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Biomedical subjects

W Günther

Publications and source records attributed to W Günther.

At least 55 records · Page 3Linked to original sources

Studying block in cloned N-methyl-D-aspartate (NMDA) receptors.

The biophysics of block of NMDA receptor channels has been investigated extensively during the past 8 years. In the last few years, cloned NMDA receptor channels have become available. Here we have discussed advantages and disadvantages of studying block phenomena in cloned NMDA receptors. Some recent work on the pore block of the cloned NMDA receptor channels was critically reviewed and extended by data about the calcium block. Novel effects of kainate on cloned NMDA receptors and of NMDA on cloned AMPA receptors were reported and discussed with respect to recent work concerning possible occurrence of NMDA-AMPA hybrid channels.

Amino Acid Sequence↗

Subunit-specific block of cloned NMDA receptors by argiotoxin636.

Cloned NMDA receptor channels of the NR1-NR2A, NR1-NR2B and NR1-NR2C type show differences in argiotoxin636 block. Mutations of an asparagine residue located at a homologous position in the TM2 region of all NMDA receptor subunits, which corresponds to the Q/R site of the AMPA receptors, alters the argiotoxin636-induced block. The results suggest that the toxin interacts at this amino acid position with the putative pore forming TM2 region of the NMDA receptor subunits. Sequence differences in the TM2 segment of NR2A and NR2C subunits are not responsible for the subtype-specific sensitivity to argiotoxin636 as revealed by site-directed mutagenesis.

Amino Acid Sequence↗

Identification and characterization of a mouse monoclonal antibody (M10) directed against canine (dog) CD8+ lymphocytes.

Monoclonal antibodies (mAb) were produced by immunizing BALB/c mice with non-adherent dog lymphocytes. M10 was specific for a subset of dog lymphocytes. M10 belonged to the IgG1 subclass and reacted with 26% of dog peripheral blood lymphocytes, 24% of spleen lymphocytes, 81% of thymus cells, 1.2% of bone marrow cells (5.8% of bone marrow lymphocytes) and 23% of PHA-stimulated lymphocytes. Immunohistology of snap-frozen thymus and spleen showed that the spleen B-cell area stained negative, whereas the spleen T-cell area and the thymus medulla exhibited positive reaction in 20-30%. The thymus cortex was strongly positive. M10 diminished cell lysis by 58% in cell mediated lysis assays (CML). Immunoblot assays revealed that M10 recognized an antigen with a molecular weight of 76 kD under non-reducing and 33 kD under reducing conditions. Finally, M10 bound to a canine CD8 alpha transfected rat T-cell line (NB2). These findings characterize M10 as an antibody directed against the dog CD8 antigen.

Animals↗

Findings of electroencephalographic brain mapping in mild to moderate dementia of the Alzheimer type during resting, motor, and music-perception conditions.

Sixteen-channel electroencephalographic (EEG) brain mapping studies were carried out under resting conditions in 41 patients with mild to moderate dementia of the Alzheimer type, diagnosed according to DSM-III-R criteria. The patients showed diffuse patterns of EEG slowing, as known from the literature. They showed increases of theta power in large bilateral brain areas and bitemporal increases of delta power as compared with both age-matched and younger control subjects. In addition, the patients had increased beta activity in comparison with the younger control group, but not with the age-matched control subjects. Functional brain mapping revealed decreases of EEG power during manual-motor and music-perception tasks in delta frequencies for patients, which was not seen in either of the two control groups. All frequency bands revealed major gender-related differences in EEG activity, which should receive more attention in future research.

Aged↗

EEG mapping investigations of psychomotor and music perception brain dysfunction in untreated schizophrenic patients.

Twenty-six untreated schizophrenic inpatients and 34 control persons were investigated using 16-channel EEG mapping during resting, manumotor and music perception tasks. Power values of activation tasks were each referenced to a separate, immediately preceding resting condition, using conventional delta, theta, alpha and 2 beta frequency bands. Results in delta and alpha bands, which maximally separated the two groups, are reported only for space reasons. Results indicated a "nonreactivity" (in all frequency bands) on the two activation paradigms in schizophrenic patients as a group. Major gender effects were obtained in normal persons, but not signs of nonreactivity comparable to patients. Subdividing patients exclusively by means of their EEG changes on activation produced meaningful clinical subgroups of "positive/negative" schizophrenics. This latter finding could contribute towards clinical utility of EEG mapping in psychiatry.

Adult↗

EEG alterations and seizures during treatment with clozapine. A retrospective study of 283 patients.

In a retrospective study, 1863 EEG recordings made during clozapine treatment of 283 patients with normal pretreatment EEG evaluations were analyzed. Furthermore, they were compared to the EEGs of the same patients without clozapine (i.e., during other neuroleptic medication). Moreover, the data of all patients who had seizures during treatment with clozapine were evaluated in case reports. Classical clinical EEG evaluation criteria for normal versus abnormal were used (including diffuse slowing and grouped alterations according to Jung 1953 and Kugler 1983). Of the 283 patients investigated, 61.5% (174) showed at least one abnormal EEG under clozapine according to these criteria. Evaluating all recorded EEGs of these patients in order to get some longitudinal information, we found a rate of 53.4% abnormal EEG recordings during clozapine treatment. Most of the EEG changes were evaluated as slight (22.5%) to moderate (10.1%) diffuse slowing and some as groups of nonparoxysmal waves (39.8%) or sharp waves (16.2%) rendering the EEGs abnormal according to the above criteria. Potential signs of increased bioelectrical cerebral reagibility such as paroxysmal activity (4.3%) or severe diffuse slowing (0.2%) were rare. A nearly linear correlation with the daily dose was found in the range up to 300 mg clozapine/day for both diffuse and grouped alterations. Possibly due to selection, adaptive mechanisms/habituation, and/or other unknown factors, the rate of alterations decreased slightly at doses above 300 mg and rose again sharply for doses over 600 mg/d. Three of the clozapine-treated patients, equivalent to 1.1%, developed seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Prolongation of a primary twin pregnancy to the 31st week of pregnancy by surgical extraction of the 1st twin in the 17th week of pregnancy for umbilical cord prolapse].

A 24-year-old woman with a twin pregnancy had a premature rupture of membranes (PROM) of the first foetus in the 16th gestational week (gw). After 9 days the umbilical cord prolapsed. In the 17th gw the foetus was extracted by vaginal hysterotomy, because of an inferior anterior wall placenta. The patient remained hospitalised receiving tocolysis, lung maturation induction and prophylactic antibiosis. The pregnancy could be prolonged for 109 days after PROM and 99 days after the extraction of the first twin. The second child was born in the 31st gw by Caesarean section, following uncontrollable labour.

Adult↗

Influence of the earth's magnetic field on resting and activated EEG mapping in normal subjects.

We found in a former investigation that by measuring sleep parameters, the REM latency is shortened in the E-W position of sleepers compared with the N-S position. This paper reports on a further neurological observation in humans concerning the influence of the earth's magnetic field: there are statistically significant differences in the EEG of normal subjects, depending on whether the subjects sit facing the N-S or E-W direction. The difference is especially pronounced in the alpha-power.

Adult↗

Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.

The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a high calcium permeability and sensitivity to channel block by extracellular magnesium. These properties, which are believed to be important for the induction of long-term changes in synaptic strength, are imparted by asparagine residues in a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the NR1 subunit, replacement of this asparagine by a glutamine residue decreases calcium permeability of the channel and slightly reduces magnesium block. The same substitution in NR2 subunits strongly reduces magnesium block and increases the magnesium permeability but barely affects calcium permeability. These asparagines are in a position homologous to the site in the TM2 region (Q/R site) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that is occupied by either glutamine (Q) or arginine (R) and that controls divalent cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor channels contain common structural motifs in their TM2 segments that are responsible for some of their ion selectivity and conductance properties.

Amino Acid Sequence↗

Synthesis of beta-D-mannosides from beta-D-glucosides via an intramolecular SN2 reaction at C-2.

The selective synthesis of beta-D-mannosides was achieved by first synthesizing beta-D-glucosides that carry a N-phenylcarbamoyl protecting group at O-3. These derivatives were transformed into the corresponding beta-D-mannosides by intramolecular nucleophilic substitution with inversion of configuration at C-2, the O-trifyl group being the leaving group. Subsequent intramolecular attack of the neighboring carbamoyl group resulted in the formation of the 2,3-carbonate of the desired beta-D-mannoside.

Carbohydrate Sequence↗

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. V. Evaluation of psychomotor training programs in depressed patients.

Parts I-III of this series used psychometric assessment of motor performance in psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in schizophrenic and affective psychoses, which was not found in "neurotic"/reactive or healthy persons. Part IV yielded signs of concomitant brain dysfunction in these patients, demonstrated by EEG mapping as well as other (SPECT/PET) neuroimaging methods. Apart from this "basic science" interest into the pathophysiology of endogenous psychoses we engaged in the development of motor training programs using the PMS as "target" syndrome. We hypothesized, that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology also. These assumptions were supported in the first two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar endogenous depressed patients, respectively (the studies on schizophrenic patients being reported finally as part VI of this series, along with the final version of our modified motor test battery). Examples of the motor training programs are provided in this paper, although the final version of the complete programs will be published separately for space reasons and for better availability for routine clinical use.

Adult↗

MRI-SPECT and PET-EEG findings on brain dysfunction in schizophrenia.

1. In this article the author reviews a series of investigations on brain dysfunction in untreated schizophrenics using manumotor and music listening tasks as activation paradigms. Methods involved were EEG mapping, Single Photon Emission Computerized Tomography (SPECT; Xenon-133 inhalation method), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET; 11-2-Deoxyglucose as tracer). 2. Major signs of brain dysfunction yielded a "nonreactivity" on both motor and music stimulation in patients displaying marked negative symptomatology, as shown consistently by EEG Mapping, SPECT and PET. In contrast, first-break patients with predominant "positive" and without underlying negative symptoms showed signs of "normal" to "diffuse hyperactivation" on such stimulations, as demonstrated by EEG and SPECT imaging methods. 3. Interestingly, MRI planimetry of the size of the corpus callosum (CC) corroborated the above findings, showing a significantly larger CC in "positive" than "negative" patients. 4. Together with functional imaging findings of other working groups and recent neuropathological theories we finally raise some speculative neurophysiological hypotheses on brain dysfunction in subgroups of schizophrenics, which might have direct implications for treatment and follow-up of these patients.

Brain↗

Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type.

Thirty-three patients with mild primary degenerative dementia according to DSM-III (MMS between 15 and 27) took part in a double-blind cross-over study of phosphatidylserine (Fidia, 300 mg/d) versus placebo. Both treatment phases lasted for 8 weeks with an 8 week washout phase in between and a 4 week washout phase before treatment phase one. Clinical global improvement ratings showed significantly more patients improving under BC-PS than under placebo during treatment phase one. The improvement carried over to the following wash-out and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. 16-channel EEG mapping findings indicated that the patients initially showed higher power values in all frequency bands (except alpha), when compared to a younger, healthy control group. BC-PS reduced the higher power values compared to placebo, shifting EEG power more towards the normal level.

Aged↗

[Adult form of metachromatic leukodystrophy with predominantly psychotic manifestations].

This is a report of one of the few cases of an adult form of metachromatic leukodystrophy with almost exclusively psychiatric symptoms. This should point out the importance of a careful organic diagnostic assessment in all patients with the first manifestation of a psychiatric disease. In this case an investigation of the patient's family confirmed the heterozygote genetic origin of the disease.

Adult↗