Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, 2011 Washington University School of Medicine
Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib
Open Dartmouth: Faculty Open Access Articles
Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factorsignal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat12/2 and IFNaßcR2/2 mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat12/2 mice and in IFNaßcR2/2 mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat12/2(N-term)) had transient infection of the liver and spleen ...
Triphasic Computed Tomography (Ct) Scan In Focal Tumoral Liver Lesions, 2011 Aga Khan University
Triphasic Computed Tomography (Ct) Scan In Focal Tumoral Liver Lesions, Saima Hafeez, Muhammad Shahbaz Alam, Zafar Sajjad, Zahid Anwar Khan, Waseem Akhter, Fatima Mubarak
Department of Radiology
OBJECTIVE: To assess the diagnostic accuracy of triphasic spiral CT in differentiating benign from malignant focal tumoral liver lesions.
METHODS: The study was conducted in Department of Radiology of Aga Khan University Hospital and Sind Institute of Urology and Transplantation, Karachi from Feb 2006 to Feb 2007. By convenient sampling, 45 patients found to have focal tumoral liver lesions were recruited for one year period and their triphasic CT scans findings were evaluated and later correlated with histopathology. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of triphasic CT scan were calculated.
RESULTS: Among 45 patients, 136 ...
The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, 2011 Philadelphia College of Osteopathic Medicine
The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames
PCOM Biomedical Studies Student Scholarship
Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H2O2), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production reaction in endothelial ...
Metabolic Regulation By C1q/Tnf-Related Protein-13 (Ctrp13): Activation Of Amp-Activated Protein Kinase And Suppression Of Fatty Acid-Induced Jnk Signaling, 2011 Johns Hopkins University School of Medicine
Metabolic Regulation By C1q/Tnf-Related Protein-13 (Ctrp13): Activation Of Amp-Activated Protein Kinase And Suppression Of Fatty Acid-Induced Jnk Signaling, Zhikui Wei, Jonathan M. Peterson, G. William Wong
A Novel Approach For A New Era: Successful Integration Of Multidisciplinary, Hepatitis C Care Within An Established Hiv Primary Care Practice, Joseph L. Yozviak Do, Facp, Orlando J. Penaloza Md, Facp, Timothy J. Friel Md
Department of Medicine
No abstract provided.
Improving Outcomes For Hispanic Patients Undergoing Peginterferon/Ribavirin Therapy For Chronic Hepatitis C In An Internist-Led, Multidisciplinary, Multi-Cultural Practice: A Unique Application Of The Medical, 2011 Lehigh Valley Health Network
Improving Outcomes For Hispanic Patients Undergoing Peginterferon/Ribavirin Therapy For Chronic Hepatitis C In An Internist-Led, Multidisciplinary, Multi-Cultural Practice: A Unique Application Of The Medical, Joseph L. Yozviak Do, Facp, Orlando J. Penaloza Md, Facp, Judith A. Knoop
Department of Medicine
No abstract provided.
Tissue-Specific Regulation Of Mouse Microrna Genes In Endoderm-Derived Tissues., 2011 University of Pennsylvania School of Medicine
Tissue-Specific Regulation Of Mouse Microrna Genes In Endoderm-Derived Tissues., Yan Gao, Jonathan Schug, Lindsay B Mckenna, John Le Lay, Klaus H Kaestner, Linda E Greenbaum
Department of Cancer Biology Faculty Papers
MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After mapping the putative promoters for these microRNA genes using H3K4me3 histone occupancy, we analyzed the regulatory modules of 63 microRNAs differentially expressed between liver and jejunum or pancreas. We determined that the same transcriptional regulatory mechanisms govern tissue-specific ...
C1q/Tnf-Related Protein-3 (Ctrp3), A Novel Adipokine That Regulates Hepatic Glucose Output, 2010 Johns Hopkins University School of Medicine
C1q/Tnf-Related Protein-3 (Ctrp3), A Novel Adipokine That Regulates Hepatic Glucose Output, Jonathan M. Peterson, Zhikui Wei, G. William Wong
Non-Contrast Mri May Predict Safety Of Gadolinium-Enhanced Mri In Patients With Cirrhosis, 2010 Division of Gastroenterology and Hpatology, Thomas Jefferson University
Non-Contrast Mri May Predict Safety Of Gadolinium-Enhanced Mri In Patients With Cirrhosis, Jonathan M. Fenkel, Md, Colin L. Smith, Md, Leela Nayak, Md, Steven K. Herrine, Md, Donald G. Mitchell, Md
Division of Gastroenterology and Hepatology Faculty Papers
Hepatorenal syndrome (HRS) is a relative contraindication to receiving gadolinium-based contrast media secondary to risk of nephrogenic systemic fibrosis (NSF)
Patients with cirrhosis frequently undergo magnetic resonance imaging (MRI) for hepatocellular cancer screening and liver transplant evaluation.
Most centers require documented serum creatinine levels within 10-14 days of performing MRIs on patients with cirrhosis.
Ascites can be readily detected on MRI without contrast enhancement.
To determine whether the presence of ascites on MRI can be used to recommend against a diagnosis of HRS without knowledge of a serum creatinine level.
The "Health" And Future Of The Physician-Scientist In Hepatology, 2010 University of Massachusetts Medical School
The "Health" And Future Of The Physician-Scientist In Hepatology, Gyongyi Szabo
No abstract provided.
Cytokines And Alcohol, 2010 University of North Carolina
Cytokines And Alcohol, Fulton Crews, Rabih Bechara, Lou Ann Brown, David Guidot, Pranoti Mandrekar, Shilpa Oak, Liya Qin, Gyongyi Szabo, Michael Wheeler, Jian Zou
Cytokines are multifunctional proteins that play a critical role in cellular communication and activation. Cytokines have been classified as being proinflammatory (T helper 1, Th1) or anti-inflammatory (T helper 2, Th2) depending on their effects on the immune system. However, cytokines impact a variety of tissues in a complex manner that regulates inflammation, cell death, and cell proliferation and migration as well as healing mechanisms. Ethanol (alcohol) is known to alter cytokine levels in a variety of tissues including plasma, lung, liver, and brain. Studies on human monocyte responses to pathogens reveal ethanol disruption of cytokine production depending upon the ...
Innate Immune Response And Hepatic Inflammation, 2010 University of Massachusetts Medical School
Innate Immune Response And Hepatic Inflammation, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc
Inflammation is a pathogenic component of various types of acute and chronic liver diseases, and it contributes to progressive liver damage and fibrosis. Cells of the innate immune system initiate and maintain hepatic inflammation though mediator production as a result of their activation by pathogen-derived products recognized by pattern recognition receptors. Innate immune cells, particularly dendritic cells, have a pivotal role in sensing pathogens and initiating adaptive immune responses by activation and regulation of T-lymphocyte responses. Although the liver provides a "tolerogenic" immune environment for antigen-specific T-cells, activation of Kupffer cells, recruited macrophages, and inflammatory cells results in production of ...
Altered Innate Immunity In Chronic Hepatitis C Infection: Cause Or Effect, 2010 University of Massachusetts Medical School
Altered Innate Immunity In Chronic Hepatitis C Infection: Cause Or Effect, Gyongyi Szabo, Serena Chang, Angela Dolganiuc
No abstract provided.
Signalling Pathways In Alcohol-Induced Liver Inflammation, 2010 University of Massachusetts Medical School
Signalling Pathways In Alcohol-Induced Liver Inflammation, Pranoti Mandrekar, Gyongyi Szabo
The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFkappaB, AP-1 leads to increased inflammatory cytokine production ...
Liver In Sepsis And Systemic Inflammatory Response Syndrome, 2010 University of Massachusetts Medical School
Liver In Sepsis And Systemic Inflammatory Response Syndrome, Gyongyi Szabo, Laszlo Romics, Gyorgy Frendl
In patients with sepsis and SIRS, the liver has two opposing roles: a source of inflammatory mediators and a target organ for the effects of the inflammatory mediators. The liver is pivotal in modulating the systemic response to severe infection, because it contains the largest mass of macrophages (Kupffer cells) in the body; these macrophages can clear the endotoxin and bacteria that initiate the systemic inflammatory response. This article summarizes the functional changes that take place in the liver during sepsis and systemic inflammatory response syndrome and discusses the cellular and molecular mechanisms that underlie clinical outcomes.
Alcohol-Induced Modulation Of Signaling Pathways In Liver Parenchymal And Nonparenchymal Cells: Implications For Immunity, 2010 University of Massachusetts Medical School
Alcohol-Induced Modulation Of Signaling Pathways In Liver Parenchymal And Nonparenchymal Cells: Implications For Immunity, Bharath Nath, Gyongyi Szabo
Alcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response ...
Diverse Regulation Of Nf-Kappab And Peroxisome Proliferator-Activated Receptors In Murine Nonalcoholic Fatty Liver, 2010 University of Massachusetts Medical School
Diverse Regulation Of Nf-Kappab And Peroxisome Proliferator-Activated Receptors In Murine Nonalcoholic Fatty Liver, Laszlo Romics, Karen Kodys, Angela Dolganiuc, Lucia Graham, Arumugam Velayudham, Pranoti Mandrekar, Gyongyi Szabo
Fatty liver is highly sensitive to inflammatory activation. Peroxisome proliferator-activated receptors (PPAR) have anti-inflammatory effects and regulate lipid metabolism in the fatty liver. We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro- and anti-inflammatory signals. Leptin-deficient, ob/ob mice and their lean littermates were challenged with single or double insults and pro- and anti-inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF-kappaB and peroxisome proliferator receptor element (PPRE). Ob/ob mice produced significantly higher serum tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 and showed increased hepatic NF-kappaB activation ...
Management Of Recurrent Hepatitis C After Liver Transplantation: A Concise Review, 2010 University of Massachusetts Medical School
Management Of Recurrent Hepatitis C After Liver Transplantation: A Concise Review, Gyongyi Szabo, Eliezer Katz, Herbert Bonkovsky
Recurrent hepatitis C infection and subsequent graft failure are increasingly recognized problems after orthotopic liver transplantation. Although many prospective therapeutic, controlled trials in primary hepatitis C disease have been reported, large-scale studies are yet to be performed in patients with posttransplant recurrent hepatitis C after liver transplantation. In this review, we summarize the current literature on the therapeutic approaches for recurrent hepatitis C and discuss the results of published studies on therapy with ribavirin or interferon (IFN) alone and on combination therapy with IFN plus ribavirin. Further, we discuss results of prophylactic approaches to the problem of recurrent hepatitis C ...
A Recent Perspective On Alcohol, Immunity, And Host Defense, 2010 University of Massachusetts Medical School
A Recent Perspective On Alcohol, Immunity, And Host Defense, Gyongyi Szabo, Pranoti Mandrekar
BACKGROUND: Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system.
METHODS: Medline and PubMed databases were used to identify published reports with particular interest in the period of 2000-2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity.
RESULTS: This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The ...
Pattern Recognition Receptors: A Contemporary View On Liver Diseases, 2010 University of Massachusetts Medical School
Pattern Recognition Receptors: A Contemporary View On Liver Diseases, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar
Pattern recognition receptors (PRRs) function as sensors of microbial danger signals enabling the vertebrate host to initiate an immune response. PRRs are present not only in immune cells but also in liver parenchymal cells and the complexity of the cell populations provide unique aspects to pathogen recognition and tissue damage in the liver. This review discusses the role of different PRRs in pathogen recognition in the liver, and focuses on the role of PRRs in hepatic inflammation, cholestasis, ischemia, repair and fibrosis. PRRs as novel therapeutic targets are evaluated.