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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 343 records · Page 19Linked to original sources

[Preliminary observations on the structure of the medio-intimal area of the rabbit coronary arteries. (A. Observations on 4-month-old rabbits)].

The presence of the diffuse intimal thickening (DIT) is commonly considered the structural basis for the early atherosclerotic involvement of the coronary arteries. In the ambit of a systematic morphometric comparison of experimental atherosclerotic plaques of aorta and coronaries, we have studied the coronary medio-intimal junctions of 4 months old rabbits. Both at sub-epicardic and intra-myocardic coronary arteries level we have found fiber structures similar to DIT. These findings may help explaining why coronary atherosclerosis in rabbits does not represent, in the usual experimental models, a lesion particularly severe nor of precocious appearance.

Age Factors↗

A putative processing enzyme from Aplysia that cleaves dynorphin A at the single arginine residue.

A peptidase activity cleaving at single arginine residues has been detected in extracts of the atrial gland of Aplysia Californica. The enzyme assay consisted of incubation of enzyme with the mammalian opioid peptide dynorphin A and detection by specific radioimmunoassay of dynorphin (1-8), a single arginine cleavage product. The peptidase activity was characterized following chromatography on DEAE-cellulose. Activity was abolished by a thiol-directed inhibitor and chelators and activated by dithiothreitol and cobalt chloride. The pH optimum was 6.2 in phosphate buffer. Analysis of the products of two substrates suggested that cleavage was occurring on the amino side of the arginine residue.

Acetylation↗

The introduction of one or two 3 beta-cholestanyl residues into benzylpenicilloyl-eicosa-L-lysines greatly potentiates their tolerogenicity for anti-benzylpenicillol IgE antibody formation.

BALB/c mice were repeatedly immunized with microgram doses of benzylpenicilloylated Ascaris protein(s) (BPO9Asc) in alum. At different stages of the immune response, BPO21 eicosa-L-lysine or two analogs containing one or two hydrophobic p-oxymethylbenzyl-3 beta-cholestanyl succinate (OSuco) groups were injected. When injected early in the immune response, the anti-BPO IgE antibody formation was much more strongly and permanently suppressed by the lipophilic conjugates than by the hydrophilic BPO21 eicosa-L-lysine. A similar, but less marked, suppressive effect was observed on the anti-BPO IgG1 response. By adoptive cell transfer experiments, it was found that the OSuco-containing derivatives induce and act via suppressor T lymphocytes, since this cell-mediated suppression was sensitive to cyclophosphamide or to treatment with anti-Lyt-2.2 antibody plus complement. When these compounds were injected into repeatedly immunized mice producing late ongoing antibody responses no differences in suppression between hydrophilic and hydrophobic derivatives were observed. In this case, the IgE response was suppressed by about 50%, while the IgG1 response was not affected. These results are compatible with the suggestion that early IgE responses are most sensitive to T cell-mediated suppression and that T suppressor cells are better induced by lipophilic than by hydrophilic antigens. The late ongoing IgE response, on the other hand, is less amenable to T cell-induced suppression and tolerogenic effects brought about by plurivalent BPO antigens operate directly on hapten-specific IgE-bearing B cells, regardless of their lipophilic character.

Animals↗

Lack of clinically important interaction between erythromycin and theophylline.

In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8 +/- 4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4 +/- 9.9 vs 63.8 +/- 14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7 +/- 2.6 vs 7.5 +/- 1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4 +/- 5.0 vs 42.1 +/- 5.4% 1,3-dimethyluric acid, 29.6 +/- 4.6 vs 30.1 +/- 5.9% 1-methyluric acid and 13.4 +/- 3.5 vs 12.5 +/- 2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.

Adult↗

Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects.

The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 micrograms/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 micrograms/l at 200 micrograms/min, 73.8 micrograms/l at 400 micrograms/min and 207 micrograms/l at 800 micrograms/min. The corresponding total clearances were 5.81/ min, 5.51/min and 3.91/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 micrograms/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Differential processing of prodynorphin and proenkephalin in specific regions of the rat brain.

Prodynorphin-derived peptides [dynorphin A (Dyn A)-(1-17), Dyn A-(1-8), Dyn B, alpha-neo-endorphin, and beta-neo-endorphin] and proenkephalin-derived peptides [[Leu]enkephalin [( Leu]Enk) and [Met]enkephalin-Arg6-Gly7-Leu8 [( Met]Enk-Arg-Gly-Leu]) in selected brain areas of the rat were measured by specific radioimmunoassays. We report here that different regions of rat brain contain strikingly different proportions of the prodynorphin and proenkephalin-derived peptides. There is a molar excess of alpha-neo-endorphin-derived peptides over Dyn B and Dyn A-derived peptides in many brain areas. [Leu]Enk concentrations exceed those of [Met]Enk-Arg-Gly-Leu in certain brain areas such as the substantia nigra, dentate gyrus, globus pallidus, and median eminence (areas rich in dynorphin-related peptides). These results indicated that (i) there is differential processing of prodynorphin in different brain regions and (ii) [Leu]Enk may be derived from Dyn A or Dyn B (or both). In certain brain regions [Leu]Enk may derive from two separate precursors (prodynorphin and proenkephalin) in two distinct neuronal systems.

Amygdala↗

[Comparative study of the effect of famotidine and cimetidine on antipyrine pharmacokinetics in the human].

In a randomized order the pharmacokinetics of antipyrine were studied following a 5 days treatment period with placebo, 1000 mg cimetidine and 40 mg famotidine daily, respectively in 7 healthy volunteers. In contrast to cimetidine, famotidine did not significantly affect the disposition of antipyrine in these subjects. Famotidine like the other guanidino-thiazole containing compound tiotidine appears to be free from this unwanted effect on drug metabolism in the liver.

Adult↗

[Treatment of anorectal fistulas: a still current problem].

95% of our patients have a simple fistula in ano. The majority of these fistulas were following a cryptoglandular abscess. No definitive incontinence occurred after laying open the fistula penetrating the anal sphincter and excision of the extrasphincteric part. In only 7% there was a temporary incontinence for faeces or flatus respectively. The recurrence rate was 5%. High fistulas are seldom an indication for a seaton. In 5% we found a complex fistula with supralevator or extrasphincteric extension. Thereby we usually performed a defunctioning colostomy. This became the permanent treatment for more than half of these patients.

Abscess↗

[Effect of metronidazole on phenazone metabolism].

Nine volunteers received in random order on three occasions either 15 mg/kg phenazone (antipyrine; in the following called phenazone, INN), 15 mg/kg phenazone and 1000 mg cimetidine or 15 mg/kg phenazone and 1000 mg metronidazole. Cimetidine prolonged phenazone half-life from 12.7 +/- 1.0 h to 15.5 +/- 1.0 h (p less than 0.05) and decreased total plasma clearance of phenazone from 40.9 +/- 3.9 ml/min to 33.9 +/- 2.9 ml/min (p less than 0.05). When metronidazole was given with phenazone to the volunteers no change of phenazone pharmacokinetics in plasma occurred. Urinary excretion of the main oxidative metabolites of phenazone (4-hydroxyphenazone, 3-hydroxymethylphenazone and norphenazone) was unaffected during cimetidine as well as metronidazole treatment. Both metronidazole and cimetidine potentiate the anticoagulant effect of warfarin. In contrast it could be shown that cimetidine does not interact with the metabolism of phenprocoumon. Whether metronidazole interferes with the pharmacokinetics of phenprocoumon should be studied in further investigations.

Adult↗

Effect of the thromboxane synthetase inhibitor Dazoxiben (UK 37-248) on the metabolism of antipyrine in patients with enhanced platelet aggregation.

The effect of the imidazole derivative Dazoxiben (400 mg daily for 1 week) on antipyrine metabolism was examined in six patients with enhanced platelet aggregation. No significant change in antipyrine saliva pharmacokinetics occurred before or after Dazoxiben treatment. The rate of formation of the three main oxidative antipyrine metabolites was similar before and after Dazoxiben. Although Dazoxiben belongs chemically to the imidazole derivatives, which exhibit inhibitory activity on drug metabolism, no influence on antipyrine disposition could be detected.

Aged↗

Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects.

Studies were designed to investigate whether the cellular immunodeficiency state observed in human glioblastoma patients could be due to inhibitory factors released by the tumor cells. Cultured human glioblastoma cells were found to secrete an interleukin 1-like factor (m.w. 22,000) and a factor (m.w. 97,000) that inhibits interleukin 2 (IL 2)-dependent T cell mechanisms. This is demonstrated by its inhibitory effect on the IL 2-induced proliferation of T cell clones and on the induction of alloreactive cytotoxic T cells in mixed lymphocyte cultures. Additionally the glioblastoma cell-derived 97,000-m.w. factor inhibited growth of neuroblasts but not of fibroblasts and thus shares the characteristics of the neuroblast growth inhibition factor (NGIF) previously detected in the supernatant of fetal rat glia cell cultures. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.

Animals↗

Dictyosomes participate in the intracellular pathway of storage proteins in developing Vicia faba cotyledons.

The main storage globulins of Vicia faba seeds, vicilin and legumin, were localized in ultrathin sections of developing cotyledons employing the protein A/colloidal gold-technique. Double labelling experiments with monospecific immunoglobulins directed against vicilin or legumin using different size classes of protein A-colloidal gold showed that both globulins are associated with protein lumps in the vacuoles of early developmental stages of the seeds and with the rough endoplasmic reticulum, the site of storage protein biosynthesis. Furthermore, vicilin and legumin have been detected in protein-containing vesicles in the cytoplasm as well as in dictyosomes and the dictyosome-derived vesicles. The association of storage globulins with the dictyosomes was also indicated by cell fractionation and immunoblotting of organelle contents derived from microsome, enriched dictyosome and protein body preparations. Protein blotting analyses employing a Concanavalin A/peroxidase technique showed that certain vicilin polypeptides were already glycosylated in the rough endoplasmic reticulum. Another part of the vicilin fraction as well as legumin polypeptides did not show any affinity to Concanavalin A. These data provide a direct evidence for a transient involvement of dictyosomes in the intracellular pathway of legume storage globulins from the rough endoplasmic reticulum to their accumulation site in the protein bodies.

Cell Fractionation↗

Identification of pro-opiomelanocortin-derived peptides in the human adrenal medulla.

Extracts from adult human adrenals contained high concentrations of immunoreactive beta-endorphin and alpha-melanotropin. Lower quantities of immunoreactive adrenocorticotropic hormone could also be detected. Distribution studies showed the presence of pro-opiomelanocortin fragments in the adrenal medulla. No alpha-melanotropin, beta-endorphin, or adrenocorticotropic hormone could be found in adrenal extracts from several other mammalian species. Analysis of the beta-endorphin-like immunoreactivity using region specific radioimmunoassays interfacing with gel filtration and reverse-phase high-performance liquid chromatography showed the majority of the beta-endorphin-like material to exist as nonacetylated beta-endorphin-(1-31) with a small percentage of lipotropin-sized molecules. The alpha-melanotropin-like immunoreactivity cochromatographed on gel filtration and reverse-phase high-performance liquid chromatography with desacetyl alpha-melanotropin. The data suggest that pro-opiomelanocortin is expressed in the adrenal medulla of humans but is not detectable in the adrenal glands of many other mammalian species.

Adrenal Cortex↗

Identification of gastrin releasing peptide-related substances in guinea pig and rat brain.

Rat and guinea pig brain extracts were examined for the occurrence of gastrin-releasing peptide (GRP)-like substances by sequence specific radioimmunoassays interfaced with gel filtration and reversed phase high performance liquid chromatography (RP-HPLC). Tryptic digestion of the immunoreactive peptides followed by RP-HPLC was used to further characterize GRP-related peptides in brain. Using these analytical techniques it was found that guinea pig brain extracts contained a peptide with characteristics identical to authentic GRP (27 amino acid residues long). A carboxyterminal fragment with the characteristics of GRP(18-27) as well as a respective aminoterminal fragment with the characteristics of GRP(1-16) were also present in guinea pig brain extracts. The GRP(18-27) seems to correspond to the bombes in related material that has been described previously in mammalian brain extracts. Rat brain extracts also contained a peptide with the characteristics of GRP(18-27). The corresponding aminoterminal fragment, however, behaved differently on RP-HPLC from authentic GRP(1-16) and it was not recognized by antibodies directed to the aminoterminal tridecapeptide fragment of authentic GRP. Similarly the GRP-like peptide from rat brain did not comigrate on RP-HPLC with authentic GRP and was unreactive to antibodies directed toward the aminoterminus of GRP.

Animals↗