Digital Commons Network^™

Survival Motor Neuron Protein Deficiency Impairs Myotube Formation By Altering Myogenic Gene Expression And Focal Adhesion Dynamics, Katherine V. Bricceno, Tara Martinez, Evgenia Leikina, Stephanie Duguez, Terence A. Partridge, Leonid V. Chernomordik, Kenneth H. Fischbeck, Charlotte J. Sumner, Barrington G. Burnett

Pediatrics Faculty Publications

While spinal muscular atrophy (SMA) is characterized by motor neuron degeneration, it is unclear whether and how much survival motor neuron (SMN) protein deficiency in muscle contributes to the pathophysiology of the disease. There is increasing evidence from patients and SMA model organisms that SMN deficiency causes intrinsic muscle defects. Here we investigated the role of SMN in muscle development using muscle cell lines and primary myoblasts. Formation of multinucleate myotubes by SMN-deficient muscle cells is inhibited at a stage preceding plasma membrane fusion. We found increased expression and reduced induction of key muscle development factors, such as MyoD and …

Iron Accumulation In Deep Cortical Layers Accounts For Mri Signal Abnormalities In Als: Correlating 7 Tesla Mri And Pathology, Justin Y. Kwan, Suh Young Jeong, Peter Van Gelderen, Han-Xiang Deng, Martha M. Quezado, Laura E. Danielian, John Butman, Lingye Chen, Elham Bayat, James Russell, Teepu Siddique, Jeff H. Duyn, Tracey A. Rouault, Mary Kay Floeter

Neurology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T2-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or …

Genetics Of Clusterin Isoform Expression And Alzheimer's Disease Risk, I-Fang Ling, Jiraganya Bhongsatiern, James F. Simpson, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted …

Com Outlook Spring 2012, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Malnutrition In Young Pakistani Children, Shela Akbar Ali Hirani

School of Nursing & Midwifery

Background: Pakistan is a developing country with the second highest infant and child mortality rate in South Asia. In this region, malnutrition underlies much of the high infant and under five child morbidity and mortality rates. Although struggle to tackle the issue of malnutrition among young Pakistani children has been going on since many decades, till yet a realistic solution for this growing problem has not been found.

Objective: This paper aims at reviewing literature to analyse the biological, maternal, socio-cultural, environmental, and politico-economical determinants of malnutrition among young children in Pakistan so that need based interventions can …

Knowledge And Attitudes About Tetanus And Rabies: A Population-Based Survey From Karachi, Pakistan, Mohammad Wasay, Abdul Malik, Ammad Fahim, Adnan Yousuf, Rajesh Chawla, Haroon Daniel, Muhammad Rafay, Iqbal Azam, Junaid Razzak

Section of Neurology

OBJECTIVE: To evaluate public knowledge regarding predisposing factors, fatality and prevention of Tetanus and Rabies and attitudes toward vaccination and post-exposure prophylaxis.

METHODS: A population-based, cross-sectional survey was conducted in all the 18 towns of Karachi, the largest metropolitan city of Pakistan, from December 2007 to January 2008. Men and women of more than 18 years of age were included in the study which used a self-reporting questionarre as its tool.

RESULTS: There were 1201 people interviewed by the study. The majority of respondents had known or heard about Tetanus (n = 973; 81%) and rabies (n = 699; 58%). …

Sick With Fear: Popular Challenges To Scientific Authority In The Vaccine Controversies Of The 21st Century, Ellen Watkins

Annual Undergraduate Conference on Health and Society

In the 20th century, vaccines were heralded as one of the greatest medical inventions in history. In the late 1990’s, however, the myth of vaccine-caused autism caught fire. Despite mountains of evidence disproving the link, panicking Americans eschewed vaccines and turned against their physicians. Why did Americans turn their backs on doctors, scientists, and the health industry? This paper follows the vaccine controversy of the last thirty years, looking in particular at the relationship between science and the media. This paper analyzes the contrast between discussion of the hypothesized link in scientific circles and in popular news sources, seeking to …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

A Role For Caveolin-1 In Desmoglein Binding And Desmosome Dynamics., D Brennan, S Peltonen, A Dowling, W Medhat, K J Green, J K Wahl, F Del Galdo, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expressed in human skin carcinomas. In addition to its well-known role in mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote cancer development and progression. However, the mechanisms by which Dsg2 activates these signaling pathways and the relative contribution of its signaling and adhesion functions in tumor progression are poorly understood. In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major protein of specialized membrane microdomains called caveolae, which functions in both membrane protein turnover and intracellular signaling. Sequence analysis revealed that Dsg2 contains a putative …

Breast Cancer Screening Practices Among American Indians And Alaska Natives In The Midwest, Christine M. Daley, Melissa Filippi, Aimee S. James, Sarah Brokenleg, Stacy Braiuca, K. A. Greiner, Won S. Choi

Journal of Health Disparities Research and Practice

American Indian and Alaska Native (AI/AN) women currently have some of the highest mortality rates from breast cancer for any racial/ethnic group in the United States and some of the lowest screening rates. However, current data are not available for regional differences in screening, which can result in dramatically different stage at diagnosis and mortality. We conducted surveys with 120 focus group participants in a needs assessment of mammography among AI/AN in the greater Kansas City metropolitan area and parts of Northeast Kansas. We found that among women under age 40, for whom recommended screenings include only annual clinical breast …

Advances In Ultrafast Time Resolved Fluorescence Physics For Cancer Detection In Optical Biopsy, R. R. Alfano

Publications and Research

We discuss the use of time resolved fluorescence spectroscopy to extract fundamental kinetic information on molecular species in tissues. The temporal profiles reveal the lifetime and amplitudes associated with key active molecules distinguishing the local spectral environment of tissues. The femtosecond laser pulses at 310 nm excite the tissue. The emission profile at 340 nm from tryptophan is non-exponential due to the micro-environment. The slow and fast amplitudes and lifetimes of emission profiles reveal that cancer and normal states can be distinguished. Time resolved optical methods offer a new cancer diagnostic modality for the medical community.

Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, Yong Xu, Daret K. St. Clair, Fang Fang, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Background: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy.

Methodology/Principal Findings: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa …

Nutritional Status In Patients With Hepatitis C, Faisal Wasim Ismail, Rustam A. Khan, Lubna Kamani, Ashfaq A. Wadalawala, Hasnain Ali Shah, Saeed Hamid, Wasim Jafri

Section of Gastroenterology

Objective: To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease.
Study design: Descriptive study.
Place and duration of study: Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011.
Methodology: Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) …

Transcriptional Regulation Of N-Acetylglutamate Synthase, Sandra Kirsch Heibel, Giselle Yvette Lopez, Maria Panglao, Sonal Sodha, Leonardo Marino-Ramirez, Mendel Tuchman, Ljubica Caldovic

Pediatrics Faculty Publications

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high …

A Community-Integrated Home Based Depression Intervention For Older African Americans: Descripton Of The Beat The Blues Randomized Trial And Intervention Costs., Laura N Gitlin, Lynn Fields Harris, Megan Mccoy, Nancy L Chernett, Eric Jutkowitz, Laura T Pizzi

Center for Applied Research on Aging and Health Research Papers

ABSTRACT: BACKGROUND: Primary care is the principle setting for depression treatment; yet many older African Americans in the United States fail to report depressive symptoms or receive the recommended standard of care. Older African Americans are at high risk for depression due to elevated rates of chronic illness, disability and socioeconomic distress. There is an urgent need to develop and test new depression treatments that resonate with minority populations that are hard-to-reach and underserved and to evaluate their cost and cost-effectiveness. METHODS/DESIGN: Beat the Blues (BTB) is a single-blind parallel randomized trial to assess efficacy of a non-pharmacological intervention to …

Neuroscience Of Personality: Principles Of The Psyche As A Living System, Dario Nardi

Systems Science Friday Noon Seminar Series

The brain is a complex living system. Using colorful slides and anecdotes, Dario Nardi, PhD will overview his hands-on research of the past 5 years in his social neuroscience lab using EEG technology to better understand the neocortex. He spends 2 to 3 hours with each subject, offering a variety of tasks from solo activities like meditating, drawing, and recalling to social activities like poker and speed-dating. The results are in. The neocortex relies upon a dynamic of modules, circuits, and holistic modes to continuously coordinate with the environment in both a top-down and a bottom-up manner. Moreover, individual differences …

The Expression Of Ecotropic Virus Integration Site-1 In Seven Cancer Cell Lines, Wendy Bindeman '12

Student Publications & Research

The ecotropic virus integration site-1 (EVI1) gene is a transcriptional repressor implicated in the control of cell proliferation and frequently over-expressed in cancerous cells. I investigated the expression of this gene across seven cancer cell lines of varying morphologies. The tested lines included leukemia lines Kasumi-3, U937, MOLT-4, and CEM, breast cancer line MCF7, colorectal cancer line HT-29, and glioblastoma line M059K. Kasumi-3 and HT-29 are documented to have high EVI1 expression. Protein concentrations were normalized with respect to actin using SDS-PAGE and Western blotting. Western blots for EVI1 showed expression of an unidentified protein with a molecular weight of …

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …

The Formal And Informal Surgical Ethics Curriculum: Views Of Resident And Staff Surgeons In Toronto., Frazer Howard, Martin F. Mckneally, Ross E.G. Upshur, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND: Understanding what staff surgeons think surgical trainees should learn and the ethical issues that trainees need to manage can strengthen surgical ethics education.

METHODS: Participants were recruited from the 15 surgical specialty and subspecialty programs at the University of Toronto. Semistructured interviews and focus groups were conducted with 13 ethics coordinators from the surgical staff and 64 resident trainees. Data were analyzed qualitatively using modified thematic analysis.

RESULTS: All coordinators and trainees felt that ethics education was an important component of surgical training. Real cases, varying teaching methods, and teachers with applicable clinical experience were valued. Trainees identified intraprofessional …

Cross-Sectional Study Identifying Forms Of Tobacco Used By Shisha Smokers In Pakistan, Sameer-Ur-Rehman, Mohammed Ali Sadiq, Maria Adnan Parekh, Ali Bin Sarwar Zubairi, Philippe. Frossard, Javaid Khan

Section of Otolaryngology, Head & Neck Surgery

Objectives: To estimate the frequency of different forms of tobacco intake such as smoker's tobacco, chewable tobacco and snuff tobacco among shisha smoker's and to study the patterns and predictors of shisha smoking affecting youth from different cities of Pakistan.
Methods: A cross-sectional study was conducted including youth from four cities. Participants were asked to fill out a data collection tool at shisha cafes, shopping malls and restaurants. Data was analyzed using SPSSv.18.
Results: A total of 406 participants, 296 (73%) males and 110 (27%) females were included in the study. There were 163 (40%) cigarette smokers; 65 (16%) chewed …

Improved Cardiac Management With A Disease Management Program Incorporating Comprehensive Lipid Profiling., John F Mcana, Neil I Goldfarb, Joseph Couto, Michelle A Henry, Gary Piefer, George M Rapier

College of Population Health Faculty Papers

The objective of this study was to evaluate the improved effectiveness of a disease management treatment protocol incorporating comprehensive lipid profiling and targeted lipid care based on lipid profile findings in patients with ischemic heart disease (IHD) or congestive heart failure (CHF) enrolled in a managed care plan. This retrospective cohort study, conducted over a 2-year period, compared outcomes between patients with a standard lipid profile to those evaluated with a comprehensive lipid profile. All adult members of the WellMed Medical Management, Inc. managed care health plan diagnosed with IHD or CHF, and continuously enrolled between July 1, 2006 and …

Cross-Sectional Study Identifying Forms Of Tobacco Used By Shisha Smokers In Pakistan, Sameer Ur Rehman, Mohammed Ali Sadiq, Maria Adnan Parekh, Ali Bin Sarwar Zubairi, Javaid Khan, Philippe M. Frossard

Department of Medicine

Objectives: To estimate the frequency of different forms of tobacco intake such as smoker's tobacco, chewable tobacco and snuff tobacco among shisha smoker's and to study the patterns and predictors of shisha smoking affecting youth from different cities of Pakistan.
Methods: A cross-sectional study was conducted including youth from four cities. Participants were asked to fill out a data collection tool at shisha cafes, shopping malls and restaurants. Data was analyzed using SPSSv.18.
Results: A total of 406 participants, 296 (73%) males and 110 (27%) females were included in the study. There were 163 (40%) cigarette smokers; 65(16%) chewed tobacco …

Understanding Unintentional Childhood Home Injuries: Pilot Surveillance Data From Karachi, Pakistan., Nukhba Zia, Uzma R. Khan, J. Razzak, Prasanthi Puvanachandra, Adnan A. Hyder

Department of Emergency Medicine

Background: Childhood injuries, an important public health issue, globally affects more than 95% of children living in low-and middle-income countries. The objective of this study is to describe the epidemiology of childhood unintentional injuries in Karachi, Pakistan with a specific focus on those occurring within the home environment.
Methods:This was a secondary analysis of a childhood unintentional injury surveillance database setup in the emergency department of the Aga Khan Hospital, Karachi, Pakistan for 3 months. The data was collected by interviewing caretakers of children under 12 years of age presenting with an unintentional injury to the emergency departments of …

Personality Traits In Juvenile Delinquents: Associations With Peer And Family Relations, Jeffrey J. Wilson M.D., Sharon E. Willams Ph.D., Evan Garner M.D., Elaine Duxbury B.A., Hans Steiner Dr. Med. Univ.

Jefferson Journal of Psychiatry

Objective: To establish family and peer correlates of personality traits shown to be predictive of future criminal recidivism.

Method: 137 incarcerated boys aged 13-18 (x = 16 ± 1.2), 35% black, 21% Hispanic, 43% white, and 1% other completed the Weinberger Adjustment Inventory (WAI) and a psychosocial history obtained by a social worker. Records were summarized using two raters who assigned numerical ratings to dimensions of family and peer relations.

Results: As expected, observer ratings of family and peer relationships were correlated with the personality characteristics of distress, denial and restraint as measured by the WAI.

Conclusion: Family and peer …

Phase I Evaluation Of Intravenous Ascorbic Acid In Combination With Gemcitabine And Erlotinib In Patients With Metastatic Pancreatic Cancer., Daniel A. Monti, Md, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Department of Medical Oncology Faculty Papers

BACKGROUND: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

METHODS AND FINDINGS: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of …

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …

Stevens-Johnson Syndrome Following Treatment With Carbamazepine For A Mood Disorder, Albert Coleman M.D., M.P.H., B. Trappler M.D.

Jefferson Journal of Psychiatry

A case of Stevens-Johnson Syndrome (SJS) induced by carbamazepine in a psychiatric patient with schizo-affective disorder is reported. The patient also had diabetes mellitus and was on glyburide which posed an initial dilemma at the onset of SJS as to the causative drug. In view of the expanding use of carbamazepine in psychiatric patients and the potentially lethal consequences of SJS, the authors suggest a risk management approach when initiating Carbamazepine therapy to reduce the incidence and morbidity of the syndrome.

Managed Mental Health Care: An Oxymoron Of Ethics?, Jonathan M. Metzl M.D.

Jefferson Journal of Psychiatry

No abstract provided.

Are Baby Boomers Who Care For Their Older Parents Planning For Their Own Future Long-Term Care Needs?, Alison Kleppinger, Julie T. Robison

UCHC Articles - Research

A rapidly expanding number of baby boomers provide care to aging parents. This study examines associations between caregiver status and outcomes related to awareness and anticipation of future long-term care (LTC) needs using 2007 Connecticut Long-Term Care Needs Assessment survey data. Baby boomers who were adult child caregivers (n = 353) vs. baby boomers who were not (n = 1242) were more likely to anticipate some future LTC needs and to have considered certain financing strategies. Although baby boomer adult child caregivers more readily anticipate some future LTC needs, they are not taking specific actions. It is important to address …