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Full-Text Articles in Medicine and Health Sciences
Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo
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
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
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
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 …
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
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
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
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 …
Immune Responses In Cystic Fibrosis: Are They Intrinsically Defective?, Dmitry Ratner, Christian Mueller
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 …
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
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 …
Treatment Practices And Outcomes Of Patients With Established Peripheral Arterial Disease Hospitalized With Acute Myocardial Infarction In A Community Setting, Frederick Spencer, Darleen Lessard, Chyke Doubeni, Jorge Yarzebski, Joel Gore, Robert Goldberg
Treatment Practices And Outcomes Of Patients With Established Peripheral Arterial Disease Hospitalized With Acute Myocardial Infarction In A Community Setting, Frederick Spencer, Darleen Lessard, Chyke Doubeni, Jorge Yarzebski, Joel Gore, Robert Goldberg
Chyke A. Doubeni
BACKGROUND: There are little contemporary data available describing the hospital and long-term outcomes of patients with peripheral arterial disease (PAD) who are hospitalized with acute myocardial infarction (AMI). The objectives of our population-based study were to examine the hospital and long-term outcomes, as well as the use of different treatment practices, among patients with established PAD who were hospitalized with AMI. METHODS: The study sample consisted of 4480 patients hospitalized with AMI at all Worcester, Mass, medical centers in 4 alternate years between 1997 and 2003. RESULTS: Among the metropolitan Worcester residents hospitalized with AMI, 13.5% had a history of …
A 25-Year Perspective Into The Changing Landscape Of Patients Hospitalized With Acute Myocardial Infarction (The Worcester Heart Attack Study), Robert Goldberg, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Joseph Alpert, James Dalen
A 25-Year Perspective Into The Changing Landscape Of Patients Hospitalized With Acute Myocardial Infarction (The Worcester Heart Attack Study), Robert Goldberg, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Joseph Alpert, James Dalen
Jorge L. Yarzebski
Over the past several decades, significant advances have been made in the primary and secondary prevention of coronary artery disease. However, effects of changing lifestyle and treatment practices on demographic and clinical profiles and on hospital outcomes of patients who present with acute myocardial infarction (AMI) have not been well characterized. We carried out a prospective population-based investigation of >25-year trends (1975 to 2001) in demographic and clinical characteristics, treatment practices, and hospital outcomes of patients who had been hospitalized with AMI. Residents of a metropolitan area (Worcester, Massachusetts) who had been hospitalized with validated AMI (n = 10,440) in …