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11.
Takuma Kitano Kaho Togawa Juri Takemori Yuya Motoki Keitaroh Kishida Saotomo Itoh Masaya Takamoto Shinsuke Taki Shigeaki Hida 《Genes to cells : devoted to molecular & cellular mechanisms》2023,28(3):226-236
Basophils produce interleukins (IL)-4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL-4 in response to IL-3 but not to high-affinity Fc receptor (FcεRI) cross-linking (CL), yet both required the immunoreceptor tyrosine-based activation motif (ITAM) containing adaptor Fc receptor γ-chain (FcRγ), while basophils activated in vitro by IL-3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL-3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation-associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP-12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL-3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL-4 production and the other to render basophils competent to respond to stimuli dependent on ITAM-containing adaptors DAP12 and FcRγ for IL-4 production. 相似文献
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Darija Jurišić Mia Zorić Geber Ivan Ćavar Dobrila Karlica Utrobičić 《Seminars in ophthalmology》2018,33(5):711-718
This study aimed to investigate the influence of silicone oil on the retinal nerve fiber layer (RNFL) thickness in patients with primary rhegmatogenous retinal detachment who underwent vitreoretinal surgery. The study included 47 patients (eyes), who underwent a pars plana vitrectomy with the silicone oil tamponade. The control group included unoperated eye of all participants. Spectral-domain optical coherence tomography (SD-OCT) was used for the measurements of peripapilar and macular RNFL thickness. The average peripapillary RNFL thickness was significantly higher in the silicone oil filled eyes during endotamponade and after its removal. The eyes with elevated IOP had less thickening of the RNFL in comparison to the eyes with normal IOP. Central macular thickness and macular volume were decreased in the silicone oil filled eyes in comparison to the control eyes. In conclusion, silicone oil caused peripapilar RNFL thickening in the vitrectomized eyes during endotamponade and after silicone oil removal. 相似文献
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Juri Sromicki Mathias Van Hemelrijck Martin O Schmiady Bernard Krüger Mohammed Morjan Dominique Bettex Paul R Vogt Thierry P Carrel Carlos-A Mestres 《Interactive Cardiovascular and Thoracic Surgery》2022,35(1)
Open in a separate window OBJECTIVESOral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).METHODSThis was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.RESULTSBetween January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).CONCLUSIONSEmergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients. 相似文献
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70 mm roll film exposed from the output phosphor of the image intensifier is a diagnostically satisfactory substitute for conventional spot films. It reduces the time and cost of the examination and the radiation dose delivered to the patient. 相似文献
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Antonello D’Andrea Juri Radmilovic Stefano Caselli Andreina Carbone Raffaella Scarafile Simona Sperlongano Giampaolo Tocci Tiziana Formisano Francesca Martone Biagio Liccardo Michele D’Alto Eduardo Bossone Maurizio Galderisi Paolo Golino 《The international journal of cardiovascular imaging》2018,34(10):1561-1561
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Stela ?iv?i?-?osi? Mirela Bu?i? ?eljko ?upan Gordana Pel?i? Martina Anu?i? Juri?i? ?eljka Jur?i? Mladen Ivanovski Sanjin Ra?ki 《Croatian medical journal》2013,54(1):65-70
During the past ten years, the efforts to improve and organize the national transplantation system in Croatia have resulted in a steadily growing donor rate, which reached its highest level in 2011, with 33.6 utilized donors per million population (p.m.p.). Nowadays, Croatia is one of the leading countries in the world according to deceased donation and transplantation rates. Between 2008 and 2011, the waiting list for kidney transplantation decreased by 37.2% (from 430 to 270 persons waiting for a transplant) and the median waiting time decreased from 46 to 24 months. The Croatian model has been internationally recognized as successful and there are plans for its implementation in other countries. We analyzed the key factors that contributed to the development of this successful model for organ donation and transplantation. These are primarily the appointment of hospital and national transplant coordinators, implementation of a new financial model with donor hospital reimbursement, public awareness campaign, international cooperation, adoption of new legislation, and implementation of a donor quality assurance program. The selection of key factors is based on the authors'' opinions; we are open for further discussion and propose systematic research into the issue.Transplantation is a widely accepted and successful life-saving treatment providing the best therapeutic benefit for hundreds of thousands of patients (1). Unfortunately, many people die while awaiting an organ transplant. A global shortage of organs available for transplantation raises many bioethical concerns, including the dilemma how to allocate limited resources to an unlimited number of needs and thus offer a fair and equal access to organ transplantation to all patients. Great efforts have been made to increase organ donation worldwide, but with only a moderate success in most of the countries. In contrast with this general trend, Croatia has recently experienced a boom in organ donation and transplantation. In 2011, Croatia had the highest rates of utilized cadaveric donors, kidney transplantations, and liver transplantations in the world (2-5) (Figure 1).Open in a separate windowFigure 1The number of kidney transplantations and the number of patients on the waiting list in Croatia between 2008 and 2011.Remarkably, only one decade ago, Croatia was lagging far behind other European countries with a low donation rate (2.7 donors per million population [p.m.p.] in 2000). The continuous improvement of the organization of the Croatian transplant program resulted in a steadily growing donor rate, which reached the highest level in 2011, with 33.6 utilized donors p.m.p (2). We analyzed the factors that might have contributed mostly to this great success. 相似文献
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Hitomi Hosoya Andrey S. Dobroff Wouter H. P. Driessen Vittorio Cristini Lina M. Brinker Fernanda I. Staquicini Marina Cardó-Vila Sara D’Angelo Fortunato Ferrara Bettina Proneth Yu-Shen Lin Darren R. Dunphy Prashant Dogra Marites P. Melancon R. Jason Stafford Kohei Miyazono Juri G. Gelovani Kazunori Kataoka C. Jeffrey Brinker Richard L. Sidman Wadih Arap Renata Pasqualini 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(7):1877-1882
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.A long-term goal in contemporary cancer nanomedicine has been to design and generate drug delivery systems that improve the narrow therapeutic window associated with conventional chemotherapeutics (1, 2). Conceptually, several nanotechnology-based entity candidates, including protocells (3), biosynthetic nanoparticles (NPs), viruses, and liposome-based nanoparticles, could be targeted for active delivery through a defined cell surface ligand receptor system and/or physically triggered for finely tuned cargo release (2, 4, 5).Numerous efforts have been made to functionalize NPs by combining them with antibodies, aptamers, peptides, vitamins, or carbohydrates (6–8), but the majority of studies involve untargeted nanoplatforms (4, 9). In practice, targeting NPs is far from trivial, and ongoing challenges include synthesis and purification, selection of an appropriate ligand receptor, and specific composition for NP conjugation. Even the conjugation reaction itself may alter the binding of the tumor-targeting moiety to its receptor through conformational changes, steric freedom restriction, or orientation distortion (10, 11). Unfortunately, the cost-to-benefit ratio of these modifications often elevate the complexity of the NP synthesis, complicating regulatory hurdles because of formulations that are heterogeneous or difficult to reproduce (10, 12, 13).To minimize such drawbacks, NPs can be functionalized via virus-based nanoplatforms as an alternative for targeted cargo delivery (14–16). In particular, filamentous bacteriophage (phage)—a prokaryotic virus—is an attractive candidate to develop a bionanomedicine for cancer therapeutics because phage particles are cost-effectively produced with biological uniformity, as well as being physically robust and stable under harsh conditions (17). Notably, phage-based nanoplatforms are biocompatible and nonpathogenic with eukaryotic organisms and are able to preserve the desired cell targeting and internalization (18). Moreover, phage particles are ideal for incorporating other NPs, which can be released after reaching the tumor site. An admixture of colloidal gold NP (AuNP) with phage particles spontaneously organizes into hydrogel network-like fractal structures (19, 20). These hydrogel networks offer convenient multifunctional integration within a single entity for tumor targeting, enhanced fluorescence and dark-field microscopy, near-infrared (NIR) photon-to-heat conversion, and surface-enhanced Raman scattering (SERS)-based detection (20, 21).In the present work, we developed a tumor targeting theranostic (meaning a combination of therapeutics and diagnostics) hydrogel-based nanoplatform that enables ligand-directed tumor targeting, multimodal imaging capability, and triggered therapeutic cargo release. Our data suggest that targeted hydrogel photothermal therapy represents a functional theranostic approach (fostering “see and treat, treat and see”) in the diagnosis and management of tumors. 相似文献
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