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Biomedical subjects

C Franke

Publications and source records attributed to C Franke.

At least 91 records · Page 5Linked to original sources
PubMed1994

A patch-clamp study on a novel gamma-aminobutyric acid activated chloride channel of crayfish deep extensor abdominal muscle.

The patch-clamp technique was used to study the effect of rapid pulses of gamma-aminobutyric acid (GABA) on excised membrane-patches in the outside-out configuration of the deep extensor abdominal muscle (DEAM) of crayfish. Channel currents reversed at the equilibrium potential of Cl- and were blocked by picrotoxin. Rare channel openings were elicited by 0.1 mM GABA, and a saturating open probability of 0.9 was reached with 10 nM GABA. The investigated channel was only sensitive to GABA and is different from a previously described GABAergic channel in crayfish that is in addition sensitive to acetylcholine and glutamate and shows three subconductance states.

Abdominal Muscles↗
PubMed1994

Block of nicotinic acetylcholine-activated channels of cultured mouse myotubes by isoflurane.

It is well known that volatile anesthetics cause muscle relaxation. A block of nicotinic acetylcholine-activated receptors (nAChRs) in staedy state by isoflurane was recently reported. Pulses of acetylcholine (ACh) were applied to outside-out patches from mouse myotubes using a system for ultra-fast solution exchange allowing the study of the block of nAChRs by isoflurane under conditions similar to the situation during synaptic transmission. Isoflurane in concentrations used during general anesthesia blocked approximately 50% of the receptors within 0.5 ms after application. The block of nAChRs could be partially relieved by application of high concentrations of ACh. Therefore, muscle relaxation and the reduction of the amplitude of postsynaptic currents by isoflurane may be caused by the block of nAChRs reported here.

Acetylcholine↗
PubMed1994

Botulinum toxin converts muscle acetylcholine receptors from adult to embryonic type.

To assess the postsynaptic consequences of botulinum toxin injection into muscle we characterized the nicotinic acetylcholine receptor (nAChR) with the patch clamp technique, using adult mouse muscle after destruction of the nerve ending and after treatment with botulinum toxin (BoTX). In both, embryonic channels with a conductance of 30 and 34 pS could be identified, whereas on adult control muscle nAChR channels had a conductance of 48 pS. The mean open times were 1.2 ms for the channels in control, 2.5 ms in denervated and 2.4 ms in BoTX-treated muscle. The dose-response curves of the maximal acetylcholine-elicited currents showed a Km of 60 mumol/L for denervated, 70 mumol/L for BoTX-treated, and 100 mumol/L for control muscle. Destruction of the nerve ending and inhibition of acetylcholine release by BoTX has the same effect as far as the increase of sensitivity of the muscle to acetylcholine is concerned. In contrast to single-fiber EMG findings in patients treated for focal dystonia no distant changes could be found in the control muscle of the BoTX-treated animals.

Animals↗
PubMed1994

The European Stroke Scale.

BACKGROUND AND PURPOSE: For detecting therapeutic effect and matching of treatment groups in stroke trials, a scale that meets the clinimetric criteria is of the utmost importance. METHODS: The European Stroke Scale consists of 14 items selected for their specificity and their prognostic value. It is designed for patients with middle cerebral artery stroke. Interrater reliability, internal consistency, and time for completion were investigated in 74 patients. Intrarater reliability was studied in 38 patients. To establish concurrent validity, two trials were performed in 20 and 44 patients. The scale was correlated with the MCA Neurological Scale, the Canadian Stroke Scale, the Scandinavian Stroke Scale, the Barthel Index, and the Rankin Scale. Correlations were calculated by means of Spearman's correlation coefficient. The trial in 44 patients also investigated the prognostic validity of the scale for 1-month and 8-month neurological, functional, and handicap status. These data were analyzed by linear regression. RESULTS: Interrater (kappa value range, 0.62 to 0.85) and intrarater (kappa value range, 0.65 to 1.00) reliability for each item was good, and internal consistency was excellent (Cronbach's alpha coefficient, 0.92). Mean time for completion was 8.2 minutes (range, 4 to 14 minutes). Correlations of the European Stroke Scale with other neurological scales ranged from 0.93 to 0.95. The correlation with the Barthel Index and the Rankin Scale was 0.84 and -0.86. The R2 values for prognostic validity ranged from 0.45 to 0.81 (P < or = .0001). CONCLUSIONS: The European Stroke Scale has been developed according to the clinimetric criteria.

Adult↗
PubMed1993

Reaction scheme for the glutamate-ergic, quisqualate type, completely desensitizing channels on crayfish muscle.

In analogy with a recently developed reaction scheme for a channel activated by acetylcholine (ACh; nicotinic), we propose a cyclical reaction scheme which agrees with all data published on the completely desensitizing channel type activated by glutamate (Glu) in crayfish muscle. For every high Glu concentrations, desensitization is mainly from the open state, while at lower Glu concentrations desensitization from the singly Glu liganded closed state contributes significantly. The latter pathway and the high Glu affinity of the desensitized channel states account for complete steady-state desensitization of the channel by Glu concentrations which occur without any channel opening.

Animals↗
PubMed1993

Desensitization of embryonic nicotinic acetylcholine receptors expressed in Xenopus oocytes.

Xenopus oocytes where injected with mRNA coding for the embryonic type of the bovine nicotinic acetylcholine receptor (nAChR). Pulses of acetylcholine (ACh) were applied to outside-out patches of the injected oocytes with the liquid filament switch. With high concentrations of ACh (10(-3) M), the ACh response desensitized rapidly; the decay could be fitted with a single exponential with a time constant of about 50 ms. In double pulse experiments, recovery from desensitization was tested. Complete recovery was observed after 5 s. The affinity of ACh to the desensitized receptor was measured by preincubating the outside-out patch with different concentrations of ACh. Preincubation with 10(-6) M ACh led to complete desensitization of the nAChRs on the patch. The results can be fitted with the molecular scheme describing activation and desensitization of the nAChR which was developed recently for embryonic nAChRs of mouse muscle.

Acetylcholine↗
PubMed1993

A molecular scheme for the reaction between acetylcholine and nicotinic channels.

In outside-out patches of mouse-muscle membrane, embryonic-like channels were activated by pulses of acetylcholine (ACh). On increasing the ACh concentration, the rate of desensitization, 1/tau d, increased linearly with the peak open probability, indicating desensitization from the open state. Desensitization had only one time constant tau d at each ACh concentration. Recovery from desensitization was only approximately 10 times slower than desensitization, whereas the probability of steady-state channel opening, declined to < 0.01 with > 10(-6) M ACh. The peak probability of opening in > 10(-4) M ACh pulse was close to 1. A linear reaction scheme was not compatible with these results. The scheme had to be expanded resulting in a circular scheme with two additional ACh binding steps to desensitized channel states. The approximate rate constants of all reaction steps in the circular scheme could be determined using computer simulations. The model predicted that clusters of channel opening had the average duration tau d at the respective ACh concentration. In cell-attached patches on intact muscle fibers, similar average cluster durations were observed at the respective ACh concentration. This indicates that tau d in the intact muscle fibers has similar values as in outside-out patches.

Acetylcholine↗
PubMed1993

Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.

1. Three families with a form of myotonia (muscle stiffness due to membrane hyperexcitability) clinically distinct from previously classified myotonias were examined. The severity of the disease greatly differed among the families. 2. Three dominant point mutations were discovered at the same nucleotide position of the SCN4A gene encoding the adult skeletal muscle Na+ channel alpha-subunit. They predict the substitution of either glutamic acid, valine or alanine for glycine1306, a highly conserved residue within the supposed inactivation gate. Additional SCN4A mutations were excluded. 3. Electrophysiological studies were performed on biopsied muscle specimens obtained for each mutation. Patch clamp recordings on sarcolemmal blebs revealed an increase in the time constant of fast Na+ channel inactivation, tau h, and in late channel openings as compared to normal controls. tau h was increased from 1.2 to 1.6-2.1 ms and the average late currents from 0.4 to 1-6% of the peak early current. 4. Intracellular recordings on resealed fibre segments revealed an abnormal tetrodotoxin-sensitive steady-state inward current, and repetitive action potentials. Since K+ and Cl- conductances were normal, only the increase in the number of non-inactivating Na+ channels has to be responsible for the membrane hyperexcitability. 5. Length, ramification and charge of the side-chains of the substitutions correlated well with the Na+ channel dysfunction and the severity of myotonia, with alanine as the most benign and glutamic acid as the substitution with a major steric effect. 6. Our electrophysiological and molecular genetic studies strongly suggest that these Na+ channel mutations cause myotonia. The naturally occurring mutants allowed us to gain further insight into the mechanism of Na+ channel inactivation.

Action Potentials↗
PubMed1992

Recovery from the rapid desensitization of nicotinic acetylcholine receptor channels on mouse muscle.

Pulses of acetylcholine (ACh) applied to outside-out patches of embryonic-like muscle membrane elicited channel currents which declined rapidly (tau d = 10-60 ms) due to desensitization. Recovery from desensitization was determined by pulse pairs, varying the pulse interval. When the pulse interval was about 300 ms, the response to the second pulse was about half that to the first pulse, i.e. about half of the channels had recovered from desensitization. The results are discussed in the frame of a cyclic reaction scheme. If this scheme includes high affinity binding of ACh to desensitized receptors, it can also explain the finding that low ACh concentrations (less than or equal to 1 microM) largely desensitize the receptors, but elicit very little channel opening.

Acetylcholine↗
PubMed1992

Acetylcholine activates two types of ion channels in sarcolemma from adult muscular dystrophic (mdx) mice.

Dissociated interosseus muscle fibres of wildtype and mdx mice were investigated to characterize acetylcholine (ACh) receptors with the single channel recording patch-clamp technique. On the muscle fibres of mdx mutants, two types of nicotinic acetylcholine receptor (nAChR) channels were found. One channel (29 pS, mean open time 2.1 ms) resembles channels on denervated and embryonic muscle and was not found on wildtype muscle where exclusively a 48 pS channel (mean open time 1.3 ms) was seen.

Acetylcholine↗
PubMed1992

Patch-clamp recordings of spiking and nonspiking interneurons from rabbit olfactory bulb slices: membrane properties and ionic currents.

Physiological and morphological properties of rabbit, Oryctolagus cuniculus, olfactory bulb interneurons were characterized by using a thin slice preparation in combination with patch-clamp measurements and Lucifer Yellow fills. Two types of interneurons, periglomerular (PG) and juxtaglomerular (JG) cells, were unequivocally distinguished in the glomerular layer. Their properties were compared to those of mitral cells. PG cells closely resembled previously described periglomerular cells in their morphology. During current clamp recording these neurons were characterized by their lack of action potentials upon depolarization. Consistent with these results no Na+ currents could be elicited in voltage clamp experiments. Two types of outward K+ currents were distinguished: one which inactivated and one which did not. From their morphology JG cells appear to be either short axon cells or external tufted cells. JG cells always responded with a single, TTX-blockable action potential in response to maintained current injection. Two types of membrane currents were identified in JG cells during voltage clamp: a fast, inactivating Na+ current that was fully activated at -80 mV, and a sustained outward current that shared some properties with a delayed rectifier K+ current. The particular relationship between the voltage dependence of the Na+ and K+ currents appeared to preclude repetitive spike activity.

Action Potentials↗
PubMed1992

Patch-clamp recordings of spiking and nonspiking interneurons from rabbit olfactory bulb slices: GABA- and other transmitter receptors.

Transmitter receptor ion channels from previously identified rabbit olfactory bulb neurons were studied by using a thin slice preparation in combination with patch-clamp measurements. PG cells, which closely resembled previously described periglomerular interneurons in their morphology, responded to microapplication of GABA, acetylcholine, norepinephrine and glycine with the activation of distinct ionic currents. JG cells, which belong either to the class of short axon cells or external tufted cells, never showed GABA responses. In mitral cells ionic currents activated by GABA, acetylcholine, norepinephrine and glutamate could be elicited. Further measurements of GABA-activated currents of PG cells were made and indicated that these cells expressed two different types of GABA receptors: one which showed fast desensitization with a decay time constant of about 5 s, and one which slowly desensitized with a decay time constant of about 20-30 s. Both types were completely inhibited by bicuculline methiodide (50 microM). GABA receptors were not blocked by Zn2+ (0.1 mM). From the dose-response relationship of the peak GABA-activated currents, an apparent dissociation constant of 50 microM was derived. From single channel measurements in excised outside-out patches, a single channel conductance of GABA-activated Cl- currents of 24 pS was obtained during continuous application of the agonist. Single channel events had a mean open time of 1.9 ms.

Animals↗
PubMed1992

[Laparoscopic laser cholecystectomy].

In an ex vivo- and an animal study a Holmium-YAG laser, a Nd:YAG laser and a CO2 laser were examined. For laparoscopic cholecystectomy the pulsed Holmium:YAG laser proved to be the best instrument. Dissecting and haemostatic effects were connected when working with a power of 4 watts. Dissected area per minute was 112 mm2, gallbladder dissection (15 cm2) can be performed in 13 min. In the animal study the cholecystectomy lasted 30 min on average when the Holmium:YAG laser was used. Bleeding was not observed, development of smoke was tolerable.

Cholecystectomy, Laparoscopic↗
PubMed1992

Activation and desensitization of embryonic-like receptor channels in mouse muscle by acetylcholine concentration steps.

1. Pulses of acetylcholine (ACh) in concentrations between 0.1 and 1000 microM were applied repetitively to outside-out patches of enzymatically denervated (14 days) mouse muscle with the liquid filament switch. Solutions superfusing the patch could be changed rapidly (within 0.2 ms). 2. Single-channel activity was studied under steady-state conditions in the outside-out and in the cell-attached mode. The single-channel conductance was 26 pS in outside-out patches, characteristic for embryonic-like channels. Apparent mean open time was about 2.5 ms, a shorter component of closed times was 800 microseconds and burst length was about 5 ms. 3. Channel currents elicited by pulses of ACh were averaged. The time-to-peak current was concentration dependent and decreased from a level of about 10 ms below 10 microM to about 400 microseconds at 100 microM-ACh. 4. For a typical experiment, the average peak current, imax, increased from -0.4 pA with 0.1 microM to -82 pA with 1000 microM-ACh, close to the value at saturation. The half-maximal response was at 60 microM-ACh. The dose-response curves for imax had double-logarithmic slopes of 1.1-1.3, consistent with two binding sites at the embryonic nicotinic acetylcholine receptor (nAChR). 5. The current elicited by ACh pulses decreased rapidly after the peak. The time constant of desensitization increased from 20-50 ms with 1000 microM-ACh to up to more than a second with 1 microM-ACh. 6. The current in steady state (fully desensitized) increased up to 10 microM-ACh, but decreased slightly to values of imax/100 to imax/500 when higher concentrations were applied. 7. In addition to the well-known differences between adult and embryonic nAChR concerning the apparent mean open time and burst length, we found differences in the slope of the dose-response curve for imax, in the ratio of peak to steady-state response, and in the rise time of the response.

Acetylcholine↗
PubMed1992

[Immunoscintigraphy using 111In-antimyosin-antibodies in the clinical diagnosis of myocarditis].

Thirty patients suspected of having acute myocarditis underwent examination with 111In-labeled antimyosin antibodies. The heart/lung ratio was used for scintigraphic evaluation, with a value of > 1.5 being regarded as positive. The values were correlated with a score based on typical clinical parameters, separating myocarditis into categories "unlikely", "possible" and "highly probable". There was complete correlation in the category "myocarditis highly probable"--with a heart/lung ratio > 1.5 (11 patients)--and in the category of "myocarditis unlikely"--with a heart/lung ratio of < or = 1.5 (5 patients). The category "myocarditis possible" included 2 cases with a scintigraphic vote for the presence of myocarditis and 12 cases against. Immunoscintigraphy with antimyosin antibodies has shown itself to be a valuable non-invasive tool in the investigation of suspected myocarditis.

Acute Disease↗
PubMed1992

[Long-term results of treatment of supra-condylar humerus fractures in children].

From 1982 to 1986, a total of 106 children with supracondylar fractures of the humerus were treated at the trauma surgery clinic in Braunschweig. Undisplaced or slightly displaced fractures were treated with plaster casts. More severely displaced fractures were initially treated by closed reduction under general anesthesia and percutaneous Kirschner wiring. In 72 cases (= 85.7%) a follow-up examination revealed a very good or good result. In 9 cases (= 10.7%) satisfactory results were found and in 3 cases (= 3.6%) unsatisfactory results. The most common complication prejudicing the result was cubitus varus. It was found in 27 cases (= 32.1%), most often with a varus under 10 degrees (19 of the 27 cases). A retrospective study of the 12 cases in which the results were classified as satisfactory or unsatisfactory showed 8 insufficient reductions in fractures with severe instability.

Adolescent↗
PubMed1991

[Effect of alfa-2b interferon on prognostic parameters and clinical events in HIV positive patients in the LAS/ARC stage].

A number of in vivo and in vitro results suggest that interferons have an antiretroviral effect on HIV. To check this, 15 HIV-positive patients who had no full-blown AIDS, were treated with recombinant interferon alpha 2b (5 mill. IU s. c. three times a week) over a period of six months. Twelve to 16 weeks after the initiation of treatment, an increase in CD 4 lymphocytes (+16%), NK cells (+16%), lymphocytes stimulation by con A (+ 176%), neopterin (+66%), and beta-2-microglobulin (+19%) was observed. By the end of the study, all these parameters had slightly decreased again. In all patients with CD4 lymphocytes greater than 0.2 c/nl, we observed a decrease in p24 antigen levels, but in patients with CD4 lymphocytes less than 0.2 c/nl, an increase. It would thus seem that any antiretroviral effect of IFN (as shown by the p24 antigen parameter) is more pronounced in patients with superior immune parameters.

AIDS-Related Complex↗