Medicine and Health Sciences Commons^™

Bicarbonate Enhances Expression Of The Endocarditis And Biofilm Associated Pilus Locus, Ebpr-Ebpabc, In Enterococcus Faecalis, Agathe Bourgogne, L Charlene Thomson, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation …

3d Visualization Of Hiv Virions By Cryoelectron Tomography, Jun Liu, Elizabeth R Wright, Hanspeter Winkler

Faculty, Staff and Student Publications

The structure of the human immunodeficiency virus (HIV) and some of its components have been difficult to study in three-dimensions (3D) primarily because of their intrinsic structural variability. Recent advances in cryoelectron tomography (cryo-ET) have provided a new approach for determining the 3D structures of the intact virus, the HIV capsid, and the envelope glycoproteins located on the viral surface. A number of cryo-ET procedures related to specimen preservation, data collection, and image processing are presented in this chapter. The techniques described herein are well suited for determining the ultrastructure of bacterial and viral pathogens and their associated molecular machines …

Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Faculty, Staff and Student Publications

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.

More Than Synaptic Plasticity: Role Of Nonsynaptic Plasticity In Learning And Memory, Riccardo Mozzachiodi, John H Byrne

Faculty, Staff and Student Publications

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit …

Social Support In An Internet Weight Loss Community, Kevin O Hwang, Allison J Ottenbacher, Angela P Green, M Roseann Cannon-Diehl, Oneka Richardson, Elmer V Bernstam, Eric J Thomas

Faculty, Staff and Student Publications

Purpose: To describe social support for weight loss shared by members of a large Internet weight loss community.

Methods: We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes.

Results: Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily …

Most Common Single-Nucleotide Polymorphisms Associated With Rheumatoid Arthritis In Persons Of European Ancestry Confer Risk Of Rheumatoid Arthritis In African Americans, Laura B. Hughes, Richard J. Reynolds, Elizabeth E. Brown, James M. Kelley, Brian Thomson, Doyt L. Conn, Beth L. Jonas, Andrew O. Westfall, Miguel A. Padilla, Leigh F. Callahan

Psychology Faculty Publications

Objective. Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population.

Methods. Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We …

Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated By Pemphigus Foliaceus Antibodies And Exfoliative Toxins., D Brennan, Ying Hu, Walid Medhat, A Dowling, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. …

The Most Important Medical Source: Aunt Mabel Knows Best., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Not so long ago, one of us was consulted by a middle-aged woman with rosacea. For many years, she had had periodic flares of red papules and pustules on her nose and the adjoining areas. The confluent telangiectasia on her cheeks gave a permanent appearance of well-applied rouge. She had seen several dermatologists and had received a wide variety of medications, all of which seemed appropriate except to her as would be subsequently revealed. She wanted a new approach, but there were limitations placed upon her request: no pills or capsules; nothing odiferous; no agent that might bleach clothing; and …

Parastomal Patch For Laparoscopic Repair Of Parastomal Hernia: Description Of The Technique, Courtney Edwards Md, Dale A. Dangleben Md, Erik J. Teicher Md, Peter Rovito Md

Department of Surgery

No abstract provided.

Incorporating Rehabilitation Services Into Oncology Site-Specific Clinical Practice Guidelines, Kathleen Leies Rn, Ocn, Kathy Sevedge Rn, Ma, Aocn, Dorothy Morrone Rnc, Ms, Ocn, Stephanie Marshall Ccer, Jennifer Roeder Mspt, Mba

Department of Medicine

No abstract provided.

Outcome Of Traumatic Aortic Rupture: A 14-Year Experience, Matthew Wilson, James K. Wu, Sanjay M. Mehta Md, Theodore G. Phillips Md, Raymond L. Singer Md, Michael F. Szwerc Md, Gary W. Szydlowski Md

Department of Medicine

No abstract provided.

The Impact Of A Mental Health-Related Diagnosis On Readmission Rates For Heart Failure, Ronald S. Freudenberger Md, Carol A. Foltz Phd, Lou A. Lukas Md, Donna F. Petruccelli Crnp, Hannah D. Paxton Rn, Mph, Victoria Sabella Bsn

Department of Medicine

No abstract provided.

The Complication Of Migration: To Place Or Not To Place An Inferior Vena Cava Filter?, Courtney Bennett Do, Stacey Smith Md

Department of Medicine

No abstract provided.

Immunologic Therapy With Cadi-05 For The Treatment Of Advanced Melanoma, Paul J. Mosca Md, Phd, Suresh G. Nair Md, Susan K. Ayre Rn, Ma, Wenjing Shi Rn, Ms, Sherrine Eid Mph, Shantu Amin Phd, Dhimant Desai Phd, Joseph J. Drabick Md, Facp, Bakulesh M. Khamar Md, Arati Sharma Phd, Svetomir N. Markovic Md, Gavin P. Robertson Phd

Department of Medicine

No abstract provided.

Multidisciplinary Survivorship Care, Sue N. Gardner Rn, Msn, Crnp, Aocnp, Gregory Harper Md, Phd, Dorothy Morrone Rnc, Ms, Ocn, Jennifer Brennan Rd, Cso, Andrea Geshan Rn, Msw, Diane Brong Lcsw, Jennifer Roeder Mspt, Mba

Department of Medicine

No abstract provided.

Evaluation Of The Care Manager Role In Primary Care, Malaika Stoll Md, Mpa, Lynn M. Deitrick Rn, Phd, Nancy Gratz Mpa, Pam Marcks, Kathleen Moser

Administration & Leadership

No abstract provided.

Effects Of Training On Physical Performance Wearing Personal Protective Equipment, David P. Swain, James A. Onate, Stacie I. Ringleb, Dayanand N. Naik, Marlene Demaio

Human Movement Studies & Special Education Faculty Publications

We evaluated the effects of wearing a weighted vest during 6 weeks of military-style training. Forty-three subjects were randomly assigned to a control group or a vest group (carrying 4-5 kg for 2 weeks, and 8-10 kg for 4 weeks), with 37 completing the study (17 vest, 20 control). Both groups performed stair climbing in addition to standard Marine Corps training for 1 hour, four times per week. Pre- and post-tests were performed while wearing military personal protective equipment, with the exception of the Marine Physical Readiness Test (PRT). Both groups significantly improved PRT scores (8.4% 3-mile run, 28-38% calisthenics) …

Aerobic Training Increases Skin Perfusion By A Nitric Oxide Mechanism In Type 2 Diabetes, Sheri R. Colberg, Laura C. Hill, Henri K. Parson, Kathleen S. Thomas, Aaron I. Vinik

Human Movement Studies & Special Education Faculty Publications

It is well known that a number of locally released vasodilatory and vasoconstrictive compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO), prostaglandins (PG), and endothelial-derived hyperpolarizing factor (EDHF) in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM). Ten previously sedentary, older individuals with T2DM (57.0 ± 3.1 years) and nine sedentary controls (53.5 ± 3.2 years) were tested before and after undertaking six months of moderate aerobic training three times weekly in a supervised setting. All subjects underwent measurement of baseline (32°C) and heat-stimulated …

Interaction Of The Mu-Opioid Receptor With Gpr177 (Wntless) Inhibits Wnt Secretion: Potential Implications For Opioid Dependence., Jay Jin, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Wade Berrettini, Robert Levenson

Department of Neurosurgery Faculty Papers

BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila …

The Neighborhood Cancer Center, Gregory R. Harper Md, Phd, Debbie Salas-Lopez Md, Mph, Keith J. Weinhold Mha, Elliot J. Sussman Md, Mba

Administration & Leadership

No abstract provided.

Inadequate Health Numeracy Affects Cancer Screening Practices In Vulnerable Populations, Sherrine Eid Mph, Dorothy Faulkner Phd

Administration & Leadership

No abstract provided.

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Identifying Factors Associated With Falls In Postmenopausal Breast Cancer Survivors: A Multi-Disciplinary Approach, Kerri M. Winters-Stone, Britta Torgrimson, Fay Horak, Alvin Eisner, Lillian Nail, Micahel C. Leo, Steve Chui, Shiuh-Wen Luoh

Community Health Faculty Publications and Presentations

Objective—To identify neuromuscular, balance and vision factors that contribute to falls in recently treated breast cancer survivors (BCS) and explore links between fall risk factors and cancer treatment

Design—Case-control plus prospective observation

Setting—Comprehensive cancer center

Participants—BCS within two years chemotherapy completion and/or on adjuvant endocrine therapy (N=59; mean age: 58 yrs)

Intervention—not applicable

Main outcome measures—Objective measures of postural control, vision and neuromuscular function included 1) a sensory organization test (SOT), 2) a visual assessment battery, 3) muscle mass by DXA, and 4) neuromuscular function with strength by repetition maximum, power by timed stair …

Differential Genome-Wide Array–Based Methylation Profiles In Prognostic Subsets Of Chronic Lymphocytic Leukemia, Meena Kanduri, Nicola Cahill, Hanna Göransson, Camilla Enström, Fergus Ryan, Anders Isaksson, Richard Rosenquist

Articles

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in …

Genetic Diversity Among Plasmodium Falciparum Field Isolates In Pakistan Measured With Pcr Genotyping Of The Merozoite Surface Protein 1 And 2, Najia Ghanchi, Andreas Martensson, Johan Ursing, Sana Jafri, Sandor Bereczky, Rabia Hussain, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Background:The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Pakistan. This study aimed to establish molecular characterization of P. falciparum field isolates in Pakistan measured with two highly polymorphic genetic markers, i.e. the merozoite surface protein 1 (msp-1) and 2 (msp-2).
Methods:Between October 2005 and October 2007, 244 blood samples from Patients with symptomatic blood-slide confirmed P. falciparum mono-infections attending the Aga Khan University Hospital, Karachi, or its collection units located in Sindh and Baluchistan provinces, Pakistan were collected. The genetic diversity of P. falciparum …

Ccl2 Responses To Mycobacterium Tuberculosis Are Associated With Disease Severity In Tuberculosis, Zahra Hasan, Jacqueline M. Cliff, Hazel M. Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain

Section of Pulmonary & Critical Care

Background

Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.

Methodology

We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, …

Guyon's Canal Syndrome Due To Tortuous Ulnar Artery With Dequervain Stenosing Tenosynovitis, Ligamentous Injuries And Dorsal Intercalated Segmental Instability Syndrome, A Rare Presentation: A Case Report., Muhammad Zeeshan, Farhan Ahmed, Darakhshan Kanwal, Qazi Saad Bin Khalid, Muhammad Nadeem Ahmed

Department of Radiology

The Guyon's canal syndrome is a well known clinical entity and may have significant impact on Patient's quality of life. We report a case of 43-year-old male who presented with complaints of pain and numbness in right hand and difficulty in writing for past one month. On imaging diagnosis of Guyon's canal syndrome because of tortuous ulnar artery was made with additional findings of DeQuervain's stenosing tenosynovitis and dorsal intercalated segmental instability syndrome with ligamentous injury and subsequently these were confirmed on surgery. Although it is a rare syndrome, early diagnosis and treatment prevents permanent neurological deficits and improve Patient's …

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker

Food for Health: Publications

Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …

Regulation Of Cellular Protein Phosphatase-1 (Pp1) By Phosphorylation Of The Cpi-17 Family, C-Kinase-Activated Pp1 Inhibitors., Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to a variety of diseases, including cardiovascular disease and cancer. Upon phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively inhibits a specific form of PP1, myosin light chain phosphatase, which transduces multiple kinase signals into the phosphorylation of myosin II and other proteins. Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.