汉族人群微卫星DXS16遗传多态性

目的获得X染色体短串联重复序列DXS16遗传多态性在河南汉族人群中的分布状况。方法应用聚合酶链反应,变性聚丙烯酰胺凝胶电泳（polyacrylamide gel ectrophoresis,PAGE）及银染色技术对110名无血缘关系的汉族个体DXS16基因座进行分型。结果观察到DXS16位点有14个等位基因片段,该STR位点的基因型分布符合Hardy—Weinberg平衡;杂合度为0．88,多态信息含量为0．885。结论DXS16在汉族人群中有较好的多态性分布;实验数据对X染色体特异性STR的群体遗传学研究及一些X连锁遗传病的基因诊断有重要意义。     

天津汉族群体D21S11、D21S1440和Penta D STR基因座遗传多态性的研究

目的:研究天津汉族群体21号染色体上D21S11、D21S1440和Penta D 3个短串联重复序列(STR)基因座遗传多态性,为唐氏综合征(DS)基因诊断和产前基因诊断提供实验依据.方法:收集天津无亲缘关系的汉族个体332例,定量荧光PCR(QF-PCR)扩增STR基因座,ABI PRISM 377测序仪检测PCR扩增产物.根据3个STR基因座的基因型分布进行Hardy-Weinberg平衡检验.计算3个STR基因座的基因型频率、观察杂合度(Ho)、多态信息量(PIC)、个体识别率(DP)、非父排除率(PE)等群体遗传学数据.结果:D21S11、D21S1440和Penta D 3个STR基因座分别检出6、4、8个等位基因,基因型分布均符合Hardy-Weinberg平衡定律.3个基因座的Ho分别为0.617、0.705、0.867,PIC分别为0.755、0.596、0.795,DP分别为0.916、0.794、0.931,PE分别为0.312、0.436、0.730.结论:D21S11、D21S1440和Penta D STR基因座在天津汉族群体杂合度高,是21号染色体良好的遗传标记,对DS的基因诊断有指导意义.     

X染色体STR基因座在法医鉴定中的应用

目的通过探讨太原地区汉族人群位于X染色体上的短串联重复序列DXS6804的遗传多态性,分析X染色体STR基因座在法医鉴定中的利与弊,以促进X染色体STR基因座在法医学实践中的应用。方法随机抽取太原无血缘关系汉族个体静脉血500μL,采集50例两代家系血进行突变观察;采集同一例健康男性尸体的心脏、肝脏、肌肉组织等进行同一性测定。乙二胺四乙酸抗凝,酚-氯仿法提取DNA,聚合酶链反应扩增,8%非变性聚丙烯酰胺凝胶电泳分型。基因座的等位基因频率采用直接计算法,与其他人群比较采用χ2检验。结果共检出5种不同的等位基因,基因多样性为0.7024。与不同地区及不同民族的等位基因频率分布进行了比较均有明显的差异。同一尸体血液,器官组织检测结果分型一致。50例两代家系观察未见突变。结论DXS6804基因座在太原地区汉族人群中有较好的多态性,X染色体STR基因座在法医鉴定中具有重要价值。     

X染色体短串联重复序列基因座的遗传多态性

目的研究DXS7424基因座在山西汉族人群中的遗传多态性。方法随机抽取山西汉族人群250名无关个体静脉血样,乙二胺四乙酸抗凝后用酚-氯仿法提取DNA,经聚合酶链反应扩增,扩增产物用8%非变性聚丙烯酰胺凝胶电泳和银染法进行检测分型,对女性基因型频率分布进行Hardy-Weinberg平衡检验,并计算法医学常用参数。结果在山西汉族人群250名无关个体中共检出7个等位基因。等位基因频率分布在0.008～0.340。女性基因型频率分布符合Hardy-Weinberg平衡。个体识别率、多态性信息含量分别为0.7367、0.7039。结论DXS7424基因座在山西汉族人群中具有较高的遗传多态性,可用于法医学涉及女性的个人识别和亲权鉴定,并为X染色体短串联重复序列数据库的建立提供了山西汉族人群的遗传学数据。     

河北中南部地区汉族群体15个STR基因座遗传多态性研究

目的 研究PowerplexTM 16荧光标记复合扩增系统的15个STR基因座在河北中南部地区汉族个体的多态性分布,建立河北中南部地区汉族群体的遗传学基础数据.方法 采用Chelex-100法应用PowerplexTM 16荧光标记复合扩增系统和ABI 3130遗传分析仪对25295例河北中南部地区汉族个体血样DNA进行检测,统计15个STR基因座的基因型分布、基因频率、杂合度(heterozygosity,Ho)、多态信息量(polymorphism information contents,PIC)、个体识别率(discrimination power,DP)、非父排除率(probability of paternity exclusion,PE)等群体遗传学参数,并进行Hand-y-Weinberg平衡检验.结果 15个基因座在群体中具有较高多态性,基因型分布均符合Handy-Weinberg平衡定律(P>0.05).共检测出293个等位基因,1364种基因型,基因频率在0.002%~51.58%之间,Ho在0.6206~0.9146之间,PIC在0.5610~0.8967之间;累积个人识别率为0.999999999999999996156,累积非父排除率为0.999999663.结论 PowerplexTM 16荧光标记复合扩增系统的15个STR基因座适合作为河北中南部汉族群体的遗传标记.     

河南汉族6个STR基因座的遗传多态性研究

目的 对河南汉族人群6个STR基因座的等位基因频率进行研究并获得群体遗传学数据.方法 对121名无血缘关系河南汉族个体的EDTA抗凝血样用酚-氯仿法提取DNA,应用多重PCR扩增技术结合聚丙烯酰胺凝胶电泳对D2S1338、D4S2639、D7S3048、D8S1132、D14S306、D18S535共6个基因座在河南地区汉族人群中的基因型分布进行分析.结果 6个STR基因座的基因型频率分布均符合Hardy-Weinberg平衡,各基因座的观察杂合度分别为0.843、0.842、0.857、0.900、0.824、0.826.结论 6个基因座在河南汉族群体中具有较高的非父排除率和个体识别率,在法医学和群体遗传学研究中有一定的应用价值.     

常染色体及Y染色体STR在兄弟鉴定中的应用

目的研究常染色体及Y染色体STR分型技术在兄弟鉴定中的应用价值。方法采用13个常染色体和6个Y-STR基因座分别检测40对兄弟和40对无关个体,ITO法计算常染色体STR基因座的兄弟关系指数(PIFS)和兄弟关系概率(WFS),分析常染色体等位基因匹配情况及Y染色体基因座相符情况,预测判断界值。结果经χ2检验,兄弟组和无关个体组间常染色体STR基因型全相同与全不同的基因座数存在显著性差异(P<0.001),半相同的基因座数无显著差异(P>0.05)。兄弟组6个Y-STR基因座分型结果均一致,无关个体组分别为2～6个不等的Y-STR基因座不匹配。结论常染色体及Y-STR基因座分型技术在兄弟鉴定中具有一定的鉴定价值,筛选更多、更佳的常染色体及Y-STR基因座对兄弟鉴定的准确性具有重要意义。     

江苏汉族群体15个STR基因座遗传多态性分析

目的分析15个短串联重复序列(STR)基因座在江苏汉族群体中的基因多态性和基因频率。方法取2010年-2011年来自江苏省的1000例无血缘关系的汉族个体。用Sinofiler 16荧光标记复合扩增系统15个STR位点进行扩增,自动基因分析仪片段分析并进行基因分型。结果累积STR等位基因共发现211个,其中罕见等位基因36个。基因型频率超过0.1的基因座型22个,其中D3S1358基因座的15/16等位基因型频率最高达到0.2225。杂合度达到了0.802±0.051,随机个体相同表型偶合率值为0.068±0.031,多态信息总量值为0.778±0.060,个体识别能力和非父排除率值分别为0.932±0.032和0.607±0.091。FGA、D12S391基因座在发生24次突变的11个基因座中有较高的突变率。结论通过大量的样本实验和等位基因频率总结,得到了江苏人群更多法医学亲权鉴定和个人识别等位基因多样性的客观数据。     

新Y染色体DYS726在山西汉族人群中遗传多态性

目的对新的DYS726基因座的基因多态性和法医学意义进行研究。方法山西汉族人群盅随机筛选110名男性,提取静脉血DNA,用基因数据库(GDB)中的引物进行聚合酶链反应(PCR)扩增,银染显色。对其筛选的等位基因测序,构建等位基因分型标准物;按照国际法医学会(ISFG)原则命名各等位基因。结果首次选择了Y染色体基因座DYS726,该基因座为4核苷酸简单重复STR。重复单位为CTTC。在110名山西汉族男性个体血样中共检出了4个等位基因。基因频率分别为11-0.0273;12-0.5455;13-0.1818;14-0.2455。基因多样性为0.6139,在法医学应用方面,其个人识别能力(DP)和非父排出率(PE)均为0.6139。结论新Y染色体基因座DYS726具有较高的遗传多态性,在法医学及人类遗传学方面具有较高应用价值。     

山西省高平地区汉族人群19个短串联重复系列基因座遗传多态性调查

目的:调查19个短串联重复系列(STR)基因座在山西省高平市汉族人群中的遗传多态性,并对其法医学应用进行评价。方法:采用Goldeneye20A STR荧光标记复合扩增试剂盒,对山西省高平市汉族210份无关个体进行扩增,利用3130XL遗传分析仪对扩增产物进行电泳分型,统计D19S433等19个STR基因座的等位基因频率和法医遗传学数据。结果:获得19个STR基因座的等位基因频率分布,分别检出10,9,15,13,13,6,8,7,7,7,10,8,9,5,17,6,11,13,17个等位基因,并分别获得19个STR基因座的杂合度观察值(Ho)、杂合度期望值(He)、个人设别能力(DP)、偶合率(PM)、非父排除率(PE)及多态信息总量(PIC)等法医遗传学参数,累积个人识别率和累积非父排除率分别为1~1.49×10-22和0.999 999 993。结论:Goldeneye20A STR荧光标记复合扩增体系的19个STR基因座在山西省高平市汉族人群中具有较高的个体识别能力和遗传多态性,对于法医学个体识别和亲子鉴定具有重要的应用价值。     

Effects of dextran sulphate (DXS) on lymphocyte localization in complement-deficient mice: evidence that the fifth component of complement is not implicated in the DXS activity

The effects of subcutaneously or intraperitoneally administered dextran sulphate (DXS) (50 mg/Kg) on the subsequent 1 h localization of intravenously injected radiolabelled lymph node cells was investigated in complement deficient mice which lack C5. DXS proved to be equally as potent in depressing cell localization in deficient as compared to normal mice. These findings indicate that the terminal complement components are not essential for DXS activity.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.