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31.
Molecular models of an oligodeoxynucleotide-peptide conjugate complexed to an RNA hairpin loop were constructed to assess the effect of stereoisomerism at the point of attachment of the peptide to the oligodeoxynucleotide on the affinity of the conjugate for an RNA target. The peptide portion of the oligodeoxynucleotide-peptide conjugate, (L-lysine)8, was covalently attached to the N-allyl group of (D)- or (L)-aspartic alcohol that was incorporated into the interior of an antisense oligodeoxynucleotide. The stereocenter in the oligodeoxynucleotide interior originates from either (D)- or (L)-aspartic alcohol. The oligodeoxynucleotide portion of the oligodeoxynucleotide-peptide conjugate forms Watson-Crick base pairs with the single-stranded RNA that flanks the RNA hairpin loop. The positively charged peptide makes specific electrostatic contacts with the negatively charged phosphate backbone of the RNA hairpin loop when attached to the N-allyl of (D)-aspartic alcohol but does not have the proper orientation to make these electrostatic contacts when attached to the N-allyl of (L)-aspartic alcohol. This modelling study emphasizes the importance of stereocontrol at the point of branching in synthesizing oligodeoxynucleotide-peptide conjugates for binding of RNA hairpin loops. 相似文献
32.
JR Kerr D Kane B Crowley N Leonard S O''Briain PV Coyle F Mulcahy 《Canadian Metallurgical Quarterly》1997,8(3):184-186
We report a 16-year-old boy, born to consanguineous parents, with mental retardation, gait disturbances and dysarthria; brain magnetic resonance showed features consistent with rhombencephalosynapsis. This condition is characterised by a hypoplastic single-lobed cerebellum. The interest of this case is the presence of common ancestors, pointing to an autosomal recessive inheritance of the malformation. 相似文献
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MV Zhernovo? SV Lebedev AA Grigoriuk IuA Krasnikov PV Kharitonski? 《Canadian Metallurgical Quarterly》1998,40(7):676-681
The influence of a constant magnetic field (strain 40 kA/m) on retina pigmentary cells of grass frog (Rana temporaria) and grey pigeon (Columba livia) eyes was investigated. Changes in the number and length of melanocytes appendixes were noticed accompanied by formation of thickenings in which melanosomes sized from 0.1 to 0.5 micron are moving. It is established that magnetic properties of eye retina pigmentary cells depend on the presence of Fe3+ in melanin. A theoretical model of paramagnetic receptor has been elaborated, according to which the induction of a magnetic field, formed by melanocyte, makes of the order 100 pT1. This value well compares with the size of magnetic field of a nervous impulse (120 pT1), extending throughout a nervous fibre of the frog sciatic nerve (Wikswo et al., 1980). This allows to suggest a possible unsynaptic way of transferring the information about the perceived magnetic field. 相似文献
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Flupirtine belongs to the class of triaminopyridines and is successfully applied clinically as a non-opiate analgesic drug with additional muscle relaxant properties. Recently it was reported that flupirtine acts like an antagonist of the N-methyl-D-aspartate (NMDA) receptor complex in neuronal cells both in vitro and in vivo. Here we have used primary cortical cells from rat embryos to demonstrate that this compound is also neuroprotective against the toxic effects caused by the prion agent PrPSc and lead acetate (Pb). These two agents display pleiotropic effects on neurons, which include activation of the NMDA receptor complex. At concentrations above 30 microM the toxic-peptide fragment of PrPSc causes apoptotic fragmentation of DNA and is consequently neurotoxic. Pb is neurotoxic at concentrations above 10 microM. Co-administration of flupirtine (10 microM) with either of these agents resulted in reduced neurotoxicity. These data indicate that the cytoprotective effect of flupirtine is measurable in vitro against these noxious agents which show their effects, including modulation of the NMDA receptor complex, pleiotropically. 相似文献
38.
OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects. RESULTS: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers. CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments. 相似文献
39.
Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation
PV Romero U Lucangelo J Lopez Aguilar R Fernandez L Blanch 《Canadian Metallurgical Quarterly》1997,10(6):1309-1315
Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome. 相似文献
40.
GW Brown PV Jallepalli BJ Huneycutt TJ Kelly 《Canadian Metallurgical Quarterly》1997,94(12):6142-6147
The fission yeast gene cdc18(+) is required for entry into S phase and for coupling mitosis to the successful completion of S phase. Cdc18 is a highly unstable protein that is expressed only once per cell cycle at the G1/S boundary. Overexpression of Cdc18 causes a mitotic delay and reinitiation of DNA replication, suggesting that the inactivation of Cdc18 plays a role in preventing rereplication within a given cell cycle. In this paper, we present evidence that Cdc18 is associated with active cyclin-dependent kinase in vivo. We have expressed Cdc18 as a glutathione S-transferase fusion in fission yeast and demonstrated that the fusion protein is functional in vivo. We find that the Cdc18 fusion protein copurifies with a kinase activity capable of phosphorylating histone H1 and Cdc18. The activity was identified by a variety of methods as the cyclin-dependent kinase containing the product of the cdc2(+) gene. The amino terminus of Cdc18 is required for association with cyclin-dependent kinase, but the association does not require the consensus cyclin-dependent kinase phosphorylation sites in this region. Additionally, both G1/S and mitotic forms of cyclin-dependent kinase phosphorylate and interact with Cdc18. These interactions between Cdc18 and cyclin-dependent kinases suggest mechanisms by which cyclin-dependent kinases could activate the initiation of DNA replication and could prevent rereplication. 相似文献