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Rheumatoid Arthritis-Associated Polymorphisms Are Not Protective Against Alzheimer's Disease, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.

RESULTS: In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).

CONCLUSIONS: RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than …

Baseline Data For Maine Pediatric And Family Practices From Arra-Funded Hit Ambulatory Practice Survey Data, Kimberley S. Fox Mpa

Population Health & Health Policy

No abstract provided.

Possible Role Of Death Receptor-Mediated Apoptosis By The E3 Ubiquitin Ligases Siah2 And Posh, Perry A. Christian, Michael V. Fiandalo, Steven R. Schwarze

Markey Cancer Center Faculty Publications

BACKGROUND: A functioning ubiquitin proteasome system (UPS) is essential for a number of diverse cellular processes and maintenance of overall cellular homeostasis. The ability of proteasome inhibitors, such as Velcade, to promote extrinsic apoptotic effects illustrates the importance of the ubiquitin proteasome system in the regulation of death receptor signaling. Here, we set out to define the UPS machinery, particularly the E3 ubiquitin ligases, that repress apoptosis through the extrinsic pathway. A cell-based genome-wide E3 ligase siRNA screen was established to monitor caspase-8 activity following the addition of TRAIL.

RESULTS: Data from the high-throughput screen revealed that targeting the RING-finger …

Four Year Experience Of Sarcoma Of Soft Tissues And Bones In A Tertiary Care Hospital And Review Of Literature, Tayyaba Z. Ansari, Nehal Masood, Asra Parekh, Rabab Z. Jafri, Syed N. Niamatullah, Adnan A. Zaidi, Masood Umer

Department of Medicine

Background:

Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.

Methods:

This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The Patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.

Results:

Out of 93 newly diagnosed Patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed Patients, 5 had soft tissue sarcoma and 9 had bone …

Inhibition Of Phosphorylated C-Met In Rhabdomyosarcoma Cell Lines By A Small Molecule Inhibitor Su11274., Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, J. Wang, Jialin C. Zheng, Yan Li, Julia A. Bridge, Steven H. Hinrichs, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.

METHODS: The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle …

Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab

Gill Heart & Vascular Institute Faculty Publications

The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for …

Nfatc1 Regulation Of Trail Expression In Human Intestinal Cells, Qingding Wang, Yuning Zhou, Heidi L. Weiss, Chi-Wing Chow, B. Mark Evers

Surgery Faculty Publications

TNF-related apoptosis-inducing ligand (TRAIL; Apo2) has been shown to promote intestinal cell differentiation. Nuclear factor of activated T cells (NFAT) participates in the regulation of a variety of cellular processes, including differentiation. Here, we examined the role of NFAT in the regulation of TRAIL in human intestinal cells. Treatment with a combination of phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187 (Io) increased NFAT activation and TRAIL expression; pretreatment with the calcineurin inhibitor cyclosporine A (CsA), an antagonist of NFAT signaling, diminished NFAT activation and TRAIL induction. In addition, knockdown of NFATc1, NFATc2, NFATc3, and NFATc4 blocked PMA/Io increased …

Multiple Courses Of Stereotactic Re-Irradiation In Recurrent Oligodendroglioma: A Case Report., Shannon Fogh, Charles Glass, David W Andrews, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit.

CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 …

Evaluation Of A Medical And Mental Health Unit Compared With Standard Care For Older People Whose Emergency Admission To An Acute General Hospital Is Complicated By Concurrent ‘Confusion’: A Controlled Clinical Trial. Acronym: Team: Trial Of An Elderly Acute Care Medical And Mental Health Unit, Rowan H. Harwood, Sarah E. Goldberg, Kathy H. Whittamore, Catherine Russell, John Rf Gladman, Rob G. Jones, Davina Porock, Sarah A. Lewis, Lucy E. Bradshaw, Rachel A. Elliot

Publications and Research

Background: Patients with delirium and dementia admitted to general hospitals have poor outcomes, and their carers report poor experiences. We developed an acute geriatric medical ward into a specialist Medical and Mental Health Unit over an eighteen month period. Additional specialist mental health staff were employed, other staff were trained in the ‘person-centred’ dementia care approach, a programme of meaningful activity was devised, the environment adapted to the needs of people with cognitive impairment, and attention given to communication with family carers. We hypothesise that patients managed on this ward will have better outcomes than those receiving standard care, and …

Download The Full Pdf Of Jefferson Surgical Solutions Spring 2011, Volume 6, Number 1

Jefferson Surgical Solutions

No abstract provided.

News In Brief

Jefferson Surgical Solutions

No abstract provided.

Those Who Give: Making A Difference Now And Down The Road: The Howell Professorship In Pancreatic Cancer Research

Jefferson Surgical Solutions

No abstract provided.

On The Job: Dr. Goldberg Spends Research Year Targeting Breast Cancer

Jefferson Surgical Solutions

No abstract provided.

Beekley’S Combat Experience Informs Research And Protocols At Home And Abroad

Jefferson Surgical Solutions

No abstract provided.

Resident Update: Lieutenant Commander Daniel R. Grabo

Jefferson Surgical Solutions

No abstract provided.

Creating Second Chances For All Ages: The Live Donor Liver Transplant Program

Jefferson Surgical Solutions

No abstract provided.

Overview

Jefferson Surgical Solutions

No abstract provided.

About The Minimally Invasive Thoracic Surgery Program

Jefferson Surgical Solutions

No abstract provided.

From The Or To The Principal’S Office: Video Assisted Thoracoscopic Surgery Offers Faster Recovery

Jefferson Surgical Solutions

No abstract provided.

Frontiers Of Oncology: Biobanking Resources For The 21St Century, Jill Barnholtz-Sloan, Mark R. Chance

Faculty Scholarship

No abstract provided.

Investigation Of Emergency Medical Technicians Practice And Beliefs Regarding The Recognition And Treatment Of Exertional Heat Stroke, Kristin Applegate

Master's Theses

Context: Current Evidence Based Practice (EBP) supports the use of rectal thermometry (T_re) for an accurate diagnosis and cold water-immersion (CWI) for the treatment of Exertional Heat Stroke (EHS) for an optimal outcome. Emergency Medical Services (EMS) play a critical role for the diagnosis and treatment of EHS as they may be the first to arrive on scene, however there is limited data regarding their implementation of EBP.  Objective: Investigate current practice regarding EHS by EMS professionals and explore the relationship that exists between EMS and Athletic Trainers (ATs).  Design: A basic qualitative design using in-person focus groups. …

The Use Of Motion Analysis Technology As An Alternative Means Of Assessing Spinal Deformity In Patients With Adolescent Idiopathic Scoliosis, Matthew J. Solomito

Master's Theses

Adolescent Idiopathic Scoliosis (AIS) is a three dimensional deformity of the spine that causes abnormal curvatures in the coronal and sagittal planes and abnormal vertebral rotations. The gold standard for diagnosing and tracking the progression of the deformity is through the use of repeated radiography and a patient can receive upwards of fifteen radiographic series over the course of treatment, which exposes this population to an increased risk of radiation-dependent complications.

This thesis presents the necessary calculations and the marker set required to make the motion capture technology a viable alternative to radiographs, in an effort to reduce the patient’s …

Medical Education Digest, Vol. 13 No. 3 (May/June 2011), Nova Southeastern University

Medical Education Digest

No abstract provided.

Standing In The Gap: The Primary Care Physician And Alzheimer’S Disease, Shirley M. Neitch

Internal Medicine

There is a huge volume of information recently published about Alzheimer’s disease, but most of it is not targeted to the average busy primary care physician, even though these PCPs are providing the bulk of care to patients with dementia. This paper is a succinct clinical review of the current state of diagnosis and treatment of Alzheimer’s disease, including citations of resources for physicians and caregivers.

Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley M. Neitch, Guillermo Madero, Shawn Maynard

Internal Medicine

Primary care physicians are frequently involved in cases in which they must decide if a patient with dementia should stop driving. The decision is complex, and there are no firm clinical guidelines available. We examined the results of a number of patients who have undergone assessment in our Driving Assessment Clinic, to determine if any of our findings correlated with the diagnosis of dementia. If any associations exist, recommendations may be possible to assist PCPs in making the decision to have patients stop driving, even if full formal testing cannot be done.

Post-Exercise Hypotension In Brief Exercise, Jeremiah G. Bush

Masters Theses & Specialist Projects

The purpose of this investigation was to examine whether a single 10 minute bout of exercise, performed at multiple intervals throughout the day to equal 30 minutes, can effectively elicit post-exercise hypotension (PEH). Secondly, it is important to explore whether a light (40% VO2R) or moderate (70% VO2R) intensity is required to elicit PEH within 10 minutes. Subjects (N=11) completed a VO2max test utilizing the Bruce Treadmill protocol. Each subject returned within 3 – 5 days to complete two separate exercising trials. A counter balanced system was employed so that each subject did not perform the same intensity rotation (Counter …

Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng

Paediatrics Publications

Induction of tumour necrosis factor-α (TNF-α) expression leads to myocardial depression during sepsis. However, the underlying molecular mechanisms are not fully understood. The aim of this study was to investigate the role of Rac1 in TNF-α expression and cardiac dysfunction during endotoxemia and to determine the involvement of phosphoinositide-3 kinase (PI3K) in lipopolysaccharide (LPS)-induced Rac1 activation. Our results showed that LPS-induced Rac1 activation and TNF-α expression in cultured neonatal mouse cardiomyocytes. The response was inhibited in Rac1 deficient cardiomyocytes or by a dominant-negative Rac1 (Rac1N17). To determine whether PI3K regulates Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective …

Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier

Paediatrics Publications

The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3 and GSK-3β, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase …

Maternal Protein Restriction Elevates Cholesterol In Adult Rat Offspring Due To Repressive Changes In Histone Modifications At The Cholesterol 7Α-Hydroxylase Promoter, Gurjeev Sohi, Kelly Marchand, Andrew Revesz, Edith Arany, Daniel B. Hardy

Paediatrics Publications

Adverse events in utero, such as intrauterine growth restriction (IUGR), can permanently alter epigenetic mechanisms leading to the metabolic syndrome, which encompasses a variety of symptoms including augmented cholesterol. The major site for cholesterol homeostasis occurs via the actions of hepatic cholesterol 7α-hydroxylase (Cyp7a1), which catabolizes cholesterol to bile acids. To determine whether posttranslational histone modifications influence the long-term expression of Cyp7a1 in IUGR, we used a protein restriction model in rats. This diet during pregnancy and lactation led to IUGR offspring with decreased liver to body weight ratios, followed by increased circulating and hepatic cholesterol levels in both sexes …

Use Of Tranexamic Acid Is A Cost Effective Method In Preventing Blood Loss During And After Total Knee Replacement, Yasir Jamal Sepah, Masood Umer, Tashfeen Ahmad, Faria Nasim, Muhammad Umer Chaudhry, Muhammad Umar

Section of Orthopaedic Surgery

Background & Purpose: Allogenic blood transfusion in elective orthopaedic surgery is best avoided owing to its associated risks. Total knee replacement often requires blood transfusion, more so when bilateral surgery is performed. Many strategies are currently being employed to reduce the amount of peri-operative allogenic transfusions. Anti-fibrinolytic compounds such as aminocaproic acid and tranexamic acid have been used systemically in perioperative settings with promising results. This study aimed to evaluate the effectiveness of tranexamic acid in reducing allogenic blood transfusion in total knee replacement surgery.
Methodology: This was a retrospective cohort study conducted on patients undergoing total knee replacement during …