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C Franke

Publications and source records attributed to C Franke.

At least 73 records · Page 4Linked to original sources
PubMed1996

Open channel and competitive block of the embryonic form of the nicotinic receptor of mouse myotubes by (+)-tubocurarine.

1. Embryonic-like nicotinic channels were studied in mouse myotubes. Channel currents were measured by patch clamping outside-out excised patches to which pulses of agonists and drugs could be applied by a liquid filament switch. The holding potential of the patches was generally around-10 to-40 mV. 2. Pulses of 100 microM or 1 mM acetylcholine (ACh) elicited average channel currents which reached a maximum open probability of 0.93 within 0.5-1.0 ms, decayed with a time constant of desensitization of 20-80 ms, and fell rapidly to zero at the end of the pulse. When such pulses together with increasing concentrations of (+)-tubocurarine (TC) were applied to outside-out patches, the time constant of current decay, tau, decreased beginning at concentrations of TC added to the test solution of > 10 microM, and the peak amplitude of the current decreased markedly at concentrations of TC of > 30 microM due to an open channel block of nicotinic channels by TC. 3. When the outside-out patches were pre-incubated with TC, the peak current elicited by pulses of 100 microM ACh or 1 mM ACh + TC decreased markedly, beginning with concentrations of TC > 30 nM due to a competitive block. 4. The results could be quantitatively modelled by computer calculations based on a circular reaction scheme containing desensitization. TC blocked the open state as well as the unliganded closed state of the embryonic-like nicotinic receptors of mouse myotubes. Also the blocked open channel was subject to desensitization. 5. The rates of block and unblock of the open channel were 3 x 10(6) M-1 S-1 and 0.8 S-1, respectively, and those of the competitive block were 0.5 x 10(6) M-1 S-1 and 0.1 S-1, respectively (at 20 degrees C).

Acetylcholine↗
PubMed1996

Activation and blockade of mouse muscle nicotinic channels by antibodies directed against the binding site of the acetylcholine receptor.

1. Using the patch-clamp technique, we have found that mouse muscle nicotinic acetylcholine receptor (nAChR) channels can be activated by low concentrations of a monoclonal antibody (MoAb), referred to as WF6, which is directed against the acetylcholine (ACh) binding site. Similar effects were seen using IgG or F(ab)2 fragments from the sera of patients with myasthenia gravis (MG), which contain polyclonal anti-nAChR antibodies. 2. The mean open times of MoAb and the slope conductance of single WF6-activated single channels were similar to those of ACh-activated channels under the same experimental conditions. 3. On outside-out patches, single channel activity was elicited by MoAb WF6 and MG F(ab)2 fragments, and was blocked by (+)-tubocurarine. We therefore concluded that MoAb WF6 and the MG F(ab)2 fragments activate the nAChR. 4. MoAb WF6 and MG F(ab)2 fragments blocked the current activated by pulsed application of 10(-4) M ACh to a significant extent. The block was partly reversible. The rate constants for the binding and dissociation of MoAb WF6 from the receptor were determined quantitatively.

Animals↗
PubMed1996

[Clinical standardization in acute abdominal pain].

The correct diagnosis in acute abdominal pain is necessary for adequate treatment. In several clinical studies it has been shown that, despite improvements in laboratory and technology medicine, errors occur in a considerable proportion of cases due to insufficient history-taking and clinical examination. By the introduction of a standardised and structured history and clinical examination, the diagnostic accuracy can be improved by at least 10%. The aim of this publication is to improve history-taking, clinical examination and diagnostic decision-making by exact definition of all relevant parameters. This was performed by a national clinical expert group, international standardisations were taken in consideration. The standardisation was based mainly on these existing international standardisations (World Organisation of Gastroenterology); however, revisions and corrections were necessary. In order to introduce the standardisation into clinical routine, a documentation form and a documentation program can be provided.

Abdomen, Acute↗
PubMed1996

Kinetics of homomeric GluR6 glutamate receptor channels.

We studied the kinetics of the unedited version of rat GluR6 glutamate (glu) receptor channels, GluR6Q, in outside-out patches using a system for submillisecond solution exchange. Half-maximum activation of the channels was reached with approximately 0.5 microM glu. The maximum slope of the double-logarithmic plot of the peak current versus glu was approximately 1.3, indicating that at least two binding steps are necessary to open the channels. Currents in response to a pulse of 10 microM glu had a short rise time (10-90% of peak current) of approximately 220 microseconds at approximately 20 degrees C. The rise time increased with falling glu concentration, reaching approximately 6.0 ms with 10 microM glu. In the continued presence of glu, the channels desensitized, and this desensitization can be described with a single time constant of approximately 7.0 ms for a pulse of 10 microM glu. The steady-state current in response to a long pulse of 10 microM glu was below 1/280th of the peak current. The time constant of desensitization was found to be independent of concentration between 30.0 and 0.3 microM glu, but to be increased for lower concentrations. After a short pulse of 1 ms duration and 10 or 0.3 microM glu, currents decayed with a time constant of approximately 2.5 ms. Recovery from desensitization after a pulse took approximately 5 s, and the half-time of recovery was approximately 2.2 s. Continuous application of low concentrations of glutamate reduced the peak currents in response to a pulse of 10 microM glu markedly. Fifty percent response reduction was observed in the continuous presence of approximately 0.3 microM glu. Our results for homomeric GluR6 agree with a cyclical reaction scheme developed for completely desensitizing, glu-activated channels on crayfish muscles.

Animals↗
PubMed1996

Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state.

Single channel recordings have shown that ketamine (Ket) decreases the open time of the nicotinic acetylcholine receptor channel (nAChR). The present experiments on simultaneous openings of the nAChRs of mouse myotubes investigate the interaction of Ket with the open as well as with the closed state of the channels. The patch-clamp technique was used to record currents activated by 10(-4) M acetylcholine (ACh) in the outside-out mode. ACh together with increasing concentrations of Ket was applied with a piezo-driven system. In a second protocol, the patches were preexposed to Ket before activation with ACh. With addition of Ket, the currents showed a biexponential decay, indicating an open-channel block. The peak current amplitude decreased reversibly and in a concentration-dependent manner. The rate constants of block (b+1) and of unblock (b-1) were modeled by computer simulation and were found to be: b+1 = 3 x 10(6) M/s, b-1 = 100/s. Preexposure of the patches to Ket revealed an additional block with a KD of approximately 2 x 10(-6) M, which is below clinical concentrations. These data suggest that Ket also interacts with the closed state of the nAChR.

Acetylcholine↗
PubMed1996

Open channel block by physostigmine and procaine in embryonic-like nicotinic receptors of mouse muscle.

Embryonic-like nicotinic channels were studied in mouse myotubes. Channel currents were measured by patch-clamping outside-out excised patches to which pulses of agonists and drugs could be applied by a liquid filament switch. The holding potential of the patches was generally around 40 mV. Pulses of 10(-4) M acetylcholine elicited average channel currents which reached a peak open probability, P(o,peak,) of 0.93 within 0.5 ms and decayed with a time constant of desensitization of 20-80 ms. When physostigmine (10(-5) to 10(-3) M) or procaine (3 x 10(-5) to 10(-3) M) was added to the acetylcholine pulses, a fast decay component of the current appeared which shortened to a time constant of 0.5 ms for the maximal drug concentrations. The fast decay was followed by a slow one which declined in amplitude with increasing concentrations of the drugs. After the end of pulses of 10 M acetylcholine plus 3 x 10(-4) M physostigmine the average current rose again, reaching a peak with approximately 5 ms delay, and then decayed slowly. The amplitude of this recovery current was approximately 0.4 P(o,peak) after 5 ms pulses and decreased with increasing pulse duration due to desensitization. The results can be quantitatively modelled based on a circular reaction scheme involving desensitization. Physostigmine and procaine bind to the open state to cause channel block. Also, the blocked channel was subject to desensitization. The rate constants of block were 6 x 10(6) M(-1) s(-1) for physostigmine and 2 x 10(6) M(-1) s(-1) for procaine, and the rate of unblocking was 200 s(-1) for both blockers (at -40 mV and 20 degrees C).

Animals↗
PubMed1996

[Costs and time savings by dilatation tracheotomy with bronchoscopic control].

Forty-seven patients underwent dilatational tracheostomy with bronchoscopic support. Bronchoscopic support during the procedure prevents perforation of the dorsal wall of the trachea and reveals any bleeding into the trachea. Complications intra- and postoperatively have not been seen as yet (follow-up up to 1 year). Duration of the procedure was 8 min versus 30 min for the conventional tracheostomy (mean values).

Bronchoscopy↗
PubMed1995

Electrophysiological characterization of nicotinic receptors of aneurally grown human myotubes.

It seems necessary to characterize electrophysiological properties of human nicotinic acetylcholine receptors (nAChR) to obtain reference values for the study of diseased muscles. We therefore investigated nAChRs in aneurally grown human myotubes using the patch-clamp technique. Pulses of acetylcholine (ACh) were applied to outside-out patches with a fast application system. The peak and the rise time of the current elicited by pulses of various concentrations of ACh were evaluated. The results were interpreted using the circular reaction scheme developed recently for the nAChR of embryonic mouse muscle. In addition, the burst duration and the slope conductance of the ACh activated channel were evaluated.

Acetylcholine↗
PubMed1995

GABAergic inhibition of crayfish deep extensor abdominal muscle exhibits a steep dose-response relationship and a high degree of cooperativity.

A patch-clamp study was done to characterize the recently found GABAergic (i.e. gamma-aminobutyric acid) inhibitory synaptic channels of crayfish deep extensor abdominal muscle. Outside-out patches were rapidly activated by GABA to measure the dose/response curves for the open probability of the channels, Po, and the rise time, tr, (time from Po = 0.1 to Po = 0.9). In some of the patches the GABA-activated currents decayed due to desensitization and such patches were not studied further. Rare channel openings were elicited with 0.1 mM GABA. The Po at this low concentration of GABA was 0.0005 to 0.01. Application of 10 mM GABA was necessary to reach the maximal Po of 0.9. The slope of the dose/response relationship in the double logarithmic plot was 5.4 +/- 1.1 (mean +/- SD; n = 9) between 0.1 mM and 0.2 mM GABA. The plot of tr versus GABA concentration had a peculiar shape, recently found to be characteristic for positive cooperativity of the binding sites. tr increased from a minimum at 10 mM GABA with declining concentrations of GABA and reached a peak at 0.4 mM GABA. Below 0.4 mM GABA, tr decreased again. With 0.2 mM GABA tr was 0.40 +/- 0.1 (mean +/- SD; n = 4) of the peak value measured at 0.4 mM GABA. Simulations were compared with the experimental results and a linear reaction scheme with five binding sites for GABA was established to describe the dose/response curves for Po and tr.

Abdominal Muscles↗
PubMed1995

Extraction of mono- and dicarboxylic acids from a curative water.

A method for the analysis of mono- and dicarboxylic acids from water is presented. For this purpose two techniques, a C(18) solid phase extraction (SPE) and a combination method of liquid-liquid extraction (LLE) and aminopropyl SPE, were tested. With the combination method all analytes, short-chain mono- and long-chain dicarboxylic acids, could be analysed in one approach. The C(18) SPE was not suitable for short-chain mono- but for dicarboxylic acids. Concentrations in the investigated water ranged from 315 mg/l (butanoic acid) to 2.9 mg/l (octanoic acid). Dicarboxylic acids were found from 5 mg/l (octanedioic acid) to 0.5 mg/l (dodecanedioic acid).

Journal Article↗
PubMed1995

[Enflurane blocks ion current through the nicotinic acetylcholine receptor].

AIM: The study investigates the influence of enflurane (EN) on macroscopic currents of the nicotinic acetylcholinergic receptor channel (nAChR). This ion channel is a representative member of the superfamily of ligand-gated receptor channels and is better characterized than all the other receptors in respect of structure and function. METHODS: For the experiments the patch-clamp technique was used to study the embryonic type of the nAChR expressed by cultured mouse-myotubes. Patch-clamp recordings were performed in the outside-out-mode from these preparations. To match the rapid desensitization kinetics of ligand-activated ion channels, a liquid filament switch technique was used for the application of agonists to the excised patches. This technique allows for change of solution within 300 microseconds. We used a saturating concentration of 10(-4) M acetylcholine (ACh), activating almost all available ion channels on a patch. Pulses of 10(-4) M ACh together with EN in different concentrations were applied repetitively. RESULTS: The current elicited by 10(-4) M ACh is reduced reversibly in a concentration-dependent manner by EN in clinically relevant concentrations: 1,44 x 10(-5) M EN inhibit about 10%, 1.44 x 10(-4) M 25%, 1.44 x 10(-3) M 35%, and 1.44 x 10(-2) M 75% of the ion flux (averaged results from 48 patches). EN decreases the time constant of the current decay. This acceleration of desensitisation kinetics is partly reversible if followed by application of 10(-4) M ACh. CONCLUSION: In this study we were able to show that EN reduces the currents of the ligand-gated embryonic-like nAChR in clinically relevant concentrations. Volatile anaesthetics are known to influence GABAA-, glutamate-, and glycine- activated receptors, which are members of the same family of ligand-gated receptor-channel units. Thus, the action of volatile anaesthetics on ligand-gated receptors may play a role in the mechanism of general anaesthesia. The interaction of volatile anaesthetics with nondepolarising neuromuscular blockers may also be based on this effect at the neuromuscular junction.

Acetylcholine↗
PubMed1995

[Improved technique of dilatation tracheostomy and initial results].

Percutaneous dilatational tracheostomy is a simple bedside procedure and can be performed with a minimum of time and staff. Tears in the posterior wall of the trachea and paratracheal displacement of the tube are possible complications. These complications can be avoided by performing the procedure under bronchoscopic control. We report on 14 dilatational tracheostomies using this new technique. As a severe complication we noted bleeding from a vein with lethal blood aspiration in one case. Bleeding during dilatational tracheostomy procedure requires changing of technique and dissection of the anterior wall of the trachea.

Bronchoscopes↗
PubMed1995

Chorismate mutase and 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase of the methylotrophic actinomycete Amycolatopsis methanolica.

Chorismate mutase (CM) and 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (DS) are key regulatory enzymes in L-Phe and L-Tyr biosynthesis in Amycolatopsis methanolica. At least two CM proteins, CMIa and CMIb, are required for the single chorismate mutase activity in the wild type. Component CMIa (a homodimeric protein with 16-kDa subunits) was purified to homogeneity (2,717-fold) and kinetically characterized. The partially purified CMIb preparation obtained also contained the single DS (DSI) activity detectable in the wild type. The activities of CMIa and CMIb were inhibited by both L-Phe and L-Tyr. DSI activity was inhibited by L-Trp, L-Phe, and L-Tyr. A leaky L-Phe-requiring auxotroph, mutant strain GH141, grown under L-Phe limitation, possessed additional DS (DSII) and CM (CMII) activities. Synthesis of both CMII and DSII was repressed by L-Phe. An ortho-DL-fluorophenylalanine-resistant mutant of the wild type (strain oFPHE83) that had lost the sensitivity of DSII and CMII synthesis to L-Phe repression was isolated. DSII was partially purified (a 42-kDa protein); its activity was strongly inhibited by L-Tyr. CMII was purified to homogeneity (93.6 fold) and characterized as a homodimeric protein with 16-kDa subunits, completely insensitive to feedback inhibition by L-Phe and L-Tyr. The activity of CMII was activated by CMIb; the activity of CMII plus CMIb was again inhibited by L-Phe and L-Tyr. A tightly blocked L-Phe- plus L-Tyr-requiring derivative of mutant strain GH141, GH141-19, that had lost both CMIa and CMII activities was isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Deoxy-7-Phosphoheptulonate Synthase↗
PubMed1995

Diagnostic scores for acute appendicitis. Abdominal Pain Study Group.

OBJECTIVE: To assess the value of predictive scores in the diagnosis of acute appendicitis. DESIGN: Multicentre evaluation with a prospective database. SUBJECTS: 1254 patients with acute abdominal pain. SETTING: 6 departments of surgery, Germany. INTERVENTIONS: To measure the performance of 10 scores on one database using standardised criteria and to compare the results with published data. MAIN OUTCOME MEASURES: The ability of a score to fulfill standardised criteria: an initial negative appendicectomy rate of 15% or less, a potential perforation rate of 35% or less, an initial missed perforation rate of 15% or less, and a missed appendicitis rate of 5% or less. RESULTS: Reevaluation of the published data showed that the Alvarado score fulfilled all four criteria and the Lindberg, the Fenyö and the Christian scores fulfilled two criteria each. If applied to our database (acute abdominal pain, suspected appendicitis), none of the scores fulfilled any of the given criteria, even if the cut-off point was varied systematically. There were significant differences among the scores. CONCLUSIONS: The original published data seemed to comply with our standardised criteria but evaluation of the scores on our database resulted in poor performances for all of them. Published data seem to be optimistically biased whereas our evaluation gives more realistic estimates of the routine performance in different clinical environments. Further well designed large scale trials are needed to investigate the clinical benefit of diagnostic scoring in acute appendicitis.

Abdominal Pain↗
PubMed1995

[Diagnostic score for acute appendicitis].

Scoring systems seem to be ideal for supporting diagnosis of acute appendicitis because they are non invasive, require no special equipment and can be used in clinical routine. Several scores for appendicitis have been developed with good results in the original publications. Unfortunately these good results could not be reproduced on a German data base. Therefore we developed a new score using multivariate statistics and a quality controlled prospective data base. The score covers 8 variables: tenderness, rebound tenderness, micturition, type of pain, leucocytes, age, relocation of pain, rigidity. Independent evaluation of the score on a Dutch database resulted in a negative appendicectomy rate of 21% and a missing appendicitis rate of 2%. The results are encouraging, so that further testing and clinical application can be recommended.

Acute Disease↗
PubMed1994

The coexistence of embryonic and adult acetylcholine receptors in sarcolemma of mdx dystrophic mouse muscle: an effect of regeneration or muscular dystrophy?

In the sarcolemma of innervated dystrophic mdx mouse muscle we found the embryonic and the adult nicotinic acetylcholine receptor, where normally after innervation only the adult type would be expected, as can be shown with comparative data from patch-clamp experiments from wildtype and wildtype-denervated muscle. As a control to the dystrophic muscle we investigated wildtype bupivacaine-treated regenerating muscle and found both receptor types there, too. Therefore we conclude that the expression of the embryonic nicotinic acetylcholine receptor in the dystrophic muscle is not a characteristic of dystrophy but a consequence of muscle regeneration.

Animals↗