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D Palm

Publications and source records attributed to D Palm.

At least 91 records · Page 5Linked to original sources
PubMed1984

Theory of ligand-receptor interactions--evidence for more than one site.

Receptor binding studies usually show heterogenic characteristics of the binding isotherm. Scatchard transformation for graphical linearization of the data presentation affects the data inhomogeneously with respect to the experimental error. Thus a non-linear fitting procedure should be preferred for data analysis. Furthermore this approach allows for reliable weighting of the measurements according to the experimental error.

Animals↗
PubMed1984

Congenital muscular dystrophy, brain malformation and ocular problems (muscle, eye and brain disease) in two German families.

We report on two brothers and an unrelated girl with congenital muscular dystrophy (CMD), brain malformation and ocular changes (strabismus, myopia, glaucoma, cataracts, retinal dystrophy). Correlations with the inherited autosomal recessive syndromes of CMD, including the Fukuyama-type CMD with CNS malformation, and the Muscle, Eye and Brain Disease published by Santavuori are discussed.

Brain Diseases↗
PubMed1984

Simple and reliable radioreceptor assay for beta-adrenoceptor antagonists and active metabolites in native human plasma.

A radioreceptor assay (RRA) for the assay of beta-adrenoceptor antagonists in native human plasma is described. The hydrophilic antagonist 3H-CGP 12177 was used as the radioligand. In contrast to the hydrophobic radioligand 3H-dihydroalprenolol, which was investigated in parallel, the beta-adrenoceptor binding of 3H-CGP 12177 by rat reticulocyte membranes was found not to be affected by inclusion of increasing proportions (0-66% of incubation volume) of human plasma in the assay. Thus, solvent extraction of drug and/or active metabolites was not necessary to avoid binding of the radioligand tracer to plasma added in the RRA. The assay of unprocessed samples was possible. Drug concentrations in plasma after oral administration of propranolol (240 mg) or carteolol (30 mg) to 6 healthy volunteers were measured by the RRA and in parallel by a chemical method. The results from both methods agreed when the plasma concentration kinetics of propranolol were investigated (elimination half-life:3.9 h). In contrast, plasma concentrations of carteolol were consistently higher according to the RRA after oral administration of the drug. Identical concentrations, however, were found by the RRA and chemical method using plasma samples spiked with carteolol. Plasma concentrations of carteolol detected by the chemical method decline monoexponentially (elimination half-life: 5.4 h). A similar half-life of elimination for parent drug was found by the RRA (5.9 h), but an additional term describing the appearance of an active metabolite was necessary to account for the biphasic drug elimination (elimination half-life of metabolite: 17.3 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

Primary rhabdomyosarcoma of the leptomeninx. Clinical, neuroradiological and pathological aspects.

Report of an eight-year-old boy presenting with untreatable focal epilepsy and slowly progressing hemiparesis combined with personality changes. Continuous diagnostic efforts eventually resulted in the diagnosis of a primary intracranial rhabdomyosarcoma several months later. The delay in making the correct diagnosis was due to the fact that the malignant process originated as a diffuse involvement of the leptomeninx, and only in later stages a tumor mass developed. Nosology and histogenesis of primary intracranial rhabdomyosarcomas are discussed.

Arachnoid↗
PubMed1984

Correlation between pharmacological response, kinetics of plasma concentration and in vitro receptor affinities exemplified with beta-adrenoceptor blocking drugs.

The clinical effect of beta-adrenoceptor blocking drugs lasts longer than the respective half lives in plasma will suggest. This apparent discrepancy is easily explained by a superposition of the function of plasma concentration kinetics and the function for competitive antagonism at beta-adrenoceptors according to the law of mass action. By taking clinical data from the literature and by using results from ligand binding studies simultaneously, this was confirmed. Furthermore, it can be stated: 1) The plasma concentrations are representative for the drug concentration at the beta-adrenoceptor sites: Dissociation of beta-blockers from the receptor site is a much faster process than elimination from plasma and thus does not prolong effects. 2) Extent of beta-adrenoceptor blocking effect in vivo can be predicted from ligand binding studies based on the respective drug concentration in plasma. If the kinetics of the drug in plasma is known, the time course of effect can be delineated. 3) Only deviations from the above function describing the time course of effect may be indicative for active metabolites or additional compartments of drug distribution. Furthermore, deviations should occur if additional drug effects (e.g. partial agonist activity) are present. In general, any drug acting on the basis of the law of mass action should obey the described relation between the time course of plasma concentration and clinical effect (e.g. cardiac glycosides).

Adrenergic beta-Antagonists↗
PubMed1983

[Vitamin K deficiency hemorrhages in 4 exclusively breast-fed infants 4 to 6 weeks of age].

Haemorrhages were observed in four wholly breastfed infants beyond the neonatal period. These infants were observed within a period of 8 weeks and showed the following characteristics: 1. Onset of bleedings was unexpected and without prior indication. 2. They were of a serious nature and involved the CNS in two children. 3. In all cases infants between 4 and 6 weeks of life were affected. 4. All infants had been wholly breastfed. 5. All were male. 6. There was a prompt improvement after administration of vitamin K or after blood or blood derivatives. Although preliminary own investigations do not indicate general lowering of vitamin-K-dependent coagulation factors in wholly breastfed infants in the postneonatal period, these 4 cases observed within a short time confirm the necessity to consider vitamin K deficiency in haemorrhages in infants in the postneonatal period. Diagnostic steps have to be initiated immediately.

Blood Transfusion↗
PubMed1983

alpha-Glucan phosphorylases catalyze the glucosyl transfer from alpha-D-glucosyl fluoride to oligosaccharides.

Regulated and nonregulated phosphorylases were found to catalyze in a slow, orthophosphate dependent reaction the direct transfer of the glucosyl residue from alpha-D-glucosyl fluoride to an oligosaccharide primer. The enzyme catalyzed formation of the glucosyl residue requires stereospecific protonation of alpha-D-glucosyl fluoride by a Brønstedt acid. The results are interpreted by a mechanism whereby phosphate acts as a proton shuttle and the cofactor pyridoxal 5'-phosphate is required to promote the acid-base function of phosphate.

Animals↗
PubMed1982

General acid-base catalysis of alpha-glucan phosphorylases: stereospecific glucosyl transfer from D-glucal is a pyridoxal 5'-phosphate and orthophosphate (arsenate) dependent reaction.

D-Glucal, containing a highly reactive double bond, can replace glucose 1-phosphate as the glucosyl donor in phosphorylase-catalyzed glucosyl transfer to a suitable oligo- or polysaccharide acceptor: D-glucal + Pi + (glucose)Pi leads to n 2-deoxy-alpha-D-glucosyl(glucose)n in equilibrium 2-deoxy-alpha-D-glucose-1-P + (glucose)n. This reaction is catalyzed by alpha-glucan phosphorylases from rabbit skeletal muscle, potato tuber, and Escherichia coli. D-Glucal is only measurably consumed by alpha-glucan phosphorylases when orthophosphate or arsenate is present. With saturating concentrations of these anions and a glucosyl acceptor, the D-glucal reaction proceeds at rates comparable with the rates of glucosyl transfer from glucose 1-phosphate and of phosphorolysis or arsenolysis of poly- or oligosaccharides. Furthermore, for the reaction to proceed, the enzyme must be in the active conformation containing the cofactor pyridoxal 5'-phosphate in its dianionic form. On the basis of proton nuclear magnetic resonance spectra, it is proposed that protonation at C-2 of D-glucal gives rise to a hypothetical 2-deoxy-beta-D-glucose intermediate, yielding as a final product (2-deoxy-alpha-D-[2(e)-2H]glucose)n alpha (1 leads to 4) saccharides. These 2-deoxy-alpha-D-glucose oligo- or polysaccharides are degraded by alpha-glucan phosphorylases by phosphorolysis or arsenolysis like natural linear and branched alpha-glucans. The absolute requirement of the D-glucal reaction for phosphate (or arsenate) and its dependency on the dianionic form of the pyridoxal 5'-phosphate bound to phosphorylase are rationalized in terms of a proton transfer relay involving juxtaposed phosphates. Phosphate--phosphate interactions were postulated by Withers et al. [Withers, S. G., Madsen, N. B., Sykes, B. D., Takagi, M., Shimomura, S., & Fukui, T. (1981) J. Biol. Chem. 256, 10759-10762].

Arsenates↗
PubMed1982

Rabbit muscle phosphorylase derivatives with oligosaccharides covalently bound to the glycogen storage site.

Linear maltooligosaccharides, e.g., maltoheptaose or terminal 4-O-methylmaltoheptaose, activated by cyanogen bromide, react covalently with rabbit muscle phosphorylases b and a (EC 2.4.1.1). Site-specific modification prevents further binding to glycogen and shifts the phosphorylase a tetramer-dimer equilibrium in favor of the dimer. Use was made of these properties to separate by affinity chromatography and gel filtration phosphorylase a dimers with specifically bound oligosaccharide from unspecifically modified products. The phosphorylase a-maltoheptaose derivative carries one oligosaccharide residue per monomer and can be distinguished from the native enzyme by its electrophoretic mobility in polyacrylamide gels or by affinity electrophoresis. Phosphorylase a preparations with covalently bound maltooligosaccharides are enzymatically active in the presence of a primer and alpha-D-glucopyranose 1-phosphate (glucose-1-P). Methylation of the nonreducing chain terminus of the bound oligosaccharide has no effect on glycogen synthesis. These findings exclude the participation of bound oligosaccharides in chain elongation. Purified covalent phosphorylase a-maltoheptaose complexes are stable dimers. They are no longer activated by glycogen. The properties of covalently modified phosphorylase-oligosaccharides are consistent with and provide direct evidence for the existence of a glycogen storage site in rabbit muscle phosphorylases. Covalent occupation of the storage site renders the affinity of glucose-1-P to phosphorylase a independent of modulation by glycogen, supporting the assumption that the glycogen storage site is involved in interactions with the catalytic site.

Animals↗
PubMed1982

Energy-dependent extrusion of cyclic 3',5'-adenosine-monophosphate. A drug-sensitive regulatory mechanism for the intracellular nucleotide concentration in rat erythrocytes.

In reticulocyte-rich suspensions of red blood cells from rats extrusion of cAMP as a regulatory mechanism of intracellular cAMP was investigated. In response to isoprenaline and/or the phosphodiesterase inhibitors Ro 20-1724 and rolipram extrusion of cAMP increases dependent on the concentration of the drugs and time of exposure. However, these drugs exert their effects on the extrusion of cAMP only indirectly, i.e. via increased intracellular levels of cAMP, since the respective EC50-values of the drugs for intracellular accumulation and extrusion of cAMP are identical (isoprenaline: approximately 50 nM; rolipram: approximately 1 microM; Ro 20-1724: 15 microM). The dependence of the rate of extrusion on intracellular levels of cAMP is characterized by a typical concentration-effect relationship from which a maximal capacity of cAMP extrusion of 3-6 nmol/10 min/10(9) cells and a half maximal effective intracellular cAMP concentration of 40-50 nmol/10(9) cells can be derived. This relationship has been inferred from either kinetic or steady-state approaches. At rapidly changing intracellular levels of cAMP an apparent time lag of extracellular cAMP accumulation is obligatorily conditioned by this relationship. Vasodilating drugs which lower the ATP content of the cells as well as the uncoupler of oxidative phosphorylation, FCCP, inhibit the extrusive process (papaverine greater than FCCP greater than dipyridamole greater than dilazep much greater than hexobendine greater than or equal to carbocromene) leading to a 3-5-fold increase of the intrato extracellular concentration gradient of cAMP. It is concluded that extrusion of cAMP is a saturable and energy-dependent process which regulates the intracellular cAMP concentration independent of the activities of adenylate cyclase and phosphodiesterase.

Adenosine Triphosphate↗
PubMed1982

Sympathomimetic effects of amezinium on the cardiovascular system and plasma catecholamines in man.

The cardiovascular effects of the sympathomimetic agent amezinium were investigated in a double-blind, placebo-controlled, randomized trial in six volunteers. Before and 2 h after oral administration of amezinium 30 mg or placebo the cardiovascular responses to orthostatic stress, induced by 80 degrees passive head-up tilt, were assessed by recording blood pressure, systolic time intervals, and echocardiogram. Plasma catecholamines were also determined. After amezinium treatment, the average supine systolic blood pressure was increased by +30 mm Hg and after tilting it remained above both the pre-treatment and placebo values. Compared to placebo, amezinium elicited only minor changes in heart rate and diastolic blood pressure. The effect of amezinium on the pre-ejection period corrected for heart rate (PEPc) and mean velocity of fiber shortening (VCFmean) indicated positive inotropic properties. Its effects were distinctly more pronounced during tilt than with the subjects supine. Plasma concentrations of noradrenaline and adrenaline were not influenced by amezinium during rest or tilt. From these results and previous research it is concluded that amezinium induces its sympathomimetic effects by preferentially inhibiting the re-uptake of noradrenaline which is released by the drug itself, or by sympathetic activation during tilt. This mechanism of action might explain the pronounced sympathomimetic effects of the drug, especially during orthostatic stress.

Adult↗
PubMed1982

[EEG-slowing after high-dose Methotrexate with citrovorumfactor-rescue. A spectralanalytic study (author's transl)].

In 23 treatment courses of high-dose Methotrexate (MTX) with Leukovorin-rescue for osteogenic sarcoma serial EEG-examinations before and after MTX-infusion were done. In 11 course Vincristine had been administered additionally. Frequency-analysis of EEG-background activity was performed by computer-based FFT. At the end of the MTX-infusion EEGs were unchanged, compared with the findings before start of treatment. At 24 and 48 hours after start of infusion, there was a slight but statistically significant slowing, recognizable from an increase of the theta/alpha-ratio (median + 48%, range -7% to + 373%) and a drop of dominant frequency (median-8%, range +12% to -53%). There was a stronger trend towards normalisation in patients, not having received Vincristine. The greatest changes were found in a patient, whose serum-MTX-concentration at 24 hours exceeded the upper therapeutic limit. The EEG-findings are discussed as an equivalent of a subclinical MTX-encephalopathy. Acute encephalopathies with severe EEG-changes and morphological changes on CT have been observed in MTX-intoxications.

Adolescent↗