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W Seifert

Publications and source records attributed to W Seifert.

At least 55 records · Page 3Linked to original sources
PubMed1989

Determination of acetylator phenotype in Caucasians with caffeine.

Acetylator status in 595 healthy Caucasian volunteers was determined with caffeine. The test group consisted of 372 males and 223 females, 18 to 78 years of age. 312 volunteers were smokers. Caffeine was taken orally as Coffein Comprette (200 mg caffeine x H2O) and urine was collected for 8 h. The metabolic ratio (MR) of 5-acetylamino-6-formylamino-1-methyluracil (AFMU) to 1-methylxanthine (MX) was determined by HPLC. In total 61.7% of the group had a MR less than 0.48 and were classified as slow acetylators. MR varied from 0.01 to 0.47 in the slow acetylators and from 0.48 to 4.7 in the fast acetylator group. Clear dependence of acetylator type upon age, sex or smoking behaviour was not observed. The present study has confirmed the caffeine test as a feasible tool to determine acetylation capacity.

Acetylation↗
PubMed1989

Determination of dextromethorphan metabolizer phenotype in healthy volunteers.

The dextromethorphan metabolizer phenotype in 450 healthy volunteers (299 men, 151 women) was determined after oral administration of a 15 mg dose. In 8 h-postdose urine samples the ratio of dextrorphan (DOP) to dextromethorphan (DMP) was measured by HPLC. Urinary excretion of DMP and DOP within 8 h after the dose varied greatly between individuals, ranging from 0-11% and 0.04-100% of dose, respectively. In 143 test subjects the fraction of the dose of DMP in urine was below the detection limit. In the remaining 307 volunteers the metabolic ratio (MR) of DOP to DMP varied from 0.07 to 2906. In 404 test subjects the MR was greater than 10 and they were classified as extensive metabolizers (90% of the entire group). Of the entire group 5% had MRs of 1-10 and less than 1, respectively. Depending on the limit for classification of poor metabolizers, their frequency was 5-10% in the Caucasian population studied. The present data are in agreement with previous findings that the oxidative metabolic polymorphisms of debrisoquin and DMP co-segregate; the frequency of the PM phenotype of dextromethorphan in Caucasian populations varies between 5 and 10%.

Adolescent↗
PubMed1989

Glutamate transport and not glutamate receptor binding is stimulated by gangliosides in a Ca2+-dependent manner in rat brain synaptic plasma membranes.

Crude as well as purified synaptic plasma membrane (SPM) preparations were analyzed for the influence of the ganglioside galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylgluc osyl ceramide (GM1) on high-affinity binding of L-[3H]glutamate. Assayed in two different buffer systems, SPM consistently exhibited increased (40-50%) binding upon incubation with GM1 plus Ca2+, as compared to controls without GM1. Incorporation experiments with 3H-labeled GM1 proved trypsin-stable insertion of GM1 into SPM, with a maximum incorporation of four times the endogenous amount (35 nmol/mg of protein). The observed increase in glutamate binding was not due to a change in the affinity of the binding sites, but to a change in the number of binding sites, and it was absolutely dependent on the presence of Ca2+. A pharmacological profile of the GM1/Ca2+-stimulated glutamate binding is presented. The original classification of the stimulatory effect as an effect on glutamate receptor binding had to be revised to take into account the observed temperature sensitivity of the ganglioside effect, its sensitivity to high osmolarity and to ultrasonication, and the lack of binding stimulation after detergent treatment of membranes or after receptor solubilization. Vesicular space measured in both SPM preparations was found to be around 7 microliters/mg of protein, in ganglioside-treated as well as in control membranes. From the data, it is concluded that a special, Na+- and Cl- -independent form of glutamate transport into resealed membrane vesicles is stimulated by gangliosides in the presence of Ca2+.

Animals↗
PubMed1989

Organ-specific and general tolerance of iotrolan 280 after intravenous administration: phase I study in healthy volunteers.

Iotrolan 280, the first water-soluble, nonionic, blood-isotonic, dimeric contrast medium, was administered intravenously to 12 healthy male volunteers. In a Phase I study with an intraindividual design in comparison with placebo, four doses between 0.15 and a maximum of 0.9 g I/kg body weight were administered in accordance with the principle of dose titration. The highest volume administered was 270.6 ml. The injection rate was 10 ml/min. The observation period was 5 days, with the exception of thyroid parameters (14 days). Iotrolan displayed good general and local tolerance. The typical side effects known from x-ray contrast media either did not occur or were minor after administration of iotrolan. No allergy-like reactions and no effects on hemodynamic parameters were observed. Although one observation is under discussion no effects of iotrolan on impulse generation and propagation in the myocardium could be confirmed. The blood and laboratory and chemical parameters analyzed showed no differences in comparison with placebo. In the treatment group with the highest dose (= 0.9 g I/kg body weight) there was one subject who showed a transient increase of the urinary glucose concentration and one case of a slight transient increase of the serum chloride concentration. No such side effects were seen in the subjects of the treatment groups with lower doses. All renal functions tests were normal. In this study iotrolan showed excellent tolerance after intravenous injection up to 0.9 g I/kg body weight.

Adult↗
PubMed1988

Calcium ions induce glutamate transport into rat brain membrane vesicles in the absence of sodium and chloride. Evidence for a novel uptake site?

Evidence is presented that glutamate binding to rat brain synaptic plasma membranes measured in Cl(-)- and Na+-free but Ca2+-supplemented buffers is partly due to uptake of glutamate into resealed membrane vesicles. An intravesicular volume of 7.9 microliter/mg protein was measured. Ca2+-induced glutamate binding to synaptic plasma membranes was found to be sensitive to low temperatures as well as to an increase in osmolarity and was abolished by short pulses of ultrasonication. None of several glutamate receptor agonists tested discriminated between basal and Ca2+-induced binding, but 4 out of 5 glutamate uptake inhibitors did. The Ca2+-induced increase in glutamate binding was the same irrespective of whether calcium acetate, calcium sulfate or calcium gluconate in either Tris-acetate of Tris-citrate buffer was used.

Animals↗
PubMed1988

Serum iron and serum bilirubin after administration of Gd-DTPA-dimeglumine. A pharmacologic study in healthy volunteers.

Gadolinium (Gd)-DTPA-dimeglumine is an extracellular contrast agent (0.5 mol/L) for magnetic resonance imaging. At a dose of 0.1 mmol/kg body weight occasional slight transient elevations of serum iron and bilirubin were observed. To verify these findings, to determine time course, and to assess probability of drug relationship, a single-blind, randomized cross-over study in 12 healthy male volunteers was conducted. Either 0.25 mmol Gd-DTPA/kg body weight or the corresponding volume control 0.5 ml 0.9% saline/kg body weight were injected intravenously with an interval of one week. No relevant clinical side effects were reported or observed. Differences between the two treatments were found for serum iron, total bilirubin, and indirect bilirubin. An increase of serum iron and total bilirubin is observed at 3 to 4 hours postinjection, with a maximum at 6 to 12 hours. At 24 hours after injection all values were back to baseline range. This is a predictable side effect of no recognizable clinical consequence. The unchanged values of the intraerythrocytic enzymes and of haptoglobin indicate the minor nature of this phenomenon. Current experiences with the clinical application of Gd-DTPA at a dose of 0.1 mmol/kg body weight suggest that serum iron and bilirubin increases with that dose are less frequent and less marked than increases shown in this study at a dose of 0.25 mmol/kg body weight.

Adult↗
PubMed1986

Immunological cross-reactivity of cultured rat hippocampal neurons with goldfish brain proteins synthesized during memory consolidation.

Ependymins are goldfish brain glycoproteins exhibiting a specifically enhanced rate of synthesis when the animals adopt a new pattern of swimming behavior. With specific antisera against ependymins it has become possible to look for ependymin-like immunoreactivity in other animal species, both qualitatively by immunofluorescence staining and quantitatively by radioimmunoassay. Ependymin-like immunoreactivity was detected not only in other fish but also in rat brain. In the rat radioimmunoassay measurements were highest for the hippocampal formation and for cultured neurons derived from the embryonic hippocampus. Immunofluorescence staining was performed on various cell culture systems derived from rat brain, in order to establish which cell type contains the antigen. Only neuronal cell populations reacted with the anti-ependymin antisera. Cells derived from embryonic rat brain hippocampus which resembled pyramidal neurons stained particularly bright for ependymin-like immunoreactivity. The antigenic material was distributed throughout the cytoplasm including the neuronal extensions. Various neuron-specific antisera have been used to counterstain the cells containing ependymin-like immunoreactivity.

Animals↗
PubMed1986

Evidence for the functional role of monosialoganglioside GM1 in synaptic transmission in the rat hippocampus.

The hippocampal slices were incubated with compounds which hydrolyze, modify or bind with sialic acid containing molecules. The efficiency of synaptic transmission was tested in the presence of these compounds. The size of the evoked extracellularly recorded potential following Schaffer collateral stimulation was used as an indicator of synaptic transmission efficiency. Sodium periodate (10 mM) and sodium perchlorate (59.2 mM) evoked a reversible (after washout) decrease in the size of the population spike. Higher concentration of sodium periodate (60 mM) abolished the size of the population spike, which was only poorly reversible after washout. Tetanus toxin, which binds to polysialogangliosides, and neuraminidase from Vibrio cholerae (an enzyme which splits off sialic acid from polysialogangliosides, leaving GM1 intact, and splits off sialic acid from sialoglycoproteins) had no influence on the size of the population spike. Cholera toxin, which binds to GM1, slightly reduced the size of the population spike. Incubation of the slices with neuraminidase from Arthrobacter ureafaciens (an enzyme which splits off sialic acid from all gangliosides, including GM1, and from sialoglycoproteins) abolished the population spike after 5 h. GM1 antiserum abolished the potential after approximately 100 min. The conclusion is drawn that of all gangliosides only GM1 is necessary to support synaptic transmission in Schaffer collateral-pyramidal cell synapses.

Animals↗
PubMed1986

Gangliosides modulate glutamate receptor binding in rat brain synaptic plasma membranes.

The influence of gangliosides on the binding of L-[3H]glutamate (Glu) to its receptor(s) on isolated rat brain synaptic plasma membranes was investigated in two different buffer systems using an in vitro filter binding assay. It was found that the tested pure monosialogangliosides GM1 and GM2 as well as the polysialogangliosides GT1b and GD1a enhanced binding by up to about 100%, but only in the presence of 5 mM calcium. The binding site involved was sensitive to quisqualate but insensitive to N-methyl-D-aspartate and kainate. GM1 did exert its stimulating effect by increasing the number of binding sites on the membranes whereas the receptor's affinity for L-Glu was unchanged. Regional differences in rat brain were found: while the hippocampus and cortex exhibited significant Ca/GM1-induced stimulation of Glu binding, the cerebellum was unaffected. Our results suggest modulation of at least one subtype of the Glu receptor by gangliosides.

Animals↗
PubMed1985

The role of monosialoganglioside GM1 in the synaptic plasticity: in vitro study on rat hippocampal slices.

Rat hippocampal slices were incubated with neuraminidase from Vibrio Cholerae. This enzyme liberates sialic acid from polysialogangliosides converting them into monosialoganglioside GM1. Thus, the tissue is enriched in GM1 content. Another set of slices was incubated with GM1 itself. Both treatments increased the magnitude of potentiation of synaptic response recorded from pyramidal cell layer following high frequency stimulation of Schaffer collateral-commissural fibers. It is concluded that enrichment of synaptic membranes in GM1 enhances the ability of these nerve endings to be potentiated.

Animals↗
PubMed1985

Bromobenzene metabolism in isolated rat hepatocytes. 18O2 incorporation studies.

Bromobenzene metabolites have been determined in incubations of hepatocytes isolated from untreated, phenobarbital-treated, and beta-naphthoflavone-treated rats. The total formation of bromobenzene metabolites was increased 9-fold in incubations with hepatocytes isolated from phenobarbital-treated rats, and the percentage of total metabolites recovered as bromobenzene-3,4-dihydrodiol and 4-bromocatechol was more than doubled, compared to incubations using hepatocytes from untreated rats. The formation of 2-bromophenol and bromobenzene-2,3-dihydrodiol was increased more than 10-fold in incubations of hepatocytes from beta-naphthoflavone-treated rats, as compared to those of hepatocytes from untreated rats, but recovery of 4-bromocatechol was unchanged. The mechanism of 4-bromocatechol formation from bromobenzene was investigated by examining the incorporation of 18O from 18O2 and H218O into 4-bromocatechol during incubations of bromobenzene with hepatocytes from untreated and phenobarbital-treated rats. Potential metabolic precursor molecules of 4-bromocatechol were also incubated individually with isolated hepatocytes, in order to clarify their roles in 4-bromocatechol formation. The results of these studies show that 4-bromocatechol is formed in intact cells almost exclusively from bromobenzene-3,4-dihydrodiol, rather than from the bromophenols. The bromophenols are, instead, mostly conjugated. The rapid and extensive conjugation of the bromophenols by intact cells may restrict their role as precursors of 4-bromocatechol, while bromobenzene 3,4-dihydrodiol is well converted into 4-bromocatechol by hepatocytes.

Animals↗
PubMed1984

Evidence for a functional role of gangliosides in synaptic transmission: studies on rat brain striatal slices.

The influence of neuraminidase from Vibrio cholerae on evoked, extracellular potentials from rat brain striatal slices was tested. Enzyme treatment abolished synaptic transmission within 90 min. Biochemical analysis of the neuraminidase-treated slices has demonstrated a 10-fold increase in the amount of free sialic acid. The thin-layer chromatography of gangliosides extracted from enzyme-treated slices showed a decrease in the amount of polysialogangliosides (GD1a, GD1b, GT1b, GQ1b) by 1.5-fold. As a consequence, the amount of monosialoganglioside (GM1), which is resistant to neuraminidase from Vibrio cholerae, increased by 1.7-fold. As the antidromic potential remained unchanged after enzyme treatment, our results suggest involvement of polysialogangliosides in cholinergic transmission in the striatum.

Animals↗
PubMed1984

Neurotrophic factor for central neurons.

A serum-free culture of dissociated neurons from embryonic rat hippocampus has been established as a rapid and quantitative in vitro test system for neurotrophic signals in the mammalian brain. By means of this cell culture bioassay, a novel low molecular weight neurotrophic factor (NTF) could be identified. NTF is essential for in vitro brain neuron development, promoting survival and neurite outgrowth. The diffusible factor is synthesized and secreted into serum-free defined medium by cultured astrocytes from rat cerebral hemispheres. The number of viable neurons responding to NTF by neurite outgrowth is dependent on the concentration of the factor. Fractionation of astroglial conditioned medium by gel filtration on columns of Sephadex G-10 recovered biological activity of NTF in a single sharp peak corresponding to an apparent molecular weight of approximately equal to 500. NTF is stable to heat and cold and resistant to trypsin and pronase. Unlike nerve growth factor, NTF has no apparent effect on the neurite outgrowth of peripheral neurons. NTF-like activity is present in situ in the mammalian brain, in certain other nonneural tissues, and in C6 and B12 glioma cell conditioned media.

Animals↗