5,10—亚甲基四氢叶酸还原酶多态性和神经管畸表的病例对照研究

目的 探讨北方乡村妇女亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）基因多态性与神经管畸形的关系。方法 用聚合酶链反应－限制性片段的多态性（ＰＣＲ－ＲＦＬＰ）技术,检测２０例生育神经管畸形患儿（ＮＴＤｓ）的妇女及７６例农村和７３例城市正常出生儿母亲的ＭＴＨＦＲ基因多态性。结果ＭＴＨＦＲ基因第６７７位核苷酸呈多态性,可分为三种类型：Ｃ／Ｃ、Ｃ／Ｔ、Ｔ／Ｔ。病例组三种基因突变频率：Ｃ／Ｃ,５％;Ｃ／Ｔ,５０％;Ｔ     

EB病毒转化的永生性人B淋巴母细胞中的MTHFR基因的表达

为检测用ＥＢ病毒转化建立的永生性人Ｂ淋巴细胞株中Ｎ＾５,Ｎ＾１０－亚甲基甲氢叶酸还原酶（ＭＴＨＦＲ）基因的表达及其ｃＤＮＡ序列,用ＥＢ病毒转化人外周血Ｂ淋巴细胞,建立永生性细胞株后,从培养细胞中提取总ＲＮＡ,用ＲＴ－ＰＣＲ法扩增ＭＴＨＦＲ基因ｃＤＮＡ的不同片段,进行ＰＡＧＥ电泳分析和ｃＤＮＡ序列测定。结果显示永生性人Ｂ淋巴母细胞中有ＭＴＨＦＲ基因表达,其ｃＤＮＡ序列与文献报道的人肝脏ＭＴＡＨＦＲ基     

血浆同型半胱氨酸与叶酸、维生素B12及还原酶的关系

目的　探讨叶酸、维生素B1 2 (VB1 2 )、血浆总同型半胱氨酸 (tHcy)、5 ,10 亚甲基四氢叶酸还原酶 (MTHFR)活性及其热敏感性基因型间的相互关系。方法　研究对象为 3 4例生育神经管畸形(NTDs)儿的母亲及 4 2例生育正常儿的母亲 ,检测指标包括tHcy、红细胞叶酸、血清叶酸和VB1 2 、MTHFR酶活性及热敏感性基因型。结果　tHcy、红细胞叶酸、血清叶酸在病例组与对照组间差异无统计学意义 ;NTDs患儿母亲VB1 2 显著低于正常儿母亲 ;tHcy与红细胞叶酸呈显著负相关 ;MTHFR热敏感性基因纯合突变组tHcy显著高于杂合突变和纯合野生组 ;血清维生素水平在MTHFR各基因型间差异无显著性 ;叶酸较低组tHcy略高于叶酸较高组 ,并与MTHFR酶活性呈显著负相关。结论　体内tHcy增高与MTHFR热敏感性基因纯合突变、酶活性下降有关 ;体内叶酸水平高低影响tHcy与MTHFR酶活性相关性。     

同型半胱氨酸诱发鸡胚神经管畸形及叶酸的保护作用

为了揭示同型半胱氨酸（ｈｏｍｏｃｙｓｔｅｉｎｅ，ＨＣＹ）是否能导致胚胎发生神经管畸形（ＮＴＤｓ）和可能的致畸机制及验证叶酸和ＶＢ１２的干预效果，本研究应用鸡胚致畸试验、扫描电镜观察、尼罗兰盐活体染色、原位ＤＮＡ片段末端标记、甲基绿—派若宁染色显示核酸法、叶酸和Ｂ１２干预实验等方法检测了用ＨＣＹ（０～１６μｍｏｌ／胚胎）的不同胚龄胚胎１２７４只。结果显示ＨＣＹ对神经胚形成期和器官形成期的胚胎均有显著的致畸性并呈剂量－反应关系（Ｐ＜０．０００１），鸡胚发生ＮＴＤｓ的主要表现是露脑，裂脑和脊柱裂。首次发现ＨＣＹ能诱发神经系统细胞凋亡过度，其部位与ＮＴＤｓ发生部位相吻合。ＨＣＹ能抑制卵黄囊血管分化；损伤羊膜组织及细胞超微结构，如微绒毛变短，胞膜上出现空洞样变等。注射５μｇ叶酸明显拮抗ＨＣＹ（８μｍｏｌ／胚胎）的致畸性，ＮＴＤｓ发生率由４３．５％降至０（Ｐ＜０．０５）；注射１μｇＶＢ１２不能明显保护胚胎（Ｐ＞０．０５）。本研究结果说明ＨＣＹ能诱导胚胎发生ＮＴＤｓ；细胞凋亡在ＮＴＤｓ发生过程中起重要作用；叶酸能有效地预防ＮＴＤｓ；ＨＣＹ自身所诱发的ＮＴＤｓ可能是多种机制相互作用或联合作用的结果     

城乡孕妇同型半胱氨酸代谢与神经管畸形的相关性研究

通过比较城乡早孕妇女血清同型半胱氨酸（Ｈｃｙ）、叶酸和维生素Ｂ１２水平，探讨Ｈｃｙ代谢与神经管畸形城乡差异的关系。随机抽取北京地区早孕妇女血清库中４１１份血清（城市１９５份，乡村２１６份），用高效液相色谱结合电化学方法检测血清中Ｈｃｙ浓度，放射免疫方法检测叶酸和维生素Ｂ１２浓度。结果：乡村孕妇Ｈｃｙ平均水平明显高于城市，分别为９．３１μｍｏｌ／Ｌ和５．７３μｍｏｌ／Ｌ；Ｂ１２水平则低于城市，分别为２１０．０９ｐｍｏｌ／Ｌ和２３３．３５ｐｍｏｌ／Ｌ，叶酸水平虽高于城市，但叶酸缺乏率的差异不显著。乡村孕妇的叶酸／Ｈｃｙ和Ｂ１２／Ｈｃｙ值均显著低于城市孕妇。提示Ｈｃｙ代谢异常与乡村神经管畸形高发有关。     

北京医院医疗信息系统

我院医疗信息系统是与ＩＢＭ中国有限公司合作开发的医疗信息管理系统，即住院管理系统，它是基于客户／服务器模式的计算机管理系统。系统配置我院医疗信息系统是由ＩＢＭ的ＲＳ／６０００（ＲｉｓｃＳｙｓｔｅｍ／６０００）Ｆ５０和３９０作为服务器，以１２口或２４口...     

鸡胚微量中同型半胱氨酸,叶酸,HCY—2抗体水平和MTHFR基因型检测？…

为建立鸡胚胎尿绒膜一血采集方法和检测胚胎血中同型半胱氨酸（ＨＣＹ）、叶酸、ＨＣＹ－２抗体及亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）基因型变化情况,采用ＨＰＬＣ法测血浆总ＨＣＹ,ＰＣＲ－ＲＦＬＰ法测纸血片ＭＴＨＦＲ,ＳＬＩＳＡ法测血清ＨＣＹ－２抗体和微生物法测纸血片血红蛋白叶酸盐。结果发现连续７ｄ给Ｄ．Ｌ－ＨＣＹ后,鸡胚血浆总ＨＣＹ浓度（１０６．９２μｍｏｌ／Ｌ）显著高于正常对照组（１４．１６μｍｏｌ／Ｌ     

THE PROGRAMME OF WORK OF COMMITTEE 2 OF ICRP ON INTERNAL DOSIMETRY

ＴＨＥＰＲＯＧＲＡＭＭＥＯＦＷＯＲＫＯＦＣＯＭＭＩＴＴＥＥ２ＯＦＩＣＲＰＯＮＩＮＴＥＲＮＡＬＤＯＳＩＭＥＴＲＹＪｏｈｎＷＳｔａｔｈｅｒａｎｄＣｈｅｎＸｉｎｇａｎ（ＮａｔｉｏｎａｌＲａｄｉｏｌｏｇｉｃａｌＰｒｏｔｅｃｔｉｏｎＢｏａｒｄ，Ｃｈｉｌｔｏｎ...     

用ELISA检测大鼠血清中肾综合征出血热病毒特异性抗体

本研究应用单克隆抗体（ＭｃＡｂ）技术，建立了三种检测大鼠血清中肾综合征出血热病毒（ＨＦＲＳＶ）特异性抗体的ＥＬＩＳＡ。通过与间接免疫荧光法（ＩＦＡＴ）对比试验发现，三种ＥＬＩＳＡ在检出大鼠血清ＨＰＲＳＶ特异性抗体的阳性率和敏感性上均明显高于ＩＦＡＴ试验，并且ＥＬＩＳＡ与ＩＦＡＴ总检出符合率为８８．５％。此外还发现由于引入小鼠抗大鼠Ｋａｐｐａ轻链ＭｃＡｂ，抗体捕捉ＥＬＩＳＡ和间接夹心ＥＬＩＳＡ具有早期诊断的特性，这些方法的建立对野生及实验动物的ＨＦＲＳＶ流行病学监测及检疫有一定价值。     

1999年上半年境外医疗器械产品注册情况(一)

序号产品名称生产厂国家注册号１气腹机ＷＩＳＡＰＧＥＳＥＬＬＳＣＨＡＦＴＦＵＲＷＩＳＳＥＮＳＣＨＡＦＴＬＩＣＨＥＮＡＰＰＡＲＡＴＥＢＡＵＭＢＨ德国９９－０００１２心电电极ＭＳＢ（Ｓ－Ｅ－Ａｓｉａ）Ｌｔｄ．新加坡９９－０００２３外科手术电极ＭＳＢ（Ｓ－Ｅ－Ａｓｉａ）Ｌｔｄ．新加坡９９－０００３４ＣＵＢＡＣｌｉｎｉｃａｌ超声骨密度仪ＭｃＣｕｅＰｌｃ英国９９－０００４５超乳玻切系统ＧｅｕｄｅｒＧｍｂＨ德国９９－０００５６听觉诱发电位系统ＩＣＳＭｅｄｉｃａｌＣｏｒｐｏｒａｔｉｏｎ美国９９－０００６７眼震电…     

Are the associations between life-style related factors and plasma total homocysteine concentration different according to polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR)? A cross-sectional study in a Japanese rural population

Mild hyperhomocysteinemia is one of the known strong risk factors for atherosclerotic diseases, and therefore it is important to clarify factors that could determine plasma total homocysteine (tHcy) level. A cross-sectional study with a random sample of 455 Japanese rural residents aged 40-69 years was conducted in 2000 to investigate the associations of plasma tHcy concentration with 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and selected life-style related factors. The frequency of the mutant allele, Valine (V) allele, was 0.40 and the prevalence of VV genotype was 14.3%. Plasma tHcy concentration in VV was significantly higher than those in two other genotypes. There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12 (P<0.001 for trend, respectively); both being stronger in VV than in other genotypes. The number of cigarettes smoked per day was positively associated with plasma tHcy concentration. A multivariate regression analysis revealed that serum folate, serum vitamin B12, and MTHFR genotype were independently associated with plasma tHcy. The inter-individual variance of plasma tHcy was more explained by serum folate and vitamin B12 than by MTHFR genotype. Higher intakes of folate, vitamin B12, and non-smoking may be important to prevent mild hyperhomocysteinemia and the eventual atherosclerotic diseases in this Japanese rural population.     

Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahydrofolate reductase C677T genotype and folate status

Risk factors established at young ages may set the stage for later cardiovascular disease (CVD). Elevated total homocysteine (tHcy) in blood is an emerging risk factor for CVD, yet few studies have been conducted in children, especially in the Mediterranean. We described plasma tHcy concentrations in a group of healthy Greek children and examined its relation with physiologic, metabolic, and genetic variables. Fasting blood samples were collected from 186 students, 11.6 +/- 0.4 years old, and tHcy, folate, vitamin B-12, and routine biochemistry variables in plasma were measured. The methylenetetrahydrolate reductase (MTHFR) C677T genotype was determined and anthropometric and dietary data were obtained. The distribution of tHcy was positively skewed with a median of 7.9 micromol/L (mean: 8.2 +/- 2.3 micromol/L; range: 4.4-22.2 micromol/L). tHcy was inversely related to plasma folate (r = -0.34, P < 0.0001), vitamin B-12 (r = -0.20, P = 0.008), and glucose (r = -0.15, P = 0.045). An interaction between the MTHFR genotype and plasma folate on tHcy was detected (P = 0.047). Specifically, the homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate (< 19.9 nmol/L), (P = 0.012). In our sample of healthy Greek children, plasma tHcy concentrations were higher than values reported in children of Northern European descent and were associated with folate, vitamin B-12, and glucose in plasma. The results also show that, similar to adults, plasma folate concentration is important in determining the contribution of the MTHFR C677T mutation to tHcy concentrations in children.     

Serum folate, total homocysteine levels and methylenetetrahydrofolate reductase 677C>T polymorphism in young healthy female Japanese

Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to be a genetic factor for influencing tHcy. However, it is not clear whether MTHFR polymorphism influences tHcy in the younger generation. To investigate the influence of MTHFR polymorphism on vascular disease risks in young Japanese females, we determined dietary intakes, serum folate and tHcy, and examined the influence of MTHFR 677C>T polymorphism in healthy junior and high school students (n=192, 12-18y). The relationships between MTHFR polymorphism and folate intake, serum folate or tHcy were investigated by dividing participants into CC, CT and TT types. Among individuals with the TT genotype, folate and tHcy levels were significantly lower (p<0.05) or higher (p<0.0001), respectively, than in those with the other genotypes; although there were no significant differences in the intake of folate among genotypes. In addition, a significant inverse correlation between folate and tHcy (p<0.05) was noted in all genotypes, even in young females, so far not examined in Asian populations. Therefore, MTHFR genotypes were proven to be a significant determinant for folate and tHcy concentrations. However, the association of increased folate intake with lower tHcy concentration, even in cases of the mutation TT type, indicates the importance of folate intake in young Japanese females for early detection of risk, as well as the prevention of vascular diseases.     

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

OBJECTIVES: To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. SUBJECTS/METHODS: Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). RESULTS: Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. CONCLUSIONS: Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.     

Total homocysteine and its predictors in Dutch children

BACKGROUND: Vitamin status, methylenentetrahydrofolate reductase (MTHFR) genotype, age, sex, and lifestyle factors are all predictors of total homocysteine (tHcy) concentrations in adults. Limited data are available about the influence of these factors on tHcy in children. OBJECTIVE: The objective was to describe tHcy and its predictors in Dutch children. DESIGN: A sample of 234 white children aged 0-19 y was analyzed cross-sectionally. RESULTS: The geometric mean tHcy concentrations were 5.1 (95% CI: 4.6, 5.6), 4.6 (4.2, 5.1), 6.2 (5.6, 6.9), 7.3 (6.7, 8.0), and 8.7 (7.9, 9.6) micromol/L in the 0-1, 2-5, 6-10, 11-14, and 15-19 y groups, respectively. Plasma folate and vitamin B-12 concentrations decreased markedly with age. The inverse association between tHcy and plasma folate seen at all ages was stronger than that between tHcy and plasma vitamin B-12. A negative association of plasma folate with tHcy was confined to folate concentrations <20 nmol/L. Homozygosity for the MTHFR 677C-->T polymorphism was identified in 8.2% of the children. The homocysteine concentration did not differ significantly between the MTHFR genotypes. CONCLUSIONS: This study provided age-specific data regarding tHcy concentrations and their predictors in the whole range of childhood. The tHcy concentration increased as a function of age in both sexes. Plasma folate was a concentration-dependent predictor of tHcy. The MTHFR 677C-->T polymorphism played a minor role in determining tHcy concentrations in children.     

Polymorphisms of key enzymes in homocysteine metabolism affect diet responsiveness of plasma homocysteine in healthy women

High plasma total homocysteine (tHcy), low dietary intake of folate and other B vitamins, and genetic polymorphisms related to metabolism of homocysteine may interactively contribute to the risk of cardiovascular disease. We investigated whether known mutations in genes regulating homocysteine metabolism affect the responsiveness of serum folate and plasma tHcy to high intake of natural folate from food. Healthy females (n = 37) aged 22-57 y volunteered to participate in a crossover dietary intervention with two 5-wk diet periods (low and high folate diets). Concentrations of serum and RBC folate, serum vitamin B-12 and plasma tHcy were measured at baseline and at the end of each diet period. The prevalences of C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene, 844ins68 of cystathionine beta-synthase (CBS) gene and A2756G mutation of methionine synthase (MS) gene were determined. Compared with the low folate diet, the high folate diet increased the serum folate concentration by 85% (P < 0.001), 77% (P < 0.001) and 55% (P < 0.05) in the subjects with the genotypes C/C (n = 19), C/T (n = 13) and T/T (n = 5), respectively, of the MTHFR gene. Also, the plasma tHcy of the subjects with the genotypes C/C, C/T and T/T was decreased by 11% (P < 0.001), 15% (P < 0.01) and 18% (P < 0.05), respectively, during the high folate diet period. The subjects carrying the G2756 allele of the MS gene (n = 15) had a more extensive reduction (P < 0.05) of plasma tHcy during the high folate diet period than the subjects with the genotype A/A (n = 22). The 844ins68 of CBS gene did not affect plasma tHcy concentrations or diet responsiveness. In conclusion, diet responsiveness of plasma homocysteine may be genetically regulated.     

The effect of MTHFR(C677T) genotype on plasma homocysteine concentrations in healthy children is influenced by gender

OBJECTIVE: To explore the influence of gender, together with folate status, on the relation between the common methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in healthy children. DESIGN: Cross-sectional study by face-to-face interview.Setting and subjects:A total of 186 sixth-grade students participated from twelve randomly selected primary schools in Volos, Greece. METHODS: Fasting tHcy, folate, and vitamin B(12) were measured in plasma. The MTHFR genotypes were determined. Anthropometric and dietary intake data by 24-h recall were collected. RESULTS: Geometric means for plasma tHcy, plasma folate and energy-adjusted dietary folate did not differ between females and males. The homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate concentrations (<19.9 nmol/l, P = 0.012). As a significant gender interaction was observed (P = 0.050), we stratified the lower plasma folate group by gender and found that the association between the genotype and tHcy was restricted to males (P = 0.026). Similar results were obtained when folate status was based on estimated dietary folate. Specifically, only TT males that reported lower dietary folate consumption (<37 microg/MJ/day) had tHcy that was significantly higher than tHcy levels of C-allele carriers (P = 0.001). CONCLUSIONS: Under conditions of lower folate status (as estimated by either plasma concentration or reported dietary consumption), gender modifies the association of the MTHFR(C677T) polymorphism with tHcy concentrations in healthy children. SPONSORSHIP: Kellog Europe.     

Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; EC 1.7.99.5) supplies the folate needed for the metabolism of homocysteine. A reduction in MTHFR activity, as occurs in the homozygous state for the 677C-->T (so-called thermolabile) enzyme variant (TT genotype), is associated with an increase in plasma total homocysteine (tHcy). OBJECTIVE: In vitro studies suggest that the reduced activity of thermolabile MTHFR is due to the inappropriate loss of its riboflavin cofactor. We investigated the hypothesis that MTHFR activity in the TT genotype group is particularly sensitive to riboflavin status. DESIGN: We studied tHcy and relevant B-vitamin status by MTHFR genotype in a cross-sectional study of 286 healthy subjects aged 19-63 y (median: 27 y). The effect of riboflavin status was examined by dividing the sample into tertiles of erythrocyte glutathionine reductase activation coefficient, a functional index of riboflavin status. RESULTS: Lower red blood cell folate (P = 0.0001) and higher tHcy (P = 0.0082) concentrations were found in the TT group than in the heterozygous (CT) or wild-type (CC) groups. However, these expected relations in the total sample were driven by the TT group with the lowest riboflavin status, whose mean tHcy concentration (18.09 micromol/L) was almost twice that of the CC or CT group. By contrast, adequate riboflavin status rendered the TT group neutral with respect to tHcy metabolism. CONCLUSIONS: The high tHcy concentration typically associated with homozygosity for the 677C-->T variant of MTHFR occurs only with poor riboflavin status. This may have important implications for governments considering new fortification policies aimed at the prevention of diseases for which this genotype is associated with increased risk.     

Relationship between dietary folate intakes,maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan

Background Adequate folate status in pregnancy is important for satisfactory pregnancy outcome. Aim of the Study The objective of the present study was to evaluate folate status in healthy pregnant women by assessing dietary folate intakes and measuring changes in folate-related biomarkers including plasma tHcy, serum vitamin B₁₂ (B₁₂), and serum and RBC folate concentrations in each trimester and to examine their relation to fetal growth. Methods From 94 pregnant women, 3-day-dietary records were obtained and blood was collected for plasma total homocysteine (tHcy), serum B₁₂, and serum and red-blood cell (RBC) folate measurements. Infant anthropometric measurements were made immediately after birth. Results Average folate intake was less than 300 μg/day with a mean energy intake of about 1800 kcal. Mean serum and RBC folate concentrations declined significantly during gestation (p < 0.05). Mean serum B₁₂ also significantly decreased (p < 0.01), whereas plasma tHcy increased from 5.1 in the first trimester to 5.9 μmol/l in the third trimester (p < 0.01). Multiple regression analyses, after controlling for maternal age, parity and pre-pregnancy body-mass index indicated that a 1.0 μmol/l increase in plasma tHcy in the third trimester corresponded to a 151 g decrease in birth weight (p < 0.01). Neither B₁₂ nor folate concentrations in all three trimesters showed any significant associations with birthweight. Plasma pyridoxal-5′-phosphate concentrations were markedly low, and were consistent with low intake of vitamin B₆ in our population. Conclusion Our data suggest that higher plasma tHcy in the third trimester is a predictor of lower birth weight. In general, the dietary intake of B-vitamins and energy may be inadequate in our population, suggesting intervention is necessary.