1,720,977 research outputs found
IN SITU SIMULTANEOUS DETECTION OF HEPATITIS C VIRUS RNA AND HEPATITIS C VIRUS-RELATED ANTIGENS IN HEPATOCELLULAR CARCINOMA
No full textBackground: The overwhelming evidence that chronic infection with the hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) is based on epidemiologic, casecontrol, and cohort studies as well as laboratory investigations. To address better the pathogenesis of HCV infection at a single cell level, the authors developed a specific reproducible method for the simultaneous detection of HCV specific sequences and antigens in liver tissue, using a combination of nonradioactive in situ hybridization and immunohistochemistry. Methods: After immunoistochemical staining of the liver sections for E2/NS-1, C22–3, C33c, C100–3 and NS-5 antigens with immunogold-silver technique, in situ hybridization was performed on the same sections using digoxigenin-labeled HCV 5 NonCoding
specific probes. The hybridization signal was detected by an antidigoxigenin, Fab fragment-alkaline phosphatase conjugate. This simultaneous detection permitted the subcellular localization of HCV RNA and antigens with excellent preservation of tissue morphology and absence of background staining. In addition the types and percentages of cells harboring HCV in tissue could be determined. Results: The in situ detection of HCV showed positive signals in both cancerous and noncancerous areas of liver tissue in six of six HCV-infected patients with HCC and in none of four controls, including three HCV negative HCC patients and one patient with epithelioid hemangioendothelioma. Two classes of infected cells were distinguished throughout the liver: (1) cells containing large amounts of negative-stranded HCV RNA, which were probably undergoing active viral replication; and (2) cells displaying positive-stranded HCV RNA only, with unpredictable levels of viral replication. Both types expressed core, envelope, and NS-3, -4, -5 proteins. HCV RNA and antigens were exclusively cytoplasmic. Detection of viral proteins was highly predictive of the presence of large amounts of HCV RNA in the same cell. Fewer HCV positive cells were consistently demonstrated in the cancerous area. Conclusions: These findings support the contention that HCVinfects hepatocytes and replicates in them, even after their malignant transformation
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
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
Transarterial Chemoembolization Plus Sorafenib: A Sequential Therapeutic Scheme for HCV-Related Intermediate-Stage Hepatocellular Carcinoma: A Randomized Clinical Trial.
No full textBackground. Recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical or ablative treatments. The aim of this prospective, single-center, placebo-controlled, randomized, double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization (TACE) combined with sorafenib as a sequential treatment regimen in delaying time to progression (TTP) of intermediate-stage HCC in patients with chronic hepatitis C virus (HCV) infection. Material and Methods. Between October, 2007 and January, 2011, 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure. All had Child-Pugh class A disease. They were randomized 1: 1 to receive sorafenib at a dose of 400 mg twice daily or placebo. Endpoints were the TTP and the rates of adverse events and toxicity. Results. Sixty-two of 80 patients (77%), 31 in the sorafenib group and 31 in the control group, completed the study. The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group (hazard ratio, 2.5; 95% confidence interval, 1.66-7.56; p <. 001). Metachronous, multicentric HCC progression occurred less frequently in sorafenib-treated patients (p <. 05). Adverse reactions to sorafenib caused withdrawal from the study of 9 (22%) patients. Conclusion. A conventional TACE procedure followed by sorafenib treatment resulted in a significantly longer TTP in patients with intermediate-stage HCV-related HCC, with no unexpected side effects. The Oncologist 2012; 17: 359-36
B-cell depletion in the treatment of mixed cryoglobulinemia.
No full textA controlled study has been carried out to assess the efficacy of rituximab (RTX), a chimeric antibody that binds to the B-cell surface
antigen CD20, in twenty patients with mixed cryoglobulinemia (MC) and HCV-positive chronic active liver disease, resistant to interferon-~,
(IFN-~,) therapy. They received an intravenous infusion of 375 mg/m 2 RTX once a week for 4 consecutive weeks. Infusion of RTX had
a good safety profile, and no severe side-effects were reported. Sixteen patients (80%) had a complete response (CR), characterized by
rapid improvement of clinical signs (disappearance of purpura, weakness, arthralgias and improvement of peripheral neuropathy), and
decreased cryocrit. CR was associated with a significant reduction in rheumatoid factor (RF) activity and anti-HCV antibody titers. Decline
of IgG anti-HCV titers in the cryoprecipitates was usually associated with a favorable response (r 0.81; p <0.005). No differences in
the dynamics of B-cell depletion and recovery were found between responders and non-responders. Molecular monitoring of the B-cell
response revealed disappearance/deletion of peripheral clones in the responders and great stability in the non-responders. RTX had a deep
impact on hepatitis C viremia: HCV RNA increased to approximately twice the baseline level in the responders, whereas it remained much
the same in the non-responders. Twelve out of 16 responders (75%) remained in remission throughout the follow-up. The results indicate
that RTX has clinical and biological activity in HCV-positive MC patients. However, in view of the increased viremia in the responders,
additional modes of application and combination of RTX with other agents need to be investigated
Impact of cryoglobulinemic syndrome on the outcome of chronic hepatitis C virus infection: A 15-year prospective study
No full textWe evaluated the influence of cryoglobulinemic syndrome (CS) on the outcome of chronic hepatitis C virus (HCV) infection in a 15-year prospective study. We assessed a cohort of 950 chronically HCV-infected patients, collected from the beginning of 1990 to the end of 2010. All patients had received a liver histologic diagnosis. Mixed cryoglobulinemia (MC) was determined in 246 patients (25.8%), of whom 184 also had CS. They were assessed every 3 months for 15 years, at least; 141 patients with CS and 601 without MC completed the study. No spontaneous clearance of cryoglobulins was noted. Type II to type III spontaneous switching was ascertained in 1.6% (0.08%/yr) patients. The estimated progression rate of liver fibrosis was lower in CS(+) than in MC(j) patients (p < 0.05). The 15-year cumulative probability of developing cirrhosis and/or hepatocellular carcinoma was higher in MC(j) than in CS(+) patients (24.9% vs. 14.2%, p < 0.005 and 20.3% vs. 7.5%, p = 0.003, respectively). Renal insufficiency, neurologic impairment, or B-cell non-Hodgkin lymphoma were significantly more frequent in CS(+) than inMC(j) patients (32.6% vs. 3%, p < 0.0001; 31.2% vs. 4.8%, p < 0.0001; and 15% vs. 7.1%, p = 0.003, respectively). However, in spite of different morbidity features and causes of death, the 15-year survival rate was similar in the 2 groups (70.2% vs. 71.7%). Antiviral therapy had an undisputable impact on patient outcome. This 15-year prospective cohort study shows that, although CS has no influence on the overall survival of HCV-infected patients, it significantly modifies the natural history of chronically HCV-infected patients. Copyright © 2013 by Lippincott Williams & Wilkins
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