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Helminths and Immunological Tolerance

Chris J.C. Johnston, Henry J. McSorley, Stephen M. Anderton, Stephen J. Wigmore, Rick M. Maizels
2014 Transplantation  
Current immunosuppression regimens for solid-organ transplantation have shown disappointing efficacy in the prevention of chronic allograft rejection and carry unacceptable risks including toxicity, neoplasia, and life-threatening infection. Achievement of immunological tolerance (long-term antigen unresponsiveness in an immunocompetent host) presents the exciting prospect of freedom from immunosuppression for transplant recipients. It is now 60 years since the first demonstration of
more » ... al tolerance in animal models of transplantation, but translation into routine clinical practice remains elusive. Helminth parasites may provide novel strategies toward achieving this goal. Helminths are remarkably successful parasites: they currently infect more than one quarter of the world's population. It is now well established that the parasites' success is the result of active immunomodulation of their hosts' immune response. Although this primarily secures ongoing survival of the parasites, helminth-induced immunomodulation can also have a number of benefits for the host. Significant reductions in the prevalence of allergy and autoimmune conditions among helminth-infected populations are well recognized and there is now a significant body of evidence to suggest that harmful immune responses to alloantigens may be abrogated as well. Here, we review all existing studies of helminth infection and transplantation, explore the mechanisms involved, and discuss possible avenues for future translation to clinical practice.
doi:10.1097/tp.0b013e3182a53f59 pmid:24025322 pmcid:PMC3940291 fatcat:fugpdjgd6ffzvj4qq3kwhsvwyy

Book Reviews

James S. McClain, Stephen T. Johnston, Roel Snieder, A J Reedman
2002 Episodes  
Stephen T. Johnston Not surprisingly, ray theory is of great importance in seismology as well since it accounts for a simplified description of the propagation of elastic waves.  ...  A J Reedman 2) and provided a figure showing the Kelvin-Bessel functions in equation 3-54.  ... 
doi:10.18814/epiiugs/2002/v25i1/008 fatcat:3d7bks7hp5ft3kswn2ioxozqgi

Monofunctional and Higher-Valent Platinum Anticancer Agents

Timothy C. Johnstone, Justin J. Wilson, Stephen J. Lippard
2013 Inorganic Chemistry  
Correspondence to: Stephen J. Lippard, lippard@mit.edu. Potential Conflict of Interest. SJL declares a financial interest in Blend Therapeutics. Supporting Information.  ...  2 J PtC = 15 Hz). 195 Pt NMR (DMSO-d 6 , 108 MHz): 1068.  ...  DNA-Binding Mechanism of Cisplatin where "G" Represents a Guanine Base H NMR (DMSO-d 6 , 400 MHz): 7.94 (s, 2H, 3 J PtH = 34 Hz), 6.31 (t, 6H, 1 J NH = 50 Hz). 13 C NMR (DMSO-d 6 , 100 MHz): 169.7 (  ... 
doi:10.1021/ic400538c pmid:23738524 pmcid:PMC3818431 fatcat:fjk6rxasenam7abs7ksvct2mb4

Brereton Greenhous, Stephen J. Harris, William C. Johnston et William G. P. Rawling, Le creuset de la guerre 1939-1945. Histoire officielle de l'Aviation royale canadienne, Tome III, Ottawa, Ministère des Approvisionnements et Services Canada, 1999, 1157 p

Christian Gagnon
2001 Bulletin d histoire politique  
Bref, l'ouvrage de Brereton Greenhous, Stephen J. Harris, William C. Johnston et William G. P.  ...  Brereton Greenhous, Stephen J. Harris, William C. J ohnston et William G. P. Rawling, Le creuset de la guerre 1939 ... 1945.  ... 
doi:10.7202/1060476ar fatcat:ns6qjas4h5bldb5re2vqymecfq

Authors' reply

Stephen M. Lawrie, J. Hall, A. M. McIntosh, D. G. C. Owens, E. C. Johnstone
2011 British Journal of Psychiatry  
doi:10.1192/bjp.198.4.324 fatcat:wuybydkajjhxhfwj4punqkfadu

"No level up!": no effects of video game specialization and expertise on cognitive performance

Fernand Gobet, Stephen J. Johnston, Gabriella Ferrufino, Matthew Johnston, Michael B. Jones, Antonia Molyneux, Argyrios Terzis, Luke Weeden
2014 Frontiers in Psychology  
Previous research into the effects of action video gaming on cognition has suggested that long term exposure to this type of game might lead to an enhancement of cognitive skills that transfer to non-gaming cognitive tasks. However, these results have been controversial. The aim of the current study was to test the presence of positive cognitive transfer from action video games to two cognitive tasks. More specifically, this study investigated the effects that participants' expertise and genre
more » ... pecialization have on cognitive improvements in one task unrelated to video gaming (a flanker task) and one related task (change detection task with both control and genre-specific images). This study was unique in three ways. Firstly, it analyzed a continuum of expertise levels, which has yet to be investigated in research into the cognitive benefits of video gaming. Secondly, it explored genre-specific skill developments on these tasks by comparing Action and Strategy video game players (VGPs). Thirdly, it used a very tight experiment design, including the experimenter being blind to expertise level and genre specialization of the participant. Ninety-two university students aged between 18 and 30 (M = 21.25) were recruited through opportunistic sampling and were grouped by video game specialization and expertise level. While the results of the flanker task were consistent with previous research (i.e., effect of congruence), there was no effect of expertise, and the action gamers failed to outperform the strategy gamers. Additionally, contrary to expectation, there was no interaction between genre specialization and image type in the change detection task, again demonstrating no expertise effect. The lack of effects for game specialization and expertise goes against previous research on the positive effects of action video gaming on other cognitive tasks.
doi:10.3389/fpsyg.2014.01337 pmid:25506330 pmcid:PMC4246654 fatcat:nz4mkda4u5dxved3olnsvztmey

Understanding and improving platinum anticancer drugs--phenanthriplatin

Timothy C Johnstone, Ga Young Park, Stephen J Lippard
2014 Anticancer Research  
Approximately half of all patients who receive anticancer chemotherapy are treated with a platinum drug. Despite the widespread use of these drugs, the only cure that can be claimed is that of testicular cancer following cisplatin treatment. This article reviews some of our recent work on phenanthriplatin, a cisplatin derivative in which a chloride ion is replaced by phenanthridine, and on one of its analogues, the previously reported pyriplatin. These cationic complexes form monofunctional
more » ... cts on DNA that do not significantly distort the duplex, yet efficiently block transcription. Cell-based assays reveal altered cellular uptake properties and a cancer cell-killing profile different from those of established platinum drugs. Mechanistic work, including a crystal structure analysis of platinum-modified DNA in the active site of RNA polymerase II, is discussed herein.
pmid:24403503 pmcid:PMC3937549 fatcat:zqh4vxsgjnbg5lz4n4ivyyoera

Robotic vs. laparoscopic distal pancreatectomy—equipoise in current clinical practice?

Chris J. C. Johnston, Jaswinder S. Samra, Stephen J. Wigmore, Anubhav Mittal
2019 Laparoscopic Surgery  
doi:10.21037/ls.2019.07.03 fatcat:737dxb6itfhulgezcagqdnfc64

Sevoflurane-induced changes in infants' quantifiable electroencephalogram parameters

Stephen McKeever, Linda Johnston, Andrew J. Davidson, Jerrold Lerman
2014 Pediatric Anaesthesia  
doi:10.1111/pan.12366 pmid:24612073 fatcat:72ykqe2jx5cupf2xqqwspllqge

Letter: Genetic counselling in Huntington's chorea

A Caro, M Jones, J Stephens, K Evans, W Walmsley, D Randall, A Johnston, J Heald
1976 BMJ (Clinical Research Edition)  
doi:10.1136/bmj.2.6032.420-b pmid:132984 pmcid:PMC1687492 fatcat:qbrb5eh6wvd2tj7rialqus4k4m

Response inhibition in the parametric Go/No-Go task in psychopathic offenders

Kathrin Weidacker, Robert J. Snowden, Frederic Boy, Stephen J. Johnston
2017 Psychiatry Research  
Previous research on response inhibition in psychopaths has failed to find consistent evidence for aberrant inhibitory ability, despite strong expectations to the contrary. However, previous examinations have utilised inhibition paradigms that suffer from critical shortcomings, such as a lack of ecological validity and overly simplistic response criteria. To assess inhibition under conditions close to the demands of everyday settings, the current study employs a parametric Go/No-go task in male
more » ... offenders (n = 77). Additionally, rather than treating psychopathy as a categorical descriptor, a dimensional approach is taken to assess the relationship between individual psychopathic traits and response inhibition performance. Results indicate significant relationships between response inhibition and individual facets of psychopathy as measured by the Psychopathy Checklist: Screening Version. A positive relationship was found between inhibitory ability and interpersonal aspects of psychopathy, reflecting an enhancement of inhibitory functioning for those scoring high on this facet. In addition, a negative association was found between psychopathic lifestyle characteristics and response inhibition. Whereas the negative association mirrors the conceptualisation of the lifestyle facet, the positive association between interpersonal psychopathic aspects and response inhibition might reflect a propensity for adaptive behaviour that enables psychopaths to adequately manipulate their victims and mask their true nature.
doi:10.1016/j.psychres.2017.01.083 pmid:28171793 fatcat:ciwadb5e5vgvxfciwlxklqpmta

A General Method to Discover Epitopes from Sera

Kurt Whittemore, Stephen Albert Johnston, Kathryn Sykes, Luhui Shen, Nicholas J Mantis
2016 PLoS ONE  
Antigen-antibody complexes are central players in an effective immune response. However, finding those interactions relevant to a particular disease state can be arduous. Nonetheless many paths to discovery have been explored since deciphering these interactions can greatly facilitate the development of new diagnostics, therapeutics, and vaccines. In silico B cell epitope mapping approaches have been widely pursued, though success has not been consistent. Antibody mixtures in immune sera have
more » ... en used as handles for biologically relevant antigens, but these and other experimental approaches have proven resource intensive and time consuming. In addition, these methods are often tailored to individual diseases or a specific proteome, rather than providing a universal platform. Most of these methods are not able to identify the specific antibody's epitopes from unknown antigens, such as un-annotated neo antigens in cancer. Alternatively, a peptide library comprised of sequences unrestricted by naturally-found protein space provides for a universal search for mimotopes of an antibody's epitope. Here we present the utility of such a non-natural random sequence library of 10,000 peptides physically addressed on a microarray for mimotope discovery without sequence information of the specific antigen. The peptide arrays were probed with serum from an antigen-immunized rabbit, or alternatively probed with serum pre-absorbed with the same immunizing antigen. With this positive and negative screening scheme, we identified the library-peptides as the mimotopes of the antigen. The unique library peptides were successfully used to isolate antigen-specific antibodies from complete immune serum. Sequence analysis of these peptides revealed the epitopes in the immunized antigen. We present this method as an inexpensive, efficient method for identifying mimotopes of any antibody's targets. These mimotopes should be useful in defining both components of the antigen-antibody complex.
doi:10.1371/journal.pone.0157462 pmid:27300760 pmcid:PMC4907474 fatcat:2yfv2z722jexbjqc2sl6f2ym6i

Do exurban communities want more development?

Dana Marie Bauer, Stephen K. Swallow, Pengfei Liu, Robert J. Johnston
2017 Journal of Land Use Science  
Analyses of additional questions related to residents' preferences for new residential developments are reported elsewhere (Johnston, et al., 2002a (Johnston, et al., , 2003a (Johnston, et al., , 2003b  ...  The probability that a particular ranking of J alternatives (1,2,…,J) has occurred is given by: Prob(1,2,…,J; ) = Prob(U 1 >U 2 >…>U J ), (5) where U j is the utility associated with alternative j (j=  ... 
doi:10.1080/1747423x.2017.1338769 fatcat:oiuacdtlt5ec3a6ndjzie3cv34

Cocos-Nazca slab window beneath Central America

Stephen T. Johnston, Derek J. Thorkelson
1997 Earth and Planetary Science Letters  
Car s Caribbean; Coc s Cocos; Naz s Nazca; J s triple junction; R s Cocos-Nazca spreading ridge. ( ) ing ridge subduction for the subducted parts of the slabs to diverge from one another.  ... 
doi:10.1016/s0012-821x(96)00242-7 fatcat:4hydds3vprdp7g5gusxcxssh5e

Human immune cell targeting of protein nanoparticles – caveospheres

Joshua J. Glass, Daniel Yuen, James Rae, Angus P. R. Johnston, Robert G. Parton, Stephen J. Kent, Robert De Rose
2016 Nanoscale  
Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated
more » ... + T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells-an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.
doi:10.1039/c6nr00506c pmid:27031090 fatcat:lklt4llf3fg35bfs4nnfotli7y
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