鼻咽癌中p73基因启动子甲基化状态及转录表达的研究

目的探讨鼻咽癌组织中p73基因启动子区甲基化状态及其对转录表达影响。方法运用甲基化特异性PCR和半定量反转录PCR法检测20例正常鼻咽上皮组织、54例鼻咽癌组织中p73基因启动子甲基化状态及其转录表达水平,分析鼻咽癌组织中p73基因甲基化与临床资料的关系以及p73基因甲基化对转录表达的影响。结果 54例鼻咽癌组织中p73基因启动子甲基化阳性率为38.89%(21/54),而正常鼻咽上皮组织中未检测到p73基因启动子甲基化;两组间p73基因启动子甲基化阳性率差异有统计学意义(P<0.01)。鼻咽癌组织中p73基因启动子甲基化与临床资料无关。21例甲基化鼻咽癌组织p73基因相对转录表达水平为1.04±0.64,33例非甲基化鼻咽癌组织p73基因相对转录表达水平为1.51±0.75,两者间有统计学差异(P<0.05),20例正常鼻咽上皮组织p73基因相对转录表达水平为1.12±0.31。结论鼻咽癌组织中p73基因甲基化与转录表达相关,是基因表达调节的一种重要方式,p73基因甲基化具有肿瘤特异性,p73基因甲基化与鼻咽癌发生发展有关。     

Dopamine D4 and D5 receptor gene variant effects on clozapine response in schizophrenia: Replication and exploration

Objectives

This study aimed to: 1) replicate previously reported associations between dopamine D4 receptor gene (DRD4) polymorphisms and antipsychotic (AP) response in a clozapine (CLZ) response sample; and 2) explore possible associations of polymorphisms across dopamine D5 receptor gene (DRD5) as well as other DRD4 regions.

Methods

DRD4 exon III 48-bp, intron I (G)_n, and 120-bp repeat polymorphisms, and three DRD4 single nucleotide polymorphisms (SNPs); and DRD5 (CA/CT/GT)_n microsatellite and four DRD5 SNPs were assessed using standard genotyping and statistical procedures.

Results

We report evidence, which does not survive correction for multiple testing, supporting previous DRD4 findings. Findings of interest include the 120-bp 1-copy allele, intron I (G)_n 142-bp/140-bp genotype, and exon III 4R allele with CLZ response. All DRD5 tests were negative.

Conclusions

Overall, these results suggest a possible minor contribution of DRD4 variants, but not DRD5 variants, towards the AP/CLZ response phenotype.     

Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine

Methamphetamine use triggers psychosis in genetically vulnerable individuals, however the exact nature of this genetic predisposition requires elucidation. In addition, adolescence may be a particular period of neurodevelopmental vulnerability to the actions of methamphetamine; interestingly, this period coincides with a higher likelihood of onset of schizophrenia and drug experimentation. In the current study we investigated whether adolescent mice heterozygous for the schizophrenia susceptibility gene neuregulin 1 (Nrg1 HET mice) exhibit altered behavioural responses to methamphetamine (0.6 or 2.4 mg/kg) in schizophrenia-relevant paradigms. The responses measured were locomotor activity in the open field test and sensorimotor gating function in the prepulse inhibition of startle paradigm (PPI). Adolescent Nrg1 HET mice displayed a subtle, transient, novelty-induced baseline locomotor hyperactivity over days, and a selective PPI deficit at the prepulse intensity-interstimulus interval (ISI) combination of 82 dB–64 ms. Adolescent Nrg1 HET mice were more sensitive to the locomotor stimulatory effects of an acute, low-dose of methamphetamine (0.6 mg/kg) relative to wild-type (WT) controls. The augmented response to acute methamphetamine observed in Nrg1 HET mice disappeared with repeated, daily dosing over 7 days. Methamphetamine did not affect average PPI (total or across different prepulse intensities), however 0.6 mg/kg methamphetamine triggered a PPI deficit selectively in Nrg1 HET mice but not WT mice at 82 dB–256 ms. Our results show that locomotor hyperactivity in Nrg1 HET mice, albeit subtle, can manifest much earlier than previously reported and that Nrg1 may confer vulnerability to the acute actions of methamphetamine, a drug known to trigger psychotic reactions in humans.     

Mu opioid receptor mRNA expression, binding, and functional coupling to G-proteins in human epileptic hippocampus

Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.     

北京地区哮喘儿童特异性IgE和TRPVl／2mRNA表达水平分析

目的探讨TRPVl和TRPV2基因表达水平与北京地区儿童哮喘的关系。方法实时定量PCR方法检测38例健康儿童,46例哮喘儿童外周血淋巴细胞中TRPVl和TRPV2mRNA表达水平差异。免疫印迹法定量检测总IgE水平,尘螨、春季花粉、秋季花粉、蟑螂和猫狗毛、真菌等特异性TgE水平,对检测结果进行多因素lo~stic回归分析。结果健康和哮喘组儿童TRPVl和TRPV2的mRNA表达水平差畀有统计学意义（P〈0．01）,真菌特异性IgE表达水平差异有统计学意义（P〈0．01）。结论TRPVl和TRPV2基因表达水平升高可能是北京地区儿童哮喘发病酌危险圆素。     

参麦注射液对大鼠急性心肌缺血及eNOS mRNA表达的影响

目的：探讨参麦注射液(SMI)预处理可能对 大鼠急性心肌缺血及心肌内皮型一氧化氮合酶(eNOS)mRNA表达的影响。方法:大鼠随机分为对照组、模型组、处理组1和处理组2，应用异丙肾上腺素建立大鼠心肌 缺血模型,以心电图ST段抬高值作为心肌缺血指标，硝酸还原酶法测定血清和心肌的NO^-₂/NO^-₃，RT-PCR检测心肌eNOS mRNA表达。结果：模型组各时点的心 电图ST段均显著高于对照组，缺血20 min时达高峰，血清和心肌NO^-₂/NO^-₃含量及 心肌eNOS mRNA表达均低于对照组；两个处理组于缺血20、30、40 min时的心电图ST段抬高 幅度均显著低于模型组，血清和心肌NO^-₂/NO^-₃含量均显著高于模型组，心肌eNOS mRNA表达强于模型组；处理组1和处理组2比较，心电图ST段抬高幅度、血清和心肌的NO^-₂/NO^-₃含量及心肌eNOS mRNA表达差异均无显著。结论：参麦注 射液可能是通过促进心肌组织eNOS mRNA表达、增强eNOS活性而提高NO水平，达到抗心肌缺 血的作用。