银川地区尿酸转运相关基因多态性与高尿酸血症相关性研究

目的 分析银川地区居民尿酸水平的影响因素,探讨溶质载体家族30成员3(SLC30A3)基因多态性与高尿酸血症发生的关系.方法 选取高尿酸血症患者614例,同期年龄和性别构成相当的尿酸正常健康体检者600例为对照组.使用Haploview软件筛选SLC30A3基因tagSNP,共得到2个SNP位点(rs13267319,rs24628779),分析SLC30A3基因多态性与银川地区居民高尿酸血症的关系.结果 银川地区居民中男性受试者尿酸水平与BMI值、腰围、收缩压、GLU呈正相关,与HDL-C呈负相关;女性受试者尿酸水平与腰围、GLU、TC、TG呈正相关,与HDL-C呈负相关.多因素Logistic回归分析显示:BMI值、收缩压、舒张压、TG、LDL-C、Cre是高尿酸血症的独立危险因素,HDL-C是高尿酸血症的保护因素.SLC30A3基因rs13267319位点在高尿酸血症组AG型和AA型比例均明显低于对照组,差异具有统计学意义(P<0.05);与GG型相比,AG型和AA型患高尿酸血症的危险性均明显降低;等位基因A相对于G对高尿酸血症有保护作用.SLC30A3基因rs24628779位点在高尿酸血症组CT型和TT型比例均明显高于对照组,差异具有统计学意义(P<0.05);与CC型相比,CT型和TT型患高尿酸血症的危险性均明显增高.等位基因C相对于T对高尿酸血症有促进作用.结论 SLC30A3基因rs13267319,rs24628779位点与银川地区居民高尿酸血症的发病机制存在明显关联.     

Cloning and functional analysis of the sequences flanking mini-Tn5 in the magnetosome-deleted mutant NM21 of Magnetospirillum gryphiswaldense MSR-1

A magnetosome-deleted mutant NM21 of Magnetospirillum gryphiswaldense MSR-1 was generated by mini-Tn5 lacZ2 transposon mutagenesis, and a 3073-bp fragment flanking mini-Tn5 lacZ2 in NM21 was cloned by Anchored PCR. Sequencing analysis showed that this fragment involved three putative ORFs; the mini-Tn5 lacZ2 was inserted into ORF1. Functional complementary test indicated that the 3073-bp fragment was required for biosynthesis of magnetosomes in M. gryphiswaldense MSR-1. The majority of proteins, which had h...     

Moderate cooling depresses the accumulation and the release of newly synthesized catecholamines in isolated canine saphenous veins

Summary Moderate cooling (from 37° to 24°C) depressed the formation of³H-dopamine and³H-norepinephrine from³H-tyrosine by isolated canine saphenous veins. Cooling reduced the evoked release ofnewly synthesized catecholamine to the same extent as tha of stored norepinephrine. Hence the augmentation by cold of the contractile response to sympathetic nerve stimulation observed in earlier work is not accompanied by an augmentated release of newly synthesized norepinephrine.Acknowledgments. This work was supported by grant HL 05883 from the National Institutes of Health. The authors want to thank F. Jordaens for his valuable technical assistance, J. Beckman for secretarial assistance and H. Hedrickson for preparing the illustrations.Recipient of training grant 80304 from the I.W.O.N.L.     

Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

benztropine类多巴胺转运蛋白配体的QSAR研究

利用Hansch方法，研究了37种benztropine类化合物diphenylmethoxy部位苯环取代基结构与其活性的定量关系，结果表明：苯环取代基的电性和体积等均是影响该类化合物与多巴胺转运蛋白亲和力的重要因素，所得到的benztropine类化合物diphenylmethoxy部位取代基的综合结构效应，对进一步研究该部位与多巴胺转运蛋白相互作用的电性和立体性质及设计新的多巴胺转运蛋白配体具有指导意义。     

多巴胺系统在甲基苯丙胺成瘾中的作用

目的:研究多巴胺系统在甲基苯丙胺成瘾中的作用。方法:通过查阅近年来国内外专家对甲基苯丙胺对多巴胺、多巴胺受体、多巴胺转运体的作用,总结多巴胺系统在甲基苯丙胺成瘾中的作用。结果:多巴胺系统在甲基苯丙胺成瘾过程中起重要作用。结论:研究清楚多巴胺系统在甲基苯丙胺成瘾中的作用,为甲基苯丙胺成瘾治疗寻找有效靶点。     

ADTIQ导致SH-SY5Y细胞凋亡和多巴胺转运体表达降低

新内源性神经毒素1-乙酰基-6,7-二羟基-1,2,3,4-四氢异喹啉(ADTIQ)生成与糖代谢密切相关,可能成为糖尿病并发PD的一个关键因素,但是其神经毒性还不清楚.针对ADTIQ的神经毒性,该研究采用SH-SY5Y细胞为模型,MTT法,Annexin V/PI双染法,Caspase 3/7活性检测细胞存活率和细胞凋亡,Western-blot检测多巴胺转运体(DAT)的表达量.结果表明,随着ADTIQ浓度增大,细胞的存活率逐渐下降,凋亡率增加,同时ADTIQ导致DAT表达降低.研究提示ADTIQ导致多巴胺神经元的凋亡与PD的发生息息相关,糖尿病引起ADTIQ增加,可能成为高糖损伤多巴胺神经元的一个重要原因.     

1．5t级农用运输车底盘与发动机匹配的综合研究

分析了目前１．５吨级农用运输车柴油机和底盘匹配不够合理的现状，综合研究了当柴油机给定后，优选传动系参数和给定底盘参数后，优选发动机参数，以达到最佳匹配的方法．     

Nucleotide-binding domains of human cystic fibrosis transmembrane conductance regulator: detailed sequence analysis and three-dimensional modeling of the heterodimer

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is encoded by the gene that is defective in cystic fibrosis, the most common lethal inherited disease among the Caucasian population. CFTR belongs to the ABC transporter superfamily, whose members form macromolecular architectures composed of two membrane-spanning domains and two nucleotide-binding domains (NBDs). The experimental structures of NBDs from several ABC transporters have recently been solved, opening new avenues for understanding the structure/function relationships and the consequences of some disease-causing mutations of CFTR. Based on a detailed sequence/structure analysis, we propose here a three-dimensional model of the human CFTR NBD heterodimer. This model, which is in agreement with recent experimental data, highlights the specific features of the CFTR asymmetric active sites located at the interface between the two NBDs. Moreover, additional CFTR-specific features can be identified at the subunit interface, which may play critical roles in active site interdependence and are uncommon in other NBD dimers.Received 16 October 2003; received after revision 16 November 2003; accepted 21 November 2003