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1.
Tessa Timmers Rik Ossenkoppele Denise Visser Hayel Tuncel Emma E Wolters Sander CJ Verfaillie Wiesje M van der Flier Ronald Boellaard Sandeep SV Golla Bart NM van Berckel 《Journal of cerebral blood flow and metabolism》2020,40(12):2464
The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods. 相似文献
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目的:临床局部辐射条件下会造成非辐射区域组织及细胞功能损害,最为突出的是对造血功能的影响。实验建立60Coγ射线左半身辐射动物模型,观察局部电离辐射对其非辐射区域骨髓巨核细胞的影响。方法:实验于2003-10/2005-03在解放军第三军医大学辐照中心和全军复合伤研究所完成。①实验动物:6~8周龄SPF级雄性昆明小鼠180只,随机数字表法分为正常对照组、全身辐射组、左半身辐射组、全身屏蔽辐射组,45只/组。②实验方法:全身辐射组小鼠固定于辐射架内;左半身辐射组小鼠麻醉后固定体位,用铅砖屏蔽右半身;全身屏蔽辐射组小鼠麻醉固定体位,用铅砖屏蔽全身。以60Coγ射线一次性辐射,剂量率68.46cGy/min。正常对照组不作任何干预。③实验评估:辐射后不同时相检测小鼠血清丙二醛含量及超氧化物歧化酶活性变化,计数外周血血小板,检测骨髓巨核祖细胞集落形成单位,观察骨髓组织病理改变及CD41a、CD61的表达。结果:全身辐射组第8天死亡2只,第9天死亡4只,其余各组无脱失。①外周血血小板计数:辐射后第2,7天,左半身辐射组外周血血小板数量显著低于正常对照组(P<0.01),但高于全身辐射组(P<0.01)。②血清丙二醛含量及超氧化物歧化酶活性变化:辐射后第2,9天,左半身辐射组血清丙二醛含量显著高于正常对照组(P<0.01),低于全身辐射组(P<0.01);血清超氧化物歧化酶活性显著低于正常对照组(P<0.01),高于全身辐射组(P<0.01)。③骨髓巨核祖细胞集落形成单位的变化:与正常对照组比较,辐射后6h左半身辐射组非辐射侧的巨核祖细胞集落形成单位显著降低(P<0.01),高于全身辐射组及左半身辐射组(P<0.01)。④骨髓组织病理改变:正常对照组有核细胞比例较高,分布均匀,并见多量散在分布的细胞龛;辐射2d后,左半身辐射组非辐射侧骨髓有核细胞较正常对照组减少,但好于全身辐射组、左半身辐射组。⑤骨髓CD41a及CD61表达的变化:辐射后2d与正常对照组比较,左半身辐射组非辐射侧骨髓CD41a及CD61阳性细胞数和相对荧光强度均显著降低(P<0.01),但高于全身辐射组、左半身辐射组(P<0.01)。结论:局部电离辐射作用后,可导致小鼠非辐射区域骨髓巨核细胞增殖能力降低,血小板减少,产生功能障碍。氧自由基激活可能参与了该损伤过程。 相似文献
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Scott E Hensley Ann S Cun Wynetta Giles-Davis Yan Li Zhiquan Xiang Marcio O Lasaro Bryan R G Williams Robert H Silverman Hildegund C J Ertl 《Molecular therapy》2007,15(2):393-403
Recent studies have indicated that type I interferon (IFN) enhances antibody responses and promotes isotype switching. In this study, we analyzed the role of type I IFN signaling during the generation of transgene product-specific antibody responses elicited by recombinant adenovirus (Ad) vectors. A vector derived from a human Ad serotype (AdHu5) induced low levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal transgene product-specific antibody responses in mice that have a defective type I IFN receptor (IFNAR(-/-)). A vector derived from a chimpanzee Ad serotype (AdC68) induced very high levels of type I IFN following infection of DCs, and surprisingly, primed stronger transgene product-specific antibody responses in IFNAR(-/-) mice compared to wild-type mice. The increased antibody response in IFNAR(-/-) mice vaccinated with the AdC68 vector was mainly due to the generation of IgG1 antibodies that were not elicited in wild-type mice. The induction of IgG1 antibodies correlated with an increase in transgene product expression in IFNAR(-/-) mice and was not associated with an increase in T helper 2 responses. We conclude that type I IFN, when induced at high levels, can downregulate transgene product expression of Ad vectors and inhibit the formation of optimal antibody responses. 相似文献
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D M Lowe W K Alderton M R Ellis V Parmar W H Miller G B Roberts J A Fyfe R Gaillard P Ertl W Snowden et al. 《Antimicrobial agents and chemotherapy》1995,39(8):1802-1808
The activity, metabolism, and mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and varicella-zoster virus (VZV) were studied. Compared to acyclovir (ACV), H2G has superior activity against VZV (50% inhibitory concentration of 2.3 microM) and Epstein-Barr virus (50% inhibitory concentration of 0.9 microM), comparable activity against HSV-1, and weaker activity against HSV-2. The antiviral effect on HSV-1 showed persistence after removal of compound. H2G was metabolized to its mono-, di- and triphosphate derivatives in virus-infected cells, with H2G-triphosphate being the predominant product. Only small amounts of H2G-triphosphate were detected in uninfected cells (1 to 10 pmol/10(6) cells), whereas the level in HSV-1-infected cells reached 1,900 pmol/10(6) cells. H2G was a substrate for all three viral thymidine kinases and could also be phosphorylated by mitochondrial deoxyguanosine kinase. The intracellular half-life of H2G-triphosphate varied in uninfected (2.5 h) and infected (HSV-1, 14 h; VZV, 3.7 h) cells but was always longer than the half-life of ACV-triphosphate (1 to 2 h). H2G-triphosphate inhibited HSV-1, HSV-2, and VZV DNA polymerases competitively with dGTP (Ki of 2.8, 2.2, and 0.3 microM, respectively) but could not replace dGTP as a substrate in a polymerase assay. H2G was not an obligate chain terminator but would only support limited DNA chain extension. Only very small amounts of radioactivity, which were too low to be identified by high-performance liquid chromatography analysis of the digested DNA, could be detected in purified DNA from uninfected cells incubated with [3H]H2G. Thus, H2G acts as an anti-herpesvirus agent, particularly potent against VZV, by formation of high concentrations of relatively stable H2G-triphosphate, which is a potent inhibitor of the viral DNA polymerases. 相似文献
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Jessica C Fanzo Matthew M Graziose Klaus Kraemer Stuart Gillespie Jessica L Johnston Saskia de Pee Eva Monterrosa Jane Badham Martin W Bloem Alan D Dangour Richard Deckelbaum Achim Dobermann Patrizia Fracassi SM Moazzem Hossain John Ingram Johann C Jerling CJ Jones Stefanus Indrayana Jap Lynnda Kiess Quinn Marshall Keith Martin Anuradha Narayan Mary Amuyunzu-Nayamongo Fré Pepping Keith P West 《Advances in nutrition (Bethesda, Md.)》2015,6(6):639-647
Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals. 相似文献
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Zusammenfassung Trotz verbesserter medikamentöser und interventioneller Therapieoptionen sterben nach wie vor mehr als zwei Drittel aller Patienten, die nach Myokardinfarkt akut herzinsuffizient werden und einen kardiogenen Schock erleiden. Frühe Diagnose und rasche Einleitung von Basismaßnahmen sind entscheidend, um die Zeit bis zur Revaskularisation zu überbrücken. Aufgrund der Schwere des Krankheitsbilds stützen sich viele Behandlungsstrategien nicht auf große randomisierte Studien, sondern auf empirisch gewonnene Erkenntnisse. Neue Entwicklungen betreffen zum einen das kontinuierliche hämodynamische Monitoring, das eine bessere Steuerung der Volumentherapie erlaubt. Zum anderen werden auch neue Prognosemarker und Pharmaka mit dem Ziel verbesserter Verlaufsbeurteilung und medikamentöser Beeinflussung des Schockgeschehens in ersten klinischen Studien erprobt. Spezielle Herausforderungen ergeben sich weiterhin durch ein begleitendes rechtsventrikuläres Pumpversagen oder hämodynamisch wirksame Herzrhythmusstörungen, die Auslöser oder Folgen des kardiogenen Schocks sein können.Ein Erratum zu diesem Beitrag können Sie unter finden. 相似文献