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Biomedical subjects

M Stadler

Publications and source records attributed to M Stadler.

At least 73 records · Page 4Linked to original sources

Fatty acids and other compounds with nematicidal activity from cultures of Basidiomycetes.

In a screening for nematicidal activities in cultures of Basidiomycetes, cultures of Pleurotus pulmonarius and Hericium coralloides exhibited toxic effects towards the saprophytic nematode Caenorhabditis elegans. Subsequently S-coriolic acid (1), linoleic acid (2), p-anisaldehyde (3), p-anisyl alcohol (4), 1-(4-methoxyphenyl)-1,2-propanediol (5), and 2-hydroxy-(4'-methoxy)-propiophenone (6) were isolated from submerged cultures of P. pulmonarius. All compounds showed nematicidal activities towards C. elegans. The most active compounds were 1 and 2 with LD50 values between 5 and 10 ppm. Compounds 1, 4, and 5 have not been previously isolated from higher fungi, 6 is a new natural product. From cultures of H. coralloides, which exhibited both repellant and nematicidal effects, a nematicidal fatty acid mixture was obtained, containing linoleic acid, oleic acid, and palmitic acid as its main components.

Animals↗

Nematicidal activities of two phytoalexins from Taverniera abyssinica.

The traditional analgesic and antipyretic Ethiopian drug "Dingetegna" is made of dried root material of Taverniera abyssinica A. Rich (Leguminosae). In a screening for nematicidal natural products, "Dingetegna" extracts showed strong nematicidal activities towards C. elegans. In the following, medicarpin and 4-hydroxymedicarpin were isolated as nematicidal constituents from the extracts. In a microwell plate assay for nematicidal activity, both compounds exhibited an LD50 of 25 micrograms/ml towards C. elegans. Beside these nematicidal effects, weak cytotoxic and antimicrobial activities were observed. In addition, both compounds inhibited oxygen consumption of axenically grown C. elegans, L 1210 cells, and filamentous fungi. Respiration in sensitive bacteria was not affected. In L 1210 cells, the incorporation of precursors into macromolecules was affected in the presence of glucose, indicating that inhibition of respiration is not the only target site of the compounds.

Animals↗

New nematicidal and antimicrobial compounds from the basidiomycete Cheimonophyllum candidissimum (Berk & Curt.) sing. I. Producing organism, fermentation, isolation, and biological activities.

Six new bisabolane type sesquiterpenoids, cheimonophyllons A (1), B (2), C (3), D (4), E (5), and cheimonophyllal (6) were isolated from the culture fluid of the basidiomycete, Cheimonophyllum candidissimum. The compounds exhibited nematicidal, weak antifungal and antibacterial as well as cytotoxic activities. The main product, cheimonophyllon A (1) (C15H22O4), was also active in the Ames mutagenicity test.

Animals↗

A solvent I detergent treated, pasteurised and highly purified factor VIII concentrate.

In an assessment of the risks of virus transmission by clotting concentrates it is clear that the currently practised procedures for virus inactivation are not equally effective against all types of viruses; neither a pasteurisation nor the solvent detergent (SID) process alone are adequate enough to inactivate viruses that are strongly resistant to heat and organic solvents. In this context, human parvovirus B19 and hepatitis A virus (HAV) are of particular concern. In order to improve this situation which still poses a risk to the haemophiliac patients, a more effective pasteurisation process has been developed that could be easily applied to an already well established factor VIII (FVIII) process in addition to the SID-treatment. Experiments using temperatures above 60 degrees C were performed prompted by two recent publications, which demonstrate that HAV becomes instable at temperatures exceeding 62 degrees C. It is the purpose of this paper to present the following progress: achievement of a pasteurisation procedure for FVIII at 63 degrees C for 10 h with no discernible change in the structure of the factor VIII/von Willebrand factor (FVIII/VWF) complex owing to a newly developed composition of stabilizers; application of this pasteurisation procedure to a purified FVIII fraction that has already been submitted to a SID-treatment: Doing so, two independent virus inactivation steps are performed as previously recommended by the International Association of Biological Standardization (IABS). Introduction of a second purification step on an anion exchange resin, achieving an additional virus reduction over the presently manufactured FVIII preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Protein Electrophoresis↗

PML protein expression in hematopoietic and acute promyelocytic leukemia cells.

Acute promyelocytic leukemia (APL) is thought to be caused by the t(15,17) translocation that fuses the PML gene to that of the retinoic acid receptor alpha (RAR alpha) and generates a PML/RAR alpha fusion protein. Yet, paradoxically, APL cells are exquisitely sensitive to retinoic acid (RA), as they terminally differentiate upon RA exposure. In this report, we have examined the expression of PML and PML/RAR alpha in normal and APL cells. By immunofluorescence or immunocytochemistry, we show that PML has a speckled nuclear pattern of expression that contrasts with that of PML/RAR alpha (mostly a micropunctuated nuclear pattern or a cytoplasmic localization). The APL-derived cell line NB4 that expresses both the PML and PML/RAR alpha genes also shows the fine micropunctuated nuclear pattern, suggesting a dominant effect of the fusion protein over the localization of wild-type PML. RA treatment of NB4 cells or clones expressing PML/RAR alpha gradually leads to a PML pattern before apparent morphologic maturation. In 14 untreated APL patients, the PML-reactive proteins were cytoplasmic (by immunocytochemistry) or both cytoplasmic and nuclear with a micropunctuated pattern (by immunofluorescence). Strikingly, in 4 patients, after 1 to 2 weeks of RA therapy, the speckled nuclear PML pattern reappeared concomitant with the onset of differentiation. These results establish that fusion of PML to RAR alpha results in an altered localization of PML that is reverted upon RA treatment. This observation, which highlights the importance of PML, is likely to be a key to unravelling the molecular mechanism of both leukemogenesis and RA-induced differentiation of APL.

Animals↗

Photometric measurement of color changes in livor mortis as a function of pressure and time. Development of a computer-aided system for measuring pressure-induced blanching of livor mortis to estimate time of death.

Until now, blanching of livor mortis in estimating time of death has generally been assessed based on subjective impressions, i.e. on whether blanching is visible after the application of pressure. We have developed a measuring system that uses digital processing to objectify the relationship between the pressure applied and blanching of postmortem lividity. The pressure is electronically registered by a strain gauge. At predefined levels (10, 20, 30, up to 100 N) the software triggers a color measurement by a commercially available tristimulus colorimeter. All parameters are measured in a single procedure and routed to the computer through a data interface. The pressure-induced color changes in the livor mortis are evaluated according to the L*, a*, b* system (CIE-LAB according to DIN 5033, DIN 6174), which closely approximates the physiology of sight. An additional color spacing formula (delta E) allows analysis of color changes irrespective of the basic skin tone. Initial measurements on cadavers showed that application of increasing pressure produced regular courses of color changes in livor mortis.

Colorimetry↗

Multistable visual perception induces a slow positive EEG wave.

Seven subjects observed a multistable pattern (stroboscopic alternative motion: SAM), and were instructed to press the button immediately after perceptual switching with the aim of detecting some neurophysiological parameters of EEG activity. Our results indicate that the EEG changes observed during multistable perception are similar to the family of event related potentials which we called perceptual switching related positivity. Furthermore, the frequency component of this potential has a similarity to the frequency content of stimulus locked P300.

Adult↗

Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. I. Producing organism, fermentation, isolation and biological activities.

Several chlorinated metabolites with nematicidal, antimicrobial, and cytotoxic activities were isolated from submerged cultures of the ascomycete Lachnum papyraceum. Three compounds were identified as (+)-mycorrhizin A (3), (+)-chloromycorrhizin A (4) and (+)-dechloromycorrhizin A (5). The occurrence of 5 as a natural product is new. Two compounds, lachnumon (1) and lachnumol A (2), were found to be new fungal metabolites with cytotoxic, nematicidal and antimicrobial activities.

Animals↗

Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. II. Structural elucidation.

The structures of two new biologically active chlorinated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum have been elucidated by NMR and mass spectroscopy. The compounds, lachnumon (1) and lachnumol A (2), which structurally are related with mycorrhizin A that also is produced by the fungus, contain an unusual chlorinated epoxide group.

Antifungal Agents↗

Effect of transforming growth factor beta on cell death of cultured rat hepatocytes.

We investigate mechanisms of regression of liver hyperplasia which occurs after induction of growth by hepatomitogens and their subsequent withdrawal. We hypothesized that transforming growth factor beta 1 (TGF-beta 1) might be involved in the control of regression. Therefore we studied the effect of this agent on DNA synthesis and death of hepatocytes cultured in vitro. Both the low basal rate of DNA synthesis of untreated cells and its increase by epidermal growth factor (10 ng/ml) were suppressed by TGF-beta 1 at concentrations higher than 0.01-0.1 ng/ml. At the same range of concentrations of TGF-beta 1, the DNA content of the cultures declined significantly and numerous dead cells could be seen in the monolayer. Time course studies showed that TGF-beta 1 (1 ng/ml) decreased DNA content in the cultures linearly to 41 +/- 7% of controls during a period of 48 h. A similar decrease occurred with vital hepatocytes in hematoxylin and eosin stained monolayers. These changes were accompanied by an extensive release of lactate dehydrogenase which began at 20 h and was 70% of the total lactate dehydrogenase content of the cultures at 40-48 h. Little formation of guanidine hydrochloride resistant bodies and no fragmentation of DNA, indicators of apoptotic cell death, were detected after TGF-beta 1 (1 ng/ml) treatment. Time lapse cinematography revealed an active detachment of the cells from the underlying collagen gel. These studies show that inhibition of DNA synthesis by TGF-beta 1 is associated with enhanced cell death in cultured hepatocytes.

Animals↗

Attractors and perceptual field dynamics of homogeneous stimulus areas.

The phenomenon of the wandering point on a blank sheet of paper in serial reproductions is the starting point of an investigation of the perceptual field structure of homogeneous stimulus areas; 609 stimulus points distributed regularly in 21 rows and 29 columns on a DIN A4 sheet were presented successively to 10 subjects and had to be reproduced immediately afterwards in order to establish empirical vector fields. These were subjected to vector-analytic procedures. A method for the decomposition of the measured vector fields into partitions from gradient potentials and circulation potentials is demonstrated. The gradient potentials of the empirical vector fields revealed a highly regular structure with four point attractors near the corners of the sheet. A model calculation of the wandering point in this potential landscape showed results comparable to the empirical phenomenon. The results are discussed in favor of Gestalt theory and against direct perception.

Attention↗

Detachment of cell surface-bound anticarcinoembryonic antigen immune complexes by phospholipase C.

CEA as well as normal cross-reacting antigens (NCA) are fixed to the cell membrane via phosphatidylinositol (PI). To find out whether these antigens are internalized after antibody contact, acid pH desorption was compared to phospholipase C (PLC)-mediated cleavage of the antigen anchor. With the former procedure, marked differences in the desorbability of individual MAbs were noted, while PLC was able to cleave off surface-bound immune complexes irrespective of the MAb involved. From this it is concluded that internalization of MAb complexes of CEA/NCA, if occurring at all, is a low efficiency process.

Antibodies, Monoclonal↗

New technique for treating occlusive and stenosing tumours of the trachea and main bronchi: endobronchial irradiation by high dose iridium-192 combined with laser canalisation.

A new technique is described for treating patients with inoperable malignant tumours causing occlusion or stenosis of the trachea or main bronchi. High dose iridium-192 (20 Ci) was introduced by an afterloading device under computer control via a 4 mm delivery tube into the tumour mass. In 29 of the 56 patients the tumour mass was canalised by a neodymium-YAG laser immediately before the afterloading delivery tube was introduced. In 44 (79%) of the patients, there was impressive relief of dyspnoea, accompanied by tumour regression observed at endoscopy and also by highly significant improvement in ventilatory function values, lung perfusion scans, and levels of arterial oxygen tension. In the other 12 patients (21%) there was no detectable improvement. The findings suggest that this recently developed combination treatment is of value in patients with advanced tumours of the trachea and main bronchi in whom there is no possibility of further treatment by external irradiation or repeated laser coagulation.

Aged↗

[New methods in the radiotherapy of bronchial carcinoma. Endobronchial small-field irradiation using the iridium-129 high-dose afterloading technic in combination with the neodymium-YAG laser].

106 patients with inoperable malignant tumours constricting the central bronchial tree underwent endobronchial small-field radiotherapy with iridium-192 at high dose between June 1983 and September 1985. Treatment was performed using the computer-guided after-loading technique and a flexible bronchoscope under local anaesthesia. In complete occlusion of a bronchus by the tumour, a neodymium YAG-laser was applied (57 patients) to allow insertion of the after-loading probe. Endoscopy showed tumour regression in 75% of the patients, accompanied by clinical improvement. Pulmonary function tests, arterial blood gas analyses and pulmonary perfusion scans yielded a highly significant improvement of data after treatment. The procedure also proved effective upon exhaustion of external radiation. Apart from its positive palliation, endobronchial small-field radiotherapy using high doses of iridium-192 also has a curative effect, thus opening up a new approach to the therapy of advanced bronchial carcinoma.

Aged↗

Direction and frequency specific processing in the perception of long-range apparent movement.

The presentation of repetitive apparent movement (AM) produces the illusion of smooth sinusoidal movement. During prolonged observation this impression vanishes periodically. On the basis of these observations, it was postulated that such long-range AM are processed via direction and frequency specific subsystems. This hypothesis was examined by means of selective adaptation. A bi-stable movement display was used to measure the adaptation effect. Generally a frequency specific reaction for horizontal and vertical movement was verifiable. In addition to this, the existence of the presumed narrow-band processing channels was confirmed by the tuning curves determined. The significance of the results for AM perception and their applicability to the processing of real movement Gestalt will be discussed.

Adaptation, Ocular↗

[New possibilities in radiotherapy of endobronchial tumors using the afterloading method in combination with laser technics].

New possibilities for radiotherapy of bronchial carcinomas are provided by the combined application of the recently introduced afterloading method used hitherto in the treatment of stenosing processes of bronchial carcinomas and the neodyme-YAG laser which opens the stenosis in such a manner that the afterloading probe can be inserted. This new method allows to perform without complications or disadvantages further combined therapies such as percutaneous irradiation (telecobalt, linear accelerator or betatron). An irradiation scheme leading to a decisive tumor regression can be established due to the fast reventilation of the lung obtained by both methods. Surprisingly, three patients could be submitted despite the small-field radiotherapy to rather important lung operations such as lobectomy and pneumonectomy which were performed without complications or disadvantages. The patients were not operable without laser and afterloading therapy. This method was applied several times in the treatment of other diseases such as oesophageal cancer and stenosing cancer of the antrum. In these cases, a normal ingestion due to tumor regression was obtained rapidly.

Brachytherapy↗