PubMed Health⌕ Search

Biomedical subjects

A J Butler

Publications and source records attributed to A J Butler.

At least 19 recordsLinked to original sources
PubMed2006

Visual cortex activation in kinesthetic guidance of reaching.

The purpose of this research was to determine the cortical circuit involved in encoding and controlling kinesthetically guided reaching movements. We used (15)O-butanol positron emission tomography in ten blindfolded able-bodied volunteers in a factorial experiment in which arm (left/right) used to encode target location and to reach back to the remembered location and hemispace of target location (left/right side of midsagittal plane) varied systematically. During encoding of a target the experimenter guided the hand to touch the index fingertip to an external target and then returned the hand to the start location. After a short delay the subject voluntarily moved the same hand back to the remembered target location. SPM99 analysis of the PET data contrasting left versus right hand reaching showed increased (P < 0.05, corrected) neural activity in the sensorimotor cortex, premotor cortex and posterior parietal lobule (PPL) contralateral to the moving hand. Additional neural activation was observed in prefrontal cortex and visual association areas of occipital and parietal lobes contralateral and ipsilateral to the reaching hand. There was no statistically significant effect of target location in left versus right hemispace nor was there an interaction of hand and hemispace effects. Structural equation modeling showed that parietal lobe visual association areas contributed to kinesthetic processing by both hands but occipital lobe visual areas contributed only during dominant hand kinesthetic processing. This visual processing may also involve visualization of kinesthetically guided target location and use of the same network employed to guide reaches to visual targets when reaching to kinesthetic targets. The present work clearly demonstrates a network for kinesthetic processing that includes higher visual processing areas in the PPL for both upper limbs and processing in occipital lobe visual areas for the dominant limb.

Adult↗
PubMed2005

Functional magnetic resonance imaging and transcranial magnetic stimulation: effects of motor imagery, movement and coil orientation.

OBJECTIVE: To compare fMRI activations during movement and motor imagery to corresponding motor evoked potential (MEP) maps obtained with the TMS coil in three different orientations. METHODS: fMRI activations during executed (EM) and imagined (IM) movements of the index finger were compared to MEP maps of the first dorsal interosseus (FDI) muscle obtained with the TMS coil in anterior, posterior and lateral handle positions. To ensure spatial registration of fMRI and MEP maps, a special grid was used in both experiments. RESULTS: No statistically significant difference was found between the TMS centers of gravity (TMS CoG) obtained with the three coil orientations. There was a significant difference between fMRI centers of gravity during IMs (IM CoG) and EMs (EM CoG), with IM CoGs localized on average 10.3mm anterior to those of EMs in the precentral gyrus. Most importantly, the IM CoGs closely matched cortical projections of the TMS CoGs while the EM CoGs were on average 9.5mm posterior to the projected TMS CoGs. CONCLUSIONS: TMS motor maps are more congruent with fMRI activations during motor imagery than those during EMs. These findings are not significantly affected by changing orientation of the TMS coil. SIGNIFICANCE: Our results suggest that the discrepancy between fMRI and TMS motor maps may be largely due to involvement of the somatosensory component in the EM task.

Adult↗
PubMed2001

Disordered sensorimotor transformations for reaching following posterior cortical lesions.

Preparation for reaches to visual targets depends on sensorimotor transformations (SMT) between target and limb coordinate systems. To examine neural substrates for SMT, we studied 19 individuals with focal lesions of the visual association cortices and white matter and 11 control subjects without brain lesions. SMT were assessed by measuring accuracy of reaches to remembered locations of visually presented targets. Results showed abnormally large SMT errors in all individuals with inferior parietal lobule (IPL) lesions and some subjects with lesions of the temporo-occipital regions and in occipital area 19. Types of abnormal errors (direction or distance) varied between subjects with similar lesions, e.g. IPL. Patterns of abnormality included dissociations of distance and direction errors and of constant and variable errors. These findings are compatible with the hypothesis of different systems for guiding distance and direction of reaches distributed among structures in superior and inferior visual association cortex.

Adult↗
PubMed2000

Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia, USA.

Pediatric emergency room visits for asthma were studied in relation to air quality indices in a spatio-temporal investigation of approximately 130,000 visits (approximately 6,000 for asthma) to the major emergency care centers in Atlanta, Georgia, during the summers of 1993-1995. Generalized estimating equations, logistic regression, and Bayesian models were fitted to the data. In logistic regression models comparing estimated exposures of asthma cases with those of the nonasthma patients, controlling for temporal and demographic covariates and using residential zip code to link patients to spatially resolved ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative risk for particulate matter less than or equal to 10 microm in aerodynamic diameter (PM10) was 1.04 per 15 microg/m3 (p < 0.05). Exposure-response trends (p < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p = 0.003) and PM10 (>60 microg/m3 vs. <20 microg/m3: odds ratio = 1.26, p = 0.004). In models with ozone and PM10, both terms became nonsignificant because of collinearity of the variables (r= 0.75). The other analytical approaches yielded consistent findings. This study supports accumulating evidence regarding the relation of air pollution to childhood asthma exacerbation.

Adolescent↗
PubMed1999

Poly(ADP-ribose) polymerase binds with transcription enhancer factor 1 to MCAT1 elements to regulate muscle-specific transcription.

Striated muscle-specific expression of the cardiac troponin T (cTNT) gene is mediated through two MCAT elements that act via binding of transcription enhancer factor 1 (TEF-1) to the MCAT core motifs and binding of an auxiliary protein to nucleotides flanking the 5' side of the core motif. Using DNA-protein and protein-protein binding experiments, we identified a 140-kDa polypeptide that bound both the muscle-specific flanking sequences of the most distal MCAT1 element and TEF-1. Screening of an expression library with the MCAT1 element yielded a cDNA encoding a truncated form of poly(ADP-ribose) polymerase (PARP). Endogenous PARP from embryonic tissue nuclear extracts migrated as a 140-kDa protein. Recombinant full-length PARP preferentially bound the wild-type MCAT1 element and was shown to physically interact with TEF-1. In addition, endogenous TEF-1 could be coimmunoprecipitated with PARP from extracts of primary skeletal muscle cells. Recombinant PARP was able to ADP-ribosylate TEF-1 in vitro. Inhibition of the enzymatic activity of PARP repressed expression of an MCAT1-dependent reporter in transiently transfected primary muscle cells. Together, these data implicate PARP as the auxiliary protein that binds with TEF-1 to the MCAT1 element to provide muscle-specific gene transcription.

Amino Acid Transport Systems, Basic↗
PubMed1998

Temporal and spatial distributions of ozone in Atlanta: regulatory and epidemiologic implications.

Relationships between ambient levels of selected air pollutants and pediatric asthma exacerbation in Atlanta were studied retrospectively. As a part of this study, temporal and spatial distributions of ambient ozone concentrations in the 20-county. Atlanta metropolitan area during the summers of 1993, 1994, and 1995 were assessed. A universal kriging procedure was used for spatial interpolation of aerometric monitoring station data. In this paper, the temporal and spatial distributions of ozone are described, and regulatory and epidemiologic implications are discussed. For the study period, the Atlanta ozone nonattainment area based on the 1-h, exceedance-based standard of 0.12 ppm is estimated to expand--from 56% of the Atlanta MSA by area and 71% by population to 88% by area and 96% by population--under the new 8-h, concentration-based standard of 0.08 ppm. Regarding asthma exacerbation, a 4% increase in pediatric asthma rate per 20-ppb increase in ambient ozone concentration was observed (p-value = 0.001), with ambient ozone level representing a general indicator of air quality due to its correlations with other pollutants. The use of spatial ozone estimates in the epidemiologic analysis demonstrates the need for control of demographic covariates in spatiotemporal assessments of associations of ambient air pollutant concentrations with health outcome.

Air Pollution↗
PubMed1997

Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs.

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.

Adult↗
PubMed1996

Visual perceptions of head-fixed and trunk-fixed anterior/posterior axes.

The purpose of the present experiment was to determine the preferred visual "straight ahead" or anterior/posterior (a/p) axis at the perceptual level. The ability of 12 neurologically normal, young adult subjects to position a rod parallel to the head and trunk a/p axes while viewing eccentrically located visual targets were studied under six conditions: 1. fixed-subjects stood erect with the head aligned to the trunk and viewed a central target while visually aligning a hand-held rod to the head and trunk a/p axis. 2. eyes-subjects moved only their eyes to view eccentric targets and aligned the rod to the head and trunk a/p axis. 3. head-trunk-subjects viewed the eccentric targets by rotating the head about a vertical axis and aligned the rod to the trunk a/p axis. 4. head-head-subjects viewed the targets as in 3 and positioned the rod parallel to the head a/p axis. 5. trunk-head-subjects viewed the targets by rotating the trunk and head as a unit about the vertical axis and aligned the rod parallel to the head a/p axis (note that the head and trunk a/p axes were misaligned by the experimenter prior to target viewing). 6. trunk-trunk-subjects viewed targets as in 5 and positioned the rod parallel to the trunk a/p axis. Subjects performed 25-35 consecutive trials within each condition. Perceptual errors were similar for aligning the rod to the trunk and head a/p axes; however, moving the trunk produced much larger constant and variable perceptual errors than moving the head. In a second experiment, four subjects controlled the position of a lighted rod held by a robot arm in complete darkness. They were instructed to align the rod to either the head or trunk a/p axis under conditions similar to the fixed, head-trunk, and head-head tasks described above. Perceptual errors were much larger when aligning the rod to the head a/p axis than to trunk a/p axis when the head was moved. This shows that the trunk a/p axis is clearly preferred at the perceptual level when visual background cues are not present. These data strongly suggest that the visual coordinate system uses a trunk-fixed a/p axis to define the subjective straight-ahead direction and right/left position of a target. Implications of these findings for sensorimotor transformations in control of upper limb movements to visual targets are discussed.

Adult↗
PubMed1995

COUP-TF II homodimers are formed in preference to heterodimers with RXR alpha or TR beta in intact cells.

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses the transcriptional activity of a number of nuclear receptors, including that of retinoid receptors (RAR and RXR) and thyroid hormone receptors (TR). Since COUP-TF is capable of binding to DNA in vitro either as a homodimer or as a heterodimer with RXR or TR, it has not been possible to distinguish between competitive DNA binding and heterodimer formation as a mechanism to account for the repression. Using a two-hybrid system we have investigated the dimerisation properties of COUP-TF II in intact cells. In conditions where COUP-TF II homodimers and RXR alpha-RAR alpha heterodimers were formed we were unable to detect the formation of heterodimers between COUP-TF II and RXR alpha. Moreover, we were unable to detect an interaction between COUP-TF II and RXR alpha on DNA. Similarly COUP-TF II homodimers and RXR alpha-TR beta heterodimers are favoured over COUP-TF II-TR beta heterodimers. We conclude that the formation of functionally inactive heterodimers is unlikely to represent a general mechanism by which COUP-TF represses the transcriptional activity of nuclear receptors and favour a model in which repression is mediated by COUP-TF homodimers competing for binding to DNA.

Animals↗
PubMed1993

Variations in soleus H-reflexes as a function of plantarflexion torque in man.

The purpose of this study was to evaluate the effects of the levels of voluntary isometric contraction on the Hoffman reflex in human soleus and medial gastrocnemius (MG) muscles. H-reflexes were recorded in sixteen healthy adults at each of 16 isometric plantarflexion (pf) torque levels ranging from 0-100% of their maximum voluntary isometric contraction (MVC) and were elicited at two intensities of stimulation: (i) supramaximal for M-response and (ii) a submaximal stimulus that produced an H-reflex in soleus that was 50% of maximum H-reflex at rest. The H-reflex peak-to-peak amplitudes were linearly related to pf torque levels ranging from 0 to 50% MVC at both supramaximal and submaximal stimulus intensities. The slope of this relationship was higher for the submaximal stimulation. Beyond 60% of MVC, the soleus H-reflex amplitude showed no further increase with increasing pf torque for both stimulus intensities. Thus, beyond 50-60% of MVC the soleus H-reflex does not provide an accurate measure of soleus motor neuron pool excitability. Further experimental results showed that the H-reflex amplitude at a given torque level depended on whether torque was increasing or decreasing. When torque was increasing, the amplitude of the H-reflex was larger than when the same torque was maintained at a constant level. In contrast, if the torque was decreasing, amplitude of the reflex was lower than when torque was increasing. Therefore, variations in H-reflex amplitudes at a given torque level may be more closely correlated to the direction of the ongoing contraction than to the actual muscle force being produced at the time the H-reflex is elicited.

Adult↗
PubMed1991

Induction of the proliferative phenotype in differentiated myogenic cells by hypoxia.

The effect of cellular differentiation on the response of cells to hypoxic stress has been evaluated using the myogenic cell line BC3H1. Aerobic myocytes were predominantly in G0/G1 of the cell cycle and could be induced into S and G2/M of the cell cycle only by replating in high serum-containing medium at subconfluent cell density. In contrast, hypoxic myocytes demonstrated marked progression into S and G2/M upon reoxygenation without replating in the presence of serum. This modulation of myocytes by hypoxia was suggested further by the induction of 100-kDa and 9-kDa proteins (PSP 100 and PSP 9) which were otherwise only detectable in myoblasts. Two-dimensional gel analysis of newly synthesized proteins demonstrated that the five major glucose/oxygen-regulated proteins (GRP/ORP 260, 150, 100, 80, and 33) were induced in hypoxic myogenic cells independent of their state of differentiation. In addition to the GRP/ORPs, synthesis of 20 and 23 other major proteins was influenced in myocytes and myoblasts, respectively. The bulk of these alterations in myoblasts (70%) were inhibitions. In contrast, 75% of the alterations in myocyte protein synthesis were either enhancements or inductions. The data show that hypoxia can modulate the myocyte phenotype and invoke proliferative characteristics. Moreover, the data suggest that ischemia will have a different effect on and prognosis for tissues with a high mitotic index compared with differentiated tissues.

Animals↗
PubMed1991

The effects of retinoic acid on heart formation in the early chick embryo.

The vitamin A derivative retinoic acid has previously been shown to have teratogenic effects on heart development in mammalian embryos. The craniomedial migration of the precardiac mesoderm during the early stages of heart formation is thought to depend on a gradient of extracellular fibronectin associated with the underlying endoderm. Here, the effects of retinoic acid on migration of the precardiac mesoderm have been investigated in the early chick embryo. When applied to the whole embryo in culture, the retinoid inhibits the craniomedial migration of the precardiac mesoderm resulting in a heart tube that is stunted cranially, while normal or enlarged caudally. Similarly, a local application of retinoic acid to the heart-forming area disrupts the formation of the cardiogenic crescent and the subsequent development of a single mid-line heart tube. This effect is analogous to removing a segment of endoderm and mesoderm across the heart-forming area and results in various degrees of cardia bifida. At higher concentrations of retinoic acid and earlier developmental stages, two completely separate hearts are produced, while at lower concentrations and later stages there are partial bifurcations. The controls, in which the identical operation is carried out except that dimethyl sulphoxide (DMSO) is used instead of the retinoid, are almost all normal. We propose that one of the teratogenic effects of retinoic acid on the heart is to disrupt the interaction between precardiac cells and the extracellular matrix thus inhibiting their directed migration on the endodermal substratum.

Animals↗
PubMed1987

Multi-centre open study of a triphasic levonorgestrel-ethinyloestradiol combined oral contraceptive ('Trinordiol').

A long-term, multi-centre open study was carried out to evaluate the efficacy, cycle control and side-effects with a triphasic, combined oral contraceptive containing levonorgestrel and ethinyloestradiol ('Trinordiol'). A total of 2517 women completing at least 1 cycle of treatment was followed up at 2 to 3-monthly intervals; the overall number of cycles on treatment was 37,090. During treatment, only 2 pregnancies occurred which were attributable to pill failure. Cycle control was good: cycle irregularities were 9.6% overall, but were most common (19.6%) during the first 3 cycles. Only 3.8% of patients withdrew from the study for this reason. Side-effects were those commonly seen with oral contraceptives, and they produced a drop-out rate of only 13.9%. There were no clinically significant effects on blood pressure or body weight. The results also suggested that 'Trinordiol' has a beneficial effect on pre-existing acne.

Acne Vulgaris↗
PubMed1987

A low-dose triphasic oral contraceptive.

Controlled clinical investigations of a three-phase, low-dose oral contraceptive combination of levonorgestrel and ethinyl estradiol were conducted at 17 sites in the United States and 60 sites in the United Kingdom. A day 1 start in cycle one with no backup contraception was used. A total of 3546 female volunteers participated in 35,036 cycles. Medication was missed in 2688 (7.7%) cycles. Nine pregnancies were reported for an uncorrected use-effectiveness rate of 0.33 per 100 woman-years. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of side effects was very low. No clinically significant variations in blood pressure means or weight means were observed. Carbohydrate and lipid metabolism studies were limited to 6 months and showed minimal alterations. Subject compliance with the preparation was excellent. It is concluded that this triphasic oral contraceptive with its varying ratios of levonorgestrel and ethinyl estradiol is an effective, predictable, and well-tolerated combination oral contraceptive.

Adolescent↗
PubMed1976

Computerization of a large antenatal serology service.

A computer scheme for a large antenatal serology service is described. A primary request form (for mother, father or child) has been developed. Standard reports are produced by the computer and are issued with a tear-off slip which should accompany subsequent specimens. Complicated reports are made by special letter. An instruction booklet is issued to all users. Information on patients and clinically significant antibodies is held in a special computer file and is regularly updated. The system provides an efficient and reliable day-to-day service and readily accessible data for retrospective research. A brief note on the computer elements of the system is provided.

Computers↗