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Biomedical subjects

U Drescher

Publications and source records attributed to U Drescher.

At least 37 records · Page 2Linked to original sources
PubMed1996

Rostral optic tectum acquires caudal characteristics following ectopic engrailed expression.

BACKGROUND: Expression of the homeobox-containing gene Engrailed (En) in an increasing rostral-to-caudal gradient in the dorsal mesencephalon is the earliest known marker for polarity of the chick optic tectum. In heterotopic transplantation experiments, En protein expression correlates well with the subsequent gradient of cytoarchitecture as well as the pattern of retinotectal projections. The En gradient also correlates with the expression of two putative retinal axon-guidance molecules, RAGS and ELF-1, which are Eph-like receptor tyrosine kinase ligands that may function in the establishment of retinotopic projections by excluding temporal axons from the caudal tectum. RESULTS: To examine the function of En in determining tectal polarity, we used the replication-competent retroviral vector RCAS to misexpress mouse En-1 throughout the chick tectal primordium. Our results show that the rostral portion of the tectum adopts a caudal phenotype: the gradient of cytoarchitectonic differentiation is abolished, and the molecular markers RAGS and ELF-1 are strongly expressed rostrally. In addition, cell membranes from rostral tectum of RCAS En-1-infected embryos preferentially repel temporal axons in in vitro membrane stripe assays. CONCLUSIONS: These results are consistent with a role for En in determining rostrocaudal polarity of the developing tectum. The demonstration that both RAGS and ELF-1 are upregulated following En misexpression provides a molecular basis for understanding the previous observation, also based on retrovirus-mediated En misexpression, that nasal axons form ectopic connections in rostral tectum, from which temporal axons are excluded.

Animals↗
PubMed1996

Novel gene families involved in neural pathfinding.

Recent studies have uncovered a bifunctional role of the diffusible axon guidance molecules netrin-1 and UNC-6 in that they attract some axons and steer others away simultaneously. Homology screens have extended the semaphorin and collapsin family to include at least 20 members, in both secreted and membrane-bound forms. Eph-related receptors and their membrane-bound ligands, the function of which have only been characterized poorly to date, have been added to the growing number of molecules involved in axon guidance and fasciculation.

Animals↗
PubMed1995

In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases.

The results of previous in vitro experiments indicate that a glycosylphosphatidylinositol (GPI)-anchored protein may play an important role in the guidance of temporal retinal axons during the formation of the topographically ordered retinotectal projection. We have purified and cloned a GPI-anchored, 25 kDa glycoprotein that is a good candidate for a molecule involved in this process. During the time of innervation by retinal ganglion cells, this protein is gradedly expressed in the posterior part of the developing tectum. In two different in vitro assay systems, the recombinant protein induces growth cone collapse and repulsion of retinal ganglion cell axons. These phenomena are observed for axons of temporal as well as nasal origin, indicating that an additional activity may be necessary to confer the nasotemporal specificity observed in previous assays. We named the protein RAGS (for repulsive axon guidance signal). The sequence of RAGS shows significant homology to recently identified ligands for receptor tyrosine kinases of the Eph subfamily.

Amino Acid Sequence↗
PubMed1993

Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced rectification.

Ligand-gated ion channels generally display a heterooligomeric subunit structure. The present report describes an electrophysiological method that provides criteria indicating the subunit stoichiometry of a recombinant GABAA receptor composed of alpha 3, beta 2 and gamma 2 subunits. Our results exclude the stoichiometries 3 alpha 1 beta 1 gamma, 1 alpha 3 beta 1 gamma, 1 alpha 1 beta 3 gamma and suggest that the possible subunit stoichiometries for this receptor are 2 alpha 1 beta 2 gamma, 2 alpha 2 beta 1 gamma or 1 alpha 2 beta 2 gamma, of which the alpha subunit composition 2 alpha 1 beta 2 gamma may be favoured. The method is based on the quantification of the outward rectification of the GABA-evoked current induced by point mutation of charged amino acids located near the ion channel pore.

Amino Acid Sequence↗
PubMed1993

Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant gamma-aminobutyric acidA receptor subtypes.

The differences in intrinsic activity and receptor subtype specificity of the newly developed benzodiazepine receptor ligands bretazenil, divaplon and abecarnil were assessed in recombinant gamma-aminobutyric acidA (GABAA) receptors expressed in mammalian cells from the subunit-cDNA combinations alpha 3 beta 2 gamma 2 and alpha 5 beta 2 gamma 2. Chloride currents induced by rapid application of GABA in the presence or absence of drugs were measured using the whole-cell configuration of the patch-clamp technique. Bretazenil displayed an intrinsic activity which amounted only to 58 +/- 7% and 35 +/- 11% of that of flunitrazepam at the alpha 3 beta 2 gamma 2 and alpha 5 beta 2 gamma 2 combination, respectively. The maximum potentiation by divaplon was only 28 +/- 5% and 21 +/- 9% of that of flunitrazepam at the respective subunit combinations. Thus, the partial agonism postulated for bretazenil and divaplon on pharmacological grounds is shown to be operative on the level of single GABAA receptors. Most strikingly, abecarnil potentiated the GABA response to the same degree as flunitrazepam at the alpha 3 beta 2 gamma 2 combination but to only 52 +/- 14% compared to flunitrazepam at the alpha 5 beta 2 gamma 2 combination. This finding demonstrates that the intrinsic activity of benzodiazepine receptor ligands can vary among the receptor subtypes with the degree of receptor modulation being influenced by the type of alpha subunit.

Benzodiazepinones↗
PubMed1991

The gamma 3-subunit of the GABAA-receptor confers sensitivity to benzodiazepine receptor ligands.

The gamma 3-subunit of the GABAA-receptor in rat brain has been identified by molecular cloning. When co-expressed with the alpha 5- and beta 2-subunits in transfected cells a high potency for GABA (Ka = 4.9 +/- 1.2 microM) and a strong cooperativity in gating the channel (H = 1.9 +/- 0.2) was observed. The GABA response was potentiated in the presence of flunitrazepam and reduced by beta CCM. An analogous bi-directional modulation of the GABA response was observed with diazepam and DMCM as tested with the subunit combinations alpha 1 beta 2 gamma 3 and alpha 3 beta 2 gamma 3 expressed in Xenopus oocytes. Since the benzodiazepine receptor ligands were virtually inactive in the absence of the gamma 3-subunit, as tested with the alpha 3 beta 2- and alpha 5 beta 2-subunit combinations, the gamma 3-subunit is a prerequisite for the benzodiazepine receptor sensitivity of the expressed GABAA-receptors. The gamma 3-subunit could functionally replace the gamma 2-subunit with regard to the bi-directional allosteric drug modulation.

Amino Acid Sequence↗
PubMed1989

[Pilot study of the action of Doqualast on dietary hyperuricemia in volunteers].

For eight days 8 healthy volunteers were treated with a formula diet and additional 1680 purine base per day. Beginning with day 5, doqualast was administered orally in a dosage of 200 mg t.i.d. Serum uric acid level was lowered by doqualast from 7.84 +/- 0.9 mg/dl to 5.09 +/- 0.8 mg/dl (p less than 0.01). Uric acid clearance increased from 7.6 +/- 2.5 ml/min to 11.5 +/- 2.4 ml/min (p less than 0.05). Excretion of uric acid in urine increased from 622 +/- 231 mg/d to 890 +/- 233 mg/d at the end of therapy. Total cholesterol in serum was lowered from 222 +/- 70 mg/dl to 159 +/- 48 mg/dl (p less than 0.05). The new uric acid lowering drug doqualast was well tolerated clinically. No adverse effects on biochemistry parameters were observed.

Adult↗
PubMed1988

Moratorium call.

Explore the source record for details and available documents.

Base Sequence↗
PubMed1987

Isolation and characterization of murine transcriptional control elements using a "shotgun" method.

In an attempt to identify novel promoter/enhancer elements in cellular genomes, an experimental "shotgun" system was designed and tested. Fragments of mouse cellular DNA were cloned into various plasmid vectors whose common reporter gene facilitates the identification of regulatory sequences. Of 120 clones analyzed, we identified one whose insert markedly increases transcriptional activity of the constructions. This genomic fragment contains a promoter element and exhibits enhancer-like properties in fibroblast cell lines of different species. Genomic analysis shows the fragment is a member of a middle repetitive sequence family, containing a 170-bp sequence with extreme purine/pyrimidine asymmetry. This stretch of cellular DNA is very sensitive to S1 nuclease digestion when present in superhelical plasmids. Isolation and characterization of sequences homologous to this fragment suggest a relationship between transcriptional activity and S1 sensitivity.

Acetyltransferases↗
PubMed1987

The murine homeo box gene product, Hox 1.1 protein, is growth-controlled and associated with chromatin.

In order to gain insight into the function of the Hox 1.1 gene, we studied the expression of the murine homeo box gene product, the Hox 1.1 protein. Monoclonal antibodies were raised against synthetic peptides of the Hox 1.1 protein to study the localization and expression pattern of this protein under various culture conditions. By means of indirect immunofluorescence we localized the Hox 1.1 protein to the nucleus in differentiated F9 and NIH 3T3 cells. During mitosis the protein was found to be associated with chromatin. Confluent NIH 3T3 cells harbored little if any Hox 1.1 protein. After "wounding" the cells in this confluent monolayer, we observed an induction of the expression of the Hox 1.1 protein. However, addition of insulin to F9 and contact-inhibited NIH 3T3 cells led to an increase of the Hox 1.1 RNA and protein expression. Thus, the induction of the Hox 1.1 protein is associated not only with the differentiation of embryonal carcinoma (EC) cells, but may also correlate with stages of cell growth.

Amino Acid Sequence↗
PubMed1986

[Results of Lambling gastric juice analysis in infants with spastic hypertrophic pyloric stenosis (SHPS)].

In 27 infants aged 20 to 65 days with clinically and roentgenologically proved hypertrophic pyloric stenosis gastric juice analyses were performed according to Lambling. Basic acid output and maximal acid output in these infants were significantly increased as compared to healthy infants of the same age group. The higher acid output in the hypertrophic pyloric stenosis group was due to higher volumes and a higher acidity of the gastric juices. Basic acid output and maximal acid output increased following pylorotomy. There is evidence, that hyperacidity in pylorus stenosis of infancy is primarily and not due to the pyloric constriction. There was a distinct correlation between the degree of metabolic alkalosis and diminished acid outputs. The findings support the thesis, that infantile hypertrophic stenosis is originated by an increased parietal cell mass. The increased acid secretion and the enhanced release of secretin and cholecystokinin are supposed to originate the hypertrophy of the pyloric muscle.

Female↗
PubMed1983

D-amino acid utilization in infants measured with the 15N-tracer technique.

The utilization rates of D-[15N] valine, D-[15N] leucine, D-[15N] phenylalanine and D-[15N] alanine were investigated in seven infants being fed parenterally. Retention of the (15)N in the protein pool varied from one amino acid to another and ranged from 23.2% for D-[15N] valine to 48.6% for D-[15N] alanine. In the case of valine it was shown that cumulative renal excretion amounted to 70% of the applied (15)N-dose, 44% being overflow of unchanged D-[15N] valine, 16.6% appearing as [15N] urea and 1.2% as [15N] ammonium. This indicates that doubling the concentrations of D-amino acid racemates compared with their L-isomer counterparts in parenteral feeding solutions must inevitably lead to imbalances. The use of D-amino acids for the purposes of parenteral nutrition remains however ineffective due to their poor and variable utilization compared to L-amino acids.

Journal Article↗
PubMed1983

15N-labelled yeast protein--a valid tracer for calculating whole-body protein parameters in infants: a comparison between [15N]-yeast protein and [15N]-glycine.

The validity of [15N]-glycine and 15N-labelled yeast protein as tracers for investigating the parameters of nitrogen metabolism in man was studied by comparisons of each tracer in three infants on different diets. Both tracers were administered with the food as a single oral dose of 0.2 mmol 15N-excess nitrogen per kg body weight. Cumulative 15N-excess excretion in the urine was measured by emission spectrometry and a three-compartment model was used to calculate the pool sizes by computer. In all three comparisons the values calculated for protein synthesis, protein breakdown, protein turnover and reutilization after administration of 15N-labelled yeast protein were slightly lower than those calculated after administration of [15N]-glycine. The particular advantage of applying a highly enriched, completely labelled [15N]-protein instead of [15N]-glycine as a tracer is that the protein, containing some 20 amino acids, doubtless gives a more accurate picture of protein metabolism than the use of a single amino acid labelled with heavy nitrogen. However, the small differences between the whole-body parameters calculated from 15N-labelled yeast protein and [15N]-glycine do not justify the general replacement of [15N]-glycine by 15N-labelled protein.

Diet↗
PubMed1981

[Cerebrospinal fluid protein levels and blood-cerebrospinal fluid ratio of glucose and electrolytes in infants and children].

The cell and protein content of the cerebrospinal fluid (CSF) and the CSF/serum ratio of glucose, sodium, potassium, calcium, phosphate and chloride were investigated in 71 children without cerebromeningeal illness and aged 0-4 weeks, 5-8 weeks, 3-6 months, 7-12 months, 1-6 years and 7-14 years. The protein content of the CSF was 730 +/- 146 (530-950) mg/l for the age group 0-4 weeks, and 530 +/- 221 (270-950) mg/l for the age group 5-8 weeks. It was significantly higher than for all subsequent age groups. The CSF glucose accounted for 68-82% of the blood glucose. The serum/CSF ratio for sodium ranged from 101 to 104%, for potassium from 55 to 64%, for calcium from 48 to 70%, for phosphate from 24-29%, and for chloride from 106 to 114%. The decrease in serum and CSF potassium and phosphate concentrations from infancy to school age was significant. The greatest difference was evident in the serum/CSF calcium ratio which was significantly higher in the age groups up to 8 weeks than in the subsequent age groups. The electrolyte concentration of CSF with elevated protein and cell values did not differ significantly from CSF of children without cerebromeningeal disorders.

Adolescent↗