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Vaccinia‐based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection 下载免费PDF全文
Ji‐Sun Kwon Jungsoon Yoon Yeon‐Jung Kim Kyuho Kang Sunje Woo Dea‐Im Jung Man Ki Song Eun‐Ha Kim Hyeok‐il Kwon Young Ki Choi Jihye Kim Jeewon Lee Yeup Yoon Eui‐Cheol Shin Jin‐Won Youn 《European journal of immunology》2014,44(8):2360-2369
Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell‐based vaccine, but the narrow breadth of T‐cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T‐cell immunodominance hierarchy in humans in an experimental setting, influenza‐primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN‐γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T‐cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV‐NP + PA showed improved protection. Taken together, a vaccinia‐based influenza vaccine expressing conserved internal proteins improved the breadth of influenza‐specific T‐cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. 相似文献
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Joongho Joh Alfred B. Jenson Arvind Ingle John P. Sundberg Shin-je Ghim 《Experimental and molecular pathology》2014
Correctly folded virus-like particles (VLPs) of papillomavirus (PV) display conformationally dependent epitopes that are type specific, maintained on authentic virions, and induce neutralizing antibodies. Alignment of the L1 amino acid (aa) sequences of 84 PVs revealed that the lengths of their N-termini are diverse and that multiple, possible initiation methionine (met) codons exist. The L1 gene of MusPV (MmuPV1), that naturally infects immunodeficient laboratory mouse strain (NMRI-Foxn1nu/Foxn1nu), has four met codons at the 1st, 2nd, 28th, and 30th aas from its N-terminus. Of these, the 3rd and 4th mets, that are at the 28th and 30th aa position from the N-termius, respectively, are located at the position where most PVs have their first met. These two mets, located at the 9th and 11th from the YLPP conserved aas of most PVs, should be considered as consensus initiation codons of PV L1s. Three L1 proteins of MusPV, starting from the 2nd, 3rd, and 4th mets, were expressed using a baculovirus expression system and characterized for their ability to self-assemble into VLPs. While MusPV L1 proteins starting from the 2nd met expressed an L1 protein that did not fold into VLPs, the L1s starting from the 3rd and 4th mets generated correct VLPs in abundant quantities. We now conclude that the highest quantity and best quality VLPs are made from the consensus L1 met of MusPV. 相似文献
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Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS. 相似文献
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【摘要】 带状疱疹是皮肤科和疼痛科的常见病,带状疱疹相关疼痛严重影响患者生活质量,也是患者就诊的最主要原因。目前国内对带状疱疹相关疼痛的诊疗和管理尚存在一定的认识不足。本共识聚焦于建立带状疱疹相关疼痛的标准化诊疗规范,组织国内皮肤科及疼痛科领域专家,以近年国内外发表的重要文献为基础综合分析,提交专家组反复讨论、修改,最终达成本共识,希望能对带状疱疹相关疼痛的临床规范化诊疗提供指导,为更多患者的全程管理带来帮助。 相似文献
107.
强脉冲光(IPL)疗法是临床上治疗睑板腺功能障碍(MGD)及MGD相关性干眼的物理疗法之一,近来日益受到临床医生的广泛关注。IPL治疗MGD及其相关干眼的原理主要是利用宽谱非相干光的光热效应、热辐射效应、杀菌、抗炎、光调节和恢复局部低氧环境等作用改善睑板腺及眼表的微环境,降低眼表组织中炎性因子水平,进而改善泪膜稳态、减轻睑缘炎症状态,达到治疗MGD及MGD相关干眼和减轻眼表疾病的眼部症状和体征的目的。作为近年来一种全新的MGD及其相关干眼的治疗方式,IPL的临床疗效及安全性逐步得到了认可。然而,目前由于IPL临床应用实践相对缺乏,产品种类较多,治疗过程中患者的个体影响因素较多以及治疗参数需要进行个性化选择,IPL治疗MGD相关干眼的临床适应证、治疗参数调节、治疗的操作流程、治疗时机和疗程的选择、疗效的评价及治疗方案的确定等均尚无规范化指导意见。干眼IPL临床应用专家共识专家组在广泛调查研究、认真讨论,并基于IPL在眼科的应用进展和作用原理对IPL的规范化操作流程制定本共识,为IPL的规范化临床应用提供推荐意见,并为我国干眼诊疗中心诊疗模式的规范提供依据。 相似文献
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《Clinical gastroenterology and hepatology》2022,20(3):631-640.e1
Background & AimsThe Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among “low-risk” mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes.MethodsA single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis.Results502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group.ConclusionThrough real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population. 相似文献
109.
Shiv Kumar Sarin Ashish Kumar Yogesh Kumar Chawla Sanjay Saran Baijal Radha Krishna Dhiman Wasim Jafri Laurentius A Lesmana Debendranath Guha Mazumder Masao Omata Huma Qureshi Rizvi Moattar Raza Peush Sahni Puja Sakhuja Mohammad Salih Amal Santra Barjesh Chander Sharma Praveen Sharma Gamal Shiha Jose Sollano 《Hepatology International》2007,1(3):398-413
The Asian Pacific Association for the Study of the Liver (APASL) Working Party on Portal Hypertension has developed consensus
guidelines on the disease profile, diagnosis, and management of noncirrhotic portal fibrosis and idiopathic portal hypertension.
The consensus statements, prepared and deliberated at length by the experts in this field, were presented at the annual meeting
of the APASL at Kyoto in March 2007. This article includes the statements approved by the APASL along with brief backgrounds
of various aspects of the disease. 相似文献
110.