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Biomedical subjects

U Quast

Publications and source records attributed to U Quast.

At least 127 records · Page 7Linked to original sources
PubMed1982

Irregular field dose determination with the weighted beam-zone method.

For successful radiotherapy, exact application of a certain dose to the target volume is as necessary as optimal sparing of included or neighbouring organs at risk. A new simple but versatile method for rapid dose determination at relevant reference points in target volumes or shielded organs at risk irradiated with irregularly shaped photon fields has proved suitable for clinical routine. The weighted beam-zone method does not need extensive individual dosimetrical measurements or sophisticated treatment planning systems. All essential influences on the absorbed dose, delivered to a regarded dose reference point can be derived from existing dose measurements in square fields, only. Since this method shows the way to include arbitrarily shaped fields into the principle of equivalent square fields with known dose, dose determination at free or shielded on or off-axis points is reduced to simple counting of dose contributing or non contributing weighted beam-zones. The influence of shielded areas on the dose distribution, according to their extent and distance, can obviously be seen. Instant dose estimation in shielded regions shows the efficiency of sparing organs at risk. The practical experiences allow standardization for typical shapes of target volumes, giving the mean reduction of the effective field size, the relative dose to organs at risk and the correct timing for shielding.

Humans↗
PubMed1982

[Optimization of large-field radiotherapy for lymphogranulomatosis].

In low stages of Hodgkin's disease radiotherapy alone is still considered to be the treatment of choice, as so called mantle fields and so called inverted Y-fields. According to the early onset of chemotherapy in stages I-IIIA radiation technique and radiation dose have to be adapted. With regard to stage, histologic type and adjuvant chemotherapy in Hodgkin's disease risks of radiation therapy are evaluated. Recommendations for modified radiation techniques are given.

Hodgkin Disease↗
PubMed1982

Temperature dependence of the benzodiazepine-receptor interaction.

The temperature dependence of the interaction of three benzodiazepines with their receptors in rat brain membranes containing about 2 microM (endogenous) gamma-aminobutyric acid was investigated. van't Hoff plots of the equilibrium dissociation constants were linear for [3H]diazepam and its N-desmethyl derivative (N-desmethyldiazepam, NDz), whereas for [3H]flunitrazepam a break between two linear portions occurred at about 10 degrees. Binding of diazepam, NDz, and flunitrazepam (for the latter, at temperature greater than 10 degrees) is enthalpy-driven (delta H approximately -40 to -50 kJ/mole with a negligible contribution from delta S. The latter result indicates that the interaction is not a simple hydrophobic association, but that it may be more complex in nature, possibly involving a conformational transition of the receptor-ligand complex. The activation energy for dissociation of the [3H]flunitrazepam- and [3H]diazepam-receptor complexes is about 100 kJ/mole. Consequently, the complexes dissociate about 100 times faster on changing temperature from 0 degrees to 37 degrees.

Animals↗
PubMed1981

[Molecular mechanism of action of benzodiazepines].

Recently, binding sites with high affinity and high specificity for the benzodiazepines have been discovered in mammalian brain. The affinity of the various benzodiazepines for these sites correlates well with the pharmacological potencies of these drugs. It is mainly for this reason that these binding sites are believed to represent the pharmacologically relevant "benzodiazepine receptors". Investigation of the binding of prazepam and metabolites to benzodiazepine receptors in rat brain homogenates reveals that prazepam has only a weak affinity to the receptor(s) with a KD of 1 microM. Its metabolite, descyclopropylmethyl-prazepam (= norprazepam) binds about 100 times more strongly (KD congruent to 15 nM). This shows that norprazepam which is the main pharmacokinetic metabolite (greater than 80% of all metabolites in plasma after oral administration of prazepam) is at the same time the biochemically active substance. Hydroxylation of the 7-membered ring of prazepam or norprazepam in position 3 does not lead to a marked increase in affinity. There is strong electrophysiological and biochemical evidence that the benzodiazepines potentiate GABAergic mechanisms in the CNS (GABA is the major inhibitory transmitter in brain). The molecular events by which the benzodiazepines modulate the GABA system are, however, completely unknown. Also, we do not know whether all pharmacological actions of the benzodiazepines (e.g. anxiolytic action, sedation, muscle relaxation) may be explained by the GABA-hypothesis. The existence of an endogenous substance--which binds to the benzodiazepine receptors--is still open to debate.

Animals↗
PubMed1981

Soybean trypsin inhibitor (Kunitz) is doubleheaded. Kinetics of the interaction of alpha-chymotrypsin with each side.

Further evidence is presented for the formation of a ternary complex between alpha-chymotrypsin (EC 3.4.21.1) and soybean trypsin inhibitor as well as between alpha-chymotrypsin and a performed complex of soybean trypsin and inhibitor (EC 3.4.21.1). This is well in agreement with our earlier sedimentation equilibrium studies. We report on different elution patterns of the ternary forms as compared to the inhibitor trypsin complex and the individual components in gel filtration studies. We also demonstrate the decrease of a given chymotryptic activity on a substrate if the solution is mixed with another one containing the preformed stoichiometric inhibitor-trypsin complex. A fourth piece of evidence for the formation of a chymotrypsin-inhibitor-trypsin complex is the appearance of a difference spectrum in absorbance, when chymotrypsin is mixed with the inhibitor-trypsin complex. Inhibition studies with purified inhibitor show that one molecule of inhibitor binds two molecules of alpha-chymotrypsin, with dissociation constants K1 about 1 microM and K2 about 300 nM at pH 8. The site with weaker affinity for chymotrypsin is specifically blocked by stoichiometric amounts of trypsin. Purification of commercially available preparations of soybean trypsin inhibitor (Kunitz) ("inhibitor") to apparent homogeneity using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and first-order association kinetics with beta-trypsin, is achieved by a combination of gel filtration and ion-exchange chromatography. The kinetics of the interaction of chymotrypsin with inhibitor or with inhibitor-trypsin complex were measured in a stopped-flow photometer by following the displacement of proflavine from the active site of chymotrypsin. A complete reaction scheme is presented with all rates and equilibrium constants as well as their pH-dependence.

Binding Sites↗
PubMed1980

Functional acetylcholine receptor from Torpedo marmorata in planar membranes.

Planar bilayer membranes containing functional acetylcholine receptor were formed from vesicles of Torpedo marmorata electric organ without extracting the acetylcholine receptor from its native environment. Native vesicles were transformed into monolayers which subsequently were apposed into planar bilayers. In the absence of agonists the membrane conductance was similar to that of lipid bilayers. Addition of carbamoylcholine or succinylcholine caused increased membrane conductance and this could be competitively inhibited by d-tubocurarine and suppressed by alpha-bungarotoxin. The amplitude of the conductance response was proportional to the number of alpha-bungarotoxin binding sites in the bilayers. Asymmetric membranes could be formed with the ligand binding sites on only one membrane surface. Desensitization of acetylcholine receptor was evident from equilibrium and kinetic data of the carbamoylcholine-activated conductance. Carbamoylcholine-induced membrane permeability was about 7 times higher for K+ and Na+ ions than for Cl-. At low levels of conductance, single-channel fluctuations of 20-25 pS in conductance and 1.3-msec lifetime were resolved in physiological saline containing carbamoylcholine. The ratio of observed channels to alpha-bungarotoxin sites present showed that a significant fraction of acetylcholine receptor in the membrane was functional. The quantitative aspects of the cation channel, the desensitization, and the ligand binding properties were in close agreement with established values. This transformation of natural acetylcholine receptor vesicles to planar bilayers conserves the essential properties of the in vivo receptor.

Animals↗
PubMed1980

Prekallikrein activator levels and side effects with human albumin preparations.

Recently the question has been raised whether the presence of prekallikrein activator (PKA) in human blood products for i.v. application could possibly cause adverse reactions in the recipient as observed now and then. Up to now a correlation between both properties is far from being established, even though in the U.S. there has been extensive discussion over some PPL batches containing elevated amounts of PKA, presumed to be causally related to an increased frequency of side reactions. As has been demonstrated in the past through wide clinical experience, human albumin is an exceptionally safe blood product. If at all, side effects sometimes seem to occur related to certain individual lots, the reason for which is still unrevealed. In the pursuit of eventually finding some association between PKA levels in and side reactions with albumin, we performed PKA measurements on a panel of commercial human albumin batches, a few of which had been reported occasionally to cause adverse reactions. The assay procedure was essentially that published (3). BOB PKA reference No 1 was included as a standard. PKA was detected in moderate amounts in huge series of albumin batches without any reported side reactions. We conclude, therefore, that PKA levels in the range of trace amounts cannot be related to side reactions with human albumin preparations.

Esterases↗
PubMed1980

Adverse reactions in connection with albumin and other plasma substitutes.

The side effects after the infusion of human albumin solutions, stabilized human serum and a modified gelatin are analysed. Diseases and indications for the application are listed. Intervals between application and side effects as well as frequency and type of symptoms are shown. Different symptoms and intervals allow the conclusion that different pathomechanism are responsible for the adverse reactions. Due to a steady improvement in production and control the number of reported adverse reactions shows a steady decrease.

Cardiovascular Diseases↗
PubMed1980

[Therapy and prognosis of the medulloblastoma: progress through late irradiation techniques (author's transl)].

Thirty patients with histologically established medulloblastoma were postoperatively irradiated at the radiological center in Essen. The patients were divided into two groups. Treatment was nonuniform in the first group consisting of 12 patients irradiated between 1969 and 1973. The second group of 18 patients was treated uniformly as regards the combined neurosurgical and radiological concept, and a new irradiation technique at the 5.7-MeV linear accelerator was employed there. While none of the patients in the first group survived longer than three years, in the second group 12 of 18 patients are in a good general state after a follow-up period between 19 and 60 months.

Adolescent↗
PubMed1980

New complete geometrical rapid-test for radiation therapy equipment.

Daily, weekly and monthly tests of all geometrical performance tolerances for isocentric radiotherapy units can be improved and simplified by a new timesparing comprehensive test procedure. Using a simple auxiliary device, an exact rapid test of isocentre, field-sizes, scales and all optical beam or isocentre indicating instruments is done at the isocentre with only one ready pack film under multiple conditions.

Quality Control↗
PubMed1979

[Side effects of whooping cough inoculation].

During 1970 to 1977 adverse reactions after pertussis vaccination were reported for 149 children, 56% male and 44% female. Their symptoms permitted to divide the vaccinees into 2 groups: one with more severe (S) and the second with other symptoms (0). No differences were observed in age and sex among the two groups. The interval between vaccination and appearance of first symptoms was longer for the 0 than for the S group. While less than one quarter of the reactions in the 0 group occurred after primovaccination, more than half of the S side effects were seen after the first vaccination. Further analysis of the S group revealed, that all but two of their symptoms (fever and encephalopathy) corresponded to the hypoglycaemic syndrome. The consequences hereof are discussed with regard to prevention and therapy.

Child↗
PubMed1979

Ligand-induced changes in membrane-bound acetylcholine receptor observed by ethidium fluorescence. 1. Equilibrium studies.

The interactions between the fluorescent probe ethidium and acetylcholine receptor enriched membranes from Torpedo californica are described. One class of saturable ethidium sites was blocked by alpha-bungarotoxin and therefore reflects direct binding to the receptor (Kd approximately 3 micrometers; stoichiometry--one ethidium site per two alpha-bungarotoxin sites). The second class of sites was nonsaturable and unaffected by alpha-toxin and was therefore considered nonspecific in nature. The increase in fluorescence intensity observed upon addition of cholinergic agonists and antagonists accurately reflects the dissociation constant and stoichiometry of the high-affinity receptor sites for these ligands. The effects of local anaesthetics are complex in nature and depend on the structure of the ligand. For carbamylcholine, the increase in flourescence intensity was due to an increase in the quantum yield of the dye bound to the membrane rather than a dye uptake. In general, ethidium appears not to strongly alter the properties of the membrane-bound acetylcholine receptor and can therefore be profitably used as a spectroscopic probe.

Acetylcholine↗
PubMed1979

Ligand-induced changes in membrane-bound acetylcholine receptor observed by ethidium fluorescence. 2. Stopped-flow studies with agonists and antagonists.

The kinetics of cholinergic ligand binding to membrane-bound acetylcholine receptor from Torpedo californica have been followed in a stopped-flow photometer, by using the fluorescent probe ethidium. The overall reaction amplitude, as a function of ligand concentration, can be fit to the law of mass action for both agonist and antagonists. All agonists show at least biphasic kinetics, and the concentration dependence of the kinetic parameters is fit by a common mechanism involving sequential binding of ligands with increasingly lower affinity. The receptor-ligand precomplexes isomerize to different noninterconvertible final complexes depending on the number of ligands bound. In contrast, the kinetics observed with antagonists cannot be fit to a common model. These kinetics are always much slower than those observed with agonists, and the relaxation rates depend only weakly on antagonist concentration.

Acetylcholine↗
PubMed1979

Ligand-induced changes in membrane-bound acetylcholine receptor observed by ethidium fluorescence. 3. Stopped-flow studies with histrionicotoxin.

Rapid kinetic studies of histrionicotoxin interactions with membrane-bound acetylcholine-receptor showed a conformational change in the receptor-histironicotoxin complex as reflected by a decrease in fluorescence intensity of the extrinsic probe ethidium. The simplest kinetic mechanism consistent with the observed data is one in which a rapid preequiliibrium exists between receptor and toxin (K = 3.33 micrometers), followed by a slow conformational change (k1 congruent to 2 X 10(-2) s-1 and k-1 congruent to 1.5 X 10(-3) s-1). The overall equilibrium constant (Kov) determined from a fit of the amplitude dependence on toxin concentration had a value of 0.25 micrometer. The data preclude kinetic mechanisms where histrionicotoxin acts as an effector, shifting equilibria between preexisting, discrete, and slowly interconverting receptor forms.

Acetylcholine↗
PubMed1979

Proton magnetic resonance studies of cholinergic ligand binding to the acetylcholine receptor in its membrane environment.

Proton magnetic resonance has been used to monitor binding of choline, a known partial agonist, to acetylcholine receptor-enriched membrane preparations from Torpedo californica electroplax. The interaction between choline and receptor led to a broadening of the resonance of the choline methyl groups and this effect was reversed by alpha-bungarotoxin, a quasi-irreversible antagonist of the acetylcholine receptor. From the concentration dependence of line broadening the equilibrium dissociation constant for choline was obtained (Kd = 190 +/- 65 microM). The temperature dependence of the parameters observed in the choline titrations gave an enthalpy of binding delta H less than 1.5 kcal/mol and allowed estimates for the dissociation rate constant of the receptor-choline complex (kdiss greater than 1.6 x 10(3) S(1) and the respective activation energy, Ea (Kdiss) approximately 5.5 kcal/mol. The association of other ligands with the membrane-bound receptor could also be studied by observing effects of varying concentrations of such ligands on the choline methyl group linewidth at a constant choline concentration.

Animals↗