1,721,079 research outputs found
Reconstitution of hepatitis B virus (HBV)-specific T cell responses with treatment of human immunodeficiency virus/HBV coinfection
No full textLiver-related mortality is an increasing problem in human immunodeficiency virus (HIV)/hepatitis B virus (HBV)-coinfected patients receiving highly active antiretroviral therapy (HAART). In HIV-negative patients, HBV chronicity is associated with a reduction in specific T cell responses that can be partially restored by treatment with lamivudine. We studied 5 HIV/HBV-coinfected patients treated with HAART, either with or without addition of a drug with specific anti-HBV activity. Our data show that reconstitution of some HBV-specific T cell responses can also occur in HIV-positive patients after a reduction in HBV load. This potential to recover T cell responses, which has been thought to be critical for HBV control, provides support for the addition of anti-HBV therapy in the treatment of HIV/HBV-coinfected patients
T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection
No full textT cells specific for a single viral epitope, but using different T cell receptors, should have flexibility in their epitope recognition to protect the infected host against the emergence of viral escape mutants. Therefore, polyclonality of the hepatitis B virus (HBV)-specific cytotoxic T lymphocyte response has been hypothesized to be a major determinant in the control of infection. We analyzed the V beta chain composition of the core 18-27-specific GD8 cells in acute and persistently HBV-infected patients using HLA-A2 tetrameric complexes and a panel of V beta antibodies. Different T cell receptors were utilized by core 18-27-specific CD8 cells both in patients with acute and chronic infection. The functional ability of these epitope-specific T cells to respond to potential viral mutations was then tested. The polyclonal HBV-specific CD8 response present in patients with acute hepatitis displayed a limited efficiency to recognize mutations introduced within the epitope. The ability of core 18-27-specific CD8 to tolerate epitope mutations was found only during persistent HBV infection. The data suggest that although a clonally heterogeneous CD8 response can be largely inhibited by the occurrence of single epitope mutations in primary HBV infection, preferential selection of T cells able to counteract the emergence of viral mutations can occur during persistent infection
T cell receptor-therapy in HBV-related hepatocellularcarcinoma.
No full textAdoptive transfer of lymphocytes expressing engineered T cell receptors (TCR) is
a promising option for cancer treatment and could include hepatocellularcarcinoma
(HCC), where therapeutic options are limited. We have recently investigated
whether hepatitis B viral antigens can act as a HCC-specific antigen and thus be
targeted by adoptively transferred HBV-specific TCR redirected T cells
The scientific basis of combination therapy for chronic hepatitis B functional cure
No full textFunctional cure of chronic hepatitis B (CHB) - or hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy - is now the goal of treatment, but is rarely achieved with current therapy. Understanding the hepatitis B virus (HBV) life cycle and immunological defects that lead to persistence can identify targets for novel therapy. Broadly, treatments fall into three categories: those that reduce viral replication, those that reduce antigen load and immunotherapies. Profound viral suppression alone does not achieve quantitative (q)HBsAg reduction or HBsAg loss. Combining nucleos(t)ide analogues and immunotherapy reduces qHBsAg levels and induces HBsAg loss in some patients, particularly those with low baseline qHBsAg levels. Even agents that are specifically designed to reduce viral antigen load might not be able to achieve sustained HBsAg loss when used alone. Thus, rationale exists for the use of combinations of all three therapy types. Monitoring during therapy is important not just to predict HBsAg loss but also to understand mechanisms of HBsAg loss using viral and immunological biomarkers, and in selected cases intrahepatic sampling. We consider various paths to functional cure of CHB and the need to individualize treatment of this heterogeneous infection until a therapeutic avenue for all patients with CHB is available
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Immune cell interactions with stellate cells modulating HBV-related liver fibrosis
Full text linkChronic infection with hepatitis B virus is a global health issue, leading to liver cirrhosis and hepatocellular carcinoma that accounts for more than six hundred thousand deaths annually. Recent work has focused on the role of Natural killer (NK) cells in liver fibrosis in other contexts. In CHB, NK cells have been shown to play an anti-viral as well as an immunoregulatory role. Here we investigate the role of NK cells in the context of CHB-driven liver fibrosis, using primary hepatic stellate cells (HSC) isolated from healthy human liver margins. Our results demonstrate that NK cells from CHB patients have a highly variable and limited potential to kill hepatic stellate cells, which is increased in patients with progressive liver fibrosis, is further enhanced by interferon-alpha pre-activation in vitro and is abrogated by antiviral therapy with nucleos(t)ide inhibitors. We have explored the role of the death ligand TRAIL expressed on NK cells in inducing apoptosis of stellate cells that express high levels of the death-inducing receptor TRAIL-R2. We observed that blockade of TRAIL on the NK cells was only able to reduce killing of HSC in selected cases but not in the whole cohort, suggesting other levels of regulation. Moreover TRAIL ligand (SuperKillerTRAIL) treatment of primary HSC did not induce a degree of apoptosis commensurate with their high expression of the death-inducing receptor TRAIL-R2. We therefore probed the expression of the inhibitory receptors TRAIL-R3 and R4. We found expression of these receptors on primary human HSC both ex vivo and after in vitro culture. The level of expression of TRAIL-R4 showed a remarkably strong correlation with the susceptibility of primary HSC to undergo apoptosis.
Furthermore, blockade of these inhibitory receptors rendered primary HSC more susceptible to apoptosis by SuperKillerTRAIL and by TRAIL-expressing NK cells. Our results are the first to demonstrate a functional role for TRAIL- R3 and -R4 in regulating susceptibility to apoptosis in primary cells. These novel findings will help us to define potential biomarkers and therapeutic targets for liver fibrosis
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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