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61.
Tóth A Wang Y Kedei N Tran R Pearce LV Kang SU Jin MK Choi HK Lee J Blumberg PM 《Life sciences》2005,76(25):2921-2932
The vanilloid receptor subtype 1 (TRPV1 or VR1) is expressed in nociceptive primary afferents of the C-fiber 'pain' pathway and has attracted considerable attention as a therapeutic target. Here, using rat TRPV1 heterologously expressed in Chinese hamster ovary cells, we show that different agonists show different patterns of modulation of the intracellular Ca2+ concentration, monitored in individual cells by fura-2 Ca2+ imaging. We identified 5 parameters (potency, maximal response, latency of response, variability of latency of response among individual cells, and desensitization) which behaved differently for different compounds. The potencies of the compounds examined ranged from EC50 values of 80 pM to 9 microM. Peak levels of induced [Ca2+]i were observed either higher (RTX) or lower (anandamide) than for capsaicin. Significant latencies of response were observed for some (e.g. RTX) but not other derivatives, with great variation among individual cells in this latency. Marked desensitization after stimulation was detected in some cases (e.g. anandamide, capsaicin); for others, no desensitization was observed. We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca2+ response. This diversity of response may provide opportunities for pharmacological exploitation. 相似文献
62.
Nuclear pore complexes mediate the rapid trafficking of target macromolecules between the nucleus and the cytoplasm but exclude non-targets. Mathematical modeling helps to define the physical properties of a transport medium that can selectively enhance the permeation of some molecules but block others. Recent pioneering work has established a basis for quantitative modeling of nuclear translocation, and we expect this field to expand rapidly. A second area where modeling of nucleocytoplasmic transport has been prominently employed is in efforts to understand the regulatory networks by which signals pass between the nuclear and cytoplasmic compartments. Recent evidence suggests that the distinctive kinetics and spatial organization of nuclear transport processes can be used to efficiently propagate signals by new and unexpected pathways. 相似文献
63.
Tangirala RS Dixon R Yang D Ambrus A Antony S Agama K Pommier Y Curran DP 《Bioorganic & medicinal chemistry letters》2005,15(21):4736-4740
Both enantiomers of 20-fluorocamptothecin and the racemate have been prepared by total synthesis. The (R)-enantiomer is essentially inactive in a topoisomerase-I/DNA assay, while the (S)-enantiomer is much less active than (20S)-camptothecin. The lactone ring of 20-fluorocamptothecin hydrolyzes more rapidly than that of camptothecin in PBS. The results provide insight into the role of the 20-hydroxy group in the binding of camptothecin to topoisomerase-I and DNA. 相似文献
64.
Kevei Z Seres A Kereszt A Kaló P Kiss P Tóth G Endre G Kiss GB 《Molecular genetics and genomics : MGG》2005,274(6):644-657
The increased amount of data produced by large genome sequencing projects allows scientists to carry out important syntenic
studies to a great extent. Detailed genetic maps and entirely or partially sequenced genomes are compared, and macro- and
microsyntenic relations can be determined for different species. In our study, the syntenic relationships between key legume
plants and two model plants, Arabidopsis thaliana and Populus trichocarpa were investigated. The comparison of the map position of 172 gene-based Medicago sativa markers to the organization of homologous A. thaliana genes could not identify any sign of macrosynteny between the two genomes. A 276 kb long section of chromosome 5 of the model
legume Medicago truncatula was used to investigate potential microsynteny with the other legume Lotus japonicus, as well as with Arabidopsis and Populus. Besides the overall correlation found between the legume plants, the comparison revealed several microsyntenic regions in
the two more distant plants with significant resemblance. Despite the large phylogenetic distance, clear microsyntenic regions
between Medicago and Arabidopsis or Populus were detected unraveling new intragenomic evolutionary relations in Arabidopsis.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
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67.
Novel aspects of systems biology and clinical cytomics. 总被引:1,自引:0,他引:1
József Bocsi Anja Mittag Ulrich Sack Andreas O H Gerstner Markus J Barten Attila Tárnok 《Cytometry. Part A》2006,69(3):105-108
The area of Cytomics and Systems Biology became of great impact during the last years. In some fields of the leading cytometric techniques it represents the cutting edge today. Many different applications/variations of multicolor staining were developed for flow- or slide-based cytometric analysis of suspensions and sections to whole animal analysis. Multispectral optical imaging can be used for studying immunological and tumorigenic processes. New methods resulted in the establishment of lipidomics as the systemic research of lipids and their behavior. All of these development push the systemic approach of the analysis of biological specimens to enhance the outcome in the clinic and in drug discovery programs. 相似文献
68.
Barbara Czakó János Marton Sándor Berényi Katarzyna Gach Jakub Fichna Martin Storr Géza Tóth Attila Sipos Anna Janecka 《Bioorganic & medicinal chemistry》2010,18(10):3535-3542
A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum. 相似文献
69.
Nemes A Takács R Gavallér H Várkonyi TT Wittmann T Forster T Lengyel C 《Canadian journal of physiology and pharmacology》2010,88(12):1166-1171
Cardiovascular autonomic dysfunction and alterations in vascular elasticity are known complications of several disorders, including diabetes mellitus, hypertension, hypercholesterolemia, aging, and chronic kidney disease. The current study was designed to test whether a relationship existed between pulse wave velocity (PWV), augmentation index (AIx), aortic elastic properties, and cardiovascular autonomic function in healthy volunteers. The study comprised 25 healthy volunteers, whose aortic strain, distensibility, and stiffness index were measured by echocardiography, whereas PWV and AIx were evaluated by Arteriograph (TensioMed, Budapest, Hungary) in all cases. Autonomic function was assessed by means of 5 standard cardiovascular reflex tests. We found that heart rate response to deep breathing, as the most reproducible cardiovascular reflex test to characterize parasympathetic function, showed low to moderate correlations with PWV (r = -0.431, p = 0.032), aortic strain (r = 0.594, p = 0.002), distensibility (r = 0.407, p = 0.043), and stiffness index (r = -0.453, p = 0.023). Valsalva ratio and autonomic neuropathy score (ANS) correlated with PWV (r = -0.557, p = 0.004 and r = -0.421, p = 0.036, respectively) and AIx (r = -0.461, p = 0.020 and r = -0.385, p = 0.057, respectively), while ANS correlated with even aortic stiffness index (r = -0.457, p = 0.022). Cardiovascular reflex tests mainly characterizing sympathetic function had no correlation with aortic stiffness parameters (p = NS for all correlations). Correlations exist between parameters characterizing aortic elasticity and parasympathetic autonomic function, as shown by standard cardiovascular reflex tests in healthy volunteers. 相似文献
70.
There is a growing interest for multiparticulate solid dosage forms such as pellets, because of their several advantages over tablets during drug therapy. It is essential to investigate the drug dissolution process which can be influenced by the composition and manufacturing process technology, too. This study was performed applying experimental design in order to evaluate the effects of independent process variables during high-shear pelletisation, taking the impeller speed (x1) and granulation binder flow rate (x2) as factors into consideration. Theophylline containing pellet formulation was prepared using a matrix consisted of ethylcellulose, microcrystalline cellulose and lactose. Dissolution profiles were modeled by the Weibull function to evaluate the power of process variables. Both process variables were powerful to influence the particle agglomeration. A linear regression was found between the particle size and the diffuse reflectance values after the Kubelka-Munk transformation. Differences in the diffuse reflectance spectra of pellet samples related to particle size offer a fast instrumental method for the in-process control. 相似文献