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Biomedical subjects

P Teale

Publications and source records attributed to P Teale.

At least 37 records · Page 2Linked to original sources

MEG based brain laterality: sex differences in normal adults.

Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips were recorded from 34 normal adults (17 males, 17 females) and the 100 msec latency component (M100) localized in left and right hemispheres. Absolute M100 location in the antero-posterior dimension was calculated for each subject. M100 sources were significantly further anterior in the right hemisphere of males. Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a subset of 17 subjects showed that in the left STG of both males and females M100 sources were located approximately midway on the STG. In the right hemisphere of males, however, M100 sources were significantly further anterior on the STG than was the case for females. The findings are compatible with a sex based difference in right STG functional anatomy, with evidence of greater hemispheric lateralization in males compared to females based upon a predominantly right hemisphere contribution.

Adult↗

Schizophrenia may alter neuromagnetic representations of attention.

When male paranoid schizophrenic subjects attended to a dichotic oddball task requiring target discrimination, their 100-ms latency left hemisphere magnetic auditory sources did not increase in strength, and their source geometry appeared to be degraded, rather than enhanced, compared with normal control subjects, implicating abnormal processing in the superior temporal gyrus.

Adult↗

Analysis of endogenous human endothelin peptides by high-performance liquid chromatography and mass spectrometry.

The three isoforms of both endothelin (ET) and big ET are not readily distinguishable by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) alone. We have previously used high-performance liquid chromatography (HPLC) linked with RIA to determine ET isoforms in various tissue extracts, and cell supernatants. Our aim was to confirm that the isoforms of ET secreted by human umbilical vein endothelial cells (HUVECs) are ET-1 and big ET-1, using HPLC linked to electrospray mass spectrometry (ESI-MS). Authentic synthetic peptide standards were used to obtain the specific ions for ET isoforms and to calculate their retention times on the HPLC system. ET-1, [Met7]-sulfoxy ET-1, ET-2, ET-3, and big ET-1 could all be separated by HPLC and by specific ions on ESI-MS. Pooled supernatant (500 ml) from 50 cultures of HUVECs was applied first to an anti-C-terminal ET-1 immunoaffinity column and then to an anti-C-terminal big ET-1 immunoaffinity column. The eluates were solid phase-extracted and then injected onto an HPLC system linked to ESI-MS. Peaks of mass intensity at the specific ions and retention times corresponding to ET-1, [Met7]-sulfoxy ET-1, and big ET-1 were found in these eluates. However, no signal was present for ET-2 or ET-3. These data confirm that HUVECs in culture produce ET-1, [Met7]-sulfoxy ET-1, and big ET-1.

Cells, Cultured↗

Magnetic auditory source imaging in macaque monkey.

We recorded magnetic auditory evoked fields from the left hemisphere of a 2-year-old 3.4 kg Macaca nemestrina monkey. Three separate components were isolated from each of three data sets with latencies of approximately 22 ms, 46 ms, and 130 ms after stimulus onset. The 46 ms latency component had clear extrema values and was selected for localization. Field values from 21 recording points were used to estimate the 3-D source location of the 46 ms latency component, termed the M46. High resolution MR images of the brain provided information for correlation of neuroanatomic structure with source location. The neuroanatomic source was found to lie in the superior aspect of the temporal lobes bilaterally. We believe the M46 is the macaque analog of the human M100. Recording of auditory evoked fields in nonhuman primates offers a valuable animal model for studying neurophysiology of human magnetoencephalographically (MEG) determined auditory sources.

Acoustic Stimulation↗

Auditory M100 component 1: relationship to Heschl's gyri.

This study was designed to localize the neuroanatomic generator of the 100 ms latency magnetic auditory evoked field (EF) component (M100) activated by an unattended tone pip. Magnetic EFs in response to 25 ms duration, 90 dB, 1 kHz tone pips were recorded from both hemispheres of nine normal adults, five males and four females, using a seven-channel second-order gradiometer. The source of the M100 was estimated, with confidence intervals, by a least squares based inverse solution algorithm. Magnetic resonance (MR) images of the brain were acquired with a 1.5 T system using a standard head coil. The superior temporal gyri (STG) were manually segmented from 1.7 mm thick coronal images, and the superior surfaces were then rendered from the 3-D volume data. Translation and rotation matrices were identified to locate the magnetoencephalography (MEG) determined sources within the reconstructed STGs. This population of 18 STGs in 9 individuals demonstrated two transverse gyri in 4 of 9 left hemispheres, and 5 of 9 right hemispheres. All 9 left hemisphere M100 sources were in or included Heschl's gyrus(i) in the confidence intervals. Seven of the 9 included Heschl's gyrus(i) on the right: the remaining two, both males, had sources slightly anterior to Heschl's gyrus(i). We conclude that all M100 source location estimates were compatible with an auditory koniocortex source in or adjacent to Heschl's gyri.

Adult↗

Neuropsychological test performance and MEG-based brain lateralization: sex differences.

Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from left and right hemispheres of 9 normal males and 12 normal females. Source location of the 100 ms latency component (M100) was localized to superior temporal lobes bilaterally using an inverse solution algorithm. All subjects also were administered the Wechsler block design and visual reproduction subtests, and the California Verbal Learning Test (CVLT). M100 source locations demonstrated significant sex differences in interhemispheric asymmetry. Males had source locations further anterior than females, with the differences most pronounced in the right hemisphere. Expected sex differences were found in neuropsychological test performance, with males performing better on block design ad visual reproduction, and females performing better on the CVLT. Across both sexes, block design scores correlated significantly with right hemisphere M100 location, with more anterior source locations associated with better performance. CVLT scores were negatively correlated with right hemisphere M100 source locations. These findings suggest MEG-based measures of interhemispheric asymmetry may be related to specific neuropsychological test performance measures.

Acoustic Stimulation↗

ELISA screening with GC-MS confirmation of the tranquilizer chlorprothixene administered in subtherapeutic doses to horses.

A commercially available generic promazine ELISA kit is available which shows cross-reactivity for the tranquilizer chlorprothixene (CPT). The ELISA test readily detects the presence of CPT or its metabolites in equine urine for up to 24 h after the i.v. and i.m. administration of sub-therapeutic doses (4.5 mg) to three horses. Maximum concentrations (CPT equivalents) are obtained 2 h after i.v. dosing. No distinct concentration peak values are observed after i.m. administration. Following solid-phase extraction, confirmation of CPT and its metabolites by electron impact mass spectrometry after sub-therapeutic administration is not successful. The use of chemical ionization mass spectrometry however revealed the presence of at least four metabolites including; chlorprothixene sulphoxide, hydroxylated chlorprothixene and hydroxylated chlorprothixene sulphoxide.

Animals↗

Auditory magnetic source localization in twins.

We recorded magnetoencephalographic (MEG) auditory evoked fields (EF) from the L and R hemispheres of 12 paris of twins, 6 monozygotic (MZ), and 6 dizygotic (DZ) and localized the source of the 100 msec latency EF component termed the M100. M100 sources exhibited greater similarity in location in MZ twin pairs, especially in the L hemisphere. These findings support the hypothesis that the functional location of processing of nonmeaningful unattended auditory stimuli may depend more heavily on left hemisphere structures. Furthermore, genetic effects are evident in these left hemisphere structures and their activity, as is a substantial amount of environmental variance.

Acoustic Stimulation↗

The development of a gas chromatographic/mass spectrometric screening procedure to detect the administration of anabolic steroids to the horse.

A screening procedure for anabolic steroid residues in horse urine has been developed based upon solid-phase extraction and gas chromatographic/mass spectrometric analysis in the selected ion mode. For moderate sample throughput the method provides a viable alternative to radioimmunoassay screening and has advantages over the latter technique due to its flexibility, specificity and ability to detect a number of steroids in a single analysis. Full automation of the gas chromatographic/mass spectrometric analysis is an additional feature of the methodology.

Anabolic Agents↗

Magnetic auditory M100 source location in normal females.

We recorded magnetoencephalographic auditory evoked fields from the left and right hemispheres of six normal adult female subjects, in response to unattended tone pips. Magnetic field data was used to estimate location, orientation, depth, and strength of the 100-ms latency evoked field component (M100). M100 source locations did not significantly differ in left and right hemispheres. Previous studies in six normal males demonstrated M100 sources to be significantly further anterior in the right hemisphere. Compared to the previously reported male subjects, M100 sources in the right hemisphere of these females were significantly further posteriorly, by a mean value of 2.1 cm. These findings, while preliminary, support sex-related functional and/or structural differences in the superior temporal lobe, and would be compatible with the female right temporal planum extending further posteriorly. They suggest MEG recordings may be a useful addition to studies of sex-related difference in brain function and/or structure.

Adult↗

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine.

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. [16,16(-2)H2]Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize [2H5]testosterone to [2H4]estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Allantois↗

The excretion of theobromine in Thoroughbred racehorses after feeding compounded cubes containing cocoa husk--establishment of a threshold value in horse urine.

Thoroughbred geldings were fed racehorse cubes containing a predetermined concentration of theobromine in the form of cocoa husk. They were offered 7 kg of cubes per day, divided between morning and evening feed, and food consumption was monitored. Urinary concentrations of theobromine were determined following the consumption of cubes containing 11.5, 6.6, 2.0 and 1.2 mg per kg of theobromine, to verify whether or not such concentrations would produce positive urine tests. Pre-dose urine samples were collected to verify the absence of theobromine before each experiment. It became apparent from the results of the first three administrations that the limit of detection of theobromine, using such procedures, would be reached at a feed level of about 1 mg per kg theobromine. Therefore the final administration, using cubes containing 1.2 mg per kg theobromine, was singled out for additional analytical work and quantitative procedures were developed to measure urinary concentrations of theobromine. It was anticipated that the results would form a basis for discussions relating to the establishment of a threshold value for theobromine in horse urine. The Stewards of the Jockey Club subsequently gave notice that they had established a threshold level for theobromine in urine of 2 micrograms/ml.

Animal Feed↗

Comparison of the use of mass spectrometry and methylene unit values in the determination of the stereochemistry of estranediol, the major urinary metabolite of 19-nortestosterone in the horse.

The stereochemistry of an isomer of 5-estrane-3,17 alpha-diol, the major metabolite of 19-nortestosterone in horse urine has been established by the use of methylene unit (MU) values. The empirical MU values of the bis-trimethylsilyl (TMS) derivatives of the eight available isomers of 5-androstane-3,17-diol and four isomers of 5-estrane-3,17 beta-diol were determined by capillary gas chromatography using three different columns. From this data the theoretical MU values for the bis-TMS derivatives of the four 5-estrane-3,17 alpha-diol isomers were predicted. Comparison of the experimentally determined MU value of the urinary metabolite with those of the theoretical values established the correct stereochemistry of the steroid. This method has been compared with the use of gas chromatography-mas spectrometry in the determination of the stereochemistry of unknown metabolites.

Animals↗

Late auditory magnetic sources may differ in the left hemisphere of schizophrenic patients. A preliminary report.

We recorded magnetoencephalographic auditory evoked fields from the left and right hemispheres of six medicated, paranoid schizophrenic subjects and six normal controls. The magnetic field data were used in estimating the location, orientation, and depth of the source generating the 100-millisecond latency evoked field component (M100). The M100 latencies were slightly shorter than simultaneously recorded vertex electroencephalographic evoked potential N100 latencies, suggesting that magnetoencephalographic and electroencephalographic recordings were examining slightly different aspects of the source(s). The M100 sources demonstrated substantial interhemispheric asymmetry in normal controls, and were located more posteriorly, with more nearly vertical orientations, over the left hemisphere. The M100 sources in schizophrenics did not exhibit the same interhemispheric asymmetry. Left hemisphere source orientation differed significantly between normal controls and schizophrenics. Discriminant function analysis correctly classified normal controls and schizophrenics at 100% using the conservative jackknife procedure on the basis of left hemisphere orientation alone. Our findings, while preliminary, support altered left hemisphere function, or possibly structure, in this group of schizophrenic subjects, and suggest that magnetoencephalographic recordings may be a useful research method in this major mental illness.

Adult↗

Gas chromatographic and gas chromatographic/tandem mass spectrometric characterization of precursors on the sesterterpene pathway for steroid biosynthesis.

An increasing amount of evidence is accumulating to support the proposal that steroidogenesis can occur by a sesterterpene pathway as well as the cholesterol pathway. Key intermediates on the sesterterpene pathway are 23,24-dinor-5-cholen-3 beta-ol (guneribol) and some of its metabolites, e.g. 23,24-dinor-4-cholen-3-one (guneribone). It has been reported that these intermediates are biosynthesized and converted to steroid hormones by a range of endocrine tissues in vitro. Monitoring the pentafluorobenzyloxime derivatives by negative ion chemical ionization mass spectrometry in the electron capture mode provided evidence for the presence of guneribone in extracts of bovine testicular and human adrenal tumour tissue. Complementary evidence was obtained from gas chromatographic/tandem mass spectrometric data generated on a triple-quadrupole instrument by monitoring daughter ions (in the multiple ion detection, MID mode) of the molecular anion of derivatized guneribone in both standards and tissue extracts. The present findings that sesterterpene pathway intermediates are present as endogenous compounds in tissue extracts, together with the previously reported radiochemical data, give further support to the sesterterpene pathway hypothesis.

Adrenal Gland Neoplasms↗

Source origin of a 50-msec latency auditory evoked field component in young schizophrenic men.

We recorded auditory evoked magnetic fields in response to 128 15-msec duration 1-KHz tone pips from both hemispheres of 6 young schizophrenic men. Auditory evoked potentials were recorded conventionally from a vertex lead. The approximately 50-msec latency component was identified in both the magnetic (M50) and electroencephalographic (EEG) (P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. Magnetic resonance imaging was used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the planum temporale in both left and right hemispheres in all subjects. Normal inter-hemispheric asymmetry (with respect to external bony landmarks) of the M50 source was not found in this patient group. Additionally, left (but not right) hemisphere source anatomy differed in several respects from data previously reported in normals.

Adult↗