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41.
A. Tchelet T. Vogel D. Helman R. Guy C. Neospouolus V. Goffin J. Djiane A. Gertler 《Molecular and cellular endocrinology》1997,130(1-2):141-152
A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus. 相似文献
42.
Surface-related triggering of the neutrophil respiratory burst. Characterization of the response induced by IgG adsorbed to hydrophilic and hydrophobic glass surfaces 总被引:1,自引:0,他引:1 下载免费PDF全文
L LIU H ELWING A KARLSSON G NIMERI C DAHLGREN 《Clinical and experimental immunology》1997,109(1):204-210
Hydrophilic and hydrophobic glass surfaces precoated with human albumin, fibrinogen, or IgG were investigated with respect to their ability to activate the neutrophil NADPH-oxidase. We found that IgG-coated surfaces induced a substantial and prolonged neutrophil production of reactive oxygen species (ROS). When a hydrophilic surface was used to support protein binding, a somewhat lower neutrophil response (around 35%) was obtained, compared with the response induced by IgG on a hydrophobic surface. The production of ROS was completely eliminated when cytochalasin B was added to the measuring system, suggesting the involvement of the cell cytoskeleton in the activation process. The relation between the intra- and extracellular generation of ROS was further assessed, and we found that most of the ROS produced were released from the cells, in agreement with a model in which the activating surfaces induce a ‘frustrated’ phagocytic response. Serum totally inhibited ‘frustrated’ phagocytosis provided that the IgG molecules were sticking to a hydrophilic surface. 相似文献
43.
44.
目的: 研究变性蛋白质在高效疏水作用色谱(HPHIC)上的保留行为及复性效率. 方法: 分别用盐酸胍(GuHCl)、尿素(Urea)和十二烷基磺酸钠(SDS)将核糖核酸酶(Rnase)等10种标准蛋白质变性,然后在流动相为硫酸铵的条件下,用HPHIC对变性蛋白质进行复性,并测定其保留时间、Z值、质量及活性回收率. 结果: 在10种变性蛋白质中有5种在HPHIC上得到复性,其保留时间、峰形、Z值与天然蛋白基本一致,其中溶菌酶和核糖核酸酶的质量和活性回收率高,复性效果好. 结论: 用HPHIC对变性的标准蛋白质进行复性,得到较好的复性效果. 相似文献
45.
HLA-A26等位基因与银屑病环境危险因素的交互作用 总被引:1,自引:0,他引:1
目的:研究银屑病HLA-A26等位基因与环境危险因素之间的交互作用。方法:采用病例对照研究方法,调查190例银屑病患者及同一地区的健康对照191例,用多聚酶链反应-序列特异性引物(PCR-SSP)方法进行HLA-A26等位基因检测,对银屑病的环境危险因素及与HLA-A等位基因间交互作用进行研究。结果:(1)受潮、感染、外伤、嗜酒、吸烟、食鱼虾、药物和精神紧张均为银屑病的环境危险因素。(2)与正常对照组相比,HLA-A26等位基因与银屑病呈显著正相关(P<0.001)。(3)HLA-A26等位基因与受潮、嗜酒和食鱼虾存在显著交互作用。结论:HLA-A26等位基因似能增加受潮、嗜酒和食鱼虾发生银屑病的易患性。 相似文献
46.
Dao Yin Xie Stefan Hassenstein Martin Oberhoff Hartmut Hanke Andreas Baumbach Kristian Hohla Karl Konstantin Haase Karl Rüdiger Karsch 《Lasers in surgery and medicine》1993,13(6):618-624
A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm2 in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc. 相似文献
47.
W. Couet B. Istin P. Seniuta D. Morel L. Potaux J. B. Fourtillan 《European journal of clinical pharmacology》1990,39(2):165-167
Summary The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin.On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption.Ponsinomycin should be use very carefully in patients treated with cyclosporin A. 相似文献
48.
The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine. 相似文献
49.
A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism 总被引:6,自引:0,他引:6
R. A. Lucas D. J. Gilfillan R. F. Bergstrom 《European journal of clinical pharmacology》1998,54(8):639-643
Objective: Olanzapine is a novel antipsychotic, which is effective against both the positive and negative symptoms of schizophrenia
and causes fewer extrapyramidal adverse effects than conventional antipsychotics. The purpose of the present study was to
assess the potential for a pharmacokinetic interaction between olanzapine and carbamazepine, since these agents are likely
to be used concomitantly in the treatment of manic psychotic disorder.
Method: The pharmacokinetics of two single therapeutic doses of olanzapine were determined in 11 healthy volunteers. The first dose
of olanzapine (10 mg) was taken alone and the second dose (10 mg) after 2 weeks of treatment with carbamazepine (200 mg BID).
Measurement of urinary 6-hydroxycortisol/cortisol excretion was used as an endogenous marker to confirm that induction of
CYP3A4 by carbamazepine had occurred.
Results: The dose of olanzapine given after a 2-week pre-treatment with carbamazepine was cleared more rapidly than olanzapine given
alone. Olanzapine pharmacokinetic values for Cmax and AUC were significantly lower after the second dose, the elimination half-life was significantly shorter, and the clearance
and volume of distribution were significantly increased.
Conclusion: Carbamazepine has been shown to induce several P450 cytochromes including CYP3A4 and CYP1A2. Since CYP1A2 plays a role in
the metabolic clearance of olanzapine, the interaction may be attributed to induction of CYP1A2 by carbamazepine, leading
to increased first-pass and systemic metabolism of olanzapine. The interaction is not considered to be of clinical significance
because olanzapine has a wide therapeutic index, and the changes in plasma concentration of olanzapine are within the fourfold
variation that occurs without concern for safety in a patient population.
Received: 22 July 1997 / Accepted in revised form: 1 June 1998 相似文献
50.
D. M. Jackson C. E. Wallsten E. Jerning P.-S. Hu A. M. Deveney 《Psychopharmacology》1998,139(4):300-310
The aim was to study firstly, the motor effects of a new 5-HT1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether
the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic
activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal
5-HT1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the
locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity
and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing.
PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249
induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction
in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant
increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D1 agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant
pre-treatment with NDL-249. Pre-treatment of rats with either the DA D1 antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D2 antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion,
5-HT1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated
probably indirectly via DA systems.
Received: 3 April 1997/Final version: 23 February 1998 相似文献