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Biomedical subjects

E R Flynn

Publications and source records attributed to E R Flynn.

At least 19 recordsLinked to original sources
PubMed2005

A biomagnetic system for in vivo cancer imaging.

An array of highly sensitive biomagnetic sensors of the superconducting quantum interference detector (SQUID) type can identify disease in vivo by detecting and imaging microscopic amounts of nanoparticles. We describe in detail procedures and parameters necessary for implementation of in vivo detection through the use of antibody-labelled magnetic nanoparticles as well as methods of determining magnetic nanoparticle properties. We discuss the weak field magnetic sensor SQUID system, the method of generating the magnetic polarization pulse to align the magnetic moments of the nanoparticles, and the measurement techniques to measure their magnetic remanence fields following this pulsed field. We compare these results to theoretical calculations and predict optimal properties of nanoparticles for in vivo detection.

Animals↗
PubMed2003

A model for frequency dependence of conductivities of the live human skull.

A mathematical model (sigma(omega) approximately equal to A omega alpha, where, sigma is identical with conductivity, omega = 2 pi f is identical with applied frequency (Hz), A (amplitude) and alpha (unit less) is identical with search parameters) was used to fit the frequency dependence of electrical conductivities of compact, spongiosum, and bulk layers of the live and, subsequently, dead human skull samples. The results indicate that the fit of this model to the experimental data is excellent. The ranges of values of A and alpha were, spongiform (12.0-36.5, 0.0083-0.0549), the top compact (5.02-7.76, -0.137-0.0144), the lower compact (2.31-10.6, 0.0267-0.0452), and the bulk (7.46-10.6, 0.0133-0.0239). The respective values A and alpha for the respective layers of the dead skull samples were (40.1-89.7, -0.0017-0.0287), (5.53-14.5, -0.0296 - -0.0061), (4.58-15.9, -0.0226-0.0268), and (12.7-25.3, -0.0158-0.0132).

Algorithms↗
PubMed2002

Conductivities of three-layer live human skull.

Electrical conductivities of compact, spongiosum, and bulk layers of the live human skull were determined at varying frequencies and electric fields at room temperature using the four-electrode method. Current, at higher densities that occur in human cranium, was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured. We used a model that considers variations in skull thicknesses to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the conductivities of the spongiform (16.2-41.1 milliS/m), the top compact (5.4-7.2 milliS/m) and lower compact (2.8-10.2 milliS/m) layers of the skull have significantly different and inhomogeneous conductivities. The conductivities of the skull layers are frequency dependent in the 10-90 Hz region and are non-ohmic in the 0.45-2.07 A/m2 region. These current densities are much higher than those occurring in human brain.

Adolescent↗
PubMed2001

Functionally separate intracellular Ca2+ stores in smooth muscle.

In smooth muscle, release via the inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)R) and ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR) controls oscillatory and steady-state cytosolic Ca(2+) concentrations ([Ca(2+)](c)). The interplay between the two receptors, itself determined by their organization on the SR, establishes the time course and spatial arrangement of the Ca(2+) signal. Whether or not the receptors are co-localized or distanced from each other on the same store or whether they exist on separate stores will significantly affect the Ca(2+) signal produced by the SR. To date these matters remain unresolved. The functional arrangement of the RyR and Ins(1,4,5)P(3)R on the SR has now been examined in isolated single voltage-clamped colonic myocytes. Depletion of the ryanodine-sensitive store, by repeated application of caffeine, in the presence of ryanodine, abolished the response to Ins(1,4,5)P(3), suggesting that Ins(1,4,5)P(3)R and RyR share a common Ca(2+) store. Ca(2+) release from the Ins(1,4,5)P(3)R did not activate Ca(2+)-induced Ca(2+) release at the RyR. Depletion of the Ins(1,4,5)P(3)-sensitive store, by the removal of external Ca(2+), on the other hand, caused only a small decrease ( approximately 26%) in caffeine-evoked Ca(2+) transients, suggesting that not all RyR exist on the common store shared with Ins(1,4,5)P(3)R. Dependence of the stores on external Ca(2+) for replenishment also differed; removal of external Ca(2+) depleted the Ins(1,4,5)P(3)-sensitive store but caused only a slight reduction in caffeine-evoked transients mediated at RyR. Different mechanisms are presumably responsible for the refilling of each store. Refilling of both Ins(1,4,5)P(3)-sensitive and caffeine-sensitive Ca(2+) stores was inhibited by each of the SR Ca(2+) ATPase inhibitors thapsigargin and cyclopiazonic acid. These results may be explained by the existence of two functionally distinct Ca(2+) stores; the first expressing only RyR and refilled from [Ca(2+)](c), the second expressing both Ins(1,4,5)P(3)R and RyR and dependent upon external Ca(2+) for refilling.

Animals↗
PubMed2000

Two Ca2+ entry pathways mediate InsP3-sensitive store refilling in guinea-pig colonic smooth muscle.

Sarcolemma Ca2+ influx, necessary for store refilling, was well maintained, over a wide range (-70 to + 40 mV) of membrane voltages, in guinea-pig single circular colonic smooth muscle cells, as indicated by the magnitude of InsP3-evoked Ca2+ transients. This apparent voltage independence of store refilling was achieved by the activity of sarcolemma Ca2+ channels some of which were voltage gated while others were not. At negative membrane potentials (e.g. -70 mV), Ca2+ influx through channels which lacked voltage gating provided for store refilling while at positive membrane potentials (e.g. +40 mV) voltage-gated Ca2+ channels were largely responsible. Sarcolemma voltage-gated Ca2+ currents were not activated following store depletion. Removal of external Ca2+ or the addition of the Ca2+ channel blocker nimodipine (1 microM) inhibited store refilling, as assessed by the magnitude of InsP3-evoked Ca2+ transients, with little or no change in bulk average cytoplasmic Ca2+ concentration. One hypothesis for these results is that the store may refill from a high subsarcolemma Ca2+ gradient. Influx via channels, some of which are voltage gated and others which lack voltage gating, may permit the establishment of a subsarcolemma Ca2+ gradient. Store access to the gradient allows InsP3-evoked Ca2+ signalling to be maintained over a wide voltage range in colonic smooth muscle.

Aniline Compounds↗
PubMed2000

Kir3.1/3.2 encodes an I(KACh)-like current in gastrointestinal myocytes.

Expression of the Kir3 channel subfamily in gastrointestinal (GI) myocytes was investigated. Members of this K(+) channel subfamily encode G protein-gated inwardly rectifying K(+) channels (I(KACh)) in other tissues, including the heart and brain. In the GI tract, I(KACh) could act as a negative feedback mechanism to temper the muscarinic response mediated primarily through activation of nonselective cation currents and inhibition of delayed-rectifier conductance. Kir3 channel subfamily isoforms expressed in GI myocytes were determined by performing RT-PCR on RNA isolated from canine colon, ileum, duodenum, and jejunum circular myocytes. Qualitative PCR demonstrated the presence of Kir3.1 and Kir3.2 transcripts in all smooth muscle cell preparations examined. Transcripts for Kir3.3 and Kir3.4 were not detected in the same preparations. Semiquantitative PCR showed similar transcriptional levels of Kir3.1 and Kir3.2 relative to beta-actin expression in the various GI preparations. Full-length cDNAs for Kir3.1 and Kir3.2 were cloned from murine colonic smooth muscle RNA and coexpressed in Xenopus oocytes with human muscarinic type 2 receptor. Superfusion of oocytes with ACh (10 microM) reversibly activated a Ba(2+)-sensitive and inwardly rectifying K(+) current. Immunohistochemistry using Kir3.1- and Kir3.2-specific antibodies demonstrated channel expression in circular and longitudinal smooth muscle cells. We conclude that an I(KACh) current is expressed in GI myocytes encoded by Kir3.1/3.2 heterotetramers.

Acetylcholine↗
PubMed1999

Inward rectifier potassium conductance regulates membrane potential of canine colonic smooth muscle.

1. The membrane potential of gastrointestinal smooth muscles determines the open probability of ion channels involved in rhythmic electrical activity. The role of Ba2+-sensitive K+ conductances in the maintenance of membrane potential was examined in canine proximal colon circular muscle. 2. Application of Ba2+ (1-100 microM) to strips of tunica muscularis produced depolarization of cells along the submucosal surface of the circular muscle layer. Significantly higher concentrations of Ba2+ were needed to depolarize preparations from which the submucosal and myenteric pacemaker regions were removed. 3. Elevation of extracellular [K+]o (from 5.9 to 12 mM) brought membrane potentials closer to EK (the Nernst potential for K+ ions), suggesting activation of a K+ conductance. This occurred at potentials much more negative than the activation range for delayed rectifier channels (Kv). 4. Forskolin (1 microM) caused hyperpolarization and a leftward shift in the dose-response relationship for Ba2+, suggesting that forskolin may activate a Ba2+-sensitive conductance. 5. Patch-clamp recordings from interstitial cells of Cajal (ICC) revealed the presence of a Ba2+-sensitive inward rectifier potassium conductance. Far less of this conductance was present in smooth muscle cells. 6. Kir2.1 was expressed in the circular muscle layer of the canine proximal colon, duodenum, jejunum and ileum. Kir2.1 mRNA was expressed in greater abundance along the submucosal surface of the circular muscle layer in the colon. 7. These results demonstrate that ICC express a Ba2+-sensitive conductance (possibly encoded by Kir2.1). This conductance contributes to the generation and maintenance of negative membrane potentials between slow waves.

Animals↗
PubMed1999

Single vs. paired visual stimulation: superposition of early neuromagnetic responses and retinotopy in extrastriate cortex in humans.

Neuromagnetic techniques were used in conjunction with magnetic resonance imaging (MRI) techniques to: (1) localize and characterize cortical sources evoked by visual stimuli presented at different locations in the lower right visual field; (2) examine the superposition of cortical responses by comparing the summation of responses to the presentation of single stimuli with responses to paired stimuli; and (3) examine the spatial resolution of magnetoencephalographic (MEG) techniques by comparing the identified source locations evoked by the presentation of single vs. paired stimuli. Using multi-dipole, non-linear minimization analyses, three sources were localized for each stimulus condition during the initial 80-170 ms poststimulus interval for all subjects. In addition to an occipital source, two extrastriate sources were identified: occipital-parietal and occipital-temporal. Each source evidenced a systematic shift in location associated with changes in stimulus placement parallel to the vertical meridian. To our knowledge, this is the first demonstration of retinotopic organization of extrastriate areas, using non-invasive neuromagnetic techniques. The paired presentation of stimuli reflected superposition of the responses evoked by single stimuli but only for early activity up to 150 ms poststimulus. Undersummation was evident after 150 ms. All sources identified for single stimuli were also identified in the paired-stimulus responses; but at the expense of larger errors for some of the estimated parameters.

Evoked Potentials, Visual↗
PubMed1999

Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells.

1. The molecular nature of the strong inward rectifier K+ channel in vascular smooth muscle was explored by using isolated cell RT-PCR, cDNA cloning and expression techniques. 2. RT-PCR of RNA from single smooth muscle cells of rat cerebral (basilar), coronary and mesenteric arteries revealed transcripts for Kir2.1. Transcripts for Kir2.2 and Kir2.3 were not found. 3. Quantitative PCR analysis revealed significant differences in transcript levels of Kir2.1 between the different vascular preparations (n = 3; P < 0.05). A two-fold difference was detected between Kir2.1 mRNA and beta-actin mRNA in coronary arteries when compared with relative levels measured in mesenteric and basilar preparations. 4. Kir2.1 was cloned from rat mesenteric vascular smooth muscle cells and expressed in Xenopus oocytes. Currents were strongly inwardly rectifying and selective for K+. 5. The effect of extracellular Ba2+, Ca2+, Mg2+ and Cs2+ ions on cloned Kir2.1 channels expressed in Xenopus oocytes was examined. Ba2+ and Cs+ block were steeply voltage dependent, whereas block by external Ca2+ and Mg2+ exhibited little voltage dependence. The apparent half-block constants and voltage dependences for Ba2+, Cs+, Ca2+ and Mg2+ were very similar for inward rectifier K+ currents from native cells and cloned Kir2.1 channels expressed in oocytes. 6. Molecular studies demonstrate that Kir2.1 is the only member of the Kir2 channel subfamily present in vascular arterial smooth muscle cells. Expression of cloned Kir2.1 in Xenopus oocytes resulted in inward rectifier K+ currents that strongly resemble those that are observed in native vascular arterial smooth muscle cells. We conclude that Kir2.1 encodes for inward rectifier K+ channels in arterial smooth muscle.

Animals↗
PubMed1998

Multi-start downhill simplex method for spatio-temporal source localization in magnetoencephalography.

A multi-start downhill simplex method is examined as a global minimization technique for fitting multidipole, spatio-temporal magnetoencephalography (MEG) data. This procedure has been performed on both simulated and empirical human visual data, known to exhibit complex field patterns due to multiple sources. Unlike some other non-linear fitting techniques the multi-start downhill simplex method does not require users to provide initial guesses for the dipole parameters, hence the fitting procedure is less time-consuming, more objective, and user-friendly. In addition, this method offers more than one adequate solution thus providing a range of uncertainty for the estimated parameters. The Multi-start downhill simplex method is used to fit the non-linear dipole spatial parameters, while the linear temporal parameters are fit using a separate linear fitting procedure. Singular value decomposition (SVD) is also used in order to improve the procedure for determining the adequate number of modeled dipoles.

Brain Mapping↗
PubMed1998

Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles.

Kv2.2, homologous to the shab family of Drosophila voltage-gated K+ channels, was isolated from human and canine colonic circular smooth muscle-derived mRNA. Northern hybridization analysis performed on RNA prepared from tissues and RT-PCR performed on RNA isolated from dispersed and selected smooth muscle cells demonstrate that Kv2.2 is expressed in smooth muscle cells found in all regions of the canine gastrointestinal (GI) tract and in several vascular tissues. Injection of Kv2.2 mRNA into Xenopus oocytes resulted in the expression of a slowly activating K+ current (time to half maximum current, 97 +/- 8.6 ms) mediated by 15 pS (symmetrical K+) single channels. The current was inhibited by tetraethylammonium (IC50 = 2.6 mM), 4-aminopyridine (IC50 = 1.5 mM at +20 mV), and quinine (IC50 = 13.7 microM) and was insensitive to charybdotoxin. Low concentrations of quinine (1 microM) were used to preferentially block the slow component of the delayed rectifier current in native colonic myocytes. These data suggest that Kv2.2 may contribute to this current in native GI smooth muscle cells.

4-Aminopyridine↗
PubMed1991

A neuromagnetic study of selective auditory attention.

Auditory event-related magnetic fields and electrical potentials were recorded from subjects who were instructed to attend to a sequence of constant pitch tones presented to one ear and ignore a concurrent sequence of tones with a different pitch presented to the other ear. Subjects' task was to detect and count longer duration 'target' tones (P = 0.1) interspersed with 'standard' tones (P = 0.4) in the attended ear and to ignore tones (both standards and targets) in the other ear. All stimuli, both attended and ignored, elicited a prominent response approximately 100 msec after tone onset (N1m). Beginning approximately 150 msec following stimulus onset, an attention-dependent modulation of the magnetic response (Ndm) was observed for each subject. In 2 subjects whose magnetic field patterns were mapped in detail, equivalent current dipole (ECD) modeling was used to estimate the sources of N1m and Ndm activity. By transforming the coordinate systems for magnetic resonance images (MRIs) and ECD solutions, the locations and orientations of ECDs were determined relative to each subject's brain structures. ECDs for both N1m and Ndm were located in auditory cortex along the posterior regions of the sylvian fissure. Monte Carlo error analyses indicated that the ECD for Ndm is near, but significantly anterior to that for N1m.

Adult↗
PubMed1989

Magnetoencephalographic comparison of cortical sensorimotor extrema evoked by flexion of index finger and thumb.

A seven sensor array (6 sensors equally spaced on a 4 cm dia. with 1 sensor at the center) was used to differentiate two close sensorimotor sources (voluntary movements of right index finger and right thumb). Magnetic field amplitude data was analyzed from a single-session recording (single sensor-array location). The sensor array was positioned to record the peak magnetic field amplitude (an extremum) of one or both digits (analyzed at 145 ms after the electromyogram). An extremum was obtained by plotting a topographic field map and also by mathematical interpolation (both) from the seven-sensor amplitudes while at a fixed location. This method of analysis graphically showed digit extrema separation in all subjects over the negative extrema and thus separation of the neural generator populations at this specific time. Statistical significance of the seven sensor amplitudes was examined by null hypotheses testing. The digit extrema separation (over the negative extrema) was influenced by errors primarily due to noise, signal-to-noise ratio = 6 +/- 2.4, and the subjects' variability in digit flexion. This analysis eliminated sensor array position error and minimized the analysis time to a single session. From the plotted distribution of extrema pertaining to a particular flexion (same subject), obtained from repeated sessions, a mean extrema location for each digit was determined. In this manner, a separation between the digit extrema was demonstrated. The mapped distribution also provided a clear display of the error in plotting extrema locations. For both digits the error in mapping extrema locations (negative only) was 0.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Mapping↗
PubMed1979

Effects of pre- and post-natal lead on affective behavior and learning in the rat.

Literature relevant to the relationship between early ingestion of inorganic lead and subsequent hyperactivity in rodents is discussed. Original research in the area is presented. Rats so exposed were not hyperactive in any of the situations investigated or under any of the dosage regimens employed. They did show hypoactivity in the open field when dosed over a prolonged period. Using a new behavior measure, lead-treated rats were found to be less active than controls in the passive avoidance situation. The possible utility of this new measure for behavioral and developmental toxicology is discussed. It is concluded that the available evidence does not support the contention that a meaningful relationship exists between early lead ingestion and hyperactive behavior. It is suggested that future research may more profitably be directed to assessing the effects of lead ingestion on behavior in stressful or fear provoking situations.

Affect↗
PubMedDate not supplied

Management of antibiotic-resistant organisms in the rehabilitation setting.

Preventing the spread of infection is a team effort. Development and use of rehabilitation-based infection control practices for control of ARO nosocomial infections must be a priority for rehabilitation research. Ongoing infection control surveillance of ARO presence, along with monitoring of resistance patterns, equips infection control practitioners with scientific data to identify appropriate barriers for use in the rehabilitation setting. Modification of antimicrobial usage may offer hope for reversing some of the damage done. With the assistance of physicians, infection control practitioners, laboratory personnel and others, we can prevent the spread of these dangerous organisms.

Enterococcus↗
PubMedDate not supplied

Nonlinear analysis of biological systems using short M-sequences and sparse-stimulation techniques.

The m-sequence pseudorandom signal has been shown to be a more effective probing signal than traditional Gaussian white noise for studying nonlinear biological systems using cross-correlation techniques. The effectiveness is evidenced by the high signal-to-noise (S/N) ratio and speed of data acquisition. However, the "anomalies" that occur in the estimations of the cross-correlations represent an obstacle that prevents m-sequences from being more widely used for studying nonlinear systems. The sparse-stimulation method for measuring system kernels can help alleviate estimation errors caused by anomalies. In this paper, a "padded sparse-stimulation" method is evaluated, a modification of the "inserted sparse-stimulation" technique introduced by Sutter, along with a short m-sequence as a probing signal. Computer simulations show that both the "padded" and "inserted" methods can effectively eliminate the anomalies in the calculation of the second-order kernel, even when short m-sequences were used (length of 1023 for a binary m-sequence, and 728 for a ternary m-sequence). Preliminary experimental data from neuromagnetic studies of the human visual system are also presented, demonstrating that the system kernels can be measured with high signal-to-noise (S/N) ratios using short m-sequences.

Computer Simulation↗