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PubMed1992

Spectroscopic imaging display and analysis.

A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain.

Humans↗
PubMed1995

Structural identification of valine hydroperoxides and hydroxides on radical-damaged amino acid, peptide, and protein molecules.

We have previously demonstrated the formation of two reactive moieties on proteins during free radical attack: hydroperoxides, and 3,4-dihydroxyphenylalanine (DOPA). Here we have undertaken the structural elucidation of the hydroperoxides of valine, the amino acid which is most susceptible to peroxidation. Exposure of L-valine to free radicals generated by radiolysis in an oxygen-saturated system produced three valine hydroperoxides. Upon treatment with sodium borohydride these were reduced to their corresponding hydroxides, which can be separated and purified by high performance liquid chromatography (HPLC). Based on spectroscopic data from high resolution chemical ionization (CI) mass spectrometry (MS), electrospray (ES) MS, electron impact (EI) MS, proton (1H) nuclear magnetic resonance (NMR) and carbon-13 (13C) NMR studies, the three valine hydroxides have been identified as beta-hydroxyvaline [(2S)-2-amino-3-hydroxy-3-methyl-butanoic acid], (2S,3S)-gamma-hydroxyvaline [(2S,3S)-2-amino-3-hydroxymethyl-butanoic acid], and (2S,3R)-gamma-hydroxyvaline [(2S,3R)-2-amino-3-hydroxymethyl-butanoic acid]. HPLC analysis of O-phthaldialdehyde (OPA) derivatives of the hydroxyvalines provides a sensitive and accurate method for quantitative measurement. This method enabled hydroxyvalines to be detected in the hydrolysates of a tripeptide (glutamyl-valinyl-phenylalanine) and a protein (bovine serum albumin) that had been gamma-radiolysed and treated with sodium borohydride. Hydroxyvaline may be useful as a marker in studying protein oxidation in some biological systems under oxidative stress.

Amino Acids↗
PubMed1995

Two miniature monitors for long-term ambulatory studies.

Two very low-power monitors are described. One typically limb-worn to record the level of physical activity of a person; the other, used with surface electrodes, to record three parameters of an EMG signal. The monitoring period can extend to days with a very accurate 'time of event' log. A novel method has been devised to double the resolution of the data gathered. A PC is used to store and process the collected data, which can be displayed or printed as one-, or four-channel, time-related histogram. The gathered data can also be analysed for trends and other statistical analysis. The hardware is relatively simple and made from low-cost components. Neither monitor uses a microprocessor for data gathering. The system is very easy to use requiring minimal operator training. Where 'no-frills' ambulatory monitoring is called for, the systems presented would compare very favourably with other commercially available monitors, either on cost, complexity of setting up, or on weight.

Circadian Rhythm↗
PubMed2005

Method for cortical bone structural analysis from magnetic resonance images.

RATIONALE AND OBJECTIVES: Quantitative evaluation of cortical bone architecture as a means to assess bone strength typically is accomplished on the basis of images obtained by means of dual-energy X-ray absorptiometry (DXA) or computed tomography. Magnetic resonance (MR) imaging has potential advantages for this task in that it allows imaging in arbitrary scan planes at high spatial resolution. However, several hurdles have to be overcome to make this approach practical, including resolution of issues related to nonlinear receive coil sensitivity, variations in marrow composition, and the presence of periosteal isointense tissues, which all complicate segmentation. The aim of this study is to develop MR acquisition and analysis methods optimized for the detection of cortical boundaries in such complex geometries as the femoral neck. MATERIALS AND METHODS: Cortical boundary detection is achieved by radially tracing intensity profiles that intersect the periosteal and endosteal boundaries of bone. Profiles subsequently are normalized to the intensity of the marrow signal, processed with morphologic image operators, and binarized. The resulting boundaries are mapped back onto the spatial image, and erroneous boundary points are removed. From the detected cortical boundaries, cortical cross-sectional area and thickness are computed. The method was evaluated on cortical bone specimens and human volunteers on the basis of high-resolution images acquired at a 1.5-Tesla field strength. To assess whether the method is sensitive to detect the expected dependencies of cortical parameters in weight-bearing bone on overall habitus, 10 women aged 46-73 years (mean age, 56 years) underwent the cortical imaging protocol in the proximal femur, and results were compared with DXA bone mineral density parameters of the hip and spine. RESULTS: Reproducibility was approximately 2%. Double oblique images of the femoral neck in the 10 women studied showed that cortical cross-sectional area correlated strongly with height (r = 0.88; p = .0008), whereas cortical diameter versus age approached significance (r = 0.61; p = .06). Measurements in specimens of some cortical parameters indicated resolution dependence. However, note that specimen ranking within each parameter remained constant across all resolutions studied. CONCLUSION: Data suggest the new method to be robust and applicable on standard clinical MR scanners at arbitrary anatomic locations to yield clinically meaningful quantitative results.

Absorptiometry, Photon↗
PubMed2006

Propylthiouracil, independent of its antithyroid effect, produces endothelium-dependent vasodilatation through induction of nitric oxide bioactivity.

OBJECTIVE: Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. The aim of this study is to investigate whether PTU has a beneficial effect on endothelial function. METHODS AND RESULTS: Ninety patients with a history of hyperthyroidism receiving either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were enrolled in this study. Brachial artery endothelium-dependent (flow-mediated dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation) responses were assessed by high-resolution ultrasound image. Data for these two groups were compared with those of 41 healthy control subjects. The FMD values were significantly increased in patients maintained on PTU versus those in the MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively; P<0.01). Nitroglycerin-mediated dilatation had no significant difference between the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%, respectively; P=0.455). On multivariate analysis, no significant relationship was found between the FMD and thyroid hormone index levels. To further elucidate whether PTU has a direct effect on endothelial function, the effect of PTU on isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced by PTU was endothelium-dependent and could be blocked by pretreatment with nitric oxide (NO) inhibitors. PTU also increased NO formation in aortic segments. CONCLUSIONS: This study demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.

Adult↗
PubMed2004

Target selectivity in EF-hand calcium binding proteins.

EF-hand calcium binding proteins have remarkable sequence homology and structural similarity, yet their response to binding of calcium is diverse and they function in a wide range of biological processes. Knowledge of the fine-tuning of EF-hand protein sequences to optimize specific biochemical properties has been significantly advanced over the past 10 years by determination of atomic resolution structures. These data lay the foundation for addressing how functional selectivity is generated from a generic ionic signal. This review presents current ideas about the structural mechanisms that provide the selectivity of different EF-hand proteins for specific cellular targets, using S100 and calmodulin family proteins to demonstrate the critical concepts. Three factors contribute significantly to target selectivity: molecular architecture, response to binding of Ca(2+) ions, and the characteristics of target binding surfaces. Comparisons of calmodulin and S100 proteins provide insights into the role these factors play in facilitating the variety of binding configurations necessary for recognizing a diverse set of targets.

Amino Acid Sequence↗
PubMed2006

High-resolution multiple-unit EEG in cat auditory cortex reveals large spatio-temporal stochastic interactions.

It has been argued that information processing in the cortex is optimised with regard to certain information theoretic principles. We have, for instance, recently shown that spike-timing dependent plasticity can improve an information-theoretic measure called spatio-temporal stochastic interaction which captures how strongly a set of neurons cooperates in space and time. Systems with high stochastic interaction reveal Poisson spike trains but nonetheless occupy only a strongly reduced area in their global phase space, they reveal repetiting but complex global activation patterns, and they can be interpreted as computational systems operating on selected sets of collective patterns or "global states" in a rule-like manner. In the present work we investigate stochastic interaction in high-resolution EEG-data from cat auditory cortex. Using Kohonen maps to reduce the high-dimensional dynamics of the system, we are able to detect repetiting system states and estimate the stochastic interaction in the data, which turns out to be fairly high. This suggests an organised cooperation in the underlying neural networks which cause the data and may reflect generic intrinsic computational capabilities of the cortex.

Animals↗
PubMed2006

General occurrence of the glucosinolate glucocochlearin within the Cochlearia genus.

A natural compound, glucocochlearin, was isolated from the aerial parts of 10 different Cochlearia species. The purification of this compound was achieved through HPLC. The identity of the product was established mainly on the basis of spectroscopic NMR (1H, 13C, COSY, TOCSY, HMQC, HMBC, J-MOD) and high resolution mass spectroscopy data. This compound can be considered as a chemomarker of the genus Cochlearia.

Brassicaceae↗
PubMed2005

High-resolution reference ranges for estradiol, luteinizing hormone, and follicle-stimulating hormone in men and women using the AxSYM assay system.

OBJECTIVES: High-resolution reference ranges are essential for reproductive hormones due to the significant day-to-day variation seen with these analytes. DESIGN AND METHODS: The performance of AxSYM assays for estradiol, luteinizing hormone (LH), and follicle-stimulating hormone was evaluated. RESULTS: These studies validate the performance of each assay, permitting high-resolution reference ranges to be established. CONCLUSIONS: The high-resolution reference range data provided herein for both normally cycling females and males should be applicable to a wide variety of clinical situations.

Adolescent↗
PubMedDate not supplied

Correlates and consequences of chronic insomnia.

Approximately one half of patients with insomnia have a primary psychiatric disorder such as a depression or anxiety. Insomnia is associated with increased risk of new or recurrent psychiatric disorders, increased daytime sleepiness with consequent cognitive impairment, poorer prognoses, reduced quality of life and high healthcare-related financial burden. Emerging data suggest that resolution of insomnia may improve psychiatric outcomes, which underscores the importance of vigorous treatment. Unfortunately, only a small percentage of patients receive such care. An ideal monotherapeutic strategy would treat both depression and insomnia. There are, however, only a handful of modern antidepressants that objectively improve sleep maintenance problems, and none do so without causing adverse next-day effects such as sedation. Thus, a significant number of patients must take adjunctive hypnotic medications, even though longer-term efficacy has not been established. New and emerging anti-insomnia agents may prove useful in the long-term treatment of chronic insomnia. Further research is needed to establish the benefits of such treatment.

Age Factors↗
PubMed2004

Cadmium complexation by bacteriogenic iron oxides from a subterranean environment.

This study quantifies the metal sorption characteristics of subterranean bacteriogenic iron oxides (BIOS) and their organic phases (intermixed intact and fragmented bacteria). A Cd2+ ion-selective electrode was used to generate high-resolution metal sorption data as a function of increasing pH. A multisite Langmuir model, along with a linear programming regression method (LPM), was applied to fit experimental data. This approach found two discrete Cd2+ binding sites for the BIOS with average -log10 equilibrium constants (pK(S,j)) of 1.06 +/- 0.19 and 2.24 +/- 0.28. Three discrete sites were obtained for the bacterial fraction, with pK(S,j) values of -0.05 +/- 0.12, 1.18 +/- 0.02, and 3.81 +/- 0.16. This indicated that the BIOS surface had a lower affinity for Cd2+ than that of the bacteria. pK(S,j) values for the BIOS were similar to those reported for pure iron oxide phases, while the organic fraction pK(S,j) spectrum was consistent with previous spectra for intact bacteria. Individual binding site densities of 0.04 +/- 0.01 and 0.05 +/- 0.02 and 0.29 +/- 0.05, 0.11 +/- 0.01, and 0.09 +/- 0.02 micromol/mg of BIOS corresponded to the iron oxide mixture and bacteria fraction, respectively. These values indicated high concentrations of strong affinity Cd2+ complexing groups on the bacterial surface. Comparison of total site densities of 0.08 +/- 0.02 and 0.48 +/- 0.06 micromol/mg of BIOS for the mixture and the bacterial phase, respectively, suggested a nonadditive character for the BIOS surface reactivity. This was emphasized by a higher affinity for Cd2+, as well as an increase in total site concentration observed for the bacterial phase. LPM was able to distinguish between the BIOS mixture and its organic fraction Cd2+ complexation characteristics. This approach is therefore a useful tool for the study of natural sorbent materials controlling metal partitioning in contaminated and pristine environments.

Journal Article↗
PubMed2005

Callus mineralization following distraction osteogenesis of the mandible monitored by scanning acoustic microscopy (SAM).

BACKGROUND: Scanning acoustic microscopy uses ultrasound to analyse histomorphology of tissues with microscopic resolution and delivers data about physical properties of the specimen. MATERIAL AND METHODS: Bony consolidation was monitored by scanning acoustic microscopy in 12 embedded specimens of dog mandibles after distraction osteogenesis. Increasing mineralization was detected by measurements of acoustic impedance (Z). RESULTS: There was a strong correlation between acoustic impedance and time of consolidation. Measurements of the speed of sound (v) provided specific information about non-mineralized zones of the distracted area. Distribution of density in the distracted area could be reconstructed by using the measurements of acoustic impedance and speed of sound. CONCLUSION: The method seems suitable for studying bone remodelling qualitatively and quantitatively.

Acoustics↗
PubMed2006

Mechanism of intracellular block of the KcsA K+ channel by tetrabutylammonium: insights from X-ray crystallography, electrophysiology and replica-exchange molecular dynamics simulations.

The mechanism of intracellular blockade of the KcsA potassium channel by tetrabutylammonium (TBA) is investigated through functional, structural and computational studies. Using planar-membrane electrophysiological recordings, we characterize the binding kinetics as well as the dependence on the transmembrane voltage and the concentration of the blocker. It is found that the apparent affinity of the complex is significantly greater than that of any of the eukaryotic K(+) channels studied previously, and that the off-rate increases with the applied transmembrane voltage. In addition, we report a crystal structure of the KcsA-TBA complex at 2.9 A resolution, with TBA bound inside the large hydrophobic cavity located at the center of the channel, consistent with the results of previous functional and structural studies. Of particular interest is the observation that the presence of TBA has a negligible effect on the channel structure and on the position of the potassium ions occupying the selectivity filter. Inspection of the electron density corresponding to TBA suggests that the ligand may adopt more than one conformation in the complex, though the moderate resolution of the data precludes a definitive interpretation on the basis of the crystallographic refinement methods alone. To provide a rationale for these observations, we carry out an extensive conformational sampling of an atomic model of TBA bound in the central cavity of KcsA, using the Hamiltonian replica-exchange molecular dynamics simulation method. Comparison of the simulated and experimental density maps indicates that the latter does reflect at least two distinct binding orientations of TBA. The simulations show also that the relative population of these binding modes is dependent on the ion configuration occupying the selectivity filter, thus providing a clue to the nature of the voltage-dependence of the binding kinetics.

Alanine↗
PubMed2006

Structural changes in the L photointermediate of bacteriorhodopsin.

The L to M reaction of the bacteriorhodopsin photocycle includes the crucial proton transfer from the retinal Schiff base to Asp85. In spite of the importance of the L state in deciding central issues of the transport mechanism in this pump, the serious disagreements among the three published crystallographic structures of L have remained unresolved. Here, we report on the X-ray diffraction structure of the L state, to 1.53-1.73 A resolutions, from replicate data sets collected from six independent crystals. Unlike earlier studies, the partial occupancy refinement uses diffraction intensities from the same crystals before and after the illumination to produce the trapped L state. The high reproducibility of inter-atomic distances, and bond angles and torsions of the retinal, lends credibility to the structural model. The photoisomerized 13-cis retinal in L is twisted at the C(13)=C(14) and C(15)=NZ double-bonds, and the Schiff base does not lose its connection to Wat402 and, therefore, to the proton acceptor Asp85. The protonation of Asp85 by the Schiff base in the L-->M reaction is likely to occur, therefore, via Wat402. It is evident from the structure of the L state that various conformational changes involving hydrogen-bonding residues and bound water molecules begin to propagate from the retinal to the protein at this stage already, and in both extracellular and cytoplasmic directions. Their rationales in the transport can be deduced from the way their amplitudes increase in the intermediates that follow L in the reaction cycle, and from the proton transfer reactions with which they are associated.

Amino Acid Sequence↗
PubMed2004

Indications and limitations of intraoperative navigation in maxillofacial surgery.

PURPOSE: Although primarily developed for neurosurgical application, intraoperative navigation has gained acceptance even in maxillofacial surgery with an increasing field of indications. We want to demonstrate our clinical experiences, focusing on the indications and limitations of intraoperative navigation. MATERIALS AND METHODS: In our department, the navigation system VectorVision (BrainLAB, Heimstetten, Germany) is used. The accuracy of this referencing method, consisting of a cortical fixed reference system and surface scanning, was checked by anatomic landmarks. Surgical treatment of 20 patients was performed with the help of the navigation system. RESULTS: The VectorVision system proved to be a useful supplement during the surgical exploration of complex anatomic regions. However, resolution of imaging data sets, errors of image fusion, and discrepancies during referencing increased the inaccuracy before surgery. The main problem was the topographic changes caused by surgery, resulting in discrepancies between the preoperative image data and the surgical site. In one case suffering from a meningioma extending to the neck, topography was changed by surgery making navigation inaccurate. CONCLUSION: Generally, a promising field for intraoperative navigation systems were small surgical approaches allowing only limited exposure. From our point of view, additional promising indications include vast tumors or recurrent tumors because of altered anatomy with lost landmarks during surgery. The same was the case of patients suffering from plexiform neurofibroma caused by neurofibromatosis type I. Further, intraoperative navigation was helpful to determine the position of foreign bodies during imaging, making the intraoperative location easier.

Adult↗
PubMed2004

Structural correlates of mild cognitive impairment.

The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.

Aged↗
PubMed2004

Radial correlation contrast--a functional connectivity MRI contrast to map changes in local neuronal communication.

A functional connectivity MRI method that groups neighboring voxels in relation to their degree of temporal cross-correlation between their time courses is presented. This grouping generates a vector field, which is assumed to provide insights into the local organization of neuronal activity. Application with high spatial resolution fMRI rat data subjected to electric forepaw sensory stimulation (156 . 156 . 1000 micron1) shows a significant localized increase of the vector field amplitude in cortical layers 4 and 2/3 of the primary sensory cortex and in layer 2/3 of the primary motor cortex, suggesting a strong correlation with local neuronal communication. Vector field phases exhibit a transition with neuronal activation from random-like orientations during rest to clusters of common orientations. Cluster size is shown to be weakly dependent on the radii of the vector field calculation, and shuffling voxel position within clusters generates a random-like vector orientation instead. This suggests that changes in vector orientations upon activation represent changes in the internal correlation between voxels that is interpreted as a change in the internal neuronal communication.

Animals↗
PubMed2005

Improved evaluation of back muscle SEMG characteristics by modelling.

Surface EMG (SEMG) as non-invasive method is a valuable tool in functional studies of movement co-ordination. The interpolation of the SEMG power (EMG mapping) gives information about intra- and inter-muscular co-ordination. It has been shown that SEMG maps of low back pain patients and healthy subjects differ. The only major drawback to SEMG is that volume conduction of muscle tissue, fat, and skin decreases the spatial and temporal resolution of signals. To improve the interpretation of SEMG signals, we have applied high pass filtering of cross covariance functions, which has proved to be useful in increasing the spatial resolution, to SEMG data of the back region. Experimental data demonstrate that SEMG signals from the back extensors show only rarely signs of action potential propagation. This behaviour, also described in the literature, can be explained by a model assuming short, deep muscle fibres, having bipolar end effects, with overlapping positions parallel to the fibre direction. This condition is fulfilled by the mm. multifidii et rotatores which are part of the m. erector spinae. Although the model is simplistic, the agreement between simulations and experiments is good.

Journal Article↗