Medicine and Health Sciences Commons^™

Germinal Center Reutilization By Newly Activated B Cells., Tanja A Schwickert, Boris Alabyev, Tim Manser, Michel C Nussenzweig

Department of Microbiology and Immunology Faculty Papers

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude …

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.

Perioperative Hyperglycemia Increases Risk For Deep Wound Infection After Major Orthopedic Surgery, Boris Mraovic, Md, Orhan Bican, Md, Javad Parvizi, Md, Jeffrey I. Joseph, D.O.

Department of Anesthesiology Faculty Papers

Total hip and knee replacement surgery are one of the most frequent major surgeries performed in the USA. In 2002, the number of primary hip and knee arthroplasty was 119,000 and 381,000, respectively. By year 2030 the number is projected to increase to 572,000 and 3,481,000 respectively.

Deep wound infection after major orthopedic surgery is one of the most serious complications causing increase in morbidity and mortality and health care costs. Various risk factors for developing infection after hip and knee replacement surgery were described including age, ASA PS status, obesity, patients' comorbidities and surgical technique factors.

Perioperative hyperglycemia may …

Growing Ambulatory Care Nurse Leaders In A Multigenerational Workforce, Beth Swan, Phd, Crnp, Faan

College of Nursing Faculty Papers & Presentations

Executive Summary:

Ambulatory care faces challenges in sustaining a nursing workforce in the future as newly licensed nurses are heavily recruited to inpatient settings and retirements will impact ambulatory care sooner than other areas.

Building a diverse team by recruiting nurses of different ages (generations) and skills may result in a more successful and robust organization.

Knowledge about generational characteristics and preferences will aid nurse leaders and recruiters in attracting high-quality, talented nurses.

Nurses of Generations X and Y can increase their likelihood of success in ambulatory care by better understanding intergenerational issues.

Stromal Caveolin-1 Levels Predict Early Ductal Carcinoma In Situ Progression To Invasive Breast Carcinoma, A. K. Witkiewicz, A. Dasgupta, G. F. Schwartz, Kh H. Nguyen, H. R. Rui, M. P. Lisanti

Department of Cancer Biology Faculty Papers

With the increased use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased substantially and it currently accounts for 20-30% of newly diagnosed breast carcinomas in United States. Breast conserving therapy with or without radiotherapy is the accepted treatment for most cases of DCIS. However, the local recurrence rate with such therapy rages from 10 to 40% with half of these patients developing invasive carcinoma. Tamoxifen, used as an adjuvant systemic therapy for DCIS, does not increase overall survival and data on reduction of local recurrence rates are conflicting.

The current classification for DCIS based on …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Regulation Of Energy Stores And Feeding By Neuronal And Peripheral Creb Activity In Drosophila., Koichi Iijima, Lijuan Zhao, Christopher Shenton, Kanae Iijima-Ando

Department of Biochemistry and Molecular Biology Faculty Papers

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores …

Il-4(-/-) Mice With Lethal Mesocestoides Corti Infections--Reduced Th2 Cytokines And Alternatively Activated Macrophages., A. E. O'Connell, L. A. Kerepesi, G. L. Vandergrift, D. R. Herbert, T J. Van Winkle, D. C. Hooper, E J. Pearce, D. Abraham

Department of Microbiology and Immunology Faculty Papers

Protection against Mesocestoides corti, a cestode that invades vital organs, is dependent on the production of IL-4, as IL-4(-/-) mice were found to have higher parasite burdens when compared with wild-type mice. The goal of this study was to investigate the role of IL-4 in immunity to M. corti, focusing on the immunological profile and on potential mediators of pathology. IL-4(-/-) mice infected with M. corti showed 100% mortality by 32 days, whereas wild-type mice survived for approximately 1 year. Parasite burdens were significantly increased in the liver, peritoneal, and thoracic cavities of IL-4(-/-) mice, associated with impaired recruitment of …

Initial Tumor Metabolic Parameters (Maximum Suv And Metabolic Volume) Predict Death From Lung Cancer And Rapid Suv Decline Is Associated With Local Control, Maria Werner-Wasik, Edward Pequignot, Terry Hyslop, Brian Shulli, Ying Xiao, Mitchell Machtay, Amy Taylor, Walter Curran, Rita Axelrod

Department of Radiation Oncology Faculty Papers

Factors associated with local failure and death from lung cancer were evaluated based on post-treatment FDG-PET imaging in patients (pts) with non-small cell lung cancer (NSCLC).

PET-CT scans were obtained 6-8 weeks after thoracic RT and approximately every 3 months thereafter.

Mepe/Of45 Protects Cells From Dna Damage Induced Killing Via Stabilizing Chk1., Shuang Liu, Hongyan Wang, Xiang Wang, Lin Lu, Ning Gao, Peter S N Rowe, Baocheng Hu, Ya Wang

Department of Radiation Oncology Faculty Papers

Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the …

Fluorescent Protein Markers To Tag Collagenous Proteins: The Paradigm Of Procollagen Vii, Hye J. Chung, Andrzej Steplewski, Jouni Uitto, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Fluorescent proteins are powerful markers allowing tracking expression, intracellular localization, and translocation of tagged proteins but their effects on the structure and assembly of complex extracellular matrix proteins has not been investigated. Here, we analyzed the utility of fluorescent proteins as markers for procollagen VII, a triple-helical protein critical for the integrity of dermal-epidermal junction. DNA constructs encoding a red fluorescent protein-tagged wild type mini-procollagen VII α chain and green fluorescent protein-tagged α chains harboring selected mutations were genetically engineered. These DNA constructs were co-expressed in HEK-293 cells and the assembly of heterogeneous triple-helical mini-procollagen VII molecules was analyzed. Immunoprecipitation …

Improved Inter-Rater Reliability For Sah Ct Grading Scales Through Application Of A Formal Definition Of Clot Thickness, William Mcbride, Md, Valerie Dechant, Md, Michael Moussouttas, Md

Department of Neurology Faculty Papers

Various scales have been devised for the prediction of vasospasm following aneurysmal rupture.

Especially prominent in these scales is their reliance upon a subjective assessment of clot thickness which introduces variability in grading across raters.

The current study seeks to compare the inter-rater reliability of the traditional Fisher and newer "Frontera" scale (Modified Fisher) when a rigid definition of thick clot is employed.

Direct Healthcare Costs Of Hip, Vertebral, And Non-Hip, Non-Vertebral Fractures., Nianwen Shi, Kathleen Foley, Gregory Lenhart, Enkhe Badamgarav

College of Population Health Faculty Papers

Limited data exist regarding the cost of non-hip, non-vertebral (NHNV) fractures. Although NHNV fractures may be less expensive than hip and vertebral fractures, they have a higher incidence rate. The objective of this study was to quantify first-year healthcare costs of hip, vertebral, and NHNV fractures. This was a claims-based retrospective analysis using a case-control design among patients with commercial insurance and Medicare employer-based supplemental coverage. Patients were > or =50 years old with a closed hip, vertebral, or NHNV fracture between 7/1/2001 and 12/31/2004, and continuous enrollment 6 months prior to and 12 months after the index fracture. Adjusted mean …

Fdg Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy: Etiology And Outcomes Compared To Patients With Hippocampal Sclerosis, C. Lopinto Khoury, M. Sperling, C. Skidmore, M. Nei, A. Zangaladze, J. Evans, A. Sharan, S. Mintzer

Department of Neurology Faculty Papers

FDG PET hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of Hippocampal Sclerosis (HS) on MRI.

Solution Structure Of The Inhibitory Phosphorylation Domain Of Myosin Phosphatase Targeting Subunit 1., Shunsuke Mori, Ryou Iwaoka, Masumi Eto, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin.1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary …

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

Subconjunctivally Implantable Hydrogels With Degradable And Thermoresponsive Properties For Sustained Release Of Insulin To The Retina., Gauri P. Misra, Ravi S.J. Singh, Tomas S. Aleman, Samuel G. Jacobson, Thomas W. Gardner, Tao L. Lowe

College of Pharmacy Faculty Papers

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying …

Mechanism Of Nsf: New Evidence Challenging The Prevailing Theory, Ben B. Newton, Phd, Sergio A. Jimenez, Md

Scleroderma Center Faculty Papers

Nephrogenic systemic fibrosis (NSF) has been associated with the administration of gadolinium-based contrast agents in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), or acute renal failure (ARF). Since the vast majority of these patients do not get NSF, it is highly likely that patient factors play a role in its development. Although free or dechelated gadolinium is thought by some to be the only trigger of NSF, recent evidence suggests that chelated gadolinium may be important. Chelated gadolinium such as Omniscan (gadodiamide) and Magnevist (gadopentetate) can directly stimulate macrophages and monocytes in vitro to release profibrotic …

Embolic Complication Of Tako-Tsubo Cardiomyopathy., Vincent M. Figueredo, S Gupta

Department of Medical Genetics Faculty Papers

No abstract provided.

Development Of A Mouse Monoclonal Antibody Cocktail For Post-Exposure Rabies Prophylaxis In Humans., Thomas Müller, Bernhard Dietzschold, Hildegund Ertl, Anthony R Fooks, Conrad Freuling, Christine Fehlner-Gardiner, Jeannette Kliemt, Francois X Meslin, Charles E Rupprecht, Noël Tordo, Alexander I Wanderler, Marie Paule Kieny

Department of Microbiology and Immunology Faculty Papers

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used …

Combination Of Vandetanib, Radiotherapy, And Irinotecan In The Lovo Human Colorectal Cancer Xenograft Model., Phyllis Wachsberger, Randy Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) …

Imrt Commissioning: Multiple Institution Planning And Dosimetry Comparisons, A Report From Aapm Task Group 119., Gary A Ezzell, Jay W Burmeister, Nesrin Dogan, Thomas J Losasso, James G Mechalakos, Dimitris Mihailidis, Andrea Molineu, Jatinder R Palta, Chester R Ramsey, Bill J Salter, Jie Shi, Ping Xia, Ning J Yue, Ying Xiao, Phd

Department of Radiation Oncology Faculty Papers

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, …

Asymmetric Deactivation Of Hiv-1 Gp41 Following Fusion Inhibitor Binding., Kristen M Kahle, H Kirby Steger, Michael J Root

Department of Biochemistry and Molecular Biology Faculty Papers

Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env) that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env interactions with cellular CD4 and a chemokine receptor. In a kinetic window between CD4 binding and membrane fusion, the N- and C-terminal regions of the gp41 ectodomain become transiently susceptible to inhibitors that disrupt Env structural transitions. In this study, we sought to identify kinetic parameters that …

Sonography Of The Neonatal Brain, Traci B. Fox

Department of Radiologic Sciences Faculty Papers

Neurosonography is a critical part of the care of the sick newborn. Sonography is superior to other modalities in imaging of the brain because it can be performed at the bedside, is easily reproducible, and does not require ionizing radiation or sedation. This article refreshes the sonographer in the normal anatomy and appear- ance of the neonatal brain using sonography, as well as some of the more common pathologic conditions that may be encountered.

Traumatic Thoracic Asia A Examinations And Potential For Clinical Trials, James S. Harrop, Md, Mitchell G. Maltenfort, Phd, Fred H. Geisler, Md, Phd, William Coleman, Phd, Linda A.T. Jones, Pt, Ms, Edward Wirth, Md, Alexander Vaccaro, Md, Phd

Department of Neurosurgery Faculty Papers

Study Design: Retrospective review of prospective database

Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A).

Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes.

Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. …

Replacement For The 10 Page Paper? A Pilot Project Using Blogs And Wikis For A Collaborative Ebm Assignment In A 3rd Year Internal Medical Clerkship, Gary E. Kaplan, Mslis, Daniel G. Kipnis, Msi, Margy Grasberger, Ms, Karen Krasznavolgyi, Mls, Anothny J. Frisby, Phd, J. Jon Veloski, Ms, Jessica Salt, Md

Academic Commons and Scott Memorial Library Staff Papers and Presentations

Objective Pilot a group assignment using blogs and wikis to develop evidence-based medicine skills in third year medical students on an internal medicine clerkship. Instead of the clerkship’s previous individual ten-page paper assignment, the students were divided into four groups of sixteen. During the clerkship, students are on geographically dispersed rotations. The earlier ten-page paper had required the students to complete a patient history and physical write-up. With the pilot project, each group was assigned a librarian and a physician faculty mentor. Each student recorded on the blog a clinical scenario and question they encountered. They were encouraged to communicate …

Somnoforme: A Century After The Introduction Of The "Ideal" Anesthetic Gas, James W. Heitz, Md

Department of Anesthesiology Faculty Papers

Since the introduction of ether as a general anesthetic, there has been a continuous quest to develop the ideal anesthetic gas. The attributes of the ideal anesthetic gas have evolved over time. At the beginning of the 20th century, the search for the ideal anesthetic was focused upon finding an anesthetic gas with rapid inhalation induction and rapid emergence that could be delivered without cumbersome apparatus and would have limited potential for toxicity. Somnoforme was a mixture of ethyl chloride, methyl chloride, and ethyl bromide designed to provide powerful efficacy with low potential for side effects by blending of several …

Toward Evidence-Based Teaching: Evaluating The Effectiveness Of Two Teaching Strategies In An Associate Degree Nursing Program, Lori S. Lauver, Phd, Rn, Margaret M. West, Phd, Rn, Timothy B. Campbell, Msn, Crnp, Jennifer Herrold, Msn, Crnp, G. C, Wood, Ms

College of Nursing Faculty Papers & Presentations

The need for evidence based teaching has become an important ideology for nurse educators who are frequently encouraged to expand their teaching strategies based on recent advances in technology and student learning styles. Traditional lecture is often preferred by students, yet the literature encourages case study methodology for the development of critical thinking. A pilot study was conducted comparing learning outcomes using two different teaching strategies: lecture and case study instruction. Recommendations for using case study as a teaching methodology are offered.

The Use Of Remote Monitoring For Internal Cardioverter Defibrillators (Icds): The Infusion Of Information Technology And Medicine, Susan Shirato, Msn, Rn, Ccrn

College of Nursing Faculty Papers & Presentations

The clinical use of automated implantable cardioverter defibrillators (AICDs) has been rapidly increasing since the results of several randomized trials confirmed the efficacy of AICDs in the secondary and primary prevention of sudden cardiac death. Patients with AICDs require high-quality care and intense follow-up to ensure safe and effective device performance. According to international guidelines these patients should be followed at 1- to 4 month intervals, depending on the device model and the patient’s clinical status (Schoenfeld, 2004). Given the expanding indications for use and the complexity of these devices, there is an urgent need to develop new means of …

Investigation Of The Effects Of A Violence Prevention Program In Reducing Kindergarten-Aged Children's Self-Reported Aggresive Behaviors, David Jack, Phd, Rn, Cpn, Cne

College of Nursing Faculty Papers & Presentations

The purpose of this study was to explore the effective of a violence prevention program on reducing self-reported acts of aggressive behaviors in kindergarten-aged children. Aggression and violence are health concerns that can have a negative impact on an individual's sense of well-being.