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Three-dimensional soft tissue prediction using finite elements. Part I: Implementation of a new procedure.

BACKGROUND AND AIM: The prediction of soft tissue esthetics is important for achieving an optimal esthetic outcome in orthodontic treatment planning. Applicable procedures have so far been restricted to two-dimensional profile predictions that have not proven to be very reliable. The goal of this investigation was therefore to develop a novel finite element-based procedure that allows a three-dimensional, easily visualized, quantitative analysis and prediction of soft tissue behavior for the clinician. The procedure to be developed should be easy to handle and not entail any additional radiation exposure for the patient. MATERIAL AND METHODS: Using a three-dimensional scanner, the facial surfaces of 20 probands were digitalized and individual FEM models were generated. RESULTS: After reduction of data redundancy via several conversion steps, a patient-specific simulation model was prepared consisting of 20,000 to 40,000 individual elements to which specific physical properties could be assigned. The average time required for generating a virtual model was 50 minutes. Problems occurring during model generation were rare (mainly shadowing phenomena and movement artifacts). CONCLUSION: The procedure outlined herein makes the reliable generation of patient-specific simulation models possible for facial soft tissue prediction in orthodontics.

Adult↗

Mimicking the two-dimensional spectrochemical series using density functional computations.

With tetragonal distortions of tetrahedral d2 complexes as examples, nonadditive and additive ligand fields are compared computationally, using Kohn-Sham density functional theory (KS-DFT) and ligand-field theory to obtain 45 linear, parametrical equations. For each complex, a "data" reduction from three nonadditive-field parameters to two parameters of the additive field occurs. The complexes V and CrX4- (where X=F, Cl, Br, I) provide the two-dimensional spectrochemical series of the sigma and pi AOM parameters, which are known semiempirically for the halide ligands. The same parametrical results can be obtained from the Kohn-Sham orbital energies of the "average of configuration" computation.

Journal Article↗

2D SENSE for faster 3D MRI.

Sensitivity encoding in two spatial dimensions (2D SENSE) with a receiver coil array is discussed as a means of improving the encoding efficiency of three-dimensional (3D) Fourier MRI. It is shown that in Fourier imaging with two phase encoding directions, 2D SENSE has key advantages over one-dimensional parallel imaging approaches. By exploiting two dimensions for hybrid encoding, the conditioning of the reconstruction problem can be considerably improved, resulting in superior signal-to-noise behavior. As a consequence, 2D SENSE permits greater scan time reduction, which particularly benefits the inherently time-consuming 3D techniques.Along with the principles of 2D SENSE imaging, the properties of the technique are discussed and investigated by means of simulations. Special attention is given to the role of the coil configuration, yielding practical setups with four and six coils. The in vivo feasibility of the two-dimensional approach is demonstrated for 3D head imaging, permitting four-fold scan time reduction.

Computer Simulation↗

The radiation induced magnetic resonance image intensity change provides a more efficient three-dimensional dose measurement in MRI-Fricke-agarose gel dosimetry.

A detailed methodology has been developed to map the spatial dose distribution in a Fricke-agarose gel based on the radiation induced image intensity change in the gel's magnetic resonance (MR) images. Besides the linear correlation between the change in the gel's spin-lattice relaxation rate and the absorbed dose, it is shown here that the radiation induced image intensity change for T1-weighted spin-echo images with TE << TR correlates exponentially to the absorbed dose. Furthermore, at the lower dose region (< 15 Gy), the correlation is fairly linear and its sensitivity is high. The minimum detectable dose is shown to be equivalent to the one obtained using the conventional R1-based approach. Since only one T1-weighted image is required for the dose evaluation, compared to the R1-based method, the total MR imaging time can be reduced from hours to a few minutes. This extensive time reduction avoids ferric ion diffusion effects and provides a practical way to simply and effectively measure the three-dimensional dose distribution using the Fricke-agarose dosimeter gel.

Gels↗

The three-dimensional structure of flavodoxin reductase from Escherichia coli at 1.7 A resolution.

Flavodoxin reductase from Escherichia coli is an FAD-containing oxidoreductase that transports electrons between flavodoxin or ferredoxin and NADPH. Together with flavodoxin, the enzyme is involved in the reductive activation of three E. coli enzymes: cobalamin-dependent methionine synthase, pyruvate formate lyase and anaerobic ribonucleotide reductase. An additional function for the oxidoreductase appears to be to protect the bacteria against oxygen radicals. The three-dimensional structure of flavodoxin reductase has been solved by multiple isomorphous replacement, and has been refined at 1.7 A to an R-value of 18.4% and Rfree 24.8%. The monomeric molecule contains one beta-sandwich FAD domain and an alpha/beta NADP domain. The overall structure is similar to other reductases of the NADP-ferredoxin reductase family in spite of the low sequence similarities within the family. Flavodoxin reductase lacks the loop which is involved in the binding of the adenosine moiety of FAD in other FAD binding enzymes of the superfamily but is missing in the FMN binding phthalate dioxygenase reductase. Instead of this loop, the adenine interacts with an extra tryptophan at the C terminus. The FAD in flavodoxin reductase has an unusual bent conformation with a hydrogen bond between the adenine and the isoalloxazine. This is probably the cause of the unusual spectrum of the enzyme. There is a pronounced cleft close to the isoalloxazine that appears to be well suited for binding of flavodoxin/ferredoxin. Two extra short strands of the NADP-binding domain probably act as an anchor point for the binding of flavodoxin.

Adenosine↗

The Cardiome Project. An integrated view of cardiac metabolism and regional mechanical function.

The goal, to develop a functioning three-dimensional computational model of the excitation, metabolism and contraction of the heart within three years, is one of the beginnings for the Cardiome Project. Our first stage will not be likely to provide highly accurate prediction of physiological behavior in general, but will be focussed so that it is adequate for at least three specific purposes: response to regional flow reduction, response to heart rate changes, and response to increased metabolic drive. We would like to make the model visualizable by three-dimensional viewing, with cross-sectional and transparency viewing approaches, illustrate the fiber directions, the arteries, the deformation with contraction and images of regional functions such as oxygen consumption, preejection strain, or lactate concentration. The display techniques developed by Hunter et al. and by McCulloch et al. would be excellent for such demonstration and teaching purposes, and should be attractive enough for public display. The Physiome Project is underway now, with growing government and private support. Now we are going from the era of molecular biology, led by the Genome Project, into a new era of integrative biology. The goal is to understand biology so deeply and so broadly that predictions about interventions can be made. Methods of experimentation and of diagnosis are critical to acquiring the data, and therefore in making the prediction, and so all aspects of our Society's efforts and interests are relevant to undertaking this grand challenge.

Adenosine↗

Regulation of collagen synthesis in fibroblasts within a three-dimensional collagen gel.

Fibroblasts cultivated within a three-dimensional collagen gel display an elongated, spindle-like morphology, reduce their proliferation rate, contact the gel to a very dense tissue, and modify their metabolic activity as compared to monolayer cultures. Collagen synthesis measured as protein-bound hydroxyproline is reduced to 5% of the values found in monolayer culture. The reduction involving type I and type III collagen is due to decreased de novo synthesis and not to enhanced degradation. Dot blot hybridization, Northern blot analysis, and in situ hybridization using collagen I- and III-specific cDNA probes demonstrate that reduced biosynthesis rates are reflected by a marked reduction of pro alpha 1 (I), pro alpha 2 (I), and pro alpha 1 (III) collagen mRNA indicating pretranslational regulation. A similar reduction was observed for actin mRNA whereas levels of tubulin mRNA were similar for fibroblasts in monolayer culture or cultivated within the three-dimensional collagen gels. The data suggest a specific reprogramming of various cellular activities in response to contact with the reconstituted extracellular matrix.

Blotting, Northern↗

Relation between 2- and 3-dimensional architecture of trabecular bone in the human spine.

By means of a new preparation technique which allows the combined 2- and 3-dimensional analysis of trabecular bone we analyzed the vertebral bodies of 22 autopsy cases. None of these cases had any skeletal disease. With increasing age bone volume was decreased in all vertebral bodies (2nd cervical to 5th lumbar body) but this decrease was more pronounced in the lower vertebrae. In the upper cervical spine there was nearly no age-related loss of trabecular bone volume. 3-D analysis demonstrated that the loss of bone tissue is due to a loss of trabecular plates which are transformed to trabecular rods by perforations. The number of plates and rods could be measured directly. In the 2nd lumbar vertebra at the age of 20 years the density of plates was 0.61 mm, the density of rods was 0.2/mm. At the age of 80 years the density of plates was 0.2/mm. The density of rods remained constant at all ages. Perforations could be seen directly. They were located mainly in trabecular plates. At higher ages they occurred in rods either. The number of vertically oriented trabeculae was about twice the number of horizontal ones. The rate of age-dependent reduction of trabeculae was the same in horizontal and vertical trabeculae. It was possible to do real 3-dimensional measurements of the diameter of trabecular rods. These values were compared to the calculated values of trabecular plates. In mean trabecular plates are thinner than rods. It could be demonstrated that microcallus formation is a common feature in the human spine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Depletion of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine in three-dimensional collagen cultures of normal human breast epithelial cells.

O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6-methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6-benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6-methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6-methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6-benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6-methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts.

Animals↗

Nitrogen fixation system of tungsten-resistant mutants of Azotobacter vinelandii.

Mutants of Azotobacter vinelandii ATCC 12837 were isolated which could fix N2 in the presence of high tungsten concentrations. The most studied of these mutants (WD2) grew well in N-free modified Burk broth containing 10 mM W, whereas the wild type would not grow in this medium. WD2 would also grow in Burk N-free broth at about the same rate as the wild type. WD2 in broth containing W exhibited 22% of the whole cell acetylene reduction activity of the wild type in broth containing Mo and showed a lowered affinity for acetylene. Two-dimensional gel electrophoresis experiments showed that N2-fixing cells of WD2 from broth containing W or Mo did not produce significant amounts of component I of native nitrogenase protein. Electron spin resonance spectra of whole cells and cell-free extracts of WD2 from broth containing W lacked any trace of the g = 3.6 resonance associated with FeMoCo.

Acetylene↗

Two-dimensional echocardiography in experimental coronary stenosis. I. Sensitivity and specificity in detecting transient myocardial dyskinesis: comparison with sonomicrometers.

The purpose of this study was to assess the sensitivity and specificity of two-dimensional echocardiography in detecting ischemia-induced transient myocardial dyskinesis. We prepared an open-chest dog model of severe coronary stenosis (90% reduction of circumflex coronary artery diameter) and induced ischemia by acutely raising myocardial oxygen requirements with i.v. isoproterenol and acute aortic constriction. The changes observed with echocardiography were compared with those obtained by intramyocardial sonomicrometers placed side by side or in an endocardial-epicardial orientation. Ischemia was defined as systolic wall expansion or thinning on sonomicrometers and two-dimensional echocardiography. We found complete agreement between sonomicrometers and two-dimensional echocardiography in all control tracings and after ischemia was induced; whenever dyskinesis occurred it was seen by both techniques. Although there was qualitative agreement between echocardiographic and sonomicrometric techniques, there were quantitative differences in the assessment of wall thickening. Such differences may be related to malalignment of the sonomicrometers, echocardiographic resolution limitations or other technical factors. We conclude that two-dimensional echocardiography is a sensitive and specific technique for detecting transient myocardial ischemia, and therefore should be useful for demonstrating exercise-induced ischemia in patients with coronary artery disease.

Animals↗

Three-dimensional electromechanical mapping: imaging in the operating room of the future.

BACKGROUND: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. METHODS: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. RESULTS: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. CONCLUSIONS: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

Animals↗

Disulfide proteome in the analysis of protein function and structure.

Many proteins undergo post-translational modification via well defined mechanisms such as acetylation, phosphorylation and glycosylation and thereby control a spectrum of biochemical processes. A growing body of evidence suggests that the reversible reduction of disulfide bonds also alters the structure and activity of proteins. Thioredoxin, a ubiquitous 12 kDa protein with a catalytically active disulfide active site (Cys-Gly-Pro-Cys), plays a central role in controlling the redox status of disulfide bonds in proteins that regulate a range of processes. Included are photosynthesis, seed germination, transcription, cell division, radical scavenging and detoxification. The ability to identify unknown functions of proteins of all types has been advanced by the emerging field of functional proteomics. In this brief review, we introduce the disulfide proteome as a tool that complements other methods for the comprehensive analysis of proteins. In so doing, the usefulness of applying this method for both in vitro and in vivo analyses is discussed for thioredoxin and other disulfide proteins, especially those occurring in plants.

Allergens↗

Identification of S-glutathionylated cellular proteins during oxidative stress and constitutive metabolism by affinity purification and proteomic analysis.

Redox modification of proteins is proposed to play a central role in regulating cellular function. However, high-throughput techniques for the analysis of the redox status of individual proteins in complex mixtures are lacking. The aim was thus to develop a suitable technique to rapidly identify proteins undergoing oxidation of critical thiols by S-glutathionylation. The method is based on the specific reduction of mixed disulfides by glutaredoxin, their reaction with N-ethylmaleimide-biotin, affinity purification of tagged proteins, and identification by proteomic analysis. The method unequivocally identified 43 mostly novel cellular protein substrates for S-glutathionylation. These include protein chaperones, cytoskeletal proteins, cell cycle regulators, and enzymes of intermediate metabolism. Comparisons of the patterns of S-glutathionylated proteins extracted from cells undergoing diamide-induced oxidative stress and during constitutive metabolism reveal both common protein substrates and substrates failing to undergo enhanced S-glutathionylation during oxidative stress. The ability to chemically tag, select, and identify S-glutathionylated proteins, particularly during constitutive metabolism, will greatly enhance efforts to establish posttranslational redox modification of cellular proteins as an important biochemical control mechanism in coordinating cellular function.

Cell Line↗

Hamatometacarpal fracture-dislocation: distinctive three dimensional computed tomographic appearance.

We report here two fully documented cases of hamatometacarpal fracture-dislocation following trauma and treated in our hospital. In our cases, the patients suffered hamate fracture in association with metacarpal dislocation. In the first case, a dorsal oblique fracture of the hamate was associated with a dorsal dislocation of the base of the fourth metacarpal. In the second case, a dorsal oblique fracture of the hamate was not associated with a dorsal dislocation of the base of the fifth metacarpal. This diagnosis should be suspected on initial review of plain radiographs, which must include an oblique view because of diagnostic difficulty for this injury. We recommend three dimensional computed tomography (3D-CT) in any patient presenting with pain after blunt trauma to the hand to prevent in diagnosis. Open reduction and internal fixation of the fracture is indicated and relevant for displaced fracture.

Adult↗

Bone displacement and the role of longitudinal ligaments during balloon vertebroplasty in traumatic thoracolumbar fractures.

STUDY DESIGN: In a human cadaveric burst fracture model with and without longitudinal ligament damage, the amount of anterior and posterior bone displacement (ABD, PBD) during balloon vertebroplasty after pedicle-screw instrumentation was investigated quantitatively. OBJECTIVES: To investigate, in a burst fracture model with and without longitudinal ligament damage, the amount of ABD, PBD, and cement leakage at various phases during balloon vertebroplasty in combination with pedicle-screw instrumentation. SUMMARY OF BACKGROUND DATA: The role of intact longitudinal ligaments in traumatic spine fractures, for prevention of bone retropulsion and subsequent reduction, has been discussed in several studies but is still up for debate. In a recent human cadaveric burst fracture study, inflatable bone tamps and calcium phosphate cement were used for the augmentation of the anterior column after pedicle-screw instrumentation. The additional balloon vertebroplasty procedure was found to be feasible and safe, but no data pertaining to unwarranted bone displacement or cement leakage during the procedure are available for burst fractures with damaged longitudinal ligaments. METHODS: Ten thoracic and 10 lumbar burst fractures, with rotation or flexion components, were created, and balloon vertebroplasty with calcium phosphate cement was performed after pedicle-screw instrumentation. Volumetric datasets (using the 3-dimensional (3D) rotational x-ray imaging technique) of the fractures were obtained during the following phases: intact, fractured, after reduction and stabilization with pedicle-screws, after inflation of the balloons, after deflation and removal of the balloons, and after injection of the cement. The amount of ABD and PBD was measured on reconstructed sagittal images and recorded together with the presence of extracorporal cement leakage. The continuity of the longitudinal ligaments was assessed after anatomic dissection. RESULTS: During the balloon vertebroplasty procedure, a significant (P < 0.05) increase of ABD (at both thoracic and lumbar level) and PBD (thoracic level) occurred after inflation of the balloons. After deflation and subsequent injection of the cement, however, the ABD and PBD returned to the preinflation levels. The absolute amount of ABD and PBD (<1 mm) during inflation was considered of little clinical importance. No differences in ABD or PBD were observed for specimens with or without continuity of the corresponding longitudinal ligament, irrespective of the level, at any of the phases during the experiment (P > 0.5 in all cases). A small amount of cement leakage was observed in the psoas compartment of one specimen with intact longitudinal ligaments. CONCLUSIONS: It is suggested that balloon vertebroplasty after pedicle-screw instrumentation may safely be used, in terms of bone displacement and cement leakage, in fracture types where damage to longitudinal ligaments is to be expected.

Aged↗

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up.

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

Adult↗

Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs.

Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate and is essential for the synthesis of thymidylate, purines and several amino acids. Inhibition of the enzyme's activity leads to arrest of DNA synthesis and cell death. The enzyme has been studied extensively as a drug target for bacterial, protozoal and fungal infections, and also for neoplastic and autoimmune diseases. Here, we report the crystal structure of dihydrofolate reductase from Mycobacterium tuberculosis, a human pathogen responsible for the death of millions of human beings per year. Three crystal structures of ternary complexes of M. tuberculosis DHFR with NADP and different inhibitors have been determined, as well as the binary complex with NADP, with resolutions ranging from 1.7 to 2.0 A. The three DHFR inhibitors are the anticancer drug methotrexate, the antimicrobial trimethoprim and Br-WR99210, an analogue of the antimalarial agent WR99210. Structural comparison of these complexes with human dihydrofolate reductase indicates that the overall protein folds are similar, despite only 26 % sequence identity, but that the environments of both NADP and of the inhibitors contain interesting differences between the enzymes from host and pathogen. Specifically, residues Ala101 and Leu102 near the N6 of NADP are distinctly more hydrophobic in the M. tuberculosis than in the human enzyme. Another striking difference occurs in a region near atoms N1 and N8 of methotrexate, which is also near atom N1 of trimethoprim, and near the N1 and two methyl groups of Br-WR99210. A glycerol molecule binds here in a pocket of the M. tuberculosis DHFR:MTX complex, while this pocket is essentially filled with hydrophobic side-chains in the human enzyme. These differences between the enzymes from pathogen and host provide opportunities for designing new selective inhibitors of M. tuberculosis DHFR.

Amino Acid Sequence↗