| 1. |
- Bousquet, J., et al.
(författare)
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ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
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| 2. |
- Bousquet, J., et al.
(författare)
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Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
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Forskningsöversikt (refereegranskat)abstract
- Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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| 3. |
- Bousquet, J., et al.
(författare)
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MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY-BLACKWELL. - 0105-4538 .- 1398-9995. ; 70:11, s. 1372-1392
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Tidskriftsartikel (refereegranskat)abstract
- Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Banerjee, D., et al.
(författare)
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Towards a test of the Weak Equivalence Principle of gravity using anti-hydrogen at CERN
- 2016
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Ingår i: 2016 Conference On Precision Electromagnetic Measurements (CPEM 2016). - 9781467391344
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Konferensbidrag (refereegranskat)abstract
- The aim of the GBAR (Gravitational Behavior of Antimatter at Rest) experiment is to measure the free fall acceleration of an antihydrogen atom, in the terrestrial gravitational field at CERN and therefore test the Weak Equivalence Principle with antimatter. The aim is to measure the local gravity with a 1% uncertainty which can be reduced to few parts of 10(-3).
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| 13. |
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| 14. |
- Perez, P., et al.
(författare)
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The GBAR antimatter gravity experiment
- 2015
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Ingår i: Hyperfine Interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540. ; , s. 21-27
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Konferensbidrag (refereegranskat)abstract
- The GBAR project (Gravitational Behaviour of Anti hydrogen at Rest) at CERN, aims to measure the free fall acceleration of ultracold neutral anti hydrogen atoms in the terrestrial gravitational field. The experiment consists preparing anti hydrogen ions (one antiproton and two positrons) and sympathetically cooling them with Be (+) ions to less than 10 mu K. The ultracold ions will then be photo-ionized just above threshold, and the free fall time over a known distance measured. We will describe the project, the accuracy that can be reached by standard techniques, and discuss a possible improvement to reduce the vertical velocity spread.
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| 15. |
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| 16. |
- Nilsson, Thomas, 1965, et al.
(författare)
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Neutron Momentum Distributions from Core Break-up Reactions of Halo Nuclei
- 1995
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Ingår i: Europhysics Letters. - 0295-5075 .- 1286-4854. ; 30:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Neutron angular distributions from violent break-up reactions of Li-11 and Be-11 have been measured at 28 MeV/u and 280 MeV/u and at 41 MeV/u and 460 MeV/u, respectively. The derived neutron momentum distributions show a narrow component in transverse momentum that is within uncertainties independent of beam energy and target charge. This component is suggested to be simply related to the momentum distribution of the loosely bound halo neutron(s) in the projectiles.
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| 17. |
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| 18. |
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| 19. |
- Humbert, F., et al.
(författare)
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Longitudinal and Transverse-Momentum Distributions of Li-9 Fragments from Break-up of Li-11
- 1995
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 347:3-4, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- Transverse and longitudinal momentum distributions of Li-9 fragments from Li-11 break-up reactions in C, Al and Pb targets have been measured at 280 MeV/u. The two-neutron removal cross-section was measured to be sigma(-2n), = 0.26 +/- 0.02 b for the carbon target, sigma(-2n) = 0.47 +/- 0.08 b for the aluminum target and sigma(-2n), = 1.9 +/- 0.4 b for the lead target. No significant difference is observed between the narrow widths (FWHM approximate to 47 MeV/c) of the transverse and longitudinal momentum distributions of the Li-9 fragments. The physical implications of this are discussed.
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| 20. |
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| 21. |
- Nilsson, Thomas, 1965, et al.
(författare)
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He-6 and neutron momentum distributions from He-8 in nuclear break-up reactions at 240 MeV/u
- 1996
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Ingår i: Nuclear Physics A. - 0375-9474. ; 598:3, s. 418-434
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Tidskriftsartikel (refereegranskat)abstract
- Neutron and He-6 momentum distributions from He-8 break-up reactions in a C target have been measured at 240 MeV/u. The two-neutron removal cross section was found to be sigma(-2n) = 0.27 +/- 0.03 b. The nature of the momentum distributions is interpreted in some simple reaction scenarios.
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| 22. |
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| 24. |
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| 27. |
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| 28. |
- Kaltenbaek, Rainer, et al.
(författare)
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Macroscopic Quantum Resonators (MAQRO) : 2015 update
- 2016
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Ingår i: EPJ Quantum Technology. - : Springer Berlin/Heidelberg. - 2196-0763. ; 3:1
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Forskningsöversikt (refereegranskat)abstract
- Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schrodinger's cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored 'quantum-classical' transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments.
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| 29. |
- Luda, Katarzyna M., et al.
(författare)
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IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis
- 2016
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Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 44:4, s. 860-874
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Tidskriftsartikel (refereegranskat)abstract
- The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ+ and CD4+CD8αα+ T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.
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| 30. |
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| 31. |
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| 32. |
- Calus, L, et al.
(författare)
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IL-21 Is Increased in Nasal Polyposis and after Stimulation with Staphylococcus aureus Enterotoxin B
- 2017
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 174:3-4, s. 161-169
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to <i>Staphylococcus aureus</i> enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation. <b><i>Methods:</i></b> IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (<i>n</i> = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; <i>n</i> = 23), and CRSwNP (<i>n</i> = 35). The expression of IL-21 by CD4+ T cells was analyzed in tissue at baseline and after 24-h stimulation of tissue fragments with <i>S. aureus</i> enterotoxin B (SEB) using flow cytometry. Finally, human nasal IL-21+CXCR5+CD4+ T cells were isolated and coincubated with human blood naive B cells to investigate their functionality. <b><i>Results:</i></b> IL-21 mRNA expression was increased in the CRSwNP group (<i>p</i> < 0.05) compared to the control group, and B-cell lymphoma-6 and B-lymphocyte-induced maturation protein-1 were upregulated in CRSwNP versus CRSsNP. Furthermore, SEB was able to increase IL-21 mRNA expression significantly (<i>p</i> < 0.01) in nasal polyps. Flow cytometry revealed that the source of IL-21 was predominantly CD4+ T cells and that IL-21+CD4+ T cells were significantly increased in polyp tissue and further increased after SEB stimulation. Finally, tissue CXCR5+CD4+ T cells derived from nasal polyp tissue were able to induce maturation of human naive B cells. <b><i>Conclusions:</i></b> IL-21- and IL-21-producing CD4+ T cells were increased in CRSwNP. In addition, SEB induced an increase in IL-21 and IL-21+CD4+ T cells, suggesting that <i>S. aureus</i> can modulate the function of Tfh cells in nasal polyps. We speculate that T-follicular helper cells and IL-21 are important in the pathophysiology of CRSwNP.
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| 33. |
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| 34. |
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| 35. |
- de Boer, W. I., et al.
(författare)
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Altered expression of epithelial junctional proteins in atopic asthma : possible role in inflammation
- 2008
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Ingår i: Canadian Journal of Physiology and Pharmacology. - : Canadian Science Publishing. - 0008-4212 .- 1205-7541. ; 86:3, s. 105-12
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, alpha-catenin, and beta-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, alpha-catenin and beta-catenin were present in the cellular membrane and less in the cytoplasm. Only beta-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. alpha-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of beta-catenin was not different. Our results suggest that the lower epithelial alpha-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium.
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| 36. |
- Eekers, Danielle B. P., et al.
(författare)
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The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology
- 2018
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Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 128:1, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (Cr) and magnetic resonance (MR) imaging. Methods: CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. Results: The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). Conclusion: In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at w.cancerdata.c and will be updated whenever required.
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| 37. |
- Granville, S, et al.
(författare)
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Optical conductivity and x-ray absorption and emission study of the band structure of MnN films
- 2005
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 72:20, s. 205127-
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Tidskriftsartikel (refereegranskat)abstract
- The band structure of MnN films prepared by ion assisted deposition has been investigated by optical conductivity and x-ray absorption and emission spectroscopies. X-ray diffraction and extended x-ray absorption fine structure show the films to be nanocrystalline but phase pure and exhibiting the known antiferromagnetic distorted rocksalt phase. X-ray emission spectroscopy of the N K-edge and x-ray absorption near edge spectroscopy of both the N K- and Mn L-edges are used to probe the occupied and empty densities of states, which compare well with the N(2p) and Mn(3d) partial densities of states calculated using the linearized muffin-tin orbital band structure method. A similar comparison is made between the measured optical conductivity and the calculated contribution from interband transitions. It is possible to associate the main features in the measured spectrum with corresponding ones in the calculated optical function. The major differences between calculated and measured spectra can be understood on the basis of a limited electron mean-free-path in these nanocrystalline films, which broadens the features in the joint density of states and relaxes the momentum conservation requirement. The calculated optical functions are analyzed in detail in terms of their dominant band-to-band contributions and in addition the polarization dependence is predicted. Temperature dependent conductivity measurements are also reported and show a clear metallic behavior and a weak Kondo-like low temperature anomaly.
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| 38. |
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| 39. |
- LAMBRECHT, G, et al.
(författare)
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THE DESIGN AND PHARMACOLOGY OF NOVEL SELECTIVE MUSCARINIC AGONISTS AND ANTAGONISTS
- 1995
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Ingår i: LIFE SCIENCES. - : PERGAMON-ELSEVIER SCIENCE LTD. ; 56:11-12
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The muscarinic pharmacology of Cl-methyl-substituted chiral compounds related to McN-A-343 and of(R)- and (S)-dimethindene has been studied. Among the McN-A-343 analogues, the (S)-enantiomers were more potent and had higher affinity than the (R)-isomers.
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| 40. |
- Mauersberger, C, et al.
(författare)
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Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation
- 2022
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Ingår i: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1:12, s. 1174-1186
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Tidskriftsartikel (refereegranskat)abstract
- Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr−/− mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. Importantly, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr−/− mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD.
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| 41. |
- Rajwa, Pawel, et al.
(författare)
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Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
- 2024
-
Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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| 42. |
- Scott, C L, et al.
(författare)
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CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells.
- 2015
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:2, s. 327-339
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Tidskriftsartikel (refereegranskat)abstract
- The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64(-)CD103(-)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses.Mucosal Immunology advance online publication, 20 August 2014; doi:10.1038/mi.2014.70.
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| 43. |
- Semmrich, Monika, et al.
(författare)
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Directed antigen targeting in vivo identifies a role for CD103(+) dendritic cells in both tolerogenic and immunogenic T-cell responses.
- 2012
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 5:2, s. 150-60
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Tidskriftsartikel (refereegranskat)abstract
- The αE integrin chain CD103 identifies a subset of migratory dendritic cells (DCs) in the gut, lung, and skin. To gain further understanding of the function of CD103(+) DCs in regulating adaptive immunity in vivo, we coupled ovalbumin (OVA) to the CD103 antibody M290 (M290.OVA). Intraperitoneal injection of M290.OVA induced OVA-specific CD8(+) and CD4(+) T-cell proliferation in lymph nodes (LNs) of wild-type but not CD103(-/-) mice, or in mice depleted of CD11c(+) cells. In the absence of maturation stimuli, systemic antigen targeting to CD103(+) DCs led to tolerance of CD8(+) T cells, whereas coadministration of adjuvant induced cytotoxic T-lymphocyte (CTL) immunity and antibody production. Mucosal intratracheal application of M290.OVA also induced T-cell proliferation in mediastinal LNs, yet the functional outcome was tolerance that inhibited subsequent development of allergic airway inflammation and immunoglobulin E (IgE) responses to inhaled OVA. These findings identify antigen targeting to CD103(+) DCs as a potential strategy to regulate immune responses in nonlymphoid mucosal tissues.
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| 44. |
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| 45. |
- Vetters, J, et al.
(författare)
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The ubiquitin-editing enzyme A20 controls NK cell homeostasis through regulation of mTOR activity and TNF
- 2019
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:9, s. 2010-2023
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Tidskriftsartikel (refereegranskat)abstract
- The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. In addition, A20 protects cells from death in an ill-defined manner. While most studies focus on its role in the TNF-receptor complex, we here identify a novel component in the A20-mediated decision between life and death. Loss of A20 in NK cells led to spontaneous NK cell death and severe NK cell lymphopenia. The few remaining NK cells showed an immature, hyperactivated phenotype, hallmarked by the basal release of cytokines and cytotoxic molecules. NK-A20−/− cells were hypersensitive to TNF-induced cell death and could be rescued, at least partially, by a combined deficiency with TNF. Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20−/− cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis.
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| 46. |
- Vlaminck, S, et al.
(författare)
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Surgery in Nasal Polyp Patients: Outcome After a Minimum Observation of 10 Years
- 2021
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Ingår i: American journal of rhinology & allergy. - : SAGE Publications. - 1945-8932 .- 1945-8924. ; 35:4, s. 449-457
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Tidskriftsartikel (refereegranskat)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) often requires surgery, but recurrence even after surgery is common. Recurrence rates largely vary in literature and asthma seems to be a comorbid factor. Objective In this study, we aim to estimate disease recurrence during a long-term follow-up, together with the investigation of possible predicting and/or influencing parameters. Methods Out of 196 patients operated for CRSwNP between 01/2000 and 01/2006, 133 patients had a follow-up of at least 10 years and could be included. The inflammatory profile at surgery was determined on nasal tissue and sinonasal secretions, and included analysis of eosinophils, eosinophilic-rich mucus (ERM) typically containing Charcot-Leyden crystals (CLC), and fungal hyphae (FH). During follow-up, recurrence, received treatments and comorbidities were collected. Results Out of the 133 included patients, local eosinophilia was present in 81% and ERM in 60%. Recurrence during follow-up was observed in 62%, and was associated with local eosinophilia and ERM (both p < 0.001). Asthma was present in 28% at inclusion, and 17% developed asthma after surgery during follow-up. The presence of asthma, at inclusion as well as developed during follow-up, was significantly associated with recurrence of CRSwNP (p = 0.001 for group comparison). Conclusion Recurrence after CRSwNP surgery is common when a long-term follow-up is taken into account. ERM detected in sinonasal secretions at surgery seems to be a predictive factor for recurrence and need for revision surgery. Asthma is a frequently found comorbid factor in CRSwNP, develops even at higher age despite surgical treatment for CRSwNP, and is also associated with a higher recurrence rate. Sustained medical care after surgery is mandatory.
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