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61.
DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life 下载免费PDF全文
Xavier Martinez Christian Brandt Fatiha Saddallah Chantal Tougne Christy Barrios Fabian Wild Gordan Dougan Paul-Henri Lambert Claire-Anne Siegrist 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(16):8726-8731
The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens. 相似文献
62.
The aim of this study was to investigate the possible correlation between the 1H MRS mobile lipid signal, necrosis and lipid droplets in C6 rat glioma. First, the occurrence of necrosis and lipid droplets was determined during tumor development, by a histological analysis performed on 34 rats. Neither necrosis nor lipid droplets were observed before 18 days post-implantation. At later stages of development, both necrosis and lipid droplets were apparent, the lipid droplets being mainly located within the necrotic areas. Using a second group of eight rats, a temporal correlation was evidenced between mobile lipid signal detected by in vivo single-voxel one- (136 ms echo time) and two-dimensional J-resolved 1H MR spectroscopy, and the presence of necrosis and lipid droplets on the histological sections obtained from the brains of the same rats. Finally, spatial distribution of the mobile lipid signal was analyzed by chemical-shift imaging performed on a third group of eight animals, at the end of the tumor growth. The spectroscopic image corresponding to the resonance of mobile lipids had its maximum intensity in the center of the tumor where necrotic regions were observed on the histological sections. These necrotic areas contained large amounts of lipid droplets. All these results suggest that mobile lipids detected in vivo by 1H MRS (136 ms echo time) in C6 rat brain glioma arise mainly from lipid droplets located in necrosis. 相似文献
63.
Chronic diarrhea,hemorrhagic colitis,and hemolytic-uremic syndrome associated with HEp-2 adherent Escherichia coli in adults infected with human immunodeficiency virus in Bangui,Central African Republic 下载免费PDF全文
Mossoro C Glaziou P Yassibanda S Lan NT Bekondi C Minssart P Bernier C Le Bouguénec C Germani Y 《Journal of clinical microbiology》2002,40(8):3086-3088
In human immunodeficiency virus (HIV)-infected adults from the Central African Republic, the occurrence of chronic diarrhea due to HEp-2 adherent Escherichia coli (EAEC) harboring virulence markers (eaeA, BFP, EAF, astA determinant of EAST/1, positive FAS test, enteropathogenic E. coli O serogroup) was shown to be associated with AIDS. We also show that EAEC that produce verotoxin (Stx2) but do not harbor the genetic markers for classical enterohemorrhagic E. coli are involved in hemorrhagic colitis and hemolytic-uremic syndrome in patients with HIV. 相似文献
64.
Laurent Parmentier Alexia Cusini Norbert Müller Haroun Zangger Mary-Anne Hartley Chantal Desponds Patrik Castiglioni Patrick Dubach Catherine Ronet Stephen M. Beverley Nicolas Fasel 《The American journal of tropical medicine and hygiene》2016,94(4):840-843
Leishmania parasites cause a broad range of disease, with cutaneous afflictions being, by far, the most prevalent. Variations in disease severity and symptomatic spectrum are mostly associated to parasite species. One risk factor for the severity and emergence of leishmaniasis is immunosuppression, usually arising by coinfection of the patient with human immunodeficiency virus (HIV). Interestingly, several species of Leishmania have been shown to bear an endogenous cytoplasmic dsRNA virus (LRV) of the Totiviridae family, and recently we correlated the presence of LRV1 within Leishmania parasites to an exacerbation murine leishmaniasis and with an elevated frequency of drug treatment failures in humans. This raises the possibility of further exacerbation of leishmaniasis in the presence of both viruses, and here we report a case of cutaneous leishmaniasis caused by Leishmania braziliensis bearing LRV1 with aggressive pathogenesis in an HIV patient. LRV1 was isolated and partially sequenced from skin and nasal lesions. Genetic identity of both sequences reinforced the assumption that nasal parasites originate from primary skin lesions. Surprisingly, combined antiretroviral therapy did not impact the devolution of Leishmania infection. The Leishmania infection was successfully treated through administration of liposomal amphotericin B. 相似文献
65.
66.
Freyssin C Verkindt C Prieur F Benaich P Maunier S Blanc P 《Archives of physical medicine and rehabilitation》2012,93(8):1359-1364
Freyssin C, Verkindt C, Prieur F, Benaich P, Maunier S, Blanc P. Cardiac rehabilitation in chronic heart failure: effect of an 8-week, high-intensity interval training versus continuous training.ObjectiveTo compare the effects of an 8-week, high-intensity interval training protocol versus continuous training.DesignRandomized controlled trial.SettingCardiac rehabilitation center.ParticipantsPatients (N=26; mean age ± SD, 54±12y) with chronic heart failure were enrolled in a cardiac rehabilitation program for 8 weeks.InterventionsPatients were randomly assigned into 2 groups that performed either interval training (IT) or continuous training (CT). IT consisted of 3 sessions of 12 repetitions of 30 seconds of exercise at very high intensity, followed by 60 seconds of complete rest. The CT group performed CT exercises, which consisted of 45 minutes of aerobic exercise.Main Outcome MeasuresParameters of gas exchanges: peak oxygen consumption (Vo2peak), first ventilator threshold (VT1), distance at six-minute walk test (6MWT), and level of anxiety and depression were measured.ResultsThe IT group increased significantly their Vo2peak, the duration of the exercise test, the oxygen pulse, oxygen consumption at the VT1, and the distance walked during the 6MWT. The CT group only increased the time at the VT1 and the distance performed at the 6MWT. The improvement in the time at the VT1 was significantly higher for the IT group than for the CT group.ConclusionsThis study shows that IT at very high intensity for patients with heart failure appears to be more effective than CT in improving indices of submaximal exercise capacity. 相似文献
67.
Philippe Bonnard Roger Sombi�� Francois-Xavier Lescure Alain Bougouma Jean Baptiste Guiard-Schmid Thierry Poynard Paul Cal��s Chantal Housset Patrice Callard Catherine Le Pendeven Joseph Drabo Fabrice Carrat Gilles Pialoux 《The American journal of tropical medicine and hygiene》2010,82(3):454-458
Liver fibrosis (LF) must be assessed before talking treatment decisions in hepatitis B. In Burkina Faso, liver biopsy (LB) remains the “gold standard” method for this purpose. Access to treatment might be simpler if reliable alternative techniques for LF evaluation were available. The hepatitis B virus (HBV)-infected patients who underwent LB was invited to have liver stiffness measurement (Fibroscan) and serum marker assays. Fifty-nine patients were enrolled. The performance of each technique for distinguishing F0F1 from F2F3F4 was compared. The area under receiver operating characteristic (AUROC) curves was 0.61, 0.71, 0.79, 0.82, and 0.87 for the aspartate transaminase to platelet ratio index (APRI), Fib-4, Fibrotest, Fibrometre, and Fibroscan. Elastometric thresholds were identified for significant fibrosis and cirrhosis. Combined use of Fibroscan and a serum marker could avoid 80% of biopsies. This study shows that the results of alternative methods concord with those of histology in HBV-infected patients in Burkina Faso. These alternative techniques could help physicians to identify patients requiring treatment. 相似文献
68.
Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency 下载免费PDF全文
Stefan D. Anker Stefan Schroeder Dan Atar Jeroen J. Bax Claudio Ceconi Martin R. Cowie Adam Crisp Fabienne Dominjon Ian Ford Hossein‐Ardeschir Ghofrani Savion Gropper Gerhard Hindricks Mark A. Hlatky Richard Holcomb Narimon Honarpour J. Wouter Jukema Albert M. Kim Michael Kunz Martin Lefkowitz Chantal Le Floch Ulf Landmesser Theresa A. McDonagh John J. McMurray Bela Merkely Milton Packer Krishna Prasad James Revkin Giuseppe M.C. Rosano Ransi Somaratne Wendy Gattis Stough Adriaan A. Voors Frank Ruschitzka 《European journal of heart failure》2016,18(5):482-489
Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. 相似文献
69.
70.
Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants 下载免费PDF全文
Jarry A Bossard C Bou-Hanna C Masson D Espaze E Denis MG Laboisse CL 《The Journal of clinical investigation》2008,118(3):1132-1142
IL-10 is an immunomodulatory cytokine that plays an obligate role in preventing spontaneous enterocolitis in mice. However, little is known about IL-10 function in the human intestinal mucosa. We showed here that IL-10 was constitutively expressed and secreted by the human normal colonic mucosa, including epithelial cells. Depletion of IL-10 in mucosal explants induced both downregulation of the IL-10-inducible, immunosuppressive gene BCL3 and upregulation of IFN-gamma, TNF-alpha, and IL-17. Interestingly, TGF-beta blockade also strongly induced IFN-gamma production. In addition, the high levels of IFN-gamma produced upon IL-10 depletion were responsible for surface epithelium damage and crypt loss, mainly by apoptosis. Polymyxin B, used as a scavenger of endogenous LPS, abolished both IFN-gamma production and epithelial barrier disruption. Finally, adding a commensal bacteria strain to mucosa explant cultures depleted of both IL-10 and LPS reproduced the ability of endogenous LPS to induce IFN-gamma secretion. These findings demonstrate that IL-10 ablation leads to an endogenous IFN-gamma-mediated inflammatory response via LPS from commensal bacteria in the human colonic mucosa. We also found that both IL-10 and TGF-beta play crucial roles in maintaining human colonic mucosa homeostasis. 相似文献