Ataxia telangiectasia(AT)is an autosomal recessive multisystem disorder with increased radiosensitivity and cancer susceptibility.The responsible gene(ATM)consists of 66 exons and a coding region of 9171 bp which prec...Ataxia telangiectasia(AT)is an autosomal recessive multisystem disorder with increased radiosensitivity and cancer susceptibility.The responsible gene(ATM)consists of 66 exons and a coding region of 9171 bp which precludes direct seq uencing as a screening assay for confirmation or exclusion of the clinical suspi cion of AT.Peripheral blood mononuclear cells of 330 patients referred for the exclusion of AT were exposed to ionizing radiation(IR)and incubated for 72 h i n the presence of phytohemagglutinin.Using bivariate BrdUHoechst/ethidium brom ide flowcytometry,the following cell cycle parameters were ascertained:(1)pro portion of non-proliferating(G0,G1)cells as a measure of mitogen response,(2)proportion of first-cycle G2-phase cells relative to the growth fraction(G2 /GF)as a measure of radiosensitivity.Of the cases tested,94.2%could be unequ ivocally assigned either to the AT-negative or the AT-positive group of patien ts.Of the AT-positive cases,11 were confirmed by ATM mutation analysis.Ninet een cases presented with non-conclusive results,mostly due to poor mitogen res ponse;however,a combination of cellcycle data with serum AFP concentrations le d to the exclusion of AT in all but two of the uncertain cases.Substitution of ionizing radiation by the radiomimetic bleomycin was additionally tested in a sm all series of patients.We conclude that cell-cycle testing complemented by ser um AFP measurements fulfills the criteria as a rapid and economical screening pr ocedure for the differential diagnosis of juvenile ataxias.展开更多
9926513 临床和电生理检查发现伴有连接蛋白32突变的 X 染色体连锁的夏科马里病/Birouk N//Neurology.-1998,50(4).-1074～1082 湘医图9926514 夏科马里病和伴有近端神经肥大的努南综合征/Silbum P A//Neurology.-1998,50(4).-1067～10...9926513 临床和电生理检查发现伴有连接蛋白32突变的 X 染色体连锁的夏科马里病/Birouk N//Neurology.-1998,50(4).-1074～1082 湘医图9926514 夏科马里病和伴有近端神经肥大的努南综合征/Silbum P A//Neurology.-1998,50(4).-1067～1073 湘医图9926515 应用 PCR 诊断 IA 型夏科特-马里病和伴有压力性瘫痪的遗传性神经病/Young P//Neurology.-1998,50(3).-760～763展开更多
欧洲肝脏研究协会（European Association for the Study of the Liver，EASL）通过回顾了1966-2011年Medline、Embase及Cochrane Library数据库中wilson病（Wilson’s disease，WD）相关文献，于2012年2月发布《wilson’s病临床实践指...欧洲肝脏研究协会（European Association for the Study of the Liver，EASL）通过回顾了1966-2011年Medline、Embase及Cochrane Library数据库中wilson病（Wilson’s disease，WD）相关文献，于2012年2月发布《wilson’s病临床实践指南））（Clinical Practice Guideline，CPG）。由于缺乏随机对照临床研究，很难为指南中所涉及问题提供中、高质量的循证医学证据，临床评估主要依据近年大量病例报道。正常饮食摄取及吸收铜含量超出机体所需，胆汁分泌是维持体内铜代谢平衡的唯一途径。WD是一种常染色体隐性遗传性铜代谢障碍疾病，由于肝细胞排泌铜障碍，导致过量铜在体内沉积，尤以肝脏及脑部为著。铜代谢异常与位于13号染色体的ATP7B基因突变有关，该基因编码肝细胞高尔基体内的铜转运P型ATP酶。ATP7B的主要功能是将铜从细胞内伴侣蛋白转运至分泌途径，包括分泌至胆汁及与无铜铜蓝蛋白（Ceruloplasmin，CPN）结合形成功能性铜蓝蛋白。WD的进展程度取决于受累组织的铜沉积量。展开更多
文摘Ataxia telangiectasia(AT)is an autosomal recessive multisystem disorder with increased radiosensitivity and cancer susceptibility.The responsible gene(ATM)consists of 66 exons and a coding region of 9171 bp which precludes direct seq uencing as a screening assay for confirmation or exclusion of the clinical suspi cion of AT.Peripheral blood mononuclear cells of 330 patients referred for the exclusion of AT were exposed to ionizing radiation(IR)and incubated for 72 h i n the presence of phytohemagglutinin.Using bivariate BrdUHoechst/ethidium brom ide flowcytometry,the following cell cycle parameters were ascertained:(1)pro portion of non-proliferating(G0,G1)cells as a measure of mitogen response,(2)proportion of first-cycle G2-phase cells relative to the growth fraction(G2 /GF)as a measure of radiosensitivity.Of the cases tested,94.2%could be unequ ivocally assigned either to the AT-negative or the AT-positive group of patien ts.Of the AT-positive cases,11 were confirmed by ATM mutation analysis.Ninet een cases presented with non-conclusive results,mostly due to poor mitogen res ponse;however,a combination of cellcycle data with serum AFP concentrations le d to the exclusion of AT in all but two of the uncertain cases.Substitution of ionizing radiation by the radiomimetic bleomycin was additionally tested in a sm all series of patients.We conclude that cell-cycle testing complemented by ser um AFP measurements fulfills the criteria as a rapid and economical screening pr ocedure for the differential diagnosis of juvenile ataxias.
文摘欧洲肝脏研究协会（European Association for the Study of the Liver，EASL）通过回顾了1966-2011年Medline、Embase及Cochrane Library数据库中wilson病（Wilson’s disease，WD）相关文献，于2012年2月发布《wilson’s病临床实践指南））（Clinical Practice Guideline，CPG）。由于缺乏随机对照临床研究，很难为指南中所涉及问题提供中、高质量的循证医学证据，临床评估主要依据近年大量病例报道。正常饮食摄取及吸收铜含量超出机体所需，胆汁分泌是维持体内铜代谢平衡的唯一途径。WD是一种常染色体隐性遗传性铜代谢障碍疾病，由于肝细胞排泌铜障碍，导致过量铜在体内沉积，尤以肝脏及脑部为著。铜代谢异常与位于13号染色体的ATP7B基因突变有关，该基因编码肝细胞高尔基体内的铜转运P型ATP酶。ATP7B的主要功能是将铜从细胞内伴侣蛋白转运至分泌途径，包括分泌至胆汁及与无铜铜蓝蛋白（Ceruloplasmin，CPN）结合形成功能性铜蓝蛋白。WD的进展程度取决于受累组织的铜沉积量。
