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Biomedical subjects

F Eckstein

Publications and source records attributed to F Eckstein.

At least 163 records · Page 9Linked to original sources
PubMed1997

Mechanobiological adaptation of subchondral bone as a function of joint incongruity and loading.

Computed tomography (CT) has been employed to determine non-invasively the distribution of subchondral bone density in joints and to evaluate their dominant loading pattern. The objective of this study was to investigate the relationship between subchondral bone adaptation, joint incongruity and loading, in order to determine to what extent the loading conditions and/or geometric configuration can be inferred from the distribution of subchondral density. Finite element models of joints with various degrees of incongruity were designed and a current remodeling theory implemented using the node-based approach. Appropriate combinations of joint incongruity and loading yielded subchondral bone density patterns consistent with experimental findings, specifically a bicentric distribution in the humero-ulnar joint and a monocentric distribution in the humero-radial joint. However, other combinations of incongruity and loading produced similar subchondral density patterns. Both the geometric joint configuration and the loading conditions influence the distribution of subchondral density in such a way that one of these factors must be known a priori to estimate the other. Since subchondral density can be assessed by CT and joint geometry by magnetic resonance imaging, the dominant loading pattern of joints may be potentially derived in the living using these non-invasive imaging methods.

Adaptation, Physiological↗
PubMed1997

Structure-function studies of the hammerhead ribozyme.

Elucidation of the catalytic mechanism and structure-function relationship studies of the hammerhead ribozyme continue to be an area of intensive research. A combination of diverse approaches, such as X ray crystallography, spectral studies, chemical modifications, sequence variations and kinetic analyses, have provided valuable insight into the cleavage mechanism of this ribozyme. The hammerhead ribozyme crystal structures have provided valuable insight into conformational deformations needed to attain the catalytically active structure. Similarly, determination of ribozyme solution structure by spectroscopic analyses and the effect of divalent metal ions on RNA folding has further aided in the construction of a model for hammermead catalysis.

Base Sequence↗
PubMed1997

[Three-dimensional thickness and volume measurements of the knee joint cartilage using MRI: validation in an anatomical specimen by CT arthrography].

PURPOSE: In the present study we intended to validate knee joint cartilage volume and thickness measurements with MRI. METHODS: Ten fresh cadaver knees (age 29 to 64 yrs.) were sagittally imaged, using a fat-suppressed FLASH-3D sequence with a resolution of 2 x 0.31 x 0.31 mm3. Then, a contrast agent was injected and the specimens submitted to CT arthrography. From both modalities the patellar, femoral, and tibial cartilages were segmented semiautomatically and reconstructed three-dimensionally. The cartilage thickness was determined independently of the sectional plane, based on a "minimal distance algorithm". RESULTS: The volumes and the regional distribution patterns yielded a very high degree of similarity on direct comparison of both imaging modalities. The average volume error between MRI and CT was 3.8% (+/- 3.0%), the correlation 0.998, the slope of the regression line 1.04 and the gamma-intercept -80 mm3. The analysis yielded no significant differences between the two methods (Wilcoxon signed rank test, 5% level) in the patella, femur, medial, and lateral tibia. CONCLUSION: The results suggest that, based on a fat-suppressed FLASH sequence with high resolution and three-dimensional concepts of digital image analysis, the cartilage volume and thickness can be analysed non-invasively and with high accuracy by MRI.

Algorithms↗
PubMed1997

[Three-dimensional thickness and volume measurements of the knee joint cartilage by MR tomography: reproducibility in volunteers].

OBJECTIVE: To determine the reproducibility of three-dimensional volume and thickness measurements of the knee joint cartilage with MRI in volunteers. METHODS: The knees of 7 healthy individuals (ages 23 to 58 yrs.) were sagittally imaged with a resolution of 2 x 0.31 x 0.31 mm3, using a fat-suppressed FLASH-3 D sequence. The knee was repositioned in between replicate acquisitions, 6 data sets being obtained in each case. After semiautomatic segmentation and three-dimensional reconstruction of the cartilage, the thickness was determined independent of the original section orientation. The coefficient of variation for repeated volume measurements and the deviations of the maximal cartilage thickness values were calculated subsequently. RESULTS: The mean variation of the cartilage volumes of the replicate measurements was 1.4% (+/- 0.8%) in the patella, 1.7% (+/- 1.5%) in the femur, 3.0% (+/- 1.2%) in the medial tibial plateau and 3.5% (+/- 2.0%) in the lateral tibial plateau. The comparison of the distribution patterns of cartilage thickness yielded a high degree of agreement. Only in rare cases deviations of more than 0.5 mm were observed. CONCLUSIONS: The results show that the presented method for determining the quantitative distribution of articular cartilage yields a high degree of precision. It offers new possibilities in screening risk groups, monitoring the course of degenerative joint disease and the investigation of functional adaptation of the cartilage to mechanical loading.

Adult↗
PubMed1997

Quantitative analysis of incongruity, contact areas and cartilage thickness in the human hip joint.

Joint incongruity and cartilage thickness have been shown to determine the contact stresses and the load partitioning between the solid and fluid phases of articular cartilage. Matrix stresses, which are relevant in the development of osteoarthrosis, can, however, not be determined experimentally but must be calculated using numerical methods. The aim of the present study was to quantify the incongruity and cartilage thickness of the human hip, in order to allow for the construction of morphologically accurate finite element models. Twelve cadaveric specimens (34-86 years), two fresh and ten fixed, were investigated. The loading configuration was based on in vivo measurements of hip joint forces during midstance. The incongruity and contact areas were determined using a polyether casting technique, in the minimally and the fully loaded state. The cartilage thickness was measured at identical coordinate points with an A-mode ultrasonic system. Generally, the contact started at lower loads at the edge of the lunate surface, and the joint space increased towards its central aspects. In some specimens the contact started in the acetabular roof, leaving a joint space of up to 2 mm in the horns of the lunate surface. In others, the initial contact was observed in the anterior and posterior horns of the lunate surface with a joint space width of up to 0.75 mm in the acetabular roof. The size of the contact areas increased from about 20% of the lunate surface to 98% at higher loads. The articular cartilage thickness ranged from 0.7 to 3.6 mm, the maxima being located in the ventral aspects of the femoral head and acetabulum. These quantitative data on joint space width, contact, and cartilage thickness in the human hip joint may be used to construct and validate finite element models which are required to elucidate the mechanical factors involved in osteoarthrosis.

Adult↗
PubMed1997

A calculation of the forces acting on the human acetabulum during walking. Based On in vivo force measurements, kinematic analysis and morphometry.

Information about the loading of the human acetabulum during walking is necessary for a functional understanding of the morphology of the pelvic girdle and the hip joint as well as for the optimization of endoprosthetic therapy in osteoarthritis. For this purpose, experimental data of the forces acting on the femur in walking taken from the literature [Bergmann et al.: J. Biomech. 1993;26: 969-990] were combined with our own kinematic and morphometric data, to transform the force vectors from the femoral into a pelvic and an acetabular frame. During the walking cycle, the resultant force vector takes a rather constant course relative to the pelvis and its orientation seems to be highly regulated to act within a small range of angles. Only small deviations occur from the angles against the vertical which the resultant peak force forms in the frontal plane (F = 11 degrees, medially orientated) and in the sagittal plane (S = 5 degrees, ventrally orientated). The experimental results form the basis for a model of the incongruous hip joint as an elastic joint, the femoral head being centered between compliant elements.

Acetabulum↗
PubMed1997

Probing accessible sites for ribozymes on human acetylcholinesterase RNA.

In order to design ribozymes for the efficient cleavage of a human acetylcholinesterase (AChE) in vitro transcript, a completely randomized decadeoxyribonucleotide (dN10) was used in conjunction with RNase H to identify suitable sites for annealing. Based on the observed cleavage pattern, ribozymes were designed to cleave the transcript at these positions. Five ribozymes so designed proved to be efficient in the transcript cleavage (k(react)/Km ranged from 0.9 x 10(4) to 68.2 x 10(4) M(-1) min(-10)). The best was 150-fold more active than the best designed on the basis of the MFold program. Thus, the RNase H mapping demonstrated a high predictive power for favorable ribozyme cleavage sites. The digestion pattern with RNase H differed dramatically from that observed with the single-strand-specific mung bean nuclease.

Acetylcholinesterase↗
PubMed1997

Hybrid rendering of multidimensional image data.

The most important rendering methods applied in medical imaging are surface and volume rendering techniques. Each approach has its own advantages and limitations: Fast surface-oriented methods are able to support real-time interaction and manipulation. The underlying representation, however, is dependent on intensive image processing to extract the object surfaces. In contrast, volume visualization is not necessarily based on extensive image processing and interpretation. No data reduction to geometric primitives, such as polygons, is required. Therefore, the process of volume rendering is currently not operating in real time. In order to provide the radiological diagnosis with additional information as well as to enable simulation and preoperative treatment planning we developed a new hybrid rendering method which combines the advantages of surface and volume presentation, and minimizes the limitations of these approaches. We developed a common data representation method for both techniques. A preprocessing module enables the construction of a data volume by interpolation as well as the calculation of object surfaces by semiautomatic image interpretation and surface construction. The hybrid rendering system is based on transparency and texture mapping features. It is embedded in a user-friendly open system which enables the support of new application fields such as virtual reality and stereolithography. The efficiency of our new method is described for 3-D subtraction angiography and the visualization of morpho-functional relationships.

Computer Graphics↗
PubMed1996

Mg(2+)-dependent conformational changes in the hammerhead ribozyme.

Conformational changes of the hammerhead ribozyme were examined by fluorescence changes of 2-aminopurine riboside incorporated either in the substrate or in the ribozyme. Fluorescence changes could be observed for both the substituted substrate and ribozyme upon complex formation, indicating a different environment for the 2-aminopurine in the complex. Ribozyme-substrate constructs for ciscleavage containing 2-aminopurine at various sites were used for the determination of binding constants of Mg2+ and Ca2+. Depending upon the site of 2-aminopurine substitutions, the fluorescence intensity upon addition of Mg2+ or Ca2+ was reduced by 0-50%. The measurements were performed in high ionic strength buffers such that base pairing in the helical regions is expected to be complete. With three of the ribozymes, the dependence of the fluorescence emission as a function of Mg2+ concentration could be fitted by single binding processes, whereas for the two remaining ribozymes a second binding process needed to be included. The binding constants range from 7600 M-1 down to 12 M-1 in 75 mM Tris-HCl (pH 7.5) and indicate the presence of multiple binding sites in the ribozymes with varying degrees of affinity toward the metal ions. Mg2+ binding constants determined in the same buffer from the Mg2+ dependence of the cleavage rate are of the order of 100 M-1; thus, Mg2+ sites directly involved in catalysis are of intermediate affinity. The ribozyme containing 2-aminopurine in loop III demonstrated the highest binding constant whereas the ribozyme with a 2-aminopurine next to a 2'-deoxy-2'-aminocytosine at the cleavage site exhibited only low metal ion affinity. The data obtained for Ca2+ are very similar to those found for Mg2+. This approach provides a first set of data describing a Mg2+ binding topography to hammerhead RNA molecules and should be useful for the analysis of other RNA molecules.

2-Aminopurine↗
PubMed1996

In vitro selection of hammerhead ribozymes containing a bulged nucleotide in stem II.

Hammerhead ribozymes were transcribed from a dsDNA template containing four random nucleotides between stems II and III, which replace the naturally occurring GAA nucleotides. In vitro selection was used to select hammerhead ribozymes capable of in cis cleavage using denaturing polyacrylamide gels for the isolation of cleaving sequences. Self-cleaving ribozymes were cloned after the first and second rounds of selection, sequenced and characterised. Only sequences containing 5'-HGAA-3', where H is A, C or U, between stems II and III were active; G was clearly not tolerated at this position. Thus, only three sequences out of the starting pool of 256 (4(4)) were active. The Michaelis-Menten parameters were determined for the in trans cleaving versions of these ribozymes and indicate that selected ribozymes are less efficient than the native sequence. We propose that the selected ribozymes accommodate the extra nucleotide as a bulge in stem II.

Base Sequence↗
PubMed1996

Site specific labelling of sugar residues in oligoribonucleotides: reactions of aliphatic isocyanates with 2' amino groups.

Considerable effort has been directed towards studying the structure and function of nucleic acids and several approaches rely on the attachment of reporter groups or reactive functional groups to nucleic acids. We report here the selective modification of 2-amino groups in oligoribonucleotides, through their reaction with aliphatic isocyanates, to give the corresponding 2'-urea derivatives in >95% yield. Furthermore, such modification with (2-isocyanato)ethyl 2-pyridyl disulfide enables subsequent coupling to other thiols (such as those contained in peptides and proteins) or to thiol-reactive electrophiles. A modified decamer was not significantly destabilized by the 2'-urea group, compared with a 2'-amino group, as demonstrated by a mere 1.3 degrees C drop in the melting temperature of the duplex.

Amines↗
PubMed1996

Diastereomeric specificity of 2',3'-cyclic nucleotide 3'-phosphodiesterase.

The diastereomers of adenosine and uridine 2',3'-cyclic phosphorothioates were tested as substrates for 2',3'-cyclic nucleotide 3'-phosphodiesterase from bovine brain. The enzyme cleaves the Sp (or exo) diastereomers efficiently, whereas the Rp (or endo) diastereomers are resistant to hydrolysis, even after long incubation. As the enzyme exhibits strong substrate inhibition the precise determination of kinetic parameters posed problems, particularly with phosphorothioates. The stereoselectivity of this enzyme is opposite to that of RNase T1 and RNase A and thus could be a useful complement in determination of the configuration of nucleoside 2',3'-cyclic phosphorothioates resulting from hydrolysis reactions of unknown stereochemical course.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1996

Magnetic resonance chondro-crassometry (MR CCM): a method for accurate determination of articular cartilage thickness?

A method for the assessment of articular cartilage thickness based on MRI is presented and its accuracy and reproducibility tested. Six specimens of human patellae were imaged, using a fat-suppressed FLASH 3D sequence, and sectioned with a high-precision band saw. The regional distribution of articular cartilage thickness was determined from the MR images and from the anatomical sections (intervals of 0.5 mm). With image analysis 50-90% of the image points were found to lie within exactly the same thickness interval in corresponding patterns, and less than 17% deviated more than 0.5 mm. More than 85% of all pixels were reproducible with MRI after new positioning of the joint. No influence of the read-out direction and no important differences between areas of thin and thick cartilage could be detected. The authors conclude that MR chondro-crassometry can provide accurate and reproducible information on cartilage thickness.

Adult↗
PubMed1996

Determination of knee joint cartilage thickness using three-dimensional magnetic resonance chondro-crassometry (3D MR-CCM).

The objective of this article was to analyze the accuracy and precision with which the quantitative distribution of articular cartilage can be determined in the knee joint using MRI. A three-dimensional (3D) technique that accounts for the out-of-plane deviation of the interface normal in strongly curved joint surfaces (3D MR-CCM) has been developed for cartilage thickness measurements. Eight cadaveric knee-joint specimens and six volunteers were imaged using a fat-suppressed gradient-echo sequence at a resolution of 2 x 0.31 x 0.31 mm3. Cartilage volumes and topographical thickness maps were obtained and compared with those derived from anatomical sections by image analysis. The deviation of the MR volumes from those of the sections was 1-12%, the coefficient of variation after repositioning ranged from 2.9% (patella) to 8.2% (lateral tibial plateau). Between 60% and 80% of all image points could be attributed to identical thickness intervals, less than 20% deviating by more than 0.5 mm. The intraobserver and interobserver reproducibilities were very high in both the specimens and the volunteers. In the knee joint, 3D reconstructions of the cartilages, and measurements that take into account the out-of-plane deviation of the interface normals (3D MR-CCM), are required.

Adult↗
PubMed1996

Assessment of normal patellar cartilage volume and thickness using MRI: an analysis of currently available pulse sequences.

OBJECTIVE: The objective of this study was to analyse the potential of magnetic resonance imaging for valid determination of patellar cartilage thickness, comparing currently available pulse sequences. DESIGN: In six patients and one cadaver the cartilage was repetitively imaged employing three spin-echo and six three-dimensional gradient-echo sequences. In the cadaveric specimen the total volume and the regional distribution of cartilage thickness were assessed and compared with the values obtained from anatomical sections by image analysis. RESULTS AND CONCLUSIONS: The FLASH and fat-suppressed FLASH sequences allowed the most accurate determination of the cartilage volume and thickness. Fat-suppression considerably increased the contrast of the cartilage to the synovial fluid, fat and bone marrow, yielding higher reproducibility of the volumetric measurements. The remaining difference from the anatomical volume and thickness may be because the calcified cartilage is not delineated by magnetic resonance imaging.

Adult↗
PubMed1996

Computer-aided three dimensional assessment of knee-joint cartilage with magnetic resonance imaging.

OBJECTIVE: An MRI-based technique for non-invasive assessment of the quantitative distribution of articular cartilage in the knee-joint was to be developed, and its accuracy and reproducibility tested. DESIGN: Three cadaveric specimens and one patient were studied and MRI measurements compared with anatomical sections or arthroscopy. BACKGROUND: Data on articular cartilage thickness is needed for the design of computer models, determination of cartilage material properties from arthroscopy and staging of osteoarthrosis. METHODS: The knees were imaged using strongly T2-weighted spin-echo and FISP-3D sequences. After digital subtraction and automatic segmentation, three-dimensional reconstruction of the cartilages was performed. Surface areas, volumes and the mean cartilage thickness were calculated, and the regional distribution displayed after trigonometric correction. RESULTS: The difference between MRI volumes and those obtained from the sections ranged from 4 to 21% with a reproducibility of +/-4 to +/-12% after repositioning. The thickness maps obtained with MRI were very similar to those from the sections. In the patient, a full-thickness defect demonstrated with MRI was verified by arthroscopy. CONCLUSIONS: Using the technique presented, the quantitative distribution of knee-joint cartilage may be analysed non-invasively, accurately, and in a very time-effective manner, in cadavers and in living subjects. RELEVANCE: To date there exists no accepted method for the accurate, fast and non-invasive assessment of articular cartilage thickness. Such a technique is, however, very helpful for generating computer models of diarthrodial joints, determination of cartilage material properties during arthroscopy, staging of joint disease, and objective control of chondroprotective treatment.

Journal Article↗