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排序方式: 共有510条查询结果,搜索用时 15 毫秒
81.
Marina Ostankovitch Frdrique-Anne Le Gal Francine Connan Dorine Chassin Jeannine Choppin Jean-Grard Guillet 《International journal of cancer. Journal international du cancer》1997,72(6):987-994
This study investigates the generation of primary melanoma cell-specific cytotoxic T lymphocytes (CTLs) in vitro. Induction of peptide-specific CTLs from unfractionated naive peripheral blood mononuclear cells from HLA-A2 healthy donors was assessed using 2 recently described 9-mer epitopes from the melanoma tumor antigen Melan-A/MART-1. The need for help from CD4+ T lymphocytes for the long-lasting induction of CTLs and the capacity of the peptide-induced CTL lines to recognize many melanoma cells were evaluated. CTL lines were obtained reproducibly when CD4+ T-lymphocyte help was provided during the primary stimulation either in an autologous way, in the case of tetanus toxoid antigen (TT) responder donors, or with allogeneic TT-activated T-helper cells, separated by an insert well, in the case of tetanus toxoid non-responder donors. We also investigated helper T-cell-derived factors that are produced by TT-activated lymphocytes. Our results strongly suggest that a complex network of cytokines like interleukin-2 (IL-2), interferon-γ, IL-6 and IL-1 exerts stimulatory effects for the initiation process of CTLs. In contrast, cytokine-like IL-4 might inhibit generation of cytolytic activity if provided by TT-activated T cells at early stages of induction. Our approach can be used to generate CTLs of a desired specificity for clinical use in adoptive immunotherapy protocols. Int. J. Cancer 72:987–994, 1997. © 1997 Wiley-Liss, Inc. 相似文献
82.
Thomas Wolfers A. Marten H. Onnink Marcel P. Zwiers Alejandro Arias-Vasquez Martine Hoogman Jeanette C. Mostert Cornelis C. Kan Dorine Slaats-Willemse Jan K. Buitelaar Barbara Franke 《Journal of psychiatry & neuroscience : JPN》2015,40(5):344-351
Background
Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV.Methods
We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging–derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest.Results
We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed.Limitations
Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks.Conclusion
This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD. 相似文献83.
Mohamad G. Fakih MD MPH Margarita E. Pena MD Stephen Shemes Janice Rey MT Dorine Berriel‐Cass RN MA Susan M. Szpunar PhD Ruth T. Savoy‐Moore PhD Louis D. Saravolatz MD 《Academic emergency medicine》2010,17(3):337-340
Objectives: Avoiding placement of unnecessary urinary catheters (UCs) in the emergency department (ED) affects UC utilization during hospitalization. The authors sought to evaluate the effect of establishing institutional guidelines for appropriate UC placement coupled with emergency physician (EP) education on UC utilization. Methods: Urinary catheter utilization was measured before and after the establishment of guidelines and EP education. Data collected included the presence of a UC on ED arrival, placement of a UC in the ED, documentation of a physician order for UC placement, reasons for placement, and compliance with the guidelines. Chi‐square analyses were used to study the association between pre‐ and postintervention time periods and catheter use. Results: A total of 377 (15%) patients had UCs; only 151 (47%) UCs initially placed in the ED had a physician order documented. UC placement was appropriately indicated in 75.5% of patients with a documented physician order, but in only 52% of cases without a documented physician order (p < 0.001). The physician intervention was associated with an overall reduction in UC utilization from 16.4% to 13% (p = 0.018). Physicians ordered 40% fewer UCs postintervention compared to preintervention. Preintervention, a physician order for UC placement was found indicated in 72.6% patients, compared to 82.2% patients with UC placed postintervention (p = 0.21). Conclusions: Establishing guidelines for UC placement and physician education in the ED were associated with a marked reduction in utilization. However, addressing appropriate UC utilization may require evaluating other factors such as nursing influence on utilization. ACADEMIC EMERGENCY MEDICINE 2010; 17:337–340 © 2010 by the Society for Academic Emergency Medicine 相似文献
84.
Cocaine withdrawal reduces GABABR transmission at entopeduncular nucleus – lateral habenula synapses
Dorine Tan Alvaro Nuno‐Perez Manuel Mameli Frank J. Meye 《The European journal of neuroscience》2019,50(3):2124-2133
Lateral habenula (LHb) hyperactivity plays a pivotal role in the emergence of negative emotional states, including those occurring during withdrawal from addictive drugs. We have previously implicated cocaine‐driven adaptations at synapses from the entopeduncular nucleus (EPN) to the LHb in this process. Specifically, ionotropic GABAA receptor (R)‐mediated neurotransmission at EPN‐to‐LHb synapses is reduced during cocaine withdrawal, due to impaired vesicle filling. Recent studies have shown that metabotropic GABABR signaling also controls LHb activity, although its role at EPN‐to‐LHb synapses during drug withdrawal is unknown. Here, we predicted that cocaine treatment would reduce GABABR‐mediated neurotransmission at EPN‐to‐LHb synapses. We chronically treated mice with saline or cocaine, prepared brain slices after two days of withdrawal and performed voltage‐clamp recordings from LHb neurons whilst optogenetically stimulating EPN terminals. Compared with controls, mice in cocaine withdrawal exhibited reduced GABAAR‐mediated input to LHb neurons, and a reduced occurrence of GABABR‐signaling at EPN‐to‐LHb synapses. We then assessed the underlying mechanism of this decrease. Application of GABABR agonist baclofen evoked similar postsynaptic responses in EPN‐innervated LHb neurons in saline‐ and cocaine‐treated mice. Release probability at EPN‐to‐LHb GABAergic synapses was also comparable between groups. However, incubating brain slices in glutamine to facilitate GABA vesicle filling, normalized GABABR‐currents at EPN‐to‐LHb synapses in cocaine‐treated mice. Overall, we show that during cocaine withdrawal, together with reduced GABAAR transmission, also GABABR‐mediated inhibitory signaling is diminished at EPN‐to‐LHb synapses, likely via the same presynaptic deficit. In concert, these alterations are predicted to contribute to the emergence of drug withdrawal symptoms, facilitating drug relapse. 相似文献
85.
Araud T Graw S Berger R Lee M Neveu E Bertrand D Leonard S 《Biochemical pharmacology》2011,(8):904-914
The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca2+, that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [125I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2 bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. 相似文献
86.
Brun V Neveu V Pers YM Fabre S Quatannens B Bastian H Clerget-Chossat N Jorgensen C Foussat A 《International immunopharmacology》2011,11(8):1074-1078
IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4+ regulatory cells able to prevent in vitro bystander T-cell proliferation and to inhibit a wide range of inflammatory diseases in mice. Our aim was to evaluate the frequency and function of joint specific Tr1 cells in the peripheral blood of severe Rheumatoid Arthritis (RA) patients. The collagen II protein was chosen to isolate Tr1 cells specific for a joint antigen. We successfully isolated Tr1 clones from 9 out of 11 RA patients. We showed that cells from patients display the same phenotype and surface marker regulation as previously shown for human Tr1 cells, characterized by expression of markers of regulation (FoxP3, CD25) at the activated but not at the resting state. Importantly, cells from patients showed Tr1 cytokine secretion (IL-10 and IFN-γ) and immunosuppressive action on bystander T cell proliferation. Based on these results, we demonstrated that collagen II specific Tr1 cells can be isolated from the blood of severe refractory patients and that these cells are not altered in their phenotype and function. 相似文献
87.
88.
Stephanie E. Smetsers Frans J. Smiers Dorine Bresters Martine C. Sonnevelt Marc B. Bierings 《British journal of haematology》2016,174(6):952-961
This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty‐eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)‐based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5‐year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non‐FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty‐two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m2 and cyclophosphamide 30 mg/kg ± anti‐thymocyte globulin ‐ no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow‐up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation‐wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non‐irradiation and busulfan‐free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder. 相似文献
89.
Thierry Kamtchoua Monica Bologa Robert Hopfer David Neveu Branda Hu Xiaohua Sheng Nicolas Corde Catherine Pouzet Gloria Zimmermann Sanjay Gurunathan 《Vaccine》2013
Background
Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.Objective
This study examined the safety and immunogenicity in adults of three doses of a pneumococcal single-antigen protein vaccine candidate formulated with aluminum hydroxide adjuvant and recombinantly derived, highly detoxified, genetically mutated pneumolysin protein (PlyD1).Methods
This phase I, randomized, placebo-controlled, observer-blinded, dose-escalating study enrolled adults (18–50 years). In a pilot safety study, participants received a single injection of 10 μg PlyD1 and were observed for 24 h. Following review of the pilot safety data, participants were randomized (2:1) to receive two injections of PlyD1 at one of three doses or placebo 30 days apart. Assignment of second injection and successive dose cohorts was made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site reactions, solicited systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included geometric mean concentrations of anti-PlyD1 IgG as determined by ELISA and functional assessment in an in vitro toxin neutralization assay.Results
The study included a total of 100 participants, including 10 in the pilot study and 90 in the randomized study. None of the participants in the pilot study had SAEs, allergic reactions, or other safety concerns. Ninety participants received two doses of or placebo (n = 30) or active vaccine candidate at 10 (n = 20), 25 (n = 20), or 50 μg (n = 20). No vaccine-related SAE or discontinuation due to an AE occurred. Most solicited reactions were mild and transient. The most frequently reported solicited reactions were pain at the injection site and myalgia. Antigen-specific IgG levels and functional activity showed dose-related increases. When comparing the three dose levels, a plateau effect was observed at the 25 μg dose.Conclusions
All dose levels were safe and immunogenic. Repeat vaccination significantly increased the level of anti-PlyD1 antibodies. Functional antibody activity was demonstrated in sera from vaccinated individuals (ClinicalTrails.gov no. NCT01444352). 相似文献90.
Geoffrey?C?Buckle Jennifer?Pfau?Collins Peter?Odada?Sumba Beccy?Nakalema Dorine?Omenah Kristine?Stiffler Corey?Casper Juliana?A?Otieno Jackson?Orem Ann?M?MoormannEmail author 《Infectious agents and cancer》2013,8(1):36