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Biomedical subjects

M Bach

Publications and source records attributed to M Bach.

At least 19 recordsLinked to original sources

High level production and localization of bovine rod cGMP-gated cation channel subunit 1 in baculovirus-infected insect cells and Saccharomyces cerevisiae.

The cGMP-gated cation channel is responsible for the last step in the vertebrate phototransduction cascade which couples light activation of rhodopsin to a change in membrane permeability. Two different expression systems, baculovirus-infected Spodoptera frugiperda (Sf9) insect cells and Saccharomyces cerevisiae, were used for the overproduction of the cGMP-gated cation channel subunit 1 of bovine rod cells. Presence of recombinant channel protein was monitored by SDS-PAGE and Western-blot analysis. Through immunogold labeling, the heterologously expressed cation channel was found to be localized predominantly in the inner compartments of the infected insect cells and in the vacuole of recombinant yeast cells.

Animals

Asymmetry of motion VEP in infantile strabismus and in central vestibular nystagmus.

Norcia et al. [1] found a nasal-temporal asymmetry of visually evoked potentials (VEP) elicited by motion stimuli in patients with infantile strabismus. Patients with infantile strabismus typically present with an asymmetry of the monocular optokinetic nystagmus (OKN). We here address the question whether the asymmetry of the motion VEP indicates a sensory defect in the afferent visual pathway that could explain the OKN asymmetry. We recorded the VEP to a horizontally oscillating vertical sinusoidal grating in 20 patients with infantile strabismus (esotropia, asymmetry of the monocular optokinetic nystagmus, latent nystagmus) and in 10 normal controls. No asymmetry occurred in the 10 controls. Eight of the 20 patients with infantile strabismus showed a clear difference between the VEPs evoked by back and forth movements with a mirror-like asymmetry between the two eyes (phase shift 180 +/- 20 degrees). However, there was no significant correlation between the degree of VEP and OKN asymmetries. Therefore, we assume that the VEP asymmetry does not reflect the primary cause of the OKN asymmetry. Rather, the OKN asymmetry may be due to a sensory-motor defect in the efferent subcortical pathway, and the VEP asymmetry could be an epiphenomenon. Some of the VEP asymmetry may be a consequence of the latent nystagmus typically released under monocular stimulation, leading to adaptation of the afferent retino-cortical pathway. This suggestion is supported by a marked VEP asymmetry that we found in two patients with an acquired central vestibular nystagmus, an abnormality most likely not combined with a primary defect of the retino-cortical pathway.

Adolescent

Isolation and characteristics of a steady-state visually-evoked potential in humans related to the motion of a stimulus.

We have examined the visual potential evoked by two motion stimuli. In the first stimulus (termed coherent motion) a random-dot pattern oscillated between phases of coherent and incoherent ("snowstorm") motion, and in the second a random-dot pattern alternated in direction of motion (termed direction change). We found that the response to the coherent motion stimulus is low-pass with respect to speed, has low contrast sensitivity and increases steadily with the contrast of the stimuli. The direction change visually-evoked potential (VEP) is band-pass with respect to speed, has high contrast sensitivity but then saturates and even reduces as the stimulus contrast is raised above 0.1. The behaviour of the direction change VEP is similar in nature to results from psychophysical experiments of motion perception and to the known properties of directionally selective cells of the cortex. On the other hand the behaviour of the coherent motion VEP suggests this may not be mediated by a mechanism specific to motion.

Contrast Sensitivity

Reactivating occupational therapy: a method to improve cognitive performance in geriatric patients.

In this prospective treatment study, the effects of two different occupational therapy strategies were compared in two samples of long-term geriatric inpatients (n = 22 in each group) with slight to moderate dementia according to DSM-III-R. Psychometric ratings after 12 weeks and 24 weeks of treatment have demonstrated that the application of a reactivating occupational therapy programme in addition to functional rehabilitation is significantly more efficient than the application of functional rehabilitation alone on levels of cognitive performance, psychosocial functioning, and the degree of contentedness with life. These results support the assumption that geriatric patients, if stimulated for a longer time, are able to mobilize latent resources of cognitive and psychosocial performance. Reactivating occupational therapy has a place in the treatment of long-term geriatric patients.

Activities of Daily Living

The Timed Test of Money Counting: a short physical performance test for manual dexterity and cognitive capacity.

The competent handling of money is an essential basis for living independently. Seventy-eight consecutively admitted patients to a geriatric hospital underwent the Timed Test of Money Counting (TTMC) which measures patients' ability to open a purse, take out all the money and count it. Further assessment included Mini-Mental State Examination (MMSE), Barthel Index of ADL, Self-maintaining and Instrumental Activities of Daily Living (IADL), grip strength and Williams' Board Test. The TTMC was reliable (inter-rater and intra-rater) and showed construct and concurrent validity with other measures of physical function. Unlike many other physical performance tests the TTMC is quickly performed and requires no special equipment or training.

Activities of Daily Living

Predictive value of alexithymia: a prospective study in somatizing patients.

In the present study, the potential role of alexithymia in predicting the long-term treatment outcome was investigated prospectively in 30 patients with DSM-III-R somatoform disorders and anxiety disorders. Using SCID interviews, diagnoses were assessed before inpatient treatment and 2 years after discharge. Patients who met criteria for DSM-III-R undifferentiated somatoform disorder at follow-up exhibited higher pretreatment alexithymia scores (as measured by the TAS) as compared with patients who showed remission of their somatoform disorder or patients who never had met criteria for a somatoform disorder. As a result stepwise logistic regression analyses, high alexithymia scores emerged as a significant predictor of persistent somatization, independent of other measures of psychopathology, sociodemographic variables, and measures of illness severity.

Adolescent

Albino-type misrouting of the optic nerve fibers not found in dissociated vertical deviation.

It has been suggested that albinolike misrouting of the visual pathway occurs in patients with dissociated vertical deviation (DVD). We re-examined this contention in ten DVD patients using visually evoked potentials. Full-field monocular pattern-onset checkerboard stimulation was employed. The visually evoked potentials were recorded simultaneously from both occipital lobes. Their differential activity during stimulation of the right eye was compared with that obtained during stimulation of the left. We found no predominance of crossed projection in any of the DVD cases. The results in nine normal subjects were similar. In 13 albino patients, however, there was a relative positivity in the contralateral hemisphere about 100 ms after pattern-onset, which reconfirmed predominance of the crossed projection. Possible artifacts are discussed that may have led to the assumption of misrouting in DVD in two previous reports.

Adolescent

Retinal and cortical activity in human subjects during color flicker fusion.

Pattern electroretinograms (PERG) and cortical visually evoked potentials (VEP) were simultaneously recorded from 7 visually normal and 1 protanopic subjects. Stimuli were color checkerboards (0.5 degrees check size), phase-reversing at 17 Hz (i.e. 34 reversals/sec). Using a stepwise sweep procedure, the luminance of the red (lambda peak = 550 nm) and green (lambda peak = 630 nm) checks varied in 11 steps in opposite directions from 0 to 30 cd/m2, embracing the subjective equiluminance point. For normal subjects at subjective equiluminance, the VEP amplitude dropped sharply down to 13 +/- 2% of the value at pure luminance contrast. The PERG, however, was only reduced to 56 +/- 10% at this point, an attenuation 4 times less than that of the VEP. In contrast to normal subjects, in the protanopic subject the PERG was sharply reduced at equiluminance, parallel to the VEP. This would be expected when L-cones are missing. Assuming that the PERG reflects the activity of the retinal ganglion cells, our findings suggest that human retinal ganglion cells respond well under the condition of equiluminant flicker fusion, which is in agreement with recent single-cell studies in the monkey. Consequently, the temporal low-pass filter, which mediates color-flicker fusion, would seem to lie central to the retinal ganglion cells.

Adult

Electrophysiological correlates of texture segregation in the human visual evoked potential.

We investigated whether the visual evoked potential (VEP) reflects cortical processing associated with preattentive texture segregation. On a visual display unit we presented stimuli with various arrangements of oriented line segments that either led to the appearance of a "preattentive" checkerboard or did not. Two presentation modes were used (pattern onset at 1 Hz and rapid pattern change at 4.3 Hz), while luminance (57 cd/m2) and contrast (92%) of the line segments remained constant. VEPs were recorded in 7 human subjects. The VEP was analyzed as a linear combination of putative components, which are evoked by either local pattern, quasi-local orientation contrast or global preattentive structure. In the transient VEP, we found a negativity over the posterior pole at a latency between 161 and 225 msec (FWHM) in the linear combination designed to extract segregation-specific components. Peak amplitude reached 3.1 +/- 0.8 microV (mean +/- SEM) at 199 msec. This negative peak appeared only for textures containing orientation contrast. Steady-state analysis of the rapid presentation also revealed a significant component (P = 0.002) associated with texture segregation. These potentials either represent processing of orientation contrast or global processing of texture segregation. The results suggest that specific surface potentials, differing from cognitive potentials, can be derived which are associated with preattentive processing.

Adult

Influence of mood on visually evoked potentials: a prospective longitudinal study.

Anecdotal observations have suggested that individual differences in mood state could be one reason for the variability of visually evoked potentials (VEP). Therefore, we designed a longitudinal study, in which VEP amplitude was measured and psychological dimensions were assessed. All subjects completed a 'mood state questionnaire' before each session. The results from the VEP measurement and from the mood questionnaire varied widely between subjects. The intraindividual reproducibility, however, was high in 15 of 20 subjects, even over 4 weeks. In some cases we found intraindividual variability of VEP amplitude to be highly correlated with some factors derived from the mood state questionnaire. An overall analysis of covariance and variance (ANCOVA) showed a significant negative correlation between VEP amplitude and the mood factor 'Tiredness' and a significant positive correlation between VEP amplitude and 'Activity'.

Adult

Structure of the small nuclear RNP particle U1: identification of the two structural protuberances with RNP-antigens A and 70K.

We have investigated the structure of the small nuclear RNP (snRNP) U1 by combining EM of complete and partially protein-deficient particles with immunoelectron microscopy employing mAbs against known components of the U1 snRNP. It was found that the two main protuberances of this particle can be identified with the U1-specific proteins A and 70K. The 70K protuberance is the one lying closer to the 5' terminus of the snRNA, as identified by its 5'-terminal m3G cap. The round-shaped main body of U1 snRNP represents its core RNP domain containing the common snRNP proteins. Functional implications of these results are discussed. Our results may also point to the physical basis for the production of autoantibodies directed against specific groups of snRNP proteins. The physical grouping of the common proteins (Sm epitopes) and the specific proteins (RNP epitopes) could result in one or the other being presented to the immune system as is the case in patients suffering from SLE or MCTD, respectively.

Antibody Specificity

The pattern-electroretinogram in glaucoma and ocular hypertension. A cross-sectional and longitudinal study.

The pattern electroretinogram (PERG) is an indicator of retinal ganglion cell function. We studied the PERG in 65 normal eyes, in 52 eyes in early stages of glaucoma, and in 28 ocular hypertensive (OHT) eyes. The PERG was recorded using steady-state high contrast (98%) counterphasing checkerboard patterns at check sizes of 0.8 degrees and 15 degrees at 16 reversals/s and 98% contrast. Stimulation area was 27 degrees x 30 degrees. When compared to normals, in glaucoma eyes PERG amplitudes are reduced to 56 +/- 3.6%, (P < 0.0001) for 0.8 degrees and to 79 +/- 4.0% (P < 0.001) for 15 degrees check sizes. Preferential reduction for the small check size allows classification of patients on an individual basis: using discriminant analysis, normal and glaucoma eyes were classified with a sensitivity of 82.7% and a specificity of 90.8%. Nineteen of 28 OHT eyes were classified as pathological. Eyes with OHT were followed up to test whether the PERG can be used to predict visual field damage. At the repeat visit 5 to 35 months later (mean follow-up 20.2 +/- 8.2 months), in eyes with normal PERGs the average loss in mean sensitivity was -0.61 +/- 0.5 dB, while in eyes with pathological PERGs it was -2.6 +/- 0.7 dB (P = 0.05). Findings suggest that the PERG can be used to discriminate between OHT patients who will develop visual field loss and those who will not. Thus, the PERG may be a test of visual function helpful to decide which OHT patients require treatment before visual field deterioration and optic nerve damage have begun.

Adult

Transfer RNA genes from Dictyostelium discoideum are frequently associated with repetitive elements and contain consensus boxes in their 5' and 3'-flanking regions.

A total of 68 different tRNA genes from the cellular slime mold Dictyostelium discoideum have been isolated and characterized. Although these tRNA genes show features common to typical nuclear tRNA genes from other organisms, several unique characteristics are apparent: (1) the 5'-proximal flanking region is very similar for most of the tRNA genes; (2) more than 80% of the tRNA genes contain an "ex-B motif" within their 3'-flanking region, which strongly resembles characteristics of the consensus sequence of a T-stem/T-loop region (B-box) of a tRNA gene; (3) probably more than 50% of the tRNA genes in certain D. discoideum strains are associated with a retrotransposon, termed DRE (Dictyostelium repetitive element), or with a transposon, termed Tdd-3 (Transposon Dictyostelium discoideum). DRE always occurs 50 (+/- 3) nucleotides upstream and Tdd-3 always occurs 100 (+/- 20) nucleotides downstream from the tRNA gene. D. discoideum tRNA genes are organized in multicopy gene families consisting of 5 to 20 individual genes. Members of a particular gene family are identical within the mature tRNA coding region while flanking sequences are idiosyncratic.

Animals

Supercritical fluid chromatography in the routine stability control of antipruritic preparations.

A recently developed system for supercritical fluid chromatography (SFC), based on independent flow and pressure control and suitable for packed and capillary columns, was tested on a routine level for the reliable, accurate and precise determination of active pharmaceutical substances in stability control. Only packed columns were used for this analysis. The chromatographic figures of merit and the validation data of the active substance alone and in two different dosage forms (accuracy, 98.8-99.2%; precision, 0.6%; linearity of response, 0.998-0.999) are comparable with the former liquid chromatographic methods. Economical (reduction of analysis time, fewer experimental steps and less sample pre-separation) and ecological (carbon dioxide of organic solvents) advantages make SFC an attractive alternative to liquid chromatography in the determination of crotamiton.

Chromatography

Protein-RNA interactions in 20S U5 snRNPs.

The interaction of the U5-specific polypeptides with U5 snRNA was investigated by comparison of the differential accessibility towards nucleases and dimethylsulfate of defined regions of U5 snRNA in purified 20S and 10S U5 snRNPs. While 20S U5 snRNPs contain eight U5-specific proteins in addition to the common proteins, the 10S U5 snRNPs contain only the latter proteins. The results indicate that only the central part of stem/loop I of U5 snRNA including internal loops IL2 and IL2', contains binding sites for U5-specific proteins, suggesting that several U5-specific proteins may be bound to U5 snRNP via protein-protein interactions. Moreover, they show that the core polypeptides do not interact with stem/loop I.

Base Sequence

Colonic fermentation of potato starch after a freeze-thaw cycle.

To estimate colonic carbohydrate fermentation following a potato meal, 13 healthy volunteers consumed 375 g potatoes containing 60 g starch on three different occasions in random order: (A) potatoes boiled and consumed fresh at 60 degrees C; (B) potatoes boiled, frozen, thawed and consumed at 20 degrees C; and (C) potatoes boiled, frozen, thawed, reheated to 90 degrees C, and consumed at 60 degrees C. End-expiratory breath hydrogen (H2) was measured every 15 min for 10-14 hr with a selective electrochemical cell. The extent of colonic carbohydrate fermentation (AUC = area under the breath H2 concentration vs time curve) in experiment B was significantly higher (+186%, P less than 0.002) than in experiment A. The breath hydrogen AUC in experiment C was higher than in experiment A (+48%, P less than 0.04) but lower than in experiment B (-94%, P less than 0.003). It is suggested that structural alterations of the starch molecule occur during freezing, thawing, and reheating and alter the availability of carbohydrates for fermentation by colonic anaerobes.

Adult

Occurrence of express saccades under isoluminance and low contrast luminance conditions.

Saccadic reaction times (SRTs) of three human subjects were analyzed. The gap paradigm was used (i.e. fixation point offset precedes target onset) to obtain high proportions of express saccades (i.e. saccades of extremely short reaction times) in the SRT distributions. In one set of experiments, the luminance of the (red) saccade target was varied from brighter to darker than the (green) background including an isoluminance condition. Express saccades were obtained in response to pure color contrast stimuli with about the same frequency and reaction time as to stimuli with both color and luminance contrast. In a second experiment, the luminance contrast of a white target on a white background was lowered below 10%. Again the number of express saccades was not reduced. Thus, in contrast to other perceptual phenomena the visual neural mechanisms underlying the generation of express saccades are not affected by isoluminance nor low contrast luminance.

Color Perception