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71.
Rival Y Stennevin A Puech L Rouquette A Cathala C Lestienne F Dupont-Passelaigue E Patoiseau JF Wurch T Junquéro D 《The Journal of pharmacology and experimental therapeutics》2004,311(2):467-475
Peroxisome proliferator-activated receptors (PPARs) regulate storage and catabolism of fats and carbohydrates. PPARgamma activity increases insulin sensitivity and adipocyte differentiation at the expense of adipogenesis and weight gain. The goal of this study was to 1) clone the promoter of the human adipocyte fatty acid binding protein (aP2) gene, namely fatty acid-binding protein-4, 2) characterize its pharmacological regulation, and 3) determine its putative predictability for adipogenesis. Among the selected PPAR agonists, rosiglitazone and pioglitazone displayed the highest maximal efficacy (E(max)) on reporter-gene assays in COS-7 cells cotransfected by either a galactosidase 4-response element-based or a human aP2 promoter-based Luc reporter vector, along with either chimeric or full-length human PPAR expression plasmids. The non-subtype-selective 2-(4-[2-(3-[2,4-difluorophenyl]-1-heptylureido)ethyl]phenoxy)-2-methyl-butyric acid (GW-2331) and the compounds [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid (L-165041), (4-((2S,5S)-5-(2-(bis(phenylmethyl)amino)-2-oxoethyl)-2-heptyl-4-oxo-3-thiazolidinyl)butyl)-benzoic acid (GW-0072), and indomethacin behaved as partial agonists relative to pioglitazone in full-length human aP2-PPARgamma2. Beyond their partial PPARgamma agonist properties, these compounds elicited a lower maximal up-regulation of mouse aP2 mRNA in 3T3-L1 adipocytes as compared with pioglitazone; these properties paralleled a time-dependent increase in neutral lipids. By contrast, the selective PPARalpha agonist 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid (BM-17.0744) neither stimulated the human aP2-PPARalpha promoter reporter-gene assay, thus demonstrating a specific interaction between PPARgamma and the aP2 promoter, nor affected lipogenesis in 3T3-L1 cells. Altogether, these data characterized a functional promoter of the human aP2 gene; its in vitro pharmacological regulation in PPARgamma-mediated reporter-gene assay may represent an interesting complement or an alternative to time-consuming procedures aiming at discriminating PPAR ligands with low lipogenic properties. 相似文献
72.
Freyssin C Verkindt C Prieur F Benaich P Maunier S Blanc P 《Archives of physical medicine and rehabilitation》2012,93(8):1359-1364
Freyssin C, Verkindt C, Prieur F, Benaich P, Maunier S, Blanc P. Cardiac rehabilitation in chronic heart failure: effect of an 8-week, high-intensity interval training versus continuous training.ObjectiveTo compare the effects of an 8-week, high-intensity interval training protocol versus continuous training.DesignRandomized controlled trial.SettingCardiac rehabilitation center.ParticipantsPatients (N=26; mean age ± SD, 54±12y) with chronic heart failure were enrolled in a cardiac rehabilitation program for 8 weeks.InterventionsPatients were randomly assigned into 2 groups that performed either interval training (IT) or continuous training (CT). IT consisted of 3 sessions of 12 repetitions of 30 seconds of exercise at very high intensity, followed by 60 seconds of complete rest. The CT group performed CT exercises, which consisted of 45 minutes of aerobic exercise.Main Outcome MeasuresParameters of gas exchanges: peak oxygen consumption (Vo2peak), first ventilator threshold (VT1), distance at six-minute walk test (6MWT), and level of anxiety and depression were measured.ResultsThe IT group increased significantly their Vo2peak, the duration of the exercise test, the oxygen pulse, oxygen consumption at the VT1, and the distance walked during the 6MWT. The CT group only increased the time at the VT1 and the distance performed at the 6MWT. The improvement in the time at the VT1 was significantly higher for the IT group than for the CT group.ConclusionsThis study shows that IT at very high intensity for patients with heart failure appears to be more effective than CT in improving indices of submaximal exercise capacity. 相似文献
73.
BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab 下载免费PDF全文
Sarah Huet Edith Szafer‐Glusman Bruno Tesson Luc Xerri Wayne J. Fairbrother Kiran Mukhyala Chris Bolen Elizabeth Punnoose Laurie Tonon Catherine Chassagne‐Clément Pierre Feugier Alain Viari Fabrice Jardin Gilles Salles Pierre Sujobert 《American journal of hematology》2017,92(6):515-519
BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab‐containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA‐targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over‐activation of AICDA (activation‐induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N‐terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow‐up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression‐free survival. 相似文献
74.
Ananian P Doddoli C Barlési F Grégoire E Aragon A Giudicelli R Thomas P 《Respiration; international review of thoracic diseases》2006,73(5):686-689
A venobronchial fistula developed between the azygous vein and the upper aspect of the right main bronchus 12 months after completion of the treatment of a stage IIIB non-small-cell lung cancer in a 54-year-old man. The fistula contained the tip of the catheter placed for chemotherapy perfusion. The reported case presented risk factors previously identified for such a complication. In addition, some clinical particularities were present, suggesting new potent risk factors and some preventive means for safe long-term central venous catheterization. 相似文献
75.
Barthelemy Tosello Meriem Zahed Floriane Guimond Karine Baumstarck Alice Faure Fabrice Michel 《The journal of maternal-fetal & neonatal medicine》2017,30(23):2864-2870
Objective: To identify the gestational age (GA) at which risk of mortality and severe outcome was minimized comparing preterm delivery and expectant management.Methods: Retrospective study performed between 2009 and 2014 of newborns with gastroschisis in three large French level III neonatal intensive care units. Each department followed two distinct strategies: elective delivery at 35 weeks’ GA and a delayed approach.Results: We included 69 gastroschisis cases. The lengths of stay lasting more than 60 days were significantly greater in the planned delivery group than in the expectant approach group (18/30 (60%) vs. 8/39 (20.5%), p?=?0.001). Gastroschisis cases receiving antenatal corticoids during the last two weeks of gestation required significantly less surgeries during their initial stay (p?=?0.003) as well as shorter parenteral feedings (p?=?0.002). A multivariate logistic regression showed that a GA of less than 36 weeks’ GA was is a pejorative factor for a stay above 60 days, regardless of whether it was a simple or complex gastroschisis, (OR=?3.8; p?=?0.021). A complex gastroschisis was a risk factor for significantly longer parenteral feedings, regardless of the center where patient is treated (Beta = ?0.3, p?=?0.035).Conclusions: Future research should focus on decisions about delivery timing by incorporating risk of neonatal morbidity. 相似文献
76.
Dagan R Kayhty H Wuorimaa T Yaich M Bailleux F Zamir O Eskola J 《The Pediatric infectious disease journal》2004,23(2):91-98
BACKGROUND: To have wide global coverage of pneumococcal serotypes, the number of serotypes covered by the current 7-valent pneumococcal conjugate vaccine must be increased. We have studied the safety and immunogenicity of an 11-valent mixed carrier vaccine (PncDT11) in infants. METHODS: The study vaccine contained polysaccharide antigens of serotypes 1, 4, 5, 7F, 9V, 19F and 23F conjugated to tetanus protein and serotypes 3, 6B, 14 and 18C conjugated to diphtheria toxoid. The vaccine was administered to Finnish (n = 117) and Israeli (n = 135) infants at ages 2, 4, 6 and 12 months concomitantly with other vaccines used in national vaccination programs. IgG antibodies to polysaccharides were determined by enzyme immunoassay from serum samples taken at ages 2, 7, 12 and 13 months. After each injection the infants were followed for 30 min to detect any immediate adverse reactions, and parents were given a diary card to report any adverse events during the next 5 days. RESULTS: No severe adverse reactions occurred, and immediate adverse reactions were rare. After each dose approximately 30% of the vaccinees experienced local reactions of which pain was the most common. Fever of >38 degrees C was reported in 33 to 53% of the vaccinees and high fever (>40 degrees C) was reported 6 times. The PncDT11 vaccine was immunogenic. The antibody concentrations after primary immunization series were higher in Israeli than in Finnish infants, but the differences were not significant for most serotypes. The difference was most marked at 13 months, a time point at which the difference was significant in 10 of 11 serotypes. CONCLUSION: PncDT11 is safe and immunogenic in infants. The use of 11-valent pneumococcal vaccine would increase the serotype coverage beyond the currently available 7-valent vaccine. 相似文献
77.
Amanda Patel Reza Sharif-Naeini Joost R. H. Folgering Delphine Bichet Fabrice Duprat Eric Honoré 《Pflügers Archiv : European journal of physiology》2010,460(3):571-581
Mechano-gated ion channels play a key physiological role in cardiac, arterial, and skeletal myocytes. For instance, opening of the non-selective stretch-activated cation channels in smooth muscle cells is involved in the pressure-dependent myogenic constriction of resistance arteries. These channels are also implicated in major pathologies, including cardiac hypertrophy or Duchenne muscular dystrophy. Seminal work in prokaryotes and invertebrates highlighted the role of transient receptor potential (TRP) channels in mechanosensory transduction. In mammals, recent findings have shown that the canonical TRPC1 and TRPC6 channels are key players in muscle mechanotransduction. In the present review, we will focus on the functional properties of TRPC1 and TRPC6 channels, on their mechano-gating, regulation by interacting cytoskeletal and scaffolding proteins, physiological role and implication in associated diseases. 相似文献
78.
Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region 总被引:2,自引:0,他引:2
Lynda El-Hassar Mathieu Milh Fabrice Wendling Nadine Ferrand Monique Esclapez Christophe Bernard 《The Journal of physiology》2007,578(1):193-211
An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3–5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7–10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo . During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity. 相似文献
79.
Sarlegna FR Sainburg RL 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,176(2):267-280
The goal of this study was to determine whether the sensory nature of a target influences the roles of vision and proprioception in the planning of movement distance. Two groups of subjects made rapid, elbow extension movements, either toward a visual target or toward the index fingertip of the unseen opposite hand. Visual feedback of the reaching index fingertip was only available before movement onset. Using a virtual reality display, we randomly introduced a discrepancy between actual and virtual (cursor) fingertip location. When subjects reached toward the visual target, movement distance varied with changes in visual information about initial hand position. For the proprioceptive target, movement distance varied mostly with changes in proprioceptive information about initial position. The effect of target modality was already present at the time of peak acceleration, indicating that this effect include feedforward processes. Our results suggest that the relative contributions of vision and proprioception to motor planning can change, depending on the modality in which task relevant information is represented. 相似文献
80.
Mollard P Woorons X Letournel M Lamberto C Favret F Pichon A Beaudry M Richalet JP 《European journal of applied physiology》2007,100(6):663-673
The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained
subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and
simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output arterialized oxygen saturation oxygen uptake ventilation ( expressed in normobaric conditions) were measured. At maximal exercise, ventilatory equivalent transport and O2 extraction (O2ERmax) were calculated. In TS, remained unchanged despite a significant reduction in at 4,500 m. SVmax remained unchanged. decreased in TS at 4,500 m, was lower in TS and greater at 4,500 m vs. sea level in both groups. Sa′O2max decreased at and above 1,000 m in TS and 2,500 m in US, O2ERmax increased at 4,500 m in both groups. decreased with altitude and was greater in TS than US up to 2,500 m but not at 4,500 m. decreased with altitude but the decrement was larger in TS at 4,500 m. In both groups in moderate hypoxia was correlated with Several differences between the two groups are probably responsible for the greater in TS at 4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in at 4,500 m (2) the greater decrement in TS due to a lower Sa′O2max and unchanged 3) the smaller increase in O2ERmax in TS, insufficient to compensate the decrease in 相似文献