Cutis laxa (CL) is a heterogeneous group of genetic and acquired disorders with at least two autosomal dominant forms caused by mutations in the elastin and fibulin-5 genes, respectively. To define the molecular basis...Cutis laxa (CL) is a heterogeneous group of genetic and acquired disorders with at least two autosomal dominant forms caused by mutations in the elastin and fibulin-5 genes, respectively. To define the molecular basis of CL in patients negative for point mutations in the elastin gene, metabolic labeling and immunoprecipitation experiments were used to study the synthesis of elastin in dermal fibroblasts. In addition to the normal 68 kDa tropoelastin (TE) protein, an abnormal, 120 kDa polypeptide was detected in the proband and her affected daughter in a CL family characterized by hernias and unusually severe and early-onset pulmonary disease including bronchiectasis and pulmonary emphysema. Mutational and gene expression studies established that affected individuals in this family carried a partial tandem duplication in the elastin locus. Immunoprecipitation experiments showed that the mutant TE was partially secreted and partially retained intracellularly. A polyclonal antibody raised against a unique peptide in the mutant TE molecule showed both intracellular and matrix staining. We conclude that elastin mutations can cause CL associated with a severe pulmonary phenotype. Synthesis of abnormal TE may interfere with elastic fiber function through a dominant-negative or a gain of function mechanism.展开更多
用血滤片测量17-羟孕酮(17-OHP)含量的方法广泛用于先天性肾上腺增生症(CAH)的筛查。如果在妊娠中有早产的可能,则在胎儿出生前用类固醇治疗来促进肺部成熟,但这样会抑制胎儿肾上腺,还会影响对这种先天性肾上腺增生症的筛查。笔者对160...用血滤片测量17-羟孕酮(17-OHP)含量的方法广泛用于先天性肾上腺增生症(CAH)的筛查。如果在妊娠中有早产的可能,则在胎儿出生前用类固醇治疗来促进肺部成熟,但这样会抑制胎儿肾上腺,还会影响对这种先天性肾上腺增生症的筛查。笔者对160名胎龄为25-35周新生儿,在其生后72-96 h,用血滤片法测量其17-OHP,将其中50名出生前没有接受类固醇治疗的新生儿与110名出生前接受类固醇治疗者进行比较。1个疗程的类固醇疗法是:地塞米松12 mg,间隔24 h 静脉注射2次。其中30例接受了半个疗程治疗。展开更多
We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD)...We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal control subjects to examine whether these genes would contribute to the KD occurrence and/or the development of coronary artery lesion (CAL) in KD.We found that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism in the promoter region was significantly higher in KD patients with CAL than in those without CAL (p = 0.012) or control subjects (p = 0.021) because of a significantly higher frequency of the GG genotype in KD patients with CAL.In addition, the frequency of the A1 allele with 11 AC repeats of KDR g.+4422(AC)11-14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD patients with CAL than in those without CAL (p = 0.013) or control subjects (p = 0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD with CAL patients.The multivariate analysis of clinical features and genotypes of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14 polymorphism was an independent risk factor for the development of CAL with the highest odds ratio among several clinical parameters (odds ratio 6.76; 95%confi-dence interval 1.05-43.48).Dual luciferase assay demonstrated that the A1 allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the A2 allele with 12 AC repeats.These findings suggested that VEGF and its receptor, KDR, genes contributed to the development of CAL in KD patients.展开更多
文摘Cutis laxa (CL) is a heterogeneous group of genetic and acquired disorders with at least two autosomal dominant forms caused by mutations in the elastin and fibulin-5 genes, respectively. To define the molecular basis of CL in patients negative for point mutations in the elastin gene, metabolic labeling and immunoprecipitation experiments were used to study the synthesis of elastin in dermal fibroblasts. In addition to the normal 68 kDa tropoelastin (TE) protein, an abnormal, 120 kDa polypeptide was detected in the proband and her affected daughter in a CL family characterized by hernias and unusually severe and early-onset pulmonary disease including bronchiectasis and pulmonary emphysema. Mutational and gene expression studies established that affected individuals in this family carried a partial tandem duplication in the elastin locus. Immunoprecipitation experiments showed that the mutant TE was partially secreted and partially retained intracellularly. A polyclonal antibody raised against a unique peptide in the mutant TE molecule showed both intracellular and matrix staining. We conclude that elastin mutations can cause CL associated with a severe pulmonary phenotype. Synthesis of abnormal TE may interfere with elastic fiber function through a dominant-negative or a gain of function mechanism.
文摘用血滤片测量17-羟孕酮(17-OHP)含量的方法广泛用于先天性肾上腺增生症(CAH)的筛查。如果在妊娠中有早产的可能,则在胎儿出生前用类固醇治疗来促进肺部成熟,但这样会抑制胎儿肾上腺,还会影响对这种先天性肾上腺增生症的筛查。笔者对160名胎龄为25-35周新生儿,在其生后72-96 h,用血滤片法测量其17-OHP,将其中50名出生前没有接受类固醇治疗的新生儿与110名出生前接受类固醇治疗者进行比较。1个疗程的类固醇疗法是:地塞米松12 mg,间隔24 h 静脉注射2次。其中30例接受了半个疗程治疗。
文摘We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal control subjects to examine whether these genes would contribute to the KD occurrence and/or the development of coronary artery lesion (CAL) in KD.We found that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism in the promoter region was significantly higher in KD patients with CAL than in those without CAL (p = 0.012) or control subjects (p = 0.021) because of a significantly higher frequency of the GG genotype in KD patients with CAL.In addition, the frequency of the A1 allele with 11 AC repeats of KDR g.+4422(AC)11-14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD patients with CAL than in those without CAL (p = 0.013) or control subjects (p = 0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD with CAL patients.The multivariate analysis of clinical features and genotypes of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14 polymorphism was an independent risk factor for the development of CAL with the highest odds ratio among several clinical parameters (odds ratio 6.76; 95%confi-dence interval 1.05-43.48).Dual luciferase assay demonstrated that the A1 allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the A2 allele with 12 AC repeats.These findings suggested that VEGF and its receptor, KDR, genes contributed to the development of CAL in KD patients.
