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Full-Text Articles in Life Sciences

Survival Of Eastern Oysters Crassostrea Virginica From Three Lines Following Experimental Challenge With Bacterial Pathogens, Javier Gomez-Leon, Luisa Villamil, Scott A. Salger, Rachel Sallum, Antonio Remacha-Trivino, Dale F. Leavitt, Marta Gomez-Chiarri Dec 2012

Survival Of Eastern Oysters Crassostrea Virginica From Three Lines Following Experimental Challenge With Bacterial Pathogens, Javier Gomez-Leon, Luisa Villamil, Scott A. Salger, Rachel Sallum, Antonio Remacha-Trivino, Dale F. Leavitt, Marta Gomez-Chiarri

Marta Gomez-Chiarri

Shellfish production is often affected by bacterial pathogens that cause high losses in hatcheries and nurseries. We evaluated the relative survival of larvae and juveniles of 3 Crassostrea virginica oyster lines: (1) GHP, a Rhode Island line; (2) NEHY, a line resistant to dermo and multinucleated sphere X diseases; and (3) FLOWERS, a line resistant to Roseovarius oyster disease, experimental challenge with Vibrio spp. isolates RE22 and RE101, causative agents of bacillary necrosis in Pacific oyster larvae, and the type strain of Roseovarius crassostreae, causative agent of Roseovarius oyster disease. All of the isolates were able to induce significant mortalities …


Infectious Necrotizing Enteritis And Mortality Caused By Vibrio Carachariae In Summer Flounder Paralichthys Dentatus During Intensive Culture, Bruno Soffientino, Todd Gwaltney, David R. Nelson, Jennifer L. Specker, Michael Mauel, Marta Gomez-Chiarri Dec 2012

Infectious Necrotizing Enteritis And Mortality Caused By Vibrio Carachariae In Summer Flounder Paralichthys Dentatus During Intensive Culture, Bruno Soffientino, Todd Gwaltney, David R. Nelson, Jennifer L. Specker, Michael Mauel, Marta Gomez-Chiarri

Marta Gomez-Chiarri

An epizootic causing mortality among cultured summer flounder Paralichthys dentatus occurred in summer of 1998 at a land-based facility on Narragansett Bay, Rhode Island, USA. The disease, flounder infectious necrotizing enteritis (FINE), was characterized by reddening around the anal area, distended abdomens filled with opaque serosanguineous fluid, enteritis and necrosis of the posterior intestine. In extreme cases of the disease, the posterior intestine was detached from the anus and was observed coming out the vent. The intestine of individuals that recovered from the dsease ended in a blind-sac; the abdomens of these fish were distended, due to food and water …


Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson Dec 2012

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …


أمراض الأطفال المزمنة, Suad Fahad Alferaih Dec 2012

أمراض الأطفال المزمنة, Suad Fahad Alferaih

Dr. Suad Fahad AlFuraih

No abstract provided.


Investigating The Antimalarial Action Of 1,2,4-Trioxolanes With Fluorescent Chemical Probes, Carmony L. Hartwig, Erica M. W. Lauterwasser, Sumit S. Mahajan, Jonathan M. Hoke, Roland Cooper, Adam R. Renslo Dec 2012

Investigating The Antimalarial Action Of 1,2,4-Trioxolanes With Fluorescent Chemical Probes, Carmony L. Hartwig, Erica M. W. Lauterwasser, Sumit S. Mahajan, Jonathan M. Hoke, Roland Cooper, Adam R. Renslo

Roland A. Cooper

The 1,2,4-trioxolanes are a new class of synthetic peroxidic antimalarials currently in human clinical trials. The well known reactivity of the 1,2,4-trioxolane ring towards inorganic ferrous iron and ferrous iron heme is proposed to play a role in the antimalarial action of this class of compounds. We have designed structurally relevant fluorescent chemical probes to study the sub-cellular localization of 1,2,4-trioxolanes in cultured Plasmodium falciparum parasites. Microscopy experiments revealed that a probe fluorescently labeled on the adamantane ring accumulated specifically in digestive vacuole-associated neutral lipid bodies within the parasite while an isosteric, but non-peroxidic congener did not. Probes fluorescently labeled …


Artemether-Lumefantrine Selects For Malaria Parasites With Decreased Lumefantrine Sensitivity Although Parasites Remain Sensitive To This Regimen In Tororo, Uganda, P. Tumwebaze, J. Bloome, O. Byaruhanga, C. Nakazibwe, A. Walakira, J. Okiring, S. L. Nsobya, Roland A. Cooper, P. J. Rosenthal Nov 2012

Artemether-Lumefantrine Selects For Malaria Parasites With Decreased Lumefantrine Sensitivity Although Parasites Remain Sensitive To This Regimen In Tororo, Uganda, P. Tumwebaze, J. Bloome, O. Byaruhanga, C. Nakazibwe, A. Walakira, J. Okiring, S. L. Nsobya, Roland A. Cooper, P. J. Rosenthal

Roland A. Cooper

Artemisinin-based combination therapies (ACTs) may select for malaria parasites with decreased drug sensitivity. We studied the sensitivity of parasites from children enrolled in treatment and prevention trials in Tororo, Uganda from June, 2010 to February, 2012. When Plasmodium falciparum malaria was diagnosed, blood was obtained, parasites (286 isolates) were cultured with serial dilutions of chloroquine (CQ), monodesethylamodiaquine (AQ), quinine (QN), dihydroartemisinin (DHA), lumefantrine (LM), or piperaquine (PQ) for 72 h, and ex vivo sensitivities were assessed by HRP-2-based ELISA. Sensitivities (nM) to CQ (median IC50 486.2; IQR 206.5-748.8), AQ (83.3; 58.4-132.4), PQ (20.3; 7.6-47.5) and QN (126.4; 74.9-196.3) varied widely; …


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 …


Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak Oct 2012

Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak

Gyongyi Szabo

Inflammation is a common element in the pathogenesis of most chronic liver diseases that lead to fibrosis and cirrhosis. Inflammation is characterized by activation of innate immune cells and production of pro-inflammatory cytokines IL-1alpha, IL-1beta, and TNFalpha. Inflammasomes are intracellular multiprotein complexes expressed in both parenchymal and non-parenchymal cells of the liver that in response to cellular danger signals activate caspase-1, and release IL-1beta and IL-18. The importance of inflammasome activation in various forms of liver diseases in relation to liver damage, steatosis, inflammation and fibrosis is discussed in this review. Elsevier B.V. All rights reserved.


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 …


Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock Oct 2012

Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock

Gyongyi Szabo

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, …


Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo Oct 2012

Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo

Gyongyi Szabo

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFNalpha induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNalpha production. Depletion of pDCs from PBMCs attenuated IFNalpha release and purified pDCs produced high levels of IFNalpha after co-culture with FL replicons or JFH-1 …


Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo Oct 2012

Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of proinflammatory cytokines, including IL-1beta. IL-1beta, type I IL-1 receptor (IL-1R1), and IL-1 receptor antagonist (IL-1Ra) are all important regulators of the IL-1 signaling complex, which plays a role in inflammation. Furthermore, IL-1beta maturation is dependent on caspase-1 (Casp-1). Using IL-1Ra-treated mice as well as 3 mouse models deficient in regulators of IL-1beta activation (Casp-1 and ASC) or signaling (IL-1R1), we found that IL-1beta signaling is required for the development of alcohol-induced liver steatosis, inflammation, and injury. Increased IL-1beta was due to upregulation of Casp-1 activity and inflammasome activation. The …


Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo Oct 2012

Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo

Gyongyi Szabo

AIM: To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide (LPS)-induced stimulation in the liver. METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5 mug/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the liver led to activation of the inflammasome, real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the protein …


Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …


The Molecular Basis Of Drug Resistance Against Hepatitis C Virus Ns3/4a Protease Inhibitors, Keith Romano, Akbar Ali, Cihan Aydin, Djade Soumana, Aysegul Ozen, Laura Deveau, Casey Silver, Hong Cao, Alicia Newton, Christos Petropoulos, Wei Huang, Celia Schiffer Oct 2012

The Molecular Basis Of Drug Resistance Against Hepatitis C Virus Ns3/4a Protease Inhibitors, Keith Romano, Akbar Ali, Cihan Aydin, Djade Soumana, Aysegul Ozen, Laura Deveau, Casey Silver, Hong Cao, Alicia Newton, Christos Petropoulos, Wei Huang, Celia Schiffer

Celia A. Schiffer

Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer …


Red Blood Cell Aggregation Parameters Measured By Capillary Tube Aggregometer Using Venous And Capillary Blood Samples, Michael Simmonds, R. Christy, Sonya Marshall-Gradisnik, Herbert Meiselman, Oguz Baskurt Oct 2012

Red Blood Cell Aggregation Parameters Measured By Capillary Tube Aggregometer Using Venous And Capillary Blood Samples, Michael Simmonds, R. Christy, Sonya Marshall-Gradisnik, Herbert Meiselman, Oguz Baskurt

Sonya Marshall-Gradisnik

The extent of red blood cell (RBC) aggregation has widely been accepted as a reliable indicator of inflammatory processes. The ability to measure RBC aggregation indexes in capillary blood samples may simplify the application of the test and may bring advantages in its clinical usage as well as application in field studies. This study compared RBC aggregation indexes measured in venous and capillary blood samples using a newly developed capillary tube aggregometer. Although strong correlations between agreegation indexes measured in capillary and venous samples were detected, the indexes measure in venous samples were higher compared to capillary samples, thus indicating …


First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris Sep 2012

First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris

Celia A. Schiffer

APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions …


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 …


Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo Jul 2012

Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of pro-inflammatory cytokines, including interleukin (IL)-1β. IL-1β, Type-I IL-1 receptor (IL1R1) and IL-1 receptor antagonist (IL-1Ra) are all part of the IL-1 superfamily that play a role in inflammation. IL-1β maturation is dependent on Caspase-1. Using wild-type (WT), Caspase-1-, IL-1R1- and IL-1Ra deficient mice fed with Lieber-DeCarli alcohol or control diet, we have identified that signaling mediated by the active IL-1β was required for development of alcohol-induced steatosis, inflammation and injury. Increased IL-1β was due to upregulation of Caspase-1 activity and inflammatory activation. The pathogenic role of IL-1 signaling in …


Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnα, Shuye Zhang, Karen Kodys, Gyongyi Szabo Jul 2012

Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnα, Shuye Zhang, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between pDCs and HCV-infected cells was required for IFNα induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNα production. Depletion of pDCs from PBMCs attenuated IFNα release and purified pDCs produced high levels of IFNα after co-culture with FL replicons or JFH-1 infected cells. IFNα …


Inhibition Of Tlr8- And Tlr4-Induced Type I Ifn Induction By Alcohol Is Different From Its Effects On Inflammatory Cytokine Production In Monocytes, Maoyin Pang, Shashi Bala, Karen Kodys, Donna Catalano, Gyongyi Szabo Jul 2012

Inhibition Of Tlr8- And Tlr4-Induced Type I Ifn Induction By Alcohol Is Different From Its Effects On Inflammatory Cytokine Production In Monocytes, Maoyin Pang, Shashi Bala, Karen Kodys, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Prolonged alcohol consumption is a significant co-factor in the progression of chronic viral infections including hepatitis C and HIV, which are both single-stranded RNA viruses. Toll like receptor 8 (TLR8), a pattern recognition receptor expressed in monocytes, senses viral single stranded RNA as a danger signal and leads to the induction of Type I interferon (IFN) as well as the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha). Lipopolysaccharide (LPS), a Toll like receptor 4 (TLR4) ligand, was shown to affect inflammatory cell activation after alcohol consumption and in HIV and HCV infections. Here we hypothesized that alcohol exposure …


Myxoma Virus Induces Type I Interferon Production In Murine Plasmacytoid Dendritic Cells Via A Tlr9/Myd88-, Irf5/Irf7-, And Ifnar-Dependent Pathway, Peihong Dai, Hua Cao, Taha Merghoub, Francesca Avogadri, Weiyi Wang, Tanvi Parikh, Chee-Mun Fang, Paula M. Pitha, Katherine A. Fitzgerald, Masmudur M. Rahman, Grant Mcfadden, Xiaoyu Hu, Alan N. Houghton, Stewart Shuman, Liang Deng Jul 2012

Myxoma Virus Induces Type I Interferon Production In Murine Plasmacytoid Dendritic Cells Via A Tlr9/Myd88-, Irf5/Irf7-, And Ifnar-Dependent Pathway, Peihong Dai, Hua Cao, Taha Merghoub, Francesca Avogadri, Weiyi Wang, Tanvi Parikh, Chee-Mun Fang, Paula M. Pitha, Katherine A. Fitzgerald, Masmudur M. Rahman, Grant Mcfadden, Xiaoyu Hu, Alan N. Houghton, Stewart Shuman, Liang Deng

Katherine A. Fitzgerald

Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells. Myxoma virus is a rabbit poxvirus that belongs to the Leporipoxvirus genus. It causes a lethal disease called myxomatosis in European rabbits but cannot sustain any detectable infection in nonlagomorphs. Vaccinia virus is a prototypal orthopoxvirus that was used as a vaccine to eradicate smallpox. Myxoma virus is nonpathogenic in mice, whereas systemic infection with vaccinia virus can be lethal even in immunocompetent mice. Plasmacytoid dendritic cells (pDCs) are potent type I interferon (IFN)-producing cells that play important roles in antiviral innate immunity. How poxviruses are sensed …


A Novel Role For The Nlrc4 Inflammasome In Mucosal Defenses Against The Fungal Pathogen Candida Albicans, Jeffrey Tomalka, Sandhya Ganesan, Elaheh Azodi, Krupen Patel, Parth Majmudar, Brian A. Hall, Katherine A. Fitzgerald, Amy G. Hise Jul 2012

A Novel Role For The Nlrc4 Inflammasome In Mucosal Defenses Against The Fungal Pathogen Candida Albicans, Jeffrey Tomalka, Sandhya Ganesan, Elaheh Azodi, Krupen Patel, Parth Majmudar, Brian A. Hall, Katherine A. Fitzgerald, Amy G. Hise

Katherine A. Fitzgerald

Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1beta production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell …


Pattern Recognition Receptors And The Innate Immune Response To Viral Infection, Mikayla R. Thompson, John J. Kaminski Iii, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald Jul 2012

Pattern Recognition Receptors And The Innate Immune Response To Viral Infection, Mikayla R. Thompson, John J. Kaminski Iii, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald

Katherine A. Fitzgerald

The innate immune response to viral pathogens is critical in order to mobilize protective immunity. Cells of the innate immune system detect viral infection largely through germline-encoded pattern recognition receptors (PRRs) present either on the cell surface or within distinct intracellular compartments. These include the Toll-like receptors (TLRs), the retinoic acid-inducble gene I-like receptors (RLRs), the nucleotide oligomerization domain-like receptors (NLRs, also called NACHT, LRR and PYD domain proteins) and cytosolic DNA sensors. While in certain cases viral proteins are the trigger of these receptors, the predominant viral activators are nucleic acids. The presence of viral sensing PRRs in multiple …


A Cluster-Based Approach For Biological Hypothesis Testing And Its Application, Ahmed Mustafa Jun 2012

A Cluster-Based Approach For Biological Hypothesis Testing And Its Application, Ahmed Mustafa

Ahmed Mustafa Dr.

No abstract provided.


Hepatitis C Screening And Testing: A Call For A National Response., Donna M. Zucker Rn, Phd, Faan Jun 2012

Hepatitis C Screening And Testing: A Call For A National Response., Donna M. Zucker Rn, Phd, Faan

Donna M. Zucker

The purpose of this brief is to convey the immediate need to coordinate and integrate hepatitis C virus (HCV) screening and testing for HIV co-infected and HCV infected clients, into primary care. In 2000, 1.25 million persons were estimated to be chronically infected with hepatitis B virus (HBV), and 2.7 million are chronically infected with HCV. Furthermore, 55% to 85% of new HCV infections become chronic. Of the 1.0 million people chronically infected with HIV, 250,000 also have HBV, and ~50,000 also have HCV, the leading cause of hepatocellular carcinoma. Liver disease is now the leading cause of death in …


Eimeria Species (Apicomplexa: Eimeriidae) From Arctic Ground Squirrels (Spermophilus Parryii ) And Red Squirrels (Tamiasciurus Hudsonicus) In Alaska And In Siberia, Russia, Robert S. Seville, Clint E. Oliver, Andrew J. Lynch, Michelle C. Bryant, Donald W. Duszynski Jun 2012

Eimeria Species (Apicomplexa: Eimeriidae) From Arctic Ground Squirrels (Spermophilus Parryii ) And Red Squirrels (Tamiasciurus Hudsonicus) In Alaska And In Siberia, Russia, Robert S. Seville, Clint E. Oliver, Andrew J. Lynch, Michelle C. Bryant, Donald W. Duszynski

Robert S. Seville

Fecal samples from arctic ground squirrels (Spermophilus parryii) collected in Alaska (n = 90) and Russia (n = 46) and from red squirrels (Tamiasciurus hudsonicus) in Alaska (n = 35) were examined for the presence of Eimeria spp. (Apicomplexa: Eimeriidae). Four species were recovered from arctic ground squirrels, including Eimeria callospermophili (prevalence = 18%), Eimeria cynomysis (23.5%), Eimeria lateralis (19%), and Eimeria morainensis (77%). A single species, Eimeria tamiasciuri (91%), was recovered from red squirrels. Eimerians recovered from arctic ground squirrels represent new host records, and the single species from red squirrels is a new geographic record. Alaskan arctic ground …


The Cooperative Breast Cancer Tissue Resource: Archival Tissue For The Investigation Of Tumor Markers, Helen Donis-Keller, Andrew Glass, Carolyn Mies, Jose Russo, Barbara Zehnbauer, Sheila Taube, Roger Aamodt Apr 2012

The Cooperative Breast Cancer Tissue Resource: Archival Tissue For The Investigation Of Tumor Markers, Helen Donis-Keller, Andrew Glass, Carolyn Mies, Jose Russo, Barbara Zehnbauer, Sheila Taube, Roger Aamodt

Helen Donis-Keller

Investigators continue to search for reliable markers of prognosis of breast cancer. For many analyses, laboratory techniques permit the use of archival paraffin-embedded tissue collected years previously and readily linked to clinical and follow-up information. Laboratory investigators have often expressed the need for such a tissue resource. We have developed a publicly availableresource of archival breast cancer specimens. The pathological material has been collected and reviewed by investigators at four institutions and currently includes breast cancer specimens from more than 9300 cases. Institutional pathologists reviewed slides and blocks using a common protocol and coding scheme. Clinical information and details of …