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Biomedical subjects

M Stadler

Publications and source records attributed to M Stadler.

At least 55 records · Page 3Linked to original sources

Gamma-band responses in the brain: a short review of psychophysiological correlates and functional significance.

The present study shows that gamma-band (40 Hz) activities exist in a number of brain structures of different species, with seemingly different functional/behavioral correlates. This rhythm has also different dynamics in various structures and under different experimental conditions: it exists spontaneously and/or can be evoked, induced or emitted with different latencies and relations to sensory-cognitive events. Recent measurements of gamma-band activity at the cellular level stress high level functional correlates such as binding of features. In contrast, field potential measurements in both humans and animals demonstrate that gamma-band responses may have multifold functions both in 'obligatory' sensory and in cognitive processing. With respect to the generators of gamma activity, experimental data hint at the existence of a distributed gamma system in the brain. Furthermore, an interpretation of gamma rhythms as universal functional building blocks is suggested.

Animals↗

Frontal gamma-band enhancement during multistable visual perception.

The aim of our study was to find out whether an increase in the gamma band may be related to the reversal phase during viewing of an ambiguous pattern. The present study describes the significant gamma band (30-50 Hz) activity increase in EEG during states of perceptual switching (reversal state). In our experiments the multistability was induced with an ambiguous stimulus pattern, known as stroboscopic alternative motion (SAM). The investigations carried out in 11 subjects included a measuring strategy with three different experimental conditions: (1) recording of spontaneous EEG as baseline; (2) recording of the EEG during naive observation of the ambiguous pattern; (3) recording of EEG during active observation of SAM. The results indicate that the multistable perception is one of the multifold cognitive processes giving rise to 40 Hz enhancement in the entire cortex. The most significant 40 Hz enhancements were measured in frontal areas and can reach increases of 40 to 50% in states of naive and active observations of SAM, respectively, in comparison to spontaneous EEG recordings. The results indicate that the increase of frontal gamma band is related to the destabilization of the perceptual system when viewing multistable patterns.

Adolescent↗

New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. VIII. Isolation, structure determination and biological activities of minor metabolites structurally related to mycorrhizin A.

Five new minor metabolites, papyracon D (6), 6-O-methylpapyracon B (9), 6-O-methylpapyracon C (10), lachnumfuran A (11) and lachnumlactone A (12a), together with the known chloromycorrhizinol A (4), have been isolated from extracts of the culture fluids of the ascomycete Lachnum papyraceum. The compounds, which structures were determined by spectroscopic methods, are structurally related to the nematicidal and antibiotic mycorrhizin A (1), which also is produced by the fungus. The nematicidal, antibiotic and cytotoxic activities of the new compounds are weaker compared to those of mycorrhizin A (1). Papyracon D (6) possesses the highest antibiotic activities while lachnumlactone A (12a) is the most nematicidal and cytotoxic.

Anti-Infective Agents↗

Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and a GAS element.

PML is a nuclear matrix protein with growth suppressing properties, whose expression is deregulated during oncogenesis. Moreover, in the t(15;17) translocation of acute promyelocytic leukaemia (APL), PML fusion to the retinoic acid receptor alpha (RAR alpha) is the likely molecular basis of leukaemogenesis. Here we show that interferons (IFNs) alpha, beta, and gamma upregulate PML mRNA expression. Analysis of 5' genomic sequences of the PML gene revealed an IFN-alpha/-beta stimulated response element (ISRE) and an IFN-gamma activation site (GAS) in the untranslated first exon. Binding of IFN signal transducers and activators of transcription (STATs) was demonstrated to be weak for the PML GAS, but strong for the PML ISRE which also seemed to contribute substantially to the IFN-gamma response. Thus, PML is a primary target gene of IFNs and would appear as a suitable candidate for mediating some of their antiproliferative effects. Abnormalities of PML structure, localisation or expression in human malignancy, constitute examples of how an IFN target gene may be altered in oncogenesis.

Amino Acid Sequence↗

Multistep tumor targeting in nude mice using bispecific antibodies and a gallium chelate suitable for immunoscintigraphy with positron emission tomography.

To improve tumor:tissue ratios in immunoscintigraphy, a three-step targeting method has been developed. The reagents used were (a) a radioactive, low molecular weight chelate prepared from ionic gallium and a phenolic polyaminocarboxylic acid, which can be labeled either with the single-photon emitter 67Ga or with the short-lived positron emitter 68Ga (t1/2 = 68 min); (b) a bispecific monoclonal antibody (bs-mAb) synthesized from the F(ab)2 fragment of the 1.1ASML antibody specific for the glycoprotein CD44v associated with a rat pancreas carcinoma cell line and the F(ab') fragment of an antibody specific for the gallium chelate; and (c) the nonradioactive gallium chelate covalently coupled to transferrin, which served as a high molecular weight blocker to prevent binding of the radioactive gallium chelate to bs-mAbs in the circulation. Targeting experiments in tumor-bearing nude mice with different doses of bs-mAbs, blocker, and 67Ga chelate were adjusted to maximize tumor to tissue contrasts and tumor uptake. Compared with the biodistribution of the 131I-labeled, native 1.1ASML antibody 24 h postinjection, a schedule using 100 pmol bs-mab 24 h later 100 pmol blocker, 15 min later 16 pmol 67Ga chelate, 1 h later examination, increased tumor:blood and tumor: liver ratios by a factor of 5 while keeping the localization of radioactivity in the tumor constant (10.1% injected dose/g). High-contrast images using either 67Ga or 68Ga were obtained within 1 h. The targeting method described enables the use of the short-lived positron emitter 68Ga and thus allows the combination of an improved immunoscintigraphy and positron emission tomography.

Animals↗

Development and biochemical characterization of a double-virus-inactivated factor VIII preparation.

This paper describes the development of a double-virus-inactivated preparation. The original goal was to inactivate and/or remove parvovirus from plasma-derived factor VIII. More recently, attention has also been focused on the controversial issue of transmission of the non-lipid-coated hepatitis A virus by preparations of factor VIII which have been solvent/detergent-treated and purified by ion-exchange chromatography.

Antiviral Agents↗

Patterns of drug resistance parameters in adult leukemia.

P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6-Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. V. Production, isolation and biological activities of bromine-containing mycorrhizin and lachnumon derivatives and four additional new bioactive metabolites.

Eight novel bioactive metabolites were isolated from submerged cultures of the ascomycete Lachnum papyraceum (Karst.) Karst, when CaBr2 was added to the cultures after the onset of secondary metabolism. Four of these metabolites (16 to 19) are bromo analogues of mycorrhizin A and lachnumon, while (l'Z)-dechloromycorrhizin A (12) and the papyracons A (13), B (14), and C (15) are non-halogenated compounds structurally related to the mycorrhizins. All compounds exhibited antimicrobial, cytotoxic, nematicidal and phytotoxic activities. The brominated mycorrhizins and lachnumons were found to be slightly less active than the chlorine-containing compounds. All mycorrhizin derivatives were mutagenic in the Ames test, suggesting DNA-alkylating properties.

Animals↗

New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. VI. Structure determination of non-halogenated metabolites structurally related to mycorrhizin A.

The structure determination of four new biologically active non-halogenated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum is described. The compounds are structurally related to the antibiotic mycorrhizin A: (l'Z)-Dechloromycorrhizin A (12), a stereoisomer of dechloromycorrhizin A (5) previously isolated from the same fungus, as well as papyracon A (13), papyracon B (14) and papyracon C (15) containing an exocyclic double bond. The amounts of the latter three increased significantly when CaBr2 was added to the culture medium. The structures were determined by spectroscopic methods.

Anti-Bacterial Agents↗

New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. VII. Structure determination of brominated lachnumon and mycorrhizin A derivatives.

The structure determination of lachnumon B1 (16) and lachnumon B2 (17), brominated derivatives of lachnumon (1), as well as mycorrhizin B1 (18) and mycorrhizin B2 (19), brominated derivatives of mycorrhizin A (3), is described. The compounds, which exhibit similar antimicrobial and nematicidal activity as their chlorinated analogues, were isolated from extracts of cultures of the ascomycete Lachnum papyraceum to which CaBr2 had been added. The structures were elucidated by spectroscopic methods.

Anti-Bacterial Agents↗

Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. III. Production of novel isocoumarin derivatives, isolation, and biological activities.

During investigations on the influence of CaBr2 on the secondary metabolism of Lachnum papyraceum, the production of mycorrhizins and lachnumon type antibiotics was strongly inhibited in bromide-containing culture media. Instead, six isocoumarin derivatives, 6-hydroymellein (6), 4-chloro-6-hydroxymellein (7), 4-bromo-6-hydroxymellein (9), 6-methoxymellein (10). 4-chloro-6-methoxymellein (11), and 4-chloro-6,7-dihydroxymellein (12) were isolated. Compounds 7, 9, 11, and 12 have never been isolated from natural sources. 6-Hydroxymellein has been isolated previously from many sources including Gilmaniella humicola and proposed to be a precursor of mycorrhizin A (see reference 6). In comparison to the mycorrhizins, the isocoumarin derivatives exhibited only weak antimicrobial, cytotoxic, phytotoxic, and nematicidal activities.

Animals↗

New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. IV. Structural elucidation of novel isocoumarin derivatives.

The structures of four new biologically active halogenated dihydroiso coumarins isolated from submerged cultures of the ascomycete Lachnum papyraceum have been elucidated by spectroscopic methods. The compounds are structurally related to lachnumon and mycorrhizin A, which are also produced by the fungus.

Anti-Infective Agents↗

Induction of the PML protein by interferons in normal and APL cells.

PML has been identified through its fusion to the RAR alpha gene in acute promyelocytic leukemia (APL). The PML protein is specifically associated to nuclear bodies (NBs) whose alterations in APL were proposed to contribute to leukemogenesis. The role of this nuclear domain (which also harbors the Sp100 autoantigen and the NDP52 protein) is unknown. Here, we show that the PML protein, like Sp100 and NDP52, is induced by interferons (IFNs alpha, beta and gamma) in a large variety of human cells. Interestingly, the NBs that contain the three IFN-induced proteins appear to be associated to speckles labelled by the IFN-mediator Mx1. These observations link NBs to IFN response pathways, which may contribute to the elucidation of the biological role of these structures. In APL cells, IFNs induced both PML and PML/RAR alpha expression, resulting in an increased sequestration of PML and RXRs in the microspeckles induced by the fusion protein. As PML has growth suppressing properties, it may mediate some of the antiproliferative effects of IFN. In APL, inactivation of PML may result in disruption of growth control.

Antineoplastic Agents↗

[Expectancy effect in recognition of persons, or: on the tendency to corroborate perceptual hypotheses].

Two policemen who had been following and observing two young men for several hours appeared as witnesses in a criminal court case. They claimed that they had observed the young men from a distance of 375 meters putting concrete slabs onto a railway track. In order to determine whether person identification is possible at a distance of 375 meters, a field experiment was carried out. The results show that person identification at a distance of 375 meters is almost impossible. Any spontaneous identification with the naked eye is based on expectations. When using a pair of binoculars, identification is possible, but the rate of false alarms is higher than 60 percent. The results are discussed with reference to theories of perceptual and social psychology.

Adult↗

Purification of factor VIII and von Willebrand factor from human plasma by anion-exchange chromatography.

Factor VIII (anti-hemophilia A factor) is isolated from human plasma. Purification is carried out by a combination of precipitation and chromatographic procedures. After precipitation, the first step in virus inactivation is achieved through the effect of a non-ionic detergent such as Tween 80, and a solvent, e.g. tri-n-butylphosphate (TnBP). By subsequent anion-exchange chromatography, a highly enriched product is isolated, consisting of a complex formed by factor VIII and von Willebrand factor (FVIII-vWF). This treatment also removes the virus-inactivating reagents to quantities in the low ppm range. The second step in virus inactivation is aimed specifically at the non-enveloped viruses and consists of pasteurization at temperatures higher than 60 degrees C for 10 h. Through the addition of stabilizers, between 80% and 90% of the initial activity of FVIII is preserved during the modified pasteurisation. Along with the possibly denatured proteins the stabilizers, such as sugars, amino acids and bivalent cations, are subsequently removed by ion-exchange chromatography. The two-fold virus inactivation, by solvent/detergent treatment and subsequent pasteurisation, allows the destruction of both lipid-enveloped and non-enveloped viruses. During the procedure FVIII is stabilized through the high content of vWF. The complex consisting of FVIII and vWF can be dissociated by adding calcium ions. Subsequently both glycoproteins from this complex are separated from one another by further anion-exchange chromatography.

Biocompatible Materials↗

Parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA alkyltransferase and P-glycoprotein as indicators of drug resistance in tumor and normal lung of patients with lung cancer.

The levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O6-alkylguanine-DNA alkyltransferase (ATase), as well as expression of P-glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non-small-cell lung cancer (NSCLC) or of small-cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance-parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemosensitivity between SCLC and NSCLC cannot be explained by differences in the GSH-system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

In patients with BCR-ABL-positive ALL in CR peripheral blood contains less residual disease than bone marrow: implications for autologous BMT.

Residual leukemic cells are detectable at frequencies as low as 1 in 10(6) normal cells in patients with Philadelphia chromosome/BCR-ABL-positive leukemias in complete remission (CR) using reverse-transcriptase polymerase chain reaction (RT-PCR) with specific nested primers. The level of minimal residual disease (MRD) in the bone marrow (BM) and the peripheral blood (PB) may favor one of the two as the source for an autologous graft. In order to quantify MRD with RT-PCR we analyzed patients ficolled cells after limiting logarithmic dilutions in normal ficolled buffy-coat cells. In six patients with BCR-ABL-pos ALL who were in CR by conventional criteria (5 in CR1 and 1 in CR2), we studied a total of nine paired BM and PB samples prior to scheduled ABMT. A positive RT-PCR signals was detectable in all samples up to dilutions ranging from 1:10(1) to 1:10(3) in PB, and at higher titers ranging from 1:10(3) to 1:10(5) in the BM. The BM titers exceeded the corresponding PB titers in all nine sample pairs by at least 1 log. The mean difference was 1.55 log (geometric mean, n = 9) and is statistically significant (p < 0.03). We conclude that residual leukemia in BCR-ABL-positive ALL preferentially locates in the BM compartment, and we assume that PB may yield autologous grafts with significantly less leukemic contamination.

Adult↗