In previous study,glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro.In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism,34 male pups w...In previous study,glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro.In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism,34 male pups were randomly assigned to NS group,low dose GA (LGA,5 μmol GA/g body weight) group and high dose GA (HGA,10 μmol GA/g body weight) group.These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am,15:00 pm and 22:30 pm and killed 12 h after the last injection.Microscopic pathology in corpus striatum was evalu-ated by HE staining.The apoptotic cells were identified by TUNEL staining.The transcript levels of caspase-3,8,9,Bax,Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting.In LGA and HGA groups,ventricle collapse,cortical atrophy by a macroscope and interstitial edema,vacuolations,widened perivascular space of bi-lateral striatum by a microscope were observed.TUNEL assay revealed that the apoptotic cells were in-creased in LGA and HGA groups.The transcript of caspase-3 was up-regulated to 2.5 fold,accompanied by the up-regulation of caspase-9,Bax and down-regulation of Bcl-2.The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups.The rat model for GA Ⅰ showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion.Further studies should be taken to investigate the underlying mechanisms.展开更多
目的探讨酪蛋白水解肽酶B同源物(caseinolytic peptidase B homolog,CLPB)基因变异所致3-甲基戊烯二酸尿症Ⅶ型的遗传学病因。方法回顾性分析1例在贵州医科大学附属医院诊断为3-甲基戊烯二酸尿症Ⅶ型患儿的分子生物学特征。提取患儿外...目的探讨酪蛋白水解肽酶B同源物(caseinolytic peptidase B homolog,CLPB)基因变异所致3-甲基戊烯二酸尿症Ⅶ型的遗传学病因。方法回顾性分析1例在贵州医科大学附属医院诊断为3-甲基戊烯二酸尿症Ⅶ型患儿的分子生物学特征。提取患儿外周血白细胞DNA,应用高通量测序技术进行基因变异分析,并用Sanger测序进行家系验证。结果患儿生后出现四肢强直、口周发绀,曾因"新生儿低钙血症、新生儿低血糖、新生儿黄疸(ABO溶血)"住院治疗。1岁1月龄因"发热4 d"后出现不能独坐、竖头不稳、进食呛咳,反复呼吸道感染,肌张力增高,尿代谢筛查示3-甲基戊烯二酸浓度为34.98 mmol/molCr。肌电图提示双侧腓总神经运动传导速度均渐慢,双侧腓浅神经感觉传导速度均轻度渐慢,且波幅均降低。脑电图在24 h内监测到18次癫痫临床发作。头颅MRI见脑发育欠佳,额叶及小脑为著;髓鞘化延迟。基因检测结果显示患儿CLPB基因存在c.1016T>G(p.L339R)和c.130delG(p.E44Sfs*5)复合杂合变异;患儿母亲携带CLPB基因c.1016T>G(p.L339R)杂合变异,患儿父亲携带CLPB基因c.130delG(p.E44Sfs*5)杂合变异。患儿的变异分别来自父亲和母亲,均为未报道过的新变异。c.130delG(p.E44Sfs*5)杂合变异按照美国医学遗传学与基因组学学会指南评价为可能致病性。结论分别来自母亲和父亲的CLPB基因c.1016T>G(p.L339R)和c.130delG(p.E44Sfs*5)复合杂合变异可能为该患儿的致病原因。展开更多
Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the ...Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.展开更多
基金supported grants from the National Natural Science Foundation of China (No. 81070699)the 11th Five-Year Plan of National Science and Technology Supporting Project (No. 2006BAI05A07)+1 种基金Sector Fund of Ministry of Health of China (No. 201002006)Key Construction Project of Clinical Subjects from the Ministry of Health of China(No. 2011-2014)
文摘In previous study,glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro.In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism,34 male pups were randomly assigned to NS group,low dose GA (LGA,5 μmol GA/g body weight) group and high dose GA (HGA,10 μmol GA/g body weight) group.These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am,15:00 pm and 22:30 pm and killed 12 h after the last injection.Microscopic pathology in corpus striatum was evalu-ated by HE staining.The apoptotic cells were identified by TUNEL staining.The transcript levels of caspase-3,8,9,Bax,Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting.In LGA and HGA groups,ventricle collapse,cortical atrophy by a macroscope and interstitial edema,vacuolations,widened perivascular space of bi-lateral striatum by a microscope were observed.TUNEL assay revealed that the apoptotic cells were in-creased in LGA and HGA groups.The transcript of caspase-3 was up-regulated to 2.5 fold,accompanied by the up-regulation of caspase-9,Bax and down-regulation of Bcl-2.The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups.The rat model for GA Ⅰ showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion.Further studies should be taken to investigate the underlying mechanisms.
文摘Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.
