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PubMedDate not supplied

The benefits of increasing spatial resolution as a means of reducing artifacts due to field inhomogeneities.

All users of NMR equipment are familiar with the desirability of achieving as high a quality of field as possible. On the other hand, it is easy to forget that the field quality of relevance in both imaging and spectroscopy is that over individual voxels, and not the whole volume. This note demonstrates in practice how performance in poor fields is improved substantially by reducing voxel size (or increasing spatial resolution), offering a potential alternative to additional shimming under appropriate circumstances. It argues that the best criterion for assessing magnet quality in spatially localized systems is the maximum field error gradient in the volume of usable field, rather than the maximum deviation in the field.

Humans↗
PubMed1994

Effects of therapy on the 1H NMR spectrum of a human glioma line.

Currently it is difficult to predict the efficacy of any therapeutic modality in individual patients. If it could be shown that successful therapy causes some chemical alteration in the tumor before gross alteration in size becomes radiologically visible, the therapeutic regimen could potentially be modified, sparing the patients longer trials of ineffective therapy. We used proton nuclear magnetic resonance spectroscopy to detect the presence of simple metabolites (such as lactic acid, creatine/phosphocreatine, N-acetyl aspartate, and the "choline" pool) in extracts of a human glioma grown subcutaneously in athymic ("nu/nu") mice. By comparing the tumor spectra obtained from untreated mice with tumor spectra from mice treated with chemotherapy or irradiation, we have shown a significant decrease in the lactate/creatine and lactate/choline values in tumors of similar size following treatment. Such information could prove valuable as a means of monitoring tumor therapy when obtained noninvasively from spatially localized in vivo spectra.

Animals↗
PubMed1994

Myocardial bioenergetic abnormalities in a canine model of left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to assess high energy phosphate compound metabolism in remodeled left ventricular myocardium. BACKGROUND: The development of heart failure several years after myocardial infarction is often unexplained. Certain abnormalities of remodeled myocardium suggest that structural changes occurring in viable myocardium after discrete myocardial damage may contribute to the later appearance of heart failure. Whether these abnormalities alter metabolism in the surviving muscle and thereby possibly contribute to ventricular dysfunction is unknown. METHODS: High energy phosphate compound metabolism was assessed using spatially localized phosphorus-31 nuclear magnetic resonance spectroscopy. Eleven dogs with documented left ventricular dysfunction, resulting from infarction produced by transmyocardial direct current shock, were compared with eight normal dogs. Analyses were performed at baseline and during coronary hyperperfusion induced by intravenous adenosine. Myocardial blood flow was measured with radioactive microspheres. RESULTS: The creatine phosphate/adenosine triphosphate (CP/ATP) ratio was significantly reduced in the left ventricular dysfunction group in both the subepicardium ([mean +/- SE] 1.94 +/- 0.08 vs. 2.32 +/- 0.13, p = 0.019) and the subendocardium (1.71 +/- 0.07 vs. 2.05 +/- 0.07, p = 0.004). Intravenous adenosine produced significant coronary hyperemia in both groups but was less marked in dogs with left ventricular dysfunction. The improvement in myocardial perfusion was accompanied by a significant increase in the subendocardial CP/ATP ratio (from 1.71 +/- 0.07 to 1.92 +/- 0.08, p = 0.01) in dogs with left ventricular dysfunction. CONCLUSIONS: An abnormal transmural distribution of high energy phosphate compounds is evident in remodeled myocardium. This abnormality may be related in part to mismatch of oxygen delivery and demand.

Adenosine↗
PubMed1996

The role of phosphoinositide-derived second messengers in oxytocin-stimulated prostaglandin F2 alpha release from endometrium of pigs.

The mechanism for prostaglandin (PG) F2 alpha release from pig endometrium after oxytocin (OT) treatment is unknown. OT may rapidly stimulate inositol (1,4,5)-trisphosphate (IP3) and diacylglycerol (DAG) formation, consistent with the concept of rapid activation of a second-messenger system. In support of this hypothesis, endometrial IP3 levels were increased (P < 0.05) within 0.5 min after treatment with 0.1 microM OT. In contrast, increased DAG formation was not detected after treatment with OT. However, similar to the stimulation of endometrial PGF2 alpha secretion observed after OT treatment (P < 0.001), PGF2 alpha release was increased (P < 0.01) after treatment with phorbol-12-myristate-13-acetate (PMA), which mimics DAG activation of protein kinase C. Further, stimulation of endometrial PGF2 alpha secretion did not result from cell death induced by PMA or OT because lactate dehydrogenase, a cytosolic marker of cellular integrity, did not leak into the medium after PMA or OT treatment. In contrast, 0.5% saponin (positive control for cell death and concomitant release of lactate dehydrogenase) increased PGF2 alpha secretion (P < 0.05) and lactate dehydrogenase release (P < 0.001). These results indicate that OT induces endometrial IP3 production in a rapid manner indicative of a second-messenger system. The finding that increased DAG was not also detected after OT treatment may reflect rapid metabolism or compartmentalized production of DAG involved in the second-messenger stimulation of phospholipase C. The high background of DAG used in the biosynthesis of cellular lipids would obscure the rather small spatially localized changes in DAG levels resulting from the activation of phospholipase C. The finding that DAG was present at approximately 10 to 20-fold higher levels than IP3 in resting cells was consistent with this conclusion.

Analysis of Variance↗
PubMed1996

Bombyxin-related peptides: cDNA structure and expression in the brain of the hornworm Agrius convolvuli [corrected].

We have cloned three cDNAs from the sweet potato hornworm Agrius convolvuli that encode precursor molecules for peptides structurally related to bombyxin, an insulin-related brain secretory peptide in Bombyx mori. The Agrius bombyxin-related peptide (ABRP) cDNAs are classified into type A and B according to their sequence similarity. The prepro-ABRPs deduced from the cDNA sequences have the insulin-like domain organization of signal peptide/B chain/C peptide/A chain. The ABRP transcripts in Agrius brain were shown to locate in four pairs of medial neurosecretory cells, the homologous group of neurosecretory cells that produce bombyxins in Bombyx brain. Genomic Southern analysis indicated the presence of multiple copies of ABRP gene in the Agrius genome. Results showed that the ABRP genes are remarkably different from the vertebrate insulin genes in the number of copy and spatial localization of the transcripts.

Amino Acid Sequence↗
PubMed2006

Human coronary microvascular effects of cardioplegia-induced stromal-derived factor-1alpha.

BACKGROUND: Stromal-derived factor-1alpha (SDF-1alpha) binds to its specific receptor, CXCR4, and plays an important role in ischemia-induced angiogenesis. Some of the effects of SDF-1alpha are likely due to effects on the microcirculation. Cardioplegia and cardiopulmonary bypass (CP/CPB) activate mitogen-activated protein kinase (MAPK) signaling pathways including p38, ERK1/2, and JNK. The purpose of the present study was to evaluate SDF-1alpha expression, and relationships between SDF-1alpha-mediated coronary microvessel response and MAPKs. METHODS: The atrial tissue of patients undergoing cardiac surgery was harvested before and after CP/CPB. Protein levels of SDF-1alpha and CXCR4 were measured by Western blot and immunohistochemistry, and plasma levels of SDF-1alpha were measured by enzyme-linked immunosorbent assay. Coronary microvessel responses to SDF-1alpha were assessed by videomicroscopy. To further elucidate SDF-1alpha/CXCR4 signaling, microvessel responses were evaluated in the presence of CXCR4 antagonist (AMD3100) and MAPK inhibitors, ERK1/2 inhibitor (UO126), p38 inhibitor (SB203580), and JNK inhibitor (ALX-159-600). RESULTS: Myocardial protein expression of SDF-1alpha was elevated after CP/CPB (9.5 +/- 3.5-fold, p = 0.03 versus before CP/CPB). Increases in SDF-1alpha spatially localized to endothelial cells, smooth muscle cells, and myocytes. Plasma levels of SDF-1alpha were increased after CP/CPB (3.2 +/- 2.8 versus 2.8 +/- 1.7 ng /mL, p = 0.03 versus before CP/CPB). Stromal-derived factor-1alpha induced coronary microvessel contraction after CP/CPB (p = 0.046 versus before CP/CPB), which was blocked by the CXCR4 antagonist. Furthermore, SDF-1alpha induced microvessel contraction was inhibited by MAPK inhibitors, ERK-1/2 (p = 0.046), p38 (p = 0.049), and JNK inhibition (p = 0.06). CONCLUSIONS: These results suggest that CP/CPB induces myocardial expression of SDF-1alpha and results in coronary microvessel contraction through MAPK signaling pathways.

Aged↗
PubMed2004

Patterning protein molecules on poly(ethylene glycol) coated Si(111).

We demonstrate spatially localized immobilization of protein molecules on high-density poly(ethylene glycol) (PEG) coated Si(111). Patterns of HO- and CH3O-terminated PEG regions are formed on silicon surfaces based on soft lithography techniques and an efficient reaction between alcohol functional groups and chlorine-terminated silicon. Activation of the HO-terminated PEG brush is achieved via either partial oxidation to form aldehyde groups or via attachment of efficient leaving groups. Protein molecules are covalently immobilized to these activated regions on the PEG/Si surface.

Adsorption↗
PubMed2006

Coordination numbers of alkali metal ions in aqueous solutions.

The level of complexity with which any biological ion interaction mechanism can be investigated, whether it is a binding mechanism in proteins or a permeation mechanism in ion channels, is invariably limited by the state-of-the-art of our understanding of the characteristic properties of ion solvation. Currently, our understanding of the energetic properties of ion solvation in aqueous phase is considered adequate enough to have helped us obtain satisfactory descriptions of the role of energetics in several biological ion interaction processes. In contrast, the lack of consensus among all the experimental structural hydration data determined more than 10 years ago, particularly regarding ion hydration numbers, has limited us to nothing better than speculation regarding the roles of local spatial environments in these mechanisms. Here we revisit experimental and theoretical work applied to probe hydration numbers of three alkali metal ions, Li(+), Na(+) and K(+), and analyze them to clarify the current state-of-the-art of our understanding of their structural hydration properties. We find that with substantial improvements over the past 10 years in areas of experimental techniques, data analysis strategies, and theoretical and computational approaches for interrogating ion hydration structures, there is now growing consensus regarding the hydration numbers of these ions. We see that under physiological conditions, ab initio methods suggest that all three ions prefer strong coordination with exactly 4 water molecules, a result we find consistent with some older experimental measurements. Ab initio molecular dynamics (AIMD) simulations invariably identify additional "loosely" coordinated water molecules at the far slopes of the principle maxima of the radial distribution profiles for Na(+) and K(+) ions. We suggest that these statistical admixtures of additional oxygen atoms have resulted in the most recent experimentally determined hydration numbers of Na(+) ions to be 5 and K(+) ions to be 6.

Metals, Alkali↗
PubMed2005

Slow cortical potential shifts preceding sensorimotor interactions.

It is well known that synchronization of cortical neurons is modulated ("gating") by the chronological interaction between somatosensory and sensorimotor events. This study tested the hypothesis that the anticipatory processes for this interaction increase the synchronization of cortical neurons as revealed by negative event-related potentials (contingent negative variation, CNV). High-resolution electroencephalographic data (128 electrodes) were recorded in 14 subjects. In the "sensorimotor interaction" condition, the subjects were waiting for a galvanic somatosensory stimulation at the left hand concomitant with a Go or NoGo stimulus (50% of Go trials triggering right hand movements). In the control condition, the Go/NoGo stimulus followed the somatosensory stimulation of 1.5s. The electroencephalographic data were spatially enhanced by surface Laplacian estimation. In the control condition, the CNV was observed only in the foreperiod between the somatosensory stimulation and Go/NoGo task (i.e. no CNV before the somatosensory stimuli). It was spatially localized in the primary sensorimotor area contralateral to the possible motor response. In the "sensorimotor interaction" condition, the CNV preceded the concomitant somatosensory stimulation and Go/NoGo task and was distributed to the frontocentral midline other than the contralateral sensorimotor area. These results suggest that the anticipatory processes for sensorimotor interactions increase the synchronization of cortical neurons in the frontocentral midline, possibly due to mechanisms sub-serving top-down attentional processes.

Adult↗
PubMed2004

The ventriloquist effect results from near-optimal bimodal integration.

Ventriloquism is the ancient art of making one's voice appear to come from elsewhere, an art exploited by the Greek and Roman oracles, and possibly earlier. We regularly experience the effect when watching television and movies, where the voices seem to emanate from the actors' lips rather than from the actual sound source. Originally, ventriloquism was explained by performers projecting sound to their puppets by special techniques, but more recently it is assumed that ventriloquism results from vision "capturing" sound. In this study we investigate spatial localization of audio-visual stimuli. When visual localization is good, vision does indeed dominate and capture sound. However, for severely blurred visual stimuli (that are poorly localized), the reverse holds: sound captures vision. For less blurred stimuli, neither sense dominates and perception follows the mean position. Precision of bimodal localization is usually better than either the visual or the auditory unimodal presentation. All the results are well explained not by one sense capturing the other, but by a simple model of optimal combination of visual and auditory information.

Acoustic Stimulation↗
PubMed2006

Regulation of sperm activation by SWM-1 is required for reproductive success of C. elegans males.

BACKGROUND: Sexual reproduction in animals requires the production of highly specialized motile sperm cells that can navigate to and fertilize ova. During sperm differentiation, nonmotile spermatids are remodeled into motile spermatozoa through a process known as spermiogenesis. In nematodes, spermiogenesis, or sperm activation, involves a rapid cellular morphogenesis that converts unpolarized round spermatids into polarized amoeboid spermatozoa capable of both motility and fertilization. RESULTS: Here we demonstrate, by genetic analysis and in vivo and in vitro cell-based assays, that the temporal and spatial localization of spermiogenesis are critical determinants of male fertility in C. elegans, a male/hermaphrodite species. We identify swm-1 as a factor important for male but not hermaphrodite fertility. We show that whereas in wild-type males, activation occurs after spermatids are transferred to the hermaphrodite, swm-1 mutants exhibit ectopic activation of sperm within the male reproductive tract. This ectopic activation leads to infertility by impeding sperm transfer. The SWM-1 protein is composed of a signal sequence and two trypsin inhibitor-like domains and likely functions as a secreted serine protease inhibitor that targets two distinct proteases. CONCLUSIONS: These findings support a model in which (1) proteolysis acts as an important in vivo trigger for sperm activation and (2) regulating the timing of proteolysis-triggered activation is crucial for male reproductive success. Furthermore, our data provide insight into how a common program of gamete differentiation can be modulated to allow males to participate in reproduction in the context of a male/hermaphrodite species where the capacity for hermaphrodite self-fertilization has rendered them nonessential for progeny production.

Amino Acid Sequence↗
PubMed2004

Investigations of the human visual system using functional magnetic resonance imaging (FMRI).

The application of functional magnetic resonance imaging (fMRI) in studies of the visual system provided significant advancement in our understanding of the organization and functional properties of visual areas in the human cortex. Recent technological and methodological improvements allowed studies to correlate neuronal activity with visual perception and demonstrated the ability of fMRI to observe distributed neural systems and to explore modulation of neural activity during higher cognitive processes. Preliminary applications in patients with visual impairments suggest that this method provides a powerful tool for the assessment and management of brain pathologies. Recent research focuses on obtaining new information about the spatial localization, organization, functional specialization and participation in higher cognitive functions of visual cortical areas in the living human brain and in further establishment of the method as a useful clinical tool of diagnostic and prognostic significance for various pathologic processes affecting the integrity of the visual system. It is anticipated that the combined neuroimaging approach in patients with lesions and healthy controls will provide new insight on the topography and functional specialization of cortical visual areas and will further establish the clinical value of the method for improving diagnostic accuracy and treatment planning.

Brain Diseases↗
PubMed2006

Environmental contamination of heavy metals from zinc smelting areas in Hezhang County, western Guizhou, China.

Total heavy metal (Cd, Cr, Cu, Pb and Zn) concentrations were evaluated in smelting waste, soil, crop and moss samples collected from the Hezhang artisanal zinc smelting areas, Guizhou, China. Soil samples from the cornfield near the smelting sites contained extremely high Cd (5.8-74 mg kg(-1)), Pb (60-14,000 mg kg(-1)) and Zn (260-16,000 mg kg(-1)) concentrations. Elevated heavy metal concentrations were also found in corn plants and total Pb (0.80-1.5 mg kg(-1)) and Cd (0.05-0.76 mg kg(-1)) concentrations in corn grain have totally or partially exceeded the national guidance limits for foodstuff. Thus, the soil-to-crop transfer of heavy metals might pose a potential health risk to the local residents. Similar to the high heavy metal levels in soil and corn, Cd, Cr, Cu, Pb and Zn concentrations in moss samples collected from the smelting sites ranged from 10 to 110, 10 to 55, 26 to 51, 400 to 1200 and 330 to 1100 mg kg(-1), respectively, exhibiting a local spatial pattern of metals deposition from the atmosphere. Based on examination of Zn/Cd and Pb/Cd ratios of the analyzed samples, we have distinguished between the flue gas dust derived and smelting waste derived metals in different environmental compartments.

Animals↗
PubMed2005

Dependence of the DPOAE amplitude pattern on acoustical biasing of the cochlear partition.

Distortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs in response to simultaneous increases in the levels of high frequency primary tones in the presence of a low frequency biasing tone of 30 Hz at 120 dB SPL. The DPOAE amplitudes plotted as functions of the biasing tone phase angle show distinctive repeatable minima, which are identical to the amplitude notches observed for the distortion products at the output of a single saturating non-linearity. The number of the amplitude minima grows with increasing order of the DPOAE, a feature that is also reproduced by the model. The model of DPOAE generation due to a single saturating non-linearity does not explain the experimentally observed asymmetry of the response of the DPOAEs to rising and falling half cycles of the biasing tone. This asymmetry is attributed to a hypothetical mechanism, which adjusts the operating point of the outer hair cell's mechanoelectrical transducer. Experimental data were consistent with a hypothesis that, for the parameters of stimulation used in this study, both lower and upper sideband DPOAEs are dominated by emission generated from a single and spatially localized place in the cochlea.

Acoustic Stimulation↗
PubMed2005

Stereotactic radiosurgery for brain AVMs: role of interobserver variation in target definition on digital subtraction angiography.

PURPOSE: We evaluated the extent of interobserver variation in contouring arteriovenous malformations (AVMs) on digital subtraction angiography (DSA) with respect to volume, spatial localization, and dosimetry and correlated our findings with the clinical outcome. METHODS AND MATERIALS: Thirty-one patients who had undergone radiosurgery for brain AVMs were studied. Six clinicians independently contoured the nidus on the original DSA. As a measure of variation, the ratio between the volumes of agreement and the corresponding encompassing volumes, as well as the absolute positional shift between the individual target volumes were derived. Using the original treatment plan, the dosimetric coverage of the individually contoured volumes with standard collimators was compared with a similar plan using dynamic conformal arcs. RESULTS: The mean contoured nidus volume was 3.6 +/- 5.6 cm3. The mean agreement ratio was 0.45 +/- 0.18 for all possible pairs of observers. The mean absolute positional shift between individually contoured volumes was 2.8 +/- 2.6 mm. These differences were more marked in previously treated groups and tended to be more pronounced in those with treatment failure. The mean coverage of the individual volumes by the 80% prescription isodose was 88.1% +/- 3.2% using conventional collimators and 78.9% +/- 4.4% using dynamic conformal arcs (p = 0.001). CONCLUSION: Substantial interobserver variations exist when contouring brain AVMs on DSA for the purpose of radiosurgical planning. Such variations may result in underdosage to the AVM and, thereby, contribute to treatment failure. The consequences of contouring variations may increase with the use of more conformal radiosurgical techniques.

Adolescent↗
PubMed2005

The utility of accurate mass and LC elution time information in the analysis of complex proteomes.

The combination of mass and normalized elution time (NET) of a peptide identified by liquid chromatography-mass spectrometry (LC-MS) measurements can serve as a unique signature for that peptide. However, the specificity of an LC-MS measurement depends upon the complexity of the proteome (i.e., the number of possible peptides) and the accuracy of the LC-MS measurements. In this work, theoretical tryptic digests of all predicted proteins from the genomes of three organisms of varying complexity were evaluated for specificity. Accuracy of the LC-MS measurement of mass-NET pairs (on a 0 to 1.0 NET scale) was described by bivariate normal sampling distributions centered on the peptide signatures. Measurement accuracy (i.e., mass and NET standard deviations of +/-0.1, 1, 5, and 10 ppm, and +/-0.01 and 0.05, respectively) was varied to evaluate improvements in process quality. The spatially localized confidence score, a conditional probability of peptide uniqueness, formed the basis for the peptide identification. Application of this approach to organisms with comparatively small proteomes, such as Deinococcus radiodurans, shows that modest mass and elution time accuracies are generally adequate for confidently identifying most peptides. For more complex proteomes, more accurate measurements are required. However, the study suggests that the majority of proteins for even the human proteome should be identifiable with reasonable confidence by using LC-MS measurements with mass accuracies within +/-1 ppm and high efficiency separations having elution time measurements within +/-0.01 NET.

Animals↗
PubMed2006

Study of reverse micelles of di-isobutyl-phenoxy-ethoxy-ethyl-dimethyl-benzyl ammonium methacrylate in benzene by nuclear magnetic resonance spectroscopy.

(1)H NMR spectroscopy was used to investigate the aggregation of the surfactant di-isobutyl-phenoxy-ethoxy-ethyl-dimethyl-benzyl ammonium methacrylate (Hyamine-M) in benzene. Adding water makes swollen reverse micelles (microemulsion droplets). The droplets also contain cadmium ions and the sodium salt of the methacrylic acid. The critical micelle concentration of Hyamine-M was determined by NMR to be 3.95 mM under the current conditions. Two-dimensional NMR NOESY spectra were used to study the conformation of the surfactant in the micelle and the spatial localization of water and counterions. We found that the surfactant molecules are folded with both phenyl fragments oriented toward the micelle exterior and the oxyethylene and NCH(3) groups in the micelle core. The water molecules and counterions are distributed around the surfactant polar groups in the micelle interior and penetrate up to both aromatic rings. The investigated system can be further utilized as a microemulsion matrix for the synthesis of cadmium-containing semiconductor nanocrystals, eventually capped with a polymer shell, or of polymer nanoparticles.

Journal Article↗
PubMed2005

Distinct spatial and temporal distribution of ZAP70 and Lck following stimulation of interferon and T-cell receptors.

T-cell receptor (TCR) stimulation results in the recruitment and activation of the proteins ZAP70 and Lck. These two proteins have been implicated in signalling derived from interferon receptors, although their precise role in this independent pathway has not been determined fully. These observations raise a fundamental question of how a given protein in a cell can be involved in more than one signalling pathway, yet each pathway is able to produce a highly specific downstream response to its own stimulant. To maintain exclusivity of response, each pathway must isolate its component molecules chemically, spatially or dynamically from other prevailing pathways. To address this question, the proteins ZAP70 and Lck were investigated following stimulation of the interferon-alpha receptor and the TCR in T cells by two different extracellular stimulants: interferon-alpha and the anti-CD3 antibody, OKT3, respectively. We first demonstrate that ZAP70 plays a pivotal role in interferon-stimulated MAPK activation, and that the tyrosine residue at position 319 of ZAP70 is important for interferon-stimulated ERK activation. Translocation of both ZAP70 and Lck to the nucleus following interferon receptor stimulation is demonstrated for the first time. Fluorescence resonance energy transfer microscopy revealed a high degree of spatial localization of the ZAP70/Lck complex within the cell following IFNalpha stimulation, in contrast to a diffuse presence following the application of OKT3. The difference in the spatio-temporal localization of these proteins following stimulation may eliminate signal crosstalk, and could explain the differentiation of the specific downstream responses of these pathways.

Active Transport, Cell Nucleus↗