33 research outputs found
Arginine depletion as a mechanism for the immune privilege of corneal allografts.
Get PDFThe cornea is an immune privileged tissue. Since arginase has been found to modulate T-cell function by depleting arginine, we investigated the expression of arginase in the cornea and its possible role in immune privilege using a murine transplant model. We found that both the endothelium and epithelium of murine corneas express functional arginase I, capable of down-regulating T-cell proliferation in an in vitro culture system. The administration of the specific arginase inhibitor N-hydroxy-nor-L-Arg to recipient mice resulted in an accelerated rejection of allogeneic C57BL/6 (B6) corneal grafts. In contrast, in vivo blockade of arginase activity had no effect in altering the course of rejection of primary skin grafts that express little, if any, arginase. In addition, the inhibition of arginase did not alter systemic T-cell proliferation. These data show that arginase is functional in the cornea and contributes to the immune privilege of the eye, and that modulation of arginase contributes to graft survival
endritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition
No full textDendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within the ER. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme IDO. CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4(+) CD25(+) and CD4(+) CD25(-) Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO(+) DCs lacked donor specificity. In the absence of any immunosuppressive treatment, i.v. administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction.</p
Sirolimus and Mycophenolate as Combination Prophylaxis in Corneal Transplant Recipients at High Rejection Risk
No full textFear of fiction: the authorial response to realism in selected works by Swift, Defoe, and Richardson
Get PDFIf Mrs. Whitehouse produced a pornographic play, it would arouse enormous interest, mainly because of Mrs. Whitehouse’s well known views on pornography. It is an ancient fact of English Literature that two of the best known pioneers of the English realistic novel, Daniel Defoe and Samuel Richardson, were Puritans. And there is an almost equally ancient critical tradition which traces the easy path of Puritan literature, in combination with other cultural forces, towards the production of realistic fiction. The central argument of this thesis is that there was no such easy path. Puritan autobiography was unrealistic in its very nature, while Puritan feeling towards fiction was hostile, with realistic, or verisimilar fiction provoking most hostility because the most deceitful. Thus the writing of a realistic novel was a radical departure for the Puritan, and one that was fraught with tension. It is this tension, or fear of fiction, and its effects on work of the two Puritan novelists, and that odd Anglican Jonathan Swift, that is the subject of this thesis. Swift joins Defoe and Richardson as an author with a special relationship with Defoe, and himself closer to a fearful anti- mimetic "tradition" than the comic tradition in which he is usually placed alongside Fielding and Sterne. Selected works of the three authors reveal their struggle with the intense problems that realism created for them, and their eventual 'solutions'. Hence by the time that Dr. Johnson made his famous critical statement against the fearful potential of realism in his fourth Rambler [31 March 1750), he was actually formalising material that had been well examined in the fiction under discussion, rather than beating an original critical path in response to Fielding's supposedly 'new' verisimilar form
Interactive Visual Exploration of Region-based Sensitivities in Fiber Tracking
Get PDFFiber tracking is a powerful technique that provides valuable insights into the complex white matter structure of the human brain. However, the processing pipeline involves many sources of uncertainty, with one notable factor being the user-defined parameters that significantly influence the resulting outputs. Among these parameters, the definition of seed-points is a crucial aspect in most fiber tracking algorithms. These seed-points are determined through regions of interest (ROI) and serve as the initial points for fiber tract generation. In this work, we present an interactive technique that utilizes seed-point sensitivities to guide the definition of regions of interest (ROI). We examine various scenarios where sensitivity information can enhance the ROI definition process and provide user guidelines and recommended actions for each scenario. Building upon this analysis, we have developed a visualization strategy that enables users to explore seed-point sensitivities effectively and facilitate the definition of optimal ROIs. We present results highlighting the benefits of the proposed visual design in the clinical pipelines.Computer Graphics and Visualisatio
Effect of Glaucoma on Corneal Graft Survival According to Indication for Penetrating Keratoplasty
No full textDesign and conduct of randomized clinical trials evaluating surgical innovations in ophthalmology: A systematic review
Get PDFPURPOSE: Surgical innovations are necessary to improve patient care. After an initial exploratory phase novel surgical technique should be compared with alternative options or standard care in randomized clinical trials (RCTs). However surgical RCTs have unique methodological challenges. Our study sought to investigate key aspects of the design, conduct and reporting of RCTs of novel surgeries. DESIGN: Systematic Review METHODS: The protocol was prospectively registered in PROSPERO (CRD42021253297). RCTs evaluating novel surgeries for cataract, vitreoretinal, glaucoma and corneal diseases were included. Medline, EMBASE, Cochrane Library and Clinicaltrials.gov were searched. The search period was January 1, 2016, to June 16, 2021. RESULTS: Fifty-two ophthalmic surgery RCTs were identified in the fields of glaucoma (n=12), vitreoretinal surgery (n=5) cataract (n=19) and cornea (n=16). A description defining the surgeon's experience or level of expertise was reported in 30 RCTs (57%); and was presented in both, control and intervention groups, in eleven (21%). Specification of number of cases performed in the particular surgical innovation being assessed prior to the trial was reported in 10 RCTs (19%); and an evaluation of quality of the surgical intervention in seven (13%). Prospective trial registration was recorded in 12 RCTs (23%), retrospective registration in 13 (25%) and there was no registration record in the remaining 28 (53%) studies. CONCLUSION: Important aspects of the study design such as surgical learning curve, surgeon's previous experience, quality assurance, and trial registration details were often missing in novel ophthalmic surgical procedures. The IDEAL framework aims to improve the quality of study design
A randomised, controlled, observer-masked trial of corneal cross-linking for progressive keratoconus in children : the KERALINK protocol
Get PDFThis work was supported by the Efficacy and Mechanism Evaluation Programme (reference 14/23/18), a MRC and NIHR partnership.Introduction: The KERALINK trial tests the hypothesis that corneal cross-linking (CXL) treatment reduces the progression of keratoconus in comparison to standard care in patients under 17 years old. KERALINK is a randomised controlled, observer-masked, multicentre trial in progressive keratoconus comparing epithelium-off CXL with standard care, including spectacles or contact lenses as necessary for best-corrected acuity. Methods and analysis: A total of 30 participants will be randomised per group. Eligible participants aged 10-16 years with progressive keratoconus in one or both eyes will be recruited. Following randomisation, participants will be followed up 3-monthly for 18 months. The effect on progression will be determined by K-2 on corneal topography. The primary outcome measure is between-group difference in K-2 at 18 months adjusted for K-2 at baseline examination. Secondary outcomes are the effect of CXL on (1) keratoconus progression, (2) time to keratoconus progression, (3) visual acuity, (4) refraction, (5) apical corneal thickness and (6) adverse events. Patient-reported effects will be explored by questionnaires. Ethics and dissemination Research Ethics Committee Approval was obtained on 30 June 2016 (ref: 14/LO/1937). Current protocol: V.5.0 (08/11/2017). Study findings will be published in peer-reviewed journals.Peer reviewe
Constraining instantaneous fluxes and integrated compositions of fluvially discharged organic matter
Get PDFAuthor Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Freymond, C. V., Lupker, M., Peterse, F., Haghipour, N., Wacker, L., Filip, F., et al. (2018). Constraining instantaneous fluxes and integrated compositions of fluvially discharged organic matter. Geochemistry, Geophysics, Geosystems, 19, 2453 2462. doi: 10.1029/2018GC007539.Fluvial export of organic carbon (OC) and burial in ocean sediments comprises an important carbon sink, but fluxes remain poorly constrained, particularly for specific organic components. Here OC and lipid biomarker contents and isotopic characteristics of suspended matter determined in depth profiles across an active channel close to the terminus of the Danube River are used to constrain instantaneous OC and biomarker fluxes and integrated compositions during high to moderate discharges. During high (moderate) discharge, the total Danube exports 8 (7) kg/s OC, 7 (3) g/s higher plant‐derived long‐chain fatty acids (LCFA), 34 (21) g/s short‐chain fatty acids (SCFA), and 0.5 (0.2) g/s soil bacterial membrane lipids (brGDGTs). Integrated stable carbon isotopic compositions were TOC: −28.0 (−27.6)‰, LCFA: −33.5 (−32.8)‰ and Δ14C TOC: −129 (−38)‰, LCFA: −134 (−143)‰, respectively. Such estimates will aid in establishing quantitative links between production, export, and burial of OC from the terrestrial biosphere.This project was funded by the Swiss National Science Foundation SNF. Grant Number: 200021_140850. F.P. acknowledges funding from NWO‐VENI grant 863.13.016. We thank the sampling crews from both field campaigns (Björn Buggle, James Saenz, Alissa Zuijdgeest, Marilu Tavagna, Stefan Eugen Filip, Silvia Lavinia Filip, Mihai, Clayton Magill, Thomas Blattmann, and Michael Albani), Daniel Montluçon for lab support and Hannah Gies for PCGC work. Figures, tables, and equations can be found in supporting information
