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961.
Cytomegalovirus vector expressing RAE‐1γ induces enhanced anti‐tumor capacity of murine CD8+ T cells
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Tihana Tršan Kristina Vuković Petra Filipović Ana Lesac Brizić Niels A. W. Lemmermann Kilian Schober Dirk H. Busch William J. Britt Martin Messerle Stipan Jonjić 《European journal of immunology》2017,47(8):1354-1367
Designing CD8+ T‐cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE‐1γ as CD8+ T cell‐based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE‐1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD‐1. CMV vector expressing RAE‐1γ potentiated expansion of KLRG1+ CD8+ T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long‐term maintenance of epitope‐specific CD8+ T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8+ T‐cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8+ T‐cell sensitive tumors. 相似文献
962.
963.
Fraser C. Henderson Sr. Claudiu Austin Edward Benzel Paolo Bolognese Richard Ellenbogen Clair A. Francomano Candace Ireton Petra Klinge Myles Koby Donlin Long Sunil Patel Eric L. Singman Nicol C. Voermans 《American journal of medical genetics. Part C, Seminars in medical genetics》2017,175(1):195-211
964.
André Karch Stefanie Castell Frank Schwab Christine Geffers Hannah Bongartz Frank M. Brunkhorst Petra Gastmeier Rafael T. Mikolajczyk 《Journal of clinical microbiology》2015,53(2):648-652
Early and appropriate blood culture sampling is recommended as a standard of care for patients with suspected bloodstream infections (BSI) but is rarely taken into account when quality indicators for BSI are evaluated. To date, sampling of about 100 to 200 blood culture sets per 1,000 patient-days is recommended as the target range for blood culture rates. However, the empirical basis of this recommendation is not clear. The aim of the current study was to analyze the association between blood culture rates and observed BSI rates and to derive a reference threshold for blood culture rates in intensive care units (ICUs). This study is based on data from 223 ICUs taking part in the German hospital infection surveillance system. We applied locally weighted regression and segmented Poisson regression to assess the association between blood culture rates and BSI rates. Below 80 to 90 blood culture sets per 1,000 patient-days, observed BSI rates increased with increasing blood culture rates, while there was no further increase above this threshold. Segmented Poisson regression located the threshold at 87 (95% confidence interval, 54 to 120) blood culture sets per 1,000 patient-days. Only one-third of the investigated ICUs displayed blood culture rates above this threshold. We provided empirical justification for a blood culture target threshold in ICUs. In the majority of the studied ICUs, blood culture sampling rates were below this threshold. This suggests that a substantial fraction of BSI cases might remain undetected; reporting observed BSI rates as a quality indicator without sufficiently high blood culture rates might be misleading. 相似文献
965.
Mercè Durban Montserrat Barragán Marta Colodron Minerva Ferrer-Buitrago Petra De Sutter Björn Heindryckx Valérie Vernaeve Rita Vassena 《Journal of assisted reproduction and genetics》2015,32(6):879-886
PurposeIntracytoplasmic sperm injection (ICSI) is widely used to achieve fertilization in the presence of severe male factor, resulting in high fertilization rates. Nevertheless, 1–3 % of couples experience complete fertilization failure after ICSI. When a male factor is identified, assisted oocyte activation (AOA) can help overcome fertilization failures. The objective of this study is to describe a case of repeated complete fertilization failures after ICSI with donor oocytes, and to investigate the molecular and functional aspects of phospholipase C zeta (PLCζ) protein in the patient semen.MethodsThe patient was a normozoospermic male who had previously fathered, through natural conception, four children by a different partner. Molecular and functional analysis of sperm-specific PLCζ in the patient and control samples by means of gene sequencing, immunocytochemistry, Western blot, mouse oocyte activation test (MOAT), and mouse oocyte calcium analysis (MOCA) were used.ResultsPLCζ expression levels and distribution were significantly disrupted, although MOAT and MOCA did not indicate a decrease in activation ability.ConclusionsNormozoospermic males can have disrupted expression and distribution of PLCζ, and reduced activation ability after ICSI in human oocytes, despite their normal activation potential in functional testing using mouse oocytes. Discrepancy among molecular and functional data might exist, as mutations in the gene sequence may not be the only cause of alteration in PLCζ protein related to activation failures.
Electronic supplementary material
The online version of this article (doi:10.1007/s10815-015-0496-0) contains supplementary material, which is available to authorized users. 相似文献966.
RORγt+ hematopoietic cells are necessary for tumor cell proliferation during colitis‐associated tumorigenesis in mice
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967.
The two‐pore domain K2P channel TASK2 drives human NK‐cell proliferation and cytolytic function
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Andreas Schulte‐Mecklenbeck Stefan Bittner Petra Ehling Frank Döring Erhard Wischmeyer Johanna Breuer Alexander M. Herrmann Heinz Wiendl Sven G. Meuth Catharina C. Gross 《European journal of immunology》2015,45(9):2602-2614
Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor‐ and virus‐infected cells without prior stimulation. Killing of target cells is a multistep process including adhesion to target cells, formation of an immunological synapse, and polarization and release of cytolytic granules. The role of distinct potassium channels in this orchestrated process is still poorly understood. The current study reveals that in addition to the voltage‐gated KV1.3 and the calcium‐activated KCa3.1 channels, human NK cells also express the two‐pore domain K2P channel TASK2 (TWIK‐related acid‐sensitive potassium channel). Expression of Task2 varies among NK‐cell subsets and depends on their differentiation and activation state. Despite its different expression in TASK2highCD56brightCD16? and TASK2lowCD56dimCD16+ NK cells, TASK2 is involved in cytokine‐induced proliferation and cytolytic function of both subsets. TASK2 is crucial for leukocyte functional antigen (LFA‐1) mediated adhesion of both resting and cytokine‐activated NK cells to target cells, an early step in killing of target cells. With regard to the following mechanism, TASK2 plays a role in release of cytotoxic granules by resting, but not IL‐15‐induced NK cells. Taken together, our data exhibit two‐pore potassium channels as important players in NK‐cell activation and effector function. 相似文献
968.
IL‐15 dependent induction of IL‐18 secretion as a feedback mechanism controlling human MAIT‐cell effector functions
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Arne Sattler Chantip Dang‐Heine Petra Reinke Nina Babel 《European journal of immunology》2015,45(8):2286-2298
Mucosal‐associated invariant T (MAIT) cells are characterized by an invariant TCRVα7.2 chain recognizing microbial vitamin B metabolites presented by the MHC‐Ib molecule MR1. They are mainly detectable in the CD8+ and CD8?CD4? “double negative” T‐cell compartments of mammals and exhibit both Th1‐ and Th17‐associated features. As MAIT cells show a tissue‐homing phenotype and operate at mucosal surfaces with myriads of pathogenic encounters, we wondered how IL‐15, a multifaceted cytokine being part of the intestinal mucosal barrier, impacts on their functions. We demonstrate that in the absence of TCR cross‐linking, human MAIT cells secrete IFN‐γ, increase perforin expression and switch on granzyme B production in response to IL‐15. As this mechanism was dependent on the presence of CD14+ cells and sensitive to IL‐18 blockade, we identified IL‐15 induced IL‐18 production by monocytes as an inflammatory, STAT5‐dependent feedback mechanism predominantly activating the MAIT‐cell population. IL‐15 equally affects TCR‐mediated MAIT‐cell functions since it dramatically amplifies bacteria‐induced IFN‐γ secretion, granzyme production, and cytolytic activity at early time points, an effect being most pronounced under suboptimal TCR stimulation conditions. Our data reveal a new quality of IL‐15 as player in an inflammatory cytokine network impacting on multiple MAIT‐cell functions. 相似文献
969.
970.
Cross‐sectional survey of the disaster preparedness of nurses across the Asia–Pacific region
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Kim Usher RN RPN A/DipNEd BA BHSc MNSt PhD FACN FACMHN Jane Mills RN BNurs MNurs GradCertEd MEd PhD Caryn West RN GDip Res Methods PhD Evan Casella Nursing Student Passang Dorji RN Aimin Guo RN Virya Koy RN George Pego RN Souksavanh Phanpaseuth RN Olaphim Phouthavong RN Jamuna Sayami RN Muy Seang Lak RN Alison Sio RN Mohammad Mofiz Ullah RN Yu Sheng RN Yuli Zang RN Petra Buettner BSc MSc PhD Cindy Woods BEd PhD 《Nursing & health sciences》2015,17(4):434-443
Healthcare workers who have received disaster preparedness education are more likely to report a greater understanding of disaster preparedness. However, research indicates that current nursing curricula do not adequately prepare nurses to respond to disasters. This is the first study to assess Asia–Pacific nurses' perceptions about their level of disaster knowledge, skills, and preparedness. A cross‐sectional survey was conducted with 757 hospital and community nurses in seven Asia–Pacific countries. Data were collected using the modified Disaster Preparedness Evaluation Tool. Participants were found to have overall low‐to‐moderate levels of disaster knowledge, skills and preparedness, wherein important gaps were identified. A majority of the variance in disaster preparedness scores was located at the level of the individual respondent, not linked to countries or institutions. Multilevel random effects modelling identified disaster experience and education as significant factors of positive perceptions of disaster knowledge, skills, and management. The first step toward disaster preparedness is to ensure frontline health workers are able to respond effectively to disaster events. The outcomes of this study have important policy and education implications. 相似文献