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Biomedical subjects

F Eckstein

Publications and source records attributed to F Eckstein.

At least 91 records · Page 5Linked to original sources
PubMed2000

Glenohumeral translation during active and passive elevation of the shoulder - a 3D open-MRI study.

Despite its importance for the understanding of joint mechanics in healthy subjects and patients, there has been no three-dimensional (3D) in vivo data on the translation of the humeral head relative to the glenoid during abduction under controlled mechanical loading. The objective was therefore to analyze humeral head translation during passive and active elevation by applying an open MR technique and 3D digital postprocessing methods. Fifteen healthy volunteers were examined with an open MR system at different abduction positions under muscular relaxation (30-150 degrees of abduction) and during activity of shoulder muscles (60-120 degrees ). After segmentation and 3D reconstruction, the center of mass of the glenoid and the midpoint of the humeral head were determined and their relative position calculated. During passive elevation, the humeral head translated inferiorly from +1.58mm at 30 degrees to +0. 36mm at 150 degrees of abduction, and posteriorly from +1.55mm at 30 degrees to -0.07mm at 150 degrees of abduction. Muscular activity brought about significant changes in glenohumeral translation, the humeral head being in a more inferior position and more centered, particularly at 90 and 120 degrees of abduction (p<0.01). In anterior/posterior direction the humeral head was more centered at 60 and 90 degrees of abduction during muscle activity. The data demonstrate the importance of neuromuscular control in providing joint stability. The technique developed can also be used for investigating the effect of muscle dysfunction and their relevance on the mechanics of the shoulder joint.

Biomechanical Phenomena↗
PubMed2000

Attempts to obtain more efficient GAC-cleaving hammerhead ribozymes by in vitro selection.

An in vitro selection was carried out to identify hammerhead ribozymes cleaving 3' to GAC triplets more efficiently than the wild type ribozyme. A double-stranded DNA containing the sequence for the hammerhead ribozyme with 10 randomizations in the catalytic core, designed for in cis cleavage, was transcribed and the cleavage product amplified by reverse transcription and PCR. After seven selection cycles, the DNA was cloned and 50 colonies sequenced. One sequence, appearing six times, was active for in cis cleavage of GAC. It was identical to the consensus sequence except for a mutation at position 7. Another cleaved GUC and two more, cleaved GUA. The cleavage rates of these ribozymes for in trans cleavage were slower than the rate of the consensus ribozyme. Interestingly, the consensus sequence was not found in the selection. This strongly suggests that the consensus hammerhead ribozyme has evolved to an optimal sequence.

Base Sequence↗
PubMed2000

Ribozyme and free alkylated base: a dual approach for sensitizing Mex+ cells to the alkylating antineoplastic drug.

N-alkyl-nitrosoureas and alkyl-triazenes are alkylating antineoplastic drugs, the efficacy of which is strongly affected by the level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In tumors, MGMT activity reduces the chemotherapeutic potential of alkylating drugs; therefore, efforts have been made to down-regulate the protein. A partial sensitization of Mex+ cells to alkylating drugs has been obtained using either free alkylated bases or oligonucleotides targeted against MGMT mRNA. In the present work, O6-methylguanine and a chemically modified ribozyme, without a cationic liposome as a carrier, were coadministered to CHO47 cells, which express a high level of human MGMT protein. The reduction of MGMT mRNA and protein enhanced the genotoxicity of the alkylating drug mitozolomide. Furthermore, the sensitivity of CHO47 cells is the same as that of CHO5 cells, which lack MGMT protein. These data indicate that a strategy in which both mRNA and protein are degradation targets can be successfully applied to down-regulate the MGMT gene.

Animals↗
PubMed2000

Validation of high-resolution water-excitation magnetic resonance imaging for quantitative assessment of thin cartilage layers.

OBJECTIVE: To employ a magnetic resonance (MR) imaging technique for quantitative assessment of thin cartilage layers, and to validate the cartilage volume and thickness measurements. METHODS: We investigated 10 normal elbow joints (age 20 to 69 years) with a 3D gradient echo sequence with selective water excitation (TR 18 ms; TE 9 ms; FA 25 degrees, resolution 1x0.25x0.25 mm2, imaging time 19 min). After interpolating the image data to a 0.125x0.125 mm2 in-plane resolution, the cartilage plates were segmented, reconstructed in 3D, and the cartilage volume and thickness determined with a 3D Euclidean distance transformation algorithm, independent of the original section plane. The cartilage volume and thickness values were compared with CT arthrography and A-mode ultrasound. RESULTS: The mean systematic difference between the elbow cartilage volume obtained from MR imaging and CT arthrography was -0.11% (-6.0 mm3) and the mean random difference 5.7% (314 mm3). Except for the fovea capitis radii, the deviations were not statistically significant (range -7.6 to +11.7%). In the humerus, the mean cartilage thickness (average = 1.35 mm) was overestimated relative to CT arthrography (+20.7%/+0.23 mm), and slightly underestimated relative to A-mode ultrasound (-6.0%/-0.05 mm). With few exceptions, there were no significant differences between MRI, CT arthrography and ultrasound in the other joint surfaces of the elbow (random deviations between 0.08 and 0.39 mm). CONCLUSIONS: The technique presented can be applied for determining the cartilage volume and 3D thickness in joints with thin cartilage layers with a reasonable degree of accuracy.

Adult↗
PubMed2000

A technique for 3D in vivo quantification of proton density and magnetization transfer coefficients of knee joint cartilage.

OBJECTIVE: To develop an MR-based method for the in vivo evaluation of the structural composition of articular cartilage. DESIGN: Five sagittal magnetic resonance imaging (MRI) protocols were acquired throughout the knee joint of 15 healthy volunteers and the boundaries of the cartilage segmented from a previously validated sequence with high contrast between cartilage and surrounding tissue. The other sequences were matched to these data, using a 3D least-squares fit algorithm to exclude motion artefacts. In this way secondary images were computed that included information about the proton density (interstitial water content) and the magnetization transfer coefficient (macromolecules, collagen). The average signal intensities of the 3D cartilage plates were extracted from these data sets and related to a phantom. RESULTS: The signal intensity data showed a high interindividual variability for the proton density (patella 31%, lateral tibia 36%, medial tibia 29%); the patella displaying higher values than the tibia (P< 0.001). There were high correlations between the three plates. The magnetization transfer coefficient also showed high variability (patella 25%, lateral tibia 32%, medial tibia 30%) with the lowest values in the medial tibia (P< 0.01) and lower correlations between the plates. The slice-to-slice variation (medial to lateral) ranged from 9% to 24%. CONCLUSION: An MR-based method has been developed for evaluating the proton density and magnetization transfer of articular cartilage in vivo and observing systematic differences between knee joint cartilage plates. The technique has the potential to supply information about the water content and collagen of articular cartilage, in particular at the early state of osteoarthritic degeneration.

Adult↗
PubMed2000

Phosphorothioate oligodeoxynucleotides: what is their origin and what is unique about them?

The development of nucleoside phosphorothioates is described in its historical context. Examples of the interaction of phosphorothioate groups, present either in oligodeoxynucleotides or in DNA, with nucleases are presented. The structural features responsible for the resistance of the phosphorothioates toward degradation by nucleases are discussed, as are the possible reasons for the high-affinity interaction of phosphorothioate oligodeoxynucleotides with certain proteins.

Animals↗
PubMed2000

Magnetic resonance-based motion analysis of the shoulder during elevation.

Changes in shoulder motion patterns are relevant in various shoulder diseases, but no in vivo information exists about the relative positions in vivo of the shoulder girdle bones and the supraspinatus muscle in three-dimensional space. Thus, the objective of this study was to perform a motion analysis of these structures during passive arm elevation using open magnetic resonance imaging and three-dimensional image processing. Fourteen volunteers were examined in five positions of abduction (30 degrees-150 degrees) with an open magnetic resonance system. After segmentation and three-dimensional reconstruction, the axis of the supraspinatus, humerus, clavicle, and the plane of the glenoid were determined, and the relative movements were calculated. The ratio for glenohumeral to scapulothoracic motion was 1.5:1 at 60 degrees and 2.4:1 at 120 degrees abduction. At 30 degrees, the axis of the supraspinatus was nearly horizontal, and during abduction a continuous elevation (+123 degrees at 150 degrees abduction) was measured. In the transverse plane, the angle between the supraspinatus and the clavicle axes became larger during abduction because of an increasing retroversion of the clavicle. The study shows specific three-dimensional motion patterns for each bone of the shoulder girdle and the supraspinatus muscle during passive elevation. The technique and results can be used for future studies in patients with pathologic changes of shoulder girdle motion.

Adult↗
PubMed2000

[A new in vivo technique for 3-dimensional analysis of the translation of femoral condyles and the menisci responding to antagonistic muscle forces].

The aim of our study was to develop a 3-D MR-based technique for the analysis of meniscal and femoral translations during flexion of the knee, and under the influence of antagonistic muscle forces in healthy subjects. In an open MR system, 5 knees were examined at 30 degrees and 90 degrees flexion using a T1-weighted 3-D gradient echo sequence. A force of 30 Newtons, first in the extending and then in the flexing direction, was applied to the distal lower leg. After three-dimensional reconstruction, the minimal distances between the centre of the tibial plateau and the posterior edge of the menisci and femoral condyles were determined. At 30 degrees flexion, the minimum distance for the meniscus was larger medially than laterally (23.2 +/- 1.8 mm vs. 16.2 +/- 3.3 mm), and this also applied to the condyles (25.1 +/- 1.5 vs. 19.0 +/- 3.0 mm). During flexion to 90 degrees, a posterior translation of 0.5 +/- 0.2 mm was observed for the lateral, and of 3.4 +/- 1.2 mm for the medial, meniscus. The condyles demonstrated a different posterior translation (lateral 2.2 +/- 0.56 mm; medial 1.8 +/- 1.9 mm). No obvious differences were found between extension and flexion muscle activity for the different positions of the knee. In the present study, a new 3-D technique is presented for the analysis of the femoral and meniscal translation at various positions of the knee, and under muscle activity. The results suggest different translation for the menisci and condyles.

Adult↗
PubMed2000

[Precision MRI-based joint surface and cartilage density analysis of the knee joint using rapid water-excitation sequence and semi-automatic segmentation algorithm].

The aim of this study was to analyse the precision of three-dimensional joint surface and cartilage thickness measurements in the knee, using a fast, high-resolution water-excitation sequence and a semiautomated segmentation algorithm. The knee joint of 8 healthy volunteers, aged 22 to 29 years, were examined at a resolution of 1.5 mm x 0.31 mm x 0.31 mm, with four sagittal data sets being acquired after repositioning the joint. After semiautomated segmentation with a B-spline Snake algorithm and 3D reconstruction of the patellar, femoral and tibial cartilages, the joint surface areas (triangulation), cartilage volume, and mean and maximum thickness (Euclidean distance transformation) were analysed, independently of the orientation of the sections. The precision (CV%) for the surface areas was 2.1 to 6.6%. The mean cartilage thickness and cartilage volume showed coefficients of 1.9 to 3.5% (except for the femoral condyles), the value for the medial femoral condyle being 9.1%, and for the lateral condyle 6.5%. For maximum thickness, coefficients of between 2.6 and 5.9% were found. In the present study we investigate for the first time the precision of MRI-based joint surface area measurements in the knee, and of cartilage thickness analyses in the femur. Using a selective water-excitation sequence, the acquisition time can be reduced by more than 50%. The poorer precision in the femoral condyles can be attributed to partial volume effects that occur at the edges of the joint surfaces with a sagittal image protocol. Since MRI is non-invasive, it is highly suitable for examination of healthy subjects (generation of individual finite element models, analysis of functional adaptation to mechanical stimulation, measurement of cartilage deformation in vivo) and as a diagnostic tool for follow-up, indication for therapy, and objective evaluation of new therapeutic agents in osteoarthritis.

Adult↗
PubMed1999

Hammerhead ribozyme mechanism: a ribonucleotide 5' to the substrate cleavage site is not essential.

Three hammerhead ribozymes with triplet specificities for cleavage 3' of CUC, GUC, and GUA have been evaluated for their sensitivity to the substitution of thymidine or 2'-deoxyuridine at central nucleotide position 16.1 in the substrate triplet. All three ribozymes cleaved their respective substrates, containing uridine or the modifications, with comparable rates. This indicates that the 2'-hydroxy group at position 16.1 is not essential for activity even though X-ray structure analysis shows it participates in H-bonding interactions. These H-bonds were considered to be of functional significance because an earlier report had provided data that thymidine at position 16.1 is deleterious for catalytic activity [Yang, J.-H., Perreault, J.-P., Labuda, D., Usman, N., and Cedergren, R. (1990) Biochemistry 29, 11156-11160].

Deoxyuridine↗
PubMed1999

Inhibition of luciferase expression by synthetic hammerhead ribozymes and their cellular uptake.

Two synthetic hammerhead ribozymes, one unmodified and the other with 2"-modifications and four phosphorothioate groups, targeting a single GUA site in the luciferase mRNA, were compared for their inhibition of gene expression in cell cultureand their cellular uptake was also analysed. A HeLa X1/5 cell line stably expressing luciferase, under an inducible promoter, was treated with these ribozymes by liposome-mediated transfection to determine their activity. Luciferase expression in cells was inhibited to approximately 50% with little difference between the unmodified and the 2"-modified ribozyme. A similar degree of inhibition was observed with two catalytically inactive ribozymes, indicating that inhibition was mainly due to an antisense effect. A ribozyme carrying a cholesterol moiety, applied to the cells without carrier, showed no inhibition. Northern blotting indicated a similar amount of cellular uptake of all ribozymes. The unmodified ribozyme was essentially evenly distributed between cytoplasm and nucleus, whereas a higher proportion of the phosphorothioate-containing ribozyme was observed in the nucleus. Fluorescence microscopy, including confocal microscopy using 5"-fluorescein-labelled ribozymes, showed that the unmodified and 2"-modified ribozymes were present in the cytoplasm and in the nucleus to a similar extent, whereas the fluorescence of the phosphorothioate-containing ribozyme was much stronger in the nucleus. Both ribozymes inhibited luciferase expression to a comparable degree, suggesting that the ribozyme in the nucleus did not contribute significantly to the inhibition. Ribozymes with a cholesterol moiety were predominantly trapped in the cell membrane, explaining their inability to interfere with gene expression.

Base Sequence↗
PubMed1999

Determination of 3D cartilage thickness data from MR imaging: computational method and reproducibility in the living.

The objective of this work was to develop a computational approach for quantifying the three-dimensional (3D) thickness distribution of articular cartilage with magnetic resonance (MR) imaging, independent of the imaging plane, and to test the reproducibility of the method in the living. An algorithm was implemented, based on a 3D Euclidean distance transformation, and its accuracy was assessed in geometric test objects, for which an analytic solution was available. The precision of the method was evaluated in six replicated MR data sets of the knee joint cartilage of eight volunteers. The algorithm produced 3D thickness values identical to those of the analytic solutions in the test objects. The reproducibility of the mean cartilage thickness in the patellar and tibial cartilages was 1.5-3.4% (root-mean-square average of the individual coefficient of variation percent), that of the maximal thickness 2.1-7.9%, and that of the thickness distribution 2.3-6.1%. The method presented allows for noninvasive analysis of 3D cartilage thickness from MR images in biomechanical and clinical investigations.

Algorithms↗
PubMed1999

The hammerhead ribozyme.

The hammerhead ribozyme is an intriguing RNA molecule with the ability to serve as a catalyst to cleave sequence-specifically RNA molecules in an intermolecular reaction. Preferentially Mg(2+) is required for optimal activity by inducing the catalytically competent conformation and by possibly acting as an acid-base catalyst. Even though the three-dimensional structure has been elucidated details of the structure-function relationship and of the mechanism remain unanswered. The hammerhead ribozyme has stimulated the concept of the sequence-specific cleavage of mRNAs intracellularly and thus to inhibit gene expression by preventing translation. This represents an area of considerable interest as it has the potential for the development of drugs.

Binding Sites↗
PubMed1999

Quantitative determination of joint incongruity and pressure distribution during simulated gait and cartilage thickness in the human hip joint.

The objective of this study was to provide quantitative data on hip-joint incongruity and pressure during a simulated walking cycle and on articular-cartilage thickness in the same set of specimens. Using a casting technique in eight specimens of the human hip (age: 18-75 years), we determined the width of the joint space (incongruity) required at minimal load for contact at four phases of the gait cycle. The pressure distribution, measured with pressure-sensitive film, was determined at physiologic load magnitudes on the basis of in vivo measurements of hip-joint forces. Cartilage thickness was assessed with A-mode ultrasound. At minimal loading, the average maximum width of the joint space ranged from 1.1 to 1.5 mm in the acetabular roof, with the contact areas located ventro-superiorly and dorso-inferiorly throughout the gait cycle. At physiological loading, the width decreased and the contact areas covered the complete articular surface during midstance and heel-off but not during heel-strike or toe-off. The pressure distribution was inhomogeneous during all phases, with average maximum pressures of 7.7 +/- 1.95 MPa at midstance. The cartilage thickness varied considerably throughout the joint surfaces; maxima greater than 3 mm were found ventro-superiorly. These data can be used to generate and validate computer models to determine the load-sharing between the interstitial fluid and the solid proteoglycan-collagen matrix of articular cartilage, the latter being relevant for the initiation of mechanically induced cartilage degeneration.

Adolescent↗
PubMed1999

Subacromial space width changes during abduction and rotation--a 3-D MR imaging study.

The objectives of this study were to determine systematic changes of the normal subacromial space width during abduction and rotation, and to analyze the spatial relationship of the supraspinatus muscle with the acromion and clavicle. 12 healthy volunteers were imaged by an open MR scanner in 5 different positions of abduction and in 3 positions of rotation. After three dimensional (3D) reconstruction and 3D Euclidian distance transformation, the minimal spatial distances between the humerus and the acromion and the humerus and clavicle were computed. The minimal acromio-humeral distance decreased significantly from 30 degrees of abduction (mean 7.0 mm +/- 1.6 mm) to 120 degrees (mean 3.9 mm; +/- 1.8 mm; p < 0.0001). At 30 degrees, the minimal distance penetrated the supraspinatus, whereas at 120 degrees it was always located lateral to the supraspinatus tendon. At 90 degrees with internal rotation (7.6 mm, +/- 2.3 mm) the minimal acromio-humeral distance was larger than in neutral rotation (5.4 mm, +/- 2.3 mm) or external rotation (4.4 mm, +/- 2.2 mm; p < 0.05), but it penetrated the supraspinatus tendon at its most vulnerable part, reaching the acromion at its anterior inferior border. We conclude that the subacromial space width changes during abduction and rotation and that the supraspinatus is in closest contact to the anterior inferior border of the acromion in 90 degrees of abduction with 45 degrees internal rotation. These values obtained in volunteers can be used as a basis for further investigations in patients with the impingement syndrome.

Acromion↗
PubMed1999

Chest size matching in single and double lung transplantation.

We applied predicted vital capacity to chest size matching between donor and recipient in lung transplantation to 15 single-lung transplant recipients with pulmonary fibrosis and to 20 double-lung transplant recipients with emphysema or non-emphysema. The predicted vital capacity of the donor was significantly correlated with the predicted vital capacity of the recipient both in double-lung transplantation (r = 0.79, p = 0.001) and single-lung transplantation (r = 0.71, p = 0.003). In double-lung transplantation, the post-transplant vital capacity was correlated with the predicted vital capacity of the recipient (r = 0.74, p = 0.002). Emphysema patients and non-emphysema patients contributed equally to this correlation. In left single lung transplantation, there was a weak correlation between the post-transplant vital capacity and the predicted vital capacity of the donor in the allograft (r = 0.57, p = 0.1095). In right single lung transplantation, the post-transplant vital capacity of the allograft tended to be correlated with the predicted vital capacity of recipient (r = 0.77, p = 0.0735). We concluded that donors were actually selected based on the comparison of predicted vital capacity between donor and recipient. In double-lung transplantation, the post-transplant vital capacity was limited by the recipient's normal thoracic volume and was not influenced by underlying pulmonary disease. In single-lung transplantation with pulmonary fibrosis, the allograft transplanted in the left chest could expand to its own size, and the allograft transplanted in the right chest could expand to the recipient's normal thoracic volume as in double-lung transplantation.

Humans↗
PubMed1999

[Quantitative determination of pressure distribution in the hip joint during the gait cycle].

The objective of this investigation was the experimental determination of the contact pressures in the hip joint for characteristic phases of the gait cycle. The joint forces determined in vivo with telemetric endoprosthesis by Bergmann et al. (1993) were converted into a pelvic reference system, based on kinematic gait analysis. In eight cadaveric hip joints (age 18-75 yrs.) the reaction forces were applied corresponding to four phases of the gait cycle (heel strike, mid-stance, heel off, toe off) and the pressure distribution determined with FUJI pressure sensitive film. We found maxima of 10 MPa during mid stance. The areas of highest pressure were located in the ventro-superior aspect of the acetabulum (anterior part of the acetabular roof) and in the dorso-inferior aspect of the lunate surface. The pressure distribution was relatively constant during the four phases and the maxima did not vary proportional to the applied load. The normal pressure distribution in the hip appears to be determined by the physiological incongruity of the articular surfaces and the inhomogeneous bony support of the acetabulum. During operative interventions this normal load transfer should be restored as accurately as possible.

Adolescent↗