entered Jefferson Medical College in 2002 (n = 227) and 2004 (n = 229) completed the Jefferson Scale of Physician Empathy at five different times: at entry into medical school on orientation day and subsequently at the end of each academic year. Statistical analyses were performed for the entire cohort, as well as for the "matched" cohort (participants who identified themselves at all five test administrations) and the "unmatched" …

Acute Memory Phase Of Sevoflurane Preconditioning Is Associated With Sustained Translocation Of Protein Kinase C-Alpha And Epsilon, But Not Delta, In Isolated Guinea Pig Hearts., Chika Okusa, Masami Miyamae, Shingo Sugioka, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Naochika Domae, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND AND OBJECTIVE: Anaesthetic preconditioning (APC) exerts cardioprotective effects by reducing infarct size and improving recovery of contractile function after ischaemia-reperfusion. The interval between brief exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase, is dependent on intracellular signalling mediating this cardioprotection. Intramyocyte translocation of protein kinase C (PKC) is known to be a key mediator in APC. We examined the relationship between the time frame of the acute memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC-alpha, delta and epsilon to the particulate fraction. METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischaemia …

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

Farber Institute for Neuroscience Faculty Papers

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

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

Division of Cardiology Faculty Papers

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

The Meaning Of Computers To A Group Of Men Who Are Homeless., Kathleen Swenson Miller, Stacey Bunch-Harrison, Brett Brumbaugh, Rekha Sankaran Kutty, Kathleen Fitzgerald

Department of Occupational Therapy Faculty Papers

The purpose of this pilot study was to explore the experience with computers and the meaning of computers to a group of homeless men living in a long-term shelter. This descriptive exploratory study used semistructured interviews with seven men who had been given access to computers and had participated in individually tailored occupation based interventions through a Work Readiness Program. Three themes emerged from analyzing the interviews: access to computers, computers as a bridge to life-skill development, and changed self-perceptions as a result of connecting to technology. Because they lacked computer knowledge and feared failure, the majority of study participants …

Predictors Of Paralysis In The Rheumatoid Cervical Spine In Patients Undergoing Total Joint Arthroplasty., Jonathan N Grauer, Edwin M Tingstad, Nahshon Rand, Michael J Christie, Alan Hilibrand

Rothman Institute Faculty Papers

BACKGROUND: Rheumatoid arthritis is sometimes associated with radiographic evidence of instability of the cervical spine, most commonly an abnormal subluxation between vertebrae. When this instability compromises the space that is available for the spinal cord, it may be predictive of paralysis. However, the prevalence of radiographic signs of instability that are predictive of paralysis among patients with nonspinal orthopaedic manifestations of rheumatoid arthritis is unknown.

METHODS: Radiographs of the cervical spine of patients with rheumatoid arthritis who had undergone total joint arthroplasty over a five-year period were retrospectively reviewed. The radiographs were evaluated for predictors of paralysis (a posterior atlantodental …