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Biomedical subjects

P Edelmann

Publications and source records attributed to P Edelmann.

At least 19 recordsLinked to original sources
PubMed2001

Morphology and dynamics of chromosome territories in living cells.

Chromosome territories formed by fluorescence-labeled sub-chromosomal foci were analyzed in time-lapse series of 3D confocal data sets of living HeLa and human neuroblastoma cells. The quantitative analysis of the chromosome territory morphology confirmed previous results obtained by visual observation [Zink et al., Hum. Genet. 102 (1998) 241-251] that chromosome territories persisted as stable entities over an observation time >4 h. The changes in morphology with time of single chromosome territories were found to be less pronounced than differences in morphology of different chromosome territories in fixed cells. The analysis of the individual motion of chromosome territories recently showed 'Brownian' diffusion-like motion at very slow rates [Bornfleth et al., Biophys. J. 77 (1999) 2871-2886]. Here, we show that the mutual motion of different chromosome territories was independent and also 'Brownian' diffusion-like.

Carbocyanines↗
PubMed2001

Conformational differences in the 3-D nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes.

Spectral precision distance microscopy was utilized to detect small but nonetheless consistently present conformational differences between the immunoglobulin heavy-chain gene clusters (IgH) that reside on the two chromosome 12 homologues in all diploid cells of the mouse. The euclidian distance (i.e., the mean arithmetic three-dimensional [3-D] distance) between the 5' most IgH gene, C mu, and the 3' most IgH gene, C alpha, was used as the indicator to define the co-presence of a condensed IgH domain and a relaxed IgH domain in the same cell. In normal and malignant B cells in which IgH is actively rearranged and transcribed, the C mu/C alpha distance (genomic distance approximately 180 kb) was found to range from 87.5 to 121 nm on the condensed IgH domain and from 154 to 207 nm on the relaxed IgH domain. In non-B cells (fibroblasts, neutrophils, and macrophages), in which IgH is inactive, the C mu/C alpha distance was found to range from 136 to 154 nm on the condensed IgH domain and from 250 to 292 nm on the related IgH domain. These results suggested that conformational differences that may predispose the relaxed IgH domain for illegitimate genetic recombinations, such as chromosomal translocations, are likely to exist in many cell types, including B cells. However, in B lymphocytes this structural predisposition may conspire with the lineage-specific ability to activate proto-oncogenes (after juxtaposition to IgH) to positively affect the preferential involvement of the relaxed IgH domain in chromosomal translocations. Additional studies are warranted to validate this working hypothesis.

Animals↗
PubMed2001

Towards a dynamical approach for the simulation of large scale, cancer correlated chromatin structures.

To understand the influence of geometrical constraints in the spatial distribution of cancer correlated "Double Minute chromosomes (DMs)" in human cell nuclei, we applied computer simulations of the nuclear 3D structure in combination with a voxel based segmentation algorithm. With this approach we determined the overlap volumes and intensities of the DMs with the chromatin free space in the simulated nucleus. For this purpose, beginning from a start configuration, simulated linear chromosome chains together with the DMs were relaxed according to the Monte Carlo process. The simulations predict a preferential positioning of DMs within the "peripheral" "Inter Chromatin Domain (ICD)" space.

Algorithms↗
PubMed2000

Three-dimensional spectral precision distance microscopy of chromatin nanostructures after triple-colour DNA labelling: a study of the BCR region on chromosome 22 and the Philadelphia chromosome.

Topological analysis of the three-dimensional (3D) chromatin nanostructure and its function in intact cell nuclei implies the use of high resolution far field light microscopy, e.g. confocal laser scanning microscopy (CLSM). However, experimental evidence indicates that, in practice, under biologically relevant conditions, the spatial resolution of CLSM is limited to about 300 nm in the lateral direction and about 700 nm in the axial direction. To overcome this shortcoming, the use of a recently developed light microscopical approach, spectral precision distance microscopy (SPDM) is established. This approach is based on the precise localization of small labelling sites of a given target in spectrally differential images. By means of quantitative image analysis, the bary centres (intensity weighted centroid analogous to the centre of mass) of these independently registered labelling sites can be used as point markers for distance and angle measurements after appropriate calibration of optical aberrations (here, polychromatic shifts). In combination with specific labelling of very small chromatin target sites with dyes of different spectral signatures by fluorescence in situ hybridization (FISH), SPDM presently allows us to analyse the nuclear topology in three-dimensionally conserved nuclei with a 'resolution equivalent', many times smaller than the conventional optical resolution. Chronic myelogeneous leukaemia (CML) is genetically characterized by the fusion of parts of the BCR and ABL genes on chromosomes 22 and 9, respectively. In most cases, the fusion leads to a translocation t(9; 22) producing the Philadelphia chromosome. SPDM was applied to analyse the 3D chromatin structure of the BCR region on the intact chromosome 22 and the BCR-ABL fusion gene on the Philadelphia chromosome (Ph) by using a new triple-colour FISH protocol: two different DNA probes were used to detect the BCR region and the third DNA probe was used to identify the location of the ABL gene. Consistent 3D distance measurements down to values considerably smaller than 100 nm were performed. The angle distributions between the three labelled sites on the Philadelphia chromosome territory were compared to two state-of-the-art computer models of nuclear chromatin structure. Significant differences between measured and simulated angle distributions were obtained, indicating a complex and non-random angle distribution.

Bone Marrow Cells↗
PubMed1999

The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity.

The three-dimensional positioning of the X-chromosomal adenine nucleotide translocase genes, ANT2 and ANT3, were compared in the active and inactive X chromosome territories (Xa and Xi) of female human amniotic fluid cell nuclei. ANT2 is located in Xq24-q25 and is transcriptionally active on Xa, but inactive on Xi. ANT3 is located in the pseudoautosomal region Xp22.3 and escapes X-inactivation. Three-color fluorescence in situ hybridization, confocal laser scanning microscopy, and three-dimensional image analysis revealed that transcriptionally active ANT2 and ANT3 genes were positioned more peripheral within their chromosome territory than the inactive ANT2 gene. The position of the latter was significantly more interior in the Xi territory. Although the volumes of both X territories were similar, 3D distances between ANT2 and ANT3 were significantly smaller in Xi compared to Xa territories reflecting different territory shapes. Our data show a correlation between 3D positioning and transcriptional activity of these X-specific genes.

Amniotic Fluid↗
PubMed1999

Quantitative motion analysis of subchromosomal foci in living cells using four-dimensional microscopy.

The motion of subchromosomal foci and of whole chromosome territories in live human cell nuclei was investigated in four-dimensional space-time images. Visualization of subchromosomal foci was achieved by incorporating Cy3-dUTP into the nuclear DNA of two different cell types after microinjection. A subsequent segregation of the labeled cell nuclei led to the presence of only a few labeled chromosome territories on a background of nonlabeled chromatin (Zink et al.,1998. Hum. Genet. 102:241-251). This procedure yielded many distinct signals in a given cell nucleus. Motion analysis in four-dimensional space-time images was performed using single-particle tracking and a statistical approach to the detection of a possible directional motion of foci relative to the center of mass of a chromosome territory. The accuracy of the analysis was tested using simulated data sets that closely mirrored the experimental setup and using microparticles of known size. Application of the analysis tools to experimental data showed that mutual diffusion-like movements between foci located on different chromosomes were more pronounced than inside the territories. In the time range observed, movements of individual foci could best be described by a random diffusion process. The statistical test for joint directed motion of several foci inside chromosome territories revealed that foci occasionally switched from random to directional motion inside the territories.

Cell Nucleus↗
PubMed1992

Brace treatment in idiopathic scoliosis.

A German multicenter study with consequent long-term follow-up of patients with idiopathic scoliosis after Milwaukee brace treatment in one out of seven Orthopaedic Clinics showed that brace weaning at the bone age of Risser 4 is followed by early loss of curve correction. According to Oberthaler et al. patients, who were furnished with a brace as outpatients, are inclined to practice a part-time wearing with different brace free intervals. In a longterm follow-up study of 328 patients with idiopathic scoliosis treated at the North German Scoliosis Center in Cuxhaven 123 compliant patients were examined 4 1/2 years after brace weaning. All were asked to wear their braces 23 hours a day and were weaned only at Risser 4-5 or Risser 5. The control rate was 93%. A gain of correction between 9 and 22% was the result. We analysed the composition of the group of 81 noncompliant patients. As far as we could find out the percentage of really non-compliant patients was only 19% compared with a total of 212 patients, who had finished their brace treatment at least 5 years ago. Eight patients (4%) with prebrace values of over 40 degrees Cobb had to be operated, though they were compliant. Based on these results, strict brace treatment in progressive idiopathic scoliosis is recommended, unless no more physiologic way of treatment is available.

Braces↗
PubMed1987

Nonsense suppression context effects in Escherichia coli bacteriophage T4.

Nonsense suppression by supE44 has been examined in a collection of 14 T4 gene 22 and gene 23 UAG mutants, for which the precise gene location is known. In concordance with previous studies, UAG followed by a pyrimidine was inefficiently suppressed. However, among positions with similar 3' nucleotides, there was considerable variation in suppression efficiency. The competition between supE44 and Release Factor 1 (RF 1) was also investigated following the introduction of a multicopy RF 1 plasmid. An inverse relationship between the efficiency of suppression and RF 1 competition was observed.

Codon↗
PubMed1981

[Equal pelvic crest or horizontal upper sacral line? (author's transl)].

The very aim in the treatment of leg length differences must be a horizontal position of the upper edge of the sacrum. The equal height of the pelvic crest is a very uncertain sign. The inclination of the upper part of the sacrum depends more or less from leg length differences and asymmetries of the pelvis. A side bending of the lumbar spine can be a consequence of both. The so called paradox lumbar scoliosis depends on a rotation of the sacrum and a non corresponding leg length difference. Whereas leg length differences can be treated causally the therapy of a sacrum rotation is only symptomatic.

Humans↗
PubMed1980

Relationship of plasma sex hormones to different parameters of obesity in male subjects.

Relationships between plasma sex hormones and different parameters of obesity (weight, ideal body weight [IBW], overweight, fat mass, and body surface) were investigated in 70 healthy nonobese and obese males, 20-40 yr of age and with a body weight of 85%-245% of IBW. Plasma sex hormones remained unaffected by weight up to approximately 160% of the IBW. Only in the massively obese subjects was plasma testosterone decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas free testosterone remained almost constant. On the other hand, plasma estrone and estradiol exhibited significant increases in obese subjects, ranging from 31.5 +/- 52.3 +/- 5.8 pg/ml for estrone, and 25.4 +/- 5.4 increasing to 44.7 +/0 5.0 pg/ml for estradiol. Similarly, free estradiol was shown to significantly increase with obesity in men from 505 +/- 118 to 991 +/- 123 fg/ml (p < 0.001). The ratios of testosterone/androstenedione, as well as of estradiol/estrone, were not affected by obesity, suggesting that reduction of the 17-oxo-group of the steroids is not influenced by the amount of fat tissue. A significant (p < 0.001) correlation was found between IBW and estrone (r = 0.80) and estradiol (r = 0.75), as well as the ratios of estrone/androstenedione (r = 0.62) and estradiol/testosterone (r = 0.86). This is consistent in its evidence indicating that fat tissue may be able to aromatize androgens. In the obese subjects, there were significant correlations between plasma sex hormones (testosterone, estrone, estradiol, and free estradiol) and the parameters of obesity used. Among these, correlations were best with IBW, overweight, and fat mass (r = 0.74-0.89; p < 0.001); body weight and body surface were less favorable.

Adult↗
PubMed1977

Mistranslation in E. coli.

Flagellin, the protomeric subunit of bacterial flagella, contains no cysteine. We have detected the incorporation of trace quantities of 35S-cysteine into flagellin, highly purified and then resolved by SDS polyacrylamide gel electrophoresis, to measure mistranslation in vivo. Under normal conditions, this value is about 6 X 10(-4) pmoles cysteine per pmole flagellin. This value is greatly increased during growth in low concentrations of streptomycin and neomycin, antibiotics which are known to stimulate misreading in vitro. Of the specific types of misreading which streptomycin stimulates in vitro, only misreading of the CGU and CGC arginine codons could give rise to illegitimate incorporation of cysteine. In agreement, partial arginine starvation increases the incorporation of 35S-cysteine into flagellin in a relA- mutant, with or without streptomycin, but has no such effect in its isogenic relA+ partner- Assuming from these results that 35S-cysteine incorporation into flagellin reflects misreading of CGU/C coda, we deduce a misreading probability per codon in the range of 10(-4).

Arginine↗
PubMed1977

On the translational error theory of aging.

Theoretical treatments of error feedback in translation have revealed that two different modes of behavior are possible, depending on the values of certain parameters. In mode I, the error frequency will rise steadily toward randomness, inevitably reaching whatever value is catastrophic for cell survival; the "error catastrophe" theory of aging implicitly assumes this mode of behavior. In mode II, the error frequency will converge to a stable value, which may or may not have toxic consequences. We have performed an experimental test of the behavior of the translation system in Escherichia coli cells: we altered the system's intrinsic fidelity by means of the error-promoting drug streptomycin, and monitored the kinetics of change in error frequency by means of a specific assay of one kind of mistranslation (incorporation of cysteine into flagellin). We find that the system behaves according to mode II. Moreover, E. coli cells in which the error frequency has stabilized at a value as high as 50 times greater than normal continue to proliferate, albeit abnormally slowly, and their viability is not detectably reduced. Earlier results by Gorini and his associates point in the same direction. These observations diminish the plausibility of the error catastrophe theory of aging.

Aging↗