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Biomedical subjects

M M Müller

Publications and source records attributed to M M Müller.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Modulation of induced gamma band activity in the human EEG by attention and visual information processing.

Here we present a series of four studies aimed to investigate the link between induced gamma band activity in the human EEG and visual information processing. We demonstrated and validated the modulation of spectral gamma band power by spatial selective visual attention. When subjects attended to a certain stimulus, spectral power was increased as compared to when the same stimulus was ignored. In addition, we showed a shift in spectral gamma band power increase to the contralateral hemisphere when subjects shifted their attention to one visual hemifield. The following study investigated induced gamma band activity and the perception of a Gestalt. Ambiguous rotating figures were used to operationalize the law of good figure (gute Gestalt). We found increased gamma band power at posterior electrode sites when subjects perceived an object. In the last experiment we demonstrated a differential hemispheric gamma band activation when subjects were confronted with emotional pictures. Results of the present experiments in combination with other studies presented in this volume are supportive for the notion that induced gamma band activity in the human EEG is closely related to visual information processing and attentional perceptual mechanisms.

Attention↗
PubMed2000

Mutagenicity of N-nitrosodiethylamine in the Ames test with S. typhimurium TA1535 is due to volatile metabolites and is not dependent on cytochrome P4502E1 induction.

N-Nitrosodiethylamine (NDEA) is carcinogenic in all investigated animal species at relatively low dosages. No threshold has been detected for these carcinogenic effects. The substance has been extensively investigated in various in vitro systems, revealing only weak mutagenicity at relatively high dosages. We reinvestigated NDEA in the Ames test with Salmonella typhimurium TA1535 to establish appropriate modifications of the standard Ames test protocol, to achieve a dose-dependent mutagenic response at a reasonably low dose range. Two main modifications were evaluated. Since the metabolism of dialkylnitrosamines is postulated to be mainly dependent on cytochrome P4502E1, a pyrazole-induced rat liver S9 was applied. The second modification involved a gastight preincubation, since metabolites of NDEA might evaporate from the incubation mixture. Cytochrome P4502E1 induction in Wistar rats was achieved by pyrazole treatment. For comparison, a rat liver S9-fraction produced by beta-naphtoflavone/phenobarbital induction was used. N-Nitrosopyrrolidine served as positive control for pyrazole-induced S9-mix with TA1535. NDEA showed no mutagenic response under all test conditions in the presence of pyrazole-induced S9-mix. A strong mutagenic response, exceeding the base rate up to 15-fold at a dose range of 25-1000 microg/plate, was observed using beta-naphtoflavone/phenobarbital-induced S9-mix, gastight preincubation and TA1535. In conclusion the Ames test with gastight preincubation can be useful for the testing of volatile compounds or substances leading to gaseous metabolites. The weak response of NDEA in the Ames test observed previously seems mainly to be due to the volatile character of its mutagenic metabolites. Our results do not support the hypothesis that cytochrome P4502E1 is a major toxifying enzyme for the formation of Ames-test-positive metabolites from NDEA.

Animals↗
PubMed2000

In vitro effects of mycophenolic acid on cell cycle and activation of human lymphocytes.

The immunosuppressant mycophenolic acid (MPA) selectively inhibits proliferation of T- and B-lymphocytes by blocking inosine 5'-monophosphate-dehydrogenase (IMPDH), the key enzyme for de-novo-synthesis of guanine nucleotides. In an in vitro study the effects of MPA on human peripheral blood lymphocyte activation markers and on cell cycle characteristics were investigated. Mononuclear cells from healthy volunteers were incubated with phytohaemagglutinin (PHA) and increasing doses of MPA. After 72 h incubation an aliquot of the cells was stained with propidium iodide and measured by FACS analyses to assess the DNA shape. In addition, the expression of the activation markers HLA-DR and CD25 on T- and B-lymphocytes was determined by flow cytometry analysis.PHA stimulation led to a significant increase of the S-phase of cell cycle. PHA stimulation clearly increased mean fluorescence intensity (MFI) of HLA-DR expression on B-lymphocytes. PHA stimulation also elevated the number of CD25 positive B-lymphocytes. Expression of HLA-DR on T-lymphocytes was not influenced by PHA, whereas CD25 expression and MFI significantly increased. All the observed PHA induced effects were reduced by co-incubation with increasing doses of MPA. The data presented show that in vitro the immunosuppressive effect of MPA can be demonstrated using FACS technology on a cellular level. MPA leads to an inhibition of cell cycle proliferation in peripheral blood lymphocytes.

B-Lymphocytes↗
PubMed2000

Concurrent recording of steady-state and transient event-related potentials as indices of visual-spatial selective attention.

OBJECTIVES: The present study investigated the effects of spatial attention on concurrently recorded visual event-related potentials (ERPs) and steady-state visual evoked potentials (SSVEPs) to isoluminant color changes embedded in rapidly flickering stimuli. METHODS: EEG was recorded while subjects attended to flickering LEDs in either the right or left visual hemifield and responded by a button press to isoluminant color changes (targets). RESULTS: Target isoluminant color changes elicited the typical ERP components P1, N1, N2 and P3, which were enhanced for attended targets compared to unattended targets. Consistent with previous findings, SSVEP amplitude was enlarged for attended flicker stimuli at posterior electrode sites contralateral to the attended visual hemifield. In addition, significant correlations were found between the N1, N2 and the SSVEP attention effects, whereas no such correlations were found between the P1, P3 and SSVEP attention effects. CONCLUSIONS: Results suggest that the SSVEP and ERP reflect partially overlapping attentional mechanisms that facilitate the discriminative processing of stimuli at attended locations.

Adult↗
PubMed2000

MEG gamma band activity in schizophrenia patients and healthy subjects in a mental arithmetic task and at rest.

OBJECTIVES: High frequency oscillations have been suggested as a correlate of cognitive processes and have recently also been implicated in aberrant forms of information processing. The present study investigated whether magnetoencephalographic (MEG) gamma band activity (20-71 Hz) can serve as an index of cognitive processes in the absence of external stimulation and to what extent gamma activity differs between healthy people and schizophrenia patients. METHODS: The amount and topography of MEG power in the gamma band range was examined in 15 schizophrenia patients and 15 healthy comparison subjects while performing a complex mental arithmetic task and at rest. RESULTS: In healthy subjects a left frontal and left fronto-temporal increase in gamma power was observed during mental arithmetic. Schizophrenia patients either failed to display such a task effect (30-45 Hz) or had reversed lateralization with enhanced activity over right frontal and right fronto-temporal regions under cognitive demands (45-71 Hz). In the frequency band from 60 to 71 Hz patients showed less gamma at fronto-temporal, posterio-temporal and occipital sites irrespective of the task. CONCLUSIONS: These results indicate, first, that gamma topography can index cognitive activation in a very complex and purely internal task. Second, groups differed in the pattern of activation during the task, a result which may be consistent with working memory dysfunction in schizophrenia. Third, the general topographic difference between healthy subjects and patients is in line with the notion of abnormalities in the thalamocortical circuit in schizophrenia.

Adult↗
PubMed2000

Mutagenicity of diesel exhaust particles from two fossil and two plant oil fuels.

Particulate matter of diesel engine exhaust from four different fuels was studied for content of polynuclear aromatic compounds and mutagenic effects. Two so-called biodiesel fuels, rapeseed oil methylesters (RME) and soybean oil methylesters (SME), were compared directly with two fossil diesel fuels with the normal (DF) and a low sulfur content (LS-DF). Diesel exhaust particles were sampled on filters from the diluted and cooled exhaust of a test engine at five different speeds and loads. Filters were weighed for total particulate matter, Soxhlet extracted with dichloromethane and the content of insoluble material determined. The soluble organic fraction was analysed for polynuclear aromatic compounds. Mutagenicity was determined using the Salmonella typhimurium/mammalian microsome assay with strains TA98 and TA100. Compared with DF, the exhaust particles of LS-DF, RME and SME contained less insoluble material, which consisted mainly of the carbon cores of diesel exhaust particles. The concentrations of individual polynuclear aromatic compounds varied widely among the different exhaust extracts, but total concentrations of the compounds were approximately double for DF and SME compared with LS-DF and RME. In TA98 significant increases in mutation rates were obtained for the soluble organic fractions of all fuels for engines running at full speed (load modes A and D), but for DF revertants were 2- to 10-fold more frequent as compared with LS-DF, RME and SME. Revertant frequencies for DF and partly for LS-DF were also elevated in TA100, while RME and SME gave no significant increase in mutations. The results indicate that diesel exhaust particles from RME, SME and LS-DF contain less black carbon and total polynuclear aromatic compounds and are significantly less mutagenic in comparison with DF. A high sulfur content of the fuel and high engine speeds (rated power) and loads are associated with an increase in mutagenicity of diesel exhaust particles.

Chromatography, High Pressure Liquid↗
PubMed2000

Health complaints and immunological markers of exposure to bioaerosols among biowaste collectors and compost workers.

OBJECTIVES: In a cross sectional study, work related health complaints and diseases of 58 compost workers and 53 biowaste collectors were investigated and compared with 40 control subjects. Levels of specific IgG antibodies to moulds and bacteria were measured as immunological markers of exposure to bioaerosols. METHODS: With a standardised protocol, the participants of the study were interviewed for work related symptoms, conditions of exposure to bioaerosols at their workplaces, exposure to bioaerosols from other sources, atopic diseases, and smoking habits. They were clinically examined by physicians specialised in occupational medicine. Also, concentrations of specific IgG antibodies against antigens of moulds and actinomycetes occurring regularly at these workplaces were measured and compared with the health complaints of the workers. RESULTS: Compost workers had significantly more symptoms and diseases of the airways (p=0.003) and the skin (p=0.02) than the control subjects. Health complaints of biowaste collectors did not differ significantly from those of the control group. Subjects with atopic diseases were underrepresented in the compost workers (p=0.003). Significantly increased antibody concentrations against fungi and actinomycetes were measured in workers at composting plants. The concentrations in biowaste collectors did not differ significantly from those in the control subjects. A significant association between the diseases and increased antibody concentrations were found in the compost workers. CONCLUSION: The high exposure to bioaerosols of compost workers is significantly associated with a higher frequency of health complaints and diseases as well as higher concentrations of specific antibodies against moulds and actinomycetes. A healthy worker effect is indicated by the underrepresentation of atopic diseases among the compost workers compared with biowaste collectors and the control group.

Adult↗
PubMed2000

Markers of endothelial dysfunction.

The endothelium is a functional barrier between vessel wall and blood stream. Assuming the total human vascular and capillary system occupies a surface area of more than 1,000 m2 which is covered by 1,013 endothelial cells, the complex role of the endothelium for hemostasis and immunological and metabolic processes becomes obvious. Dysfunction of the endothelium is a critical factor in the pathogenesis of vascular diseases and thrombus formation. This paper provides a brief review of physiological endothelial functions and summarizes measurable changes in products released from endothelial cells under pathological conditions which were associated with endothelial dysfunction.

Animals↗
PubMed2000

Adhesion molecule behavior during rejection and infection episodes after heart transplantation.

In cardiac transplant recipients the release of soluble cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune activation. It is uncertain whether there is a specific pattern of release during infection or cardiac allograft rejection. In a prospective study, 30 consecutive cardiac allograft recipients were followed for a median period of 11.4 months (range 1-34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E-Selectin (sE-Selectin) were measured in addition to acute phase proteins (C-reactive protein, alpha1-antitrypsin), complement factors (C3, C4) and beta2-microglobulin. The measured serum levels were correlated with the clinical status of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy subjects served as controls. Six days before biopsy-proven cardiac allograft rejection sICAM-1-release started to increase (p < 0.05) as compared to uneventful clinical status. The peak concentration of sICAM-1 was measured three days before rejection. On the day of rejection, serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were increased, whereas sE-Selectin was not markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were elevated at the day of diagnosis and both parameters reached peak levels three days after onset of chemotherapy. In multivariate analysis soluble adhesion molecules only weakly discriminated between rejection and infection (sensitivity: 13%, specificity: 95%). Although, in combination with routine blood parameters the discriminatory power could be improved (sensitivity: 85%, specificity: 85%) the clinical utility of these markers in non-invasive monitoring is limited.

Adult↗
PubMed2000

Serum osteocalcin and urinary crosslaps are suitable markers of bone turnover in response to short-term hormone replacement therapy.

In this study we evaluated the effect of short-term hormone replacement therapy (HRT) on bone formation (serum osteocalcin) and resorption markers (urinary type I collagen peptides (crosslaps), urinary total free pyridinoline (TPYRI) and urinary free deoxypyridinoline (DPYRI)) as well as female sex hormones (serum estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH)) in a group of early postmenopausal women with severe estrogen deficiency. The 46 healthy postmenopausal women with serum estradiol levels < 10 ng/l were subsequently divided into two groups, according to their compliance with HRT. In the group taking HRT significant changes from baseline values could be observed in estradiol, FSH, urinary crosslaps and serum osteocalcin levels after 6 months, whereas no changes could be observed in LH, TPYRI and DPYRI from baseline values. In the group which refused HRT all values were increased relative to baseline values, indicating increased bone turnover. Serum osteocalcin and urinary crosslaps were significantly decreased in women taking HRT in comparison to the group refusing HRT. After 6 months the treated patients showed a decrease in urinary crosslaps of 42% (SD 12%) and in serum osteocalcin of 24% (SD 6%) in comparison with baseline values. In patients who refused HRT, urinary crosslaps were increased by 43% (SD 20%) and serum osteocalcin levels decreased by 2% (SD 9%) compared to baseline values. In postmenopausal women suffering from severe estrogen deficiency (estradiol < 10 ng/l) serum osteocalcin and urinary crosslaps are significantly increased, indicating a clear correlation between estrogen deficiency and an increase in bone resorption as well as bone formation. The recommended HRT dose was sufficient to reduce the rate of bone turnover to premenopausal values. Serum osteocalcin and urinary crosslaps are suitable candidates not only for the assessment of a high postmenopausal bone turnover, but also for monitoring the response to and for verifying the actual intake of HRT or other antiresorptive treatment.

Administration, Oral↗
PubMed2000

Oscillatory cortical activities in the gamma band in the human EEG induced by visual stimuli--representation of the stimulus?

The present work presents three experiments investigating cortical activities in the gamma band in humans. On the basis of theoretical models and animal experiments, synchronized oscillatory neuronal activity is discussed as the key mechanism by which the brain binds information processesed in different cortical areas to form a percept. Using an identical stimulation design--the same as used in animal studies--it was shown that induced gamma band responses in the EEG resemble the same features as those found in the intracortical recordings of animals. In addition, the present work demonstrates that these cortical activities are not higher harmonics of the alpha band and that they are sensitive to the features of the stimulus. These results support the notion that gamma band activity is not just a by-product of neuronal activity and that alpha- and gamma band activities most certainly represent different cortical functional states.

Adult↗