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OX40/OX40 ligand interactions in T-cell regulation and asthma 总被引:1,自引:0,他引:1
The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy in established disease rather than at disease onset is unknown. Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited. 相似文献
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Colish J Walker JR Elmayergi N Almutairi S Alharbi F Lytwyn M Francis A Bohonis S Zeglinski M Kirkpatrick ID Sharma S Jassal DS 《Chest》2012,141(3):674-681
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Ducas RA Philipp RK Jassal DS Wassef AW Weldon E Hussain F Schmidt C Khadem A Ducas J Grierson R Tam JW 《The Canadian journal of cardiology》2012,28(4):423-431
Background
Guidelines for reperfusion in ST-elevation myocardial infarction (STEMI) were recently adopted by the Canadian Cardiovascular Society. We have developed a blended model of prehospital thrombolytic (PHL) therapy or primary percutaneous coronary intervention (PPCI) activation, in order to achieve guideline times.Methods
In our urban centre of 658,700 people, emergency medical services (EMS) were trained to perform and screen electrocardiograms (ECGs) for suspected STEMI. Suspected ECGs were transmitted to a physician's hand-held device. If the physician confirmed the diagnosis they coordinated initiation of either PHL or PPCI. In cases where physicians found the prehospital ECG negative for STEMI (PHENST), patients were transported to the closest emergency room.Results
From July 21, 2008 to July 21, 2010, the Cardiac Outcomes Through Digital Evaluation (CODE) STEMI project received 380 transmitted calls. There were 226 confirmed STEMI by the on-call physician, 158 (70%) received PPCI, 48 (21%) received PHL, and 20 (9%) had angiography but no revascularization. The PPCI, median time from first medical contact to reperfusion was 76 minutes (interquartile range [IQR], 64-93). For PHL, median time from first medical contact to needle was 32 minutes (IQR, 29-39). The overall mortality rate for the STEMI patients was 8% (PHL = 4 [8.3%], PPCI = 8 [5%], medical therapy = 7 [35%]). There were 154 PHENST patients, 44% later diagnosed with acute coronary syndrome. The mortality rate for PHENST was 14%.Conclusions
Through a model of EMS prehospital ECG interpretation, digital transmission, direct communication with a physician, and rapid coordinated service, we demonstrate that benchmark reperfusion times in STEMI can be achieved. 相似文献9.
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Rebecca A. James Davinder Singh‐Grewal Senq‐J Lee Jim McGill Navid Adib 《Journal of paediatrics and child health》2016,52(3):262-271
The lysosomal storage disorders are a collection of progressive, multisystem disorders that frequently present in childhood. Their timely diagnosis is paramount as they are becoming increasingly treatable. Musculoskeletal manifestations often occur early in the disease course, hence are useful as diagnostics clues. Non‐inflammatory joint stiffness or pain, carpal tunnel syndrome, trigger fingers, unexplained pain crises and short stature should all prompt consideration of a lysosomal storage disorder. Recurrent ENT infections, hepatosplenomegaly, recurrent hernias and visual/hearing impairment – especially when clustered together – are important extra‐skeletal features. As diagnostic and therapeutic options continue to evolve, children with lysosomal storage disorders and their families are facing more sophisticated options for screening and treatment. The aim of this article is to highlight the paediatric presentations of lysosomal storage disorders, with an emphasis on the musculoskeletal features. 相似文献