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991.
Ehrlich HJ Berezuk G Fritsch S Aichinger G Singer J Portsmouth D Hart MK El-Amin W Kistner O Barrett PN 《Vaccine》2012,30(29):4377-4386
Background
Cell culture technologies have the potential to improve the robustness and flexibility of influenza vaccine supply and to substantially shorten manufacturing timelines. We investigated the safety, immunogenicity and efficacy of a Vero cell culture-derived seasonal influenza vaccine and utilized these studies to establish a serological correlate of vaccine protection.Methods
Two multicenter, randomized, double-blind phase III trials were undertaken in the US during the 2008–2009 Northern hemisphere influenza season, in young (18–49 years) and older (50–64 years and ≥65 years) adult subjects. 7250 young adults were randomized 1:1 to receive either Vero-derived vaccine or placebo. 3210 older adult subjects were randomized 8:1 to receive either Vero-derived vaccine or a licensed egg-derived vaccine. Serum hemagglutination inhibition antibody titers were assessed 21 days post-vaccination. Vaccine efficacy in preventing cell culture-confirmed influenza infection was determined for the young adult population. Local and systemic adverse events were recorded in both studies.Results
The Vero-derived vaccine was safe and well tolerated in both young and older adults. All US and European immunological licensing thresholds were comfortably met in both populations. Vaccine efficacy in young adults was 79% against A/H1N1 viruses antigenically matching the corresponding vaccine strain and 78.5% for all antigenically matched influenza viruses. A hemagglutination inhibition antibody titer of ≥1:15 provided a reliable correlate of protection for the Vero-derived influenza vaccine, with no additional benefit at titers >1:30. Bridging of the correlate of protection established in the young adult population to the older adult immunogenicity data demonstrated the likely effectiveness of the Vero-derived vaccine in the older adult population.Conclusions
A Vero cell culture-derived seasonal influenza vaccine is safe, immunogenic and protects against infection with influenza virus. The novel vaccine technology has the potential to make a substantial contribution to improving influenza vaccine supply.Clinical trial registration
The studies are registered with ClinicalTrials.gov, numbers NCT00566345 and NCT00782431. 相似文献992.
993.
OBJECTIVE: To use statistical techniques to identify underlying subtypes of juvenile idiopathic arthritis (JIA) that best explain the observed relationships of clinical and laboratory variables, and to compare the statistically derived subtypes with those defined by the International League of Associations for Rheumatology (ILAR) criteria and examine them for HLA associations. METHODS: Information on 572 patients diagnosed as having JIA was summarized by 10 clinical and laboratory categorical variables (age at onset, large joint involvement, small joint involvement, polyarthritis, symmetric arthritis, spinal pain, fever, psoriasis, antinuclear antibodies [ANA], and rheumatoid factor). Latent class analysis (LCA) was used to identify underlying ("latent") classes that explained the relationships among the observed variables. Statistical models incorporating 5-8 latent classes were applied to the data. RESULTS: The 7-class model was the most appropriate. Patterns of joint involvement and the presence of ANA were influential in determining latent classes. There was some correspondence between the latent classes and the ILAR categories, but they did not coincide completely. Significant differences between the latent classes were seen for 3 HLA haplotypes (DRB1*04-DQA1*03-DQB1*03, DRB1*13-DQA1*01-DQB1*06, and DRB1*08-DQA1*0401-DQB1*0402). CONCLUSION: LCA provides a novel approach to the task of identifying homogeneous subtypes within the umbrella of JIA. In further work, the identified latent classes will be examined for associations with other candidate genes and for differences in outcome. 相似文献
994.
BACKGROUND: The mechanisms responsible for the accumulation of eosinophils in pleural fluid are not fully understood. The purpose of this study was to evaluate the relationship between eosinophil accumulation and the levels of interleukin (IL)-5, IL-3, and granulocyte/macrophage colony-simulating factor (GM-CSF) in pleural effusions. METHODS: We evaluated 30 patients with eosinophilic pleural effusions (eosinophil count > 10% nucleated cells in pleural fluid) and 10 patients with noneosinophilic pleural effusions. The patients with eosinophilic pleural effusions included 22 patients with post-coronary artery bypass graft surgery pleural effusions and 8 patients with eosinophilic pleural effusions caused by other causes. IL-5, IL-3, and GM-CSF in all pleural fluids were measured using enzyme-linked immunosorbent assay kits. RESULTS: The mean level of IL-5 in eosinophilic pleural effusions (283.1 +/- 341.6 pg/mL) was significantly (p < 0.025) higher than that in the noneosinophilic effusions (28.2 +/- 19.0 pg/mL). The absolute eosinophil count and percentage correlated significantly with the level of IL-5 in all patients (r = 0.55, p < 0.001, and r = 0.54, p < 0.001, respectively). There was no significant correlation between IL-5 levels and RBC counts in all patients (r = 0.24, p > 0.05). GM-CSF and IL-3 levels were below the detectable range in all pleural fluids. CONCLUSION: There is a significant relationship between the levels of IL-5 in pleural fluid and the total number and percentage of eosinophils in the pleural fluid. IL-5 seems to be related to the eosinophil accumulation associated with blood or air in the pleural space and other eosinophilic pleural effusions. 相似文献
995.
996.
Caplin J. L.; Dymond D. S.; Barrett D. S.; Rees R. S. O.; Rees G. M.; Spurrell R. A. J. 《European heart journal》1985,6(11):985-988
Mycotic aneurysms are a rare but recognized complication ofinfective endocarditis. Aneuryms of the pulmonary artery areusually associated with infected congenital heart lesions andespecially with persistent ductus arteriosus. This report dealswith a patient with a persistent ductus who developed multiplemycotic aneurysms in the right lung following infective endocarditis,and whose management was complicated by anomalous venous drainageof most of the contralacteral lung. Surgical closure of theductus to reduce pulmonary blood flow failed to prevent haemoptysis,and further surgery to ligate the feeder arteries to the aneurysmswas required. 相似文献
997.
Regulation of microfilament organization and anchorage-independent growth by tropomyosin 1. 总被引:2,自引:1,他引:2 下载免费PDF全文
J Boyd J I Risinger R W Wiseman B A Merrick J K Selkirk J C Barrett 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(25):11534-11538
Variants of chemically immortalized Syrian hamster embryo cells that had either retained (supB+) or lost (supB-) the ability to suppress tumorigenicity when hybridized with a fibrosarcoma cell line were subcloned. Both supB cell types are nontumorigenic; however, the supB- but not supB+ cells exhibit conditional anchorage-independent growth. Alterations of actin microfilament organization were observed in supB- but not supB+ cells that corresponded to a significant reduction of the actin-binding protein tropomyosin 1 (TM-1) in subB- cells. To examine the possibility of a direct relationship between TM-1 expression and the subB- phenotype, subB+ cells were transfected with an expression vector containing the TM-1 cDNA in an antisense orientation. The antisense-induced reduction of TM-1 levels in supB+ clones caused a microfilament reorganization and conferred anchorage-independent growth potential that were indistinguishable from those characteristic of supB- cells. These data provide direct evidence that TM-1 regulates both microfilament organization and anchorage-independent growth and suggest that microfilament alterations are sufficient for anchorage-independent growth. 相似文献
998.
Patrick Barrett 《Australasian journal on ageing》2006,25(3):114-118
This paper makes a case for examining late life frailty as a dynamic social phenomenon. There is increasing interest in the issue of late life frailty from biomedical researchers, but less so from researchers using the perspectives and methods of social gerontology given a concern that to focus on aspects of functional decline tacitly endorses negative views of ageing. This paper begins by introducing an example of the way frailty in older people is referred to in regional health policy initiatives in New Zealand, before discussing issues around the definition of frailty and its significance. It concludes by noting that, while the term frailty is problematic, social gerontology has a contribution to make in understanding processes of loss of capacity in later life and the social and institutional context within which that occurs, and thus has a contribution to make in policy planning and service delivery. 相似文献
999.
van Herwaarden MA Katz PO Gideon RM Barrett J Castell JA Achem S Castell DO 《Dysphagia》2003,18(3):211-217
The effects of age and gender on the upper esophageal sphincters (UES) and pharyngeal manometric parameters were investigated in 84 healthy subjects (45 men, 39 women, mean age=44 years, range = 18–91). Manometric recordings were performed with solid-state circumferential transducers. Subjects older than 60 years (n = 23) showed a significant lower UES resting pressure. In addition, during water swallows they had a higher UES residual pressure, shorter UES relaxation interval and UES relaxation duration, and a decreased UES relaxation rate. Furthermore, pharyngeal contraction had significant higher amplitude and longer duration in subjects older than 60 years during water swallows. Some of these findings were also observed during cookie and pudding swallows. Women had a higher UES resting pressure and a longer UES relaxation interval than men. The observed changes with increasing age indicate loss of basal tone and decreased compliance of the UES. Increased pharyngeal contraction amplitude and its prolonged duration in the elderly might be compensatory to this. These physiologic effects of age and gender on UES and pharyngeal parameters should be taken into account during analysis of manometric studies.
The first author was financially supported by the Netherlands Digestive and Disease Foundation and the Netherlands Organization for Scientific Research (NWO). 相似文献
1000.
Groopman JE; Hartzband PI; Shulman L; Salahuddin SZ; Sarngadharan MG; McLane MF; Essex M; Gallo R 《Blood》1985,66(3):742-744
The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS. 相似文献