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21.
Martine E. Laethem Frans M. Belpaire Pascal Wijnant Marie-Thrse Rosseel Marc G. Bogaert 《Chirality》1994,6(5):405-410
The influence of endotoxin-induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to α1-acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)-enantiomer were higher than those of the (S)-enantiomer, while for verapamil the reverse was true. Protein binding and intrinsic clearance are the main factors responsible for this enantioselectivity. After endotoxin treatment, for the three drugs tested the plasma concentrations and the plasma binding of both enantiomers were significantly increased. This effect was more pronounced for (R)-propranolol, (R)-oxprenolol, and (S)-verapamil than for their respective antipodes. The enantioselective effect of endotoxin on the plasma concentrations of the drugs studied seems mainly due to the enantioselective increase in binding to α1-acid glycoprotein. © 1994 Wiley-Liss, Inc. 相似文献
22.
Jacques J. H. Hens Marina De Wit Lodewijk V. Dekker Frans Boomsma A. Beate Oestreicher Frank Margolis† Willem Hendrik Gispen Pierre N. E. De Graan 《Journal of neurochemistry》1993,60(4):1264-1273
Abstract: The involvement of B-50, protein kinase C (PKC), and PKC-mediated B-50 phosphorylation in the mechanism of Ca2+-induced noradrenaline (NA) release was studied in highly purified rat cerebrocortical synaptosomes permeated with streptolysin-O. Under optimal permeation conditions, 12% of the total NA content (8.9 pmol of NA/mg of synaptosomal protein) was released in a largely (>60%) ATP-dependent manner as a result of an elevation of the free Ca2+ concentration from 10?8 to 10?5M Ca2+ The Ca2+ sensitivity in the micromolar range is identical for [3H]NA and endogenous NA release, indicating that Ca2+-induced [3H]NA release originates from vesicular pools in noradrenergic synaptosomes. Ca2+-induced NA release was inhibited by either N- or C-terminal-directed anti-B-50 antibodies, confirming a role of B-50 in the process of exocytosis. In addition, both anti-B-50 antibodies inhibited PKC-mediated B-50 phosphorylation with a similar difference in inhibitory potency as observed for NA release. However, in a number of experiments, evidence was obtained challenging a direct role of PKC and PKC-mediated B-50 phosphorylation in Ca2+-induced NA release. PKC pseudosubstrate PKC19-36, which inhibited B-50 phosphorylation (IC50 value, 10?5M), failed to inhibit Ca2+-induced NA release, even when added before the Ca2+ trigger. Similar results were obtained with PKC inhibitor H-7, whereas polymyxin B inhibited B-50 phosphorylation as well as Ca2+-induced NA release. Concerning the Ca2+ sensitivity, we demonstrate that PKC-mediated B-50 phosphorylation is initiated at a slightly higher Ca2+ concentration than NA release. Moreover, phorbol ester-induced PKC down-regulation was not paralleled by a decrease in Ca2+-induced NA release from streptolysin-O-permeated synaptosomes. Finally, the Ca2+- and phorbol ester-induced NA release was found to be additive, suggesting that they stimulate release through different mechanisms. In summary, we show that B-50 is involved in Ca2+-induced NA release from streptolysin-O-permeated synaptosomes. Evidence is presented challenging a role of PKC-mediated B-50 phosphorylation in the mechanism of NA exocytosis after Ca2+ influx. An involvement of PKC or PKC-mediated B-50 phosphorylation before the Ca2+ trigger is not ruled out. We suggest that the degree of B-50 phosphorylation, rather than its phosphorylation after PKC activation itself, is important in the molecular cascade after the Ca2+ influx resulting in exocytosis of NA. 相似文献
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24.
Mario H.J. Vogt Elisabet H. Stet Ronney A. De Abreu Jos P.M. Bökkerink Lambert H.J. Lambooy Frans J.M. Trijbels 《生物化学与生物物理学报:疾病的分子基础》1993,1181(2):189-194
The importance of methyl-thioIMP (Me-tIMP) formation for methylmercaptopurine ribonucleoside (Me-MPR) cytotoxicity was studied in Molt F4 cells. Cytotoxicity of Me-MPR is caused by Me-tIMP formation with concomitant inhibition of purine de novo synthesis. Inhibition of purine de novo synthesis resulted in decreased purine nucleotide levels and enhanced 5-phosphoribosyl-1-pyrophosphate (PRPP) levels, with concurrent increased pyrimidine nucleotide levels. The Me-tIMP concentration increased proportionally with the concentration of Me-MPR. High Me-tIMP concentration also caused inhibition of PRPP synthesis. Maximal accumulation of PRPP thus occurred at low Me-MPR concentrations. As little as 0.2 μM Me-MPR resulted already after 2 h in maximal inhibition of formation of adenine and guanine nucleotides, caused by inhibition of purine de novo synthesis by Me-tIMP. Under these circumstances increased intracellular PRPP concentrations could be demonstrated, resulting in increased levels of pyrimidine nucleotides. So, in Molt F4 cells, formation of Me-tIMP form Me-MPR results in cytotoxicity by inhibition of purine de novo synthesis. 相似文献
25.
Frans A. Prins Ronnie van Diemen-Steenvoorde Jan Bonnet Ingrid Cornelese-ten Velde 《Histochemistry and cell biology》1993,99(6):417-425
Reflection contrast microscopy (RCM) of ultrathin sections was recently introduced as a sensitive technique for visualization with enhanced definition in immunogold histochemistry. Experience of using RCM as a major tool in immunocytochemical research in different fields is summarized, e.g. oncology, nephrology and embryology. The sensitive visualization of immunocytochemical labels, gold particles or peroxidase-diaminobenzidine deposits in or on ultrathin sections, by RCM instead of electron microscopy is demonstrated. RCM of ultrathin sections is an adequate light microscopical alternative for immunoelectron microscopy, since an overview of both label and tissue is obtained with a high image definition and high contrast of label. In the studies presented, RCM is shown to provide a better gradation in staining intensity and staining pattern than other light microscopical methods. Moreover, a precise localization of multiple labels is obtained with this method. Besides the applications shown, ultrathin section visualization by RCM is very useful for correlative light- and electron microscopical studies of fine structures. Commercially available fluorescence microscopes can be adapted for proper RCM functioning; an adaptation scheme and list of microscopes tested is provided. 相似文献
26.
27.
Hall Robert D.; Riksen-Bruinsma Tjitske; Weyens Guy; Lefbvre Marc; Dunwell Jim M.; Tunen Arjen Van; Krens Frans A. 《Journal of experimental botany》1997,48(2):255-263
A highly-efficient protocol for the large-scale isolation ofguard cell protoplasts from sugar beet (Beta vulgaris L.) hasbeen developed. Optimization of conditions for culturing theseprotoplasts resulted in extensive cell division and colony formation,at frequencies exceeding 50%. Plants can subsequently be regeneratedfrom these guard cell-derived colonies. This provides definitiveconfirmation that, in sugar beet leaf protoplast populations,only guard cells are the source of totipotent protoplasts. Thesefindings are the outcome of a directed, non-empirical approachto overcoming plant cell recalcitrance which was initiated byexploiting computer-assisted microscopy to couple in vitro responseto cell origin. The results reaffirm the conclusion that, inplants, extreme degrees of cytodifferentiation need not entailterminal specialization. The responsive nature of this systemcan be ascribed to the unique use of cultures essentially comprisinga single in vivo cell type. A uniform model system has thusbeen created with potential for widespread application. Theirdistinct morphological (and mechanical) features make guardcells a valuable choice for studying various fundamental aspects,not only of stomatal physiology, but also of plant cell (de)differentiation,differential gene expression etc. Furthermore, an applied valuefor such a system can also be envisaged. Results indicate thatthese cells are highly amenable to genetic manipulation techniques.The importance of these observations to our understanding ofplant cell function and behaviour is discussed. Key words: Beta, guard cells, stomatal physiology, totipotency, transformation 相似文献
28.
Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation 总被引:2,自引:0,他引:2
Angenita F. van Lieburg Marian A. J. Verdijk Frans Schoute Marjolijn J. L. Ligtenberg Bernard A. van Oost Franz Waldhauser Maria Dobner Leo A. H. Monnens Nine V. A. M. Knoers 《Human genetics》1995,96(1):70-78
Nephrogenic diabetes insipidus (NDI) usually shows an X-linked recessive mode of inheritance caused by mutations in the vasopressin type 2 receptor gene (AVPR2). In the present study, three NDI families are described in which females show clinical features resembling the phenotype in males. Maximal urine osmolality in three female patients did not exceed 200 mosmol/kg and the absence of extra-renal responses to 1-desamino-8-d-arginine vasopressin was demonstrated in two of them. All affected females and two asymptomatic female family members were shown to be heterozygous for an AVPR2 mutation. Skewed X-inactivation is the most likely explanation for the clinical manifestation of NDI in female carriers of an AVPR2 mutation. It is concluded that, in female NDI patients, the possibility of heterozygosity for an AVPR2 gene mutation has to be considered in addition to homozygosity for mutations in the aquaporin 2 gene. 相似文献
29.
Christophe Philippe Ccile Arnould Frdrique Sloan Hans van Bokhoven Saskia D. van der Velde-Visser Michle Chery H. Hilger Ropers Simone Gilgenkrantz Anthony P. Monaco Frans P. M. Cremers 《Genomics》1995,27(3)
In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome (Philippe et al., Genomics 17: 147-152, 1993). Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region. 相似文献
30.
Frans B.M. de Waal 《Animal behaviour》1984,32(3):765-773
In previous research, male chimpanzees (Pan troglodytes) were found to be more ‘conciliatory’ than females, in that after aggressive incidents males more often engaged in socially positive contact with former opponents. The first part of the present paper presents similar results for a large breeding troop of rhesus monkeys (Macaca mulatta). To investigate further the possible sex difference in postconflict behaviour, a series of experiments was carried out on small isosexual groups of young rhesus monkeys, three male and three female groups. Food competition was created by providing either a single apple piece (Monopoly test) or a handful of small pieces (Equality test). Observations lasted for 30 min, and behaviour in tests without food provisioning was also recorded. The predicted response to food was an increase in aggression followed by restorative behaviour, such as grooming. In Equality tests both sexes showed similar responses, i.e. increased aggression and decreased grooming and cohesiveness. In Monopoly tests, however, their responses differed. After the aggression increase, which occurred in all groups, males showed a significant increase in grooming and cohesiveness, whereas females showed the (non-significant) opposite trend. Another sex difference was that changes in grooming and aggression frequencies were related to the rank order in female groups, but not in male groups. Since there was no evidence for a direct causal connection between grooming and aggression, a new model is introduced which links grooming behaviour to the type of food provision rather than to the social disturbance by aggression. According to this model inequality in food distribution causes social tensions. Males actively try to reduce these tensions, whereas females do not. Some alternative explanations are also discussed. 相似文献