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Biomedical subjects

M Bach

Publications and source records attributed to M Bach.

At least 19 recordsLinked to original sources

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

Electron microscopy of U4/U6 snRNP reveals a Y-shaped U4 and U6 RNA containing domain protruding from the U4 core RNP.

We describe the electron microscopic investigation of purified U4/U6 snRNPs from human and murine cells. The U4/U6 snRNP exhibits two morphological features, a main body approximately 8 nm in diameter and a peripheral filamentous domain, 7-10 nm long. Two lines of evidence suggest that the peripheral domain may consist of RNA and to contain U6 RNA as well as the 5' portion of U4 RNA. (a) Separation of the U4/U6 snRNA interaction regions from the core domains by site-directed cleavage of the U4 snRNA with RNase H gave filament-free, globular core snRNP structures. (b) By immuno and DNA-hybridization EM, both the 5' end of U4 and the 3' end of U6 snRNA were located at the distal region of the filamentous domain, furthest from the core. These results, together with our observation that the filamentous U4/U6 domain is often Y shaped, correlate strikingly with the consensus secondary structure proposed by Brow and Guthrie (1988. Nature (Lond.), 334:213-218), where U4 and U6 snRNA are base paired in such a way that two U4/U6 helices together with a stem/loop of U4 snRNA make up a Y-shaped U4/U6 interaction domain.

Animals

[Pattern ERG in ocular hypertension and glaucoma. Effect of pattern size, contrast and retinal eccentricity].

We have previously shown that check-size-specific changes of the Pattern-Electroretinogram (PERG) can be used to detect early glaucoma. This time we conducted a study to determine whether different check sizes, contrasts and eccentricities can improve the diagnostic yield. We examined 15 normal eyes (15 subjects), 32 eyes (24 patients) in stage I or II glaucoma and 36 eyes (25 patients) with ocular hypertension (OHT). Visual acuity was always better than 0.8. The stimuli were checkerboards, phase-reversing at 16 rev/s. The check sizes were 0.8 degrees or 15 degrees with contrast at 60% or 98%. The stimulation area was either "full-field" (27 degrees x 30 degrees), "central" (less than or equal to 7 degrees) or "paracentral" (greater than 7 degrees). In the glaucoma group, all PERG amplitudes were significantly reduced compared to normals: maximally for stimuli of 0.8 degrees, 98% contrast, full-field to 51% +/- 18%, and least for stimuli of 15 degrees, 98% contrast, central (to 70% +/- 20%). Under paracentral stimulation, the amplitude was reduced to 55% and in the central condition to 64%. The single-most-sensitive stimulus to separate normal and glaucoma patients was 0.8 degrees, 60% contrast and full-field, as the variance was low for this condition. Only 4 patients (8.5%) were incorrectly classified using these parameters; when 8 different stimuli were entered into the discriminant analysis, the rate was marginally reduced to 3 patients (6.4%). Seventy-five percent of the OHT eyes were classified as pathological. These results confirm previous findings that in early glaucoma, PERG amplitudes are more reduced using check sizes of 0.8 degrees compared to 15 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroretinography

[Atrophy of the ganglion cells reduces pattern ERG not only in fine but also in coarse test patterns].

The pattern electroretinogram (PERG) is thought to be generated by the retinal ganglion cells. For coarse patterns, however, it has been suggested that the PERG is due to nonlinear summation of luminance responses. To test this hypothesis, we recorded the PERG in 8 patients with unilateral complete optic atrophy due to trauma or advanced glaucoma. Stimuli were phase-reversing checkerboards (7.8/s) with checks of 0.8 degrees and 15 degrees in size and with flashes. Retinal stimulation subtended 26 degrees x 34 degrees. In all 8 subjects, the PERG was greatly diminished using a check size of 0.8 degrees. With a check size of 15 degrees, the PERG was similarly diminished, while the flash responses were not reduced. Any overall luminance component of the stimulus, e.g., incomplete balance of light and dark areas, evoked strong luminance responses both in normal eyes and in eyes with optic nerve atrophy. Thus, intact ganglion cells seem to be necessary for a normal PERG regardless of the coarseness of the pattern. It is possible that different mechanisms (variable ganglion cell classes) contribute to the PERG response with different check sizes. Earlier reports, contradictory to these findings, are discussed. If the PERG reflects ganglion cell function even for large check sizes, stimulation of the ganglion cells with less optical degradation would be possible, enlarging its range of applications.

Attention

The protective effect of cyclosporine against cirrhotic alteration of the liver.

We have successfully applied the immunosuppressive drug cyclosporine in patients with primary biliary cirrhosis and in some patients with chronic active hepatitis. After several years of treatment, we have found a histologic remission tendency in cirrhotic alteration of some patients. This observation indicates that cyclosporine could have protective effects against fibrosis or cirrhotic alteration. To clarify this, we treated Sprague-Dawley rats in which the cirrhotic alteration of the liver was induced by injection of 0.5 ml/kg body weight carbon tetrachloride intramuscularly twice a week with cyclosporine (orally); the control animals were given saline solution instead of cyclosporine. After 6 weeks, we examined the liver histologically to determine the grade of fibrosis and cirrhosis and the grade of fatty degeneration; in group 2 we gave 1 mg/kg body weight cyclosporine daily, and in group 3 it was given every second day. We found excellent protective effects of cyclosporine against cirrhotic alteration in both groups compared with the control group. In group 3 only 25% of the animals showed grade 3 fibrosis and cirrhosis; however, the rate in the control animals (group 4) was 64.3%. In the daily application of cyclosporine (group 2) we found reduced effects of the drug compared with group 3. In group 1 we ordered 10 mg/kg body weight cyclosporine, which causes severe hepatotoxicity. In group 5, animals with hepatic damage from carbon tetrachloride were treated from the third week with cyclosporine. The effect of cyclosporine was not as beneficial compared with the groups in which we ordered cyclosporine from the first week. These results suggest excellent anticirrhotic effects of cyclosporine. This drug should be ordered as early as possible in the treatment of chronic hepatic damage and in an adequate minimal dosage.

Alanine Transaminase

Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group).

In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris