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Papatheodoridis GV Manesis EK Manolakopoulos S Elefsiniotis IS Goulis J Giannousis J Bilalis A Kafiri G Tzourmakliotis D Archimandritis AJ 《Hepatology (Baltimore, Md.)》2008,48(5):1451-1459
The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >or=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >or=7 and/or stage >or=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >or=200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. CONCLUSION: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >or=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up. 相似文献
995.
Goepfert PA Horton H McElrath MJ Gurunathan S Ferrari G Tomaras GD Montefiori DC Allen M Chiu YL Spearman P Fuchs JD Koblin BA Blattner WA Frey S Keefer MC Baden LR Corey L;NIAID HIV Vaccine Trials Network 《The Journal of infectious diseases》2005,192(7):1249-1259
BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants). RESULTS: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001). CONCLUSIONS: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity. 相似文献
996.
CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex 下载免费PDF全文
Dias DC Dolios G Wang R Pan ZQ 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(26):16601-16606
Selective protein degradation targeted by members of the F-box protein family plays pivotal roles in cell biology. It is widely accepted that an F-box protein directs substrate ubiquitination within a Skp1.CUL1.F-box protein.ROC1 (SCF-ROC1) E3 ubiquitin ligase complex. This assembly utilizes the CUL1 molecular scaffold, allowing the F-box protein to position its bound substrate for ubiquitination by a ROC1-recruited E2-conjugating enzyme. Here, we describe an alternative mechanism for assembling an F-box protein-based E3 complex through a previously uncharacterized cullin, CUL7, identified by mass spectrometry as a ROC1-interacting protein. CUL7 is a large polypeptide containing a cullin domain, which is responsible for ROC1 binding, and a DOC domain, which is also present in the anaphase-promoting complex. Remarkably, CUL7 assembles an SCF-ROC1-like E3 ubiquitin ligase complex consisting of Skp1, CUL7, the Fbx29 F-box protein, and ROC1. In contrast to CUL1 that binds Skp1 by itself, CUL7 interacts with the Skp1.Fbx29 complex, but not with Skp1 alone. Strikingly, CUL7 selectively interacts with Skp1.Fbx29 but not with Skp1.betaTRCP2 or Skp1.Skp2. Thus, CUL7 may define a previously uncharacterized, Fbx29-mediated, and ubiquitin-dependent proteolysis pathway. 相似文献
997.
Infliximab for steroid-refractory acute GVHD: a case series 总被引:3,自引:0,他引:3
Jacobsohn DA Hallick J Anders V McMillan S Morris L Vogelsang GB 《American journal of hematology》2003,74(2):119-124
Acute and chronic graft-versus-host disease (GVHD) remain major barriers to successful hematopoietic stem cell transplantation (SCT). TNF-alpha has been implicated in the pathogenesis of GVHD and TNF-alpha blockade has been explored for treatment of GVHD. The development of a chimeric mouse/human monoclonal antibody (infliximab) which binds to cells producing TNF-alpha, allowing for not only the neutralization of TNF-alpha but also lysis of the cells producing the TNF-alpha, makes this an attractive drug to explore in GVHD. We report on 11 patients with acute GVHD who were treated with infliximab after failing other therapies. The survival was very poor, in keeping with previously published reports of steroid-refractory acute GVHD. Two patients with severe diarrhea from acute GI GVHD resolved their symptoms after treatment with infliximab. Only these two patients survived. It appears that of all acute GVHD manifestations, gastrointestinal GVHD may be more responsive to treatment with infliximab than others. Caution is recommended when using this agent since it may exacerbate active infections, particularly aspergillosis. Furthermore, we do not know the correct dose or schedule to use with this drug. Given these data, controlled studies assessing dose and timing of administration may be warranted to study infliximab in acute GVHD. 相似文献
998.
999.
Gonzalo Grazioli Beatriz Merino Silvia Montserrat Bàrbara Vidal Manel Azqueta Carles Pare Georgia Sarquella-Brugada Xavier Yangüas Ramon Pi Lluis Til Jaume Escoda Josep Brugada Marta Sitges 《Revista espa?ola de cardiología》2014
Introduction and objectives
Despite the established diagnostic value of the electrocardiogram in preparticipation screening of athletes, some cardiac structural changes can be missed, particularly in early disease stages. The aim of this study was to evaluate the prevalence of cardiac structural changes via the systematic use of echocardiography in preparticipation screening of competitive athletes.Methods
Professional athletes or participants in a competitive athletic program underwent a screening that included family and personal medical history, physical examination, electrocardiography, exercise testing, and Doppler echocardiography.Results
A total of 2688 athletes (67% men; mean age [standard deviation], 21 [10] years) were included. Most of the echocardiographic evaluations (92.5%) were normal and only 203 (7.5%) showed changes; the most frequent change was left ventricular hypertrophy, seen in 50 athletes (1.8%). Cessation of athletic activity was indicated in 4 athletes (0.14%): 2 for hypertrophic cardiomyopathy (electrocardiography had shown changes that did not meet diagnostic criteria), 1 pectus excavatum with compression of the right ventricle, and 1 significant pulmonary valve stenosis; the rest of the changes did not entail cessation of athletic activity and only indicated periodic monitoring.Conclusions
Although rare, some cardiac structural changes can be missed on physical examination and electrocardiography; in contrast, they are easily recognized with echocardiography. These findings suggest the use of echocardiography in at least the first preparticipation screening of competitive athletes to improve the effectiveness of programs aimed at preventing sudden death in athletes.Full English text available from:www.revespcardiol.org/en 相似文献1000.
Sophie Mavrogeni Petros P. Sfikakis Georgia Karabela Efthymios Stavropoulos Georgios Spiliotis Elias Gialafos Stylianos Panopoulos Vasiliki Bournia Dionisia Manolopoulou Genovefa Kolovou George Kitas 《International journal of cardiology》2014