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911.
Sorafenib in advanced clear-cell renal-cell carcinoma 总被引:1,自引:0,他引:1
912.
913.
Henri S Siret C Machy P Kissenpfennig A Malissen B Leserman L 《European journal of immunology》2007,37(5):1184-1193
Skin-draining LN contain several phenotypically distinguishable DC populations, which may be immature or mature. Mature DC are generally considered to have lost the capacity to acquire and present newly encountered Ag. Using antibody-opsonized liposomes as Ag carriers, we show that mature DC purified from skin explants are able to efficiently capture liposomes, process Ag encapsulated within them and activate Ag-specific CD4(+) T cells. Explant DC from mice with Langerhans cells (LC) expressing the primate diphtheria toxin receptor that were exposed to diphtheria toxin in vivo presented Ag as well as explant DC from wild-type mice, indicating that LC are not required and dermal DC are probably responsible for this presentation. We further show that all DC subtypes from LN that capture opsonized Ag are capable of cross-presenting it to CD8(+) T cells. Induction of additional maturation in vivo by LPS or treatment with double-stranded RNA did not alter the Ag presentation capacity of the skin or LN DC subtypes. These results suggest that mature DC present in skin-draining LN may play an important role in the induction of primary and/or secondary immune responses against Ag delivered to the LN that they take up by receptor-mediated endocytosis. 相似文献
914.
Xiang Y John P Yakushin SB Kunin M Raphan T Cohen B 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,177(4):551-572
We characterized the three-dimensional kinematics and dynamics of quadrupedal gait of young adult rhesus and cynomolgus monkeys
while they walked with diagonal and lateral gaits at 0.4–1.0 m/s on a treadmill. Rigid bodies on the wrist, ankle, and back
were monitored by an optical motion detection system (Optotrak). Kinematic data could be normalized using characteristic stride
length, reducing variance due to different gait styles, to emphasize common characteristics of swing and stance parameters
among animals. Mean swing phase durations fell as walking speed increased, but the swing phase durations increased at each
walking velocity as a linear function of increases in amplitude, thereby following a main sequence relationship. The phase
plane trajectories of the swing phases, i.e., plots of the relation of the rising and falling limb velocity to limb position
in the sagittal (X–Z) plane, had unique dynamic characteristics. Trajectories were separable at each walking velocity and increases in swing amplitude
were linearly related to peak swing velocities, thus comprising main sequences. We infer that the swing phase dynamics are
set by central neural mechanisms at the onset of the swing phases according to the intended amplitude, which in turn is based
on the walking velocity in the stance phases. From the many dynamic similarities between swing phases and rapid eye movements,
we further suggest that the swing phases may be generated by neural mechanisms similar to those that produce saccades and
quick phases of nystagmus from a signal related to sensed or desired walking velocity.
Grants: This work was supported by National Institute of Health Grants EY11812, EY04148, DC05204, and EY01867. 相似文献
915.
Castelli FA Leleu M Pouvelle-Moratille S Farci S Zarour HM Andrieu M Auriault C Ménez A Georges B Maillere B 《European journal of immunology》2007,37(6):1513-1523
To understand the inter-individual and virus-independent variability of CD4+ T cell responses to HCV components, we evaluated the effect on these responses of HLA II molecules in uninfected healthy donors. Using HLA II-specific binding assays, we identified, in the Core and NS3 proteins, 21 long fragments and 24 15-mer peptides that bound to four to eight of the most preponderant HLA II molecules. We then evaluated the priming capacity of eight long promiscuous peptides in 12 HLA-unrelated healthy donors. The NS3 1250-1264 peptide primed T cells in all the naive donors, while five others were stimulating in at least half of the individuals. We also report sequences that bind to multiple HLA II molecules but are weakly immunogenic. We therefore conclude that (i) broad HLA II specificity is only a prerequisite for a peptide to be stimulating in multiple individuals, and (ii) promiscuous peptides widely differ in their capacity to prime CD4+ T cells from uninfected healthy donors. We suggest that these priming differences result from inter-individual variations in the peptide-specific T cell repertoire. Interestingly, five of the most immunogenic peptides we identified correspond to frequently targeted T cell epitopes in infected patients. 相似文献
916.
Konstantin Tsinman Oksana Tsinman Ram Lingamaneni Saijie Zhu Bernd Riebesehl Arnaud Grandeury Michael Juhnke Bernard Van Eerdenbrugh 《Pharmaceutical research》2018,35(8):161
Purpose
The goal of the study was to evaluate a miniaturized dissolution-permeation apparatus (μFLUX? apparatus) for its ability to benchmark several itraconazole (ITZ) formulations for which in vivo PK data was available in the literature.Method
Untreated and micronized powders of ITZ and various enabling formulations of ITZ (commercial Sporanox® solid dispersion, a Soluplus®-based solid dispersion and a nanosuspension) were introduced to the donor compartment of μFLUX? apparatus. Donor and acceptor chambers were divided from each other by a lipophilic membrane. In addition to the flux evaluations, changes in solid state as a function of time were investigated to gain further insight into the flux changes observed over time for the solid dispersion formulations.Results
Initial flux values from Sporanox®, the nanosuspension and the micronized ITZ showed ratios of 52/4/1 with a decreasing flux from nanosuspension and both solid dispersions after 2.5–3 h. Although the initial flux from the Soluplus® formulation was 2.2 times lower than the one observed for Sporanox®, the decrease in flux observed was milder and became ~ 2 times higher than Sporanox® after approximately 2.5 h. The total amounts of ITZ in the receiver compartment after 240 min showed the same rank order as the rodent AUCs of these formulations reported in literature.Conclusions
It was demonstrated that in vitro flux measurements using lipophilic artificial membranes could correctly reproduce the rank order of PK results for ITZ formulations. The drop in flux over time for solid dispersions could be backed by experimental indications of crystallization.917.
Katia Iglesias Stéphanie Baggio Karine Moschetti Jean-Blaise Wasserfallen Olivier Hugli Jean-Bernard Daeppen Bernard Burnand Patrick Bodenmann 《Quality of life research》2018,27(2):503-513
Purpose
Frequent Emergency Department users are likely to experience poor quality of life (QOL). Case management interventions are efficient in responding to the complex needs of this population, but their effects on QOL have not been tested yet. Therefore, the aim of our study was to examine to what extent a case management intervention improved frequent Emergency Department users’ QOL in a universal health coverage system.Methods
Data were part of a randomized controlled trial designed to improve frequent Emergency Department users’ QOL at the Lausanne University Hospital, Switzerland. A total of 250 frequent Emergency Department users (≥?5 attendances during the previous 12 months) were randomly assigned to the control (n?=?125) or the intervention group (n?=?125). The latter benefited from case management intervention. QOL was evaluated using the WHOQOL-BREF at baseline, two, five and a half, nine, and twelve months later. It included four dimensions: physical health, psychological health, social relationship, and environment. Linear mixed-effects models were used to analyze the change in the patients’ QOL over time.Results
Patients’ QOL improved significantly (p?<?0.001) in both groups for all dimensions after two months. However, environment QOL dimension improved significantly more in the intervention group after 12 months.Conclusions
Environment QOL dimension was the most responsive dimension for short-term interventions. This may have been due to case management’s assistance in obtaining income entitlements, health insurance coverage, stable housing, or finding general health care practitioners. Case management in general should be developed to enhance frequent users’ QOL.Trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT01934322918.
Ketsia Yekpe Bernard Bataille Ryan Gosselin Tahmer Sharkawi Jean-Sébastien Simard 《Pharmaceutical development and technology》2018,23(6):646-654
AbstractThis study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing. 相似文献
919.
Andrew D. Ablett Adrian D. Wood Rebecca Barr Jordan Guillot Alison J. Black Helen M. Macdonald David M. Reid Phyo K. Myint 《Annals of epidemiology》2018,28(8):557-562.e2
Purpose
To examine the cross-sectional association between anticholinergic medication burden (ACB) and a history of falls, bone mineral density, and low trauma fractures in middle-aged women aged under 65 years from the Aberdeen Prospective Osteoporosis Screening Study.Methods
ACB (0 = none, 1 = possible, ≥2 = definite) was calculated from medication use for 3883 Caucasian women [mean age (SD) = 54.3 (2.3) years] attending the second Aberdeen Prospective Osteoporosis Screening Study visit (1997–2000). Outcomes were examined using logistic regression. Model adjustments were selected a priori based on expert opinion.Results
Of 3883 participants, 3293 scored ACB = 0, 328 scored ACB = 1, and 262 scored ACB ≥2. High ACB burden (≥2) was associated with increased odds (ACB = 0 reference) for falls (fully adjusted odds ratio [95% confidence intervals] = 1.81 [1.25–2.62]; P = 0.002) and having low bone mineral density (lowest quintile-20%) at Ward's triangle (3.22 [1.30–7.99]; P = 0.01). A history of falls over the year prior to the study visit in participants with ACB score ≥2 was 32 per 100. For ACB categories 1 and 0, a history of falls per 100 was 21 and 22, respectively.Conclusions
The risk of falling associated with ACB observed in older age may also extend to middle-aged women. 相似文献920.