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Biomedical subjects

G Böhm

Publications and source records attributed to G Böhm.

At least 73 records · Page 4Linked to original sources

Histology of tissue adjacent to an HAC-coated femoral prosthesis. A case report.

We studied the fixation of a cementless titanium femoral prosthesis partially coated with hydroxyapatite ceramic (HAC) 10.4 months after implantation. Histomorphological investigation showed extensive new bone formation between the HAC coating and the bone bed; morphometry showed bone contact indices of up to 91.60%. There were a number of resorption lacunae on the HAC coat with depths of up to 76.6 microns and widths of up to 453 microns. Our results confirmed that considerable bone remodelling had taken place and that the apatite-coated prosthesis had united with bone despite the lack of appreciable immediate press-fit. Hydroxyapatite particles which had been released did not appear to show any negative effects on the stability of the implant.

Aged↗

Stabilization of creatinase from Pseudomonas putida by random mutagenesis.

Creatinase (creatine amidinohydrolase, EC 3.5.3.3) from Pseudomonas putida is a homodimer of 45 kDa subunit molecular mass, the three-dimensional structure of which is known at 1.9 A resolution. Three point mutants, A109V, V355M, and V182I, as well as one double mutant combining A109V and V355M, and the triple mutant with all three replacements, were compared with wild-type creatinase regarding their physical and enzymological properties. High-resolution crystal data for wild-type creatinase and the first two mutants suggest isomorphism at least for these three proteins (R. Huber, pers. comm.). Physicochemical measurements confirm this prediction, showing that the mutations have no effect either on the quaternary structure and gross conformation or the catalytic properties as compared to wild-type creatinase. The replacement of V182 (at the solvent-exposed end of the first helix of the C-terminal domain) does not cause significant differences in comparison with the wild-type enzyme. The other point mutations stabilize the first step in the biphasic denaturation transition without affecting the second one. In sum, the enhanced stability seems to reflect slight improvements in the local packing without creating new well-defined bonds. The increase in hydrophobicity generated by the introduction of additional methyl groups (A109V, V182I) must be compensated by minor readjustments of the global structure. Secondary or quaternary interactions are not affected. In going from single to double and triple mutants, to a first approximation, the increments of stabilization are additive.

Cloning, Molecular↗

Structural relationships of homologous proteins as a fundamental principle in homology modeling.

Protein structure prediction is based mainly on the modeling of proteins by homology to known structures; this knowledge-based approach is the most promising method to date. Although it is used in the whole area of protein research, no general rules concerning the quality and applicability of concepts and procedures used in homology modeling have been put forward yet. Therefore, the main goal of the present work is to provide tools for the assessment of accuracy of modeling at a given level of sequence homology. A large set of known structures from different conformational and functional classes, but various degrees of homology was selected. Pairwise structure superpositions were performed. Starting with the definition of the structurally conserved regions and determination of topologically correct sequence alignments, we correlated geometrical properties with sequence homology (defined by the 250 PAM Dayhoff Matrix) and identity. It is shown that both the topological differences of the protein backbones and the relative positions of corresponding side chains diverge with decreasing sequence identity. Below 50% identity, the deviation in regions that are structurally not conserved continually increases, thus implying that with decreasing sequence identity modeling has to take into account more and more structurally diverging loop regions that are difficult to predict.

Bacterial Proteins↗

[Chondromatous tumors in MRT: clinical picture in relation to localization and histopathology].

19 patients with histologically verified cartilaginous tumours (chondromas, chondrosarcomas) were examined with magnetic resonance imaging (MRI) in order to assess differences regarding the MR appearance of these tumours which would provide information on the biological behaviour of these lesions. MR findings were then correlated with histopathology. With regard to the signal behaviour of cartilaginous tumours a good correlation with histopathology could be established insofar as the relatively hypocellular tumours composed of hyaline cartilage exhibited a high signal level on T2-weighted images. There were no significant differences regarding signal characteristics of cartilaginous tumours in various anatomical locations. However, lesions located in the pelvis and the long bones showed predominantly peripheral enhancement whereas tumours of the skull base and larynx exhibited diffuse enhancement patterns in the majority of cases. 10 tumours (6 benign, 4 malignant) exhibited a lobular appearance. No relevant information in respect of tumour grading could be obtained.

Adult↗

Correlation functions as a tool for protein modeling and structure analysis.

Proteins present unique folding structures whose conformations are determined primarily by their amino acid sequences. At present, there is no algorithm that would correlate the sequences with the structures determined by X-ray analysis or NMR. Comparative modeling of a new protein sequence based on the known structure of a functionally related protein promises to yield model structures that may provide relevant properties of the protein. To analyze the quality of a model structure, a set of correlation functions was derived from calculations on a subset of proteins from the structure database. Twenty-three highly resolved protein structures with resolutions of at least 1.7 A from various protein families were used as the primary database. The purpose of this initial work was to find highly sensitive functions (including statistical error limits for the parameters) that describe properties of "real" proteins. Each correlation described is characterized by the correlation coefficient, the parameters for linear or nonlinear regression (coefficients of the equation), standard deviation and variance, and the confidence limits describing the statistical probability for values to occur within these limits, e.g., the natural variability of the property under examination. In addition, a method was developed for creating reasonably misfolded proteins. The ability of a correlation function to discriminate between the native structure and the misfolded conformations is expressed by the reliability index, which indicates the sensitivity of a correlation function. The term correlation functions thus summarizes a variety of efforts to find a mathematical description for the properties of protein structures, for their correlation, and for their significance.

Computer Simulation↗

Bicaval pulmonary connection in tricuspid atresia using an extracardiac tube of autologous pediculated pericardium to bridge inferior vena cava.

From August 1989 to April 1991, four children, 1.5 to 4 years old with type IIb tricuspid atresia underwent total right heart bypass by means of a bicaval pulmonary connection using an extracardiac conduit of pediculated pericardium between the inferior vena cava and the main pulmonary artery. The tube was made from a large rectangular flap of the patient's own pericardium, pediculated along the right border, ensuring a vascular supply. The diameter of the tube, calibrated on a Hegar probe, equals that of the inferior vena cava, and the length is adapted to bridge the gap between the inferior vena cava and the main pulmonary artery. All four patients had an uneventful postoperative course. Assisted ventilation was stopped on the next morning and the chest tubes removed on the 2nd or 3rd day. The liver was only moderately enlarged and no pleural effusions developed. Sinus rhythm was permanent. Echocardiographic monitoring 6-10 months after the hospital discharge showed patent tubes, no collapse during the cardiac cycle, and no wall thickening and a laminar flow. The advantages of the pediculated pericardial tube are that no prosthetic material is used. There is no thrombogenicity or antigenicity. These tubes retain a growth potential, and we believe that this material is suitable for use in young patients.

Child, Preschool↗

Morphometric analysis of cartilaginous tumors.

144 chondromas and chondrosarcomas have been investigated. Morphometry has been performed: the relative volume density of tumor cell nuclei (Vv%n) and the nuclear area have been measured. The results show that the relative volume density of nuclei is a useful parameter, regarding the localisation of the tumors, to discriminate chondromas and chondrosarcomas, while the nuclear area is no safe criterion to separate these entities.

Cell Nucleus↗

Quantitative analysis of protein far UV circular dichroism spectra by neural networks.

A new method based on neural network theory is presented to analyze and quantify the information content of far UV circular dichroism spectra. Using a backpropagation network model with a single hidden layer between input and output, it was possible to deduce five different secondary structure fractions (helix, parallel and antiparallel beta-sheet, beta-turn and random coil) with satisfactory correlations between calculated and measured secondary structure data. We demonstrate that for each wavelength interval a specific network is suitable. The remaining discrepancy between the secondary structure data from neural network prediction and crystallography may be attributed to errors in the determination of protein concentration and random noise in the CD signal, as indicated by simulations.

Circular Dichroism↗

[Direct diagnosis of the atherosclerotic vascular wall: possibilities and limits of intravascular ultrasound].

The clinical application of intravascular ultrasound still awaits established criteria for the interpretation of normal and diseased arterial wall structures. The aim of this preclinical study was to evaluate sonographic features of normal and atherosclerotic human arteries in vitro and to correlate these findings with histological cross-sections. Seventy-four segments from 33 human postmortem arteries of various anatomic locations were studied in saline solution using a mechanical 20-MHz transducer in a 6F catheter. In normal arteries, close correlations were found between sonographic and morphometric measurements of total wall thickness (r = 0.89), lumen circumference (r = 0.99), and of lumen area (r = 0.89, all p less than 0.001). Of 29 histologically verified atherosclerotic lesions, 19 were calcified, and all of them were correctly diagnosed with IVUS; however, acoustic shadowing prevented quantitative plaque evaluation. Of 10 fibromuscular lesions, six (60%) were correctly diagnosed with IVUS, using either direct morphologic criteria (n = 4) or indirect signs of vessel wall irregularity (n = 2), while the remainder (n = 4) were missed by IVUS due to a similar echodensity compared with the surrounding tissue. Thus, there was an overall sensitivity of 86% for the detection of atherosclerotic lesions by IVUS. In animal experiments in vivo, the feasibility of high-quality-imaging in pulsatile arteries was confirmed and pathologic changes in vein grafts were visualized. We conclude that IVUS carries the potential to directly assess arterial wall changes in vivo. The method appears very sensitive in the detection of calcified plaque, whereas fibromuscular lesions may often not be readily distinguished from normal surrounding tissue. This may limit the clinical usefulness of IVUS at the present time.

Adult↗

Analysis of soft tissue tumors by an attributed minimum spanning tree.

Histologic slides of 22 soft tissue tumors (9 malignant fibrous histiocytoma, 8 fibrosarcoma, 2 rhabdomyosarcoma, 2 osteosarcoma, 1 Askin tumor) were Feulgen stained. Using an automated image analyzing system (Cambridge 570) at low magnification (25x), the tumor cell nuclei were segmented. The geometrical center of the nuclei was considered the vertex. A basic graph was constructed according to the neighborhood condition of O'Callaghan. Neighboring tumor cell nuclei were visualized by connecting edges. Several features of tumor cell nuclei were measured, including area, surface, major and minor axis of best fitting ellipsis and extinction (DNA content). Nuclear features are attributed to the vertices. The differences, or "distances," between features of connected vertices are attributed to the corresponding edges, which are dependent on the attributes. Thus, different minimum spanning trees (MST) result. Each MST can be decomposed into clusters using a suitable decomposition function on the edges, which rejects an edge if its attributes differ from the mean of the attributed values of surrounding edges more than a neighbor dependent bound (lower limit). Taking into account the length and other attributes of edges (e.g., differences in orientation of the major axis), clusters of different nuclear orientation can be detected. A cluster tree can be constructed by defining the geometric center of a cluster as a new vertex, and by computing the neighborhood of the cluster vertices. The result is an attributed MST containing characteristic structural properties of the image (in cases of sarcomatous tumors, local orientation of tumor cell nuclei and local DNA abnormalities).

Cell Nucleus↗