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E Schmid

Publications and source records attributed to E Schmid.

At least 109 records · Page 6Linked to original sources
PubMed1992

Expression of the mouse tyrosinase gene during embryonic development: recapitulation of the temporal regulation in transgenic mice.

Pigment in mammals is produced in melanocytes of the skin derived from the neural crest and in the pigmented epithelial cells of the retina derived from the optic cup. Tyrosinase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1) is regarded as the key enzyme in pigment synthesis in both these cell types. In this study, we have investigated the temporal regulation of expression of the tyrosinase gene during early eye development and in the developing hair follicle of the mouse by in situ hybridization and have asked whether transgenes would precisely mimick this pattern. We show that the mouse tyrosinase gene is expressed in the pigment epithelium of the retina as early as day 10.5 of gestation. In the hair follicle, tyrosinase gene expression in melanocytes is detected from day 16.5 onwards. This cell type-specific and temporal expression is largely reproduced in transgenic mice carrying a tyrosinase minigene. Our results suggest that sequences in the immediate vicinity of the mouse tyrosinase gene are sufficient to provide cell-type specificity and developmental regulation in melanocytes and in the pigment epithelium.

Animals↗
PubMed1992

Multiple mRNA isoforms of the transcription activator protein CREB: generation by alternative splicing and specific expression in primary spermatocytes.

We have characterized cDNA clones representing mouse CREB (cyclic AMP responsive element binding protein) mRNA isoforms. These include CREB delta and CREB alpha, of which the rat and human homologues have been previously identified. Both encode proteins with CRE-binding activity and identical transactivation potential. The additional CREB mRNA isoforms potentially encode CREB related proteins. From the structural organization of the mouse CREB gene we conclude that the multiple transcripts are generated by alternative splicing. Furthermore we show that specific CREB mRNA isoforms are expressed at a high level in the adult testis. Expression of these isoforms is induced after commencement of spermatogenesis. In situ hybridization suggests that this expression occurs predominantly in the primary spermatocytes. Comparison of the CREB gene with the recently isolated CREM (cAMP responsive element modulator) cDNAs illustrates that the two genes have arisen by gene duplication and have diverged to encode transcriptional activators and repressors of the cAMP signal transduction pathway.

Amino Acid Sequence↗
PubMed1992

The surgical anatomy of the dorsal carpal branch of the ulnar artery: basis for a neurovascular dorso-ulnar pedicled flap.

In order to design a neurovascular flap from the dorso-ulnar aspect of the midhand for pedicled transfer to adjacent or distant locations, the surgical anatomy of the dorsal carpal branch of the ulnar artery (DCBUA) was studied in 12 cadavers. The DCBUA was identified in all specimens. It originates from the ulnar artery 1.6 to 4.4 centimeters proximal to the ulnar styloid, passing deep to the flexor carpi ulnaris tendon, and spirals superficially to the extensor retinaculum around the ulnar border of the wrist. Its terminal branches supply an undetermined area of skin overlying the ulnar metacarpals and the ulnar hypothenar region, either by direct cutaneous supply (3/12 specimens) or by septo-cutaneous perforators (8/12 specimens). The DCBUA is closely related to the dorsal sensory branch of the ulnar nerve, with which it supplies a common neurovascular territory.

Arteries↗
PubMed1992

Chromosome analysis in a population living in an area of Germany with the highest fallout deposition from the Chernobyl accident.

Chromosome analyses were carried out in 1989 in peripheral lymphocytes of 30 persons from the region in southeast Bavaria (Berchtesgaden) that received the highest radiocesium deposition (> 42 kBq/m2) in Germany. These persons belonged to a group for whom body burdens of radiocesium had been surveyed in 1987. Chromosome analyses had been performed by Stephan and Oestreicher for members of the same group in the period 1987-1990, and these authors have reported elevated rates of chromosome aberrations. Pohl-Rüling et al. (1991) have, likewise, concluded that there have been increased rates of chromosome aberrations in the population of the nearby Salzburg region in 1987. In the study reported here we do not see any elevations compared to our large pre-Chernobyl control group. The difference between our findings and the report of earlier increases cannot be fully explained in terms of the known temporal decrease of the rate of dicentrics and ring chromosomes.

Accidents↗
PubMed1992

Clastogenicity of 2-chlorobenzylidene malonitrile (CS) in V79 Chinese hamster cells.

The clastogenicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated at various exposure conditions. CS efficiently induced chromatid-type aberrations in a dose-dependent manner provided the cells could run through at least one or two S-phases during a 20-h exposure over a 3-h exposure followed by a 20-h recovery period (cell cycle time 8-10 h). The induction of SCEs indicates an S-dependent mechanism. The hydrolysis products o-chlorobenzaldehyde and malonitrile were inactive in these experiments.

Animals↗
PubMed1992

Radiation-induced chromosome aberrations analysed by fluorescence in situ hybridization with a triple combination of composite whole chromosome-specific DNA probes.

Fluorescence in situ hybridization (FISH) with a combination of three composite whole chromosome-specific DNA probes for human chromosomes 1, 4 and 12 was used to analyse in vitro radiation-induced dicentrics and symmetrical translocations in peripheral lymphocytes. Translocations could be rapidly and efficiently detected by FISH. Their frequencies were 1.8-fold higher than the frequencies for dicentrics at a given dose. The dose-response curves for translocations and dicentrics were linear quadratic with a significant higher quadratic component for translocations. The application of FISH for scoring stable translocations for biological dosimetry of radiation exposures is discussed.

Adult↗
PubMed1992

Deficiency of an enzyme of tyrosine metabolism underlies altered gene expression in newborn liver of lethal albino mice.

Mice homozygous for albino deletions encompassing the locus alf/hsdr-1 die shortly after birth. Lethality is thought to be the consequence of hypoglycemia, which results from the failure to activate hormone-dependent genes in liver and kidney encoding enzymes important for gluconeogenesis. Within the region in which alf/hsdr-1 has been defined by physical mapping, we identified the gene encoding fumarylacetoacetate hydrolase (FAH), an enzyme of tyrosine metabolism. Lack of FAH activity should lead to accumulation of toxic tyrosine metabolites. In man, genetically determined FAH deficiency is the primary defect in tyrosinemia type I, a fatal liver disease of infants. Northern blot and in situ hybridization analysis of mouse tissues showed that the cell types that normally express FAH correspond to those that exhibit a phenotype in alf/hsdr-1 deletion mice. Moreover, we could mimic aspects of the alf/hsdr-1 deletion phenotype in vitro by treating primary hepatocyte cultures with an intermediate of tyrosine metabolism. These findings strongly suggest that alf/hsdr-1 encodes FAH and that absence of FAH is responsible for neonatal lethality in albino deletion mice. Mechanisms by which this metabolic defect might bring about alterations in gene expression characteristic of the alf/hsdr-1 deletion phenotype are discussed.

Amino Acid Sequence↗
PubMed1992

Molecular characterization of the mouse tyrosinase gene: pigment cell-specific expression in transgenic mice.

Tyrosinase is the key enzyme in melanin synthesis, and is expressed in the pigment epithelium of the retina, a cell layer derived from the optic cup; and in neural crest-derived melanocytes of skin, hair follicle, choroid, and iris. The tyrosinase gene has been cloned and shown to map to the well-characterized c-locus (albino locus) of the mouse. Subsequent studies demonstrated that a functional tyrosinase minigene was able to rescue the albino phenotype in transgenic mice. The transgene was expressed in a cell type-specific manner in skin and eye. During development of the mouse, the tyrosinase gene is expressed in the pigment epithelium of the retina as early as day 10.5 of gestation. In the hair follicle, tyrosinase gene expression is detected from day 16.5 onwards. This cell-type-specific expression is largely reproduced in transgenic mice. Our results suggest that sequences in the immediate vicinity of the mouse tyrosinase gene are sufficient to provide cell type-specificity and developmental regulation in melanocytes and the pigment epithelium.

Albinism↗
PubMed1992

Multiple effects on liver-specific gene expression in albino lethal mice caused by deficiency of an enzyme in tyrosine metabolism.

alf/hsdr-1 is a locus in the mouse defined by albino deletions to be essential for neonatal viability. Homozygous deletion of alf/hsdr-1 leads to a pleiotropic phenotype in liver and kidney, including impaired perinatal activation of hormone-dependent genes, and the induction of detoxifying enzymes and early-response genes. To elucidate the molecular basis of this complex phenotype, we have identified the gene mapping at alf/hsdr-1 by positional cloning, using overlapping albino locus deletions to define the location of alf/hsdr-1. The gene encodes fumarylacetoacetate hydrolase, FAH, an enzyme of tyrosine metabolism. Genetically determined FAH deficiency in man leads to a severe liver failure in infants. In mice, we find that the normal sites of expression of FAH correlate tightly with cell-types which display abnormalities in albino lethal mice. The identification of the Fah gene as a candidate for alf/hsdr-1 offers a novel explanation for the complex phenotype, one into which all aspects can be accommodated. The phenotype can now be understood as a sequence of responses to toxic electrophilic metabolites.

Animals↗
PubMed1991

Channel permeant cations compete selectively with noncompetitive inhibitors of the nicotinic acetylcholine receptor.

Previous work suggests that noncompetitive inhibitor (NCI) ligands and channel permeant cations bind to sites within the nicotinic acetylcholine receptor ion channel. We have used ethidium as a fluorescent probe of the NCI site to investigate interactions between NCI ligands and channel permeant cations. We found that ethidium can be completely displaced from the receptor by a variety of inorganic monovalent and divalent cations. The rank order of monovalent cation affinities was found to be Tl+ greater than Rb+ greater than or equal to K+ greater than Cs+ greater than Na+ greater than Li+. The monovalent cation Kd values vary markedly over a 40-fold range, from 3 to 121 mM. The Kd values and rank order correspond to values determined previously from electrophysiological data. Hill plots of the back titrations yield slopes of 1.0 for all monovalent cations, indicating a single class of independent sites, as shown previously for NCI ligands. Scatchard analysis of ethidium binding in the presence of Tl+ reveals a reduction in affinity and no changes in the maximal number of sites. In the presence of agonist the kinetics of ethidium dissociation induced by the addition of phencyclidine or cations alone or the simultaneous addition of both are nearly identical. The ethidium dissociation rate induced by either phencyclidine or cations is regulated by the occupation of the agonist sites in a similar manner. These results indicate that the effect of cations on NCI ligand binding occurs by mutually exclusive competition. We suggest that NCIs can regulate cation binding at a physiological cation recognition site that is likely part of the cation permeation path through the receptor channel.

Animals↗
PubMed1991

The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina.

The mouse c locus encodes tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis, which is expressed in the pigment epithelium of the retina and in melanocytes derived from the neural crest. To define regulatory regions of the gene that are important for cell type-specific expression, a deletion series of the tyrosinase 5' region was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and electroporated into tyrosinase-expressing and -nonexpressing cell lines. We show that 270 base pairs 5' of the transcriptional start site is sufficient for CAT expression in a human and a mouse melanoma cell line. This 5' flanking fragment, when cloned in the context of a tyrosinase minigene construct and injected into fertilized eggs of an albino mouse strain, is sufficient for cell type-specific expression in mice. The transgenic mice were pigmented in both skin and eyes. In situ hybridization analysis shows that the 270-base-pair regulatory region contains elements sufficient for specific expression of the transgene both in the pigmented epithelial cells of the retina, which are derived from the optic cup, and in neural crest-derived melanocytes.

Animals↗
PubMed1991

Mitotic spindle damage induced by 2-chlorobenzylidene malonitrile (CS) in V79 Chinese hamster cells examined by differential staining of the spindle apparatus and chromosomes.

A 3-h exposure of V79 Chinese hamster cells with the sensory irritant 2-chlorobenzylidene malonitrile (CS) caused apolar mitoses in a dose-dependent manner. With a preparation and staining technique that allows for the visualization of the spindle apparatus and the chromosomes it was found that unlike in Colcemid-induced c-metaphases residual spindle fibers or microtubule material were present in the majority of CS-induced c-metaphases. The observation suggests different mechanisms for the induction of the c-mitotic effect by the two spindle poisons.

Animals↗
PubMed1991

Induction of chromosome aberrations and sister chromatid exchange by indirectly acting mutagens in immortal mouse and rat hepatocyte lines.

Two immortalized, differentiated mouse (FMH-202) and rat (NRL-Cl-A) hepatocyte lines were examined for their capacity to activate the indirectly acting mutagens aflatoxin B1 (AFB1), cyclophosphamide (CP), benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) into DNA reactive metabolites as determined by the induction of structural chromosome aberrations (CA) and sister chromatid exchange (SCE). The rat and mouse hepatocyte lines were able to efficiently activate either AFB1, BaP and DMBA, or BaP and DMBA, respectively, as shown by significant clastogenic responses. SCE induction was apparent in both cell lines in response to each of the compounds. Due to the observed long-term maintenance of various liver specific functions (at least 3-4 years) as well as the capability to metabolize xenobiotics (at least 30 passages) these cells may be a suitable assay system for the detection of indirectly acting mutagens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Analysis of the aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells.

The aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS), a chemical used as a riot control agent, and its hydrolysis products o-chlorobenzaldehyde and malonitrile was studied at various exposure conditions in V79 Chinese hamster cells. Chromosomes were counted in metaphase preparations with preserved cytoplasm. A significant increase in the number of aneuploid cells was found after CS and o-chlorobenzaldehyde exposure but not after malonitrile exposure. o-chlorobenzaldehyde, which also introduced high levels of polyploid cells, seems to be an important metabolite for the aneuploidogenic effectiveness of CS.

Aneuploidy↗
PubMed1991

Medicaid wrap-up.

The 72nd Legislature restored Medicaid cuts, expanded coverage for infants and pregnant women. While no dramatic changes are right around the corner, Texas is poised for a major re-examination of the Medicaid program.

Budgets↗
PubMed1990

[The urease rapid test (CLO test). Attempt at statistical analysis for the evaluation of Campylobacter colonization in the gastric antrum].

CLO-tests: A statistical analysis for the evaluation of the presence of Campylobacter pylori in antral mucosal biopsies. Antral biopsies taken in a sample of 475 endoscopy patients were positive for CLO on 21% of 77 controls, compared with 39% of non-ulcer dyspepsia (NUD) patients without and 69% with a history of former peptic ulcer. Epigastric pain was associated with a positive CLO-test more frequently than belching or heart burn. Patients with NUD of Turkish or Yugoslavian nationality had a significantly higher rate of positive CLO-reactions compared with Germans or Italians with the same diagnosis. In 96 patients with peptic ulcer, the percentage of positive CLO-test decreased significantly in old persons.

Adult↗
PubMed1990

[Pre- and postoperative ultrasonic studies in stomach carcinoma and in colonic carcinoma].

Ultrasonographic findings in gastric cancer are essential for assessment of operability. In surveillance programs, endoscopy is important in detecting secondary gastric carcinomas, whereas ultrasonographic examination has no clinical value. Preoperative ultrasonography in colorectal carcinoma focuses on detection of liver metastases and, if metastases are detected, on assessment of resectability. Sonographic surveillance at short intervals in thus important for possible therapeutic interventions.

Colorectal Neoplasms↗