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Biomedical subjects

H Betz

Publications and source records attributed to H Betz.

At least 235 records · Page 13Linked to original sources
PubMed1986

Primary structure of a developmentally regulated nicotinic acetylcholine receptor protein from Drosophila.

Acetylcholine is a major excitatory neurotransmitter in the central nervous system of insects. Using DNA probes of the Torpedo nicotinic acetylcholine receptor (AChR) we have isolated two overlapping cDNA clones encoding a putative neuronal AChR protein from the fruitfly, Drosophila melanogaster. The predicted mature protein consists of 497 amino acids, has a calculated mol. wt of 57 340 and shows extensive homology to known AChR subunits from different species along its entire amino acid sequence. Northern analysis revealed a hybridizing mRNA of 3.2 kb in late embryo and in pupae. Expression of the corresponding AChR gene thus characterizes periods of neuronal differentiation in Drosophila.

Journal Article↗
PubMed1986

The detection of intracranial carotid artery disease by continuous-wave Doppler sonography.

We have investigated 6,587 patients with directional continuous-wave (c-w) Doppler sonography of the carotid arteries during the last 33 months, and have developed criteria for the diagnosis of a significant increase in peripheral resistance of the internal carotid artery in conjunction with 1,671 retrograde brachial and direct carotid angiograms. We distinguished stenoses proximal (15 cases) and distal (4) to the origin of the ophthalmic artery, supraclinoid internal carotid artery occlusions (8), stenoses (2) and acute occlusions (10) of the middle cerebral artery. Stenoses in the carotid siphon (proximal or distal to the origin of the ophthalmic artery) of at least 60% reduction in lumen diameter showed a reduction of the relative end-diastolic flow velocity (modified Pourcelot's index) of more than 40%; additionally, stenoses proximal to the origin of the ophthalmic artery exhibited a variable alternating flow, or flow reversal, in the supratrochlear artery. Stenoses distal to the origin of the ophthalmic artery rarely revealed the theoretically expected increase in orthograde flow velocity in the supratrochlear artery. Stenoses of the middle cerebral artery consisting of more than atherosclerotic irregularities proved to be an exception. Supraclinoid occlusions of the internal carotid artery were reliably demonstrated by Doppler sonography. However, the majority of acute occlusions of the middle cerebral artery could not be detected by this means, probably due to anastomoses between the anterior and the middle cerebral arteries, which were detected by angiography. Thus, we believe that c-w Doppler sonography is a reliable tool to detect stenoses of the carotid siphon of more than 60% reduction in lumen diameter and and supraclinoid carotid artery occlusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗
PubMed1986

[Doppler sonographic diagnosis of basilar stenoses and obliterations].

We have examined 10,162 patients during the past 5 years using directional continuous-wave Doppler sonography of the vertebral arteries. On the basis of 1,989 retrograde brachial angiograms, we have developed sonographic criteria for demonstrating a significant increase in the peripheral resistance of both distal vertebral arteries and/or the basilar artery. All 11 cases of basilar artery stenosis of at least 60% reduction in lumen diameter (as shown by angiography) exhibited an approximately 40% or higher reduction in the sum of the modified Pourcelot indices of both vertebral arteries in comparison with age-matched controls. The 3 stenoses below 60% reduction in lumen diameter were not detected by sonography. Even a good collateral circulation through rete-mirabile anastomoses did not normalize the modified Pourcelot indices. One case of persistent primitive trigeminal artery with thin-calibred vertebral arteries was also detected by sonography. The high percentage of patients with one hypoplastic vertebral artery in the group of basilar artery stenoses indicates an increased risk for atherosclerosis of the basilar and/or the distal vertebral artery in these patients. All 14 angiographically verified occlusions of the basilar artery were detected by sonographic criteria independent of the occlusive localization. Thus, we believe that directional continuous-wave Doppler sonography is a reliable technique for detecting basilar artery stenoses of at least 60% reduction in lumen diameter and basilar artery occlusions.

Aged↗
PubMed1986

[Doppler ultrasonic evaluation of the efficiency of extra-intracranial anastomoses].

We report on the results obtained by means of directional continuous-wave Doppler sonography in 33 patients with superficial temporal-to-middle cerebral artery anastomoses. Recurrent transient ischaemic attacks or a recent mild neurological deficit were considered as justification for bypass surgery in cases of angiographically proven occlusions of one or both internal carotids, severe intracranial carotid artery disease, or stenoses and occlusions of the M-1 segment of the middle cerebral artery. The efficiency of the anastomosis was evaluated by the modified Pourcelot indices (relative end-diastolic flow velocity) of the preauricular superficial temporal artery and of the bypass-supplying branch at the edge of the burr-hole. The influence of intermittent compression of the bypass-supplying branch on the modified Pourcelot index of the ipsilateral common carotid was used as a further criterion for sonographic evaluation. All efficient anastomoses, defined by a modified Pourcelot index of at least 0.20 at the edge of the burr-hole, exhibited an average reduction of 0.08 in the relative end-diastolic flow velocity in the common carotid during compression. In the 18 patients with unilateral occlusion of the internal carotid, bypass surgery was predominantly efficacious (by the above criterion) in those patients who showed a reduction in the sum of the modified Pourcelot indices of the remaining brain-supplying arteries of at least 10% as compared with age-matched controls. The subgroups of existing and absent collaterals through the ophthalmic artery did not show any differences with respect to the percentage of efficient anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Expression of synaptophysin during postnatal development of the mouse brain.

The expression of the synaptic vesicle membrane protein, synaptophysin, was analyzed during postnatal development of the mouse cerebrum using a quantitative immunoblotting procedure. From birth to adulthood, the relative contents of synaptophysin increased 80-fold, reaching a final level of 3.5 micrograms/mg of total protein. The time course of accumulation suggests that synaptophysin expression is correlated with synaptogenesis. Thus synaptophysin may be used as a reliable marker of nerve terminal differentiation.

Animals↗
PubMed1986

Detection of carotid thrombi with indium-111 platelet scintigraphy.

In order to prove that platelet scintigraphy (PSC) is able to detect carotid thrombi formations, we performed PSC in 15 patients directly before or immediately after a percutaneous carotid angiography. PSC was successful in demonstrating iatrogenic fresh carotid thrombi in 13 out of 15 cases. Out of 53 patients with cerebrovascular disease and carotid stenosis a pathologic platelet accumulation was seen in 39 carotid arteries, 31 on the symptomatic side; more often in slight- and middle-sized stenoses than in high degree stenoses. We assume that in these cases PSC detected carotid thrombi which caused arterio-arterial emboli.

Angiography↗
PubMed1986

The glycine receptor deficiency of the mutant mouse spastic: evidence for normal glycine receptor structure and localization.

Homozygotes of the mutant mouse spastic exhibit reduced binding of 3H-strychnine to homogenates from various regions of the CNS compared with unaffected littermates (White and Heller, 1982). Here we report evidence that the spastic mutation coincides with a reduced concentration and an unaltered structure of the glycine receptor in spinal cord. Scatchard analysis of 3H-strychnine binding revealed a single binding site with a Bmax of 267 +/- 62 fmol/mg protein for spastic and of 864 +/- 220 fmol/mg protein for control mice; no difference was found for the corresponding KD values. Also Ki values of glycine for 3H-strychnine binding and displacement of 3H-strychnine by beta-alanine and taurine were indistinguishable for both preparations. Photoaffinity labeling of synaptic membranes with 3H-strychnine identified an Mr = 48,000 polypeptide in both control and spastic mouse membranes. Tryptic digestion of these membranes produced radiolabeled peptide fragments of identical molecular weights, suggesting that the proteolytic cleavage sites around the antagonist binding site are conserved in the mutant glycine receptor protein. Glycine receptors from both control and mutant mice were purified by affinity chromatography on aminostrychnine agarose. SDS/PAGE revealed three polypeptides of Mr = 48,000, 58,000, and 93,000 in both receptor preparations. Monoclonal antibodies directed against different subunits of the glycine receptor were applied to an enzyme-linked immunosorbent assay. The same pattern of immunoreactivity was obtained for glycine receptor from spinal cord of spastic homozygotes, control mice, and rats, suggesting conservation of the antigenic epitopes in the mutant receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1986

The vertebrate glycine receptor protein.

Glycine is a major inhibitory neurotransmitter in the central nervous system. The postsynaptic receptor for this amino acid is a transmembrane ion channel protein which, after affinity purification on an antagonist column, contains three polypeptides of Mr 48,000, 58,000 and 93,000. Biochemical and immunological data show that these polypeptides have different functional properties and topologies with respect to the postsynaptic membrane. A model summarizing the currently available structural data is presented.

Animals↗
PubMed1985

Biochemical characterization of two nicotinic receptors from the optic lobe of the chick.

We have studied putative nicotinic acetylcholine receptors in the optic lobe of the newborn chick, using 125I-labeled alpha-bungarotoxin, a specific blocker of acetylcholine receptors in the neuromuscular junction, and [3H]acetylcholine, a ligand which in the presence of atropine selectively labels binding sites of nicotinic character in rat brain cortex (Schwartz et al., 1982). [3H]Acetylcholine binds reversibly to a single class of high affinity binding sites (KD = 2.2 X 10(-8) M) which occur at a tissue concentration of 5.7 pmol/g. A large fraction (approximately 60%) of these binding sites is solubilized by Triton X-100, sodium cholate, or the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Solubilization increases the affinity for acetylcholine and several nicotinic drugs from 1.5- to 7-fold. The acetylcholine-binding macromolecule resembles the receptor for alpha-bungarotoxin present in the same tissue with respect to subcellular distribution, hydrodynamic properties, lectin binding, and agonist affinity rank order. It differs from the toxin receptor in affinity for nicotinic antagonists, sensitivity to thermal inactivation, and regional distribution. The solubilized [3H]acetylcholine binding activity is separated from the toxin receptor by incubation with agarose-linked acetylcholine, by affinity chromatography on immobilized Naja naja siamensis alpha-toxin, and by precipitation with a monoclonal antibody to chick optic lobe toxin receptor.

Acetylcholine↗
PubMed1985

Purification and characterization of the glycine receptor of pig spinal cord.

A large-scale purification procedure was developed to isolate the glycine receptor of pig spinal cord by affinity chromatography on aminostrychnine agarose. After an overall purification of about 10 000-fold, the glycine receptor preparations contained three major polypeptides of Mr 48 000, 58 000, and 93 000. Photoaffinity labeling with [3H]strychnine showed that the [3H]strychnine binding site is associated with the Mr 48 000 and, to a much lesser extent, the Mr 58 000 polypeptides. [3H]Strychnine binding to the purified receptor exhibited a dissociation constant KD of 13.8 nM and was inhibited by the agonists glycine, taurine, and beta-alanine. Gel filtration and sucrose gradient centrifugation gave a Stokes radius of 7.1 nm and an apparent sedimentation coefficient of 9.6 S. Peptide mapping of the [3H]strychnine-labeled Mr 48 000 polypeptides of purified pig and rat glycine receptor preparations showed that the strychnine binding region of this receptor subunit is highly conserved between these species. Also, three out of six monoclonal antibodies against the glycine receptor of rat spinal cord significantly cross-reacted with their corresponding polypeptides of the pig glycine receptor. These results show that the glycine receptor of pig spinal cord is very similar to the well-characterized rat receptor protein and can be purified in quantities sufficient for protein chemical analysis.

Animals↗
PubMed1985

Doppler sonography in basilar artery occlusion.

We have investigated 6,972 patients with directional continuous-wave Doppler sonography within the last three and a half years, and have derived criteria for the sonographic diagnosis of basilar artery occlusion or tight stenosis in conjunction with 1,071 retrograde brachial angiograms. By sonographic patterns, we have suspected obstruction of the basilar artery or of both distal vertebral arteries in nine cases. Either bilateral sonographic silence or the absence of a diastolic flow component of the vertebral arteries served as criteria in the sonographic evaluation. Angiography of the vertebro-basilar system, performed in eight cases, showed near or complete occlusion in the distal vertebrals or in the proximal basilar artery. Degrees of stenosis less than an 80 percent reduction in lumen diameter could not be detected sonographically. Two further basilar artery occlusions were detected by means of angiography despite negative Doppler sonography: one of these patients showed an extensive collateral circulation between the posterior inferior and the superior cerebellar arteries, and one patient had an occlusion only of the middle and rostral thirds of the basilar artery, the proximal third and the anterior inferior cerebellar arteries being widely patent. Thus, we believe that directional CW Doppler sonography is very useful in the diagnosis of near or complete occlusion of both distal vertebral arteries or of the proximal basilar artery.

Angiography↗
PubMed1985

[Doppler sonography in intracranial circulation disorders of the internal carotid artery. A comparative Doppler sonography-angiography study].

During the past 33 months we have investigated 6,587 patients using directional continuous-wave Doppler sonography of the carotid arteries. On the basis of 1,671 retrograde brachial and direct carotid angiograms we have developed criteria for demonstrating a significant increase in the peripheral resistance of the internal carotid artery. We distinguished stenoses proximal (15 cases) and distal (4) to the origin of the ophthalmic artery, supraclinoid internal carotid artery occlusions (8), stenoses (2) and obliterations (10) of the middle cerebral artery that developed suddenly. Stenoses in the carotid siphon (proximal or distal to the origin of the ophthalmic artery) showed a reduction of more than 40% in the relative end-diastolic flow velocity (modified Pourcelot's index); in addition, stenoses proximal to the origin of the ophthalmic artery exhibited an alternating flow, or flow reversal, in the supratrochlear artery to a variable extent. Stenoses distal to the origin of the ophthalmic artery only rarely revealed the increase in orthograde flow velocity that had been theoretically expected in the supratrochlear artery. Stenoses of the middle cerebral artery exceeding the extent of atherosclerotic irregularities proved to be an exception. Supraclinoid obliterations of the internal carotid artery were reliably demonstrated by Doppler sonography. However, the reliably demonstrated by Doppler sonography. However, the majority of the occlusions of the middle cerebral artery that developed suddenly could not be detected by this means, probably due to anastomoses between the anterior and middle cerebral arteries, which were detected by means of angiography. Thus, we believe that continuous-wave Doppler sonography is a reliable tool for detecting stenoses of the carotid siphon of more than 60% reduction in lumen diameter as well as supraclinoid carotid artery occlusions. Resistance to the cerebral blood flow that is located more peripherally cannot be diagnosed reliably by this method.

Brain Ischemia↗
PubMed1985

Distribution of glycine receptors at central synapses: an immunoelectron microscopy study.

The distribution of receptors for a neurotransmitter was investigated cytochemically for the first time in the central nervous system, at synapses established on cells of the ventral horn of the rat cervical spinal cord. Three monoclonal antibodies (mAb's) raised against glycine receptors were used. Immunofluorescent staining already showed discontinuous labeling at the surface of neurons, and immunoenzymatic electron microscopy further revealed that the antigenic determinants were confined to the postsynaptic membrane and concentrated at the level of the synaptic complex. More specifically, one mAb directed against the receptive subunit of the oligomeric receptor recognized an epitope on the extracellular side of the plasma membrane, whereas two other mAb's bound to the cytoplasmic face. Epitopes for the last two mAb's were more accurately localized with protein A-colloidal gold, using an intermediate rabbit anti-mouse immunoglobulin serum. (a) In addition to the presence of gold particles in areas facing the presynaptic active zone (visualized with ethanolic phosphotungstic acid), the labeling extended beyond this zone for approximately 50-60 nm, which corresponds to the width of one presynaptic dense projection. (b) The distances between the mid membrane and the gold particles were different for the two mAb's (with means of 21.7 +/- 8.5 nm and 29.8 +/- 10.4 nm, respectively). The data suggest that one of the recognized epitopes is close to the plasma membrane, whereas the second protrudes into the cytoplasm. Our results indicate that the receptor is a transmembrane protein which has a restricted spatial distribution on the postsynaptic neuronal surface.

Animals↗
PubMed1985

[Sonographic determination of spinal canal width. Comparison of computed tomography, myelography and conventional roentgen study of the lumbar spine].

Sonographic evaluation of the width of the spinal canal is inferior compared to CT or myelography, concerning accuracy and especially quantity of information received. The advantage of sonography is the lacking of X-ray exposure, the non-invasive procedure and the low cost of apparatus and operational time. For these reasons sonography is favoured as a screening method in detecting spinal canal stenosis in a group whose handicap was largely occupational or sport-related.

Female↗
PubMed1984

Solubilization and characterization of the beta-bungarotoxin-binding protein of chick brain membranes.

The previously characterized ( Rehm , H., and Betz, H. (1982) J. Biol. Chem. 257, 10015-10022) neuronal binding protein for the presynaptic neurotoxin beta-bungarotoxin (beta-BuTx) was solubilized from synaptic membrane fractions of chick brain using the nonionic detergent Triton X-100. 125I-beta-BuTx bound to the solubilized protein with a dissociation constant (KD) of 1.9 +/- 0.1 nM. This binding of 125I-beta-BuTx was Ca2+-dependent and pharmacologically specific. From different basic proteins tested, only unlabeled beta-BuTx and its antagonist dendrotoxin inhibited 125I-beta-BuTx binding. Potassium ions were required during solubilization and binding in order to detect 125I-beta-BuTx-binding activity. Sedimentation in sucrose/H2O and sucrose/D2O gradients and gel exclusion chromatography on Sepharose 6B indicated a s20,w of 12.8 +/- 0.6 S and a Stokes radius of 8.6 +/- 0.2 nm for the solubilized beta-BuTx-binding component. From these data, the protein molecular weight of the beta-BuTx binding site was calculated to be 431,000 +/- 45,000.

Animals↗
PubMed1984

[New developments concerning the neuron cell membrane: advances in the structural analysis of transmembrane ion channels].

Information processing in the brain requires the activation of electrically and chemically gated ion channels in the neuronal plasma membrane. Recently, the function and the molecular composition of some of these membrane proteins have become the subject of extensive biochemical and biophysical analysis. From the currently available data, it is proposed that the architecture of different neuronal ion channels obeys common structural principles which may have resulted from a divergent evolution of a limited number of ancestor transmembrane polypeptides.

Animals↗