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3-dimensional analyses of trabecular bone structure in osteoporosis reveal that perforations of individual trabeculae are common. They result in a reduction of the stability of the trabecular network by inducing mechanically incompetent trabeculae. Reparative mechanisms, like microcallus formations, may also lead to errors when measuring trabecular bone density.
AIMS: Evaluation of a three-dimensional reconstruction method to show the changes of right ventricular volume and systolic function when patients undergo pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: In the examination of 11 patients (four female, seven male; age 56+/-10 years) before and after pulmonary thromboendarterectomy, end-diastolic and end-systolic right ventricular volumes were determined as a sum total of the calculated volumes of derived parallel slices of the right ventricle. Using a Tomtec workstation and a Vingmed CFM 800 echocardiography device, the acquired data were ECG-and respiration-triggered in the course of transthoracic examination, using step intervals of 5 degrees. The ventricular outline was traced manually on 5mm slices from longitudinal cut planes. For subsequent correction, their area measurements were displayed and the volume cross-checked against the volume from orthogonal cut planes. End-diastolic and end-systolic volumes could be quantified in 11/11 cases before surgery, but data could only be attained for 9/11 patients after surgery, because a limited apical window rendered the postoperative three-dimensional reconstruction impossible in two cases. Before surgery, right ventricular size was larger than normal and systolic function was clearly impaired in all of the patients (end-diastolic volume: 121+/-37 ml; end-systolic volume 91+/-30 ml; ejection fraction 25+/-8%). The decrease in mean pulmonary artery pressure after surgery was significant (47+/-8 vs 26+/-8 mmHg; P<0.05). End-diastolic and end-systolic right ventricular volumes had been reduced (80+/-33 ml and 54+/-31 ml respectively), and the ejection fraction had increased (36+/-9%). CONCLUSIONS: Successfully performed pulmonary thromboendarterectomy leads to a significant reduction of right ventricular chamber size and improvement of systolic function, which can be determined with great precision and quite easily, using transthoracic three-dimensional echocardiography. Published by Elsevier Science Ltd. All rights reserved.
PURPOSE: Organ delineation is one of the most tedious and time-consuming parts of radiotherapy planning. It is usually performed by manual contouring in two-dimensional slices using simple drawing tools, and it may take several hours to delineate all structures of interest in a three-dimensional (3D) data set used for planning. In this paper, a 3D model-based approach to automated organ delineation is introduced that allows for a significant reduction of the time required for contouring. METHODS AND MATERIALS: The presented method is based on an adaptation of 3D deformable surface models to the boundaries of the anatomic structures of interest. The adaptation is based on a tradeoff between deformations of the model induced by its attraction to certain image features and the shape integrity of the model. To make the concept clinically feasible, interactive tools are introduced that allow quick correction in problematic areas in which the automated model adaptation may fail. A feasibility study with 40 clinical data sets was done for the male pelvic area, in which the risk organs (bladder, rectum, and femoral heads) were segmented by automatically adapting the corresponding organ models. RESULTS: In several cases of the validation study, minor user interaction was required. Nevertheless, a statistically significant reduction in the time required compared with manual organ contouring was achieved. The results of the validation study showed that the presented model-based approach is accurate (1.0-1.7 mm mean error) for the tested anatomic structures. CONCLUSION: A framework for organ delineation in radiotherapy planning is presented, including automated 3D model-based segmentation, as well as tools for interactive corrections. We demonstrated that the proposed approach is significantly more efficient than manual contouring in two-dimensional slices.
PURPOSE: Conformal irradiation (3D-CRT) of non-small-cell lung carcinoma (NSCLC) is largely based on precise definition of the nodal clinical target volume (CTVn). A reduction of the number of nodal stations to be irradiated would facilitate tumor dose escalation. The aim of this study was to design a mathematical tool based on documented data to predict the risk of metastatic involvement for each nodal station. METHODS AND MATERIALS: We reviewed the large surgical series published in the literature to identify the main pretreatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications. Starting with the primary site of the tumor as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. Statistical analysis used the inversion of probability trees method described by Weinstein and Feinberg. Validation of the software based on 134 patients from two different populations was performed by receiver operator characteristic (ROC) curves and multivariate logistic regression. RESULTS: Analysis of all of the various parameters of pretreatment staging relative to each level of the ATS map results in 20,000 different combinations. The first parameters included in the tree, depending on tumor site, were histologic classification, metastatic stage, nodal stage weighted as a function of the sensitivity and specificity of the diagnostic examination used (positron emission tomography scan, computed tomography scan), and tumor stage. Software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. Double cross validation confirmed the methodology. A 10% cutoff point was calculated from ROC and logistic model giving the best prediction of mediastinal lymph node involvement. CONCLUSION: To more accurately define the CTVn in NSCLC three-dimensional conformal radiotherapy, we propose a software that evaluates the risk of mediastinal lymph node involvement from easily accessible individual pretreatment parameters.
Ionizing radiation (IR) is an important component in the therapy of localized prostate cancer. Identification of protein alterations during IR-induced apoptosis prostate cancer cells is an important step toward understanding the new metabolic status of the dying cell. In the present study, we report changes in protein profile that define the execution phase of the apoptotic response in the in vitro model of tumorigenic radiation-transformed SV40-immortalized human prostate epithelial cells (267B1-XR), induced to undergo programmed cell death by IR. We employed an approach that involves use of analytical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) coupled with Western blotting with specific antisera. Our results point out that apoptotic cells experience significant reduction in the levels of the intermediate filament proteins, keratins-18, 19, vimentin and the associated 14-3-3 adapter proteins. At the same time, molecular chaperones such as glucose-regulated protein 94, calreticulin, calnexin, and protein disulfide isomerase exhibit marked accumulation in these dying cells. The present data indicate that apoptosis-associated processes in prostate epithelial cells include solubilization of the rigid intermediate filament network by specific proteolysis as well as increased levels of endoplasmic reticulum (ER) proteins with chaperone functions.
Hyperthermic treatment reduces protein synthesis and modifies amino acid transport in Escherichia coli. The present study examined the role of nutrient availability on these processes. Cultures of E. coli in log phase were aliquoted into growth medium with or without complete amino acid supplementation and exposed to 37, 44, or 48 degrees C for 10 min. Amino acid supplementation increased radiolabelled arginine uptake at 48 degrees C when compared with unsupplemented cells. Exposure to 48 degrees C also reduced protein synthesis in both groups by at least 50% as reflected by labelled arginine incorporation. Two-dimensional gel electrophoresis indicated that this heat-related decrement in synthesis was most apparent in basic proteins. Total density analysis of the fluorographs demonstrated reductions in basic proteins of 15% at 44 degrees C and 89% at 48 degrees C, while acidic proteins only showed an 80% reduction at 48 degrees C. Amino acid supplementation appears to raise the baseline, but not to modify the final results of hyperthermia-induced inhibition of protein synthesis. The sensitivity of basic protein synthesis seems to be a key event in this process.
The anoxic layers of marine sediments are dominated by sulfate reduction and methanogenesis as the main terminal oxidation processes. The aim of this study was to analyze the vertical succession of microbial populations involved in these processes along the first 4.5 m of a tidal-flat sediment. Therefore, a quantitative PCR approach was applied using primers targeting the domains of Bacteria and Archaea, and key functional genes for sulfate reduction (dsrA) and methanogenesis (mcrA). The sampling site was characterized by an unusual sulfate peak at 250 cm depth resulting in separate sulfate-methane transition zones. Methane and sulfate profiles were diametrically opposed, with a methane maximum in the sulfate-depleted zone showing high numbers of archaea and methanogens. The methane-sulfate interfaces harbored elevated numbers of sulfate reducers, and revealed a slight increase in mcrA and archaeal 16S rRNA genes, suggesting sulfate-dependent anaerobic oxidation of methane. A diversity analysis of both functional genes by PCR-denaturing gradient gel electrophoresis revealed a vertical succession of subpopulations that were governed by geochemical and sedimentologic conditions. Along the upper 200 cm, sulfate-reducing populations appeared quite uniform and were dominated by the Deltaproteobacteria. In the layers beneath, an apparent increase in diversity and a shift to the Firmicutes as the predominant group was observed.
The eight-variable model for the giant neuron localized in the esophageal ganglia of the marine pulmonate mollusk Onchidium verruculatum is reduced to four- and-three-dimensional systems by regrouping variables with similar time scales. These reduced models replicate the complex behavior including beating, periodic bursting and aperiodic bursting displayed by the original full model when the parameter Iext representing the intensity of the constant DC current stimulation is varied across a wide range. The complex behavior of the full model arises from the interaction of fast and slow dynamics, and depends on the time scale Cs of the slow dynamics. The four-variable reduced model is constructed independently from the parameter Cs so that it reproduces the two-dimensional bifurcation structure of the full model for the two parameters Iext and Cs. The three-variable reduced model is derived for a specific value of Cs. The parameters of this model are tuned so that its one-parameter bifurcation diagram for Iext closely matches that of the full model. Correspondence between bifurcation structures ensures that both reduced models reproduce the various discharge patterns of the full model. Similarity between the full and reduced models is also confirmed by comparing mean firing frequencies and membrane potential waveforms in various regimes. The reduction exposes the factors essential for reproducing the dynamics of the full model; indeed, it shows that the eight variables representing the membrane potential and seven gating variables of six ionic currents in the full model account, in fact, for three basic processes responsible for excitability, post-discharge refractoriness and slow membrane modulation.
Proteins of dog bronchoalveolar lavage fluid, obtained by washing the epithelial lining layer of lungs with phosphate-buffered saline, were separated by two-dimensional electrophoresis. Due to the low protein and high salt content of the bronchoalveolar lavage fluid, samples had to be concentrated and desalted. Following electrophoresis the protein spots were visualized by silver staining. Comparing the two-dimensional protein patterns of bronchoalveolar lavage fluid with that from serum, several lung-specific proteins were detected. The most prominent protein, most probably a surfactant-associated protein, showed isoforms with isoelectric points in the range of pH 4.2-4.8, and a molecular mass of 32 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction with dithiothreitol.
OBJECTIVE: The purpose of this study was to examine the long-term stability of depressive personality disorder. METHOD: The subjects included 142 outpatients with axis I depressive disorders at study entry; 73 had depressive personality disorder. The patients were assessed by using semistructured diagnostic interviews at baseline and in four follow-up evaluations at 2.5-year intervals over 10.0 years. Follow-up data were available for 127 (89.4%) of the patients. RESULTS: The 10.0-year stability of the diagnoses of depressive personality disorder was fair, and the rate of depressive personality disorder declined over time. The dimensional score was moderately stable over 10.0 years. Growth curve analyses revealed a sharp decline in the level of depressive personality disorder traits between the baseline and 2.5-year assessments, followed by a gradual linear decrease. Reductions in depressive personality disorder traits were associated with remission of the axis I depressive disorders. Finally, depressive personality disorder at baseline predicted the trajectory of depressive symptoms over time in patients with dysthymic disorder. CONCLUSIONS: Depressive personality disorder is moderately stable, particularly when assessed with a dimensional approach. However, the diagnosis rate and traits of depressive personality disorder tend to decline over time. The degree of stability for depressive personality disorder is comparable to that for the axis II disorders in the main text of DSM-IV. Finally, depressive personality disorder has prognostic implications for the course of axis I mood disorders, such as dysthymic disorder.
Hydrophobic proteins are difficult to analyze by two-dimensional electrophoresis (2-DE) because of their intrinsic tendency to self-aggregate during the first dimension (isoelectric focusing, IEF) or the equilibration steps. This aggregation renders their redissolution for the second dimension uncertain and results in the reduction of the number and intensity of protein spots, and in undesirable vertical and horizontal streaks across gels. Trifluoroethanol (TFE) is traditionally used at high concentration to solubilize peptides and proteins for NMR studies. Depending upon its concentration, TFE strongly affects the three-dimensional structure of proteins. We report here a phase separation system based on TFE/CHCl(3), which is able to extract a number of intrinsic membrane proteins. The addition of TFE in the in-gel sample rehydration buffer to improve membrane protein IEF separation is also presented. The procedure using urea, thiourea, and sulfobetaine as chaotropic agents was modified by the addition of TFE and removing of sulfobetaine at an optimized concentration in the solubilization medium used for the first dimension. When using membrane fractions isolated from Escherichia coli, the intensity and the number of spots detected from 2-DE gels that used TFE in the solubilization medium were significantly increased. The majority of the proteins identified using peptide mass fingerprinting and tandem mass spectrometry (MS/MS) were intrinsic membrane proteins, proteins of beta barrel structure or transmembrane proteins.
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Schrödinger's equation of a three-body system is a linear partial differential equation (PDE) defined on the 9-dimensional configuration space, R9, naturally equipped with Jacobi's kinematic metric and with translational and rotational symmetries. The natural invariance of Schrödinger's equation with respect to the translational symmetry enables us to reduce the configuration space to that of a 6-dimensional one, while that of the rotational symmetry provides the quantum mechanical version of angular momentum conservation. However, the problem of maximizing the use of rotational invariance so as to enable us to reduce Schrödinger's equation to corresponding PDEs solely defined on triangular parameters--i.e., at the level of R6/SO(3)--has never been adequately treated. This article describes the results on the orbital geometry and the harmonic analysis of (SO(3),R6) which enable us to obtain such a reduction of Schrödinger's equation of three-body systems to PDEs solely defined on triangular parameters.
OBJECTIVE: The purpose of this study was to prospectively evaluate the clinical utility and accuracy of intraoperative three-dimensional fluoroscopy as an adjunct for the placement of a complex spinal instrumentation. METHODS: The Siemens Iso-C three-dimensional fluoroscopy unit in the combination with the Stealth Treon computer volumetric navigational system was used. A total of 279 spinal instrumentation screws or transpedicular cannulations were performed in 69 patients. Accuracy, operative time, and amount of fluoroscopy utilization time were assessed for transforaminal lumbar interbody fusion (TLIF) and kyphoplasty cases. RESULTS: Only 4 percutaneous transpedicular lumbar screws out of 265 total (1.5%) were malpositioned. Average operative time for TLIF cases was 185 minutes (range 114-311 minutes) for one-level and 292.6 minutes (range 173-390 minutes) for two-level procedures. Biplanar fluoroscopy utilization time was 93 seconds (range 27-280 seconds) for one-level procedures and 216 seconds (range 80-388 seconds) for two-level procedures. Average surgery duration for kyphoplasty was 60 minutes (range 36-79 minutes) for one-level procedures and 68.5 minutes (range 65-75 minutes) for two-level cases. Biplanar fluoroscopy utilization time was 41.3 seconds per case (range 25-62 seconds). CONCLUSIONS: Use of intraoperative three-dimensional fluoroscopy for image guidance in minimally invasive complex spinal instrumentation procedures is feasible and safe. This technique provides excellent visualization of three-dimensional relationships. This potentially results in improved accuracy of screw positioning and the ability to detect misplaced screws prior to wound closure. This technique also potentially results in a significant reduction in radiation exposure for both the patient and the staff.
Upon entering mammalian cells, Pseudomonas exotoxin A (PE) is proteolytically processed by furin to produce an N-terminal fragment of 28 kDa and a C-terminal fragment of 37 kDa. Cleavage is followed by the reduction of a key disulfide bond (cysteines 265-287). This combination of proteolysis and reduction releases the 37 kDa C-terminal fragment, which then translocates to the cytosol where it ADP-ribosylates elongation factor 2 and inhibits protein synthesis. To investigate toxin reduction, furin-nicked PE or a hypercleavable mutant, PEW281A, was subjected to various treatments and then analyzed for fragment production. Reduction was evident only when unfolding conditions and a reducing agent were applied. Thermal unfolding of PE, as evidenced by changes in alpha-helical content and increased sensitivity to trypsin, rendered nicked toxin susceptible to protein disulfide isomerase- (PDI-) mediated reduction. When subcellular fractions from toxin-sensitive cells were incubated with nicked PE, toxin unfolding and reducing activities were present in the membrane fraction but not the soluble fraction. These data indicate that PE reduction is a two-step process: unfolding that allows access to the Cys265-287 disulfide bond, followed by reduction of the sulfur-sulfur bond by PDI or a PDI-like enzyme. With regard to cellular processing, we propose that the toxin's three-dimensional structure retains a "closed" conformation that restricts solvent access to the Cys265-287 disulfide bond until after a cell-mediated unfolding event.
BACKGROUND AND AIMS: The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information and to monitor future therapeutic strategies of stroke patients. We tested the following hypotheses: (1) that changes in axonal integrity along the corticospinal tract after stroke can be detected as a reduction in fractional anisotropy; and (2) that sustained low fractional anisotropy is indicative of axonal loss and therefore is correlated with poor motor outcome, as measured by specific neurological motor scores. METHODS: We developed a segmentation tool based on magnetic resonance diffusion tensor imaging in conjunction with three dimensional fibretracking for longitudinal studies of the corticospinal tract, and used specific neurological motor scores to test the hypotheses in five stroke patients within the first week and 30 and 90 days after the stroke. RESULTS: Reduction in fractional anisotropy within the first weeks after stroke reflected a decline in axonal integrity, leading to Wallerian degeneration, and demonstrated a correlation between the temporal evolution of fractional anisotropy and motor function in patients with poor motor outcome. CONCLUSION: The study demonstrated the feasibility of fibretracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy in the segmented corticospinal tract is a sensitive measure of structural changes after stroke.
After preclinical studies and evaluation of radiation exposures, intraoperative three-dimensional (3D) C-arm based imaging is now available for the facial skeleton. Fourteen patients admitted for surgical treatment of zygomaticomaxillary complex (ZMC) fractures were included in the study. Preoperative diagnostics and surgical treatment were performed as usual. Intraoperatively, after open reduction, a cone-beam computed tomography (CBCT) dataset was generated using the SIREMOBIL Iso-C3D (Siemens Medical Solutions, Erlangen, Germany). After DICOM-import in eFilm Workstation axial, coronal and sagittal reconstructions were evaluated by five examiners with the help of six defined criteria. In our study, secondary reconstructions were available after 6 min, excluding the time needed for the evaluation of the images. Especially the positioning of the isocentre of the SIREMOBIL Iso-C3D proved to be uncomplicated. Because of the size of the datasets, assessment of the symmetry of the malar projection proved difficult. Best scoring results were found regarding the visualization of the fragment position, bony anchorage of the screws and the fitting of the plates. Remarkable was the low level of metal artefacts in primary and secondary reconstructions. In conclusion, our results demonstrate intraoperative CBCT using the SIREMOBIL Iso-C3D suitable for assessment of postoperative results following ZMC reduction.
In this paper we describe the application of three-dimensional (3D) imaging and computer-generated models in the management of orbital deformity. The technique was found to be particularly useful in posttraumatic deformity and fibrous dysplasia involving the orbit. Further application was found in cases of radiation hypoplasia, high facial cleft, and facial atrophy. Funding restrictions necessitate appropriate selection of cases when using new and expensive 3D imaging rather than traditional and less expensive methods. To remain within a realistic budget only those patients who will clearly benefit from the third dimension compared with traditional methods of assessment and management should be selected. These include patients requiring precise reduction or secondary reconstruction in which there is a matched normal anatomical component for comparison. This application is also only beneficial where the planned reconstruction is dimensionally stable.