肺癌患者RASSF1A启动子甲基化状态及其基因表达水平

目的探讨肺癌RAS相关区域家族1A(RASSF1A)启动子CpG岛甲基化状态和基因表达水平与肺癌发生的关系。方法用甲基化特异性PCR检测RASSF1A启动子CpG岛甲基化状态,实时定量PCR检测RASSF1A mRNA的表达水平。结果在肺癌组织中RASSF1A启动子甲基化频率为53.33%(24/45),在正常肺组织中发生甲基化的频率为13.04%(3/23)(P<0.05)。正常肺组织中RASSF1A mRNA全部表达,肺癌组织中表达缺失率为28.89%(13/45),且表达量低于正常肺组织(P<0.05);不同年龄、性别、肿瘤大小、恶性程度、肿瘤分类中其表达量无显著差异;RASSF1A甲基化与其mRNA表达水平下降密切相关。结论肺癌中RASSF1A基因启动子甲基化频率明显升高,其表达普遍下调或缺失,提示RASSF1A启动子甲基化在肺癌发生、发展中起一定作用。     

宫颈癌中RASSF1A基因微卫星的不稳定性

Ras相关区域家族1A(ras association domain family 1A,RASSF1A)基因是新近克隆出来的一种肿瘤抑制基因[1],其在调节细胞周期和细胞凋亡方面具有重要作用。RASSF1A基因失表达见于多种人类肿瘤中。本研究选择RASSF1A基因内的两个微卫星多态标记,对110例宫颈组织进行微卫星不稳定     

孕妇外周血中RASSF1A基因甲基化状态研究

目的探讨RASSF1A基因作为孕妇外周血中胎儿特异性标记物的可行性。方法随机选取43例的外周血样本,其中妊娠晚期孕妇标本40例、健康未妊娠女性标本3例,以及早期妊娠行流产的绒毛组织样本5例。利用甲基化敏感限制性内切酶PCR(MSRE-PCR)及荧光定量PCR的方法,检测血细胞、绒毛和血浆DNA的RASSF1A基因甲基化状态。结果健康未妊娠妇女血浆及孕妇血细胞中均未检出甲基化RASSF1A基因;绒毛组织中甲基化RASSF1A基因检出率为100%;孕妇血浆中甲基化RASSF1A基因检出率为92.5%。妊娠晚期孕妇血浆RASSF1A基因含量Ct平均值为30.43±2.37。结论在母体和胎儿DNA中,RASSF1A基因甲基化状态有明显差异,用实时荧光定量PCR可对孕妇血浆RASSF1A基因进行定量,提示了RASSF1A基因是无创产前诊断的一个潜在标记物。     

人RASSF1A基因的真核表达载体的构建及其表达

目的 通过构建人RASSF1A基因的真核表达载体,为研究其在肿瘤细胞凋亡、细胞周期阻滞、细胞增殖抑制等方面奠定基础.方法 采用RT-PCR从人外周血的单个核细胞RNA中扩增出人RASSF1A基因的全长cDNA,利用DNA重组技术将其插入到真核表达栽体pcDNA3.1(+)中获得重组质粒.利用脂质体将重组质粒转染入人鼻咽癌细胞株CNE-2中,采用RT-PCR.westem-blot检测RASSF1A的瞬时表达.结果 酶切图谱分析及基因测序证明人RASSF1A基因已被完整、正确地插入到pcDNA3.1(+)质粒载体中,RT-PCR及Western-blot结果显示转染细胞的RASSF1A表达水平上调.结论 成功构建了RASSF1A基因的真核表达栽体pcDNA3.1(+)/RASSF1A.     

RASSF1基因研究进展

2000年,Reinhard等在染色体3p21.3区发现了RASSF1基因。随后的研究显示,RASSF1- A、-B、-C三种不同转录剪接本分别参与了细胞凋亡和多种恶性肿瘤发生发展机制。     

抑癌基因RASSF1A微卫星变异与宫颈癌发生发展的关系

目的 探讨抑癌基因RASSF1A微卫星变异在宫颈癌发生发展中的作用及其与HPV感染的关系.方法 选择RASSF1A基因的两个微卫星多态标记位点,采用PCR技术对宫颈组织进行杂合性丢失与微卫星不稳定性的检测,同时检测宫颈组织中HPV16的感染状况.结果 两位点的LOH发生率在宫颈癌组织临床分期及病理分级之间差异有统计学意义(P＜0.05).双位点的LOH及MSI在宫颈癌有无淋巴结转移间差异有统计学意义(P＜0.05).RASSF1A基因的LOH发生率在HPV16感染阳性组中明显高于阴性组(P＜0.05).结论 RASSF1A基因的改变是宫颈癌发生过程中的较晚期事件,RASSF1A基因的LOH与MSI对于宫颈癌的筛查、早期诊断及判断预后可能具有临床实用价值.RASSF1A基因的LOH与HPV16感染二者共同作用在宫颈癌的发生发展过程中更有意义.     

卵巢癌患者血液中RASSF1A基因甲基化的检测及其意义

目的 探讨循环肿瘤DNA中RASSF1A基因的甲基化及其与卵巢癌的关系。方法 应用甲基化特异性PCR（MSP）方法,对51名正常健康人、51例卵巢癌患者和51例卵巢良性肿瘤患者循环DNARASSF1A基因的甲基化进行了检测。结果 51名正常健康人和51例卵巢良性肿瘤患者循环DNARASSF1A基因甲基化的发生率均为0;51例卵巢癌患者循环肿瘤DNARASSF1A甲基化的发生率为43．1％（22／51,P〈0．05）。RASSF1A甲基化与卵巢癌组织学类型无明显相关性（P〉0.05）。临床Ⅰ期和Ⅱ期循环肿瘤DNARASSF1A基因甲基化的发生率明显低于临床Ⅲ期和Ⅳ期（P〈0．05）;高和中分化组RASSF1A基因甲基化的发生率低于低分化组（P〈0．05）。结论 RASSF1A基因甲基化在卵巢癌的发生和发展过程中起重要作用。卵巢癌患者的循环肿瘤DNA中可以检测到RASSF1A基因的甲基化,与卵巢癌的临床分期和组织学分级有关。循环肿瘤DNA中RASSF1A甲基化的检测有助于卵巢癌的诊断和预后判定。     

Ras相关区域家族1A基因及其与肺癌相关的研究进展

新近在肺癌和乳腺癌的研究中发现的Ras相关区域家族1A(Ras-association domain family 1A,RASSF1A)基因位于染色体3p21.3,是一种新型的肿瘤抑制基因(tumor suppressor gene,TSG).研究表明,RASSF1A主要通过介导细胞凋亡、阻断细胞周期进展等机制发挥抑癌作用,而该基因的表遗传失活与肺癌等多种恶性肿瘤的发生、发展和预后密切相关.同时其高甲基化的启动子可能是一种新的肿瘤标记物,可应用于肿瘤的诊断、治疗及其他众多领域,有着广阔的临床应用前景.     

Ras相关结构域家族蛋白1A基因与肿瘤

Ras作为一个在人类肿瘤研究中重要的癌基因,已成为目前研究得最为深入的基因之一。研究发现,Ras基因除了具有促进细胞牛长、增殖的作用外还具有一个非常重要的功能——抑制细胞生长、促进细胞凋亡和衰老。2000年,一个与鼠Ras效应蛋白Nore1和Maxp 1高度同源的蛋白编码基因——Ras相关结构域家族蛋白1A(RAS associalion domain family proteinlA,RASSF1A)基因的发现引起了研究者们的广泛关注,对其结卡勾、功能、分布和表达情况的研究发现,     

p16、RASSF1A在肝细胞性肝癌患者肿瘤组织及血浆中异常甲基化的检测及临床意义

目的探讨原发性肝细胞性肝癌(HCC)患者肿瘤组织及血浆中p16及RASSF1A启动子区的甲基化状态及其在HCC早期无创诊断中的意义。方法采用甲基化特异性PCR技术检测60例HCC患者肿瘤组织、癌旁组织、血浆及60例正常肝脏患者肝组织及血浆中p16、RASSF1A基因启动子区域的甲基化状态,分析其与肝癌患者临床病理参数之间的关系。结果 60例HCC患者血浆、肿瘤组织及癌旁中p16基因甲基化率分别为68.3%(41/60)、63.3%(38/60)和41.7%(25/60);RASSF1A基因异常甲基化检出率分别为73.3%(44/60)、70.0%(42/60)和36.7%(22/60);60例正常肝脏患者肝组织及血浆p16、RASSF1A未检测到基因启动子区域的甲基化,差异有统计学意义(P=0.000)。HCC患者外周血浆和癌组织中p16、RASSF1A基因的甲基化率与患者年龄、性别、AFP、有无肝炎病毒感染(HBV)、有无肝硬化、Child分级、肿瘤个数、包膜完整与否、有无癌栓、是否复发、病理分级、肿瘤分期无统计学相关性。结论 HCC患者肿瘤组织及血浆DNA中可检测到RASSF1A基因和p16基因的甲基化,外周血p16基因和RASSF1A基因的甲基化检测对肝癌筛查有重要意义,可能成为HCC新的肿瘤分子标记物。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.     

A comparative study of the effects of dimebon,obsidan, finoptin,and cordaron on the functional state of ischemic focus and size of necrotic zone in experimental myocardial infarction

Dimebon, an antihistamine agent, exerts a moderate antianginal effect, improving the function of ischemic focus in the myocardium and decreasing the necrotic zone in experimental myocardial infarction. Dimebon is less active than obsidan, finoptin (except for the size of the necrotic zone), and cordaron. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 642–644, December, 1996     

Effects of sex steroid hormones on lipid peroxidation and glutathione antioxidant system in rat skin

Effects of estradiol and testosterone on the intensity of lipid peroxidation and contents of glutathione redox system components in the dermis and epidermis of rat skin were studied. Only estradiol induced considerable dose-dependent and tissue-specific biphasic antioxidant effects on the skin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 663–666, December, 1999     

Adhesion and growth of CaCo2 cells on surface-modified PEEK substrata

A series of surface-functionalized poly(ether ether ketone) (PEEK) films has been prepared by selective wet-chemistry; they are hydroxylated polymer (PEEK-OH) obtained by reduction, aminated polymer (PEEK-[]-NH2) prepared by coupling a diisocyanate reagent to PEEKOH (PEEK-[]-NCO) followed by hydrolysis, and carboxylated and aminocarboxylated polymers (PEEK-[]-GABA and PEEK-Lysine) resulting from the coupling of aminoacids to PEEK-[]-NCO. The aminated and carboxylated substrata promoted the adhesion and growth of CaCo2 cells in the presence of serum. Fibronectin (FN), an extra-cellular matrix protein, has been covalently fixed and/or adsorbed on various PEEK substrata, in the presence or not of a polymeric surfactant (Pluronic F68). The performances of the FN-grafted substrata (PEEK-[]-FN(1) and PEEK-[]-FN(2)) were significantly higher than those of reference substrata simply coated with FN (PEEK-OH(+FN)(1) and (2), PEEK-[]-NH2(+FN)(1) and (2)), considering the adhesion and spreading of CaCo2 cells in the absence of serum. Moreover, the stability of the adherent cells on the FN-adsorbed substrata dramatically depended on the experimental conditions applied during the PEEK coating with FN.