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Biomedical subjects

W Schmid

Publications and source records attributed to W Schmid.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Trisomy-21 screening using AFPplus in the eastern part of Switzerland].

Two years after introduction of maternal serum screening for Down's syndrome in German-speaking Switzerland, based on measurements of alpha-fetoprotein, unconjugated estriol and total beta-HCG, results were analyzed of the two cytogenetic laboratories in Zurich and of a separate collective of the Department of Obstetrics at the University of Zurich. In a total of 489 cases with increased risk for Down's syndrome (> or = 1:380 at term) 19 (1:26; approximately 4%) had an abnormal fetal karyotype from which 16 had a trisomy 21. 13 out of these 16 mothers were aged below 35 years. Thus, after ultrasound, maternal serum screening detects the highest percentage of fetuses with chromosomal abnormalities. At the Department of Obstetrics 2962 serum screening tests were performed during a period of 2 1/2 years. 14.6% of the women were > or = 35 years old, 7.6% showed increased risk and 14 fetuses had an abnormal karyotype including 10 with Down's syndrome. 7 of these 10 were detected by the serum test. Nevertheless, the limited sensitivity of serum screening, its limitation predominantly to detection of fetuses with Down's syndrome and the rather late stage of screening, make effective first trimester screening mandatory.

Adult↗
PubMed1995

Effects of kainic acid induced seizures on immediate early gene expression in mice with a targeted mutation of the CREB gene.

The present study examined the response of immediate early genes following kainic acid induced seizures in mice lacking the alpha and delta isoforms of CREB. mRNA levels for c-fos, c-jun, and Krox-24 were measured following limbic seizure activity and were found to be induced in wild type as well as CREB mutant mice. This effect was also seen for these three mRNAs at the protein level as well as for FOS-B. Furthermore the time course of expression of FOS, JUN, KROX-24, and FOS-B proteins were essentially the same in CREB mutant mice as compared to wild-type controls. These data suggest that CREB alpha and delta are not required for the induction of immediate early genes following pharmacologically induced seizures.

Activating Transcription Factor 2↗
PubMed1995

Molecular genetic analysis of glucocorticoid signaling during mouse development.

Glucocorticoids are important in a number of developmental processes in mammals around birth. The pathway of gluconeogenesis is activated in liver shortly after birth due to the combined effects of glucocorticoids and glucagon. We have defined the essential cis-regulatory elements directing hormone-dependent liver-specific expression of the gene for tyrosine aminotransferase, a key gluconeogenic enzyme. The hormone response elements synergize with cell-type specific elements. In the case of glucocorticoids, the glucocorticoid-dependent enhancer is composed of the glucocorticoid response element and binding sites for liver cell-enriched transcription factors, in particular hepatocyte nuclear factor-3. The dependence of the respective enhancer motifs on each other restricts the hormonal activation of the tyrosine aminotransferase gene in liver in response to a hormonal signal. To further understand the role of glucocorticoid signaling via the type II glucocorticoid receptor (GR) in the perinatal period and earlier during development, we have studied the expression of the mouse GR gene. Expression of the gene is controlled by at least three promoters, one of which is only active in T-lymphocytes. Expression of GR mRNA has been detected as early as day 9.5 of mouse development. To specifically address the role of glucocorticoid signaling via the GR during development, we have disrupted the GR gene by homologous recombination in mouse embryonic stem cells. The majority of GR mutants die shortly after birth and analysis so far has revealed defects in lung, liver, and adrenal function.

Animals↗
PubMed1995

Molecular genetic analysis of glucocorticoid signalling in development.

A null mutation of the glucocorticoid receptor was generated by homologous recombination. Mutant newborn mice showed impaired lung development, hypertrophy of the adrenal cortex and a strongly reduced size of the adrenal medulla. Phenylethanolamine N-methyltransferase (PNMT) was undetectable in the adrenals of the mutant mice. Serum levels of corticosterone were moderately and ACTH levels were strongly elevated in the mutants. A weaker but significant increase of corticosterone and ACTH was observed already in heterozygous animals. This points to a dysregulation of the HPA axis due to defective feedback regulation via the glucocorticoid receptor. Liver gluconeogenetic enzymes were reduced to a variable degree. Whereas survival of heterozygous mutants was not affected, most of the homozygous mutant mice died during the perinatal period.

Animals↗
PubMed1995

Rapid detection of sex chromosomal aneuploidies by PCR.

In this report we present a method to determine sex chromosomal aneuploidies by duplex polymerase chain reaction with sufficient precision to distinguish between one, two and more copies of X and Y sequences. We coamplified an autosomal gene segment (exon 33 of neurofibromatosis type I gene on chromosome 17) as an internal standard for our sequence of interest (AMXY) on X and Y chromosomes. By using this standard as a reference for two gene copies we could visually estimate the relative gene dosage for the X-, and Y-specific AMXY sequences in the DNA sample under consideration. We have evaluated this method in normal males and females and in patients with known sex chromosomal aneuploidies and have found it to be a reliable and quick tool for detection of numerical sex chromosomal abnormalities.

Aneuploidy↗
PubMed1994

Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors.

The cAMP response element binding protein (CREB) has been implicated as a key regulator in the transcriptional control of many genes. To assess the functional importance of CREB in vivo and its role in development, we used gene targeting to generate mice with a disruption of the CREB gene. Homozygous mutant mice appeared healthy and exhibited no impairment of growth or development. In this report we demonstrate that CREB and two other members of the CREB/ATF family, cAMP response element modulation protein (CREM) and activating transcription factor 1 (ATF1), appear to form a unique subgroup within this extensive class of transcription factors. Examination of CREM mRNA and protein levels in CREB mutant mice demonstrated overexpression of CREM in all tissues examined, but no change in ATF1 levels. These data demonstrate that CREB is not the sole mediator of cAMP-dependent transcriptional regulation and probably acts in concert with a specific subset of cAMP response element-binding proteins to transduce the cAMP signal and, in its absence, these same proteins can compensate for CREB function in vivo.

Activating Transcription Factor 1↗
PubMed1994

Hepatocytic transcription factor expression in human embryonal carcinoma and yolk sac carcinoma cell lines: expression of HNF-3 alpha in models of early endodermal cell differentiation.

Retinoic acid treatment of the multipotent human embryonal carcinoma cell line GCT 27 X-1 induced differentiation into an epithelial cell type which morphologically resembled rodent visceral endoderm in vitro. The differentiated cells expressed some markers characteristic of yolk sac, such as cytokeratin 19 and extracellular matrix proteins, but none of the secreted serum proteins produced by normal yolk sac or liver. HNF-3 alpha expression increased upon retinoic acid-induced GCT 27 X-1 differentiation. This increase in HNF-3 alpha expression may characterize an early stage in the differentiation of extraembryonic endoderm. In support of this hypothesis, we found that a yolk sac carcinoma cell line with a phenotype similar to rodent visceral endoderm expressed transcripts for HNF-1 alpha, -1 beta, -3 alpha, -3 beta, -3 gamma, and 4, whereas yolk sac carcinoma cell lines resembling rodent parietal endoderm expressed transcripts for HNF-3 alpha. The results support the conclusion that hepatocytic transcription factors, particularly HNF-3 alpha, may play an important role in early endodermal differentiation in man.

Animals↗
PubMed1994

The transcription factor CREB is not phosphorylated at serine 133 in axotomized neurons: implications for the expression of AP-1 proteins.

The present study has investigated whether nerve fiber transection alters the phosphorylation of serine at position 133 (Ser133) of the transcription factor CREB (phosphoCREB). Activation of CREB by phosphorylation has a major function in the control of gene transcription. PhosphoCREB was visualized by antisera that specifically react with an epitope comprising the phosphorylated Ser133 of CREB as well as of CREM and ATF1 proteins. In untreated rats, nuclear immunoreactivity (IR) of phosphoCREB was consistently visible, e.g. in the cortex, thalamic and hypothalamic compartments and central termination areas of primary somatosensory afferents. Transection of peripheral (sciatic nerve), cranial (hypoglossal and facial nerve) and central (medial forebrain bundle and mammillo-thalamic tract) nerve fibers did not increase phosphoCREB-IR in the axotomized neurons between 5 min and 30 days post-axotomy. In contrast, phosphoCREB-IR appeared after 24 h in glial cells adjacent to the axotomized motoneurons and persisted up to 4 weeks. This increase in glial phosphoCREB-IR was paralleled by enhanced expression of the CREB protein itself. Between 20 min and 24 h following sciatic nerve transection, the number of phosphoCREB labeled nuclei also increased in neurons of the ipsilateral superficial dorsal horn of lumbar L3-L5 spinal cord segments. These data suggest that phosphorylation of Ser133 in CREB/CREM/ATF1 proteins is not involved in the transcriptional control of early-response genes such as c-jun in axotomized neurons following nerve transection. This is in contrast to the reported phosphorylation of CREB and its trans-acting effects on immediate-early genes such as c-fos after transynaptic neuronal excitation.

Afferent Pathways↗
PubMed1994

Improvement of masticatory function after orthodontic treatment. Two case reports.

In patients with temporomandibular joints dysfunction (TMD), the masticatory function is often altered in that: (1) the intercuspal position (ICP) is less frequently achieved; (2) the mean vertical displacement from ICP at the end of opening is above normal; and (3) the isometric muscle contraction pattern during closure tends to be suppressed. We describe two cases of growing patients with severe malocclusion, who showed the same functional alterations as patients with TMJ before treatment, and normalization of the masticatory function after orthodontics.

Child↗
PubMed1993

[Direct genetic diagnosis in Huntington's chorea].

Huntington's disease is a late manifesting autosomal dominant neurodegenerative disorder. It is characterized by motor disturbance, loss of cognitive functions and psychiatric manifestations. Recently, the disease causing mutation, an unstable DNA sequence in the coding region of the Huntington gene on chromosome 4p, has been identified. A trinucleotide (CAG) repeat is expanded over the normal range and can easily be detected by standard laboratory methods. Accurate genetic testing can now be offered in clinically questionable cases and to subjects at risk for Huntington's disease. Furthermore, there seems to be a correlation between the size of the expanded CAG repeat and the age of onset in affected individuals. We have investigated more than 130 individuals from different affected families and illustrate the advantages and the clinical application of the new method.

Adult↗
PubMed1993

Characterization of the nuclear proteins binding the CACCC element of a glucocorticoid-responsive enhancer in the tyrosine aminotransferase gene.

The nuclear proteins which act synergistically with the glucocorticoid receptor to induce transcription of the tyrosine aminotransferase gene include factors recognizing the CACCC element. We have purified and characterized the proteins from rat liver nuclei which bind to the CACCC motif in the glucocorticoid-inducible enhancer of the gene. Three protein-DNA complexes (C1, C2, and C3) were detected in band-shift assays. The protein component of complex C1 also binds a GC motif (a Sp1 binding site) and is recognized by anti-Sp1 antiserum. The proteins forming complexes C2 and C3 have been purified by DNA-affinity chromatography and their molecular masses (75-80 kDa and 35-40 kDa, respectively) have been determined by ultraviolet cross-linking to radio-labelled DNA and SDS/PAGE. The DNA-affinity-purified C2 and C3 activities do not bind significantly to the GC motif and are not recognized by anti-Sp1 antiserum. Methylation interference analysis indicates that the nucleotides of the CACCC element bound by the C2 and C3 proteins correspond to those of the glucocorticoid-responsive enhancer which are contacted in vivo following glucocorticoid administration. Our data suggest that these proteins contribute to glucocorticoid-induced transcription of the tyrosine aminotransferase gene.

Animals↗