Diseases Commons^™

Hla Class I Supertype Associations With Clinical Outcome Of Secondary Dengue Virus Infections In Ethnic Thais, Sasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V. Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J. Thomas, Richard G. Jarman, Anon Srikiatkhachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L. Rothman, Henry A.F. Stephens

Sharone Green

BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.

OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.

METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures.

RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) …

News From Cart, Patricia Fanning, Amos Nwosu

Patricia J. Fanning

No abstract provided.

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Sharone Green

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …

Interview With Celia Schiffer, Celia Schiffer

Celia A. Schiffer

Celia Schiffer, a Professor in Biochemistry and Molecular Pharmacology; a former Director of UMass Center for AIDS Research; and a Founder and Co-Director for the Institute for Drug Resistance (University of Massachusetts Medical School, MA, USA). Schiffer has an undergraduate degree in physics from the University of Chicago, with a PhD in biophysics from University of California, San Francisco (CA, USA). She was a postdoctoral associate first at the ETH in Zurich and then at Genentech in San Francisco. Schiffer has published more than 100 peer reviewed journal articles. Her laboratory primarily uses structural biology, biophysical and chemistry techniques to …

Prototypical Recombinant Multi-Protease Inhibitor Resistant Infectious Molecular Clones Of Human Immunodeficiency Virus Type-1, Vici Varghese, Yumi Mitsuya, W. Jeffrey Fessel, Tommy F. Liu, George Melikian, David Katzenstein, Celia Schiffer, Susan Holmes, Robert Shafer

Celia A. Schiffer

The many genetic manifestations of HIV-1 protease inhibitor (PI) resistance present challenges to research into the mechanisms of PI-resistance and the assessment of new PIs. To address these challenges, we created a panel of recombinant multi-PI resistant infectious molecular clones designed to represent the spectrum of clinically relevant multi-PI resistant viruses. To assess the representativeness of this panel, we examined the sequences of the panel's viruses in the context of a correlation network of PI-resistance amino acid substitutions in sequences from more than 10,000 patients. The panel of recombinant infectious molecular clones comprised 29 of 41 study-defined PI-resistance amino acid …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery Goad, Ani Amloian, Fady Makar

Jeff Goad

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Alan Rothman

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …

Cooperative Effects Of Drug-Resistance Mutations In The Flap Region Of Hiv-1 Protease, Jennifer Foulkes-Murzycki, Christina Rosi, Nese Yilmaz, Robert Shafer, Celia Schiffer

Celia A. Schiffer

Understanding the interdependence of multiple mutations in conferring drug resistance is crucial to the development of novel and robust inhibitors. As HIV-1 protease continues to adapt and evade inhibitors while still maintaining the ability to specifically recognize and efficiently cleave its substrates, the problem of drug resistance has become more complicated. Under the selective pressure of therapy, correlated mutations accumulate throughout the enzyme to compromise inhibitor binding, but characterizing their energetic interdependency is not straightforward. A particular drug resistant variant (L10I/G48V/I54V/V82A) displays extreme entropy-enthalpy compensation relative to wild-type enzyme but a similar variant (L10I/G48V/I54A/V82A) does not. Individual mutations of sites …

Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …

Human Monoclonal Antibody Mbl-Hcv1 Delays Hcv Viral Rebound Following Liver Transplantation: A Randomized Controlled Study, R. Chung, F. Gordon, M. Curry, T. Schiano, S. Emre, K. Corey, J. Markmann, M. Hertl, J. Pomposelli, E. Pomfret, S. Florman, M. Schilsky, Teresa Broering, Robert Finberg, Gyongyi Szabo, Phillip Zamore, U. Khettry, Gregory Babcock, Donna Ambrosino, Brett Leav, Mark Leney, H. Smith, Deborah Molrine

Gyongyi Szabo

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-alpha and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated …

Type Iii Interferons, Il-28 And Il-29, Are Increased In Chronic Hcv Infection And Induce Myeloid Dendritic Cell-Mediated Foxp3+ Regulatory T Cells, Angela Dolganiuc, Karen Kodys, Christopher Marshall, Banishree Saha, Shuye Zhang, Shashi Bala, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND AND AIMS: Hepatitis C virus (HCV) is difficult to eradicate and type III interferons (IFN-lambda, composed of IL-28A, IL-28B and IL-29) are novel therapeutic candidates. We hypothesized that IFN-lambda have immunomodulatory effects in HCV- infected individuals. MATERIALS AND METHODS: We analyzed the expression of IFN-lambda and its receptor (composed of IL-10R2 and IFN-lambdaR subunits) in the blood and livers of patients with chronic (c)HCV infection compared to controls (those who cleared HCV by sustained virological response, SVR, and those with liver inflammation of non-viral origin, non-alcoholic steatohepatitis, NASH). We also compared the proliferative capacity of dendritic cells (DCs) obtained …

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 …

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 …

Ethanol Facilitates Hcv Replication Via Upregulation Of Gw182 And Hsp90 In Human Hepatoma Cells, Terence Bukong, Wei Hou, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Alcohol use and hepatitis C virus (HCV) infection synergize to cause liver damage and microRNA-122 (miR-122) appears to play a key role in this process. Argonaute 2 (Ago2), a key component of the RNA-induced silencing complex, has been shown to be important in modulating miR-122 function during HCV infection. However, GW182, a critical component of processing bodies (GW-bodies) that is recruited by Ago2 to target mRNA has not been assessed in HCV infection. To characterize the role of GW182 in the pathogenesis of HCV infection, we determined its transcription and protein expression in an HCV J6/JFH1 culture system. Here we …

Reduction In Hepatic Inflammation Is Associated With Less Fibrosis Progression And Fewer Clinical Outcomes In Advanced Hepatitis C, Chihiro Morishima, Mitchell Shiffman, Jules Dienstag, Karen Lindsay, Gyongyi Szabo, Gregory Everson, Anna Lok, Adrian Di Bisceglie, Marc Ghany, Deepa Naishadham, Timothy Morgan, Elizabeth Wright

Gyongyi Szabo

OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological …

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 …

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 …

Aids, Social Work, And The "Duty To Protect", Frederic Reamer

Frederic G Reamer

This article discusses social workers' obligation in cases where clients with aquired immune deficiency syndrome (AIDS) pose a threat to a third party. Emphasis is on cases where a client diagnosed with AIDS withholds that information from a sexual partner. Legal and ethical issues concerning the limits of confidentiality and the social worker's "duty to protect" third parties are reviewed. Relevant case law and emerging ethical standards in various professions are summarized. The author reviews legal precedents concerning disclosure of confidential information without a client's permission and discusses their relevance to AIDS cases. Implications and guidelines for social workers are …

Aids And Ethics, Frederic Reamer

Frederic G Reamer

The seriousness of the AIDS crisis is well known. Since the first case was documented in Los Angeles in 1981, the media have been filled with research updates, documentaries, and exposes on the dreaded disorder. Reports and case studies have ranged from informative to sensational. They have included serious academic studies, educational overviews targeted for the general public, and columns in weekly tabliods.

Aids And Social Work, Frederic Reamer

Frederic G Reamer

Social workers are becoming increasingly involved in casework and social policy debate related to the acquired immune deficiency syndrome (AIDS) crisis. To enhance their delivery of services and contribution to policy formulation, social workers need to be familiar with a wide range of ethical and civil liberties issues that have been generated by the AIDS epidemic. This article provides an overview of six major ethical and civil liberties issues pertaining to social work practice related to AIDS: (1) mandatory screening and testing of clients for the immunodeficiency virus (HIV), (2) client access to health insurance, (3) professionals' duty to treat …

Retention In Care And Connection To Care Among Hiv-Infected Patients On Antiretroviral Therapy In Africa: Estimation Via A Sampling-Based Approach, Elvin Geng

Elvin H Geng

No abstract provided.

Retention In Care For Hiv-Infected Patients In Resource-Limited Settings: Challenges And Opportunities, Elvin Geng

Elvin H Geng

No abstract provided.

Trends In Hiv-Infected Patients Accessing Antiretroviral Therapy In Kenya, Uganda And Tanzania Between 2002 And 2009, Elvin Geng

Elvin H Geng

No abstract provided.

Correcting Mortality For Loss To Follow-Up: A Nomogram Applied To Antiretroviral Treatment Programmes In Sub-Saharan Africa, Elvin Geng

Elvin H Geng

No abstract provided.

Diminishing Availability Of Publicly Funded Slots For Antiretroviral Initiation Among Hiv-Infected Art-Eligible Patients In Uganda, Elvin Geng

Elvin H Geng

No abstract provided.