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Biomedical subjects

T Dierks

Publications and source records attributed to T Dierks.

At least 91 records · Page 5Linked to original sources

Disorders of smooth pursuit eye movement and auditory N100 in schizophrenic patients.

Attentional factors are thought to affect eye-tracking patterns. The present study examined the hypothesis that specific quantitative features of eye tracking would be correlated with the amplitude of a component of the auditory evoked potential, the N100, which is known to be enhanced by arousal and selective attention. We studied 12 clinically stable schizophrenic patients by means of DC-electro-oculography. The frequency and amplitude of different types of saccades (catchup, backup, anticipatory saccades, and square wave jerks) were assessed. The results suggest that small and large saccades, as classified by a simple amplitude criterion (4 degrees), have differential meanings and indicate that enhanced amplitudes of small saccades are an effect of arousal.

Adult↗

Differential validity of psychometric tests in dementia of the Alzheimer type.

Forty-nine patients with a clinical diagnosis of probable dementia of the Alzheimer type underwent an extensive test battery designed to evaluate cognitive deficits according to NINCDS/ADRDA criteria. All patients demonstrated signs of impairment on this test battery. One day later, they were administered a second test battery that consisted of the Mini-Mental State Examination (MMS), the Alzheimer's Disease Assessment Scale (ADAS), the SKT test (SKT), and the Brief Cognitive Rating Scale (BCRS) to assess the construct validity, sensitivity, and possible shortcomings of these tests. A control group of 47 age-matched persons was administered the same test battery to allow a comparison with reference values from other studies. Due to the design of the study, values of controls and patients did not overlap. Intercorrelations in patients were above 0.65 (p < 0.05 after Bonferroni correction) for all four cognitive tests. The ADAS and BCRS appeared to document the whole course of the disease in patients studied. The best differentiation with the SKT test could be obtained in mild to moderate dementia; however, due to the test's construction, a floor effect demonstrated its limitations in the case of severe dementia. Results obtained with the MMSE indicated the contrary: a ceiling effect showed its lack of differentiation in mild dementia. Therefore, a combination of tests should be used in the evaluation of cognitive deficits in the course of dementia of the Alzheimer type.

Activities of Daily Living↗

[Importance of the EEG in early and differential diagnosis of dementia of the Alzheimer type].

The development of new parameters in the quantitative evaluation of EEG provides new diagnostic opportunities for the clinician. Reviewing all published papers on EEG and dementia over the last 10 years revealed 30 out of 428 studies discussing EEG alterations in relation to the severity of the disease. This approach provides useful information for early and differential diagnosis of dementia. Besides a generalised slowing-down represented by an increase of delta and theta and a decrease of alpha and beta in the frequency spectrum (also characterised by a reduction of the peak frequency), the topography of the alterations changes depending on the severity of the disease. For instance, the alpha activity loses its normally occipital orientation. In early stages of the disease, it is measured parietally ("anteriorized"). In advanced stages, the activity is equally distributed over the scalp. Some studies found significant alterations even in early stages of the disease, most pronounced in theta and beta activity, making the EEG a useful tool for the early diagnosis of dementia. But studies on the differential diagnostic value are lacking. The value of EEG could be improved after parameters like the EEG segmentation or the traditional parameters combined with cognitive stimulation have been sufficiently evaluated.

Aged↗

Quantitative topographical analysis of effects of single thiopental bolus on human electroencephalogram.

The aim of present study was to characterize the topographical effect of thiopental on the EEG during induction of anesthesia. A multichannel (19 channels) digital EEG was recorded in 10 patients undergoing surgical treatment. The period during induction of anaesthesia before intubation was investigated in regard to peak frequency, amplitude, topography, and amplitude in conventional frequency bands. The main findings were a slowing of the EEG with a simultaneous increase of amplitude in the predominant EEG frequency (peak frequency) during induction. The topographical analysis showed a clear change of localization of the peak frequency in the occipito-frontal direction. Berger described the effect of thiopental on electrical cortical activity as early as 1933. Since then, many studies have investigated its influence on the EEG, but few have tried to characterize the effects of topographical changes in a quantitative way.

Adult↗

EEG and auditory evoked potential P300 compared with psychometric tests in assessing vigilance after benzodiazepine sedation and antagonism.

We have compared the EEG and auditory evoked wave P300 with psychometric tests in assessing vigilance after flumazenil antagonism of midazolam sedation in 12 healthy volunteers. Measurements were made before and after midazolam 0.1 and 0.2 mg kg-1 i.v., and immediately and 30, 60, 120 and 240 min after administration of flumazenil 1 mg. The sedative effects of midazolam and antagonism by flumazenil resulted in alterations in EEG, P300 and psychometric tests (syndrome short test, letter cancellation, choice reaction and recognition). However, 60 and 120 min after flumazenil a decrease in test performance indicating rebound sedation was seen only in P300 mapping. Thus P300 mapping was a sensitive method of detecting subtle differences in vigilance. Rebound sedation occurred even when midazolam 0.2 mg kg-1 was antagonized with an adequate dose of flumazenil. We suggest that it is advisable to supervise patients for at least 240 min after flumazenil antagonism of midazolam 0.2 mg kg-1.

Adult↗

Kinetic study of the aspartate/glutamate carrier in intact rat heart mitochondria and comparison with a reconstituted system.

The homologous exchange of external [14C] aspartate/internal aspartate catalyzed by the aspartate/glutamate carrier of rat heart mitochondria was investigated using aspartate-loaded, glutamate-depleted mitochondria. An inhibitor-stop technique was developed for kinetic studies by applying pyridoxal phosphate. Direct initial rate determinations from the linear phase of [14C] aspartate uptake were insufficiently accurate at high external and/or low internal substrate concentrations. Therefore, the full time-course of [14C] aspartate uptake until reaching isotope equilibrium was fitted by a single exponential function and was used to calculate reliable initial steady-state rates. This method was applied in bisubstrate analyses of the antiport reaction for different external and internal aspartate concentrations. The kinetic patterns obtained in double reciprocal plots showed straight lines converging on the abscissa. This result is consistent with a sequential antiport mechanism. It implies the existence of a catalytic ternary complex that is formed by the translocator and substrate molecules bound from both sides of the membrane. The Km values for aspartate were clearly different for the external and the internal sides of the membrane, 216 +/- 23 microM and 2.4 +/- 0.5 mM, respectively. These values indicated a definite transmembrane asymmetry of the carrier. The same asymmetry became evident when investigating the isolated protein from bovine heart mitochondria after reconstitution into liposomes. In this case the Km values for external and internal aspartate were determined to be 123 +/- 11 microM and 2.8 +/- 0.6 mM, respectively. This comparison demonstrates a right-side out orientation of the carrier after insertion into liposomal membranes. The sequential transport mechanism of the aspartate/glutamate carrier, elucidated both in proteoliposomes and in mitochondria, also seems to be a common characteristic of other mitochondrial antiport carriers.

Amino Acid Transport Systems, Acidic↗

Reaction mechanism of the reconstituted oxoglutarate carrier from bovine heart mitochondria.

The transport mechanism of the reconstituted oxoglutarate carrier, purified from bovine heart mitochondria, was studied kinetically. A complete set of half-saturation constants (Km) was established for the two different substrates oxoglutarate and malate on both the external and the internal sides of the membrane. The internal affinities for oxoglutarate (Km 0.17 mM) and malate (Km 0.7 mM) were higher than the corresponding external affinities (Km 0.3 mM and 1.4 mM, respectively). The exclusive presence of a single transport affinity for each substrate on one side of the membrane indicated a unidirectional insertion of the oxoglutarate carrier into the liposomal membrane. The Km values and also the maximum exchange rates (8-11 mumol.min-1.mg protein-1) for oxoglutarate and malate were independent of the nature of the counter substrate on the other side of the membrane. Under these defined conditions we analyzed the antiport mechanism in two-reactant initial velocity studies varying both the internal and external substrate concentrations. From the kinetic patterns obtained, a sequential type of mechanism became evident, implying that one internal and one external substrate molecule form a ternary complex with the carrier before transport occurs. A quantitative analysis of substrate interaction with the unloaded or single-substrate-occupied carrier revealed that rapid-equilibrium random conditions were fulfilled, characterized by a fast and independent binding of internal and external substrate. This kinetic mechanism agrees with previous results obtained in intact mitochondria. Considering also the data available for other mitochondrial carriers, a common kinetic mechanism (sequential type) for this carrier family is suggested.

Animals↗

Electroencephalographic mapping during isoflurane anesthesia for treatment of mental depression.

Seven patients undergoing isoflurane anesthesia were studied using electroencephalographic (EEG) mapping, a computer-assisted technique of EEG processing that permits the analysis of the spatial distribution of frequency components of the human EEG. After induction with thiopental, the patients were hyperventilated (carbon dioxide tension, 25 to 28 mm Hg) with 4% isoflurane in oxygen until a burst-suppression EEG appeared. Brain electrical activity was compared before anesthesia, at 0.5 to 0.8% and 1.8 to 2.1% isoflurane, during bursts, and after anesthesia. Starting from an alpha EEG with occipital predominance, a distinct alpha activation appeared over the whole cortex during 0.5 to 0.8% isoflurane. Decreased alpha amplitude with a maximum over the frontotemporal regions was observed during 1.8 to 2.1% isoflurane. Bursts consisted of high amplitude in all frequency bands. In the delta and the theta bands, voltage was very low before isoflurane administration, and increased in relation to depth of anesthesia. A minimum in delta and theta amplitudes occurred over both central regions. The dominant frequency, defined as the frequency component with the highest amplitude in the frequency spectrum, decreased from 8 to 4 and finally to 1 Hz, while its amplitude increased from 3 to 13 microV. As anesthesia deepened, the dominant frequency shifted from the occiput to the frontal cortex. Brain mapping transfers an immense amount of electroencephalographic (EEG) data into a comprehensive, easily readable image of brain function during anesthesia for therapy of mental depression. To make use of this technique in the operating room, further investigation and development toward on-line mapping are necessary.

Adult↗

Topography of the quantitative electroencephalogram in dementia of the Alzheimer type: relation to severity of dementia.

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.

Aged↗

The mitochondrial aspartate/glutamate and ADP/ATP carrier switch from obligate counterexchange to unidirectional transport after modification by SH-reagents.

The influence of various SH-reagents on the aspartate/glutamate carrier was investigated in the reconstituted system. When liposomes carrying partially purified carrier protein were treated with 5,5'-dithiobis(2-nitrobenzoic acid) or N-ethylmaleimide, antiport activity was strongly reduced. Several mercury compounds exerted a dual effect. They completely blocked the antiport and, in addition, induced an efflux pathway for internal aspartate. The maximum rate of this unidirectional flux was comparable to the original antiport activity. Induction of efflux always was coupled to inhibition of antiport. Efflux was neither due to unspecific leakage of proteoliposomes nor to a possible contamination by porin, but depended on active carrier protein, as elucidated by the sensitivity to proteinases and protein-modifying reagents. Besides efflux of aspartate, HgCl2 and mersalyl also induced a slow efflux of ATP from liposomes carrying coreconstituted aspartate/glutamate and ADP/ATP carrier. The two efflux activities could be discriminated taking advantage of the differential effectiveness of several inhibitors and proteinases. Although basic carrier properties were changed by the applied mercurials (Dierks, T., Salentin, A. and Krämer, R. (1990) Biochim. Biophys. Acta 1028, 281), aspartate and ATP efflux could clearly be correlated with the aspartate/glutamate and the ADP/ATP carrier, respectively. When purifying these two translocators the respective efflux activity copurified with the antiporter, thus elucidating that the two different transport functions are mediated by the same protein. These results argue for a participation of the aspartate/glutamate and the ADP/ATP carrier in the generally observed increase of mitochondrial permeability after treatment with SH-reagents.

Adenosine Diphosphate↗

Pore-like and carrier-like properties of the mitochondrial aspartate/glutamate carrier after modification by SH-reagents: evidence for a performed channel as a structural requirement of carrier-mediated transport.

Upon modification of the reconstituted aspartate/glutamate carrier by mercury reagents the antiporter was converted into a unidirectional efflux carrier (Dierks, T., Salentin, A., Heberger, C. and Krämer, R. (1990) Biochim. Biophys. Acta 1028, 268). In addition to this basic change in the mechanism, the mercurials, reacting with exofacial cysteines, also affected the internal binding site of the carrier leading to an unmeasurable high Km and to a drastically reduced substrate specificity. The spectrum of efflux substrates comprised small anions from chloride to glutamate, but not cationic amino acids and ATP, hence resembling pore-like properties. However, in the efflux state important carrier properties were also observed. The activation energy (86 kJ/mol) was as high as for the antiport. Furthermore, efflux was inhibited by the presence of external substrate. This trans-inhibition strongly suggests that the external binding site of the carrier, prerequisite in the antiport mechanism, also is involved in conformational transitions during efflux function. However, antiport no longer is catalyzed after switching to the efflux state. Reversion of the induced efflux carrier to the antiport state was achieved using dithioerythritol, thereby further restoring substrate specificity and saturation kinetics. A model for antiport-efflux interconversion is presented suggesting that two reactive cysteines have to be modified in order to uncouple the inward and outward directed component of antiport. The pore-type characteristics of efflux are taken as evidence that a channel-like structure determines the selectivity of unidirectional transport. This intrinsic channel of the protein then is required for substrate translocation also during antiport function.

Adenosine Diphosphate↗

P3 topography in psychiatry and psychopharmacology.

Endogenous components of event related potentials are of particular interest in psychiatric diseases because of their relations to cognitive and behavioral processes. We studied the topography of these potentials in order to find out whether there are different scalp distributions in schizophrenic and depressive patients in relation to the psychopathological state and compared to normal controls. Furthermore variations of the topographical scalp distribution of P300 in normal volunteers after administration of physostigmine and biperiden was investigated. We demonstrated a clear relationship of the P300 amplitude with the negative symptom axis and found different topographical scalp distributions in different groups and experimental conditions. Topography of event related potentials is therefore a promising field of investigation for a better understanding of psychiatric disorders.

Adolescent↗

Kinetic discrimination of two substrate binding sites of the reconstituted dicarboxylate carrier from rat liver mitochondria.

The kinetic interaction of various substrates and inhibitors with the dicarboxylate carrier from rat liver mitochondria was investigated using the isolated and reconstituted carrier protein. Due to their inhibitory interrelation the ligands could be divided into two classes: dicarboxylates, sulphate, sulphite and butylmalonate on the one hand and phosphate, thiosulphate and arsenate on the other. The mutual inhibition of substrates or inhibitors taken from one single class was found to be competitive, whereas the kinetic interaction of ligands when taken from the two different classes could be described as purely non-competitive. The half-saturation transport constants Km and the corresponding inhibition constants Ki of one single ligand, either used as substrate or as inhibitor, respectively, were found to be very similar. These kinetic data strongly support the presence of two different binding sites at the dicarboxylate carrier for the two different classes of substrates considering the external side of the reconstituted protein. When these two sites were saturated simultaneously with malate and phosphate, the turnover of the carrier was considerably reduced, hence indicating that a non-catalytic ternary complex is formed by the two substrates and the carrier molecule.

Animals↗