Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 43

Full-Text Articles in Medicine and Health Sciences

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown Dec 2012

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …


Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader Dec 2012

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …


Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown Dec 2012

Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown

Dr Robert Brown

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a …


Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk Nov 2012

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …


Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …


Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo Oct 2012

Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …


Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo Oct 2012

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …


An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano Oct 2012

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …


Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer Oct 2012

Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer

Gyongyi Szabo

The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of …


Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc Oct 2012

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …


Thirty-Year (1975 To 2005) Trends In The Incidence Rates, Clinical Features, Treatment Practices, And Short-Term Outcomes Of Patients [Less Than] 55 Years Of Age Hospitalized With An Initial Acute Myocardial Infarction, David Mcmanus, Stephen Piacentine, Darleen Lessard, Joel Gore, Jorge Yarzebski, Frederick Spencer, Robert Goldberg Sep 2012

Thirty-Year (1975 To 2005) Trends In The Incidence Rates, Clinical Features, Treatment Practices, And Short-Term Outcomes Of Patients [Less Than] 55 Years Of Age Hospitalized With An Initial Acute Myocardial Infarction, David Mcmanus, Stephen Piacentine, Darleen Lessard, Joel Gore, Jorge Yarzebski, Frederick Spencer, Robert Goldberg

Jorge L. Yarzebski

Sparse data are available describing recent trends in the magnitude, clinical features, treatment practices, and outcomes of comparatively young adults hospitalized with acute myocardial infarction (AMI). The objectives of this population-based study were to describe 3 decade-long trends (1975 to 2005) in these end points in adults 1,703 residents of the Worcester (Massachusetts) metropolitan area 25 to 54 years of age who were hospitalized with initial AMIs at all central Massachusetts medical centers during 15 annual periods from 1975 through 2005. Overall hospital incidence rate (per 100,000 residents) of initial AMI in our study population was 66 (95% confidence interval …


Six-Month Mortality And Cardiac Catheterization In Non-St-Segment Elevation Myocardial Infarction Patients With Anemia, Wen-Chih Wu, Molly Waring, Darleen Lessard, Jorge Yarzebski, Joel Gore, Robert Goldberg Sep 2012

Six-Month Mortality And Cardiac Catheterization In Non-St-Segment Elevation Myocardial Infarction Patients With Anemia, Wen-Chih Wu, Molly Waring, Darleen Lessard, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: It is unknown how anemia influences the invasive management of patients with non-ST-segment elevation myocardial infarction (NSTEMI) and associated mortality. We investigated whether receipt of cardiac catheterization relates to 6-month death rates among patients with different severity of anemia. METHODS: We used data from the population-based Worcester Heart Attack Study, which included 2634 patients hospitalized with confirmed NSTEMI, from three percutaneous coronary intervention-capable medical centers in the Worcester (Massachusetts, U.S.A.) metropolitan area, during five biennial periods between 1997 and 2005. Severity of anemia was categorized using admission hematocrit levels: less than or equal to 30.0% (moderate-to-severe anemia), 30.1-39.0% (mild …


Milwaukee Police Department Retirees: Cardiovascular Disease Risk And Morbidity Among Aging Law Enforcement Officers, Sandra Ramey, Nancy Downing, W. Franke Sep 2012

Milwaukee Police Department Retirees: Cardiovascular Disease Risk And Morbidity Among Aging Law Enforcement Officers, Sandra Ramey, Nancy Downing, W. Franke

Nancy R Downing

This study explored the self-reported prevalence of cardiovascular disease (CVD) and accompanying risk factors among 165 male retirees 43 years and older (M = 56.2, SD = 7.1) from the Milwaukee Police Department (MPD) compared to 671 individuals of similar age and income who responded to the 2005 Wisconsin Behavioral Risk Factor Surveillance System (BRFSS). CVD and other risk factors were more prevalent in the MPD retirees than the general population (CVD 15.2% vs. 9.5%, p = .036; hypertension 51.5% vs. 36.2%, p = .001; hypercholesterolemia 62.4% vs. 44.4%, p = .001; overweight and obesity 85.1% vs. 74.7%, p = …


Exploring Differences Between Community-Based Women And Men With A History Of Mental Illness, Cheryl Forchuk, Elsabeth Jensen, Rick Csiernik, Catherine Ward-Griffin, Susan Ray, Phyllis Montgomery, Linda Wan Aug 2012

Exploring Differences Between Community-Based Women And Men With A History Of Mental Illness, Cheryl Forchuk, Elsabeth Jensen, Rick Csiernik, Catherine Ward-Griffin, Susan Ray, Phyllis Montgomery, Linda Wan

Rick Csiernik

Relatively little is understood concerning the role of gender in persons with a history of mental illness residing in the community. This paper aims to explore gender's effect using data from the Community Research University Alliance project entitled, Mental Health and Housing. The primary five-year longitudinal study examined housing situations for psychiatric consumer/survivors in a mid-size, central Canadian region in an effort to improve the number and quality of appropriate housing situations. Data from 887 subjects in the original research underwent secondary analysis with particular relevance to differences between gender and indicators of health status including psychiatric history, levels of …


Diversity And Homelessness: Minorities And Psychiatric Survivors, Cheryl Forchuk, Elsabeth Jensen, Rick Csiernik, Carolyn Gorlick, Susan Ray, Helene Berman, Pamela Mckane, Libbey Joplin Aug 2012

Diversity And Homelessness: Minorities And Psychiatric Survivors, Cheryl Forchuk, Elsabeth Jensen, Rick Csiernik, Carolyn Gorlick, Susan Ray, Helene Berman, Pamela Mckane, Libbey Joplin

Rick Csiernik

No abstract provided.


Immune Responses In Cystic Fibrosis: Are They Intrinsically Defective?, Dmitry Ratner, Christian Mueller Aug 2012

Immune Responses In Cystic Fibrosis: Are They Intrinsically Defective?, Dmitry Ratner, Christian Mueller

Christian Mueller

Cystic fibrosis (CF), the most common lethal single-gene disorder affecting Northern Europeans and North Americans, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cftr is a chloride channel and a regulator of other ion channels, and many aspects of the CF phenotype are directly related to ion channel abnormalities attributable to CFTR mutation. Lung disease is the most common limitation to the quantity and quality of life for patients with CF. One aspect that continues to be enigmatic is the observed alterations in innate and adaptive immune responses to certain pathogens. Altered responses to Pseudomonas …


Tubercular Pancreatic Abscess Presenting As Fever And Cystic Pancreatic Lesion With Endoscopic Management., Jonathan Fenkel, Maya Spodik, Bheema Singu, Anthony Infantolino, Sandeep Deshmukh, David Loren Aug 2012

Tubercular Pancreatic Abscess Presenting As Fever And Cystic Pancreatic Lesion With Endoscopic Management., Jonathan Fenkel, Maya Spodik, Bheema Singu, Anthony Infantolino, Sandeep Deshmukh, David Loren

Sandeep Deshmukh

Isolated pancreatic tuberculosis is a rare presentation of tubercular infection. There are few reported cases of pancreatic tuberculosis diagnosed by endoscopic ultrasound with fine-needle aspiration (EUS FNA), though EUS is often used in the evaluation of pancreatic cystic lesions. We present a case of a tubercular pancreatic abscess presenting as a cystic lesion in a patient with undiagnosed immunodeficiency. The abscess was aspirated by EUS FNA and treated with endoscopic drainage and anti-mycobacterial medications.


A Prospective Study Of The Rate Of Progression In Compensated, Histologically Advanced Chronic Hepatitis C, Jules Dienstag, Marc Ghany, Timothy Morgan, Adrian Di Bisceglie, Herbert Bonkovsky, Hae-Young Kim, Leonard Seeff, Gyongyi Szabo, Elizabeth Wright, Richard Sterling, Gregory Everson, Karen Lindsay, William Lee, Anna Lok, Chihiro Morishima, Anne Stoddard, James Everhart Jul 2012

A Prospective Study Of The Rate Of Progression In Compensated, Histologically Advanced Chronic Hepatitis C, Jules Dienstag, Marc Ghany, Timothy Morgan, Adrian Di Bisceglie, Herbert Bonkovsky, Hae-Young Kim, Leonard Seeff, Gyongyi Szabo, Elizabeth Wright, Richard Sterling, Gregory Everson, Karen Lindsay, William Lee, Anna Lok, Chihiro Morishima, Anne Stoddard, James Everhart

Gyongyi Szabo

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes …


The Associations Between Victimization, Feeling Unsafe, And Asthma Episodes Among Us High-School Students, Monica Swahn, Robert Bossarte May 2012

The Associations Between Victimization, Feeling Unsafe, And Asthma Episodes Among Us High-School Students, Monica Swahn, Robert Bossarte

Monica H. Swahn

We examined the associations between victimization, missed school because of feeling unsafe, and asthma episodes among US high-school students using the 2003 Youth Risk Behavior Survey. Cross-sectional analyses on adolescents with asthma (n=1943) showed that any victimization and missed school because of feeling unsafe significantly increased the odds of having an asthma episode in the past year (adjusted odds ratio [OR]=1.45; 95% confidence interval [CI] = 1.07, 1.95 and adjusted OR = 2.93; 95% CI = 1.90, 4.53, respectively). Victimization and feeling unsafe are important but poorly understood risk factors for asthma.


A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski Apr 2012

A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski

Vladimir Torchilin

A variety of DNA vaccine prime and recombinant viral boost immunization strategies have been developed to enhance immune responses in humans, but inherent limitations to these strategies exist. There is still an overwhelming need to develop safe and effective approaches that raise broad humoral and T cell-mediated immune responses systemically and on mucosal surfaces. We have developed a novel mucosal immunization regimen that precludes the use of viral vectors yet induces potent T cell responses. Using hepatitis B surface Ag (HBsAg), we observed that vaccination of BALB/c mice with an i.m. HBsAg-DNA vaccine prime followed by an intranasal boost with …


Long-Stay Patients In State Psychiatric Hospitals At The End Of The 20th Century, William Fisher, Paul Barreira, Jeffrey Geller, Andrew White, Alisa Lincoln, Marylou Sudders Apr 2012

Long-Stay Patients In State Psychiatric Hospitals At The End Of The 20th Century, William Fisher, Paul Barreira, Jeffrey Geller, Andrew White, Alisa Lincoln, Marylou Sudders

Alisa Lincoln

OBJECTIVES: The purpose of this study was to assess the characteristics of long-stay patients in contemporary state psychiatric hospitals and to identify factors representing possible barriers to alternative placements for these patients. METHODS: All patients in inpatient units of the Massachusetts Department of Mental Health who had been hospitalized for at least three years as of April 1, 1999, were assessed by their treatment teams with a standardized data collection instrument. Domains assessed included medical problems, need for nursing care, psychiatric diagnosis, and history of problematic behaviors. RESULTS: The 330 individuals identified as long-stay patients had an array of medical …


Insurance Status And Length Of Stay For Involuntarily Hospitalized Patients, William Fisher, Paul Barreira, Alisa Lincoln, Lorna Simon, Andrew White, Kristen Roy-Bujnowski, Marylou Sudders Apr 2012

Insurance Status And Length Of Stay For Involuntarily Hospitalized Patients, William Fisher, Paul Barreira, Alisa Lincoln, Lorna Simon, Andrew White, Kristen Roy-Bujnowski, Marylou Sudders

Alisa Lincoln

General and private psychiatric hospitals are becoming increasingly common as sites for involuntary hospitalization. Unlike the public facilities that these settings are supplanting, these hospitals must pay strict attention to issues associated with reimbursement, insurance status, and managed care. This article examines the effects of insurance status on length of stay for involuntarily hospitalized patients in general and private hospitals in Massachusetts. Using a two-stage sampling procedure, data on episodes of involuntary hospitalization were gathered and assessed using multiple regression. The primary effect was found between patients with Medicare, who had the longest stays, and individuals who were uninsured, who …


A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski Apr 2012

A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski

Tatyana Levchenko

A variety of DNA vaccine prime and recombinant viral boost immunization strategies have been developed to enhance immune responses in humans, but inherent limitations to these strategies exist. There is still an overwhelming need to develop safe and effective approaches that raise broad humoral and T cell-mediated immune responses systemically and on mucosal surfaces. We have developed a novel mucosal immunization regimen that precludes the use of viral vectors yet induces potent T cell responses. Using hepatitis B surface Ag (HBsAg), we observed that vaccination of BALB/c mice with an i.m. HBsAg-DNA vaccine prime followed by an intranasal boost with …


Validation Of The Chads2 Clinical Prediction Rule To Predict Ischaemic Stroke. A Systematic Review And Meta-Analysis., Claire Keogh, Emma Wallace, Ciara Dillon, Borislav Dimitrov, Tom Fahey Apr 2012

Validation Of The Chads2 Clinical Prediction Rule To Predict Ischaemic Stroke. A Systematic Review And Meta-Analysis., Claire Keogh, Emma Wallace, Ciara Dillon, Borislav Dimitrov, Tom Fahey

Borislav D Dimitrov

The CHADS2 predicts annual risk of ischaemic stroke in non-valvular atrial fibrillation. This systematic review and meta-analysis aims to determine the predictive value of CHADS2. The literature was systematically searched from 2001 to October 2010. Data was pooled and analysed using discrimination and calibration statistical measures, using a random effects model. Eight data sets (n = 2815) were included. The diagnostic accuracy suggested a cut-point of ≥ 1 has higher sensitivity (92%) than specificity (12%) and a cut-point of ≥ 4 has higher specificity (96%) than sensitivity (33%). Lower summary estimates were observed for cut-points ≥ 2 (sensitivity 79%, specificity …


Predicting Streptococcal Pharyngitis In Adults In Primary Care: A Systematic Review Of The Diagnostic Accuracy Of Symptoms And Signs And Validation Of The Centor Score., Jolien Aalbers, Kirsty O'Brien, Wai-Sun Chan, Gavin Falk, Conor Teljeur, Borislav Dimitrov, Tom Fahey Mar 2012

Predicting Streptococcal Pharyngitis In Adults In Primary Care: A Systematic Review Of The Diagnostic Accuracy Of Symptoms And Signs And Validation Of The Centor Score., Jolien Aalbers, Kirsty O'Brien, Wai-Sun Chan, Gavin Falk, Conor Teljeur, Borislav Dimitrov, Tom Fahey

Borislav D Dimitrov

BACKGROUND: Stratifying patients with a sore throat into the probability of having an underlying bacterial or viral cause may be helpful in targeting antibiotic treatment. We sought to assess the diagnostic accuracy of signs and symptoms and validate a clinical prediction rule (CPR), the Centor score, for predicting group A β-haemolytic streptococcal (GABHS) pharyngitis in adults (> 14 years of age) presenting with sore throat symptoms. METHODS: A systematic literature search was performed up to July 2010. Studies that assessed the diagnostic accuracy of signs and symptoms and/or validated the Centor score were included. For the analysis of the diagnostic …


Parameters For Establishing Humanized Mouse Models To Study Human Immunity: Analysis Of Human Hematopoietic Stem Cell Engraftment In Three Immunodeficient Strains Of Mice Bearing The Il2rgamma(Null) Mutation, Michael Brehm, Amy Cuthbert, Chaoxing Yang, David Miller, Philip Diiorio, Joseph Laning, Lisa Burzenski, Bruce Gott, Oded Foreman, Anoop Kavirayani, Mary Herlihy, Aldo Rossini, Leonard Shultz, Dale Greiner Mar 2012

Parameters For Establishing Humanized Mouse Models To Study Human Immunity: Analysis Of Human Hematopoietic Stem Cell Engraftment In Three Immunodeficient Strains Of Mice Bearing The Il2rgamma(Null) Mutation, Michael Brehm, Amy Cuthbert, Chaoxing Yang, David Miller, Philip Diiorio, Joseph Laning, Lisa Burzenski, Bruce Gott, Oded Foreman, Anoop Kavirayani, Mary Herlihy, Aldo Rossini, Leonard Shultz, Dale Greiner

Philip J diIorio Jr

"Humanized" mouse models created by engraftment of immunodeficient mice with human hematolymphoid cells or tissues are an emerging technology with broad appeal across multiple biomedical disciplines. However, investigators wishing to utilize humanized mice with engrafted functional human immune systems are faced with a myriad of variables to consider. In this study, we analyze HSC engraftment methodologies using three immunodeficient mouse strains harboring the IL2rgamma(null) mutation; NOD-scid IL2rgamma(null), NOD-Rag1(null) IL2rgamma(null), and BALB/c-Rag1(null) IL2rgamma(null) mice. Strategies compared engraftment of human HSC derived from umbilical cord blood following intravenous injection into adult mice and intracardiac and intrahepatic injection into newborn mice. We observed …


Human Immune System Development And Rejection Of Human Islet Allografts In Spontaneously Diabetic Nod-Rag1null Il2rgammanull Ins2akita Mice, Michael Brehm, Rita Bortell, Philip Diiorio, Jean Leif, Joseph Laning, Amy Cuthbert, Chaoxing Yang, Mary Herlihy, Lisa Burzenski, Bruce Gott, Oded Foreman, Alvin Powers, Dale Greiner, Leonard Shultz Mar 2012

Human Immune System Development And Rejection Of Human Islet Allografts In Spontaneously Diabetic Nod-Rag1null Il2rgammanull Ins2akita Mice, Michael Brehm, Rita Bortell, Philip Diiorio, Jean Leif, Joseph Laning, Amy Cuthbert, Chaoxing Yang, Mary Herlihy, Lisa Burzenski, Bruce Gott, Oded Foreman, Alvin Powers, Dale Greiner, Leonard Shultz

Philip J diIorio Jr

OBJECTIVE: To create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system.

RESEARCH DESIGN AND METHODS: We backcrossed the Ins2(Akita) mutation onto the NOD-Rag1(null) IL2rgamma(null) strain and determined 1) the spontaneous development of hyperglycemia, 2) the ability of human islets, mouse islets, and dissociated mouse islet cells to restore euglycemia, 3) the generation of a human immune system following engraftment of human hematopoietic stem cells, and 4) the ability of the humanized mice to reject human islet …


A Zebrafish Unc-45-Related Gene Expressed During Muscle Development, Letitiah Etheridge, Philip Diiorio, Charles Sagerstrom Mar 2012

A Zebrafish Unc-45-Related Gene Expressed During Muscle Development, Letitiah Etheridge, Philip Diiorio, Charles Sagerstrom

Philip J diIorio Jr

We report the isolation and expression pattern of zebrafish unc45r, a gene related to Caenorhabditis elegans unc-45. UNC-45 is a muscle-specific protein thought to interact with myosin and promote the assembly of muscle thick filaments during C. elegans development. Zebrafish Unc45r shares sequence features with C. elegans UNC-45, including three tetratricopeptide repeats and a CRO1/She4p homology domain. unc45r is expressed in mesoderm adjacent to the dorsal midline during late gastrula stages and is coexpressed with muscle specific genes in somitic mesoderm during development of trunk skeletal muscle. unc45r is also expressed in cranial skeletal muscle as well as in cardiac …


Patterns And Predictors Of Mammography Utilization Among Breast Cancer Survivors, Chyke Doubeni, Terry Field, Marianne Yood, Sharon Rolnick, Charles Quessenberry, Hassan Fouayzi, Jerry Gurwitz, Feifei Wei Jan 2012

Patterns And Predictors Of Mammography Utilization Among Breast Cancer Survivors, Chyke Doubeni, Terry Field, Marianne Yood, Sharon Rolnick, Charles Quessenberry, Hassan Fouayzi, Jerry Gurwitz, Feifei Wei

Chyke A. Doubeni

BACKGROUND: Improvements in cancer detection and treatment have resulted in increasing numbers of breast cancer survivors. Information regarding the use of mammography by breast cancer survivors is limited. METHODS: The use of surveillance mammography was examined over a 5-year period in a retrospective cohort of women age>or=55 years who were diagnosed with incident primary breast cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated health systems. RESULTS: Of the 797 women included in the study, 80% (n=636) underwent mammograms during the first year after treatment for breast cancer. The percentage of women having mammograms during each yearly …


Perceived Accessibility As A Predictor Of Youth Smoking, Chyke Doubeni, Wenjun Li, Hassan Fouayzi, Joseph Difranza Jan 2012

Perceived Accessibility As A Predictor Of Youth Smoking, Chyke Doubeni, Wenjun Li, Hassan Fouayzi, Joseph Difranza

Chyke A. Doubeni

PURPOSE: Youths who smoke are more likely to perceive that cigarettes are easily accessible, but the relationship between perceived accessibility of cigarettes and the risk of smoking is not clear. The objective of this study was to determine whether perceived accessibility predicted future smoking among youths. METHODS: This study used data from the second Development and Assessment of Nicotine Dependence in Youth (DANDY-2) study, a 4-year (2002-2006) cohort study that began with 1,246 sixth-grade students in 6 Massachusetts communities. DANDY-2 comprised 11 waves of in-person interviews. A total of 1,195 students who were aged 11 to 14 years at the …