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排序方式: 共有181条查询结果,搜索用时 15 毫秒
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C.Z. DONG H. DE ROCQUIGNY E. RMY S. MELLAC M.C. FOURNI-ZALUSKI B.P. ROQUES 《Chemical biology & drug design》1997,50(4):269-278
Specific interactions between the 72-amino acid nucleocapsid protein NCp7 of the human immunodeficiency virus, type 1 and the genomic RNA are essential for virus replication. Studies on the mechanism of action of NCp7 require a direct visualization of its complexes with nucleic acids and the determination of binding affinities. To facilitate these investigations, fluorescent NCp7 derivatives were developed by introduction in the NCp7 sequence of a non-natural amino acid, (S)-β-(9-acridinyl)alanine (Aca) obtained by a chiral synthetic method. Three fluorescent NCp7 derivatives were obtained by introducing this amino acid at different positions. As shown by NMR, the three-dimensional structure of NCp7 is not altered by introduction of Aca. The fluorescent peptides were found to be as potent as their precursors in interacting with nucleic acids and in promoting HIV-1 genomic RNA dimerization. Moreover, because of their fluorescent properties, these NCp7s can be used at submicromolar concentrations to directly visualize and quantify protein-nucleic acid interactions in solution or after gel electrophoresis. This could facilitate the development of new antiviral agents aimed at inhibiting the functions of NCp7 and studies on the intracellular traffic of NCp7 within the preintegration complex. 相似文献
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The paper reports results of an analysis based on face-to-face interviews with two samples of Prague women aged 20-49: (1) a probabilistic sample (h = 718) of the Prague female population; and (2) a sample of 152 inpatients treated for substance dependence/abuse. Of the inpatients, 79% were diagnosed as alcohol dependent only, 15% as both alcohol dependent and drug dependent/abusers, 6% as drug dependent only. With very few exceptions, those with drug problems among the inpatients abused analgesics, hypnotics, or anxiolytics. With data obtained from the general population sample, two-stage hierarchical logistic regression was run with each of the eleven differently defined substance uses as dependent variables. Four demographic variables were entered as predictors into the regression equations in the first stage. From the seven potential risk factors of substance use statistically significant predictors were entered stepwise in stage two. The major result of the study is the specificity of the pattern of predictors related to each of the eleven considered substance uses. It is also found that in the general population the use of a particular substance is generally uncorrelated with the use of other substances. Alcohol use (even heavy alcohol use) has no relation to smoking, to the use of analgesics, hypnotics, anxiolytics-and is connected with a specific pattern of predictors. 相似文献
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Edoardo Ferlazzo Chiara Sueri Sara Gasparini Emilio Russo Vittoria Cianci Michele Ascoli 《Expert review of clinical pharmacology》2017,10(10):1103-1108
Introduction: despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future.Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or ‘time-to-event’ design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient’s ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed.Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients’ and clinicians’ needs. 相似文献
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Hon YY; Fessing MY; Pui CH; Relling MV; Krynetski EY; Evans WE 《Human molecular genetics》1999,8(2):371-376
The molecular basis for the genetic polymorphism of thiopurine S -
methyltransferase (TPMT) has been estab-lished for Caucasians, but it
remains to be elucidated in African populations. In the current study, we
determined TPMT genotypes in a population of 248 African-Americans and
compared it with allele frequencies in 282 Caucasian Americans. TPMT
genotype was determined in all individuals with TPMT activity indicative of
a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n
= 21 Caucasians) and a control group with TPMT activity indicative of a
homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23
African-Americans, n = 21 Caucasians). No mutant alleles were found in the
high activity control groups. The overall mutant allele frequencies were
similar in African-Americans and Caucasians (4.6 and 3.7% of alleles,
respectively). However, while TPMT*3C was the most prevalent mutant allele
in African-Americans (52.2% of mutant alleles), it represented only 4.8% of
mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and
TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant
alleles), whereas TPMT*3A was the most prevalent mutant allele in
Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing
a single nucleotide transition (G644A), leading to an amino acid change at
codon 215 (Arg-->His), was found in one African-American with
intermediate activity. These data indicate that the same TPMT mutant
alleles are found in American black and white populations, but that the
predominant mutant alleles differ in these two ethnic groups.
相似文献
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目的 :研究硝苯吡啶以及硝苯吡啶与格列本脲合用对空腹大鼠和肾上腺素诱发高血糖大鼠血糖水平的影响。方法 :本实验采用葡萄糖氧化酶法测定血糖含量。结果 :硝苯吡啶 2 .5mg/kgig使空腹大鼠血糖水平显著升高(P <0 .0 1 ) ,并加重肾上腺素诱发的高血糖反应。而硝苯吡啶与降糖药格列本脲 0 .9mg/kg合用时不影响空腹大鼠的血糖水平 ,硝苯吡啶对肾上腺素诱发高血糖大鼠灌胃格列本脲后的降血糖作用亦无明显影响。结论 :尽管硝苯吡啶对空腹大鼠以及肾上腺素诱发高血糖大鼠有显著升高血糖的作用 ,但对格列本脲的降血糖作用无明显不良影响 相似文献
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目的 :采用RP HPLC法同时测定了注射用甲氧异腈中两种主要成份二氧硫脲 (FSA)和四 (甲氧基异丁基异腈 )络铜 (I)氟硼酸盐 (MIBI)的含量。方法 :以甲醇、磷酸二氢铵 ( 80∶2 0 )为流动相 ,检测波长 2 1 5nm ,HPLC法测定含量。结果 :试验表明 ,FSA和MIBI在 2 5~ 1 2 5μg/ml,50~ 2 50 μg/ml范围内呈良好的线性关系 ,回归方程分别为Y =0 .2 3 0 .0 2X(r =0 .994 6) ,Y =-2 .1 9 0 .0 3X(r =0 .9998) ,相对标准偏差分别为 1 .2 5%和 0 .4 2 %。结论 :该方法简便、准确、可靠 相似文献