[Side-effects of factor VIII substitution in patients with hemophilia A (author's transl)].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Reuter.
Explore the source record for details and available documents.
Adrenergic beta receptors are located on the heart cell surface membrane and can be identified directly by ligand-binding studies in intact cells. The maximal specific binding capacity of a labeled beta-adrenergic antagonist, [3H]-CGP, corresponds to about 6000 receptors per cell. Binding of adrenergic agonist results in changes in the membrane ion permeability for Ca which appears to involve an increase in the cAMP content of cardiac cells. Studies employing tracer methods and electrophysiological techniques suggest that the number of functional Ca channels in myocardium is regulated by beta-adrenergic receptors through the involvement of cAMP-mediated phosphorylation.
We have used primary cultures of hearts from newborn rats to study beta-adrenoceptor properties in living myocardial cells. Receptors were labelled with the lipophilic antagonists 3H-(+/-)-carazolol and 125I-(+/-)-cyanopindolol (CYP) or with the hydrophilic antagonist 3H-(+/-)-CGP 12177. Under equilibrium conditions all ligands bound to a saturable homogeneous class of specific sites with a maximal binding capacity of approximately 100 fmol/mg protein (corresponding to approximately 5000 sites/cell). After 90-180 min preincubation of intact cells with 3H-carazolol or 3H-CGP 12177 only 80% of these antagonists could be displaced from specific binding sites by competing ligands. In the simultaneous presence of the antagonist (-) timolol 100% of specifically bound radiolabelled ligand remained displaceable. In competitive displacement experiments the radioligands did not affect the apparent affinity of the displacing nonlabelled antagonists timolol and CGP 12177, but agonist affinity was markedly changed. The apparent KD values for (-)-isoprenaline were 1560 and 2720 nmol/l in the presence of carazolol and CYP, but only 32 nmol/l in the presence of CGP 12177. This antagonist-dependent difference in agonist KD values was observed only in intact cells but not in membrane particles prepared from heart homogenates of newborn rats, where high agonist affinity was seen during displacement of all radioligands. The KA value for isoprenaline-stimulated cAMP accumulation in living cells was 30 nmol/l in 5-day cultures. A direct proportionality existed between agonist receptor occupation and cAMP accumulation in the presence of CGP 12177 as estimated by the KA/KD ratio. In the presence of carazolol the KA/KD ratio decreased from 1 to 0.02 suggesting that low affinity receptors were not coupled functionally to adenylate cyclase. These results indicate that some lipophilic antagonists which appear to be inert competitive ligands in fragmented membranes, alter receptor binding properties in intact cells. These antagonists seem to promote the transformation of receptor sites into a new "inactivated" state where competitive interactions between different ligands are inhibited.
Depolarizing voltage steps induce inward and outward currents in voltage-clamped, internally perfused neurons from the snail Helix roseneri. Addition of the catalytic subunit of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) to the internal perfusing medium results in an increase in the net outward current, with no apparent effect on the inward current. Catalytic subunit inactivated by 5,5'-dithiobis(2-nitrobenzoic acid) is without effect, indicating that the increase in net outward current results from protein phosphorylation rather than an unspecific effect of protein perfusion. Decreasing the external Ca2+ concentration from 10 to 1 mM eliminates the effect of catalytic subunit, suggesting that Ca2+ plays an important role in this response. This suggestion is supported by the fact that the stimulation by catalytic subunit can be mimicked by increasing the Ca2+ concentration in the internal perfusion medium and can be prevented by intracellular perfusion with 10 mM EGTA. The results are consistent with the hypothesis that cyclic AMP-dependent protein phosphorylation regulates the Ca2+-activated K+ conductance in these cells.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The activity of the selenoenzyme glutathione peroxidase (EC 1.11.1.9) was determined in platelets of 15 patients with acute myocardial infarction and 13 control subjects. The platelets of the patients had significantly lower activities of the enzyme (P(t) greater than 0.99). This may be related to the pathogenesis of the disease.
This article summarizes some essential steps leading to one of the most prominent beta-adrenergic effects on the heart, the increase in force of contraction. Binding of beta-adrenergic agonists and antagonists, activation of the enzyme adenylate cyclase by agonist binding, increase in membrane permeability to calcium ions, possibly via cyclic AMP, and increase in force of contraction and its relation to enhanced calcium influx are briefly discussed.
Delayed potassium channels were studied in internally perfused neurone somata from land snails. Relaxation and fluctuation analysis of this class of ion channels revealed Hodgkin-Huxley type K channels with an average single channel conductance (gamma K) of 2.40 +/- 0.15 pS. The conductance of open channels is independent of voltage and virtually all K channels seem to be open at maximum K conductance (gk) of the membrane. Voltage dependent time constants of activation of gK, calculated from K current relaxation and from cut-off frequencies of power spectra, are very similar indicating dominant first-order kinetics. Ion selectivity of K channels was studied by ion substitution in the external medium and exhibited the following sequence: Tl+ greater than K+ greater than Rb+ greater Cs+ greater than NH4+ greater Li+ greater than Na+. The sequence of the alkali cations does not conform to any of the sequences predicted by Eisenman's theory. However, the data are well accommodated by a new theory assuming a single rate-limiting barrier that governs ion movement through the channel.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Employing the Haemonetics Blood Processor (IFC), a relatively pure platelet concentrate can be prepared by collecting only the first portion of the PRP leaving the centrifuge bowl (Fraction I). A subsequent fraction containing RBC and WBC contaminants (Fraction II) can be purified by means of a second centrifugation, using a conventional blood bank centrifuge (Fraction II), if transfusion of these contaminants would be detrimental to the recipient. Utilising the new 1.4% Na3-citrate anticoagulant, platelet metabolic parameters (ATP, ADP, AMP, lactate and pyruvate) as well as O2-uptake, were determined in Fraction I and II prepared from 10 normal healthy subjects. In contrast to previous studies reporting marked dysfunction in platelets contained in Fraction II when standard ACD-A was used during IFC, we observed no significant difference (Student's t test) in the present study between Fractions I and II, in regard to platelet metabolism, when using the new anticoagulant. It is further concluded that the second centrifugal manipulation does not exert a detrimental effect on platelet metabolism.
Explore the source record for details and available documents.
Weather situations connected with small pressure gradients show a statistically significant correlation with the liability to heart-attacks. Changes from cyclonic to anticyclonic situations with descending air-motion lead to a rise of the number of heart-attacks in summer. In winter the change from anticyclonic to cyclonic pressure distributions seems to be critical.
Explore the source record for details and available documents.
Explore the source record for details and available documents.