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Biomedical subjects

G Hennig

Publications and source records attributed to G Hennig.

At least 19 recordsLinked to original sources
PubMed2002

Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs.

Our aim was to evaluate topographically specific gastric motility changes induced by graded vagal activation. A recently developed method of constructing spatio-temporal maps of motility from video movies was adapted to the in vitro perfused guinea-pig stomach with an intact vagal nerve supply. In the unstimulated preparation, spontaneous activity was low or absent. Bilateral vagal stimulation with frequencies as low as 0.2 Hz triggered weak anally, and in some cases orally, propagating antral contractions at rates of about 5-6 min-1. Upon stimulation with higher frequencies, antral contractions increased significantly in length (starting more proximally) and amplitude, and produced large pressure peaks of up to 25 hPa, with maximal effects at 2-4 Hz. In contrast, the speed of propagation and the interval between peristaltic waves did not change with vagal stimulation at any frequency. Vagal stimulation also produced a significant and frequency-dependent enlargement of the fundus with a maximal effect at 4 Hz. It is concluded that a very low tonic vagal activity is apparently necessary and sufficient to express basic antral motility, while more sustained vagal activity is necessary for high-amplitude gastric contractions and significant sustained fundic relaxation. The constant interval between propagating contractions supports the concept that vagal input impinges on intrinsic enteric neural circuits that have a modulatory role in the myogenic mechanism underlying slow-wave peristalsis, rather than directly on gastric musculature.

Animals↗
PubMed1998

Identification of motor neurons to the circular muscle of the guinea pig gastric corpus.

The projections of enteric neurons to the circular muscle of the guinea pig gastric corpus were investigated systematically by using the retrogradely transported fluorescent carbocyanine dye 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI), applied to the muscle layer or myenteric plexus in vitro. DiI-labeled motor neuron cell bodies were located up to 6.3 mm aboral, 17 mm oral, and up to 20 mm circumferential to the DiI application site. Labeled nerve fibers ran for long distances from the DiI application site toward the greater and lesser curvatures, where they coursed parallel to the bundles of the "gastric sling" muscle. The majority of labeled cells were located toward the lesser curvature of the stomach. Nerve cell bodies that were aboral to the DiI application site were usually small, immunoreactive for choline acetyltransferase, and, thus, were likely to be excitatory motor neurons. Neurons that were located orally were larger, fewer in number, and immunoreactive for nitric oxide synthase and, thus, were likely to be inhibitory motor neurons. Application of DiI directly to the myenteric plexus filled neurons up to 15 mm aborally and up to 21 mm orally but labeled few neurons circumferentially. All nerve cells that were filled from either the circular muscle or the myenteric plexus had Dogiel type I morphological features. These results demonstrate a clear polarity of projection of inhibitory and excitatory motor neurons and a functionally continuous innervation of the circular and gastric sling muscle layers. Nonmotor neurons in the myenteric plexus were demonstrated, but neurons with Dogiel type II morphological features are apparently absent.

Animals↗
PubMed1996

Mechanisms identified in the transcriptional control of epithelial gene expression.

Epithelium-specific gene expression is fundamental in both embryogenesis and the maintenance of adult tissues, and impairment of epithelial characteristics contributes to diseases such as cancer. We have here analyzed the 5'-region of the epithelial (E-) cadherin gene in order to understand mechanisms of epithelium-specific transcription and loss of expression during epithelial-mesenchymal transitions. The regulatory region of the mouse epithelial cadherin gene is composed of a promoter (from position -94 to the transcription start site) and a 150-base pair enhancer located in the first intron. The 5'-promoter consists of positive regulatory elements (a CCAAT-box and two AP-2 binding sites in a GC-rich region) and the palindromic element E-Pal that activates and represses transcription in epithelial and mesenchymal cells, respectively. The enhancer of the first intron stimulates the activity of heterologous promoters exclusively in epithelial cells. This epithelium-specific enhancer consists of three elements (E I to E III; E II and E III bind AP-2) that are necessary and sufficient for activity. We thus propose two regulatory mechanisms by which epithelial specificity of epithelial cadherin expression is determined: suppression of promoter activity in mesenchymal cells by E-Pal and enhancement of activity in epithelial cells by both E-Pal and the epithelium-specific enhancer.

Animals↗
PubMed1995

Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo.

E-cadherin has been identified as a tumor (invasion) suppressor gene, which is mutated in 50% of diffuse-type human gastric carcinomas. In other carcinomas, the expression of E-cadherin is down-regulated in the poorly differentiated cells such as from breast, bladder, lung and colon. We have here examined the in vivo properties of the genomic E-cadherin promoter in well and poorly differentiated carcinoma cell lines in order to gain insights into the mechanisms of E-cadherin down-regulation in tumors. In vivo footprinting analysis revealed that positive regulatory elements of the E-cadherin promoter (a GC-rich region, the CCAAT-box and a palindromic element) are specifically bound by transcription factors in E-cadherin-expressing but not in non-expressing cells. The tested cell systems include more than a dozen carcinomas cell lines as well as mammary epithelial cells where E-cadherin expression can be switched off by activation of a Fos-estrogen receptor fusion protein and rhabdomyosarcoma cells where E-cadherin expression was induced by transfection with E1A. Mapping of DNase I hypersensitive sites showed that the chromatin structure in the promoter region is loosened in expressing but condensed in non-expressing cells. Furthermore, the endogenous E-cadherin promoter is specifically methylated at CpG sites in the undifferentiated cells. We also show that the in vivo properties of the promoter in E-caherin-negative carcinoma cells are similar as in mesenchymal cells, i.e. fibroblasts or sarcoma cells. These data suggest that silencing of the E-cadherin promoter during epithelialmesenchymal transition and tumor progression is due to a loss of factor binding in vivo and to chromatin rearrangement in the regulatory region.

Animals↗
PubMed1993

Transcriptional activation and transformation by chimaeric Fos-estrogen receptor proteins: altered properties as a consequence of gene fusion.

We have generated a series of conditionally active Fos and FosB proteins by fusion with a C-terminal fragment of the human estrogen receptor (ER) which harbours the ligand binding site and the overlapping hormone-inducible transactivation domain TAF-2. The chimaeric Fos-ER proteins showed estrogen-inducible activation of TRE (TPA-responsive element)-directed transcription and hormone-dependent transformation of fibroblasts. These properties of the fusion proteins were independent of the transregulatory and transforming properties of their normal non-fused counterparts c-Fos, v-Fos, FosB-L and FosB-S. Thus c-Fos-ER and FosB-S-ER were strong transforming proteins in the presence of hormone, although c-Fos and FosB-S possess only marginal oncogenic properties. In addition, all fusion proteins showed increased transactivation in the presence of estrogen, again most noticeable in the case of c-Fos-ER and FosB-S-ER. The ER-fusion thus basically eliminated the differences in the transactivating potential seen among the various native Fos proteins. Our data therefore provide evidence: (i) that the hormone binding domain of the human estrogen receptor, apart from delivering hormonal control to a heterologous protein, can have profound effects on the activity of certain transcription factors, particularly on proteins with weak oncogenic and/or transregulatory potential, and (ii) that the transforming potential of c-Fos and FosB-S can be dramatically elevated by increasing their transactivating properties.

3T3 Cells↗
PubMed1991

Non-leucine residues in the leucine repeats of Fos and Jun contribute to the stability and determine the specificity of dimerization.

Various transcription factors, including C/EBP, GCN4 and members of the Fos, Jun and Myc families have been shown to form highly specific complexes via alpha-helical structures referred to as leucine zippers. Experimental evidence has suggested that dimerization involves the formation of hydrophobic bonds between leucine residues in laterally aligned coiled coil structures. However, the specificity of interaction between leucine zipper proteins is not understood. In this study, we show that amino acids, which are located in positions a, e, and g are instrumental in the formation of Fos/Jun heterodimers, presumably by establishing intermolecular electrostatic and hydrophobic interactions. These residues are highly conserved in proteins of the Fos or Jun families but completely different between Fos and Jun, suggesting that these residues determine the specificity of interaction. This conclusion is supported by the observation that the substitution of amino acids in position a or g in Fos with the corresponding Jun amino acids facilitates the association of two Fos leucine repeats. In addition, we show that a conserved histidine residue, located 7 amino acids (i.e., two alpha-helical turns) C-terminally to the 5th leucine in Fos and Jun, is also important for complex formation.

Amino Acid Sequence↗
PubMed1984

[Transscleral magnetic fixation of the retina in complicated retinal detachment. A preliminary report of our experiences].

The authors describe a new technique for transscleral fixation of a detached retina. A small metal pin is brought into contact with the surface of the retina and is held in position by an extraocular magnet. This technique has been used successfully on three patients with giant tears and with large retinotomies as a preparation for silicone oil injection. In comparison with other fixation methods it was found to be relatively easy, and the incidence of trauma was low.

Humans↗
PubMed1978

Technique and results of the colonic conduit, continent by means of a new magnetic stoma seal an experimental study.

On the basis of satisfactory results with a new magnetic stoma seal in colostomy patients this seal, consisting of a magnetic ring and cap, was used in an experimental study to convert the colonic conduit into a continent reservoir. Complete continence was obtained in all of the 12 animals which survived the operation. All rings were well accepted by the tissue when the procedure was staged by implanting the ring transperitoneally several weeks prior to fashioning of the conduit. Residual urine was low, owing to an ideal energy-balance pattern. Coloureteric reflux was successfully prevented in all cases where a long-tunnel-modification of the Leadbetter-Clarke technique was used. Hyperchloraemic acidosis and deterioration in renal function were not observed. All conduits were infected.

Animals↗
PubMed1978

[Technique and results of the colon conduit, continent by means of a new magnetic stoma seal. An animal experiment study. Enterocystoplasty as model of continent urinary diversion. Review and comparison of the results of colocystoplasty, coloprostatoplasty and colourethroplasty (authors transl)].

On the basis of satisfactory results with a new magnetic stoma seal in colostomy patients, this seal, consisting of a magnetic ring and cap, was used in an experimental study to convert the colonic conduit into a continent reservoir. The aim of the study, involving 16 dogs, was to find a method of ring implantation that would avoid infection of the ring and yield complete continence in a higher percentage than had been achieved so far in patients. Complete continence was obtained in all animals but there was a 75% incidence of immediate and delayed infection of the magnetic ring when the ring was inserted transcutaneously. In contrast, all rings were well accepted by the tissue when the procedure was staged with the ring being implanted transperitoneally several weeks prior to fashioning of the conduit. The general problems arising from the colonic conduit when used as continent reservoir are known from the results of colocystoplasty, coloprostatoplasty and colourethroplasty, which are reviewed and compared with our observations. Residual urine was low due to an ideal energy-balance pattern. Coloureteric reflux was successfully prevented in all cases operated on by a long-tunnel modification of the Leadbetter-Clarke technique. Hyperchloremic acidosis and renal function deterioration were not observed. All conduits were infected.

Animals↗
PubMed1975

[Colostomy continence achieved with an implanted circular magnet (author's transl)].

A new method of providing a colostomy continent for faeces and gas is described. It consists of the subcutaneous implantation of a magnetic ring which is led outside through the lumen of the colon and sutured to the skin. The colostomy is closed with a magnetic cover. The procedure has been used in 17 patients with a permanent colostomy after rectal excision and has been highly successful.

Colostomy↗
PubMed1975

The influence of insulin on glucose and fatty acid metabolism in the isolated perfused rat hind quarter.

Glucose and fatty acid metabolism of resting skeletal muscle were studied by perfusion of the isolated rat hind leg with a hemoglobin-free medium. Tissue integrity was demonstrated by normal ATP, ADP and creatine phosphate levels, by a sufficient oxygen supply, and by a normal appearance of perfused muscle specimens under the electron microscope. The rates of glucose and fatty acid uptake, and of lactate, alanine, glycerol and fatty acid release were constant over a perfusion period of 60 min. Insulin (1 unit/l) caused a more than threefold increase in glucose uptake, a stimulation of lactate production, and a 20% increase in the muscular glycogen levels. Fatty acids and alanine release were significantly diminished by insulin, but glycerol release did not change. The uptake of oleate by the rat hind leg was dependent on the medium concentration in a range of 0.7-1.9mM oleate, and was stimulated by insulin. Glucose uptake was not influenced by oleate, whether sodium was present or not. When the leg was perfused with [1-14C]oleate, 75% of the incorporated fatty acids were found in muscle lipids, 10% were oxidized to CO2, and 5% were recovered in bone lipids. The absolute amount of oleate oxidation was not altered by insulin. In all experiments with and without glucose in the medium, 70-80% of the 14C label incorporated into muscle lipids was found in the triglyceride fraction. In the presence of glucose, insulin significantly increased the incorporation of [1-14C]oleate into muscle triglycerides, whereas no insulin effect, either on fatty acid uptake or on triglyceride formation, could be observed when glucose was omitted from the perfusate. The present results indicate that a "glucose-fatty acid cycle" as found in rat heart muscle does not operate in resting peripheral skeletal muscle tissue. They also demonstrate that the stimulating effect of insulin on muscular fatty acid uptake and triglyceride synthesis is dependent on glucose supply. This finding can be intrepreted as a stimulation of fatty acid esterification by sn-glycerol 3-phosphate derived from an increased glucose turnover, which is in turn due to insulin.

Animals↗
PubMed1975

[Continent colostomy through magnetic closure in animal experiments on dogs].

In dog experiments a continent colostomy be means of magnetic occlusion has been developed. Around a terminal anus praeter a silicon-coated ringmagnet was placed between muscular fascia and subcutaneous fascia. The colon was pulled through the lumen of the ring and sutured to the skin. There has been a primary wound healing. There was no leakage of gas and faeces beneath the magnetic cap, thus providing an excellent closure of the colostomy. After removal of the cap spontaneous defecation took place.

Animals↗