Life Sciences Commons^™

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

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 …

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 …

Do Australian Adolescent Female Fake Tan (Sunless Tan) Users Practice Better Sun-Protection Behaviors Than Non-Users?, Melinda Williams, Sandra Jones, Peter Caputi, Donald Iverson

Don C. Iverson

Objective: To determine differences in sun-protection behaviours, and incidence of sunburn, between Australian adolescent female fake tan users and non-users. Design: Cross sectional survey. Method: 398 adolescent females aged 12 to 18 years participated in a survey at public venues, schools, and online. The main outcome measures were self-reported fake tan usage in the past 12 months, frequency of sunburns and habitual sun-protection behaviours. Setting: Surveys were completed in New South Wales, Australia. Results: The prevalence of self-reported use of fake tanning products in the past 12 months among Australian adolescent females was 34.5%. Female fake tan users were significantly …

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

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 …

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 …

Failure Of Alpha-Galactosylceramide To Prevent Diabetes In Virus-Inducible Models Of Type 1 Diabetes In The Rat, Prerna Chopra, Philip Diiorio, Steven Pino, S. Brian Wilson, Nancy Phillips, John Mordes, Aldo Rossini, Dale Greiner, Leonard Shultz, Rita Bortell

Philip J diIorio Jr

BACKGROUND: Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes.

MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes.

RESULTS: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all …

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 …

Net Superoxide Levels: Steeper Increase With Activity In Cooler Female And Hotter Male Lizards, Cissy Ballen, Mo Healey, Mark Wilson, Michael Tobler, Erik Wapstra, Mats Olsson

Mark R Wilson

"Ectotherms increase their body temperature in response to ambient heat, thereby elevating their metabolic rate. An often inferred consequence of this is an overall upregulation of gene expression and energetic expenditure, and a concomitant increased production of reactive oxygen species (e. g. superoxide) and, perhaps, a shortened lifespan. However, recent work shows that this may be a superficial interpretation. For example, sometimes a reduced temperature may in fact trigger up-regulation of gene expression. We studied temperature and associated activity effects in male and female Australian painted dragon lizards (Ctenophorus pictus) by allowing the lizards to bask for 4 h versus …