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M Matzke

Publications and source records attributed to M Matzke.

35 records · Page 2Linked to original sources

Recognition memory deficits in amyotrophic lateral sclerosis assessed with event-related brain potentials.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) has been shown to cause neuropsychological deficits. The present investigation sought to delineate memory deficits by recording cognitive event-related potentials (ERPs). SUBJECTS AND METHODS: Eight ALS patients and 8 matched controls were subjected to a 2-phase recognition memory test. During the first phase words were presented consecutively on a video-screen with one-third of the words being repeated. The subject had to press buttons according to whether a word had been repeated or not. During the second phase (delay 1 h) a second list containing 33% old items from phase 1 and 66% new words was shown with an old/new decision required. RESULTS: ALS patients showed less accurate recognition in the second phase. The ERPs of the controls showed a reliable difference between old and new items in both phases. This difference was nearly absent in the patients in both phases. CONCLUSION: The ERP pattern suggests abnormal memory processes in ALS. The results are compared with data from similar experiments in Huntington's and Alzheimer's disease and are interpreted in terms of an encoding deficit in ALS.

Adult↗

Human brain potentials to reading syntactic errors in sentences of different complexity.

In order to determine if an event-related brain potential (ERP) effect described for syntactic violations (P600/SPS) varies with the amount of reprocessing entailed by a violation, number incongruencies were presented either within simple declarative or within subordinate clauses. ERPs were recorded while 12 German subjects read the stimulus materials presented word by word on a video monitor. The ERPs showed a P600/SPS effect for all sentence types, which was smallest in amplitude and earliest in latency for simple declarative sentences. This effect therefore qualifies as a metric for the amount and timing of syntactic reprocessing entailed by a syntactic error. In addition, a late frontal negativity (1000-1400 ms range) was found for the simple declarative sentences.

Adult↗

Brain potentials and time estimation in humans.

Several parameters of the event-related potential (ERP) were assessed while 12 healthy volunteers performed a time production task. Each trial consisted of a series of 20 flashes presented at regular intervals on a videomonitor (interval 768 ms). After these flashes the subjects had to estimate the time it would take for an additional five flashes and to press a button upon the 5th interval. ERPs were recorded from 19 electrodes with three effects being of interest: (1) possible emitted potentials at the times at which flashes had occurred, if the series had continued, (2) the ERP to probe flashes presented during the production period, and (3) the slow potential shift during the estimation period. In addition reaction times were recorded. While ERP effects (1) and (2) were not informative with respect to time estimation processes, the slow potential shift with a frontopolar distribution appears to index time-keeping functions in humans.

Adult↗

An electrophysiological analysis of altered cognitive functions in Huntington disease.

BACKGROUND: Neuropsychological deficits are a main feature of Huntington disease (HD) with previous data suggesting involvement of memory functions and visual processing. OBJECTIVE: To increase the knowledge about cognitive malfunction in HD in the domains of visual processing and memory by the use of modern electrophysiological techniques (event-related potentials [ERPs]). DESIGN: A case-control design was used. Three ERP paradigms were used; a parallel visual search paradigm allowed for the simultaneous processing of a multi-element visual array in search of a target stimulus, while a serial search paradigm with varied numbers of distractor items necessitated a serial one by one scanning of the arrays. The third experiment was a word-recognition memory task. SETTING: The measurements were obtained in a neurophysiological laboratory of a university hospital. PATIENTS AND CONTROLS: Nine patients with HD and 9 control subjects matched for age, sex, and education were studied. MAIN OUTCOME MEASURES: Components of averaged ERPs were quantified by latency and amplitude measures and subjected to statistical analysis. Behavioral measures (search time, hit rate, and recognition accuracy) were assessed as well. RESULTS: The early visual components showed a significant latency shift (delay of about 50 milliseconds) in HD. In the search paradigms the P3 components differentiating target and standard stimuli were virtually absent in HD as was the ERP effect indexing word recognition. This was accompanied by a marked delay in search times and lower hit rates in the search tasks and a grossly reduced recognition accuracy in the memory task. CONCLUSIONS: The results suggest marked impairments of patients with HD in early visual sensory processing (early components). Deficits in visual search might be attributed to an impairment to deploy attentional resources across the visual field and/or an inability to control eye movements. The ERPs in the memory task differed grossly from similar data obtained by others in patients with Alzheimer disease, suggesting a different neural basis for the amnesia in HD.

Adult↗

Event-related brain potentials to unfamiliar faces in explicit and implicit memory tasks.

The purpose of this study was to investigate electrophysiological correlates related to the recognition of repeated faces in the intact human by means of event-related brain potentials (ERPs). A group of young healthy adults performed a continuous face recognition task, in which 240 unfamiliar faces were flashed upon a computer screen with 80 of the faces being repetitions. The subjects had to classify faces as previously seen and previously unseen faces. The concomitantly recorded ERPs from 19 scalp sites revealed a more positive going waveform for the correctly classified repeated faces beginning at about 280 ms (old/new effect). The same subjects performed a similar task with visually presented concrete nouns as stimuli. The old/new effect in this task showed a similar distribution, amplitude and onset latency. It is thus concluded that the old/new effect is not specific to the materials to be memorized. In contrast, the old/new effect in an implicit face repetition experiment (with the detection of famous persons being the task) showed a different distribution. It is argued that the differential distribution might reflect the different requirements of the two tasks (explicit vs. implicit task). Recent interpretations of the old/new effects are discussed.

Adult↗

Molecular and cytogenetic analyses of stably and unstably expressed transgene loci in tobacco.

To study the influence of genomic context on transgene expression, we have determined the T-DNA structure, flanking DNA sequences, and chromosomal location of four independent transgene loci in tobacco. Two of these loci were stably expressed in the homozygous condition over many generations, whereas the other two loci became unstable after several generations of homozygosity. The stably expressed loci comprised relatively simple T-DNA arrangements that were flanked on at least one side by plant DNA containing AT-rich regions that bind to nuclear matrices in vitro. Of the unstably expressed loci, one consisted of multiple incomplete T-DNA copies, and the second contained a single intact T-DNA; in both cases, however, binary vector sequences were directly contiguous to a right T-DNA border. Fluorescence in situ hybridization demonstrated that the two stably expressed inserts were present in the vicinity of telomeres. The two unstably expressed inserts occupied intercalary and paracentromeric locations, respectively. Results on the stability of transgene expression in F1 progeny obtained by intercrossing the four lines and the sensitivity of the four transgene loci to inactivation in the presence of an unlinked "trans-silencing" locus are also presented. The findings are discussed in the context of repetitive DNA sequences and the allotetraploid nature of the tobacco genome.

Amino Acid Sequence↗

Flexibility in the structure of human information processing.

The studies reported in this chapter argue for a flexible organization of higher mental processes, including perceptual and attentional systems in the visual modality and attentional systems related to action. There is electrophysiologic evidence that the visual perceptual system has a modularized structure, and that selection of perceived features is adjustable to sensory, conceptual, and utility constraints, both with respect to the hierarchy of selection cues and the transmission of information between perception and action. A distributed neural network subserves these functions and may therefore provide a source for plasticity and reorganization after brain damage by flexibility in the allocation of resources to various stages of stimulus analysis.

Cognition↗

Hierarchical visual stimuli: electrophysiological evidence for separate left hemispheric global and local processing mechanisms in humans.

Using reaction time measurements it has been shown that the neural processing of hierarchically composed visual stimuli may be mediated by partly distinctive mechanisms of global and local features analysis. Patients with focal left hemisphere brain lesions showed an impairment of local and patients with right hemisphere lesions of global stimulus perception. Our experiment was designed to extend the investigations of global/local feature analysis using the event-related brain potential (ERP) technique in healthy subjects. Thirteen subjects viewed a series of hierarchically composed non-linguistic stimuli in a divided attention condition in order to detect target stimuli which could be present at both local and global feature level, ERP analysis showed a posterior negative component (Ne) to be the correlate of early global/local information processing. When local targets were presented there was an effect of the global (non-target) level (termed 'distractor level') upon the onset of Ne but not vice versa. This supports the view of separate cortical mechanisms of global/local feature analysis. At odds with the previous patient data was the finding that both global and local level information was predominantly processed from the left hemisphere.

Adult↗

Brain potential correlates of number errors in the Turkish language.

Event-related potentials (ERPs) were recorded from 16 native speakers of Turkish while they watched Turkish sentences flashed upon the screen of a videomonitor. The sentences were three words long and contained a verb at the terminal position that was manipulated (1) to have either the correct or the incorrect number with regard to the subject of the sentence, and (2) to be semantically appropriate, inappropriate or to be a pseudoverb. The ERPs from 19 scalp channels revealed a more positive waveform at the left-fronto-temporal site with an onset latency of about 200 ms for the verbs having the wrong number regardless of the semantic appropriateness of the word, while at right fronto-temporal sites a more negative waveform was observed for plural words only. This number incongruency ERP-effect in Turkish is clearly at odds with findings from other languages.

Adult↗

Determination of the thermal neutron flux in a fast neutron beam by use of a boron-coated ionization chamber.

The thermal neutron distribution in slow and fast neutron beams is usually determined using the foil activation method. In this work a small magnesium walled ionization chamber, in which the inner surface of the wall has been coated with 10B to increase the sensitivity for thermal neutrons, is used to estimate the thermal neutron component of the beam. After calibration and determination of the directional response in a thermal neutron beam a comparison with foil activation at different depths in water was performed to investigate the reliability of the ionization measurements. The chamber was used in a computer controlled water phantom to measure the depth and lateral distribution of the thermal neutron dose. With this arrangement two-dimensional scans of the thermal neutrons could be performed quickly and with high accuracy.

Biophysical Phenomena↗

Mode of action of the leukotriene synthesis (FLAP) inhibitor BAY X 1005: implications for biological regulation of 5-lipoxygenase.

Five-lipoxygenase (5-LOX) inhibition is gaining increasing importance as a novel approach to therapy of allergic asthma and other inflammatory diseases. Presently, two types of inhibitors are known, direct 5-LOX inhibitors (LOI) and the FLAP (five lipoxygenase activating protein) binding leukotriene synthesis inhibitors (LSI). The 5-LOX selective and orally active quinoline LSI, BAY X 1005, shares many mechanistic features with the indole LSI, MK-886. The binding of BAY X 1005 to FLAP correlates with LTB4 synthesis inhibition. BAY X 1005 has been shown to bind to the 18 kD protein FLAP. BAY X 1005 inhibits 5-LOX translocation from the cytosol to membranes and reverses 5-LOX translocation. The use of BAY X 1005 has helped to elucidate part of the complex FLAP/5-LOX interaction by showing that FLAP appears to represent a 5-LOX substrate transfer protein channelling endogenous and exogenous arachidonic acid to the leukotriene synthetizing 5-LOX. This notion presented by our group in 1992 has stimulated further mechanistic studies. These findings have additionally led to the hypothesis that substrate competition is not confined to the LSI/FLAP interaction but may also be true for the LOI/5-LOX interaction and that even mixed LSI/LOI 5-LOX inhibitors are feasible, yet have not been described. Further mechanistic work on LSI will be orientated not only to further elucidate the complex FLAP/5-LOX interaction, but also to identify FLAP-related eicosanoid binding proteins.

Arachidonate 5-Lipoxygenase↗

Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials.

The effects of oxazepam and a standardized extract of kava-roots (WS1490, W. Schwabe, Karlsruhe) on reaction time and event-related potentials (ERPs) were investigated in a visual search paradigm using a double-blind design in young, healthy males. Significant effects of oxazepam were obtained in a number of psychometric tests as well as search time and quality. Several ERP components of different latency, topography and functional significance were affected by the medications. Oxazepam led to a reduction of the amplitude of the parietal N1, frontal N2, posterior contralateral N2, and occipital P3 components. WS 1490 was associated with a greater posterior N1, posterior contralateral N2, and occipital P3. The effects are discussed in the light of the functional properties of the components and provide clues as to the psychological site of action of the drugs.

Adult↗

Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task.

Twelve healthy volunteers were tested in a double-blind crossover study to assess the effects of oxazepam and an extract of kava roots (Piper methysticum) on behavior and event-related potentials (ERPs) in a recognition memory task. The subjects' task was to identify within a list of visually presented words those that were shown for the first time and those that were being repeated. The repeated words were associated with an increased positivity beginning approximately 250 ms poststimulus. Oxazepam led to a reduction of a negative component in the 250-500 ms range for both old and new words and to a reduction of the old/new difference in the ERP associated with a significantly worse recognition rate. Kava on the other hand showed a slightly increased recognition rate and a larger ERP difference between old and new words.

Adult↗

Succinamopine: a new crown gall opine.

Agrobacterium tumefaciens strains can incite plant tumors consisting of transformed cells that synthesize novel metabolites called opines. The pattern of opine synthesis is dictated by plasmid-borne genes in the pathogen; additional plasmid genes confer on the pathogen the ability to catabolize the same pattern of opines synthesized. One group of A. tumefaciens strains, AT181, EU6, and T10/73, contains closely related tumor-inducing (Ti) plasmids that encode the ability to degrade the opine nopaline; but tumors incited by these strains do not synthesize nopaline. We demonstrated by Southern blot hybridization that AT181(pTi) has no DNA homologous to the nopaline synthase gene of pTi T37, a nopaline Ti plasmid that appears to be most closely related to this group based on fingerprint analysis. Tumors incited by these seemingly anomalous strains contain a new opine that we designate succinamopine. Its structure is analogous to that of nopaline, with asparagine replacing arginine. Evidence for the structure of succinamopine, as well as those of two related metabolites, succinamopine lactam and succinopine lactam, will be published elsewhere. Ability to catabolize succinamopine, succinamopine lactam, and succinopine lactam is encoded by pTi AT181, pTi EU6, and pTi T10/73, but not by any of 15 other Ti and root-inducing plasmids tested. Three avirulent strains tested did not catabolize succinamopine, succinamopine lactam, or succinopine lactam. We propose that pTi AT181, pTi EU6, and pTi T10/73 be designated the succinamopine Ti plasmids.

Amino Acids↗

BAY X1005, a new selective inhibitor of leukotriene synthesis: pharmacology and pharmacokinetics.

The enantiomer BAY X1005 [(R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid] potently inhibits LTB4 synthesis in isolated PMNL of various species (IC50 mumol/l, human 0.22, rat 0.026, mouse 0.039) and LTC4 synthesis in mouse macrophages (IC50 0.021 mumol/l). Due to high protein binding the in vitro potency for LTB4 synthesis inhibition in whole blood is lowered to 17 mumol/l as determined by RIA. BAY X1005 is selective for the 5-lipoxygenase pathway leaving 12-HETE and HHT unaltered, as determined in human whole blood. After oral application BAY X1005 inhibits edema formation and myeloperoxidase activity in the arachidonate-induced mouse ear inflammation test (ED50 48.7 and 7.9, respectively). Oral activity in the rat ex vivo is found in whole blood for LTB4 synthesis inhibition (ED50 11.8 mg/kg p.o.). BAY X1005 demonstrates a high bioavailability (f 86%) with a Cmax of 13 mg/l and t1/2 of 3.5 h in the rat at 10 mg/kg p.o. Thus, the pharmacodynamic, pharmacokinetic profile and safety aspects of the leukotriene synthesis inhibitor BAY X1005 allow testing in man for its therapeutic potential in inflammatory and allergic diseases.

Administration, Oral↗