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Biomedical subjects

M Wittmann

Publications and source records attributed to M Wittmann.

At least 19 recordsLinked to original sources

Stimulus-dependent processing of temporal order.

Two distinct conceptualisations of processing mechanisms have been proposed in the research on the perception of temporal order, one that assumes a central-timing mechanism that is involved in the detection of temporal order independent of modality and stimulus type, another one assuming feature-specific mechanisms that are dependent on stimulus properties. In the present study, four different temporal-order judgement tasks were compared to test these two conceptualisations, that is, to determine whether common processes underlie temporal-order thresholds over different modalities and stimulus types or whether distinct processes are related to each task. Measurements varied regarding modality (visual and auditory) and stimulus properties (auditory modality: clicks and tones; visual modality: colour and position). Results indicate that the click and the tone paradigm, as well as the colour and position paradigm, correlate with each other. Besides these intra-modal relationships, cross-modal correlations show dependencies between the click, the colour and the position tasks. Both processing mechanisms seem to influence the detection of temporal order. While two different tones are integrated and processed by a more independent, possibly feature-specific mechanism, a more central, modality-independent timing mechanism contributes to the click, colour and position condition.

Acoustic Stimulation↗

Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis.

BACKGROUND: Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. OBJECTIVE: To explore the impact of staphylococcal alpha-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. METHODS: Adult patients with AD were screened for cutaneous colonization with alpha-toxin producing S. aureus. As alpha-toxin may induce necrosis, CD4(+) T cells were incubated with sublytic alpha-toxin concentrations. Proliferation and up-regulation of IFN-gamma on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4(+) T cells was detected with the Electrophoretic Mobility Shift Assay. RESULTS: Thirty-four percent of the patients were colonized with alpha-toxin producing S. aureus and alpha-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic alpha-toxin concentrations induced a marked proliferation of isolated CD4(+) T cells. Microarray analysis indicated that alpha-toxin induced particularly high amounts of IFN-gamma transcripts. Up-regulation of IFN-gamma was confirmed both on the mRNA and the protein level. Stimulation of CD4(+) T cells with alpha-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. CONCLUSION: alpha-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic alpha-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that alpha-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.

Adult↗

Patterns of referring of patients with frontotemporal lobar degeneration to psychiatric in- and out-patient services. Results from a prospective multicentre study.

Dementia with frontotemporal lobar degeneration (FTLD) is clinically characterized by the occurrence of various psychiatric symptoms. In a recent study, the hospital-based prevalence of FTLD and the circumstances of the patients' admission to German psychiatric state hospitals were estimated. On the basis of further continuous assessment, this original FTLD group (n = 33) has been enlarged to 58 patients. The authors here present demographic and clinical data, and reasons for admission to geriatric psychiatry hospitals in comparison with 17 patients, who primarily attended the Memory Disorders Clinic of the University of Regensburg. The results implicate that both institutions see patients with different clinical syndromes: (1) patients were primarily referred to the Memory Disorders Clinic presenting memory and/or speech difficulties as the leading symptoms; (2) major reasons for hospitalisation of patients with FTLD in geriatric psychiatry hospitals were behavioural disturbances; (3) late-onset FTLD (>65 years) was more common than previously assumed in both institutions, and (4) increasing age at admission increased the likelihood to obtain a limited diagnostic approach of brain imaging (only cranial computer tomography) to evaluate the cause of dementia.

Adult↗

Rescattering of ultralow-energy electrons for single ionization of Ne in the tunneling regime.

Electron emission for single ionization of Ne by 25 fs, 1.0 PW/cm(2) laser pulses at 800 nm has been investigated in a kinematically complete experiment using a "reaction microscope." Mapping the complete final state momentum space with high resolution, a distinct local minimum is observed at P(e parallel )=0, where P(e parallel ) is the electron momentum parallel to the laser polarization. Whereas tunneling theory predicts a maximum at zero momentum, our findings are in good agreement with recent semiclassical predictions which were interpreted to be due to "recollision."

Journal Article↗

[Managing patients with chronic orofacial pain in the outpatient departments of dental and maxillofacial surgeons. Results of a survey].

OBJECTIVE: The aim of this study was to evaluate the significance attributed by dental and maxillofacial surgeons to the ambulatory management of chronic orofacial pain syndromes. MATERIALS AND METHODS: All the dentists and oral and maxillofacial surgeons working in ambulatory capacities within a county of the German Rhine Area were asked to answer a questionnaire on demographic data, diagnostic and therapeutic principles, and the use of analogue scales, surgical, minimal-invasive or pharmacological procedures. RESULTS AND DISCUSSION: Seventy-two ambulatory institutions reported 985 patients suffering from temporomandibular disorders (40.2%), headache-syndromes associated with facial pain (18.2%), and atypical odontalgia respectively phantom tooth pain (17.0%). Patients were characterized by prior dental treatment or trauma (41.9%), female gender (66.8%), middle age (81.1%, 20-60 years), very frequent change of therapists (54.6%) and long-term perseverance of pain (61.1% >6 months). Only 7% of therapists used visual or numerical analogue scales to assess pain intensity. Therapeutic procedures consisted of analgesics (15.7%) and further surgical procedures (47.7%). Pain therapists were rarely involved (12.5%). CONCLUSION: Dental and maxillofacial surgeons should apply an interdisciplinary and multimodal approach to diagnostics and therapy at an earlier stage in order to optimize the pain management of patients with chronic orofacial pain.

Adult↗

Coincident fragment detection in strong field photoionization and dissociation of H2.

Electron-ion momentum spectroscopy is used to investigate the correlated electronic and nuclear motion in fragmentation of H2 in 4 x 10(14) W/cm(2), 25 fs laser pulses at 795 nm. Reaction channel dependent photoelectron spectra indicate that besides the main, stepwise H2 ionization H2(+) dissociation mechanism resulting in the products H(1s) + H(+) + e(-) a second new mechanism has to be assumed. The momentum distribution of H(+) ions in the dissociation channels H(1s) + H(+) + e(-) and 2H(+) + 2e(-) is found to be independent of the kinetic energy of the photoelectrons.

Journal Article↗

Localization and physiological roles of metabotropic glutamate receptors in the direct and indirect pathways of the basal ganglia.

Our current understanding of the circuitry of the basal ganglia, and the pathophysiology of Parkinson's disease has led to major breakthroughs in the treatment of this debilitating movement disorder. Unfortunately, there are significant problems with the currently available pharmacological therapies that focus on dopamine replacement or dopaminergic agonists. Because of this, much effort has been focused on developing novel targets for the treatment of Parkinson's disease. The metabotropic glutamate receptors are a family of G-protein coupled receptors activated by glutamate. These receptors are differentially distributed throughout the basal ganglia in a manner suggesting that they may provide novel targets for the treatment of movement disorders. In this review we summarize anatomical and physiological data from our work and the work of other laboratories describing the distribution and physiological roles of metabotropic glutamate receptors in the basal ganglia with emphasis on possible therapeutic targets.

Afferent Pathways↗

Effects of different fibre sources and fat addition on cholesterol and cholesterol-related lipids in blood serum, bile and body tissues of growing pigs.

Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that the use of citrus pulp increased serum cholesterol concentrations when levels were low in the corresponding low-BFS diets (low-fat and soy bean diets), but caused no further increase in the coconut-oil/palm kernel oil blend diet. From the present results it seems that fermentable hemicelluloses have a more favourable effect of decreasing metabolic cholesterol and related traits than hardly digestible fibre, fermentable cellulose or, particularly, pectin. Furthermore, some types of fibre expressed a certain potential to reduce cholesterol content of fat pork and pork products by up to 10% (experiment 1) and 25% (experiment 2).

Adipose Tissue↗

Activation of group I metabotropic glutamate receptors produces a direct excitation and disinhibition of GABAergic projection neurons in the substantia nigra pars reticulata.

A pathological increase in excitatory glutamatergic input to substantia nigra pars reticulata (SNr) from the subthalamic nucleus (STN) is believed to play a key role in the pathophysiology of Parkinson's disease. We present an analysis of the physiological roles that group I metabotropic glutamate receptors (mGluRs) play in regulating SNr functions. Immunocytochemical analysis at the light and electron microscopic levels reveal that both mGuR1a and mGluR5 are localized postsynaptically in the SNr. Consistent with this, activation of group I mGluRs depolarizes SNr GABAergic neurons. Interestingly, although both group I mGluRs (mGluR1 and mGluR5) are expressed in these neurons, the effect is mediated solely by mGluR1. Light presynaptic staining for mGluR1a and mGluR5 was also observed in some terminals forming symmetric synapses and in small unmyelinated axons. Consistent with this, activation of presynaptic mGluR1a and mGluR5 decreases inhibitory transmission in the SNr. The combination of direct excitatory effects and disinhibition induced by activation of group I mGluRs could lead to a large excitation of SNr projection neurons. This suggests that group I mGluRs are likely to play an important role in the powerful excitatory control that the STN exerts on basal ganglia output neurons.

Animals↗

Separation of recollision mechanisms in nonsequential strong field double ionization of Ar: the role of excitation tunneling.

Vector momentum distributions of two electrons created in double ionization of Ar by 25 fs, 0.25 PW/cm(2) laser pulses at 795 nm have been measured using a "reaction microscope." At this intensity, where nonsequential ionization dominates, distinct correlation patterns are observed in the two-electron momentum distributions. A kinematical analysis of these spectra within the classical "recollision model" revealed an (e,2e)-like process and excitation with subsequent tunneling of the second electron as two different ionization mechanisms. This allows a qualitative separation of the two mechanisms demonstrating that excitation-tunneling is the dominant contribution to the total double ionization yield.

Journal Article↗

A system for the assessment and training of temporal-order discrimination.

Two programs were developed for psychophysical assessment and training of temporal-order thresholds in the visual and auditory modalities. Order threshold is defined as the minimum onset interval between two sensory events (stimulus onset asynchrony, SOA) that must exist before an observer is able to indicate the correct order of the events. Brain-injured patients with aphasia and children with language-learning impairments, i.e. those who have been diagnosed as performing poorly on temporal-order tasks and in discriminating stop-consonant vowel syllables, can effectively be trained by a feedback training procedure in which the SOA is manipulated. The performance in the temporal-order task and the ability to discriminate phonemes improves with this procedure. In the diagnostic program, the SOA is changed by an adaptive procedure that generates a sequence of SOAs converging to the threshold and is driven by the responses of the subject. The feedback-training program begins with the presentation of SOAs, which are slightly above the individual order threshold; they are subsequently varied according to the responses of the subject.

Aphasia↗

Activation of metabotropic glutamate receptor 1 inhibits glutamatergic transmission in the substantia nigra pars reticulata.

The substantia nigra pars reticulata is a primary output nucleus of the basal ganglia motor circuit and is controlled by a fine balance between excitatory and inhibitory inputs. The major excitatory input to GABAergic neurons in the substantia nigra arises from glutamatergic neurons in the subthalamic nucleus, whereas inhibitory inputs arise mainly from the striatum and the globus pallidus. Anatomical studies revealed that metabotropic glutamate receptors (mGluRs) are highly expressed throughout the basal ganglia. Interestingly, mRNA for group I mGluRs are abundant in neurons of the subthalamic nucleus and the substantia nigra pars reticulata. Thus, it is possible that group I mGluRs play a role in the modulation of glutamatergic synaptic transmission at excitatory subthalamonigral synapses. To test this hypothesis, we investigated the effects of group I mGluR activation on excitatory synaptic transmission in putative GABAergic neurons in the substantia nigra pars reticulata using the whole cell patch clamp recording approach in slices of rat midbrain. We report that activation of group I mGluRs by the selective agonist (R,S)-3,5-dihydroxyphenylglycine (100 microM) decreases synaptic transmission at excitatory synapses in the substantia nigra pars reticulata. This effect is selectively mediated by presynaptic activation of the group I mGluR subtype, mGluR1. Consistent with these data, electron microscopic immunocytochemical studies demonstrate the localization of mGluR1a at presynaptic sites in the rat substantia nigra pars reticulata. From this finding that group I mGluRs modulate the major excitatory inputs to GABAergic neurons in the substantia nigra pars reticulata we suggest that these receptors may play an important role in basal ganglia functions. Studying this effect, therefore, provides new insights into the modulatory role of glutamate in basal ganglia output nuclei in physiological and pathophysiological conditions.

Animals↗

Hemispheric specialisation for self-paced motor sequences.

Temporal aspects of motor control were investigated in patients with infarction to the brain with two finger-tapping tests. In the self-paced tapping task patients with cortical left-hemispheric lesions were slowed down and patients with left-hemispheric subcortical injuries were consistently faster as compared with control subjects and patients with right hemispheric cortical lesions. The results point to the dominant control of the left-hemisphere in voluntarily timed action and to a special time range of 250-300 ms involved in motor behaviour.

Adult↗

HPLC analysis of complete BZ systems. Evolution of the chemical composition in cerium and ferroin catalysed batch oscillators: experiments and model calculations.

In the last few years many new reaction routes and intermediates have been discovered in the mechanism of the Belousov-Zhabotinsky (BZ) reaction with the aid of high performance liquid chromatography (HPLC). These previous HPLC studies, however, were limited to the Ce(4+)-organic substrate (malonic or bromomalonic acid) systems only. Very recently some measurements were made on a cerium catalysed full BZ system but only in its induction period. The present work follows the evolution of the main chemical components in a cerium and in a ferroin catalysed full BZ system from the start until the end of the oscillatory regime in a batch reactor. While recording the potential oscillations of a bromide selective electrode we measured from time to time the concentration of the following components: malonic and bromomalonic acids and bromate as main components; malonyl malonate, ethanetetracarboxylic and bromoethenetricarboxylic acids which are recombination products of organic free radicals; oxidized intermediates: tartronic, oxalic (OA) and mesoxalic (MOA) acids, and brominated products: dibromoacetic and tribromoacetic acids. Recombination products are generated in the intervals when the autocatalytic reaction is "switched off". In the course of the autocatalytic periods, however, the organic radicals react with the inorganic bromine dioxide radical mainly which leads to the formation of MOA and OA. Due to a very fast Ce(4+)-MOA reaction, MOA can be detected in the ferroin catalysed BZ system only. Our model calculations deal exclusively with the cerium catalysed system. The suggested new Marburg-Budapest-Missoula (MBM) model includes both negative feedback loops (bromous acid-bromide ion Oregonator type and bromine dioxide-organic free radicals Radicalator type feedback) and the recently discovered radical-radical recombination reactions. Comparison of the experimental data with the model calculations shows a good qualitative agreement but some open problems still remain. To overcome these problems oxygen atom transfer and other redox reactions are proposed.

Journal Article↗

Detection of clonal T cell receptor gamma gene rearrangements in cutaneous T cell lymphoma by LightCycler-polymerase chain reaction.

Cutaneous T cell lymphoma is thought to be characterized by a monoclonal T cell infiltrate in the skin that can be detected by polymerase chain reaction-based amplification of T cell receptor gamma gene rearrangements. We sought to establish a new, simple, and fast LightCycler-based real-time polymerase chain reaction assay for the detection of monoclonality in cutaneous T cell lymphoma, which was suitable for routine laboratory application. Monoclonal T cell receptor gamma gene rearrangements were detected by polymerase chain reaction with consensus primers using: (i) a thermocycler followed by polyacrylamide gel electrophoresis; (ii) a Light Cycler followed by melting curve analysis; and (iii) a LightCycler and subsequent polyacrylamide gel electrophoresis. The detection limit of monoclonal Jurkat T cells diluted in polyclonal peripheral blood mononuclear cells was: (i) 1--3% by thermocycler--polymerase chain reaction and polyacrylamide gel electrophoresis; (ii) 10% by LightCycler--polymerase chain reaction and melting curve analysis; and (iii) 1% by LightCycler--polymerase chain reaction and polyacrylamide gel electrophoresis. In skin biopsies of 22 cutaneous T cell lymphoma patients, a monoclonal or biclonal T cell infiltrate was detected in: (i) 15 of 22 (68%) by thermocycler--polymerase chain reaction and polyacrylamide gel electrophoresis; (ii) 13 of 22 (59%) by LightCycler--polymerase chain reaction and melting curve analysis; and (iii) 16 of 22 (72%) by LightCycler--polymerase chain reaction and polyacrylamide gel electrophoresis. All three techniques revealed negative results in skin biopsies from 26 patients with benign dermatitis. In conclusion, LightCycler--polymerase chain reaction and melting curve analysis is a fast, simple and specific method to detect monoclonal T cell infiltrates in cutaneous T cell lymphoma. Sensitivity of LightCycler--polymerase chain reaction and polyacrylamide gel electrophoresis is slightly higher compared with sensitivity of thermocycler--polymerase chain reaction and polyacrylamide gel electrophoresis. Melting curve analysis, however, is less sensitive compared with polyacrylamide gel electrophoresis, and in case of negative results of the melting curve analysis, it is recommended to resolve LightCycler--polymerase chain reaction samples by gel electrophoresis.

Adult↗

[The education program for patients with COPD from Bad Reichenhall].

An education program for patients with COPD is presented. This program was created for inpatient pulmonary rehabilitation at the Klinik Bad Reichenhall. We intend to improve the patients' acceptance of disease and their understanding of therapy. Furthermore we want to impart basic knowledge about COPD and its treatment. The patients should be motivated to manage the disease in an active and more independent way: They should control the natural course of their disease by learning preventive and restorative health care behaviours and self-help activities in case of acute exacerbations. The aim is to attain the acceptance of changing life-style.

Adaptation, Psychological↗

Activation of group III mGluRs inhibits GABAergic and glutamatergic transmission in the substantia nigra pars reticulata.

The GABAergic projection neurons of the substantia nigra pars reticulata (SNr) exert an important influence on the initiation and control of movement. The SNr is a primary output nucleus of the basal ganglia (BG) and is controlled by excitatory inputs from the subthalamic nucleus (STN) and inhibitory inputs from the striatum and globus pallidus. Changes in the output of the SNr are believed to be critically involved in the development of a variety of movement disorders. Anatomical studies reveal that metabotropic glutamate receptors (mGluRs) are highly expressed throughout the BG. Interestingly, mRNA for group III mGluRs are highly expressed in STN, striatum, and globus pallidus, and immunocytochemical studies have shown that the group III mGluR proteins are present in the SNr. Thus it is possible that group III mGluRs play a role in the modulation of synaptic transmission in this nucleus. We performed whole cell patch-clamp recordings from nondopaminergic SNr neurons to investigate the effect of group III mGluR activation on excitatory and inhibitory transmission in the SNr. We report that activation of group III mGluRs by the selective agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 100 microM) decreases inhibitory synaptic transmission in the SNr. Miniature inhibitory postsynaptic currents studies and paired-pulse studies reveal that this effect is mediated by a presynaptic mechanism. Furthermore we found that L-AP4 (500 microM) also reduces excitatory synaptic transmission at the STN-SNr synapse by action on presynaptically localized group III mGluRs. The finding that mGluRs modulate the major inputs to SNr neurons suggests that these receptors may play an important role in motor function and could provide new targets for the development of pharmacological treatments of movement disorders.

2-Amino-5-phosphonovalerate↗