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Isolation and characterization of human polyreactive pneumococcal polysaccharide antibodies

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Open Journal of Immunology 2012年第3期2卷 98-110页

作者： Rebecca S. Thompson Noor m. Khaskhely Kristin R. malhotra David J. Leggat Jason mosakowski Sadik Khuder Gary R. mcLean m. A. julie Westerink Department of medical microbiology and Immunology University of Toledo Toledo USA Department of medicine University of Toledo Toledo USA School of Human Sciences London Metropolitan University London UK

Natural antibodies serve as the body’s first line of defense against pneumococcal challenge. Polyreactive human pneumococcal polysaccharide IgG antibodies have not been extensively studied. We analyzed human polyreactive antibodies that bind multiple pneumococcal polysaccharides, including PPS14 and PPS23F. These antibodies were isolated from single pneumococcal polysaccharide specific B cells allowing for the analysis of human immunoglobulins with natively paired variable regions. Although isolated individually, these antibodies demonstrated similar characteristics. most antibodies possessed a variable light chain with a CDR3 length made up of nine amino acids and relatively high number of flexible amino acids in combined VH/VL. While these antibodies were polyreactive and structurally alike, kinetic analysis revealed unique KD values. Variable chains are responsible for antigen recognition whereas antibody fine specificity is affected by isotype structure. To investigate the contribution of the constant region of these isotypes and their effect on antibody avidity to pneumococcal polysaccharide, the polyreactive variable regions were expressed as IgG1 or IgG2 and subjected to kinetic analysis. The IgG1 antibodies uniformly had a stronger avidity to PPS14 and PPS23F compared to IgG2. To further document the importance of the constant region in antibody avidity and fine specificity, analysis of antibody F(ab)’2 fragment binding to PPS14 and PPS23F resulted in similar KD values. These studies suggest that antigen recognition by polyreactive antibodies is determined by a conserved variable light chain CDR3 length and longer, more flexible variable heavy CDR3s when compared to pneumococcal polysaccha-ride-specific sequences while differences in specific avidities are modulated by antibody isotype.

关键词： B Cell Pneumococcal Polysaccharide Polyreactive Natural Isotype

medicinal plants of Chinese Pharmacopoeia and Daodi:Insights fromphylogeny and biogeography

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Chinese Herbal medicines 2018年第3期10卷 269-278页

作者： Di Lei Jie wu Christine Leon Lin-fang Huang julie A.Hawkins School of Biological Sciences University of ReadingReading RC6 6BXUnited Kingdom Institute of Chinese materia mediea China Academy of Chinese Medical SciencesBeijing 100700China Royol Botanic Gardens KewRichmondSurrey TW9 3ABUnited Kingdom Institute of medicinal Plant Development Peking Union Medical College&Chinese Academy of Medical SciencesBeijing 100193China

Objective: The Chinese Pharmacopoeia(2015) includes 584 plant medicines, of which 284 also contain high quality subsets, so called "Daodi" components, where Daodi denotes superior clinical properties compared to non-Daodi counterparts despite being sourced from the same species. Commercial and clinical drivers of selection for Daodi have been described elsewhere. Our objective is to investigate the overall composition of Daodi to determine in what ways medicines with Daodi as a whole differ from the other plants of the Chinese Pharmacopoeia. A further objective is to characterise the Chinese Pharmacopoeia and Daodi in terms of the plant species including their traits and ***: We used trait analysis to identify whether Daodi species were significantly different from the remaining Chinese Pharmacopoeia plant species in any traits. We used biogeographic methods and an existing classification of Daodi into 10 regions to identify spatial patterns amongst the species. Regression and binomial analyses were used to test for over-and under-use of plant families and endemic *** for lineages were visualized using phylogenetic ***: We found that Daodi species(species with any Daodi subset) were more likely to be roots that are "hot" or "warm", and less likely to be "oxic", according to traditional Chinese medicine(TCm) concepts. Roots were over-represented in the Bei region, and whole plants over-represented in Guang. Both the Chinese Pharmacopoeia and Daodi indicated preferences for families not common in previously studied ethnopharmacopoeias, and fewer endemic species were represented than expected by ***: Using the phylogenetic and biogeographical methods, we highlighted patterns of plant use,and the biological characters of Daodi medicinal plants. Our study points towards cultural preferences in need of scientific explanation.

关键词： biogeography Chinese Pharmacopoeia Daodi phylogeny

SINGLE-WALLED CARBON NANOTUBES: NOVEL mATERIALS FOR ELECTROCHEmISTRY AND TEmPLATES FOR mETAL NANOPARTICLE FORmATION

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SINGLE-WALLED CARBON NANOTUBES: NOVEL MATERIALS FOR ELECTROC...

第十一届北京分析测试学术报告会暨展览会(BCEIA 2005)

作者： Thomas m.Day Virginia Ruiz Neil R.Wilson julie V.macpherson Patrick R.Unwin Departments of Chemistry & Physics University of Warwick

Single-walled carbon nanotubes(SWNTs)are unique materials which have many interesting physical and electrical *** such,SWNTs are attracting considerable interest as an electrode material,usually after deposition on a ...

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从支付者角度考察成人咽炎的经济负担

中国药物经济学 2009年第2期4卷 64-73页

作者： Alan R Salkind julie m Wright 李凌艳吴晶

目的:虽然临床治疗指南不提倡给患有病毒性咽炎的成人患者处方抗生素,但是内科医生还是经常这样做。从支付者角度考察这种医疗行为的经济负担还没有被研究过。本研究的目的就是评估这种行为所产生的费用。方法:从支付者角度研究咽炎管... 详细信息

目的:虽然临床治疗指南不提倡给患有病毒性咽炎的成人患者处方抗生素,但是内科医生还是经常这样做。从支付者角度考察这种医疗行为的经济负担还没有被研究过。本研究的目的就是评估这种行为所产生的费用。方法:从支付者角度研究咽炎管理的疾病负担(Cost-of-Illness)。利用美国国家流动医疗调查(National Ambulatory medical Care Survey)的数据获得当前成人咽炎流动门诊和抗生素处方的模式。将直接成本和抗生素耐药成本汇总估计咽炎管理的总费用。耐药成本通过建立一个将抗生素使用量与耐药性肺炎链球菌感染相关联的模型计算。依照美国传染病学会(IDSA)临床治疗指南有关咽炎管理的相关规定,对当前医疗模式的成本产出与非抗生素治疗的成本产出进行了比较和敏感度分析。结果:在基础分析中,当前医疗模式的总费用为12亿美元,其中抗生素耐药的成本占总费用的36%(4.26亿美元)。如果遵从IDSA临床治疗指南,医疗成本可以降至5.59亿美元,其中抗生素耐药成本占6.8%(3790万美元)。遵从IDSA临床治疗指南并减少门诊次数的30%,可以降低成本至3.72亿美元,其中抗生素耐药成本占1.4%(530万美元)。采用非抗生素治疗策略可以节省额外的8800万美元成本。结论:当前的医疗模式表明在咽炎治疗中处方抗生素有着广泛的经济影响,给支付者带来很大的经济负担,然而遵从临床治疗指南可以减少耐药性,降低成本。利益相关者、支付者、内科医生和其它医疗提供者应该不断加强对临床治疗指南的依从性,从而降低医疗成本。

关键词：成人抗生素耐药疾病负担分析咽炎

In VitroAnti-Diabetic Activities and Phytochemical Analysis of Bioactive Fractions Present in meriandra dianthera, Aloe camperiand a Polyherb

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American Journal of Plant Sciences 2017年第3期8卷 533-548页

作者： mussie Sium Patrick Kareru Beatrice Kiage-mokua Kaushal Sood John Langley julie Herniman Department of Chemistry College of Science Eritrea Institute of Technology Asmara Eritrea Department of Chemistry Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya Department of Food Science and Technology Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya Centre for Studies in Biotechnology Dibrugarh University Dibrugarh India Department of Chemistry University of Southampton Southampton UK

This paper reports the in vitro anti-diabetic profile of certain medicinal plants traditionally used in Eritrea for the management of type 2 diabetes. The crude methanolic extracts and fractions of meriandra dianthera, Aloe camperi, a Polyherb and their fractions were investigated. The in vitro screening of the crude extracts has generally elicited a dose dependent α-glucosidase and α-amylase inhibition activities. m. dianthera displayed the highest α-glucosidase inhibitory activity (IC50: 0.074 ± 0.032 mg/mL) at the highest concentration tested (0.800 mg/mL) relative to A. camperi, the Polyherb and Acarbose (IC50: 0.37 ± 0.052, 0.56 ± 0.024 and 0.55 ± 0.029 respectively). The α-glucosidase inhibition activities of A. camperi and m. dianthera, except for the Polyherb and Acarbose, were significantly different (P mg/mL). The percentage α-amylase inhibitions of m. dianthera, A. camperi, the Polyherb and Acarbose, at the highest concentrations (0.800 mg/mL), were 78.3%, 15.9%, 16.4%, and 82.9% respectively. A. camperi and the Polyherb displayed lower α-amylase inhibitory activities (IC50: 1.72 ± 0.06 and 2.57 ± 0.07 mg/mL respectively) compared to Acarbose and m. dianthera (IC50: 0.31 ± 0.01 and 0.43 ± 0.02 mg/mL respectively). For the α-amylase inhibition activity, even at lower concentrations (0.025 mg/mL), there were statistically significant differences (P mong the values generated for all the extracts. The in vitro anti-diabetic screening of the fractions, at 0.800 mg/ml, displayed characteristic enzyme inhibition activities. Generally, the non-polar fractions showed higher enzyme inhibitory activities compared to the polar fractions. The most bioactive non-polar fractions, thus, were subjected to GC-mS analysis and presented various essential oils, fatty acid methyl esters (FAmEs) and benzoic acid derivatives in those plants.

关键词： Anti-Diabetic α-Glucosidase α-Amylase GC-mS Essential Oils Fatty Acid methyl Esters

Evaluating Potential Vaccine Antigens in both the Chlamydia trachomatisand Chlamydia muridarumIntravaginal mouse Challenge models

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World Journal of Vaccines 2019年第2期9卷 49-69页

作者： Robin m. Kaufhold melissa A. Boddicker Jodie A. Field Bob J. Lucas Joseph m. Antonello Amy S. Espeseth julie m. Skinner Jon H. Heinrichs Jeffrey G. Smith Department of Infectious Diseases/Vaccines MRL (West Point PA) Merck & Co. Inc. Kenilworth NJ USA Present Address Teva Pharmaceuticals West Chester Pennsylvania USA Department of Biometrics Research MRL (West Point PA) Merck & Co. Inc. Kenilworth NJ USA Present Address Sanofi Pasteur Swiftwater Pennsylvania USA Present Address Moderna Therapeutics Cambridge Massachusetts USA

Identifying relevant animal challenge models adds to the complexity of human vaccine development. murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (mOmP) vaccine formulations to be protective (p C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in mOmP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.

关键词： Chlamydia mouse Challenge model Intravaginal Challenge Sexually Transmitted Diseases

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浅析轮胎行业的全球性影响

现代橡胶技术 2014年第1期40卷 1-8页

作者：何敏 julie m.Panko marisa L.Kreider Kenneth m.Unice

以在轮胎制造和轮胎使用寿命期间对人类的生活环境和身体健康具有长期潜在影响为课题,制订了一个能够对全球轮胎工业造成影响的轮胎工业规划(TIP)。这个轮胎工业规划(TIP)最初是由11家全球最大的轮胎制造企业的CEO们提出的,他们要求该... 详细信息

以在轮胎制造和轮胎使用寿命期间对人类的生活环境和身体健康具有长期潜在影响为课题,制订了一个能够对全球轮胎工业造成影响的轮胎工业规划(TIP)。这个轮胎工业规划(TIP)最初是由11家全球最大的轮胎制造企业的CEO们提出的,他们要求该规划必须保持中立,从全球观点出发,采用正确的科学方法进行研究,并定期将研究结果直接向他们汇报。我们采用的方法包括:(1)通过确定数据空缺和优先考虑的数据需求的全球性文献综述来了解目前的知识现状;(2)编制能说明在使用寿命期间由轮胎产生的磨损颗粒特性的研究程序;(3)了解对人类和环境有害的潜在毒害性;(4)对环境中的磨损颗粒物进行量化。研究结果表明,磨损颗粒物是胎面胶与公路路面以不同的粒径和形态形成的混合物;颗粒物的水生毒性很低,对人体的潜在毒性也很低。全球抽样研究结果表明,颗粒物广泛分布于环境中,但其在环境空气和沉积物中的浓度很低。我们得出的结论是:轮胎磨损颗粒物直接危害人类和环境的风险很低。TIP正在进行的研究工作包括:(1)对在整个轮胎寿命周期轮胎与道路的磨损颗粒物释放的化学物质的潜在风险进行评估;(2)与经合组织(经济合作与发展组织OECD)合作对应用于轮胎工业的新型纳米复合材料的案例进行研究,并撰写一份应用新型纳米材料的最佳实践指南;(3)对在轮胎生产过程中与炭黑/白炭黑纳米颗粒物发生接触所存在的潜在风险进行评估。

关键词：轮胎行业磨损颗粒物分析全球性影响

mitigation of Hypoxic Ecosystems Using Hemolymph Analysis of Callinectes sapidus and Procambarus clarkii in Relation to Spartina Grasses

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Open Journal of Ecology 2016年第8期6卷 484-495页

作者： Natalie Bush Edward Bush Christopher Green julie Anderson Pamela Blanchard Nathan Bush Jennifer Conover St. Joseph’s Academy Baton Rouge LA USA LSU AgCenter Baton Rouge LA USA LSU AgCenter Aquaculture Research Station Baton Rouge LA USA LSU AgCenter and Louisiana Sea Grant Baton Rouge LA USA Health and Human Resources Baton Rouge LA USA Department of mathematics Texas A & M University College Station TX USA Louisiana Universities marine Consortium Chauvin LA USA

In the past 80 years, Louisiana has lost over one million acres in land, affecting plants and crustaceans that live in these environments. The first objective of this research was to determine the relationship between diffused oxygen in water and time with the behavioral and physiological health of Callinectes sapidus (blue crab) and Procambarus clarkii (crawfish). After 24 hours, manual dexterity, or the amount of time it takes for a crustacean to flip itself over increased under hypoxic conditions. Hemolymph was extracted and tested for lactate, glucose, and protein. Crawfish were also exposed to this same procedure. An additional crawfish study comparing Spartina plants to assimilate oxygen for aeration compared to mechanical aeration was conducted. The hypoxic groups for all three studies at the 0.05 level had a significantly greater manual dexterity time and greater amounts of lactate and glucose. The protein was significantly higher in hypoxia-exposed crawfish. Time and aeration affect the health of crustaceans, and plants were shown to effectively provide normoxic oxygen levels at a similar level as mechanical aeration. These studies support the importance of marsh grasses for the coast and crustacean viability.

关键词： Coastal Restoration Barrier Island mitigation marine Ecology

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2015年第7期21卷 2096-2101页

作者： Jean-Florian Guion-Dusserre Veronique Lorgis julie Vincent Leila Bengrine Francois Ghiringhelli Department of medical Oncology Centre Georges-Fran?ois Leclerc Institut National de la Santé et de la Recherche médicale University of Burgundy

AIm:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic ***:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 *** 90 min)concurrently with folinic acid(400 mg/m2 *** 120 min)followed by fluorouracil(400 mg/m2 ***)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 *** response was evaluated by computed tomography scan every 4 ***:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of *** response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were *** grade 3 hematological toxicities and one grade 3 digestive toxicity *** adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 ***:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.

关键词： Biliary tract cancer Intrahepatic cholangiocarcino