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31.
Carlsson M Cain P Holmqvist C Stahlberg F Lundback S Arheden H 《American journal of physiology. Heart and circulatory physiology》2004,287(1):H243-H250
Variations in total heart volume (atria plus ventricles) during a cardiac cycle affect efficiency of cardiac pumping. The goals of this study were to confirm the presence, extent, and contributors of total heart volume variation during the cardiac cycle in healthy volunteers with the use of MRI. Eight healthy volunteers were examined by MRI at rest. Changes in total cardiac volume throughout the cardiac cycle were calculated using the following methods: 1) planimetry derived from gradient-echo cine images and 2) flow-sensitive sequences to quantify flow in all vessels leading to and from the heart. The maximum total heart volume diminished during systole by 8.2 +/- 0.8% (SEM, range 4.8-10.6%) measured by method 1 and 8.8 +/- 1.0% (SEM, range 5.6-11.8%) by method 2 with good agreement between the methods [difference according to Bland-Altman analysis -0.6% +/- 1.0% (SD), intraclass correlation coefficient = 0.999]. This decrease in volume is predominantly explained by variation at the midcardiac level at the widest diameter of the heart with a left-sided predominance. In the short axis of the heart, the change of slice volume was proportional to the end-diastolic slice volume. The present study has confirmed the presence of total heart volume variation that predominantly occurs in the region of atrioventricular plane movement and on the left side. The total heart volume variation may relate to the efficiency of energy use by the heart to minimize displacement of surrounding tissue while accounting for the energy required to draw blood into the atria during ventricular systole. 相似文献
32.
Rohrlack T Christoffersen K Kaebernick M Neilan BA 《Applied and environmental microbiology》2004,70(8):5047-5050
Laboratory experiments identified microviridin J as the source of a fatal molting disruption in Daphnia species organisms feeding on Microcystis cells. The molting disruption was presumably linked to the inhibitory effect of microviridin J on daphnid proteases, suggesting that hundreds of further cyanobacterial protease inhibitors must be considered potentially toxic to zooplankton. 相似文献
33.
Smith G Ruhland T Mikkelsen G Andersen K Christoffersen CT Alifrangis LH Mørk A Wren SP Harris N Wyman BM Brandt G 《Bioorganic & medicinal chemistry letters》2004,14(15):4027-4030
Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC(50)=150 nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2-4.6 mg/kg s.c. 相似文献
34.
AIMS: The purpose of the study was to compare the growth of Mycobacterium avium subsp. paratuberculosis (Map) and the degree of contamination on Herrold's egg yolk medium (HEYM) and modified L?wenstein-Jensen medium (LJ). METHODS AND RESULTS: Culture of 2513 faecal samples from dairy cows was performed on each of the two media. The media were read after 5, 8 and 12 weeks of incubation. Overall, the proportion of contaminated samples was significantly higher on LJ (14.2%) than on HEYM (13.2%) after 12 weeks but the degree of contamination was slightly less on LJ. After 8 weeks of incubation, only 1.0% of the samples were Map positive in LJ with 4.9% on HEYM. After 12 weeks of incubation, 3.3% of the samples were Map positive in LJ whereas 6.9% were positive in HEYM. All suspect and culture positive samples were confirmed by IS900 PCR. CONCLUSIONS: HEYM supported growth of Map significantly better and faster than LJ, however it could not be determined conclusively which of the two media that provided the highest degree of decontamination when the incubation time was also included. SIGNIFICANCE AND IMPACT OF THE STUDY: HEYM should be the primary medium rather than LJ for detection of Map in cattle. 相似文献
35.
Strøm CC Kruhøffer M Knudsen S Stensgaard-Hansen F Jonassen TE Orntoft TF Haunsø S Sheikh SP 《Comparative and Functional Genomics》2004,5(6-7):459-470
Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat. 相似文献
36.
Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency--involvement of protein kinase A type I 总被引:2,自引:0,他引:2
Holm AM Aukrust P Aandahl EM Müller F Taskén K Frøland SS 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(11):5772-5777
Common variable immunodeficiency (CVID) is a heterogeneous group of B cell deficiency syndromes. T cell abnormalities are present in a high proportion of patients with CVID, suggesting impaired T cell-mediated stimulation of B cells. Based on the importance of IL-10 for B cell function and the involvement of the cAMP/protein kinase A type I (PKAI) system in IL-10 synthesis, we examined IL-10 secretion in T cells from CVID patients and controls, particularly focusing on possible modulatory effects of the cAMP/PKAI system. Our main findings were: 1) anti-CD3 and anti-CD3/anti-CD28 activated T cells from CVID patients secreted less IL-10 than healthy controls. This defect was not related to varying proportions of T cell subsets (e.g., CD4(+)/CD8(+), CD45RA(+)/RO(+), or CD28(-) T cells); 2) PKAI activation through the cAMP agonist 8-CPT-cAMP markedly inhibited IL-10 secretion from T cells through CD3 and CD28 activation in both patients and controls, but the sensitivity for cAMP-dependent inhibition was increased in CVID; 3) selective PKAI inhibition by Rp-8-Br-cAMPS markedly increased IL-10 secretion in anti-CD3 and anti-CD3/anti-CD28-stimulated T cells in both patients and controls. Even at the lowest concentrations of Rp-8-Br-cAMPS, IL-10 secretion in CVID patients reached levels comparable to those in controls. Our findings suggest impaired secretion of IL-10 by T cells from CVID patients, suggesting a possible link between T cell deficiency and impaired B cell function in CVID. The involvement of the cAMP/PKAI system in this defect suggests a novel target for therapeutic immunomodulation in CVID. 相似文献
37.
Defective stress kinase and Bak activation in response to ionizing radiation but not cisplatin in a non-small cell lung carcinoma cell line 总被引:3,自引:0,他引:3
Viktorsson K Ekedahl J Lindebro MC Lewensohn R Zhivotovsky B Linder S Shoshan MC 《Experimental cell research》2003,289(2):256-264
We have here examined ionizing radiation (IR)-induced apoptotic signaling in one IR-sensitive small cell lung carcinoma (SCLC) and one resistant non-small cell lung carcinoma (NSCLC) cell line, both harboring mutant p53. In the sensitive SCLC cell line, IR induced conformational modulation of Bak and Bax, mitochondrial depolarization, and nuclear fragmentation. These events were not observed in the IR-resistant NSCLC cell line. However, in the same cells, cisplatin, a DNA-damaging drug, induced Bak and Bax modulation, mitochondrial depolarization, and nuclear fragmentation. Pre-mitochondrial signaling events were examined in order to further characterize the differing IR response. In the SCLC cell line, IR-induced apoptotic signaling was found to involve a MEKK1-related pathway and activation of the stress-activated kinases JNK and p38. In comparison, the NSCLC cell line had higher basal levels of activity of JNK and p38, and IR treatment did not further activate these kinases. However, NSCLC cells were sensitive to Bak modulation and apoptosis induced by a kinase-active mutant of MEKK1. Together, the results delineate a mechanism of IR resistance in NSCLC cells and indicate that IR and cisplatin induce Bak modulation and apoptosis via different pathways. 相似文献
38.
To examine how hippocampal neurons respond to a mismatch between retrieved and actual experience, we trained rats to find a hidden platform at a particular location in an annular watermaze and then moved the platform. Several cells that were silent at the new platform location before the move fired vigorously when the rat found the goal. The new activity was paralleled by reduced discharge in a subset of simultaneously recorded interneurons. The pattern of activity returned toward its original configuration as the rat learned the new location. The activation of specific hippocampal neurons following dislocation of a target object may be essential for synaptic plasticity and adaptive modification of the animal's representation of the environment. 相似文献
39.
Øyvind Melien Laila S Nilssen Olav F Dajani Kristin Larsen Sand Jens-Gustav Iversen Dagny L Sandnes Thoralf Christoffersen 《BMC cell biology》2002,3(1):5-11
Background
Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44mapk) and ERK2 (p42mapk) in hepatocytes. The molecular pathways that convey their signals to ERK1/2 are only partially clarified. In the present study we have explored the role of Ca2+ and Ca2+-dependent steps leading to ERK1/2 activation induced by norepinephrine and prostaglandin (PG)F2α.Results
Pretreatment of the cells with the Ca2+ chelators BAPTA-AM or EGTA, as well as the Ca2+ influx inhibitor gadolinium, resulted in a partial decrease of the ERK response. Furthermore, the calmodulin antagonists W-7, trifluoperazine, and J-8 markedly decreased ERK activation. Pretreatment with KN-93, an inhibitor of the multifunctional Ca2+/calmodulin-dependent protein kinase, had no effect on ERK activation. The Src kinase inhibitors PP1 and PP2 partially diminished the ERK responses elicited by both norepinephrine and PGF2α.Conclusion
The present data indicate that Ca2+ is involved in ERK activation induced by hormones acting on G protein-coupled receptors in hepatocytes, and suggest that calmodulin and Src kinases might play a role in these signaling pathways. 相似文献40.