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Biomedical subjects

A Schmid

Publications and source records attributed to A Schmid.

At least 145 records · Page 8Linked to original sources
PubMed1996

A method of resolution improvement by the measurement of cell membrane capacitance.

When measuring cell membrane electrical capacitance in whole cell configuration using alternating currents, the resolution decreases with increasing membrane conductance and pipette resistance. Improved resolution was attained by the dual-frequency method which was modified as to control the voltage amplitude of one of the measuring frequencies. A model circuit was developed for the verification of the method. This circuit allows measurement of calibrated capacitance changes even in the range of 5 to 20 fF. Moreover, the method was applied to capacitance measurements on pancreatic exocrine acinar cells. The results of measurements on the model as well as on pancreatic acinar cells are presented. The principle can also be applied to other hardware and software methods for measuring electrical cell membrane parameters.

Animals↗
PubMed1996

[Gastrectomy with radical lymphadenectomy--standard therapy of adenocarcinoma of the stomach].

From January 1992 to December 1995, 208 patients with adenocarcinoma of the stomach were admitted for surgical treatment; total gastrectomy was performed in 152 patients. Improvement of survival rates in comparison to earlier European studies could be obtained by radical resection and routinely performed D2-lymphadenectomy without an increase in morbidity or hospital lethality. The results from Japanese researchers could not be reached.

Adenocarcinoma↗
PubMed1996

[Possibilities and limitations of drugs to protect the liver].

In this paper preventive liver protective agents for the prophylaxis of hepatopathies due to functional stress, and curative protective agents for therapy of existing liver damage are distinguished. Preventive liver protective agents are key substances in the metabolism of proteins, carbohydrates, lipids, and sulfur. For curative liver protective agents, inhibitors of RNA and protein synthesis, calcium antagonists and inhibitors of sulfhydryl (-SH) containing enzymes are proposed and substantiated.

Amino Acids↗
PubMed1995

Characterization of single potassium channels in mouse pancreatic acinar cells.

1. Single K(+)-selective channels with a conductance of about 48 pS (pipette, 145 mM KCl; bath, 140 mM NaCl + 4.7 mM KCl) were recorded in the patch-clamp whole-cell configuration in isolated mouse pancreatic acinar cells. 2. Neither application of the secretagogues acetylcholine (second messenger, inositol 1,4,5-trisphosphate) or secretin (second messenger, cAMP), nor addition of the catalytic subunit of protein kinase A to the pipette solution changed the activity of the 48 pS K+ channel. 3. Intracellular acidification with sodium propionate (20 mM) diminished activity of the 48 pS channel, whereas channel open probability was increased by cytosolic alkalization with 20 mM NH4Cl. 4. BaCl2 (5 mM), TEA (10 mM) or apamin (1 microM) added to the bath solution had no obvious effect on the kinetics of the 48 pS channel. Similarly, glibenclamide and diazoxide failed to influence the channel activity. 5. When extracellular NaCl was replaced by KCl, whole-cell recordings revealed an inwardly rectifying K+ current carried by a 17 pS K+ channel. 6. The inwardly rectifying K+ current was not pH dependent and could largely be blocked by Ba2+ but not by TEA. 7. Since the 48 pS K+ channel is neither Ca2+ nor cAMP regulated, we suggest that this channel could play a role in the maintenance of the negative cell resting potential.

Acetylcholine↗
PubMed1995

Role of sterols in the functional reconstitution of water-soluble mitochondrial porins from different organisms.

Experiments were performed on lipid bilayer membranes with water-soluble mitochondrial porins from different eukaryotic organisms, such as Dictyostelium discoideum, Paramecium, and rat liver, to study the requirements of functional reconstitution of the porins. The water-soluble porins lost their associated lipids and sterols and are unable to form channels in lipid bilayer membranes. We demonstrate that the water-soluble porins regain their channel-forming ability after preincubation of the polypeptides with sterols in the presence of detergents. Mitochondrial porin from Dictyostelium discoideum maintained after this procedure its original properties, in particular the voltage dependence. Water-soluble mitochondrial porins from Paramecium tetraurelia and from rat liver were also activated upon preincubation with different sterols in detergent but showed voltage-dependences that were different from those of detergent-purified porins. Furthermore, the voltage dependence depended on the sterol used for preincubation. Interestingly, the preincubation with sterols can likewise be used to activate detergent-purified mitochondrial porins that may have lost associated sterol during isolation and purification procedures.

Animals↗
PubMed1995

Splice variants of the human EP3 receptor for prostaglandin E2.

The EP3 receptor for prostaglandin E2 (PGE2) mediates various biological activities such as uterine contraction, inhibition of gastric acid secretion, presynaptic inhibition of neurotransmitter release and potentiation of platelet aggregation. In an attempt to understand the molecular basis of this diversity of biological function, we cloned full-length cDNAs encoding EP3 receptors for PGE2 from human uterus cDNA libraries. Seven cDNA variants were identified which code for six distinct EP3-receptor isoforms. Sequencing revealed that the receptor isoforms differ in their intracellular C-terminal domains. Southern blot experiments indicate that the isoforms are generated by alternative splicing. The EP3-receptor gene is expressed in various tissues with high expression in kidney and pancreas, as demonstrated by Northern blot analysis. All receptors, stably expressed in baby hamster kidney (BHK) cells, bind PGE2 specifically with similar Kd of 2.2-5.8 nM. The binding of [3H]PGE2 is competed with by unlabelled prostaglandins in the order sulprostone (a PGE2-like agonist) approximately PGE2 >> PGF2 alpha > Iloprost (a prostacyclin analogue) > PGD2, which is specific for EP3 receptors. Analysis of the signal-transduction pathways demonstrated that all receptors respond with inhibition of forskolin-induced cAMP accumulation with an IC50 of 0.1-3 nM PGE2. In addition, some isoforms induce an increase in intracellular free calcium ([Ca2+]i) at PGE2 concentrations greater than or equal to 10 nM. These results may offer an explanation for the different physiological responses observed in various tissues following activation of EP3 receptors.

Amino Acid Sequence↗
PubMed1995

Conditioned pleasure attenuates the startle response in rats.

The acoustic startle response of rats was found to be attenuated if elicited in the presence of a conditioned stimulus predicting reward. During conditioning, animals received a total of 21 pairings of light with palatable food and sucrose solution, whereas controls received food and sucrose in the absence of light. The amplitude of the acoustic startle response was significantly reduced in the presence of light in conditioned animals, but not in controls. It is assumed that a conditioned response to light is the activation of a central state of pleasure. We therefore suggest that "pleasure-attenuated startle" reflects a mechanism by which a defensive or aversive response is attenuated during a pleasant, hedonic state.

Acoustic Stimulation↗
PubMed1995

Capacitative Ca2+ influx and a Ca2+-dependent nonselective cation pathway are discriminated by genistein in mouse pancreatic acinar cells.

We have investigated the effect of genistein on the hormone-stimulated Ca2+ influx and on a 28pS nonselective cation channel in mouse pancreatic acinar cells using the Ca2+ indicator fluo3 and the patch-clamp technique. The identity of the Ca2+ influx pathway has not been established in this cell type so far. Therefore we have investigated the Ca2+-dependent nonselective cation channel as a potential pathway for Ca2+ influx. Capacitative Ca2+ entry was induced by depletion of intracellular Ca2+ stores with 500nM acetylcholine or with the Ca2+ ATPase inhibitor 2,5di-tert- butylhydroquinone. In the presence of 100microM genistein, Ca2+ release was unimpaired, whereas Ca2+ influx was reversibly suppressed. Patch-clamp experiments demonstrated that genistein had no effect on Ca2+-activated nonselective cation channels, the activity of which was measured in excised membrane patches (inside/out) or in the whole-cell configuration. Therefore we conclude that this 28pS nonselective cation channel does not contribute to Ca2+ influx into mouse exocrine pancreatic cells. With the exception of genistein and tyrphostin 25, other tyrosine kinase inhibitors such as methyl-2,5-dihydroxycinnamate, lavendustin A, herbimycin A, and tyrphostin B56 were without effect on Ca2+ signalling. Thus, the involvement of tyrosine phosphorylation in the activation of the Ca2+ entry mechanism in mouse pancreatic acinar cells is unclear.

Animals↗
PubMed1995

[Nerve-neuroendocrine complexes in stomach mucosa in Zollinger-Ellison syndrome].

Nerve fibre-neuroendocrine cell complexes (NF-NEC-C's) are neuroendocrine cells located in the lamina propria of the gastro-intestinal tract directly connected with nerve fibres of Meissner's plexus. We report on a patient with sporadic Zollinger-Ellison syndrome (ZES) with electron microscopically demonstrated multiple NF-NEC-C's in non-antral gastric mucosa. It is suspected that in ZES the hypergastrinaemia may represent a trophic stimulus for the proliferation of NF-NEC-C's in the gastric mucosa.

Adult↗
PubMed1995

huckebein specifies aspects of CNS precursor identity required for motoneuron axon pathfinding.

huckebein encodes a putative zinc finger protein expressed in a subset of Drosophila CNS precursors, including the NB 4-2/GMC 4-2a/RP2 cell lineage. In huckebein mutant embryos, GMC 4-2a does not express the cell fate marker EVEN-SKIPPED; conversely, huckebein overexpression produces a duplicate EVEN-SKIPPED-positive GMC 4-2a. We use Dil to trace the entire NB 4-2 lineage in wild-type and huckebein mutant embryos. Loss of huckebein does not affect the number, position, or type of neurons in the NB 4-2 lineage; however, all motoneurons show axon pathfinding defects and never terminate at the correct muscle. Thus, huckebein regulates aspects of GMC and neuronal identity required for proper motoneuron axon pathfinding in the NB 4-2 lineage.

Animals↗
PubMed1995

[Autologous bone marrow transplantation in intestinal carcinoma].

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Bone Marrow Transplantation↗
PubMed1995

[Electronic data processing-assisted high dosage therapy with stem cell transplantation at the Donauspital].

Organization of high dose chemotherapy with stem cell transplantation essentially requires EDV-support. "ONCOBASE" has been adapted into the Donauspital network on May 1, 1992. We report about the 2-year clinical experience with ONCOBASE: 1. ONCOBASE effectively supports communication between the ward, ambulance and hospital pharmacy (where all cytostatics are prepared). 2. ONCOBASE provides better surveillance concerning all therapeutic procedures including cytostatic drugs and supportive therapies. 3. ONCOBASE allows the generation of medical letters which include all drugs and supportive therapies delivered. 4. Since ONCOBASE is a database program, all informations concerning the patients are registered. These include cumulative drug doses, information on side effects, blood cell kinetics after previous therapies, kinetics of tumor markers and results of further examinations. 5. ONCOBASE permits rapid data exchange with other hospital networks using the communication data record governed by the "Arbeitskreis für EDV der deutschen Gesellschaft für Hämatoonkologie".

Antineoplastic Agents↗
PubMed1994

Biochemical, molecular, and functional characterization of porin isoforms from potato mitochondria.

The mitochondrial outer membrane of eukaryotic cells contains a voltage-dependent anion channel termed porin. In the organisms studied so far only one type of porin has been identified at the protein level. Here we present a biochemical and molecular genetic analysis of two different porin polypeptides of M(r) 34,000 and 36,000 from the outer membranes of potato mitochondria (termed POM 34 and POM 36, respectively). N-terminal sequencing and the use of labeled oligonucleotide mixtures derived from these amino acid sequences allowed the isolation of cDNA clones encoding the 34- and 36-kDa proteins. They have similar steady state protein levels and share about 75% identical amino acids suggesting that they represent isoforms. In addition, a third cDNA clone coding for a slightly different isoform of the 36-kDa protein was characterized. The polypeptides encoded by the three cDNA clones share the highest degree of sequence identity with mitochondrial porins from fungi and mammals. Tentative models of the secondary structure of the 34- and 36-kDa proteins suggest the occurrence of a 16-stranded beta-barrel typical for bacterial and mitochondrial porins. Purification of the 34-kDa protein by hydroxyapatite chromatography allowed conductance measurements in artificial bilayers. The 34-kDa protein is a voltage-dependent, channel-forming component with single channel conductances of 3.5 and 2.0 nanosiemens in 1 M KCl. In spite of the striking functional similarities to mitochondrial porins from other organisms neither the 34- nor the 36-kDa proteins are able to complement the respiratory defect of a yeast por- mutant.

Amino Acid Sequence↗