Search PubMed⌕ Search

Biomedical subjects

M Bach

Publications and source records attributed to M Bach.

At least 127 records · Page 7Linked to original sources
PubMed1991

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↗
PubMed1991

[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↗
PubMed1991

[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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Solution structure of human U1 snRNA. Derivation of a possible three-dimensional model.

The solution structure of human U1 snRNA was investigated by using base-specific chemical probes (dimethylsulfate, carbodiimide, diethylpyrocarbonate) and RNase V1. Chemical reagents were employed under various conditions of salt and temperature and allowed information at the Watson-Crick base-pairing positions to be obtained for 66% of the U1 snRNA bases. Double-stranded or stacked regions were examined with RNase V1. The dat gained from these experiments extend and support the previous 2D model for U1snRNA. However, to elucidate some aspects of the solution data that could not be accounted for by the secondary structure model, the information gathered from structure probing was used to provide the experimental basis required to construct and to test a tertiary structure model by computer graphics modeling. As a result, U1 snRNA is shown to adopt an asymmetrical X-shape that is formed by two helical domains, each one being generated by coaxial stacking of helices at the U1 snRNA cruciform. Chemical reactivities and model building show that a few nucleotides, previously proposed to be unpaired, can form A.G and U.U non Watson-Crick base-pairs, notably in stem-loop B. The structural model we propose for regions G12 to A124 integrates stereochemical constraints and is based both on solution structure data and sequence comparisons between U1 snRNAs.

Alkylating Agents↗
PubMed1990

Structure-probing of U1 snRNPs gradually depleted of the U1-specific proteins A, C and 70k. Evidence that A interacts differentially with developmentally regulated mouse U1 snRNA variants.

The interaction of the U1-specific proteins 70k, A and C with U1 snRNP was studied by depleting gradually U1 snRNPs of the U1-specific proteins by Mono-Q chromatography at elevated temperatures (20-37 degrees C). U1 snRNP species were obtained which were selectively depleted of either protein C, A, C and A, or of all three U1-specific proteins C, A and 70k while retaining the common proteins B' to G. These various types of U1 snRNP particles were used to study the differential accessibility of defined regions of U1 RNA towards nucleases V1 and S1 dependent on the U1 snRNP protein composition. The data indicate that in the U1 snRNP protein 70k interacts with stem/loop A and protein A with stem/loop B of U1 RNA. The presence or absence of protein C did not affect the nuclease digestion patterns of U1 RNA. Our results suggest further that the binding of protein A to the U1 snRNP particle should be independent of proteins 70k and C. Mouse cells contain two U1 RNA species, U1a and U1b, which differ in the structure of stem/loop B, with U1a exhibiting the same stem/loop B sequence as U1 RNA from HeLa cells. When we used Mono Q chromatography to investigate possible structural differences in the two types of U1 snRNPs, we observed that protein A was always preferentially lost from U1b snRNP as compared to U1a snRNPs. This indicates that one consequence of the structural difference between U1a and U1b is a lowering of the strength of binding of protein A to U1b snRNP. The possible functional significance of this finding is discussed with respect to the fact that U1b RNA is preferentially expressed in embryonal cells.

Animals↗
PubMed1990

U1-specific protein C needed for efficient complex formation of U1 snRNP with a 5' splice site.

One of the functions of U1 small nuclear ribonucleoprotein (snRNP) in the splicing reaction of pre-mRNA molecules is the recognition of the 5' splice site. U1 snRNP proteins as well as base-pair interactions between U1 snRNA and the 5' splice site are important for the formation of the snRNP-pre-mRNA complex. To determine which proteins are needed for complex formation, the ability of U1 snRNPs gradually depleted of the U1-specific proteins C, A, and 70k to bind to an RNA molecule containing a 5' splice site sequence was studied in a nitrocellulose filter binding assay. The most significant effect was always observed when protein C was removed, either alone or together with other U1-specific proteins; the binding was reduced by 50 to 60%. Complementation of protein C-deficient U1 snRNPs with purified C protein restored their 5' splice site binding activity. These data suggest that protein C may potentiate the base-pair interaction between U1 RNA and the 5' splice site.

Animals↗
PubMed1990

Variability of the steady-state visually evoked potential: interindividual variance and intraindividual reproducibility of spatial frequency tuning.

At low contrast levels there is good agreement between the psychophysical contrast sensitivity function and the tuning curve of the visually evoked potential (i.e., VEP amplitude vs spatial frequency). At high contrast, however, some researchers have found bimodal VEP tuning curves whereas others have not. We studied the VEP in 22 subjects in a short-term cross-sectional study and in 13 subjects in a longitudinal study over 8 sessions covering 28 days. Grating stimuli with 60% contrast were square-wave modulated in time (7.8 reversals/s) and space (0.06-16 cycles/degree). We found large interindividual variance in the shape of the tuning curves; about half of the subjects showed a unimodal shape, while the other half showed a bimodal one (with a 'notch' between 1 and 2 cycles/degree). These features turned out to be stable in the longitudinal study, where variability could mainly be ascribed to a multiplicative influence common to all spatial frequencies. The marked interindividual differences in the shape of the tuning curve, which seem to be intraindividually stable, may explain previous discrepancies. It is not yet clear why the notch exists in about half of our subjects.

Adult↗
PubMed1990

Electron microscopy of small nuclear ribonucleoprotein (snRNP) particles U2 and U5: evidence for a common structure-determining principle in the major U snRNP family.

We have studied by electron microscopy the structures of native small nuclear ribonucleoprotein (snRNP) particles U2 and U5 from HeLa cells. The structure of native U2 snRNP is characterized by a main body 8 nm in diameter with one additional domain about 4 nm long and 6 nm wide. Electron micrographs show that the 20S U5 snRNP, which contains at least seven U5-specific proteins in addition to the common proteins, has an elongated structure measuring 20-23 nm in length and 11-14 nm in width. Two main structural domains can be distinguished: a small head and a large elongated body about twice the size of the head. In addition to the head, the body of the 20S U5 snRNP possesses three short protuberances. The U2 and U5 core RNP particles--that is, of the snRNPs U2 and U5 without the snRNP-specific proteins, look much simpler and smaller under the electron microscope. They both are round in shape with a diameter of approximately 8 nm. With respect to their size, appearance, and fine structure, the U2 and U5 snRNP cores not only closely resemble each other but also share these properties with the core domain of U1 snRNP. We propose that the characteristic shape of each of the major snRNP species U1, U2, U4/U6, and U5 is determined by (i) a core domain containing the proteins that are common to all members of this family, which has the same shape for each member, and (ii) peripheral structures, which for snRNPs U1, U2, and U5 arise from the specific proteins, that give each of these snRNP species its characteristic shape.

Antibodies, Monoclonal↗
PubMed1990

The position of delusional parasitosis in psychiatric nosology and classification.

Discussions on the nosological position of delusional parasitosis (DP) have resulted in a wide range of opinions. In the present study in 34 patients with DP, the various and contradictory opinions concerning DP positioning in psychiatric nosology were examined through clinical, psychopathological, and polydiagnostic analyses using VRC, DSM-III, DSM-III-R and ICD-9. The psychopathological analyses with VRC as well as the polydiagnostic comparisons with other classification systems indicated that DP is neither a nosological entity nor due to a specific psychiatric illness. As our results showed, DP is a nosologically unspecific syndrome, which may occur superimposed on all psychiatric disorders.

Delusions↗
PubMed1990

[The pattern electroretinogram in early glaucoma and ocular hypertension].

The pattern electroretinogram (PERG) reflects the activity of the retinal ganglion cells. To assess its value to detect early glaucoma damage, we recorded the PERG in 44 normal eyes, in 52 eyes with early stages of glaucoma, and in 34 eyes with elevated intraocular pressure but normal visual fields (ocular hypertension, OHT). All eyes had a decimal acuity of greater than or equal to 0.8. We used checkerboard patterns for the stimulation with check sizes of 0.8 degrees and 15 degrees, a contrast of 98% and a reversal rate of 16/s. Compared to the controls, in eyes with early glaucoma PERG amplitude was reduced to 50% using 0.8 degrees (p less than or equal to 0.0001) and to 74% using a check size of 15 degrees (p less than or equal to 0.001). However, due to the high interindividual variability, confidence limits overlapped to a large extent. Based on the preferential reduction at 0.8 degrees vs 15 degrees, a sensitivity of 74% and a specificity of 92% were achieved using a two-dimensional logistic regression; 50% of the OHT eyes were thus classified as pathological. These results suggest that the PERG can detect retinal ganglion cell damage before measurable changes in the visual field occur if responses to two check sizes are evaluated.

Adult↗
PubMed1990

RNP, Sm and SS-B antigens from calf thymus: molecular stability upon enzymatic digestion.

RNP, Sm and SS-B nuclear antigens from calf thymus were studied with respect to the size distribution on sucrose gradients as well as to the molecular integrity and related structural changes when they were subjected to enzymatic digestions under different conditions. Making a difference with RNP particles, the Sm size distribution is concentration dependent, a property in accordance with the complexity of the Sm particles in comparison with the RNPs. The use of combined effects of temperature, endogenous proteases and RNase A, allowed us to gain insight into the limits of stability of the three antigenic particles. Following treatments in the absence of RNAse A, the degradation products (32-38 Kd molecular weight) of the 70 Kd RNP polypeptide remain stable and associated with other molecules within the RNP particle. It was also found that the phosphate groups of the SS-B protein moiety are only accessible to alkaline phosphatase if the RNA of the SS-B particle is degraded by the action of RNAse A.

Animals↗
PubMed1990

[Amblyopia: reading speed in comparison with visual acuity for gratings, single Landolt Cs and series Landolt Cs].

In the treatment of amblyopia in preschool children, a means of predicting later reading ability would be helpful. This prediction might be possible using a test for visual acuity where the results correlate with reading ability in adult patients with amblyopia. We measured the following four parameters in 18 experienced readers with strabismic amblyopia: (1) time spent reading ten lines of a standard text in one of three magnifications, (2) visual acuity for gratings, (3) visual acuity for single Landolt Cs, and (4) visual acuity for crowded Landolt Cs (one Landolt C flanked by two full rings on each side each at a distance of 2.6 min of arc). The reading text was presented on paper at a distance of 40 cm; the subject had a choice of three magnifications. The acuity tests were generated by a computer on a VDU at 4.6 m. The relative impairment of the amblyopic eye was defined as the quotient between the performance of the amblyopic and the good eye. In addition, the difference between the times spent reading the ten lines with the amblyopic and with the good eye was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗