Role of modifying alleles in the heritable colorectal cancer syndromes with polyps

It is proposed, based on in vitro studies on hereditary colorectal cancer syndromes (adenomatosis of the colon and rectum, ACR), that the presence/absence of specific abnormal culture phenotypes within and between such ACR kindreds will demonstrate the interaction of a modifying allele with its proposed major polyposis gene, influencing expression of this major gene, at least in vitro. Such in vitro evidence would suggest that the variability of clinical phenotype was due, at least in part, to such gene-gene interaction and this should be considered as well as the influence of enviornmental agents on the development of both pre-malignant lesions and clinical cancer in such cancer-prone families.     

辽宁省血红蛋白病调查报告

本文报告了辽宁省血红蛋白病的调查情况,普查人群12,686人,包括汉、满、蒙、回、朝鲜及锡泊族六个民族。对辽宁省血红蛋白病的人群发生率,类型及地理分布进行了探讨。     

Detection of mRNA levels for the estrogen alpha, estrogen beta and androgen nuclear receptor genes in archival breast cancer tissue

Previous studies in our laboratory have shown association of nuclear receptor expression and histological breast cancer grade. To further investigate these findings, it was the objective of this study to determine if expression levels of the estrogen alpha, estrogen beta and androgen nuclear receptor genes varied in different breast cancer grades. RNA extracted from paraffin embedded archival breast tumour tissue was converted into cDNA and cDNA underwent PCR to enable quantitation of mRNA expression. Expression data was normalised against the 18S ribosomal gene multiplex and analysed using ANOVA. Analysis indicated a significant alteration of expression for the androgen receptor in different cancer grades (P=0.014), as well as in tissues that no longer possess estrogen receptor alpha proteins (P=0.025). However, expression of estrogen receptors alpha and beta did not vary significantly with cancer grade (P=0.057 and 0.622, respectively). Also, the expression of estrogen receptor alpha or beta did not change, regardless of the presence of estrogen receptor alpha protein in the tissue (P=0.794 and 0.716, respectively). Post-hoc tests indicate that the expression of the androgen receptor is increased in estrogen receptor negative tissue as well as in grade 2 and grade 3 tumours, compared to control tissue. This increased expression in late stage breast tumours may have implications to the treatment of breast tumours, particularly those lacking expression of other nuclear receptor genes.     

Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats

The effect of various drugs affecting catecholaminergic mechanisms on the precipitated morphine withdrawal syndrome was studied in rats which had developed a medium degree of dependence. Administration of low doses of d-amphetamine, cocaine, and L-Dopa shortly before precipitating withdrawal by levallorphan induced a dose-dependent increase of dominant withdrawal signs such as jumping and a decrease of recessive signs such as wet dog shaking; signs such as diarrhea and ptosis decreased, whereas rhinorrhea, salivation and lacrimation increased. A qualitatively very similar change in withdrawal signs occurred when withdrawal was precipitated in extremely highly dependent rats and/or increasing doses of the antagonist were administered. Therefore, the effects of the above drugs are interpreted as potentiation of withdrawal. Pretreatment with higher doses of the same drugs provoked strong stereotyped behaviour which obviously suppressed the occurrence of other motor signs.Activation of noradrenergic or dopaminergic mechanisms with desipramine or apomorphine induced an increase in the intensity of withdrawal, which was, however, much more pronounced after the former than the latter drug. When catecholamines (CA) were previously depleted by alpha-methyl-para-tyrosine (AMT), apomorphine lost a great part of its effectiveness. Blockade of CA synthesis by AMT alone resulted in decreased jumping while at the same time writhing largely increased, thus, inducing a profile of signs characteristic for a weak withdrawal. Selective inhibition of noradrenaline synthesis by FLA-63 resulted in a reduction in withdrawal intensity. Ro 4-4602 + L-Dopa, given after AMT, antagonized and reversed the reduction of withdrawal, but this effect was not so pronounced when by additional pretreatment with FLA-63 NA levels remained low. It is concluded that of both brain CA especially noradrenaline is involved in the manifestation of the morphine withdrawal syndrome.     

代谢酶基因多态性与结直肠癌的易感性

目的研究代谢酶细胞色素P450（cytochrome P450s,CYP）1A1、谷胱甘肽转移酶（glutathione—S-transferase,GST）M1和T1、尿苷二磷酸葡萄糖醛酸转移酶（UDPglucumnosyltransferase,UGT）1A7基因多态性与结直肠癌的易感性及其交互作用。方法2002年5月在浙江省嘉善县开展的现场病例对照研究及单纯病例研究,获得140例结直肠癌患者和343名健康对照,用PCR-限制性片段长度多态性等方法检测CYP1A1、GSTM1、GSTT1和UGT1A7的基因多态,并应用非条件logistic回归方法进行数据分析。结果CYPIA1 MspI多态（非编码区T6235C）C／C基因型、T／C和C／C基因型者相对于T／T基因型者的OR值分别为0．493（95％CI：0．254—0．956）和0．638（95％CI：0．427—0．952）,具有统计学意义;GSTM1、GSTT1非缺陷型与缺陷型的分布频率对照组和病例组比较差异无统计学意义;对照组和病例组UGT1A7变异／变异型基因与野生纯合型基因比较差异有统计学意义（OR=2．501,95％CI：1．456—4．296）。单纯病例研究分析,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用,COR值分别为2．617（95％CI：1．015—6．752）和3．935（95％CI：1．323—11．706）;而CYPlAl与GSTM1、CYP1A1与UGT1A7之间无交互作用。结论CYP1A1 MspI变异型可降低机体对结直肠癌的易感性,而UGT1A7的变异／变异基因型可增加结直肠癌的罹患风险,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用。     

肉瘤样肾细胞癌组织中P53基因突变

为了明确Ｐ５３基因突变与肾癌发生发展的关系，采用Ｎｏｒｔｈｅｒｎｂｌｏｔ方法和免疫组织化学方法对３７例肾癌新鲜标本进行Ｐ５３基因检测。结果显示：７例Ｐ５３ｍＲＮＡ表达明显高于正常对照，９例（２４．３％）Ｐ５３蛋白过表达；３７例肾癌组织中３例为肉瘤样肾细胞癌或组织中含肉瘤样癌细胞成分，此３例（１００．０％）均有Ｐ５３ｍＲＮＡ和Ｐ５３蛋白过表达，都有肾门或腹膜后淋巴结转移；３４例透明细胞和颗粒细胞癌中４例（１１．８％）Ｐ５３ｍＲＮＡ高表达，６例（１７．６％）Ｐ５３蛋白过表达，其中１例有肾静脉癌栓，１例有肾门淋巴结转移，另１例取自切口转移癌组织。结果表明：肉瘤样肾细胞癌中有频繁的Ｐ５３基因突变，可能是肾癌细胞向肉瘤样癌细胞转化的关键因素之一。     

RNA tumor viruses, DNA tumor viruses and developmental switches: a unifying hypothesis

It is hypothesized that oncogenic viruses (both RNA and DNA tumor viruses) use cellular differentiation switches as part of their mechanism for viral replication. Chemical or radiation-induced carcinogenesis is the result of mutations which also affect these differentiation switches and their cellular controls. A transformed cell is characterized by the uncontrolled and inappropriate expression of embryonic (developmental) sequences. Many of the oncogenic viruses, both RNA and DNA, are lineage- and stage-specific in the cells they can productively infect, in keeping with their means of replication. The interaction between virus and host cellular controls determines whether recognizable neoplasia will result from viral infection.     

新生儿呼吸窘迫综合征ABCA3基因遗传缺陷的研究

目的 分析ATP结合盒式蛋白转运子亚单位基因ABCA3遗传缺陷与新生儿呼吸窘迫综合征(NRDS)的关系,从中探讨汉族人群NRDS发病的遗传机制.方法 收集在新生儿重症监护病房住院的11例重症NRDS患儿的临床资料,采集患儿和97例无关正常对照的血样,采用PCR扩增、DNA直接测序技术对11例患儿进行ABCA3基因序列分析,对于新发现的ABCA3错义突变在97例健康对照中进行单链构象多态性检测.对1例生后13 h死亡的NRDS患儿进行肺组织光镜和电镜检测.结果 在11例患儿中发现了3个ABCA3基因外显子遗传变异、1个剪切位点碱基变异和几个国外报道及尚未报道的ABCA3单核苷酸多态性(SNP).3个ABCA3基因外显子遗传变异分别为c.2169 G＞A (p.M723I)、c.1010 T＞G (p.V337G)、c.4972 A＞G(p.S1658G),1个剪切位点变异为Exon 30+2 T/G,发现的SNP位点包括未报道过的213 C ＞T(p.F71F)、Exon 21+ 34C/T和已报道的c.1059C＞T(p.F353F)等.1例生后12 h死亡的患儿携带c.2169G＞A纯合变异,该变异位于第17号外显子,碱基的变异导致第723位氨基酸由异亮氨酸代替蛋氨酸,97例健康对照者中未发现此变异.肺组织电镜检测显示该例肺泡Ⅱ型上皮细胞的板层小体变小、浓缩,电子致密物边集.结论 ABCA3基因突变可能是部分临床不能解释的重症NRDS患儿的遗传学病因或遗传背景,识别NRDS患儿ABCA3基因变异情况,有助于治疗措施的选择及评价,并为开展NRDS遗传咨询和早期预防性干预提供依据.     

HEXIM1在先天性心脏病室间隔缺损中的突变及表达研究

目的通过筛查HEXIM1基因在室间隔缺损(ventricular septal defect,VSD)外周血中的突变和心肌组织中的表达情况,探讨HEXIM1基因与VSD发病机制的关系。方法采用PCR-DNA测序技术对100例单纯性室间隔缺损的患儿外周血进行基因编码序列突变筛查;以β-actin为内对照,用RT-PCR方法检测HEXIM1基因在14例室间隔缺损引产胎儿中mRNA的表达情况。结果所有研究对象的HEXIM1基因测序后同GenBank人类HEXIM1编码序列进行比较,有3例患儿(单纯性室间隔缺损)分别存在单核苷酸的多态性(SNP);与正常心肌组织相比,VSD引产胎儿心肌组织中HEXIM1基因mRNA表达呈下降趋势(P<0.05)。结论本实验收集的病例标本中没有发现HEXIM1基因编码区的突变,基因转录水平异常可能是该基因参与VSD形成的一种潜在机制。