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Biomedical subjects

W S Warren

Publications and source records attributed to W S Warren.

At least 19 recordsLinked to original sources

All-ultraviolet time-resolved coherent anti-Stokes Raman scattering.

We report all-UV coherent anti-Stokes Raman scattering (CARS) in calcite with 250-280 nm pump, Stokes, probe, and anti-Stokes light. UV CARS efficiency is approximately 7x higher than for comparable scattering in the visible, 480-540 nm. Time-resolved UV CARS reveals lengthening of the dephasing time of 1086 cm(-1) CO3(2-) internal vibrations from 4 to 7 ps with increasing vibrational excitation, consistent with a phonon depletion model.

Journal Article↗

Experimental characterization of intermolecular multiple-quantum coherence pumping efficiency in solution NMR.

The behavior of intermolecular multiple-quantum coherences in a variety of simple liquids with different chemical and magnetic properties is investigated experimentally and modeled by numerical simulations based on modified Bloch equations. The effects of spin concentration, temperature, intramolecular conformational flexibility, chemical exchange, and spin-spin coupling on the formation of high-order coherences are examined. It is shown that any process that makes the Larmor frequency time-dependent may interfere with the formation of these coherences. Good agreement is achieved between experiments and simulation, using independently known values of the magnetization density, the rate constants for translational diffusion, spin-spin and spin-lattice relaxation, and radiation damping.

Algorithms↗

High-resolution, >1 GHz NMR in unstable magnetic fields.

Resistive or hybrid magnets can achieve substantially higher fields than those available in superconducting magnets, but their spatial homogeneity and temporal stability are unacceptable for high-resolution NMR. We show that modern stabilization and shimming technology, combined with detection of intermolecular zero-quantum coherences (iZQCs), can remove almost all of the effects of inhomogeneity and drifts, while retaining chemical shift differences and J couplings. In a 25-T electromagnet (1 kHz/s drift, 3 kHz linewidth over 1 cm(3)), iZQC detection removes >99% of the remaining inhomogeneity, to generate the first high-resolution liquid-state NMR spectra acquired at >1 GHz.

Chemical Phenomena↗

Resurrection of crushed magnetization and chaotic dynamics in solution NMR spectroscopy.

We show experimentally and theoretically that two readily observed effects in solution nuclear magnetic resonance (NMR)-radiation damping and the dipolar field-combine to generate bizarre spin dynamics (including chaotic evolution) even with extraordinarily simple sequences. For example, seemingly insignificant residual magnetization after a crusher gradient triggers exponential regrowth of the magnetization, followed by aperiodic turbulent spin motion. The estimated Lyapunov exponent suggests the onset of spatial-temporal chaos and the existence of chaotic attractors. This effect leads to highly irreproducible experimental decays that amplify minor nonuniformities such as temperature gradients. Imaging applications and consequences for other NMR studies are discussed.

Journal Article↗

Intermolecular zero-quantum coherence imaging of the human brain.

The first intermolecular zero-quantum coherence (iZQC) MR images of the human brain at 4T are presented. To generate iZQC images, a modified echo-planar imaging pulse sequence was used which included an additional 45 degrees RF pulse and a correlation gradient. The observability and nonconventional contrast of human brain iZQC images at 4T is demonstrated. Axial images are presented for various pulse sequence parameters, and a zero-quantum relaxation map is obtained.

Brain↗

Numerical studies of intermolecular multiple quantum coherences: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI.

A fast, efficient numerical algorithm is used to study intermolecular zero-quantum coherences (iZQCs) and double-quantum coherences (iDQCs) in two applications where the three-dimensional structure of the magnetization is important: high-resolution NMR in inhomogeneous fields and contrast enhancement in MRI. Simulations with up to 2 million coupled volume elements (256 x 256 x 32) show that iZQCs can significantly narrow linewidths in the indirectly detected dimension of systems with inhomogeneous fields and explore the effects of shape and orientation of the inhomogeneities. In addition, this study shows that MR images from iZQC and iDQC CRAZED pulse sequences contain fundamentally new contrast, and a modified CRAZED pulse sequence (modCRAZED) can isolate the contrast from chemically inequivalent spins.

Algorithms↗

Functional magnetic resonance imaging with intermolecular multiple-quantum coherences.

For the first time, we demonstrate here functional magnetic resonance imaging (fMRI) using intermolecular multiple-quantum coherences (iMQCs). iMQCs are normally not observed in liquid-state NMR because dipolar interactions between spins average to zero. If the magnetic isotropy of the sample is broken through the use of magnetic field gradients, dipolar couplings can reappear, and hence iMQCs can be observed. Conventional (BOLD) fMRI measures susceptibility variations averaged over each voxel. In the experiment performed here, the sensitivity of iMQCs to frequency variations over mesoscopic and well-defined distances is exploited. We show that iMQC contrast is qualitatively and quantitatively different from BOLD contrast in a visual stimulation task. While the number of activated pixels is smaller in iMQC contrast, the intensity change in some pixels exceeds that of BOLD contrast severalfold.

Brain↗

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Animals↗

Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue.

White adipose tissue (WAT) is innervated by postganglionic sympathetic nervous system (SNS) neurons, suggesting that lipid mobilization could be regulated by the SNS [T. G. Youngstrom and T. J. Bartness. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R744-R751, 1995]. A viral transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), was used to identify the origins of the SNS outflow from the brain to WAT neuroanatomically. PRV was injected into epididymal or inguinal WAT (EWAT and IWAT, respectively) of Siberian hamsters and IWAT of rats. PRV-infected neurons were visualized by immunocytochemistry and found in the spinal cord, brain stem (medulla, nucleus of the solitary tract, caudal raphe nucleus, C1 and A5 regions), midbrain (central gray), and several areas within the forebrain. The general pattern of infection of WAT in both species was more similar than different and resembled that seen after PRV injections into the adrenal medulla in rats (A. M. Strack, W. B. Sawyer, J. H. Hughes, K. B. Platt, and A. D. Loewy. Brain Res. 491: 156-162, 1989). EWAT versus IWAT injected hamsters had relatively less labeling in the suprachiasmatic, dorsomedial, and arcuate nuclei. Overall, it appeared that the SNS innervation of WAT originates from the general SNS outflow of the central nervous system and therefore may play a significant role in lipid mobilization.

Adipose Tissue↗

Quantum treatment of intermolecular multiple-quantum coherences with intramolecular J coupling in solution NMR.

A recently introduced density matrix picture for dipolar effects in solution NMR (1996, J. Chem. Phys. 105, 874) gave complete solutions for intermolecular multiple-quantum coherences for single-component samples without scalar couplings. This paper, for the first time, shows that this quantum picture can lead to explicit signal expressions for multicomponent samples of molecules with internal scalar couplings (here assumed to generate a first-order spectrum) and long-range dipolar couplings. Experimental observation of a triplet in the indirectly detected dimension for a heteronuclear CRAZED sequence (13CHCl3 sample, ZQ or 2Q coherences) gives clear evidence that the coupling is due to the intermolecular dipolar coupling. We also make comparisons with classical pictures which introduce the dipolar demagnetization field in multicomponent spin systems.

Magnetic Resonance Spectroscopy↗

False-positive results of genetic testing in cystic fibrosis.

We describe a patient in whom newborn immunoreactive trypsin screening and mutation analysis suggested a diagnosis of cystic fibrosis; however, the clinical course and sweat test results were not consistent with the diagnosis. Direct sequencing of the patient's genomic DNA showed compound heterozygosity for delta F508 and F508C, a polymorphism not associated with clinical disease.

Cystic Fibrosis↗

Homogeneous NMR spectra in inhomogeneous fields.

Researchers interested in high-resolution nuclear magnetic resonance (NMR) spectroscopy have long sought higher magnetic fields to enhance resolution and simplify spectra. Magnets with substantially larger fields than those available in the best commercial spectrometers are available, but the inhomogeneity is unacceptable for high-resolution spectra. A detection method (termed HOMOGENIZED) is presented that removes inhomogeneity while retaining chemical shift differences and J couplings. With existing inhomogeneous magnets, this method could nearly double the largest resonance frequency available for high-resolution NMR. The HOMOGENIZED sequence is based on observations of intermolecular zero-quantum coherences between a solute molecule and solvent molecules that are micrometers away; as long as the field is homogeneous over this short distance, sharp resonances are recovered without echoes. Experimental demonstrations and a detailed density matrix theory to explain the effect are presented.

Aprotinin↗

Imaging with intermolecular multiple-quantum coherences in solution nuclear magnetic resonance.

A magnetic resonance imaging technique based on intermolecular multiple-quantum coherences in solution (the correlated spectroscopy revamped by asymmetric z gradient echo detection or CRAZED experiment) is described here. Correlations between spins in different molecules were detected by magnetic-field gradient pulses. In order for a correlation to yield an observable signal, the separation between the two spins must be within a narrow band that depends on the area of the gradient pulses. The separation can be tuned from less than 10 micrometers to more than 1 millimeter, a convenient range for many applications.

Acetone↗

The role of MRI when relapsing polychondritis is suspected but not proven.

Relapsing polychondritis (RP), while relatively rare, presents a characteristic clinical picture. Based upon a symptom complex of auricular, nasal, and respiratory chondritis associated with ocular and otic complaints, diagnosis can frequently be made with confidence in the absence of histologic confirmation. We present a case where a therapeutic intervention was required without sufficient criteria for diagnosis. Magnetic resonance imaging (MRI) proved useful in initial evaluation and allowed follow-up imaging demonstrating a gratifying response to steroid treatment. We believe that MRI has an important role in the diagnosis and subsequent evaluation of patients with proven or suspected RP, particularly those with tracheal involvement.

Airway Obstruction↗

The pineal gland: photoreception and coupling of behavioral, metabolic, and cardiovascular circadian outputs.

Although removal of the pineal gland has been shown to have very little effect on the mammalian circadian system in constant darkness (DD), several recent reports have suggested that the mammalian pineal gland may be more important for circadian organization in nocturnal rodents than was previously believed. Removal of the pineal gland (PINX) facilitates the disruptive effects of constant bright light on wheel-running rhythmicity. This suggests at least two possibilities for the role of the pineal gland in the mammalian circadian system. First, pinealectomized rats may perceive ambient light intensity to be brighter than do sham-operated (SHAM) rats. Second, the pineal gland, probably via its secretion of melatonin, may also be involved in coupling components of the circadian system. Coupling, as we see it, may occur at several levels of organization: (1) between retinohypothalamic afferents and suprachiasmatic nuclei (SCN) oscillatory neurons, (2) among multiple SCN oscillators, (3) between the SCN and their multiple outputs, and/or (4) among the multiple circadian outputs themselves. In this study we show that PINX rats free-run with a longer period in four different light intensities than do SHAM rats. Moreover, the rate of increase of tau is greater among PINX rats than among SHAM rats. This supports the first hypothesis. We also show that in PINX rats the circadian rhythms of wheel running, general activity, body temperature, and heart rate are all more disrupted in constant bright light than are those of SHAM rats, and each rhythmic output is disrupted in parallel. This supports the second hypothesis. Melatonin is probably not involved in coupling presynaptic elements of SCN afferents in the retinohypothalamic tract to pacemaking cells within the SCN, since enucleation has no effect on SCN 2-[125I]iodomelatonin (IMEL) binding. Together the data do not discount either of the two hypotheses but do restrict the possible levels at which the pineal gland is involved in coupling. These data also further support a growing body of literature indicating that the pineal gland and its hormone melatonin play a role in mammalian circadian organization.

Animals↗

The suprachiasmatic nucleus controls the circadian rhythm of heart rate via the sympathetic nervous system.

The mammalian suprachiasmatic nucleus (SCN) controls a wide variety of circadian behavioral and physiological processes. The specific motor output pathway(s) by which these diverse processes are controlled are unknown. The only established motor output of this system is the regulation of pineal melatonin synthesis via the sympathetic nervous system. It is therefore possible that other peripheral circadian rhythms are regulated similarly. To address this issue, body temperature (BT), general activity (GA), wheel-running activity (WR), and heart rate (HR) were recorded in laboratory rats, and the effects of SCN lesion (SCNX) and of pharmacological sympathectomy with guanethidine (GUAN) on these multiple circadian rhythms were determined. The SCNX abolished circadian patterns in all motor outputs, whereas sham animals showed robust rhythms in all measures. In contrast, guanethidine, which depleted peripheral but not central catecholamine content, selectively reduced HR circadian rhythmicity. Other rhythms (BT, GA, and WR) were unaffected. These results suggest that the SCN influences some peripheral targets via circadian regulation of the sympathetic nervous system, and other circadian outputs are regulated via different, unknown pathways.

Animals↗

Differential binding of Pseudomonas aeruginosa to normal and cystic fibrosis tracheobronchial mucins.

Pseudomonas aeruginosa infection is a leading cause of deterioration of pulmonary function in patients with cystic fibrosis (CF). The interaction of the bacterium with CF and non-CF tracheobronchial mucins was examined to understand the biochemical basis for the high susceptibility of the lungs of CF patients to infection by P.aeruginosa. The binding of radiolabelled bacteria to pure mucins in solid-phase assays was not significantly above non-specific binding to various blocking agents, such as bovine serum albumin, Tween 20, milk powder and polyvinyl pyrrolidine. Further, there was a tendency for the bacteria to be excluded from plastic wells and membranes coated with mucin. Therefore, an indirect approach involving the binding of radiolabelled P.aeruginosa to asialo GM1 ganglioside, the putative receptor for the bacteria on tracheal cells, was used to compare the interaction of CF and non-CF mucins with the bacteria. Highly purified preparations of CF mucin were consistently better inhibitors of the binding of the bacteria to asialo GM1 ganglioside than non-CF mucin preparations. In the case of the binding of a stable mucoid strain, the difference was statistically significant (P < 0.001) at all concentrations of mucin tested. For the non-mucoid strain, the difference was significant only at the higher concentrations. Of the saccharides tested similarly, sialyl lactose and the oligosaccharide portion of asialo GM1 were found to be good inhibitors. The increased binding of the bacteria to CF mucin was further confirmed by a solution binding assay in which the binding of 125I-labelled mucin to unlabelled bacteria was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗