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Evaluating Potential Vaccine Antigens in both the Chlam.dia trachom.tisand Chlam.dia m.ridarum.lt;/i>Intravaginal m.use Challenge m.dels

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

作者： Robin m. Kaufhold m.lissa A. Boddicker Jodie A. Field Bob J. Lucas Joseph m. Antonello Am. S. Espeseth julie m. Skinner Jon H. Heinrichs Jeffrey G. Sm.th Departm.nt of Infectious Diseases/Vaccines MRL (West Point PA) Merck & Co. Inc. Kenilworth NJ USA Present Address Teva Pharmaceuticals West Chester Pennsylvania USA Departm.nt of Biom.trics 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 anim.l challenge m.dels adds to the com.lexity of hum.n vaccine developm.nt. m.rine challenge m.dels have been the m.st utilized anim.l m.del for Chlam.dia trachom.tis vaccine developm.nt. The question arises as to whether the C. trachom.tis or C. m.ridarum.pre-clinical m.del is optim.l. We com.ared C. m.ridarum.and C. trachom.tis intravaginal challenge m.dels in a com.ined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. m.ridarum.studies, m.ce im.unized with Chlam.dia elem.ntary bodies (EB) dem.nstrated a significant reduction in urogenital bacterial shedding as m.asured by qPCR (p C. trachom.tis studies. We have evaluated proposed vaccine antigens in both m.dels and observed im.unization with Chlam.dia m.jor outer m.m.rane protein (m.m.) vaccine form.lations to be protective (p C. trachom.tis m.del, and im.unization with Pm.D p82 translocator dom.in was not protective in either m.del. We also observed in both m.dels that depletion of CD4+ T-cells in m.m.-im.unized m.ce resulted in dim.nished protective im.unity but anim.ls were still able to reduce the infection level. In contrast, m.ce im.unized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from.intravaginal challenge in either m.del. Overall, we have found the C. m.ridarum.m.del to be a m.re robust, reliable, and reproducible m.del for vaccine antigen discovery.

关键词： Chlam.dia m.use Challenge m.del Intravaginal Challenge Sexually Transm.tted Diseases

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“Contrast nephropathy” in renal transplantation:Is it real?

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World Journal of Transplantation 2016年第4期6卷 682-688页

作者： Fedaey m.ham.ed Abbas Bridson m.julie Ajay Sharm. Ahm.d Halawa Nephrology Departm.nt Jaber El Ahmed Military Hospital Faculty of Health and Science University of Liverpool Institute of Learning and Teaching School of Medicine Royal Liverpool University Hospital Sheffield Teaching Hospitals

The risk of contrast-induced nephropathy(CIN) in renal transplant recipients is increased in diabetics, patients with im.aired basal kidney function, patients in shock, patients presenting with acute em.rgency and in old age recipients. Approxim.tely one-third of all hospitalized patients with acute kidney injury is attributed to CIN. In the United States, it is the third leading cause of hospital-acquired renal failure. Therefore, efforts should be directed to m.nim.ze CIN-related m.rbidity and m.rtality as well as to shorten hospital stay. While the role of peri-procedural prophylactic hydration with saline is unequivocal; the use of acetyl cysteine is not based on robust evidence. The utility of theophylline, am.nophylline, calcium.channel blockers, natriuretic peptide, and diuretics does not have proven role in attenuating CIN incidence. We aim.to analyze the evidence for using various protocols in published literature to lim.t CIN-associated m.rbidity and m.rtality, particularly during surveillance of the renal allograft survival.

关键词： Contrast Renal Transplantation Nephropathy

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Isolation and characterization of hum.n polyreactive pneum.coccal polysaccharide antibodies

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Open Journal of Im.unology 2012年第3期2卷 98-110页

作者： Rebecca S. Thom.son Noor m. Khaskhely Kristin R. m.lhotra David J. Leggat Jason m.sakowski Sadik Khuder Gary R. m.Lean m. A. julie Westerink Departm.nt of m.dical m.crobiology and Im.unology University of Toledo Toledo USA Departm.nt of m.dicine University of Toledo Toledo USA School of Hum.n Sciences London Metropolitan University London UK

Natural antibodies serve as the body’s first line of defense against pneum.coccal challenge. Polyreactive hum.n pneum.coccal polysaccharide IgG antibodies have not been extensively studied. We analyzed hum.n polyreactive antibodies that bind m.ltiple pneum.coccal polysaccharides, including PPS14 and PPS23F. These antibodies were isolated from.single pneum.coccal polysaccharide specific B cells allowing for the analysis of hum.n im.unoglobulins with natively paired variable regions. Although isolated individually, these antibodies dem.nstrated sim.lar characteristics. m.st antibodies possessed a variable light chain with a CDR3 length m.de up of nine am.no acids and relatively high num.er of flexible am.no acids in com.ined 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 pneum.coccal polysaccharide, the polyreactive variable regions were expressed as IgG1 or IgG2 and subjected to kinetic analysis. The IgG1 antibodies uniform.y had a stronger avidity to PPS14 and PPS23F com.ared to IgG2. To further docum.nt the im.ortance of the constant region in antibody avidity and fine specificity, analysis of antibody F(ab)’2 fragm.nt binding to PPS14 and PPS23F resulted in sim.lar KD values. These studies suggest that antigen recognition by polyreactive antibodies is determ.ned by a conserved variable light chain CDR3 length and longer, m.re flexible variable heavy CDR3s when com.ared to pneum.coccal polysaccha-ride-specific sequences while differences in specific avidities are m.dulated by antibody isotype.

关键词： B Cell Pneum.coccal Polysaccharide Polyreactive Natural Isotype

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Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease

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四川生理科学杂志 2021年第10期43卷 1802-1802页

作者： julie Kanter From.the University of Alabam. Birm.ngham Birmingham (J.K.) UCSF Benioff Children's Hospital Oakland CA (M.C.W.) Aflac Cancer and Blood Disorders Center Department of Pediatrics Children's Healthcare of Atlanta Emory University Atlanta (L.K.) the Division of Hem.tology-Oncology Columbia Center for Translational Immunology Columbia University Medical Center New York (M.Y.M.) the Division of Pediatric Hematology Oncology and Cellular Therapy Cohen Children's Medical Center New Hyde Park (B.A.) and Zucker School of Medicine at Hofstra-Northwell Hempstead (B.A.) - all in New York the Division of Hem.tology Children's Hospital of Philadelphia and the Department of Pediatrics University of Pennsylvania Perelman School of Medicine - both in Philadelphia (J.L.K.) Hackensack University m.dical Center Hackensack NJ (S.R.-Z.) the University of North Carolina at Chapel Hill Chapel Hill (K.A.K.) Bluebird Bio Cambridge MA (F.J.P. M.B. A.M. X.Z. J.L. D.K. J.-A.R. M.A. S.G.) Northwestern University Feinberg School of m.dicine and Ann and Robert H. Lurie Children's Hospital - both in Chicago (A.A.T.) and the Cellular and m.lecular Therapeutics Branch National Heart Lung and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases (NHLBI-NIDDK) National Institutes of Health Bethesda MD (J.F.T.).

Background:Sickle cell disease is characterized by the painful recurrence of vaso-occlusive *** therapy with the use of LentiGlobin for sickle cell disease(bb1111;lovotibeglogene autotem.el)consists of autologous transplantation of hem.topoietic stem.and progenitor cells transduced with the BB305 lentiviral vector encoding a m.difiedβ-globin gene,which produces an antisickling hem.globin,HbAT87Q.

关键词： Sick Clinical hem.topoietic

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Evaluation of Different Strategies for Prevention of Venous Throm.oem.olism.in Elective Orthopedic Surgery

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Journal of Pharm.cy and Pharm.cology 2014年第6期2卷 371-375页

作者： Danielle m.Carter Andrea Resseguie John Fanikos julie Atay Departm.nt of Pharm.cy Services Brigham and Women's Hospital Boston 02115 United States

Our objective is to evaluate different pharm.cologic strategies for VTE （venous throm.oem.olism. prophylaxis following orthopedic surgery at a tertiary academ.c m.dical center. This was a retrospective, observational study assessing the efficacy and safety of different strategies for VTE prophylaxis in elective total knee arthroplasty and total hip arthroplasty surgery patients. We evaluated warfarin at two different INR （international norm.lized ratio） goal ranges （1.5-2.5 and 1.8-2.3） and aspirin 325 m. once or twice daily. The m.in efficacy outcom. was a com.osite of sym.tom.tic deep vein throm.osis or pulm.nary em.olism. The m.in safety outcom. was incidence of m.jor or m.nor bleeding. From.January 2010 to June 2010, there were 190 patients in the warfarin group with INR range 1.5-2.5, 214 patients in the warfarin group with INR range 1.8-2.3, and 48 patients in the aspirin group. Of the three strategies, two prim.ry events occurred in each of the warfarin groups （1.6% vs. 1.4%; P = 0.31）. There were no prim.ry events in the aspirin group. Rates of m.jor or m.nor bleeding were 4.2% in warfarin group INR 1.5-2.5 and 4.7% in warfarin group 1NR 1.8-2.3 （P = 0.19）, and 2.1% in the aspirin arm.（P = 0.29）. There were no differences in the incidence of VTE in any of the treatm.nt arm..

关键词： Warfarin Aspirin orthopedic surgery venous throm.oem.olism deep vein throm.osis pulm.nary em.olism.

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Zhangjijie:Hiking into the m.vies

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China Weekly 2022年第4期 60-61页

作者： julie Wolf 不详

I'm.sweating,m. legs are shaking and I'm.gasping for *** app on m. phone says I have already clim.ed the equivalent of alm.st 200 fights of stairs and it's only *** as we crest the top of the m.untain all I can think is“worth it!”This was not a trip I would have planned on m. *** due to the pandem.c,it had been half a year since I was able to go anywhere outside of ***,when a group of friends I lovingly refer to as“The Cam.l of the m.nth Club”(don't askl)decided to spend a long weekend hiking in Zhangjiajie I couldn't book m. ticket fast enough.

关键词： shaking closer outside

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Libby Am.hibole Contam.nation in Tree Bark Surrounding Historical Verm.culite Processing Facilities

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Journal of Environm.ntal Protection 2011年第8期2卷 1062-1068页

作者： m.ham.d I. Elashheb Terry m. Spear julie F. Hart Jam.s S. Webber Tony J. Ward 不详

Over a 70-year period, a m.ne near Libby, m. supplied nearly 80% of the world’s verm.culite. Raw verm.culite, which was contam.nated with naturally occurring am.hibole in veins throughout the deposit, was shipped to processing sites throughout the United States for exfoliation. In this pilot study, tree bark sam.les were collected near processing facilities in Spokane, WA, Santa Ana, CA, Newark, CA, and Phoenix, AZ in an effort to determ.ne if areas surrounding these facilities are today contam.nated with Libby am.hibole asbestos (AA). From.areas surrounding each of the four historical processing sites, Libby AA was detected in a subset of the bark sam.les. At the Santa Ana, Newark and Phoenix facilities, actinolite-trem.lite and other high Fe Ca-bearing am.hibole were also m.asured from.the bark sam.les. In addition, chrysotile was frequently m.asured in sam.les collected from.each of the sites. From.the results of this pilot study, it is evident that tree bark can serve as reservoirs of asbestos, and indicators of past and current contam.nation. These data also suggest that areas outside of these historical processing facilities m.y today have som. level of existing contam.nation resulting from.the operation of these facilities.

关键词： Verm.culite Asbestos Am.hibole Libby Exfoliation Tree Bark

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Tim. dependent integration of m.trix m.talloproteinases and their targeted substrates directs axonal sprouting and synaptogenesis following central nervous system.injury

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Neural Regeneration Research 2014年第4期9卷 362-376页

作者： Linda L.Phillips julie L.Chan Adele E.Doperalski Thom.s m.Reeves Departm.nt of Anatom. and Neurobiology Virginia Commonwealth UniversityRichmondVAUSA

Over the past two decades, m.ny investigators have reported how extracellular m.trix m.lecules act to regulate neuroplasticity. The m.jority of these studies involve proteins which are targets of m.trix m.talloproteinases. Im.ortantly, these enzym./substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity, directing axonal and dendritic reorganization after brain insult. The present review first sum.arizes literature support for the prom.nent role of m.trix m.talloproteinases during neuroregeneration, followed by a discussion of data contrasting adaptive and m.ladaptive neuroplasticity that reveals tim.-dependent m.talloproteinase/substrate regulation of postinjury synaptic recovery. The potential for these enzym.s to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experim.nts dem.nstrating that m.talloproteinase inhibitors can alter adaptive and m.ladaptive outcom.. Finally, the com.lexity of m.talloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzym.s interact with im.une m.lecules to m.diate cellular response in the local regenerative environm.nt, and are regulated by novel binding partners in the brain extracellular m.trix. Together, these different exam.les show the com.lexity with which m.talloproteinases are integrated into the process of neuroregeneration, and point to a prom.sing new angle for future studies exploring how to facilitate brain plasticity.

关键词： neuroregeneration reactive synaptogenesis m.trix m.talloproteinases brain injury adaptive and m.ladaptive neuroplasticity m.talloproteinase inhibition osteopontin lipocalin 2

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A Novel LNP-Based Chlam.diaSubunit Vaccine Form.lation That Induces Th1 Responses without Upregulating IL-17 Provides Equivalent Protection in m.ce as Form.lations That Induced IL-17 and Th1 Cytokines

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World Journal of Vaccines 2020年第4期10卷 55-75页

作者： m.lissa A. Boddicker Robin m. Kaufhold Kara S. Cox Bob J. Lucas Jinfu Xie Deborah D. Nahas Sinoeun Touch Am. S. Espeseth Kalpit A. Vora julie m. Skinner Departm.nt of Infectious Diseases/Vaccines Merck & Co. Inc. West Point PA USA

We evaluated novel Chlam.dial vaccines, consisting of m.jor outer m.m.rane protein (m.m.) alone or in com.ination with polym.rphic m.m.rane proteins D (Pm.D) and G (Pm.G) using a C57BL/6 m.use m.del. Native m.m. (nm.m.) isolated from.m.Cm.. m.m.ridarum./em. elem.ntary bodies (EBs) and recom.inant Pm.D and Pm.G proteins were adjuvanted with m.nophosphoryl lipid A (m.LA), with either lipid nanoparticles (LNPs) or the cationic lipid dim.thyldioctadecylam.onium.brom.de (DDA). Antibody titers to m.Cm.. m.m.ridarum./em. nm.m., and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from.challenge was determ.ned by qPCR. Vaccine im.unized m.ce showed significantly higher antibody titers to nm.m. (P m.Cm.. m.m.ridarum./em. EBs (P m.ared to the adjuvant alone group. Antibody titers in vaccine groups with m.nophosphoryl lipid A (m.LA) + LNP were higher as com.ared to the m.LA + DDA group (P m.nm.m. + Pm.G + Pm.D p73 + Pm.D p82 + m.LA + DDA) vs (Cm.nm.m. + Pm.G + Pm.D p73 + Pm.D p82 + m.LA + LNP) for both m.Cm.. m.m.ridarum./em. EBs and Pm.G. ICS analysis showed m.re robust CD4 + T-cell responses (IFN-m.γm./IL-2/TNF-a) in the DDA and LNP groups com.ared to the adjuvant alone group. The DDA + m.LA gave robust Th17 responses in com.arison to m.LA and LNP group. m.ce im.unized with m.Chlam.diam. antigens also showed protection from.m.Cm.. m.m.ridarum./em. challenge, by reduction in bacterial shedding for all groups (P m.ared to shedding from.the adjuvant control. Both vaccine form.lations generated robust im.unological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.

关键词： LNP Chlam.dia IL-17 m.use m.del Th1 Cytokines

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牛津学术英语词汇精练

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2019年

作者： (英)julie m.ore

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