辛伐他汀对自发性高血压大鼠左心室肥厚的影响及与蛋白激酶B表达的关系

目的探讨辛伐他汀逆转左心室肥厚(LVH)的作用及其分子生物学机制。方法16只雄性自发性高血压大鼠(SHR)分为SHR对照组和SHR治疗组,分别给予安慰剂及辛伐他汀灌胃治疗,年龄、性别、数量配对的Wistar Kyoto(WKY)大鼠给予安慰剂治疗作为正常对照组,观察辛伐他汀对大鼠收缩压和左心室重量/体重比值(LVW/BW)的影响,采用逆转录聚合酶链反应(RT PCR)检测心肌组织心钠素mRNA表达,RT PCR和Western印迹检测心肌组织蛋白激酶B(PKB)的mRNA和蛋白表达水平。结果(1)SHR对照组和SHR治疗组大鼠的收缩压分别为221mmHg±10mmHg(1mmHg=0.133kPa)和217mmHg±8mmHg,均显著高于正常对照组大鼠(126mmHg±6mm Hg),差异有统计学意义(均P<0.01),SHR治疗组大鼠收缩压与SHR对照组相比,差异无统计学意义(P>0.05)。(2)SHR对照组大鼠的LVM/BW为4.10mg/g±0.13mg/g,明显高于正常对照组(3.04mg/g±0.12mg/g),差异有统计学意义(P<0.01),而SHR治疗组的LVM/BW(3.73mg/g±0.08mg/g)明显低于SHR对照组(P<0.01)。(3)SHR对照组大鼠心肌组织心钠素的mRNA表达水平(0.44±0.03)明显高于正常对照组(0.17±0.03),SHR治疗组心钠素的表达水平(0.27±0.03)明显低于SHR对照组(均P<0.01)。(4)SHR对照组大鼠PKB的mRNA表达水平(0.45±0.05)和蛋白表达水平(62±     

乙型肝炎病毒感染后表型不一致的单卵孪生子基因组CpG岛甲基化谱差异分析

目的进行乙型肝炎病毒感染后表型不一致的单卵孪生子基因组CpG岛甲基化谱差异分析,以发现可能的差异甲基化基因。方法采用改良甲基化间区位点扩增技术,根据人基因组CpG岛甲基化位点的两种主要碱基组合,-CGCG-和-CCGG-,用3种不同的酶切组合（SmaⅠ—XmaⅠ、HpaⅡ-MspⅠ、BssHⅡ—PauⅠ／BsePⅠ）,同时采用Personal Molecular Imager FX分子成像系统及放射自显影相结合的方法,经Quantity One 4．4．0凝胶图像分析软件进行差异条带分析,分离回收差异甲基化条带并克隆人T载体,阳性克隆进行测序,将测序结果进行BLAST分析,初步了解与乙型肝炎病毒感染后表型不一致的单卵孪生子相关的差异甲基化基因情况。结果在一对表型一致的单卵孪生子间基因组CpG岛甲基化分析显示条带几乎相同,而在另一对表型一致以及一对表型不一致的单卵孪生子之间均存在差异甲基化条带,前者差异甲基化条带数目少于后者,将得到的差异甲基化条带克隆人T载体,目前测序分析得到4个可能与乙型肝炎病毒感染后表型不一致的单卵孪生子相关的差异甲基化基因。结论乙型肝炎病毒感染后表型不一致的单卵孪生子间基因组CpG岛甲基化水平有差异,其对疾病表型的影响及机制尚需后续深入研究。     

Open access echocardiography has diagnostic yield similar to outpatient echocardiography and is highly rated by general practitioners and patients

BACKGROUND: Open access echocardiography is widely available to General Practitioners (GP). There is little data comparing the proportion of echocardiographic studies which are abnormal in open access series with that in hospital outpatient practice. This study compares the diagnostic yield from echocardiograms performed for similar indications by open access and hospital out patient requested groups and assesses the attitudes of GPs and patients to open access echocardiography. METHODS: The reports of 151 consecutive patients who had open access echocardiograms were analysed using predefined criteria for an abnormal study. The reports of 100 consecutive patients who had a new outpatient requested echocardiograms for similar indications were used as the control group. The attitudes of GPs and patients to the open access service were also assessed. RESULTS: Fifty seven percent of patients in the open access group and 51% in the hospital requested group had abnormal studies (p>0.05). 92% of GPs who responded to the questionnaire thought the report was easy to understand while 69% thought it led to a change in patient management. 74% said a clinic referral would have been made without this service and 79% preferred a management strategy to be included in the report. 90% of patients had been informed of the result by their GP. CONCLUSIONS: Open access echocardiography has a diagnostic yield similar to echocardiograms requested on new hospital outpatients in a district general hospital setting. GPs and patients report high levels of satisfaction with this service.     

Rett综合征的临床特征及MeCP2的基因型与表型的关系研究

目的 总结Rett综合征(RTT)的临床特点,探讨甲基化CpG结合蛋白2(MeCP2)基因突变型与表型的关系。方法 北京大学第一医院儿科1987年以来诊断的RTT66例,每1～2年对本组患儿进行1次临床随访,并观察左旋肉碱的治疗反应。应用PCR、测序方法对39例患儿进行突变基因分析。结果 患儿3～38个月起病,59例(89％)患儿于7个月～6岁丧失手的功能,66例(100％)患儿1—5岁出现手的刻板动作,56例(85％)患儿11个月～8岁语言完全丧失,21％的患儿于2岁9个月～15岁丧失原已获得的行走能力。头围小、惊厥、呼吸节律异常、咬牙、脊柱侧凸或后凸均很常见。左旋肉碱治疗17例,8周后6例症状改善。39例进行．MeCP2基因分析者中有25例(64％)发现突变,其中2例无义突变C502T(氨基酸改变R168X)患儿均死亡,2例C397T(氨基酸改变R133C)和1例A398T(氨基酸改变R133H)突变者均保留语言。结论 RTI。特征性的表现为头围增长缓慢,手的失用与刻板动作,语言倒退,左旋肉碱可以改善部分患儿的临床症状。MeCP2基因型与表型之间有一定的相关性。     

Alport综合征基因点突变后蛋白结构的改变及与表型的关系

目的 分析COL4A5基因不同点突变后的蛋白结构,探讨基因突变对编码蛋白二级结构的影响及与表型的关系。方法 以临床确诊的2例X连锁遗传型Alport综合征患者为研究对象,他们的基因突变类型均为点突变导致的甘氨酸替代:患者1,其家系为症状较重的青少年型,基因检测确定为COL4A5中的g.3246G>T导致p.G1015V;患者2,其家系为症状较轻的成年型,基因检测确定为COL4A5中的g.3290G>A导致p.G1030S。应用E.coli分别表达患者α5(Ⅳ)链的含有突变位点的结构域及对照α5(Ⅳ)链的同一结构域,圆二色谱检测并比较它们二级结构的差异。结果 与对照相比,患者1重组蛋白的圆二色谱最低峰所在的波长由200 nm,变为近220 nm处,而且峰度降低。患者2重组蛋白的检测结果与对照相比改变较轻微,最低峰所在的波长不变,但峰度增加。二级结构分析显示,来自对照的重组蛋白主要以β折叠和无规卷曲为主,无α螺旋结构。与对照蛋白相比,来自患者1的重组蛋白中出现了约占八分之一的α螺旋结构;来自患者2的重组蛋白仍然以β折叠和无规卷曲为主,但是β折叠的比例下降而无规卷曲增多。结论位于α5(Ⅳ)链同一结构域的两个不同位置的甘氨酸被不同的氨基酸替代,它们的临床表型截然不同,α5(Ⅳ)链的二级结构也存在显著差异。而且,二级结构的改变程度与相应     

β-Adrenoceptor polymorphisms

There can be no doubt that ₁-, ₂- and ₃-adrenoceptor genes have genetic polymorphisms. Two single nucleotide polymorphisms have been described for the ₁- (Ser49Gly; Gly389Arg), three for the ₂- (Arg16Gly; Gln27Glu; Thr164Ile) and one for the ₃-adrenoceptor subtype (Trp64Arg) that might be of functional importance. The possibility that changes in expression or properties of the -adrenoceptors due to single nucleotide polymorphisms might have phenotypic consequences influencing their cardiovascular or metabolic function or may contribute to the pathophysiology of several disorders like hypertension, congestive heart failure, asthma or obesity is an idea that has attracted much interest during the last 10 years. At present, it appears that these -adrenoceptor polymorphisms are very likely not disease-causing genes, but might be risk factors, might modify disease and/or might influence progression of disease. The aim of this review is to provide an overview of the functional consequences of such -adrenoceptor polymorphisms in vitro, ex vivo and in vivo.     

Refinement of behavioural traits in animals for the genetic dissection of eating disorders

Both twin and family studies have revealed the involvement of genetic factors in disorders that affect the regulation of body weight, such as obesity and anorexia nervosa. However, pinpointing the genes that contribute to these human disorders has not yet been very successful. In contrast, genetic studies in animals have been basic for the identification of many genes involved in the regulation of various physiological processes of energy metabolism. We thus plan to review here ways in which findings from animal studies and what is known about behavioural diversity in the human population with eating disorders can be combined. This would probably optimise phenotype-based candidate gene analysis in humans.     

食管癌肿瘤浸润淋巴细胞体外增殖和表型变化的研究

目的;寻找新的ＴＩＬ刺激物,摸索解除ＴＩＬ抑制状态和提高扩增效率的最佳条件。方法：通过黄芪、干地黄水提物联合细胞因子,采用＾３Ｈ－ＴｄＲ掺入法及流式细胞仪对９例食管癌ＴＩＬ的增殖及表型进行了分析。结果：在促增殖作用方面,黄芪联合ＩＬ－２、ＩＬ－２＋ＩＬ－４、ＩＬ－２＋ＴＮＴ－α均较单用其细胞因子有明显增强作用。而干地黄对ＴＩＬ增殖无明显协同作用。食管癌ＴＩＬ表型分析发现ＣＤ４＾＋Ｔ细胞为主,诱导后ＣＤ４＾＋Ｔ细胞明显增多。ＣＤ４／ＣＤ８比值由２．８：１上升至９．９：１。结论：黄芪有明显协同细胞因子促进食管癌ＴＩＬ增殖的作用,激活的食管癌ＴＩＬＣＤ４＾＋Ｔ细胞占绝对优势。     

Assessment of FMR1 Gene Mutation at-Risk Status in Young Children

Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene, is the most commonly inherited cause of developmental disability. Fragile X syndrome occurs relatively equally in all racial and ethnic groups and is one of the few disorders affecting child behavior for which the exact gene is identified. Furthermore, from infancy, both males and females with this syndrome are predisposed for manifesting characteristic cognitive, emotional, and behavioral challenges. The purpose of this article is to illuminate the multisystemic and multifaceted phenotype of the FMR1 gene mutation by means of the parent response Biopsychosocial Screening Inventory for Fragile X, for which preliminary studies show promise.     

妇产科临床142例平衡结构畸变重排断裂点分在研究

142例平衡结构畸变的分析结果显示，妇产科临床重排断裂除较多累及近端着丝粒染色体14、15、22号外，7、8号染色体受累频率也显著性偏高。而2、4、5、6号染色体不仅断裂点的分布频率显著性偏低，而且有关平衡结构畸变个体的表型异常显著性增高。分析同时表明，重排断裂在3种不同G显带上的分布是非随机的，但在脆性位点是随机的。重排断裂点的这种分布规律既可能与染色体的内在分子结构有关，也可能与选择机制相联系。