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991.
Imprinted polymers were prepared for nicotinamide and its positional isomers. The influence of porogenic solvent and functional monomer on recognition properties of the polymer was compared. The results indicated that two functional groups, the heterocyclic nitrogen and the amide group, in the nicotinamide or isonicotinamide molecule have a synergistic effect in binding to the polymer. The polymers prepared with nicotinamide and isonicotinamide can be used as HPLC stationary phase for the separation of positional isomers of nicotinamide or isonicotinamide, while the polymer prepared with picolinamide showed no specificity toward the template. The mechanisms for the differences in recognition are discussed. In addition to the retention of polymers to their templates the polymers also displayed excellent retention to nicotinic acid and isonicotinic acid, compounds structurally similar to the template. This dual recognition property of the polymer may be useful in circumstances where the preparation of a polymer for a specific template may be problematic because of poor stability or solubility. 相似文献
992.
ObjectiveTo see whether a behaviourally based group parenting programme, delivered in regular clinical practice, is an effective treatment for antisocial behaviour in children.DesignControlled trial with permuted block design with allocation by date of referral.Setting Four local child and adolescent mental health services.Participants141 children aged 3-8 years referred with antisocial behaviour and allocated to parenting groups (90) or waiting list control (51).InterventionWebster-Stratton basic videotape programme administered to parents of six to eight children over 13-16 weeks. This programme emphasises engagement with parental emotions, rehearsal of behavioural strategies, and parental understanding of its scientific rationale.ResultsReferred children were highly antisocial (above the 97th centile on interview measure). Children in the intervention group showed a large reduction in antisocial behaviour; those in the waiting list group did not change (effect size between groups 1.06 SD (95% confidence interval 0.71 to 1.41), P<0.001). Parents in the intervention group increased the proportion of praise to ineffective commands they gave their children threefold, while control parents reduced it by a third (effect size between groups 0.76 (0.16 to 1.36), P=0.018). If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16%.ConclusionsParenting groups effectively reduce serious antisocial behaviour in children in real life conditions. Follow up is needed to see if the children''s poor prognosis is improved and criminality prevented.
What is already known on this topic
Children who persistently display a high level of antisocial behaviour are at high risk of social rejection, juvenile delinquency, and long term unemployment; the cost to society is highWhile some behaviourally based parenting programmes have been shown to be effective in university centre trials with volunteers or specially selected cases, most trials of psychological treatments for children in real life settings have shown no effectWhat this study adds
An evidence based intervention is available for use in regular clinical practice that effectively reduces antisocial behaviour in referred childrenThe intervention works well with children at risk of criminality from a combination of highly antisocial behaviour, multiple psychopathology, and social deprivation 相似文献993.
Aromatase and COX-2 expression in human breast cancers 总被引:8,自引:0,他引:8
Brodie AM Lu Q Long BJ Fulton A Chen T Macpherson N DeJong PC Blankenstein MA Nortier JW Slee PH van de Ven J van Gorp JM Elbers JR Schipper ME Blijham GH Thijssen JH 《The Journal of steroid biochemistry and molecular biology》2001,79(1-5):41-47
We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen. 相似文献
994.
Weller J Sun GC Zhou B Lan Q Hiruma K Riddiford LM 《Insect biochemistry and molecular biology》2001,31(8):827-837
The cDNAs for two members of the nuclear receptor superfamily were isolated from the tobacco hornworm, Manduca sexta. The deduced amino acid sequence of MHR4 shows 93-95% identity in the DNA-binding domain and the first portion of the hinge (D) region with the germ cell nuclear factor (GCNF)-related factors (GRFs) of the silkworm, Bombyx mori, and the mealworm, Tenebrio molitor, and with a genomic sequence from the fruit fly, Drosophila melanogaster. Northern blot hybridization showed that a 7.5 kb MHR4 mRNA appeared in Manduca abdominal epidermis just as the ecdysteroid titer began to decline during the larval molt, disappeared about 12 h later, then transiently reappeared shortly before larval ecdysis. During the pupal and adult molts, a similar pattern of expression was seen (the very end of the adult molt was not studied). At peak times of expression in the epidermis, MHR4 mRNA was also present in fat body and the central nervous system (CNS). The deduced amino acid sequence of Manduca FTZ-F1 is 100% and 96% identical to that of B. mori and Drosophila betaFTZ-F1, respectively, in the DNA-binding domain and the adjacent hinge region including the FTZ-F1 box. Northern blot analysis showed that the >9.5 kb betaFTZ-F1 mRNA appeared in Manduca epidermis during the decline of the ecdysteroid titer in the larval, pupal and adult molts as the first peak of MHR4 mRNA declined, then it disappeared in the larval and pupal molts before the second peak of MHR4 appeared. betaFTZ-F1 mRNA was also found in fat body and the CNS at the time of peak expression in the epidermis during the larval and pupal molts. Both MHR4 and betaFTZ-F1 mRNAs were found in the testis during the onset of spermatogenesis in the prepupal period. 相似文献
995.
996.
纤维连接蛋白对支气管上皮细胞抗氧化损伤保护作用的研究 总被引:4,自引:0,他引:4
目的和方法:为验证整合素分子激活对支气管上皮细胞(BEC)的抗氧化性保护作用,本实验用臭氧(O3)攻击培养的兔BEC,测定细胞的^3H释放率、乳酸脱氢酶(LDH)释放活性及脂质过氧化产物丙二醛(MDA)含量,反映细胞损伤程度;观察纤维连接蛋白(Fn)及人工合成的精-甘-天冬氨酸片段(RGD肽)的保护效应。结果:①臭氧攻击使BEC的^3H释放率增高,Fn处理可减少臭氧所致的^3H释放,钙调素抑制剂W7能抑制Fn的这一作用,RGD可减轻臭氧所致的^3H释放;②臭氧攻击后细胞上清液中LDH释放增多,Fn或RGD处理均能降低LDH释放,W7阻断Fn的这一效奕;③臭氧作用后明显提高细胞内MDA含量,Fn或RGD可降低MDA含量;④臭氧攻击使细胞内GSH含量下降,Fn或RGD可增加BEC内GSH的含量;⑤Fn可增强BEC内过氧化氢酶(CAT)活性,但可被W7阻断,RGD则显示有剂量依赖性促进作用。结论:Fn及其特异识别片段与BEC的整合素分子结合后,可减轻臭氧对BEC细胞的损伤,其机理与经钙调素途径上调BEC抗氧化能力有关。 相似文献
997.
998.
Liu Q Sham JS Shimoda LA Sylvester JT 《American journal of physiology. Lung cellular and molecular physiology》2001,280(5):L856-L865
To determine the role of endothelium in hypoxic pulmonary vasoconstriction (HPV), we measured vasomotor responses to hypoxia in isolated seventh-generation porcine pulmonary arteries < 300 microm in diameter with (E+) and without endothelium. In E+ pulmonary arteries, hypoxia decreased the vascular intraluminal diameter measured at a constant transmural pressure. These constrictions were complete in 30-40 min; maximum at PO(2) of 2 mm Hg; half-maximal at PO(2) of 40 mm Hg; blocked by exposure to Ca(2+)-free conditions, nifedipine, or ryanodine; and absent in E+ bronchial arteries of similar size. Hypoxic constrictions were unaltered by indomethacin, enhanced by indomethacin plus N(G)-nitro-L-arginine methyl ester, abolished by BQ-123 or endothelial denudation, and restored in endothelium-denuded pulmonary arteries pretreated with 10(-10) M endothelin-1 (ET-1). Given previous demonstrations that hypoxia caused contractions in isolated pulmonary arterial myocytes and that ET-1 receptor antagonists inhibited HPV in intact animals, our results suggest that full in vivo expression of HPV requires basal release of ET-1 from the endothelium to facilitate mechanisms of hypoxic reactivity in pulmonary arterial smooth muscle. 相似文献
999.
高原移居者红细胞滤过指数的变化及其机理 总被引:2,自引:0,他引:2
Xi AQ 《中国应用生理学杂志》2001,17(1):51-54
目的:探讨不同海拔和同一海拔高底氧环境不同血色素范围对高原健康人红细胞流变特性的影响及其可能发生的机制。方法:检测不同海拔高度(2260m、3300m、4080m)对320健康人EFI、SOD、和MDA的影响。结果:随海拔高度的升高,高原健康人EFI和MDA含量明显升高,而红细胞SOD活性明显降低;EFI与MDA呈正相关,而与红细胞SOD活性呈负相关。同一海拔低氧环境Hb增高者,EFI和MDA升高,而红细胞SOD活性降低;随海拔升高,EFI和MDA含量明显升高,而红细胞SOD活性明显降低。结论:不同海拔红细胞流变学和氧自由基代谢差异性的形成,低氧环境起核心作用;而随海拔高度升高和同一海拔低氧环境自由基代谢异常加重者是导致高原健康人红细胞流变学异常的中心环节。 相似文献
1000.
Uings IJ Balasubramanian P McLoughlin PG Yin Q Dash L Beresford A Kearney S Barrett RW McKinnon M England BP 《Cytokine》2001,15(1):10-19
AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each chain that antagonises the action of the eosinophil-specific cytokine, interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides derived from AF18748 and demonstrated that the first five amino acids of the peptide do not contribute to receptor binding activity. The shortened peptide blocked IL-5-dependent adhesion of eosinophils with an IC(50)of 350 pM, and had no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha or fMet-Leu-Phe. The peptides were rapidly broken down in mouse plasma through cleavage of a single chain of the dimer. However, this breakdown did not correlate with loss of biological activity, indicating that the asymmetric peptide fragment retains full receptor binding capacity. The activity of AF18748 disappeared rapidly from the blood following intravenous injection into mice. Coupling of polyethylene glycol to the N-terminus of AF18748 resulted in a moderate loss in biological potency (IC(50)30 nM), but the resulting conjugate persisted in the circulation for more than 8 h after injection. Despite its high potency at the human IL-5 receptor, AF18748 was unable to antagonise the activity of IL-5 on murine B13 cells, or on canine eosinophils, indicating that the peptide is highly specific for the human IL-5 receptor. 相似文献