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排序方式: 共有745条查询结果,搜索用时 31 毫秒
1.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
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E Spranzi JY Djeu SL Hoffman PK Epling-Burnette DK Blanchard 《Canadian Metallurgical Quarterly》1993,82(5):1578-1585
The present study shows that extracellular adenosine triphosphate (ATP) has the capacity to mediate dose-dependent lysis of the monocytic leukemia cell line THP-1. The lysis, assessed by 51Cr release, was found to be selective for ATP, because adenosine diphosphate (ADP) or other nucleotides were less effective in their ability to lyse the cells. The amount of 51Cr released was particularly enhanced by the stimulation of the cells with 1,000 U/mL of interferon gamma (IFN-gamma) for 3 days, and the sensitivity was time and dose dependent. Analysis of the mechanism of lysis indicated that the fully ionized form, ATP4-, mediated the lysis, because the addition of cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in the culture medium of a 6-hour 51Cr release assay increased the percent specific lysis. Therefore, the ATP receptors on THP-1 cells were classified as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin complex plays a role in the regulation of the lysis by extracellular ATP of THP-1 cells, because antagonists of this complex, such as trifluoperazine or KN-62, were found to inhibit the ATP-mediated cell lysis. 相似文献
4.
The majority of Ss included in studies of psychopathology are typically receiving psychoactive medication. In view of concerns regarding the confounding effects of psychoactive medication, it appears that researchers should provide information regarding at least the drug status of the Ss studied. A review of the articles on adult psychopathology that appeared in the Journal of Abnormal Psychology during a 5-yr period, however, revealed that nearly 50% of reports on Ss presumably receiving psychoactive medications failed to specify the medication status of those Ss. Few studies (15%) provided adequate information regarding the types and dosages of psychoactive drugs received by the Ss. It is argued that researchers should provide a full report of the psychoactive drugs received by research participants and, when participants are unmedicated, to indicate the reasons for drug-free status. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
Blanchard Edward B.; Appelbaum Kenneth A.; Guarnieri Patricia; Neff Debra F.; Andrasik Frank; Jaccard James; Barron Kevin D. 《Canadian Metallurgical Quarterly》1988,56(3):427
Tension and vascular headache patients, initially treated with biofeedback and/or relaxation training in either a minimal therapist contact protocol (3 visits) or an intensive individual protocol (10 or 16 visits) were followed-up prospectively for 2 years. In the first study, for the first 6 months of follow-up, half of all patients continued to keep headache diaries and were seen monthly and the other half had only minimal contact. The results at 1-year follow-up, based on 4 weeks of daily headache diaries, revealed equally good maintenance from both treatment protocols and from both follow-up conditions. In Study 2, we found that patients remained improved over pretreatment baseline levels at the 2-year follow-up regardless of initial treatment intensity. Approximately three quarters of vascular patients who were initially improved at posttreatment remained improved at 2 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
6.
Bourque Paul; Blanchard Louis; Saulnier Jo?l; Vézina Jean 《Canadian Metallurgical Quarterly》1992,24(1):118
Studied the relationship among age, physical health status, and psychic and somatic symptoms of depression among elderly adults. Human Ss: 318 male and female Canadian older adults (aged 65–102 yrs). Information on sociodemographic factors and health status was obtained using the Older American Research Scale, French version, by R. Lefran?ois et al (1988). A French version by P. Bourque and D. Beaudette (1982) of the Beck Depression Inventory was also used. The results were evaluated according to each S's sex, age, institutionalized residence status, and health status. Statistical tests were used. (English abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
7.
Blanchard Kimberly A.; Morgenstern Jon; Morgan Thomas J.; Lobouvie Erich W.; Bux Donald A. 《Canadian Metallurgical Quarterly》2003,17(4):328
Negative consequences are an important component of the substance use change process, yet no standardized measure exists to assess consequences of use. This study evaluated the psychometric properties of the Inventory of Drug Use Consequences, a self-report measure assessing drinking and drug use consequences. Participants (N=252) were assessed at entry into outpatient substance abuse treatment. Items loaded strongly on 1 factor, and internal consistency of the total scale was high. Fifteen items with the highest correlations with the total scale were chosen to represent the construct. The shortened measure exhibited good internal consistency, convergent and discriminant validity, and detected change over time and may be the measure of substance use consequences that is lacking in the field. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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F Davodeau MA Peyrat A Necker R Dominici F Blanchard C Leget J Gaschet P Costa Y Jacques A Godard H Vie A Poggi F Romagné M Bonneville 《Canadian Metallurgical Quarterly》1997,158(12):5603-5611
Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses. 相似文献
10.
In vitro triggering of somatic mutation in human naive B cells 总被引:1,自引:0,他引:1
D Razanajaona S Denépoux D Blanchard O de Bouteiller YJ Liu J Banchereau S Lebecque 《Canadian Metallurgical Quarterly》1997,159(7):3347-3353
During T cell-dependent immune response, germinal center B cells accumulate somatic mutations in their Ig V(D)J genes and give rise to affinity-selected B cells. We tested several culture conditions for triggering somatic mutation in human tonsillar naive slgD+CD23+ cells after cross-linking their membrane Igs. CD40 activation, in the presence of exogenous cytokines (IL-2, IL-4, and IL-10), induced proliferation and isotype switch without somatic mutation. In contrast, after coculture with anti-CD3-activated cloned T cells, somatic mutation accumulated in a fraction of naive B cells. Mutations included shared as well as independent events in clonally related sequences, allowing reconstitution of genealogic trees generated in vitro. Naive tonsillar B cells sorted for slgD expression can be induced to mutate their Ig V(H) gene upon coculture with activated T cells, thereby providing a model to study somatic hypermutation in vitro. 相似文献