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991.
Krogh-Madsen T Schaffer P Skriver AD Taylor LK Pelzmann B Koidl B Guevara MR 《American journal of physiology. Heart and circulatory physiology》2005,289(1):H398-H413
We recorded transmembrane potential in whole cell recording mode from small clusters (2-4 cells) of spontaneously beating 7-day embryonic chick ventricular cells after 1-3 days in culture and investigated effects of the blockers D-600, diltiazem, almokalant, and Ba2+. Electrical activity in small clusters is very different from that in reaggregates of several hundred embryonic chick ventricular cells, e.g., TTX-sensitive fast upstrokes in reaggregates vs. TTX-insensitive slow upstrokes in small clusters (maximum upstroke velocity approximately 100 V/s vs. approximately 10 V/s). On the basis of our voltage- and current-clamp results and data from the literature, we formulated a Hodgkin-Huxley-type ionic model for the electrical activity in these small clusters. The model contains a Ca2+ current (ICa), three K+ currents (IKs, IKr, and IK1), a background current, and a seal-leak current. ICa generates the slow upstroke, whereas IKs, IKr, and IK1 contribute to repolarization. All the currents contribute to spontaneous diastolic depolarization, e.g., removal of the seal-leak current increases the interbeat interval from 392 to 535 ms. The model replicates the spontaneous activity in the clusters as well as the experimental results of application of blockers. Bifurcation analysis and simulations with the model predict that annihilation and single-pulse triggering should occur with partial block of ICa. Embryonic chick ventricular cells have been used as an experimental model to investigate various aspects of spontaneous beating of cardiac cells, e.g., mutual synchronization, regularity of beating, and spontaneous initiation and termination of reentrant rhythms; our model allows investigation of these topics through numerical simulation. 相似文献
992.
Feeding of larval blue whiting and Atlantic mackerel: a comparison of foraging strategies 总被引:1,自引:0,他引:1
N. Hillgruber M. Kloppmann † E. Wahl H. von Westernhagen 《Journal of fish biology》1997,51(SA):230-249
Fish larvae employ different feeding strategies depending on area and season of spawning and hatching of larvae. Feeding and growth of larvae of blue whiting Micromesistius poutassou and mackerel Scomber scombrus from Porcupine Bank and the Celtic Shelf Break, west of Ireland, were compared based on prey concentrations in the environment and larval feeding behaviour. Both species were adapted to different environmental conditions. The mesopelagic blue whiting spawned in oceanic water that was well mixed. It was characterized by low production and low prey densities with minimum prey densities <1.0 organism 1−1 . Larvae of the Atlantic mackerel hatched later in the season in more productive water that was well stratified. Prey densities in the mackerel environment reached up to 1001−1 . Blue whiting larvae displayed a rather random distribution in the water column. Mackerel larvae <7 mm standard length ( L s ) were concentrated above the thermocline, while larvae >7 mm traversed the thermocline into deeper layers. Mackerel larvae >5mm L s displayed marked cannibalism, exceeding 70%. Daily ration calculated on the basis of gut contents was rather low in both species: between 2.6 and 5.0% in blue whiting, but only 0.6 to 5.4% in mackerel. The results are discussed in relation to the respective environment both species encounter during their early larval life. 相似文献
993.
Yu X Coulson BS Fleming FE Dyason JC von Itzstein M Blanchard H 《Journal of molecular biology》2011,413(5):929-939
Rotaviruses ubiquitously infect children under the age of 5, being responsible for more than half a million diarrhoeal deaths each year worldwide. Host cell oligosaccharides containing sialic acid(s) are critical for attachment by rotaviruses. However, to date, no detailed three-dimensional atomic model showing the exact rotavirus interactions with these glycoconjugate receptors has been reported. Here, we present the first crystallographic structures of the rotavirus carbohydrate-recognizing protein VP8? in complex with ganglioside GM3 glycans. In combination with assessment of the inhibition of rotavirus infectivity by N-acetyl and N-glycolyl forms of this ganglioside, our results reveal key details of rotavirus-ganglioside GM3 glycan recognition. In addition, they show a direct correlation between the carbohydrate specificities exhibited by VP8? from porcine and by monkey rotaviruses and the respective infectious virus particles. These novel results also indicate the potential binding interactions of rotavirus VP8? with other sialic acid-containing gangliosides. 相似文献
994.
M. Hartmann I. L. Meek G. K. van Houwelingen H. P. C. M. Lambregts G. J. Toes A. C. van der Wal C. von Birgelen 《Netherlands heart journal》2011,19(11):482-485
We present the case of a 75-year-old woman with a medical history of rheumatoid arthritis treated with hydroxychloroquine, who was admitted with acute left-sided heart failure due to a hydroxychloroquine-induced cardiomyopathy as supported by endomyocardial biopsy. 相似文献
995.
996.
Background
Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated.Methods
In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls) spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw.Results
The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744). The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001) and FCFM (p = 0.048), regardless of asthma or atopy.Conclusion
FCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and both histological and FCFM elastic fibre patterns points towards a structure-function relationship between extracellular matrix in the airway wall and lung function.Trial registration
Netherlands Trial Register NTR1306 相似文献997.
Olszak AM van Essen D Pereira AJ Diehl S Manke T Maiato H Saccani S Heun P 《Nature cell biology》2011,13(7):799-808
998.
Steven S An Peter S Askovich Thomas I Zarembinski Kwangmi Ahn John M Peltier Moritz von Rechenberg Sudhir Sahasrabudhe Jeffrey J Fredberg 《Respiratory research》2011,12(1):8
Background
A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma.Methods
Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds.Results
Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo.Conclusions
This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases. 相似文献999.
Effects of the Commercial Flame Retardant Mixture DE-71 on Cytokine Production by Human Immune Cells
Thit Mynster Kronborg Juliana Frohnert Hansen Claus Henrik Nielsen Louise Ramh?j Marie Frederiksen Katrin Vorkamp Ulla Feldt-Rasmussen 《PloS one》2016,11(4)
IntroductionAlthough production of polybrominated diphenyl ethers (PBDEs) is now banned, release from existing products will continue for many years. The PBDEs are assumed to be neurotoxic and toxic to endocrine organs at low concentrations. Their effect on the immune system has not been investigated thoroughly. We aimed to investigate the influence of DE-71 on cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with Escherichia Coli lipopolysaccharide (LPS) or phytohaemagglutinin-L (PHA-L).ResultsAt non-cytotoxic concentrations (0.01–10 μg/mL), DE-71 significantly enhanced secretion of IL-1β, IL-6, CXCL8, IL-10, and TNF-α (p<0.001–0.019; n = 6) from LPS-stimulated PBMCs. IFN-γ, TNF-α, IL-17A, and IL-17F (p = <0.001–0.043; n = 6) secretion were enhanced from PHA-L-stimulated PBMCs as well. Secretion of IL-1β, IL-2, IL-10, IL-8 and IL-6 was not significantly affected by DE-71.ConclusionsWe demonstrate an enhancing effect of DE-71 on cytokine production by normal human PBMCs stimulated with LPS or PHA-L ex vivo. 相似文献
1000.