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111.
A decrease of the transient outward potassium current (Ito) has been observed in cardiac hypertrophy and contributes to the altered shape of the action potential (AP) of hypertrophied ventricular myocytes. Since the shape and duration of the ventricular AP are important determinants of the Ca2+ influx during the AP (QCa), we investigated the effect of ascending aortic stenosis (AS) on QCa in endo- and epicardial myocytes of the left ventricular free wall using the AP voltage-clamp technique. In sham-operated animals, QCa was significantly larger in endocardial compared to epicardial myocytes (803 +/- 65 fC pF(-1), n = 27 vs. 167 +/- 32 fC pF(-1), n = 38, P < 0.001). Ascending aortic stenosis significantly increased QCa in epicardial myocytes (368 +/- 54 fC pF(-1), n = 42, P < 0.05), but did not alter QCa in endocardial myocytes (696 +/- 65 fC pF(-1), n = 26). Peak and current-voltage relation of the AP-induced Ca2+ current were unaffected by AS. However, the time course of the current-voltage relation was significantly prolonged in epicardial myocytes of AS animals. Model calculations revealed that the increase in QCa can be ascribed to a prolonged opening of the activation gate, whereas an increase in inactivation prevents an excessive increase in QCa. In conclusion, AS significantly increased AP-induced Ca2+ influx in epicardial but not in endocardial myocytes of the rat left ventricle. 相似文献
112.
Equine arteritis virus (EAV) is the etiological agent of equine viral arteritis, a contagious viral disease of equids. EAV is the prototype virus of the arteriviruses, a group of small enveloped viruses with positive single-stranded RNA genomes. Because apoptosis or programmed cell death is believed to play an important role in the biogenesis of several cytopathogenic viruses, we examined whether EAV was able to induce cell apoptosis in vitro. To do this, Vero cells were infected with EAV at a multiplicity of infection of 0.1 tissue culture infectious dose (TCID50) per cell, and analyzed at various time intervals for the appearance of apoptotic signs. Fragmentation of chromosomal DNA into nucleosomal oligomers and caspase activation were observed in the infected cells at the time (e.g. 24 h postinfection) where a noticeable cytopathic effect was observed. The kinetics of the DNA fragmentation correlated with that of the production of progeny virus, so that viral multiplication was not interrupted by the apoptotic cell damage. All these data provide evidence that EAV is able to induce apoptotic cell death in vitro. 相似文献
113.
Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function
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Udo Seedorf Martin Raabe Peter Ellinghaus Frank Kannenberg Manfred Fobker Thomas Engel Simone Denis Fred Wouters Karel W.A. Wirtz Ronald J.A. Wanders Nobuyo Maeda Gerd Assmann 《Genes & development》1998,12(8):1189-1201
Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(−/−) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein. 相似文献
114.
B. Denis A. Lefort R. M. Flipo F. Tubach M. Lemann P. Ravaud D. Salmon X. Mariette O. Lortholary 《Clinical microbiology and infection》2008,14(2):183-186
This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-α blocker therapy. All TB cases ( n = 21) complicating TNF-α blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-α antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-α antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed. 相似文献
115.
B Denis A Lefort R M Flipo F Tubach M Lemann P Ravaud D Salmon X Mariette O Lortholary 《Clinical microbiology and infection》2008,14(2):183-186
This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed. 相似文献
116.
Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart 总被引:15,自引:2,他引:15
Céline Marionneau Brigitte Couette Jie Liu Huiyu Li Matteo E. Mangoni Joël Nargeot Ming Lei Denis Escande Sophie Demolombe 《The Journal of physiology》2005,562(1):223-234
Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle ( C t ) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart. 相似文献
117.
A. Belli J. R. Lacour P. V. Komi R. Candau C. Denis 《European journal of applied physiology》1995,70(6):510-517
The present study was designed to study intra-individual step variability measured both on vertical displacement of the body (Z) and on step time (t) parameters by means of a kinematic arm and during treadmill running. A group of 17 subjects ran successively at 60%, 80%, 100% and 140% of their maximal aerobic velocity (v
amax). The total number of steps analysed was 6116. The absolute Z step variability (Z) ranged between 5 mm and 21 mm while the absolute t variability (t) ranged between 6 ms and 40 ms. Step variabilities were due to step asymmetry (from 38.5% to 48.5% of the step variability) and to stride variability. For submaximal velocities (60%, 80%, and 100%v
amax) both t and Z were independent of velocity or body dimensions whereas differences between subjects were significant (P < 0.01) for Z. On the other hand, variabilities were significantly increased when velocity was changed from submaximal to the 140%v
amax level. Furthermore, at submaximal levels Z was linked to the subject's energy cost of running (P < 0.05). Therefore, the intra-individual step variability should not be neglected in future studies on mechanical efficiency of running and it is suggested that, to obtain a good accuracy (better than 1%,P < 0.05) on mean value and variability of the mechanical parameters, measurements should be performed on at least 32–64 consecutive steps, which corresponds to about 15 to 20 s of running. 相似文献
118.
119.
T lymphocytes may be separated into subsets according to their expression of CD45 isoforms. The CD45R0+ T cell subset has been reported to proliferate in response to recall antigen and to mitogenic mAb to a much greater extent than the CD45RA+ subset. This difference could be due to more efficient coupling of the T cell antigen receptor complex to mitogenic signaling pathways. To investigate this possibility, CD3 antigen-induced calcium signals, diacylglycerol (DAG) production and protein kinase C (PKC) activation levels were compared in CD45RA+ and CD45R0+ human T lymphocyte subsets derived from peripheral blood. The mean CD3-induced rise in intracellular calcium was 80% greater in CD45R0+ than in CD45RA+ cells. Basal DAG levels in CD45R0+ cells were found to be, on average, 60% higher than in CD45RA+ cells (p = 0.002), but the CD3-induced production of DAG over background was not different in the two subsets (p = 0.4). Basal PKC activity, and CD3-induced PKC activation levels over background, were found to be 50% and 140% higher, respectively, in CD45R0+ cells than in CD45RA+ cells (p = 0.015 and 0.023). The CD45R0+ subset contained a higher proportion of cells expressing activation markers, such as CD25, CD71 and major histocompatibility complex class II, when compared to the CD45RA+ subset. Our results suggest that the elevated basal DAG levels observed in the CD45R0+ subset may reflect the recent activation of these cells. Both the higher basal DAG and CD3-induced elevation in intracellular calcium observed in the CD45R0+ cells may contribute to the greater PKC activation signals triggered by CD3 mAb in this subset. These findings elucidate the greater response of CD45R0+ T cells to mitogenic stimuli compared to CD45RA+ cells. 相似文献
120.
Papillomaviruses (HPV) are involved in proliferation of epithelial cells and are implicated in several human malignancies. We determined the capability of activated macrophages to exert cytostatic and/or cytolytic activities against HPV type 16 DNA-transformed cells. Both NIH-3T3 and A31-3T3 cells transformed with HPV DNA were susceptible to killing by activated macrophages; however, transformed and nontransformed cells were not susceptible to killing by soluble mediators. The HPV-transformed cells were as resistant as their nontransformed counterparts to recombinant TNF-alpha. These data suggest that the killing of the HPV-16-transformed 3T3 cells by macrophages occurred by a mechanism independent of TNF-alpha. 相似文献