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Open Journal of Statistics 2017年第2期7卷 254-263页

作者： Frank D. Lewis Gordon J. Horn Robert Russell NeuroRestorative Research Institute Medical College of Georgia Augusta University Augusta USA NeuroRestorative Research Institute College of Medicine Florida State University Orlando USA NeuroRestorative Research Institute Benedictine University Carbondale USA

This study evaluated the impact of chronicity (onset of injury to admission in-terval) on three domains of functional outcomes for a large group of traumatic brain injured (TBI) survivors. Subjects included 528 TBI adults who were treated in post-hospital residential rehabilitation centers. Subjects were assigned to one of three chronicity groups: 1) Early Interval (EI), 2.00 - 8.00 months n = 245, 2) Mid Interval (MI), 8.01 - 24.00 months n = 129, and (3) Late Interval (LI), 24.01 months and greater n = 154. Functional status was assessed with the MPAI-4. RM MANCOVA was applied to evaluate differences among groups from admission to discharge. Rasch analysis demonstrated satisfactory construct validity and internal consistency (Person reliability = 0.90 - 0.94, Item reliability = 0.99) for the admission and discharge MPAI-4s. Controlling for LOS and age, the RM MANCOVA revealed that each chronicity group showed significant improvement in MPAI-4 abilities, adjustment, and participation indices from admission to discharge (p chronicity group. Of the three groups, EI participants presented as the most disabled at admission but also made the greatest gains when assessed at discharge.

关键词： TBI Multivariate Analysis chronicity Outcome Post-Hospital Rehabilitation MPAI-4 Raschanalysis Functional Assessment

The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

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World Journal of Gastroenterology 2007年第1期13卷 104-124页

作者： Stephan Menne Paul J Cote Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca New York United States Department of Microbiology and Immunology Georgetown University Medical Center Washington DC United States

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and preventi

关键词： Woodchuck Woodchuck hepatitis virus Hepatitis B virus Neonatalacquired infection Adult-acquired infection Resolution chronicity Humoral immune response Cellular immune response Antiviraltherapy Immunotherapy Combination therapy Hepatocellular carcinoma

Effective intrahepatic CD8＋ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes

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Cellular & Molecular Immunology 2016年第6期13卷 805-815页

作者： Aaron Ochel Marcin Cebula Mathias Riehn Upneet Hillebrand Christoph Lipps Reinhold Schirmbeck Hansjorg Hauser Dagmar Wirth Model Systems for Infection and Immunity Helmholtz Centre for Infection Research Inhoffenstr. 7 38124 Braunschweig Germany Clinic for Internal Medicine I University Hospital UIm Albert-Einstein-Allee 23 89081 UIm Germany Experimental Hematology Medical School Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Current address Institute for Immunology Justus-Liebig University Giessen BFS Schubertstr. 81 35390 Giessen Germany

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.

关键词： antigen load chronicity immune modulation T-cell exhaustion

Establishment of chronic hepatitis C virus infection:Translational evasion of oxidative defence

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World Journal of Gastroenterology 2014年第11期20卷 2785-2800页

作者： Shiu-Wan Chan Faculty of Life Sciences The University of ManchesterManchester M13 9PTUnited Kingdom

Hepatitis C virus(HCV)causes a clinically important disease affecting 3%of the world *** is a single-stranded,positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae *** virus establishes a chronic infection in the face of an active host oxidative defence,thus adaptation to oxidative stress is key to virus *** a small RNA virus with a limited genomic capacity,we speculate that HCV deploys a different strategy to evade host oxidative *** of counteracting oxidative stress,it utilizes oxidative stress to facilitate its own *** is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first *** is particularly true when HCV utilizes an internal ribosome entry site element in translation,which is distinctive from that of cap-dependent translation of the vast majority of cellular genes,thus allowing selective translation of genes under conditions when global protein synthesis is ***,we were the first to show that HCV translation was stimulated by an important prooxidant-hydrogen peroxide in hepatocytes,suggesting that HCV is able to adapt to and utilize the host antiviral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish *** how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes *** chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity,which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants.

关键词： Hepatitis C virus Oxidative stress Hydrogen peroxide Translation Internal ribosome entry site chronicity Persistence