IFRD1基因在房间隔缺损患者心房肌组织中表达的变化及意义

目的探讨IFRD1(interferonrelateddevelopmentalregulator1)基因mRNA在房间隔缺损(ASD)患者心房肌组织中表达水平的变化,分析IFRD1基因异常表达在ASD病因及病理生理学中的意义。方法获取10例单纯Ⅱ孔型ASD患者和8例正常人右房心耳肌组织标本,采用RTPCR技术检测心房肌组织中IFRD1基因mRNA的表达丰度。结果IFRD1基因在正常心房肌组织中的表达丰度为(60.56±22.07)%,在ASD患者心房肌组织中的表达丰度为(30.95±11.81)%,显著低于正常对照(t=3.6560,P<0.01)。结论IFRD1基因在心房肌组织中的异常表达可能与ASD的病因及病理生理学有关。     

α1,3 FUCT Ⅶ mRNA及Sle~x抗原在非小细胞肺癌组织中的表达及其与转移的关系

目的探讨α1,3FUCT Ⅶ基因mRNA及Slex在非小细胞肺癌组织,癌旁正常肺组织中的表达,及其与临床病理因素的关系。方法应用RT-PCR法及免疫组织化学催化放大法(CSA)检测α1,3FUCT Ⅶ基因mRNA734.2及Slex在66例非小细胞肺癌组织,20例癌旁正常肺组织中的表达。结果α1,3FUCT Ⅶ基因mRNA在腺癌组织(0.79±0.19)强于鳞癌组织中(0.51±0.12),差异有统计学意义(P*<0.05)。Slex的表达在腺癌阳性率为86%(31/36),鳞癌为63.3%(19/30),差异有统计学意义(P*<0.05)。α1,3FUCTⅦ基因mRNA及Slex的表达与TNM分期、分化程度、淋巴结转移、组织学类型及性别有关,与年龄无关(P>0.05)。结论α1,3FUCT Ⅶ基因mRNA及Slex过表达可能与非小细胞肺癌发生及转移相关,其检测可作为判断患者肺癌转移的一项重要参考指标。     

生存素mRNA在膀胱移行细胞癌中表达及其临床意义

目的研究生存素mRNA在膀胱移行细胞癌(TCC)中的表达,及其与TCC的病理分级、临床分期的相关性。方法用半定量逆转录聚合酶链反应法对30例TCC患者的肿瘤组织、3例良性前列腺增生症(BPH)和2例外伤所致膀胱破裂患者的膀胱组织进行生存素mRNA检测。结果30例TCC组织生存素mRNA表达全部呈阳性,而3例BPH患者和2例膀胱破裂患者均呈阴性。TCCⅠ级、Ⅱ级、Ⅲ级患者生存素mRNA与肌动蛋白mRNA灰度比值分别为0·95±0·12,1·25±0·16,1·52±0·10,组间差异显著(P<0·01);TCC临床分期未突破基底膜、侵及浅肌层、侵及深肌层的患者生存素mRNA、与b-MGmRNA灰度比值分别为1·00±0·26,1·23±0·16,1·47±0·17,组间差异均显著(P<0·05)。结论膀胱粘膜生存素mRNA的表达可用于TCC患者的辅助诊断及恶性程度和预后的判断。     

生存素在大肠癌中的表达及其与血管生成的关系

目的研究生存素(survivin)在大肠癌组织中的表达及其与血管生成的关系。方法应用RT-PCR方法检测52例大肠癌组织,48例癌旁正常粘膜组织中生存素mRNA的表达,序列分析验证PCR扩增的正确性;用免疫组织化学法检测52例大肠癌组织中生存素蛋白、凋亡指数(AI)、增殖指数(LI)和微血管密度(MVD)。结果大肠癌组织中生存素mRNA阳性表达率为67.3%,而癌旁正常组织阳性表达率为25.0%(P<0.01);生存素mRNA表达与大肠癌患者性别、肿瘤大小、病理类型、淋巴结转移、远处转移及临床分期无明显相关关系。序列分析结果:所扩增生存素与人生存素序列具有99%的同源性。免疫组化检测显示大肠癌组织中生存素蛋白阳性表达率为51.9%(27/52)。生存素表达阳性组的凋亡指数为(0.67±0.18)%,显著低于生存素表达阴性组(1.14±0.42)%,(P<0.01);生存素表达阳性组的LI(51±22)%,MVD(21.4±8.2),显著高于生存素表达阴性组的(27±18)%,(P<0.01)和(14.2±5.4)(P<0.05)。结论(1)生存素表达与大肠癌患者性别、肿瘤大小、病理类型、淋巴结转移、远处转移及临床分期无明显相关关系。生存素抑制凋亡和促进增殖可能是参与大肠癌发生的重要机制。(2)生存素与大肠癌血管生成关系密切。     

KAI1基因在宫颈癌组织中的表达及临床意义

目的探讨KAI1基因在宫颈癌组织中的表达及临床意义。方法采用逆转录聚合酶链反应(RTPCR)方法检测53例新鲜宫颈标本组织中KAI1mRNA的表达水平,进行定量分析并与临床病理资料比较。结果正常宫颈KAI1mRNA表达量为(0.309±0.093)、宫颈上皮内瘤变(1.608±0.289),宫颈癌(0.948±0.910)。晚期及有淋巴结转移的宫颈癌KAI1mRNA表达量减少,差异有统计学意义(χ2=6.114,P=0.0471;t=4.67,P=0.0003),与肿瘤分化程度无关(χ2=2.8318,P=0.2427)。结论KAI1基因表达与宫颈癌临床分期及转移有关。     

Bcl2相互作用蛋白 3在子宫内膜组织中的表达及其在子宫内膜异位症发病中的意义

目的探究 Bcl2相互作用蛋白 3(BCL2 Interacting Protein 3,BNIP3)表达变化与正常子宫内膜周期的关系及在子宫内膜异位症( EMs)发病中的意义。方法从 GEO数据库获得 GSE51981、GSE6364、GSE4888、GSE25628的基因表达谱,通过生物信息学手段比较正常子宫内膜周期组增殖期到分泌期基因表达变化,分析基因富集情况以及 BNIP3在正常子宫内膜月经周期中的表达变化;比较数据集中正常子宫内膜周期组人群与内异症病人差异趋势表达基因以及各样本中 BNIP3的表达,总结其在 EMs发病中的意义;取 23例Ⅲ?Ⅳ EMs病人正位及异位子宫内膜组织,以及 25例因子宫肌瘤行子宫切除术病人的子宫内膜组织作为正常对照,通过实时荧光定量 qRT?PCR及蛋白质印迹法( Western Blot)检测 BNIP3在各组织中的表达,验证 BNIP3表达变化同 EMs发病的关系。结果 GSE4888、GSE6364、GSE51981数据集中, BNIP3在增殖期与分泌期相对表达量分别为 100.22±16.54、332.80±32.29,487.68±100.09、1425.83±157.47,8.36±0.69、9.82±0.71,均差异有统计学意义( P＜0.0001); GSE25628数据集中, BNIP3在正常子宫内膜组织、 EMs病人正位、 EMs病人异位子宫内膜组织中的表达量分别为( 10.11± 0.72)、(9.19±0.56)、(8.52±0.57)三组间对比差异有统计学意义;临床样本中,正常内膜组织、 EMs正位内膜组织、 EMs异位内膜组织中 BNIP3的 mRNA表达别为 1.15±0.57、0.56±0.19、0.36±0.08,三组间对比差异有统计学意义; BNIP3蛋白在正常子量分,宫内膜组织、 EMs正位内膜组织、 EMs异位内膜组织中的表达水平分别为 1.00±0.41、0.58±0.20、0.38±0.12,三组间对比均差异有统计学意义。结论 BNIP3在子宫内膜组织中的表达降低与 EMs的发生具有相关性。     

初发急性非淋巴细胞白血病SSBP2 mRNA表达研究

目的:探讨SSBP2 mRNA在初发急性非淋巴细胞白血病中的表达。方法:利用半定量RT-PCR检测64例初发急性非淋巴细胞白血病患者及20例正常对照SSBP2 mRNA表达,以β-actin作为内参照。结果:64例初发ANLL患者及20例正常对照均表达SSBP2。与正常对照比较,初发ANLL患者SSBP2mRNA表达水平为(0.410±0.216)与对照组(0.383±0.172)差异无显著性(P>0.05)。结论:初发ANLL中SSBP2mRNA表达无异常改变,SSBP2表达可能并不参与急性非淋巴细胞白血病的发生。     

小儿法乐四联症心肌细胞C-myc基因表达的病理学研究

目的探讨C-myc基因在法乐四联症发生、发展中的作用。方法采用免疫组织化学二步法检测C-myc基因在法乐四联症患者心肌细胞中的表达。结果C-myc基因在该症患者心肌细胞中的阳性表达率为86%(17/20),阳性细胞数为(41.7±2.8)%;其中强阳性(+++)6例(35.3%);阳性(++)7例(41.2%);弱阳性(+)4例(23.3%);正常对照组心肌细胞的阳性表达率仅为11.1%(2/18),且均为弱阳性;阳性细胞数为(5.4±1.1)%,两组相比差异非常显著(P<0.01)。结论C-myc基因在法乐四联症发生、发展中具有重要作用,C-myc基因的激活和高表达促进了该症的形成和发展。     

肽转运载体2 mRNA在脂多糖致急性肺损伤大鼠肺组织中的表达(英文)

目的研究肽转运载体(PEPT)2 mRNA在脂多糖(LPS)致急性肺损伤大鼠肺组织的表达。方法健康雄性SD大鼠分为正常对照组,生理盐水组,LPS 0.5mg·kg-12,4和8h组。光镜下观察肺组织病理变化,测定肺湿/干重比、支气管肺泡灌洗液(BALF)中蛋白含量和肺组织髓过氧化物酶(MPO)活性;半定量RT-PCR检测肺组织PEPT2 mRNA表达。结果气管内给予LPS 0.5mg·kg-1,大鼠肺组织呈现典型的炎症病理变化,如肺泡充血、出血、水肿、中性粒细胞浸润、肺泡壁增厚和透明膜形成等。LPS 2,4和8h组大鼠肺湿/干重比(4.72±0.18,5.06±0.17和5.12±0.16)明显高于正常对照组和生理盐水组(4.12±0.15和4.14±0.11)。与正常对照组和生理盐水组〔(1.26±0.12)和(1.25±0.07)U·g-1湿组织〕相比,LPS2,4和8h组大鼠肺MPO活性〔(1.96±0.15),(2.23±0.10)和(2.34±0.12)U·g-1湿组织〕明显增高。LPS 2,4和8h组大鼠BALF中蛋白含量〔(36.6±2.9),(86.9±3.5)和(92.2±2.7)mg·L-1〕明显高于正常对照组和生理盐水组〔(29.3±1.3)和(29.4±2.7)mg·L-1〕。LPS各组大鼠肺组织PEPT2 mRNA的表达水平与正常对照组和生理盐水组相比无明显变化。结论PEPT2 mRNA在LPS致急性肺损伤大鼠肺组织中的表达水平无明显变化。     

宫颈鳞癌组织中泛素偶联酶E2、食管癌相关基因4 表达情况与预后的关系

目的探究宫颈鳞癌组织中泛素偶联酶E2(UBE2C)、食管癌相关基因4(ECRG4)表达水平及其与病人预后关系。方法选取2010年6月至2014年6月天门市第一人民医院收治的宫颈鳞癌病人73例、宫颈上皮瘤变病人62例、因子宫肌瘤需行全子宫切除术病人54例为研究对象。术中分别收集宫颈鳞癌病人宫颈鳞癌组织、宫颈上皮瘤变病人瘤变组织和子宫肌瘤病人正常宫颈组织。分别采用实时荧光定量逆转录聚合酶链式反应(qRT-PCR)和免疫组织化学染色法检测UBE2C、ECRG4mRNA和蛋白表达水平。分析二者表达水平与病人临床病理特征及预后关系。结果正常宫颈组织、宫颈上皮内瘤变组织、宫颈鳞癌组织中UBE2C mRNA［(1.01±0.29)、(1.97±0.63)、(3.64±1.21)］表达水平、UBE2C 蛋白高表达率(20.37%、51.61%、68.49%)依次显著升高(P<0.05)，ECRG4 mRNA［(1.02±0.31)、(0.75±0.26)、(0.51±0.19)］表达水平、ECRG4 蛋白高表达率(66.67%、43.55%、26.03%)依次显著降低(P<0.05)。UBE2C、ECRG4蛋白在低、中、高分化宫颈鳞癌病人癌组织中高表达率比较，差异有统计学意义(P<0.05)。UBE2C、ECRG4蛋白在Ⅰ~Ⅱ、Ⅲ期FIGO分期及有无淋巴结转移病人癌组织中高表达率比较，差异有统计学意义(P<0.05)。宫颈鳞癌组织中UBE2C mRNA与ECRG4 mRNA表达水平呈负相关(P<0.05)。UBE2C蛋白高表达组病人5年总生存率明显低于UBE2C蛋白低表达组，ECRG4蛋白高表达组病人5年总生存率明显高于ECRG4蛋白低表达组，均差异有统计学意义(34.00%比65.22%，73.68%比33.33%，P<0.05)。FIGO分期Ⅲ期、淋巴结转移、UBE2C高表达、ECRG4低表达均是影响宫颈鳞癌病人发生不良预后的独立危险因素(P<0.05)。结论宫颈鳞癌组织中UBE2C mRNA及蛋白表达水平明显升高，ECRG4 mRNA及蛋白表达水平明显降低，与病人5年总生存率低有关，可能是影响宫颈鳞癌病人发生不良预后的独立危险因素。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.