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U Zeidler

Publications and source records attributed to U Zeidler.

At least 19 recordsLinked to original sources
PubMed1996

The effect of free radicals on the conductance induced by alamethicin in planar lipid membranes: activation and inactivation.

Exposure to ionizing radiation of planar lipid membranes doped with alamethicin gives rise to an increase and to a subsequent decrease of the membrane conductance. Both effects are due to the presence of radiation-induced free radicals of water radiolysis as was shown by addition of various radical scavengers. The increase of the conductance was found to be a consequence of free radical-initiated lipid peroxidation favouring the formation of active ion channels. The decrease of the conductance observed at larger radiation doses is due to an inactivation of alamethicin monomers. The characteristic D37 dose of inactivation was found to be about two orders of magnitude larger than in the case of gramicidin A. The comparatively high sensitivity of the latter is due to the presence of its four tryptophan residues. Inactivation of trichorzianine AIIIc, an analogue of alamethicin with a C-terminal tryptophanol residue, occurs at radiation doses two orders of magnitude lower than observed with alamethicin.

Alamethicin↗
PubMed1995

Photodynamic and radiolytic inactivation of ion channels formed by gramicidin A: oxidation and fragmentation.

Ion channels formed by the peptide gramicidin A in planar lipid membranes have been reported to react very sensitively upon irradiation of the membrane by ionizing radiation (radiolysis), by UV light (photolysis), or by visible light in the presence of appropriate photosensitizers (photodynamic inactivation). In all three cases the effect is due to the presence of the four tryptophan residues of the pentadecapeptide. Modifications of these amino acids--due to an interaction with free radicals formed upon water radiolysis or due to light absorption--have been found to reduce the membrane conductance by many orders of magnitude. The present study was intended to correlate functional changes, observed at the level of single ion channels, with changes of the molecular structure identified by mass spectrometry. About 98% of the inactivated channels showed a single-channel conductance of virtually zero, while about 2% of the channels present before irradiation are converted to a state of reduced conductance (and reduced lifetime). On the structural level, irradiation in the presence of the photosensitizer Rose Bengal was found to produce oxidation and fragmentation of the peptide at the positions of the tryptophan residues. Our results provide evidence that the main effect of radiolysis, or of photodynamic treatment, is the cleavage of the peptide backbone leading to immediate closure of an open ion channel.

Amino Acid Sequence↗
PubMed1995

Radiation-induced and free radical-mediated inactivation of ion channels formed by the polyene antibiotic amphotericin B in lipid membranes: effect of radical scavengers and single-channel analysis.

This paper is part of a study on the effect of ionizing radiation on ion channels in biological membranes. Ion channels formed by polyene antibiotics amphotericin B or nystatin represent clusters of conjugated double bonds. As a consequence of this structural peculiarity, the conductance of lipid membranes--in the presence of polyene channels--has been found to decrease by several orders of magnitude at comparatively small doses of ionizing radiation. The phenomenon shows an inverse dose-rate behaviour similar to that of radiation-induced lipid peroxidation. We report on experiments performed in the presence of various radical scavengers, at varying cholesterol concentrations, and with different lipids. They support the view that channel inactivation is due to free radical-induced peroxidation of the polyenes leading to a destabilization of the barrel-like structure of the ion channels. Radiation-induced channel closing is shown for the first time at the level of single-ion channels.

Amphotericin B↗
PubMed1994

Methylation sensitivity of the enhancer from the human papillomavirus type 16.

The human papillomavirus type 16 is associated with anogenital cancer. Transcription of the viral transforming genes E6 and E7 is under the control of an epithelial cell type-specific enhancer. In the enhancer core, we have identified a regulatory element that is recognized by a novel nuclear factor named MSPF (methylation-sensitive papillomavirus transcription factor). Mutating the MSPF binding site strongly affects the enhancer activity. The MSPF recognition sequence 5'-ATGCGNNNNCGCCT-3' contains two CpG dinucleotides, potential targets for 5-cytidine methylation. DNA recognition by MSPF is strictly methylation-sensitive, since introduction of 5-methylcytidine into either CpG abolishes complex formation. Moreover, CpG methylation of the MSPF binding site suppresses the activity of the enhancer and of the MSPF enhanson subfragment in vivo. In the cervical carcinoma cell line CaSki, which has integrated multiple transcriptionally inactive human papilloma virus 16 genomes, a few of the viral genomes are methylated at the MSPF binding site. These findings suggest that viral transcription can be suppressed by methylation of the regulatory region, an event that prevents binding of the cellular transcription factor MSPF.

3T3 Cells↗
PubMed1993

Independent effects of interleukin 1 on proteoglycan synthesis and proteoglycan breakdown of bovine articular cartilage in vitro.

We studied the effects of human recombinant interleukin-1 beta on proteoglycan metabolism of bovine articular cartilage in organ culture. IL-1 was more potent in inhibiting synthesis (IC50 4 ng/mL) than in stimulating breakdown of proteoglycans (EC50 200 ng/mL). Inhibition of proteoglycan synthesis began to plateau earlier (2 days) than stimulation of proteoglycan release (4 days). Both effects could be neutralized with a polyclonal anti-IL-1 beta antibody; however, higher antibody titers were required to block IL-1 effects on proteoglycan synthesis than to neutralize those on proteoglycan release. Chloroquine, but not hydrocortisone, blocked IL-1-mediated proteoglycan breakdown. Both drugs, however, augmented IL-1-induced inhibition of proteoglycan synthesis. Our data suggest that the effects of IL-1 on articular cartilage proteoglycan synthesis and proteoglycan breakdown can be regulated independently.

Animals↗
PubMed1984

Investigation of the antitumor activity of new epoxide derivatives. Part I: s-Triazinetrione derivatives.

The noteworthy cytostatic activity of triglycidyl-s-triazinetrione and the planned clinical testing of this new active substance induced us to subject this class of substances to closer examination. By chemical reaction of one of the three glycidyl groups present it was possible to introduce wide variations in the properties of the compounds, whilst still retaining the active principle. A number of these substances possessed very high antitumor activity as revealed in the leukemia screening test (P 388; mouse). The influence of other substituents within the glycidyl groups affecting the reactivity of the epoxides groups was also examined.

Animals↗
PubMed1981

[Is it necessary to treat the autonomous thyroid adenoma?].

A treatment of the autonomous nodule in an euthyroid patient is still in question. We therefore compared our findings in treated and untreated patients with this disease. Pooling all datas of untreated patients, one got worse in 84 observed years while one got completely normal in 67 years. None of the 16 patients exposed to organic iodine developed a hyperthyroidism. In hyperthyroid patients with an autonomous nodule of the thyroid the disease was controlled by one low-dose Iodine-131 treatment in 82%, while the others needed one further dose to get euthyroid. Because of the high rate of spontaneous remission and the low complication rate were recommend a treatment of the autonomous thyroid nodule in euthyroidism only in selected cases. A careful follow-up should be done in all patients with thyroid disease, treated or untreated; an exacerbation of disease can be controlled by an Iodine-131-treatment.

Adenoma↗
PubMed1981

Holoprosencephaly in monozygotic twins - clinical and computer tomographic findings.

Of monozygotic male twins with holoprosencephaly, one showed by computer tomographic (CAT) scan a mild type with orbital hypotelorism, flat nose, bilateral cleft lip, and cleft palate associated with an intermaxillary rudiment. By CAT scan, the other boy had the alobar type with marked orbital hypotelorism, flat nose, absent nasal bridge, and median cleft lip. Lymphocyte chromosomes were apparently normal. A review of the literature shows a heterogeneous patient material in that most pertinent cases involved dizygotic twins, and some of these presumably had chromosome abnormalities.

Brain↗
PubMed1975

[Radioimmunologic determination of total IgE and allergen-specific IgE-antibodies in diffuse neurodermitis].

Total IgE levels in sera of 165 patients with atopic dermatitis and 79 patients with dermatoses as well as normal control patients were determined by radioimmunoassay (Phadebas, Pharmacia). Although the mean value for patients with atopic dermatitis was found far above the mean value for normal controls, 38% of patients showed total IgE serum levels within the normal range. Highest IgE serum levels were observed in patients with the generalized form of the disease and in patients with asthma and allergic rhinitis. No direct correlation however, to severity of disease could be found. In a series of 50 patients prick tests were compared to total IgE serum levels and to levels of allergen specific antibodies determined by radioallergosorbent-test (RAST). Extracts of grass pollens and of animal dandruff were used. There was complete agreement between results of skin testing and RAST in at least 80%. While cross reactions were common with grass pollen extracts in RAST, there was no cross-over with animal dandruff. No correlation was found between titer of allergen specific antibody and severity of skin lesions. IgE specific antibody could be detected in 48% of patients with normal total IgE serum levels and in 82% of patients with elevated values.

Allergens↗