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Biomedical subjects

M Hoke

Publications and source records attributed to M Hoke.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of growth factor binding, Ca2+ signaling and cell growth by polysulfonated azo dyes related to the antitumor agent suramin.

The ability of the polysulfonated antitumor drug suramin and six related polysulfonated azo dyes to inhibit the cell growth, platelet-derived growth factor (PDGF)-receptor binding, and intracellular Ca2+ signaling of Swiss 3T3 fibroblasts was studied. Some of the azo dyes were more potent inhibitors of PDGF binding than was suramin. The concentration giving 50% inhibition (IC50) of PDGF binding was 0.5 microM for the most potent azo dye as compared with 10 microM for suramin. The azo dyes were generally more potent inhibitors of nonmitochondrial Ca2+ uptake and of inositol(1,4,5)trisphosphate-mediated Ca2+ release in permeabilized Swiss 3T3 cells than was suramin, and they were more potent inhibitors of PDGF-induced Ca2+ signaling in intact Swiss 3T3 cells. The azo dyes were only as effective as or less effective than suramin in inhibiting the growth of Swiss 3T3 cells, with IC50 values of between 74 and 361 microM being noted for the dyes as compared with 70 microM for suramin. The difference between the growth-inhibitory activity of the azo dyes and that of suramin could not be explained by metabolism of the compounds, which was not detectable in either Swiss 3T3 cells or human liver slice preparations. The results suggest that suramin and some of the azo dyes have actions on cell growth in addition to inhibition of growth factor binding and of Ca2+ signaling.

3T3 Cells↗
PubMed1992

Inhibition of growth factor binding and intracellular Ca2+ signalling by dextran sulfates of different sizes and degrees of sulfation.

The ability of dextran sulfates of varying molecular sizes (5-500 kDa) and degrees of sulfate substitution (0.3-1.9) to inhibit the binding of platelet-derived growth factor (PDGF) to intact Swiss 3T3 fibroblasts and to inhibit inositol(1,4,5)trisphosphate-dependent release of Ca2+ in permeabilized Swiss 3T3 cells was examined in the present study. Significant correlations were found between increased molecular size of the dextran sulfates and inhibition of both PDGF binding (r = 0.77) and Ca2+ release (r = 0.72). The degree of sulfate substitution did not correlate with inhibition of either activity.

3T3 Cells↗
PubMed1991

Human auditory evoked gamma-band magnetic fields.

We have discovered a ca. 40-Hz transient magnetic oscillatory response, evoked in the human brain by the onset of auditory stimuli, consisting of four or more cycles locked in phase to stimulus onset in approximately the 20- to 130-ms poststimulus interval. The response originates in the supratemporal auditory cortex, some millimeters deeper and anterior to the source of the larger-amplitude slow-wave M100 component of the evoked magnetic field and moves in a posterior arcing trajectory 1 cm or more in length. The oscillatory cortical activation elicited by auditory stimuli may be similar to the gamma-band cortical oscillations elicited by olfactory and visual stimuli and may represent an essential component of auditory perceptual processing.

Acoustic Stimulation↗
PubMed1991

A timesaving BERA technique for frequency-specific assessment of the auditory threshold through tone-pulse series stimulation (TOPSTIM) with simultaneous gliding high-pass noise masking (GHINOMA).

A new stimulation paradigm is described for eliciting frequency-specific auditory brainstem responses (ABR) by stimulation with a series of seven Gaussian-shaped tone pulses with carrier frequencies descending, in half-octave steps, from 4,000 to 500 Hz, and an interstimulus interval between consecutive pulses of 18 ms. The pause between two consecutive series is 54 ms so that the interval between two tone pulses of the same frequency is 162 ms (stimulus repetition rate approximately 6/s). Simultaneously a high-pass noise masker is presented whose lower cut-off frequency is continuously diminished in such a way that, when a tone pulse is presented, the cut-off frequency of the masker is exactly one octave above the carrier frequency of the pulse. Forward masking effects of preceding tone pulses as well as forward and simultaneous masking effects of the high-pass noise suppress activity originating from those regions of the cochlea which are located basalwards to the region to be stimulated by the respective pulse, thus enhancing the frequency specificity, especially for low-frequency stimuli of higher intensity. The new stimulation paradigm was tested in 12 normal hearing subjects and turned out to be suitable to elicit frequency-specific ABR with frequencies as low as 500 Hz and intensities as low as 10 dB nHL. The main advantage of the described technique is that the time required for a complete assessment of the auditory threshold at seven test frequencies (covering the relevant speech frequency range) is substantially shorter as compared to conventional techniques so that it can routinely be employed in pedaudiology, where infants usually have to be investigated in sedation.

Acoustic Stimulation↗
PubMed1991

On the biomagnetic inverse problem in the case of multiple dipoles.

Series of Monte Carlo simulations have been carried out which were based on the assumption that two dipoles with a distance of 0.5-2 cm are located in a homogeneous semi-infinite volume conductor (depth 3 cm), and that the magnetic field component perpendicular to the surface of the volume conductor is recorded by means of a magnetometer with infinitesimal coil diameter. Moving-dipole models (all parameters time-dependent), rotating-dipole models (dipole locations fixed, dipole orientation and amplitudes time-dependent) as well as fixed-dipole models (dipole locations and orientations fixed, amplitudes time-dependent) were considered. The algorithm used to retrieve the model parameters from the simulated field distributions (biomagnetic inverse procedure) was based on a transformation of the standard least-squares fit procedure into a minimization procedure with respect to the nonlinear parameters (dipole locations and orientations), which was solved iteratively by means of the Fletcher-Powell algorithm. It was found that the resolving power of the biomagnetic inverse procedure is highly dependent on the relative orientation of the two dipoles, the temporal overlap of the dipole moments, and the correlation of successive samples of the superimposed noise. The results obtained in this study suggest that the resolving power of the biomagnetic inverse procedure for conditions typically found in the case of auditory evoked magnetic fields is not better than 2 cm for the moving-dipole approach, and not better than 1 cm for the fixed-dipole approach, provided that no additional a priori information is available. In practice, the situation is probably even worse since the depth of the generators is usually larger than assumed in this study.

Algorithms↗
PubMed1991

Neuromagnetic evidence of functional organization of the auditory cortex in humans.

The influence of two physical stimulus parameters (frequency and intensity) and of one sensation parameter (pitch) on the auditory evoked magnetic field (AEF) was quantified by approximating the measured magnetic field distribution by that of an equivalent current dipole (ECD) embedded in a homogeneous semi-infinite volume conductor. The main results are as follows: The depth of the ECD increases with increasing frequency, but decreases with increasing intensity. In the case of a complex tone with missing fundamental it is the virtual pitch that determines the ECD location and not the spectral contents of the stimulus.

Auditory Cortex↗
PubMed1991

Auditory cortical basis of tinnitus.

The waveforms of the auditory evoked magnetic field (AEF) in normal-hearing individuals and patients suffering from tinnitus are distinctly different. In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200, or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100, or N1) is significantly augmented. A very characteristic feature turned out to be the amplitude ratio of the two waves M200 and M100. Below the age of 50, the amplitude ratio M200/M100 represents a clear-cut criterion to distinguish between tinnitus patients and individuals without tinnitus. In tinnitus patients, the ratio is less than 0.5 independent of age, whereas, in young and middle-aged normal-hearing individuals, it is greater than 0.5. Since in normal-hearing individuals the average amplitude ratio decreases linearly with age, the clusters of amplitude ratios of the two groups begin to overlap beyond the age of 50. The hypothesis is put forward that the decrease of the average amplitude ratio in normal-hearing individuals reflects a degenerative process probably initiated by multiple exogenous and endogenous factors, which leads to both an increased excitability of the generators of a particular component of wave M100 and a sustained neural activity in the generators of one particular component of wave M200 and eventually gives rise to the sensation of tinnitus. The absence or poor development of wave M200 is a concomitant phenomenon, resulting from the involved generators being less responsive to external stimuli. Our hypothesis has been supported by one exemplary case in which we were able to trace the process of tinnitus remission during a period of 256 days after acute onset of tinnitus (due to an acute noise trauma), showing a recovery of the amplitude ratio from an initial value of 0 to a normal value of approximately 1.

Acoustic Stimulation↗
PubMed1990

Identification of sources of brain neuronal activity with high spatiotemporal resolution through combination of neuromagnetic source localization (NMSL) and magnetic resonance imaging (MRI).

The locations of the origin of wave M100 of the auditory evoked magnetic field in response to tone bursts of different carrier frequencies, obtained through dipole localization methods (DLM), were related to cerebral structures, displayed by coronal MRI (magnetic resonance imaging) tomograms of the respective subjects. This was done by displaying the landmarks which served as reference for the neuromagnetic measurements in MRI tomogram (reference plane). All calculated source locations project exactly onto the transverse temporal gyri (Heschl) in which the primary auditory cortex, the supposed origin of wave M100, is located. The results highlight the exceptional capabilities of a combination of these 2 non-invasive, high-resolution techniques for functional diagnosis.

Auditory Cortex↗
PubMed1990

Objective evidence for tinnitus in auditory-evoked magnetic fields.

The waveforms of the auditory-evoked magnetic field in normal hearing individuals and patients suffering from tinnitus are distinctly different. In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200 or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100 or N1) is significantly augmented. A characteristic feature was the amplitude ratio of the two waves, M200 and M100. Below the age of 50, the amplitude ratio M200:M100 represents a criterion to distinguish tinnitus patients from individuals without tinnitus. In tinnitus patients, the ratio is less than 0.5, independent of age, whereas, in young and middle-aged normal-hearing individuals, it is greater than 0.5. Since in normal-hearing individuals the average amplitude ratio decreases linearly with age, the clusters of amplitude ratios of the two groups begin to overlap after the age of 50. The hypothesis is put forward that the decrease of the average amplitude ratio in normal-hearing individuals reflects a degenerative process, probably initiated by multiple exogenous and endogenous factors, which leads to both an increased susceptibility of the generators of a particular component of wave M100 and a sustained neural activity in the generators of one particular component of wave M200 and eventually gives rise to the sensation of tinnitus. The absence or poor development of wave M200 is a concomitant phenomenon, resulting from the involved generators being less responsive to external stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗