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Biomedical subjects

M M Müller

Publications and source records attributed to M M Müller.

At least 19 recordsLinked to original sources
PubMed2003

Sustained division of the attentional spotlight.

By voluntarily directing attention to a specific region of a visual scene, we can improve our perception of stimuli at that location. This ability to focus attention upon specific zones of the visual field has been described metaphorically as a moveable spotlight or zoom lens that facilitates the processing of stimuli within its 'beam'. A long-standing controversy has centred on the question of whether the spotlight of spatial attention has a unitary beam or whether it can be divided flexibly to disparate locations. Evidence supporting the unitary spotlight view has come from numerous behavioural and electrophysiological studies. Recent experiments, however, indicate that the spotlight of spatial attention may be divided between non-contiguous zones of the visual field for very brief stimulus exposures (&<100 ms). Here we use an electrophysiological measure of attentional allocation (the steady-state visual evoked potential) to show that the spotlight may be divided between spatially separated locations (excluding interposed locations) over more extended time periods. This spotlight division appears to be accomplished at an early stage of visual-cortical processing.

Attention↗
PubMed2003

Determination of fifteen nucleotides in cultured human mononuclear blood and umbilical vein endothelial cells by solvent generated ion-pair chromatography.

The paper describes the development of a method for the determination of 15 nucleotides in cultured mononuclear blood and umbilical vein endothelial cell lysates by solvent generated ion-pair chromatography. The phase system is generated via a mobile phase of 100 mM phosphoric acid adjusted to pH 6.2 with triethylamine. Nucleotides are eluted by applying a linear magnesium ion gradient. The method is robust, highly reproducible and easily adaptable to other cell lysates and allows the separation and quantitation of the nucleotides with detection limits in the range from 17 (ADP) to 126 (CDP) pmol in 20-microl aliquots.

Chromatography, High Pressure Liquid↗
PubMed2003

[Muscle cell proteins are selectively released into the blood stream by marathon running].

In 19 marathon runners of both sexes, plasma concentrations of total creatine kinase (CK) activity, CKMB mass, myoglobin and troponin I were determined before and immediately after the race. Total CK activity and myoglobin increased significantly in all runners and showed neither a correlation with the individual age of the runners nor with the time they needed to reach the goal. In 12 of the runners, CKMB mass increased during the race to a level suggesting myocardial necrosis. However, the runners did not show any detectable deterioration of cardiac function after the race. The appearance of considerable amounts of muscle proteins in plasma precipitated by the muscle strain during the race seems explained by damage of skeletal muscle detected by histological studies. These phenomena may also be a consequence of profoundly disturbed cellular permeability, perhaps due to a kind of local stunning of muscle tissue by prolonged muscular strain.

Adult↗
PubMed2002

Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG.

We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred.

Artifacts↗
PubMed2002

Endothelial cell compatibility of azithromycin and erythromycin.

Phlebitis is a severe local adverse event related to the use of parenteral macrolides. In order to evaluate the effect of azithromycin and erythromycin on human venous endothelial cells, we set up an in vitro model. The intracellular levels of purine nucleotides, as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and guanosine 5'-triphosphate (GTP), were measured by means of high-performance liquid chromatography. Incubation of cells with 2 mg/mL azithromycin and erythromycin resulted in a rapid decline of intracellular ATP from 12.5 +/- 0.9 nmol/million cells to 4.1 +/- 0.3 and 2.6 +/- 0.4 nmol/million cells, respectively, after 60 min. In addition, ADP was extensively depleted from 2.1 +/- 0.17 nmol/million cells to 0.8 +/- 0.09 and 0.8 +/- 0.13 nmol/million cells after 60 min. After exposure of 0.5 mg/mL azithromycin and erythromycin, no significant decline of intracellular high-energy phosphate levels occurred after 20 and 60 min. Based on these results, solutions of azithromycin and erythromycin may not be well tolerated and may cause local adverse reactions even if diluted according to the manufacturer's recommendation.

Anti-Bacterial Agents↗
PubMed2001

Modulation of induced gamma band responses and phase synchrony in a paired associate learning task in the human EEG.

It has been proposed that associative learning is accomplished by the formation of cell assemblies and synchronous activity among the neurons of such an assembly. Induced gamma band responses (GBRs) and phase synchrony between electrode sites are discussed as a signature of activity within a cell assembly. To examine the activation of this network due to memory recall, a paired associate learning paradigm was used. EEG was analyzed in the frequency domain. Results showed a significant increase of induced GBRs at posterior and anterior electrode sites in the recall sequence of the learning condition. Furthermore, phase synchrony revealed a broad distribution pattern of phase synchrony between posterior and frontal electrode sites.

Adult↗
PubMed2001

Determination of the effects of mycophenolic acid on the nucleotide pool of human peripheral blood mononuclear cells in vitro by high-performance liquid chromatography.

Immunosuppressive drugs are needed to prevent the rejection of transplanted organs by the immune system. Immunosuppressive antimetabolites act by interrupting cell metabolism. Their mechanism of action can be studied in vitro by measuring the inhibition of biochemical activities which is reflected by changes in the nucleotide content. In our experiments, human peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were used. After PBMC stimulation with phytohaemagglutinin (PHA) to mimic activation occurring at a rejection crisis, cells were exposed to varying concentrations of different immunosuppressants (i.e., mycophenolic acid, cyclosporin A and prednisolone) for 68 h at 37 degrees C. Changes in nucleotide content were observed by determining the concentrations of 15 nucleotides using a newly developed HPLC method. The results obtained for mycophenolic acid (MPA; final concentrations in a range between 0.1 and 5 micromol/l), cyclosporin A (CsA; final concentrations between 100 ng/ml and 1 microg/ml) and prednisolone (final concentrations between 0.5 and 10 micromol/l) are given as percentage changes in nucleotide content versus controls and are expressed as mean +/- confidence interval. The possibility of synergistic effects was investigated by incubating the cells with mixtures of all three immunosuppressive drugs varying the amount of mycophenolic acid. In addition, we have shown the effects of MPA/guanosine co-incubation on the intracellular nucleotide levels. Stimulation of peripheral blood mononuclear cells with phytohaemagglutinin led to a significant increase of pyrimidine and purine nucleotides versus control values (100%). Pyrimidine (CTP, UDP, UTP) and purine nucleotides (GDP, GTP, ADP, ATP) were elevated up to 153+/-14% and 142+/-17%, respectively. Under co-incubation of cells with MPA, the GTP level decreased in a dose-related manner to 56+/-3% of control at a MPA final concentration of 5 micromol/l. Concomitantly, an increase of UTP values to 203+/-18% versus control was observed under co-incubation with 1 micromol/l MPA. Co-incubation of mononuclear cells with guanosine (50 micromol/l) compensated for the effects of MPA on intracellular GTP levels. Combination of MPA, CsA and prednisolone did not alter intracellular nucleotide profiles of PBMC compared to those under MPA incubation alone. The depletion of the guanine nucleotide pool and concomitant increase of uridine nucleotides under the influence of the immunosuppressive drug mycophenolic acid is caused by its inhibitory effects on the key enzyme of de novo purine biosynthesis, inosine 5'-monophosphate dehydrogenase (IMPDH).

Chromatography, High Pressure Liquid↗
PubMed2001

In vitro effects of mycophenolic acid on the nucleotide pool and on the expression of adhesion molecules of human umbilical vein endothelial cells.

The immunosuppressive drug mycophenolate mofetil (MMF) and its active metabolite mycophenolic acid (MPA) selectively inhibit inosine 5'-monophosphate dehydrogenase (IMPDH), and therefore interfere with cellular guanine nucleotide biosynthesis. IMPDH is additionally involved in the synthesis of membrane glycoproteins, some of which are adhesion receptors known to play an active part in the regulation of cell-cell contacts, which are crucial in the process of recruitment and transendothelial infiltration of activated leucocytes in the transplanted organ. As a consequence, MPA leads to a reduction of cellular infiltrates in the course of transplant rejection. In the present study, the effects of MPA on human umbilical vein endothelial cells (HUVEC) are investigated at both molecular and cellular levels. In our experiments, HUVECs are treated with tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) in order to mimic activation occurring at a rejection crisis. The dose-dependent influence of concomitant incubation with MPA (5-20 micromol/l; 48 h, 37 degrees C, 5% CO2) on their intracellular nucleotide profile is observed by determining the concentrations of purine and pyrimidine nucleotides, using a HPLC method based on solvent generated ion-exchange. The possibility of synergistic effects is investigated by incubating endothelial cells with mixtures of three different immunosuppressants (mycophenolic acid; cyclosporin A, 100 ng/ml; prednisolone, 1 micromol/l)--a combination commonly used after transplantation--varying the amount of MPA (5-20 micromol/l). Stimulation with TNFalpha does not significantly modulate the intracellular levels of nucleotides quantitated. In the presence of MPA concentrations of at least 5 micromol/l, GTP levels (68+/-12%) are significantly decreased compared to controls (100%). At a concentration of 20 micromol/l MPA, the GTP amount is reduced to 58+/-7%. In contrast to these observations, the levels of UDP and UTP are increasing significantly under coincubation with MPA concentrations greater than 5 micromol/l. At 20 micromol/l MPA, UDP and UTP are increased to 147+/-19% and 114+/-11%, respectively. All other nucleotides (CTP, ADP, ATP) reveal no significant alterations in their intracellular concentrations under the conditions applied. Incubation of TNFalpha-treated HUVEC monolayers, with a mixture of three immunosuppressive drugs varying the amount of MPA, show no significant differences compared with the data observed after incubation with MPA alone. In addition, the influence of MPA (10 micromol/l) on a cellular level is observed by measuring the cell surface expression of adhesion molecules on cytokine-stimulated HUVECs, using TNFalpha (10 ng/ml), interferon-gamma (100 ng/ml), interleukin-1beta (10 ng/ml) and interleukin-8 (20 ng/ml). Expression of the intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) was assessed by flow cytometry. Activation of endothelial cell monolayers with TNFalpha significantly increases the mean fluorescence intensity of VCAM-1 (361+/-14%) and ICAM-1 (429+/-47%) surface expression, compared to controls, and additionally induces E-selectin expression (2919+/-134%). The same tendencies, but in a lesser degree, are observed under stimulation of cells with either IFNgamma or IL-1beta. Incubation with a combination of TNFalpha and MPA leads to a significant reduction in VCAM-1 (329+/-13%) and E-selectin (2613+/-167%) expression, compared to the values obtained for HUVEC incubated with the cytokine alone. Treatment of the cells with IL-1beta/MPA also reduces the expression of VCAM-1 to a level significantly lower than the level observed after stimulation with IL-1beta. Incubation with MPA alone reveals no significant modulation in the expression of all surface molecules tested compared to the values of unstimulated HUVECs. The experiments show that the immunosuppressive action of MPA not only inhibits lymphocyte proliferation but also decreases the expression of adhesion molecules on endothelial cells, which are the first target of the cellular rejection process.

Cell Adhesion Molecules↗
PubMed2001

Genotoxicity of N-nitrosodicyclohexylamine in V79 cells in the sister chromatid exchange test and the single cell gel assay.

Dicyclohexylaminexnitrite is used in chemical formulations as an anti-corrosion agent. N-Nitrosodicyclohexylamine (N-NO-DCHA) can be formed by nitrosation from dicyclohexylamine during the application of these formulations. As most of the nitrosamines are genotoxic carcinogens, the genotoxic potential of N-NO-DCHA was investigated in V79 Chinese hamster cells in the single cell gel assay and the sister chromatid exchange (SCE) test. In addition, N-NO-DCHA cytotoxicity was determined in the neutral red assay. Neutral red uptake was suppressed up to 50% after 24 h incubation at a concentration of approximately 135 microM. In the single cell gel assay, a significantly elevated and dose-dependent induction of DNA lesions was detected in a concentration range from 5 microM to 100 microM (P<0.001). The use of proteinase K (1 mg/ml) in the lysing solution did not influence these results. In the SCE analysis, a significant induction of SCE was found at a minimum concentration of 5 microM N-NO-DCHA as well. A dose-dependent SCE induction could be detected up to the maximum concentration tested in the assay (100 microM). In conclusion, N-NO-DCHA is genotoxic in V79 cells in the single cell gel assay and the SCE test. With respect to human health hazard prevention, a substitution of dicyclohexylaminexnitrite in chemical formulations used to prevent corrosion is recommended.

Animals↗
PubMed2001

Genotoxic effects of N-nitrosodicyclohexylamine in isolated human lymphocytes.

Dicyclohexylamine x nitrite is classified as an "experimental equivocal tumorigenic agent" by the National Toxicology Program. Since no genotoxic effects of the substance itself are known, the reported tumorigenic potential of dicyclohexylamine x nitrite could be due to generation of N-nitrosodicyclohexylamine (N-NO-DCHA), which occurs under conditions of use and can be detected in foils that contain dicyclohexylamine x nitrite. Therefore, we investigated possible mutagenic properties of N-NO-DCHA in the Ames test and the cytokinesis-block micronucleus assay with human lymphocytes. Since N-NO-DCHA is not commercially available, the substance was synthesized and purified by thin-layer chromatography. Identity was confirmed by gas chromatography/mass spectroscopy (GC/MS) and 1H- and 13C-NMR. More than 97% purity was achieved. Stability and availability in the solvent were checked by GC/MS. N-NO-DCHA induced micronuclei in isolated human lymphocytes at a dose range of 15-100 micrograms/ml (= 71.4-476.2 microM), exceeding the base rate significantly at one or two nontoxic concentrations in four out of six experiments. For the Ames test, arochlor-1254-, beta-naphthoflavone/phenobarbital- and pyrazole-induced S9-fractions were used with Salmonella typhimurium TA100, TA1535, TA98 and TA104. No effects were seen in the Ames test, with the exception of microcolony induction at doses higher than 250 micrograms (= 1.2 mmol) N-NO-DCHA/plate using TA104 and 20% arochlor-1254 induced S9 at pH 6.5. In conclusion, N-NO-DCHA was negative in the Ames test using TA98, TA100 and TA1535, inconclusive using TA104, and weakly genotoxic in the in vitro micronucleus test with isolated human lymphocytes. With regard to the tumorigenicity of the majority of nitrosamines, our data underline the necessity of further studies on possible genotoxic effects of N-NO-DCHA.

Cell Count↗
PubMed2001

Suppression of the auditory middle-latency response and evoked gamma-band response in a paired-click paradigm.

When two clicks are presented within 500 ms and the clicks are separated by several seconds, a typical finding is a suppression of the amplitude of the P50 component of the middle-latency auditory-evoked response. In the present study, we investigated whether only the P50 or also the earlier components Po, Na, Pa and Nb, and the exogenous components N100 and P200 exhibit an amplitude suppression to the second click. In addition, we studied the suppression behaviour of the auditory-evoked 40-Hz gamma-band response in the time and frequency domain. We found a significant amplitude suppression to the second click for all components of the auditory-evoked potential following Po, which was most pronounced at electrode Cz. When testing the successive peaks and troughs of the evoked 40-Hz gamma-band response in the time domain, we found a significant amplitude suppression for peaks and troughs with the same latency and polarity as the middle-latency components following Po, which was most pronounced at electrodes Fz and Cz. Consequently, the amplitude of the 40-Hz evoked gamma-band response in the frequency domain paralleled the findings of the time domain, with a significant amplitude suppression to the second tone, which was most pronounced at electrodes Fz and Cz. Results are discussed with reference to the early sensory-gating hypothesis.

Acoustic Stimulation↗
PubMed2001

Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers.

In this study we evaluated the routine practice and clinical application of serum crosslaps to urinary-crosslaps, -N-telopeptide-related fraction of type 1 collagen, -deoxpyridinoline, -totalpyridinoline and serum osteocalcin. The utility of both the serum and urine immunoassays for bone formation and resorption marker were tested in a cohort of 593 female and male patients from our outpatient clinic for osteology and rheumatology and compared to important osteoporosis risk factors like age, gender, E2 deficiency, bone density and chronic renal failure. The biochemical maker of bone formation, serum osteocalcin exhibit significant correlations to all five tested serum and urinary markers of bone resorption (p < 0.0001) crosswise to all different groups of patients. The group of chronic renal failure patients showed no significant correlation between the tested bone turnover parameters and the serum creatinine level except a significant increase and correlation for serum crosslaps and for the ratio of serum and urinary crosslaps. Associations between the age of the patients and the markers of bone turnover were rather poor. We found a significant, negative association between serum and urinary bone turnover markers and bone density and were interested, whether in patients with bone density < 2.5 SD an enhanced bone turnover could be detected in the same way as for E2 deficiency. Applying a discriminant analysis it was possible to discriminate between the patient with BD < 2.5 SD and those with BD > 1.0 SD with a sensitivity of 70% and a specificity of 65% using serum crosslaps. In case of urinary crosslaps the discriminatory power was slightly lower (sensitivity: 65.6%, specificity: 67.5%) and for serum osteocalcin the discriminatory power was negligible higher (sensitivity: 79%, specificity: 56%). The highly significant correlation between the urinary and serum crosslinked peptides by ELISA and serum osteocalcin supports the concept that these respective indices of bone formation and resorption both in urine and serum reflect a coupled process in vivo with sensitivity and specificity to pathological bone density, estrogen deficiency and chronic renal failure.

Adult↗
PubMed2001

Functional correlates of macroscopic high-frequency brain activity in the human visual system.

The present article reviews empirical findings of large-scale gamma oscillations in the human brain, in the context of their functional correlates. Evidence supporting the fact that high-frequency neuronal oscillations are involved in several aspects of visual processing is presented, with a focus on bottom-up and top-down visual feature processing, selective attention, and emotional evaluation. This evidence suggests that visual processing involves the integrated activity of wide spread neuronal assemblies that can be studied with respect to time course and topography, employing frequency-domain analyses. Possible mechanisms underlying these phenomena are considered. Furthermore, the effects of attention and motivation, as well as characteristics of experimental paradigms are discussed as determinants of reliability and validity of measures of high-frequency oscillations.

Animals↗
PubMed2001

Human large-scale oscillatory brain activity during an operant shaping procedure.

The present study aimed at examining the oscillatory brain-electric correlates of human operant learning using high-density electroencephalography (EEG). Induced gamma-band activity (GBA) was studied using a fixed-interval reinforcement schedule with a variable limited hold period, which was decreased depending on response accuracy. Thus, participants' behavior was shaped during the course of the learning session. After each response, numbers indicating the money value of that response served as reinforcing stimuli. Random reinforcement and self-paced button pressing without reinforcement were added as control conditions. GBA around 40 Hz was enhanced at posterior electrodes in response to visual feedback stimuli during shaping and random reward compared to the self-paced pressing condition where no visual feedback was provided. Furthermore, shaping was associated with a pronounced left frontal lower gamma (20-30 Hz) increase in response to feedback stimuli, whereas this pattern was not observed in the random reinforcement and self-paced pressing conditions. The present findings are in line with the notion that macroscopic high-frequency dynamics of neuronal cell assemblies may be regarded as a mechanism involved in learning and memory formation.

Adult↗
PubMed2001

Effects of emotional arousal in the cerebral hemispheres: a study of oscillatory brain activity and event-related potentials.

OBJECTIVE: The present study aimed at examining the time course and topography of oscillatory brain activity and event-related potentials (ERPs) in response to laterally presented affective pictures. METHODS: Electroencephalography was recorded from 129 electrodes in 10 healthy university students during presentation of pictures from the international affective picture system. Frequency measures and ERPs were obtained for pleasant, neutral, and unpleasant pictures. RESULTS: In accordance with previous reports, a modulation of the late positive ERP wave at parietal recording sites was found as a function of emotional arousal. Early mid gamma band activity (GBA; 30-45 Hz) at 80 ms post-stimulus was enhanced in response to aversive stimuli only, whereas the higher GBA (46-65 Hz) at 500 ms showed an enhancement of arousing, compared to neutral pictures. ERP and late gamma effects showed a pronounced right-hemisphere preponderance, but differed in terms of topographical distribution. CONCLUSIONS: Late gamma activity may represent a correlate of widespread cortical networks processing different aspects of emotionally arousing visual objects. In contrast, differences between affective categories in early gamma activity might reflect fast detection of aversive stimulus features.

Adult↗
PubMed2001

Diversity of endophytic fungi of single Norway spruce needles and their role as pioneer decomposers.

The diversity of endophytic fungi within single symptomless Norway spruce needles is described and their possible role as pioneer decomposers after needle detachment is investigated. The majority (90%) of all 182 isolates from green intact needles were identified as Lophodermium piceae. Up to 34 isolates were obtained from single needles. Generally, all isolates within single needles had distinct randomly amplified microsatellite (RAMS) patterns. Single trees may thus contain a higher number of L. piceae individuals than the number of their needles. To investigate the ability of needle endophytes to act as pioneer decomposers, surface-sterilized needles were incubated on sterile sand inoculated with autoclaved or live spruce forest humus layer. The dry weight loss of 13-17% found in needles after a 20-week incubation did not significantly differ between the sterilized and live treatments. Hence, fungi surviving the surface sterilization of needles can act as pioneer decomposers. A considerable portion of the needles remained green during the incubation. Brown and black needles, in which the weight loss had presumably taken place, were invaded throughout by single haplotypes different from L. piceae. Instead, Tiarasporella parca, a less common needle endophyte, occurred among these invaders of brown needles. Needle endophytes of Norway spruce seem thus to have different abilities to decompose host tissues after needle cast. L. piceae is obviously not an important pioneer decomposer of Norway spruce needles. The diversity of fungal individuals drops sharply when needles start to decompose. Thus, in single needles the decomposing mycota is considerably less diverse than the endophytic mycota.

Ascomycota↗