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Biomedical subjects

A Hofmann

Publications and source records attributed to A Hofmann.

At least 127 records · Page 7Linked to original sources
PubMed1989

Transcriptional characteristics of in vitro assembled chromatin assayed by microinjection into Xenopus laevis oocytes.

Plasmid DNA was in vitro assembled into chromatin using an S-150 extract of Xenopus laevis oocytes. By varying the assembly temperature and DNA concentration it is possible to generate fully or partially assembled molecules. The fate of the in vitro preassembled molecules injected into X. laevis oocyte nuclei and their transcriptional activity were studied. Completely reconstituted molecules underwent a rearrangement of their chromatin structure after injection and showed reduced transcriptional activity compared to protein-free DNA or partially reconstituted chromatin.

Animals↗
PubMed1989

Restriction analysis of lambda EMBL3 background recombinants: occurrence of lambda phages carrying a head to tail oriented left arm DNA sequence.

Eight representative recombinant background clones of lambda EMBL3 were analysed using KpnI, BamHI, SalI, EcoRI and HindIII digestion. We found that lambda EMBL3 carries its own left arm in the BamHI cloning site. In the way, recombinant molecules were found to be generated which can grow on Escherichia coli strain NM539. In all cases analysed, the left arm DNA was inserted in a head to tail orientation. Seven clones carried a restored BamHI site at the cos site-BamHI site connection. In the region where the inserted left arm and the right arm were ligated, BamHI cloning produces a large palindromic sequence consisting of two polylinkers. This BamHI site was incompletely cleaved in all cases analysed. We assume that a part of the lambda DNA molecule in this region shows a cruciform structure prohibiting recognition or cleavage of this site by restriction endonuclease BamHI.

Bacteriophage lambda↗
PubMed1989

Effects of new 4-aminopyridine derivatives on neuromuscular transmission and on smooth muscle contractility.

The effects of new 4-aminopyridine (4-AP) derivatives were investigated in the isolated mouse phrenic nerve-hemidiaphragm preparation under single impulse stimulation and tetanic conditions. The basic 4-AP structure was modified in position 3 on the pyridine nucleus by introducing different substituents. Results were compared to those obtained with 4-AP and 3,4-diaminopyridine. The compounds were tested for their antagonistic effect against calcium antagonists and botulinum toxin A. The effect on smooth muscle was investigated on the isolated guinea-pig ileum. Physico-chemical parameters of the test compounds were determined by the partition coefficient and ionization constant. Finally structure-activity relationship analysis revealed that the activity was highly related to lipophilicity and the steric volume. So far 4-AP itself provided the most advantageous molecular structure.

Aminopyridines↗
PubMed1988

Pharmacodynamic profile of CQP 201-403, a novel 8 alpha-amino-ergoline.

The profile of action in animals of CQP 201-403, a novel 8 alpha-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and be more potent than bromocriptine (Parlodel).

Animals↗
PubMed1988

Different regulatory elements are required for cell-type and stage specific expression of the Xenopus laevis skeletal muscle actin gene upon injection in X.laevis oocytes and embryos.

In the present study, we demonstrate by transcript mapping that the injected Xenopus skeletal muscle alpha-actin gene is transcribed and spliced in Xenopus oocytes but not correctly initiated at the alpha-actin promoter. This leads to correctly spliced transcripts even if constructs without putative promoter sequences are injected. On the other hand, alpha-actin transcripts are translated in injected oocytes as shown by the detection of alpha-actin protein. By contrast, correctly initiated alpha-actin transcripts can be found in neurula embryos when the injected clone contains 5' flanking sequences extending from +27 to -680. alpha-actin gene fragments without the 680 nucleotides 5' flanking region are activated unspecifically after midblastula transition, whereas the clones carrying this region are activated correctly at the end of gastrulation. Cell type specific expression seems to be modulated by sequences within the transcribed region.

Actins↗
PubMed1987

Upstream sequences of dosage-compensated and non-compensated alleles of the larval secretion protein gene Sgs-4 in Drosophila.

The X chromosomal gene Sgs-4 coding for a larval secretion protein of Drosophila melanogaster is expressed stage and tissue specifically and is hyperexpressed in male larvae of most Drosophila stocks which show dosage compensation. We analysed three Sgs-4 alleles which differ in the size of their coding region, in the intensity of their expression and in the level of dosage compensation. The size and amount of Sgs-4 proteins directly reflect those of RNAs. Different RNA sizes result from different numbers of 21 bp repeats within the structural genes. We sequenced 2.8 kb of DNA upstream of the transcription initiation site of the three alleles. Sequences known to be essential for correct gene expression were located. The only difference within DNA sequences from -1 to -1200 between two alleles with different degrees of expression and differing in dosage compensation is a C to T transition at -344 within a supposed consensus sequence for ecdysone receptor complex binding (ECR). This mutation is partly located within a region of dyad symmetry. Alleles with identical expression show identical mutations within a GTT-rich region at -1.2 kb, but differ within a GT-rich region at -2.0 kb. A polyadenylated 0.5 kb RNA was found to be transcribed from the GTT-rich region of the strand opposite to that of Sgs-4. The corresponding gene is active only in larval salivary glands and, therefore, is named gland specific gene, gsg.

Alleles↗
PubMed1987

Regulatory sequences of the Sgs-4 gene of Drosophila melanogaster analysed by P element-mediated transformation.

The X chromosomally located allele Sgs-4c for a larval secretion protein of Drosophila melanogaster is normally expressed in female larvae of the strain Oregon R and is hyperexpressed in male larvae exhibiting dosage compensation; the allele Sgs-4d in the strain Samarkand is weakly expressed and is not hyperexpressed in male larvae showing a dosage effect. P element-mediated transformation of upstream DNA sequences from both alleles combined with Sgs-4d coding and downstream sequences was performed to localize sequences which are responsible for the level of gene expression and for hyperexpression of Sgs-4c in male larvae. Our results demonstrate that weak expression and dosage effect are inherited with the upstream region from -1 to -838. This Samarkand fragment differs from the homologous Oregon R region only by a C to T transition at -344 which lies within an assumed binding sequence for the ecdysone receptor complex of dyad base symmetry. Replacing the Samarkand upstream region from -1 to -838 by the Oregon R region restores normal Sgs-4 expression and dosage compensation. Hyperexpression in male larvae displays high sensitivity to position effect and is nearly completely inhibited in one transformed line under heterozygous conditions. The integration of an Sgs-4d transposon into a weak spot of polytene chromosome 2L results in a decrease in gene expression. The GTT- and GT-rich regions at -1.2 and -2.0 kb do not obviously influence Sgs-4 expression but possibly play a role in induction of stage-specific chromosome puffing.

Animals↗