Digital Commons Network^™

A Phase I/Iia Clinical Trial Of A Recombinant Rho Protein Antagonist In Acute Spinal Cord Injury., Michael G Fehlings, Nicholas Theodore, James Harrop, Gilles Maurais, Charles Kuntz, Chris I Shaffrey, Brian K Kwon, Jens Chapman, Albert Yee, Allyson Tighe, Lisa Mckerracher

Department of Neurosurgery Faculty Papers

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or …

The Variable Presentations Of Anaplastic Spindle Cell Squamous Carcinoma Associated With Tall Cell Variant Of Papillary Thyroid Carcinoma., Pallavi P Gopal, Kathleen T Montone, Zubair Baloch, Madalina Tuluc, Virginia Livolsi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In 1976, Hawk and Hazard described the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). While the lesions they described had cytologic features of papillary carcinoma, they showed more aggressive behavior with a greater propensity for extrathyroid extension and lymphovascular invasion than classic PTC. In 1991, Bronner and LiVolsi described a series of patients with TCV that progressed to spindle cell squamous carcinoma (SCSC), a unique form of anaplastic thyroid carcinoma. This study describes the variable clinical and pathologic presentations in 31 patients with anaplastic SCSC arising in association with TCV.

METHODS: The surgical pathology archives as well …

Early Toxicity Predicts Long-Term Survival In High-Grade Glioma., Y. R. Lawrence, M Wang, Adam Dicker, David W Andrews, Walter J Curran, J M Michalski, L Souhami, W-Ka Yung, M Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known.

METHODS: Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. The association between acute and late toxicity was analysed using a stepwise logistic regression model. The association between the occurrence of acute NT and survival was analysed as an independent variable.

RESULTS: There were 2610 analysable patients (86% glioblastoma, 10% anaplastic astrocytoma). All received a systemic agent during radiation (83% chemotherapy, 17% …

Aging Is Associated With Positive Responding To Neutral Information But Reduced Recovery From Negative Information, Carien M. Van Reekum, Stacey M. Schaefer, Regina C. Lapate, Catherine J. Norris, Lawrence L. Greischar, Richard J. Davidson

Dartmouth Scholarship

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 …

Phase 1 Pilot Study Of E-Mail Support For People With Long Term Conditions Using The Internet., Bryony Sheaves, Ray B. Jones, Graham R. Williamson, Rohan Chauhan

School of Nursing and Midwifery

BACKGROUND: Use of the Internet for people with Long Term Conditions (LTCs) can have a positive effect on knowledge, social support, behavioural and clinical outcomes, yet there is concern that a 'digital divide' prevents some patients from benefitting. While some patients do not have access to the Internet, others that do may still lack expertise or the confidence to make full use of it. The aim of this pilot study was to develop an intervention and test methods for a definitive randomised controlled trial (RCT) of anonymous personal online email support for patients in this latter group. METHODS: Recruitment success …

Multicentric Hepatic Ebv-Associated Smooth Muscle Tumors In An Aids Patient: A Case Report, Investigation Of Mtor Activation And Review Of The Literature, Qi Shen, Wei Feng, Michael S Long, Xiuzhen Duan, Siraya Jaijakul, Cesar A Arias, Robert E Brown, Bihong Zhao

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS …

Response To An Abnormal Ovarian Cancer-Screening Test Result: Test Of The Social Cognitive Processing And Cognitive Social Health Information Processing Models, Michael A. Andrykowski, Edward J. Pavlik

Behavioral Science Faculty Publications

All cancer screening tests produce a proportion of abnormal results requiring follow up. Consequently, the cancer-screening setting is a natural laboratory for examining psychological and behavioural response to a threatening health-related event. This study tested hypotheses derived from the social cognitive processing and cognitive-social health information processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n = 278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), …

Long-Term Calorie Restriction, But Not Endurance Exercise, Lowers Core Body Temperature In Humans, Andreea Soare, Roberto Cangemi, Daniela Omodei, John O. Holloszy, Luigi Fontana

Open Access Publications

Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7 ± 9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western …

Episodic Memory Retrieval, Parietal Cortex, And The Default Mode Network: Functional And Topographic Analyses, Carlo Sestieri, Maurizio Corbetta, Gian Luca Romani, Gordon L. Shulman

Open Access Publications

The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g., episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative "default" processes such as episodic memory retrieval. Using functional magnetic resonance imaging, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting-state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal …

Asthma Control In Oman : National Results Within The Asthma Insights And Reality In The Gulf & The Near East (Airgne) Study, Nasser Al-Busaidi, Joan B. Soriano

Sultan Qaboos University Medical Journal

Objectives: The Asthma Insights and Reality (AIR) study in the Gulf and Near East (one of a worldwide series of surveys conducted in adults and children to assess asthma control) was conducted in Oman to assess how closely asthma control meets international guidelines recommendations. Methods: From January 2007 to March 2008, asthmatics receiving treatment or currently suffering from asthma symptoms were interviewed among nationals randomly surveyed from the most populated urban areas in Oman (Muscat, Sohar and Nizwa). The standard AIR questionnaire was used to assess symptom severity, health care utilisation, limitation of activity and medication use. Results: From 201 …

Beta-Blocker Initiation And Adherence After Hospitalization For Acute Myocardial Infarction., Vittorio Maio, Pharmd, Ms, Msph, Massimiliano Marino, Phd, Mary Robeson, Md, Joshua J Gagne, Pharmd, Ms

College of Population Health Faculty Papers

Aims: We sought to: (1) estimate the proportion of patients who initiated beta-blocker therapy after acute myocardial infarction (AMI) in Regione Emilia-Romagna (RER); (2) examine predictors of post-AMI beta-blocker initiation; and (3) assess adherence to such therapy.

Methods and Results: Using healthcare claims data covering all of RER, we identified a cohort of 24,367 patients with a hospitalization for AMI between 2004 and 2007, who were discharged from the hospital alive and without contraindications to beta-blocker therapy. We estimated the proportion of eligible patients with at least one prescription for a beta-blocker following discharge and performed a multivariable logistic regression …

Nonuniform High-Gamma (60-500 Hz) Power Changes Dissociate Cognitive Task And Anatomy In Human Cortex, Charles M. Gaona, Mohit Sharma, Zachary V. Freudenburg, Jonathan D. Breshears, David T. Bundy, Jarod Roland, Dennis L. Barbour, Gerwin Schalk, Eric C. Leuthardt

Open Access Publications

High-gamma-band (>60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that …

Evidence-Based Genomic Diagnosis Characterized Chromosomal And Cryptic Imbalances In 30 Elderly Patients With Myelodysplastic Syndrome And Acute Myeloid Leukemia., Renu Bajaj, Fang Xu, Bixia Xiang, Katherine Wilcox, Autumn J Diadamo, Rachana Kumar, Alexandra Pietraszkiewicz, Stephanie Halene, Peining Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells.

RESULTS: The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.519 megabases (Mb). Clinically significant recurrent deletions of 5q (involving the RPS14 gene), 12p12.3 (ETV6 gene), 17p13 (TP53 gene), 17q11.2 (NF1 gene) and 20q, double minutes containing the MYC gene and …

A Test Of The Role Of The Medial Temporal Lobe In Single-Word Decoding., Karol Osipowicz, Tyler Rickards, Atif Shah, Ashwini Sharan, Michael Sperling, Waseem Kahn, Joseph Tracy

Department of Neurology Faculty Papers

The degree to which the MTL system contributes to effective language skills is not well delineated. We sought to determine if the MTL plays a role in single-word decoding in healthy, normal skilled readers. The experiment follows from the implications of the dual-process model of single-word decoding, which provides distinct predictions about the nature of MTL involvement. The paradigm utilized word (regular and irregularly spelled words) and pseudoword (phonetically regular) stimuli that differed in their demand for non-lexical as opposed lexical decoding. The data clearly showed that the MTL system was not involved in single word decoding in skilled, native …

Safety And Efficacy Of Abt-089 In Pediatric Attention-Deficit/Hyperactivity Disorder: Results From Two Randomized Placebo-Controlled Clinical Trials., Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J. Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli

Journal Articles: Psychiatry

OBJECTIVE: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home …

Teaching Daily Living Skills To Young Adults With Autism : The Creation Of A Curriculum Guide For Special Education Teachers, Stephanie Iwanciow Haas

Capstone Projects and Master's Theses

The purpose of this thesis project was to compile a curriculum on teaching daily living skills for students transitioning from the school system to adulthood that is research-based and differentiated for students at various skill levels. A multi-level review procedure was implemented to develop the curriculum. First, a review of the literature was conducted to identify the topics and instructional methods to be included in the curriculum. Second, a panel of national experts were sent a draft of the curriculum to assess the accuracy and clarity of the information provided. Third, parents were surveyed to determine what they thought was …

Genetics Of Sputum Gene Expression In Chronic Obstructive Pulmonary Disease, Weiliang Qiu, Michael H. Cho, John H. Riley, Wayne H. Anderson, Dave Singh, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David A. Lomas, James D. Crapo, Terri H. Beaty, Bartolome R. Celli, Stephen I. Rennard, Ruth Tal-Singer, Steven M. Fox, Edwin K. Silverman, Craig P. Hersh, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested …

The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). Aspirin and clopidogrel are two frequently used anti-clotting agents with different mechanisms of action. Since LRPT may potentially be co-administered with either one of these agents, these studies were conducted to assess the effects of steady-state LRPT on the antiplatelet activity of steady-state clopidogrel or aspirin. Bleeding time …

Medical Encounter Characteristics Of Hiv Seroconverters In The Us Army And Air Force, 2000–2004, Shilpa Hakre, David Brett-Major, Darrell E. Singer, Robert J. O'Connell, Warren B. Sateren, Jose L. Sanchez, Brian K. Agan, Nelson L. Michael, Paul T. Scott

Journal Articles: Epidemiology

BACKGROUND AND METHODS: Active duty US Army and Air Force military personnel undergo mandatory biennial HIV antibody screening. We compared pre- and post-HIV seroconversion health status by conducting a case-control study, which evaluated all medical encounters and sociodemographic factors among incident HIV seroconverters and HIV-negative controls from June 2000 through February 2004.

RESULTS: A total of 274 HIV seroconverters and 6205 HIV-negative personnel were included. In multivariate analysis restricted to male personnel (cases = 261, controls = 5801), single marital status (adjusted odds ratio [AOR] = 14.37), clinical indicators or symptoms within four years of HIV diagnosis (AOR = 6.22), …

The Prevalence Of Adhd In Candidates For Gastric Bypass Surgery: Are Overeating And Obesity Accounted For By The Attention Deficits And Impulisivity Of Adhd?, Andrea M. Parry

PCOM Psychology Dissertations

The purpose of this study was to determine the prevalence of Attention Deficit-Hyperactivity Disorder (ADHD) and general psychological characteristics in an adult, presurgery population of patients seeking Gastric Bypass (GB). An ADHD diagnosis was defined as clinically significant scores as measured by the Conners Adult ADHD Rating Scale (CAARS). Other psychological characteristics were assessed using the Minnesota Multiphasic Personality Inventory – Second Edition (MMPI-2). The sample was selected from a homogeneous adult outpatient population. Participants meeting inclusion criteria presented for psychological assessment preparatory to GB surgery at the office of Dr. Steven Walfish. Participants were excluded if they failed to …

Measuring Alcohol Craving: Development Of The Alcohol Craving Experience Questionnaire., Dixie J. Statham, Jason P. Connor, David J. Kavanagh, Gerald F.X. Feeney, Ross Mc D. Young, Jon May, Jackie Andrade

School of Psychology

To develop a measure of craving based on the Elaborated Intrusion (EI) theory of desire and to examine the construct, concurrent and discriminant validity of the instrument.

Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish

The Texas Heart Institute Journal

Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13—an enzyme crucial to the initiation of collagen degradation—as part of their plaque-stabilizing effect.

We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and …

Ventral Hernia Repairs: 10 Year Single Institution Review At Thomas Jefferson University Hospital, Frederick C. Sailes, Md, Jason Walls, Md, Daria Guelig, Md, Mike Mirzabeigi, Ma, William D. Long, Ms, Albert Crawford, Phd, John H. Moore Jr, Md, Facs, Steven E. Copit, Md, Gary A. Tuma, M.D, James Fox, Md

Department of Surgery Faculty Papers

Abstract

Background Definitive repair of recurrent ventral hernias using abdominal wall reconstruction techniques is an essential tool in the armentarium for general and plastic surgeons. Ramirez 1 et al describes the “component separation” technique to mobilize the rectus-abdominus internal oblique and external oblique flap to correct the defect. The recurrence rate of incisional hernias increases to 20% after gastric bypass or extensive weight loss.2 The incidence of ventral hernias after failed recurrent hernia repair increases to 40%.3 It has been reported that utilizing the sliding myofascial flap repair technique, the recurrence rate was reduced to 8.5%.4

Materials and Methods This …

Web-Based Interventions For Weight Loss And Weight Maintenance Among Rural Midlife And Older Women: Protocol For A Randomized Controlled Trial., Patricia A. Hageman, Carol H. Pullen, Melody Hertzog, Linda S, Boeckner, Susan Noble Walker

Journal Articles: Physical Therapy

BACKGROUND: Weight loss is challenging and maintenance of weight loss is problematic among midlife and older rural women. Finding effective interventions using innovative delivery methods that can reach underserved and vulnerable populations of overweight and obese rural women is a public health challenge.

METHODS/DESIGN: This Women Weigh-In for Wellness (The WWW study) randomized-controlled trial is designed to compare the effectiveness of theory-based behavior-change interventions using (1) website only, (2) website with peer-led support, or (3) website with professional email-counseling to facilitate initial weight loss (baseline to 6 months), guided continuing weight loss and maintenance (7-18 months) and self-directed weight maintenance …

Surgical Management Of Double-Chambered Right Ventricle In Adults, Ahmad K Darwazah, Mohammed Eida, Vivian Bader, Mohammed Khalil

The Texas Heart Institute Journal

Double-chambered right ventricle is a congenital anomaly in which the right ventricle is divided into 2 portions by anomalous muscle bundles. These cases often present in children, but rarely in adults.

We discuss 2 cases of double-chambered right ventricle, in patients aged 42 and 35 years. When cases remain asymptomatic until adulthood, they can present with unusual symptoms that lead to incorrect diagnosis. Our cases represent 2 very different manifestations of double-chambered right ventricle, which differ in presentation, in the site of abnormal obstructive muscle bundles, and in the presence of associated lesions. Both of our patients underwent successful surgical …

Internal Medicine Problems As They Present To The Cardiologist, Ira Martin Grais

The Texas Heart Institute Journal

No abstract provided.

Usefulness Of The Echocardiographic Multi-Parameter Score (Emps) In Evaluating Left Ventricular Global Heart Function, Bingyuan Zhou, Junhua Yang, Xiangjun Yang, Yongming He, Caiming Zhao, Sudan Xu, Huifeng Wang

The Texas Heart Institute Journal

In this study, we established a new index by combining several echocardiographic parameters to quantify heart failure. We selected 233 consecutive patients who underwent both echocardiographic and plasma B-type natriuretic peptide (BNP) tests within 24 hours after referral for suspected heart failure. The echocardiographic parameters included systolic function, diastolic function, left ventricular chamber remodeling, valvular lesions, systolic pulmonary arterial pressure, and regional wall-motion abnormality. Each factor was scored from 1 to 3 points according to its severity. The total point from these 6 factors is the echocardiographic multi-parameter score (EMPS).

The EMPS for 37, 51, 77, and 38 patients from …

Prehypertension: A Meta-Analysis Of The Epidemiology, Risk Factors, And Predictors Of Progression, Xiaofan Guo, Liling Zou, Xingang Zhang, Jue Li, Liqiang Zheng, Zhaoqing Sun, Jian Hu, Nathan D Wong, Yingxian Sun

The Texas Heart Institute Journal

We investigated the prevalence and risk factors of prehypertension, as well as the predictors of progression from prehypertension to hypertension. To do this, we performed a systematic review and meta-analysis of cross-sectional and longitudinal studies, after unrestricted searches of PubMed and The Cochrane Library through September 2010. In addition, we reviewed references, major textbooks, and review articles. Pooled prevalence, standardized mean differences, and odds ratios were estimated by using a random-effects model.

Twenty-six articles met our inclusion criteria; these included 20 cross-sectional and 6 longitudinal studies, with a total sample of 250,741 individuals. The overall pooled prevalence of prehypertension was …

Referrals To A Regional Allergy Clinic - An Eleven Year Audit., Ray B. Jones, Paul Hewson, Edward R. Kaminski

School of Nursing and Midwifery

BACKGROUND: Allergy is a serious and apparently increasing public health problem yet relatively little is known about the types of allergy seen in routine tertiary practice, including their spatial distribution, co-occurrence or referral patterns. This study reviewed referrals over an eleven year period to a regional allergy clinic that had a well defined geographical boundary. For those patients confirmed as having an allergy we explored: (i) differences over time and by demographics, (ii) types of allergy, (iii) co-occurrence, and (iv) spatial distributions. METHODS: Data were extracted from consultant letters to GPs, from September 1998 to September 2009, for patients confirmed …

Wild-Type And Mutant Sod1 Share An Aberrant Conformation And A Common Pathogenic Pathway In Als., Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane Mckenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady, Robert H Brown

Farber Institute for Neuroscience Faculty Papers

Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal …