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A Gibson

Publications and source records attributed to A Gibson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Electrical impedance tomography of human brain activity with a two-dimensional ring of scalp electrodes.

Previously, electrical impedance tomography (EIT) has been used to image impedance decreases in the exposed cortex of rabbits during brain activity. These are due to increased blood volume at the site of the stimulated cortex; as blood has a lower impedance than brain, the impedance decreases. During human brain activity similar blood flow changes have been detected using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). If blood volume also changes then the impedance of human cortex will change during brain activity; this could theoretically be imaged with EIT. EIT data were recorded from a ring of 16 scalp electrodes in 34 recordings in 19 adult volunteers before, during and after stimulation with (1) a visual stimulus produced by an 8 Hz oscillating checkerboard pattern or (2) sensory stimulation of the median nerve at the wrist by a 3 Hz electrical square wave stimulus. Reproducible impedance changes, with a similar timecourse to the stimulus, were seen in all experiments. Significant impedance changes were seen in 21 +/- 5% (n = 16, mean +/- SEM) and 19 +/- 3% (n = 18) of the electrode measurements for visual and somatosensory paradigms respectively. The reconstructed 2D EIT images showed reproducible impedance changes in the approximate region of the stimulated cortex in 7/16 visual and 5/18 somatosensory experiments. This demonstrates that reproducible impedance changes can be measured during human brain activity. The final images contained spatial noise; the reasons for this and strategies to reduce this in future are discussed.

Adult↗
PubMed2001

Validation of a 3D reconstruction algorithm for EIT of human brain function in a realistic head-shaped tank.

Previous work has demonstrated that electrical impedance tomography can be used to image human brain activity during evoked responses, but two-thirds of the reconstructed images fail to localize an impedance change to the expected stimulated cortical area. The localization failure may be caused by modelling the head as a homogenous sphere in the reconstruction algorithm. This assumption may lead to errors when used to reconstruct data obtained from the human head. In this study a 3D reconstruction algorithm, based on a model of the head as a homogenous sphere, was characterized by simulating the algorithm model, the head shape and the presence of the skull in saline-filled tanks. EIT images of a sponge, 14 cm3 volume with a resistivity contrast of 12%, were acquired in three different positions in tanks filled with 0.2% saline. In a hemispherical tank, 19 cm in diameter, the sponge was localized to within 3.4-10.7% of the tank diameter. In a head-shaped tank, the errors were between 3.1 and 13.3% without a skull and between 10.3 and 18.7% when a real human skull was present. A significant increase in localization error therefore occurs if an algorithm based on a homogeneous sphere is used on data acquired from a head-shaped tank. The increased error is due to the presence of the skull, as no significant increase in error occurred if a head-shaped tank was used without the skull present, compared to the localization error within the hemispherical tank. The error due to the skull significantly shifted the impedance change within the skull towards the centre of the image. Although the increased localization error due to the skull is not sufficient to explain the localization errors of up to 50% of the image diameter present in the images of some human subjects, the future use of a realistic head model in the reconstruction algorithm is likely to reduce the localization error in the human images due to the presence of the skull.

Algorithms↗
PubMed2001

Effects of limb-length discrepancy on gait economy and lower-extremity muscle activity in older adults.

BACKGROUND: The amount of limb-length discrepancy necessary to adversely affect gait parameters in older adults is unknown, with information being largely anecdotal. This investigation was conducted to determine the effects of limb-length discrepancy on gait economy and lower-extremity muscle activity in older adults. METHODS: Forty-four men and women ranging in age from fifty-five to eighty-six years with no evidence of limb-length discrepancy of >1 cm participated in the study. Subjects walked on a treadmill at a self-selected normal walking pace with artificial limb-length discrepancies of 0, 2, 3, and 4 cm applied in a randomly selected order. Indirect calorimetry was used to measure oxygen consumption and minute ventilation. Electromyography was used to measure muscle activity of the right and left quadriceps femoris, plantar flexors, gluteus maximus, and gluteus medius. Heart rate, the rating of perceived exertion, and frequency of gait compensation patterns were also measured. RESULTS: There was a significant increase in oxygen consumption and the rating of perceived exertion with 2, 3, and 4-cm artificial limb-length discrepancies; a significant increase in heart rate, minute ventilation, and quadriceps activity in the longer limb with 3 and 4-cm artificial limb-length discrepancies; and a significant increase in plantar flexor activity in the shorter limb with a 4-cm artificial limb-length discrepancy compared with the same parameters with no artificial limb-length discrepancy. CONCLUSIONS: Both oxygen consumption and the rating of perceived exertion were greater with a 2-cm artificial limb-length discrepancy than they were with no artificial limb-length discrepancy. There appears to be a breakpoint between 2 and 3 cm of artificial limb-length discrepancy in older adults with regard to the effects on most other physiological parameters. A 3-cm artificial limb-length discrepancy is likely to induce significant quadriceps fatigue in the longer limb. Elderly patients with substantial pulmonary, cardiac, or neuromuscular disease may have difficulty walking with a limb-length discrepancy as small as 2 cm.

Aged↗
PubMed2000

Sildenafil citrate on nitrergic transmission in anococcygeus muscles from the urogenital system of male and female mice.

The effects of sildenafil on nitrergic relaxations were compared in anococcygeus muscles from male and female mice. In muscles from both sexes, sildenafil (10-300 nM) produced a weak, direct relaxation of carbachol-induced tone, and increased both the amplitude and duration of nitrergic relaxations. The most marked effect was on nitrergic duration (300-400% increase with 300 nM sildenafil); no differences in potency were observed between male (EC(50), 30 nM) and female (EC(50), 25 nM). The rate of onset for potentiation of nitrergic duration was similar in both sexes; but, on washout, the effects of sildenafil declined more slowly in the male muscle. Relaxations to both nitric oxide (NO) and sodium nitroprusside were also increased in amplitude and duration by 50 nM sildenafil, while those to forskolin and papaverine were unaffected. The results demonstrate that sildenafil causes a similar, potent and selective potentiation of nitrergic transmission in urogenital smooth muscle from both male and female mice.

Animals↗
PubMed2000

Quantitative evaluation of simian immunodeficiency virus infection using NASBA technology.

The most commonly used animal model for the study of HIV-1 infection in humans is the infection of non-human primates by simian immunodeficiency virus (SIV). The animal hosts used most frequently are different species of macaques, which are readily infected with SIV, and can therefore be used to study natural infection, pathogenesis, therapy, and vaccine efficacy. The study of HIV-1 infection in humans relies heavily on the quantification of HIV-1 load (i.e. viral RNA) in patient plasma. Given the importance of HIV-1 RNA levels in humans, it follows that SIV RNA levels in animals are also relevant to the study of infection in this model system. This report describes the development of the isothermal amplification-based NASBA technology for the quantification of SIV RNA load in macaque plasma. Evaluation of the assay using model systems demonstrated that the assay is accurate and reproducible over nearly four orders of magnitude. Viral RNA load data were compared to other infection measurements in the macaque system. Further, the assay was used to provide copy number levels of SIV RNA in macaque plasma samples, permitting characterization of viral load during the course of SIV infection.

Animals↗
PubMed2000

Two-dimensional finite element modelling of the neonatal head.

Electrical impedance tomography (EIT) could allow the early diagnosis of infant brain injury following birth asphyxia. The purpose of this work was to determine the effect of variations in skull, scalp or cerebrospinal fluid (CSF) resistivity, as these vary in clinical conditions and could degrade image quality. These factors were investigated using finite element models of the adult and neonatal head. The results suggest that there is a wide range over which the resistivity of the neonatal skull has little effect on the sensitivity to a central impedance change. The scalp and CSF appear to shunt current away from the brain; when their resistivity was decreased from normal values, this shunting effect increased and caused a decrease in sensitivity to a central resistance change. The resistivity of neonatal skull has not, to our knowledge, been directly measured and will anyway vary within and between individuals; this work suggests that EIT will be relatively insensitive to variations in neonatal skull impedance.

Adult↗
PubMed1999

Characterisation of nitrergic transmission in the isolated anococcygeus muscle of the female mouse.

Field stimulation of anococcygeus muscles from female mice produced frequency-dependent relaxations of carbachol-induced tone, which were independent of the oestrus cycle but were abolished by the nitric oxide synthase (NOS) inhibitor L-N(G)-nitroarginine (L-NOARG; 100 microM) and the soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one (ODQ; 5 microM); L-NOARG inhibition was reversed by L-, but not D-arginine. The selective phosphodiesterase V inhibitor zaprinast (1-130 microM) directly relaxed tone and enhanced both the amplitude and duration of field stimulation-induced relaxations; the effect on amplitude was greater at lower frequencies of stimulation, while increased duration dominated at higher frequencies. The duration, but not the amplitude, of relaxations to exogenous nitric oxide (NO; 15 microM) was also increased by zaprinast. The mouse anococcygeus provides a useful model for pharmacological investigation of nitrergic neurotransmission in female urogenital smooth muscle.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Correlation between store-operated cation current and capacitative Ca2+ influx in smooth muscle cells from mouse anococcygeus.

In mouse anococcygeus cells, simultaneous measurements of membrane currents and changes in intracellular Ca2+ were obtained using "perforated-patch" whole-cell recordings and Fura-2 microfluorimetry. Carbachol (50 microM) and cyclopiazonic acid (10 microM) produced a biphasic inward current; a transient Ca2+-dependent chloride current (I(ClCa)), followed by a smaller, sustained current (I(DOC)) This response was mirrored by a biphasic increase in the intracellular Ca2+ concentration. SKF96365 (1-{beta-[3-(4-methoxyphenyl) propoxyl]-4-methoxyphenethyl}-1H-imidazole; 10 microM) and Cd2+ (100 microM) inhibited both I(DOC) and the sustained increase in intracellular Ca2+; La3+ (400 microM) inhibited neither response. The results confirm that the non-selective cation current I(DOC) underlies capacitative Ca2+ influx supporting sustained contractions in this tonic smooth muscle.

Animals↗
PubMed1999

Assessment and calibration of a low-frequency system for electrical impedance tomography (EIT), optimized for use in imaging brain function in ambulant human subjects.

An EIT system has been produced that has been optimized for imaging impedance changes with scalp electrodes during brain activity in ambulant subjects. It can record from 225 Hz to 65 kHz, has a small headbox on a lead 10 m long, and has software programmable electrode selection. In calibration experiments in a small cylindrical tank filled with potassium chloride solution and samples of cucumber, noise was less than 1% with averaging, and acceptable images were produced at frequencies down to 1800 Hz. This suggests that EIT can be performed at low frequencies, which are likely to give larger signals during brain activity. Future work will include trials in humans and improvement of the current source and isolation.

Brain Chemistry↗
PubMed1999

Subcellular localization and endocytosis of homomeric gamma2 subunit splice variants of gamma-aminobutyric acid type A receptors.

The expression of alpha and beta gamma-aminobutyric acid type A receptor subunits produces GABA-gated channels which require the incorporation of either the gamma2 or gamma3 subunit for benzodiazepine modulation. Here we examine the role of the gamma2 subunit splice variants, gamma2S and gamma2L which differ by eight amino acids in the major intracellular domain, in mediating cell surface expression. Using immunocytochemistry we have demonstrated that when expressed alone, the gamma2S subunit can access the cell surface and internalize constitutively. In contrast, alpha1, beta2 and gamma2L are retained predominantly in the endoplasmic reticulum (ER) when expressed alone. Replacing the insert which differentiates gamma2L from gamma2S (LLRMFSFK) with eight alanines produces a phenotype identical to gamma2S. Both gamma2 subunits fail to produce high molecular weight oligomers observed for alpha1beta2 and alpha1beta2gamma2 heterooligomers and do not form functional ion channels. Surface expression of gamma2S is repressed upon the coexpression of alpha1 or beta2 subunits, resulting in ER-retained heterooligomers, suggesting that homomeric gamma2S is unlikely to occur in vivo. However, its independent maturation to surface competence and preferential assembly with alpha and beta subunits may ensure the production of functional benzodiazepine-sensitive receptors. Furthermore, the presence of the gamma2 subunit appears to confer an endocytotic capacity to these heterooligomeric receptors.

Animals↗
PubMed1999

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells.

The sarcoplasmic reticulum Ca-ATPase inhibitor thapsigargin (Tg; 0.4-100 nM) produced concentration-related, strong and sustained contractions of the mouse-isolated anococcygeus muscle; these contractions were dependent on extracellular calcium but were only partially reduced (by about 50%) in the presence of verapamil (10 and 100 microM). The verapamil-resistant component of the Tg-induced contraction was relaxed by the general calcium entry blockers SKF96365 (0.4-40 microM) and cadmium (50-300 microM), and by the tyrosine kinase inhibitor genistein (10-180 microM). In single smooth muscle cells loaded with Fura-2, addition of Tg (100 nM) to calcium-free medium produced a small, transient increase in fluorescence; subsequent addition of calcium (2.5 mM) produced a larger and sustained increase which was abolished on return to calcium-free conditions, but was only partially reduced by verapamil (10 microM; by about 30%). Manganese quenching of Fura-2 was enhanced in cells treated with Tg. The verapamil-resistant calcium influx was reduced by SKF96365 (20 microM) and to a lesser extent by genistein (40 microM); cadmium (200 microM) produced an initial decrease in fluorescence followed by a marked increase. These results demonstrate that, in the mouse anococcygeus, Tg can cause sustained contractions and elevations of calcium influx in the presence of verapamil; the time-course, calcium dependence and, although to a lesser extent, pharmacology of these effects generally support the proposal that excitation-contraction coupling in this tonic smooth muscle involves sustained capacitative calcium influx.

Animals↗
PubMed1998

Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia.

BACKGROUND: Ataxia is the commonest neurological manifestation of coeliac disease. Some individuals with genetic susceptibility to the disease have serological evidence of gluten sensitivity without overt gastrointestinal symptoms or evidence of small-bowel inflammation. The sole manifestation of disease in such patients may be ataxia. We describe the clinical, radiological, and neurophysiological features of this disorder. METHODS: Patients with ataxia attending the neurology outpatient clinics at the Royal Hallamshire Hospital, Sheffield, UK, were screened for gluten sensitivity as shown by the titre of antibody to gliadin. Those with other causes of ataxia were excluded. We carried out clinical, neurophysiological, neuroradiological, and, in two cases, neuropathological examinations. FINDINGS: 28 patients with gluten ataxia were identified. All had gait ataxia and most had limb ataxia. Those with more severe gait ataxia had longer disease duration. No patient had tremor or other extrapyramidal features. 19 patients showed some form of peripheral neuropathy on neurophysiological examination. 16 patients had no gastrointestinal symptoms. Distal duodenal biopsy showed lymphocytic infiltration in two patients, and changes compatible with coeliac disease in 11. Six patients had evidence of cerebellar atrophy on magnetic-resonance imaging. Necropsy was done on two patients who died; there was lymphocytic infiltration of the cerebellum, damage to the posterior columns of the spinal cord, and sparse infiltration of the peripheral nerves. INTERPRETATION: Gluten sensitivity is an important cause of apparently idiopathic ataxia and may be progressive. The ataxia is a result of immunological damage to the cerebellum, to the posterior columns of the spinal cord, and to peripheral nerves. We propose the term gluten ataxia to describe this disorder.

Adult↗
PubMed1998

Sorting mechanisms regulating membrane protein traffic in the apical transcytotic pathway of polarized MDCK cells.

The transcytotic pathway followed by the polymeric IgA receptor (pIgR) carrying its bound ligand (dIgA) from the basolateral to the apical surface of polarized MDCK cells has been mapped using morphological tracers. At 20 degreesC dIgA-pIgR internalize to interconnected groups of vacuoles and tubules that comprise the endosomal compartment and in which they codistribute with internalized transferrin receptors (TR) and epidermal growth factor receptors (EGFR). Upon transfer to 37 degreesC the endosome vacuoles develop long tubules that give rise to a distinctive population of 100-nm-diam cup-shaped vesicles containing pIgR. At the same time, the endosome gives rise to multivesicular endosomes (MVB) enriched in EGFR and to 60-nm-diam basolateral vesicles. The cup-shaped vesicles carry the dIgA/pIgR complexes to the apical surface where they exocytose. Using video microscopy and correlative electron microscopy to study cells grown thin and flat we show that endosome vacuoles tubulate in response to dIgA/pIgR but that the tubules contain TR as well as pIgR. However, we show that TR are removed from these dIgA-induced tubules via clathrin-coated buds and, as a result, the cup-shaped vesicles to which the tubules give rise become enriched in dIgA/pIgR. Taken together with the published information available on pIgR trafficking signals, our observations suggest that the steady-state concentrations of TR and unoccupied pIgR on the basolateral surface of polarized MDCK cells are maintained by a signal-dependent, clathrin-based sorting mechanism that operates along the length of the transcytotic pathway. We propose that the differential sorting of occupied receptors within the MDCK endosome is achieved by this clathrin-based mechanism continuously retrieving receptors like TR from the pathways that deliver pIgR to the apical surface and EGFR to the lysosome.

Animals↗