Biomedical subjects

E Schulze

Publications and source records attributed to E Schulze.

148 records · Page 9Linked to original sources

PubMedDate not supplied

Pulmonary atresia with hypoplastic right ventricle. A clinical embryological study.

An unusual case of pulmonary atresia with an aberrant karyotype of 46,XX,t(6;8)(p21.2;q11.2) is reported. Fetal ultrasonic examination at the 20th week of gestation revealed a hypoplastic right ventricle and an intact interventricular septum. Authors summarize their postnatal findings in fetal heart and the large adjacent vessels with special reference to the pathogenesis of this rare congenital heart defect. The observation delineates right-ventricular outflow tract obstruction associated with an abnormal pulmonary blood supply. The anatomy of the systemic pulmonary collaterals was studied and correlated with multifocal disorders in the system of the pharyngeal arch arteries in the early embryonic development.

Amniocentesis↗

PubMedDate not supplied

Divergence between genotype and phenotype in relatives of patients with the intron 2 mutation of steroid-21-hydroxylase.

We studied 95 patients and their relatives with the classical salt wasting (SW) and simple virilizing (SV) form of CAH. SSCP/heteroduplex analysis allowed fast and efficient screening for the most common 21-hydroxylase mutations (e.g. deletions, splice site mutation in intron 2 (bp 656), Ile172Asn mutation in exon 4) and determination of the relative intensities of CYP21A and CYP21B genes. The splice site mutation in intron 2 was found as the most frequent cause of 21-hydroxylase deficiency (35% of our patients). There is a strong genetic association between the mutation in intron 2 and the SW form of CAH. On the other hand, about 20% of our patients with the intron 2 mutation have the SV phenotype. Interestingly, homozygous splice site mutations in intron 2 were also detected in some parents or other relatives with no phenotypic changes typical for CAH (clinical evaluation, steroid hormone levels). In those patients with SV-CAH and especially in the relatives with the homozygous intron 2 mutation and an unaffected phenotype, the splice site mutation could be "leaky". mRNA-splicing in the adrenal cortex should result in a high degree of normal mRNA species. This is in contrast to in vitro expression studies of CYP21B genes containing the intron 2 mutation, performed by other groups. However, the results of in vitro expression studies are not always reflecting the in vivo conditions in the adrenal cortex. This situation is in good agreement with the variable degree of normal spliced mRNA and different phenotypic severity in intron mutations found in thalassemia.

Adrenal Hyperplasia, Congenital↗

PubMedDate not supplied

Allele-dropout using PCR-based diagnosis for the splicing mutation in intron-2 of the CYP21B-gene: successful amplification with a Taq/Pwo-polymerase mixture.

The splicing mutation in intron 2 (nucleotide 656) of the 21-hydroxylase gene (CYP21B) is the most common mutation causing congenital adrenal hyperplasia (CAH). Homozygosity for nt656G is associated with the classical phenotype of CAH. In several studies, a number of clinically asymptomatic relatives of CAH-patients were genotyped as nt656G homozygotes. We have proposed that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one allele (in most cases nt656C) during PCR amplification. Here, we report the successful amplification of all alleles at nt656 with a Taq/Pwo DNA polymerase mixture in the primary PCR reaction. The results were independent from the type of polymerase used for sequencing reactions as the second step in mutation analysis.

Adrenal Hyperplasia, Congenital↗

PubMedDate not supplied

Potential triple helix-mediated inhibition of IGF-I gene expression significantly reduces tumorigenicity of glioblastoma in an animal model.

Oligonucleotide-directed triple helix formation is a powerful approach to block transcription of specific genes. Although the oligonucleotide triplex approach is efficient for inhibiting gene expression in cultured cells, suppression is transient. We developed an approach which inhibits insulin-like growth factor-I (IGF-I) expression following stable transfection of C6 rat glioblastoma cells with a plasmid from which an RNA is transcribed that codes for the third strand of a potential triple helix. We tested the ability of this expression vector to inhibit IGF-I gene expression in vitro as well as tumorigenesis in an animal. A dramatic reduction of IGF-I RNA and protein levels in cultured cells occurred following transfection of rat C6 cells with a eukaryotic expression plasmid encoding the oligopurine variant of the triple helix but not the oligopyrimidine or a control sequence. The cells transfected with the oligopurine variant displayed morphological changes, upregulation of major histocompatibility complex I, and increased expression of protease nexin I. Dramatic inhibition of tumor growth occurred in nude mice following injection of transfected C6 cells. To our knowledge, this is the first example of tumor growth inhibition in an animal model employing a triple helix approach.

Amyloid beta-Protein Precursor↗