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Safety,immunogenicity,and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide,microbial epitopes and chemokine genes in mice and olive baboons

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The Journal of Biomedical research 2017年第4期31卷 321-332页

作者： Nyamongo Onkoba Ruth M.Mumo Horace Ochanda Charles Omwandho Hastings S.Ozwara Thomas G.Egwang Department of Tropical & Infectious Diseases Institute of Primate Research Nairobi P O. Box 24481-00502 Kenya School of Biological Sciences University of Nairobi Nairobi P. O. Box 30197-00100 Kenya Department of Biochemistry School of Medicine University of Nairobi Nairobi P. O. Box 30197-00100 Kenya Kirinyaga University College Kerugoya P O. Box 143-10300 Kenya med-Biotech Laboratories Kampala P O. Box 9364 Uganda

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial *** present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin（BCG）,tetanus toxoid（TT） and a chemokine *** baboons and BALB/c mice were randomly assigned into vaccine and control *** vaccine group animals were primed and boosted twice with pIres plasmids encoding the SERA5 ＋ BCG ＋ TT alone,or with either CCL5 or CCL20 and the control group with pIres plasmid vector *** and baboons were challenged with *** ANKA and *** H strain parasites,*** was determined by observing for injection sites reactogenicities,hematology and clinical *** and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine *** pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~＋（P〈0.01）,CD 8~＋ T cells（P〈 0.001） activation and IgG anti-SE36 antibodies responses（P〈 0.001） at week 4 and 8 post vaccination compared to the control *** mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons（P〈0.05）and enhanced survivorship（P〈 0.001） with no clinical signs of malaria compared to the control *** results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.

关键词： malaria DNA vaccines serine repeat antigen chemokines cross-species protection immunogenicity safety

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B-Aware研究中术中知晓患者的创伤后应激障碍

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麻醉与镇痛 2011年第5期7卷 68-74页

作者： Kate Leslie, MBBS, MD, MEpi, FANZCA Matthew T. V. Chan, MBBS, FANZCA Paul S. myles, MBBS, MD, MPH, FANZCA, FCARSCI, FRCA Andrew Forbes, MSc, PhD Timothy J. McCulloch, MBBS, BSc （med）, FANZCA 谢珺田（译） Department of Anaesthesia and Pain Management Royal Melbourne Hospital Department of Pharmacology University of Melbourne Melbourne Australia Department of Anaesthesia and Intensive Care The Chinese University of Hong Kong Hong Kong People＇s Republic of China Department of Anaesthesia and Perioperative medicine Alfred Hospital Academic Board of Anaesthesia and Perioperative medicine Monash University Melbourne National Health and medical research council Canberra Department of Epidemiology and Preventive medicaine Monash University Melbourne Department of Anaesthetics University of Sydney Department of Anaesthetics Royal Prince Alfred Hopital Sydney Australia 不详

背景术中知晓的长期影响差异巨大，部分患者没有任何长期影响，而另一些患者则可导致严重和持久的心理障碍。本研究比较了随机化B—Aware研究中，发生明确术中知晓患者与未发生明确术中知晓患者创伤后应激障碍（postlraumaticstressdiso... 详细信息

背景术中知晓的长期影响差异巨大，部分患者没有任何长期影响，而另一些患者则可导致严重和持久的心理障碍。本研究比较了随机化B—Aware研究中，发生明确术中知晓患者与未发生明确术中知晓患者创伤后应激障碍（postlraumaticstressdisorder，PTSD）的发生率。方法我们采用配对群体设计，旨在随访发生明确术中知晓的13例患者。每1例发生术中知晓的患者均按年龄、性别、手术类型、手术日期及手术医院配比4例对照。以临床术后应激障碍评分对每1例术中知晓及对照患者进行面对面的访谈。结果本研究收集数据资料的时间从2006年6月到2007年3月，随访的中位数时间5．3年（范围4．3-5．7年）。其间发生明确术中知晓的13例患者中6例去世，7例患者中的5例（71％）与25例对照中的3例（12％）在随访时点表现符合PTSD的诊断标准（校正的比值比=13．3[95％的可信区间为1．4-650]，P=0．02）。症状出现时间中位数时间为术后14天（范围7-243天），症状持续时间的中位数为4．7年（范围4．4-5．6年）。结论PTSD在B-Aware研究中有明确术中知晓的患者中常见而且持久。全麻下应强化预防患者术中知晓的措施。

关键词：创伤后应激障碍术中知晓患者手术类型 PTSD 中位数心理障碍数据资料

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ARMS interacts with α-syntrophin: implications for the localization and signaling of EphA4 at the neuromuscular synapse

ARMS interacts with α-syntrophin: implications for the loca...

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中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会

作者： Kwok-On. Lai Juan Carlos Arévalo Stanley C. Froehner Marvin E. Adams Moses V. Chao Nancy Y. Ip Dept. of Biochemistry Hong Kong Univ. of Science and Technology Skirball Institute of Biomolecular medicine New York Univ. Sch. of med. New YorkNY 10016USA Dept. of Physiology ＆ Biophysics Univ. of Washington SeattleWA 98195 USA Dept. of Physiology ＆ Biophysics Univ. of Washington SeattleWA 98195 USA Skirball Institute of Biomolecular medicine New York Univ. Sch. of med. New YorkNY 10016USA Dept. of Biochemistry Hong Kong Univ. of Science and Technology

＜正＞Recent accumulating evidence suggests that both Eph and Trk receptors play important roles at the neuromuscular junctions （NMJ）. The identification of ARMS （ankyrin repeat-rich membrane spanning） as a novel substrate for these receptors prompted us to investigate the potential functions of ARMS at the NMJ. In this study, we showed that ARMS was expressed in developing muscle and became concentrated at the NMJ during the first postnatal week. Using yeast two-hybrid screening, we identified the PDZ domain protein α-syntrophin as an ARMS-interacting partner in muscle. The expression profile of α-syntrophin in muscle was similar to that exhibited by ARMS and EphA4. Interestingly, overexpression of α-syntrophin induced ARMS clustering in a PDZ-dependent manner. Moreover, only α- and β2-syntrophins, but not β1 syntrophin, were able to interact with ARMS and induce the formation of ARMS clusters. In an attempt to identify other components of the ARMS/syntrophin complex, we found that ARMS associated with EphA4 and that this interaction resulted in an enhanced Jak and Stat tyrosine phosphorylation, which was further augmented by α-Syntrophin in a PDZ-dependent manner. More importantly, tyrosine phosphorylation of EphA4 induced by ephrin-A1 was attenuated in C2C12 myotubes upon the inhibition of ARMS and a-syntrophin expression by siRNA transfection. Finally, disrupted localization of ARMS and EphA4 at the NMJ was observed in a-syntrophin null mice. Taken together, our findings suggest an important role of ARMS in regulating postsynaptic signaling events through syntrophin-mediated localization of receptor tyrosine kinases.

关键词： Eph receptor receptor tyrosine kinase PDZ neuromuscular junction syntrophin

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二氢吡啶类钙拮抗剂对钙调素依赖性环核苷酸磷酸二酯酶的抑制机理

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华西医科大学学报 1992年第1期23卷 17-20页

作者：吴兆锋 Rajendra K.Sharma Jerry H.Wang 华西医科大学生物化学教研室 Dept med Biochem Univ CaglaryCalgaryAlbertaCanadaT2N 4N1

用单克隆抗体纯化的60kd为亚基的牛脑钙调素依赖性环核苷酸磷酸二酯酶的动力学研究表明,二氢吡啶类钙拮抗剂Nicardipine和Felodipine是该酶的“部分”竞争性抑制剂。因为近饱和浓度的药物抑制该酶活性仅能达到某限定值,且Dixon作图法不... 详细信息

用单克隆抗体纯化的60kd为亚基的牛脑钙调素依赖性环核苷酸磷酸二酯酶的动力学研究表明,二氢吡啶类钙拮抗剂Nicardipine和Felodipine是该酶的“部分”竞争性抑制剂。因为近饱和浓度的药物抑制该酶活性仅能达到某限定值,且Dixon作图法不呈直线关系。该酶被一定浓度Felo-dipine抑制时,增加Nicardipine浓度可逆转酶的抑制而达到Nicardipine的最大抑制水平,Nicardipine不影响典型的竞争性抑制剂甲基异丁基黄嘌呤对该酶的抑制作用,说明该酶活性中心以外存在和二氢吡啶结合的部位。

关键词：二氢吡啶类钙拮抗剂钙调素依赖性环核苷酸磷酸二酯酶部分竞争性抑制

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