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991.
Luca Micci Emily S. Ryan Rémi Fromentin Steven E. Bosinger Justin L. Harper Tianyu He Sara Paganini Kirk A. Easley Ann Chahroudi Clarisse Benne Sanjeev Gumber Colleen S. McGary Kenneth A. Rogers Claire Deleage Carissa Lucero Siddappa N. Byrareddy Cristian Apetrei Jacob D. Estes Jeffrey D. Lifson Michael Piatak Jr. Nicolas Chomont Francois Villinger Guido Silvestri Jason M. Brenchley Mirko Paiardini 《The Journal of clinical investigation》2015,125(12):4497-4513
Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non–AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4+ T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21–treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection. 相似文献
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Jenny Bj?rkqvist Steven de Maat Urs Lewandrowski Antonio Di Gennaro Chris Oschatz Kai Sch?nig Markus M. N?then Christian Drouet Hal Braley Marc W. Nolte Albert Sickmann Con Panousis Coen Maas Thomas Renné 《The Journal of clinical investigation》2015,125(8):3132-3146
Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. 相似文献
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Evaluation of a Standardized Program for Training Practicing Anesthesiologists in Ultrasound‐Guided Regional Anesthesia Skills 下载免费PDF全文
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Kim R. Blasdell Hilda Guzman Steven G. Widen Cadhla Firth Thomas G. Wood Edward C. Holmes Robert B. Tesh Nikos Vasilakis Peter J. Walker 《The American journal of tropical medicine and hygiene》2015,92(2):405-410
The Le Dantec serogroup of rhabdoviruses comprises Le Dantec virus from a human with encephalitis and Keuriliba virus from rodents, each isolated in Senegal. The Kern Canyon serogroup comprises a loosely connected set of rhabdoviruses many of which have been isolated from bats, including Kern Canyon virus from California, Nkolbisson virus from Cameroon, Central African Republic, and Cote d''Ivoire, Kolente virus from Guinea, Mount Elgon bat and Fikirini viruses from Kenya, and Oita virus from Japan. Fukuoka virus isolated from mosquitoes, midges, and cattle in Japan, Barur virus from a rodent in India and Nishimuro virus from pigs in Japan have also been linked genetically or serologically to this group. Here, we analyze the genome sequences and phylogenetic relationships of this set of viruses. We show that they form three subgroups within a monophyletic group, which we propose should constitute the new genus Ledantevirus. 相似文献