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Biomedical subjects

M F James

Publications and source records attributed to M F James.

At least 19 recordsLinked to original sources
PubMed2001

Detection of pharmacologically mediated changes in cerebral activity by functional magnetic resonance imaging: the effects of sulpiride in the brain of the anaesthetised rat.

Blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was used to study the effects of the D(2)-like receptor selective antagonist, sulpiride, at 2 Tesla in the brain of the alpha-chloralose anaesthetised rat. Region of interest (ROI) analysis indicated significant (P<0.05) bilateral increases in BOLD signal intensity in the frontal cortex following a single administration of sulpiride (10 mg/kg i.v.). BOLD signal changes were slow in onset and increased gradually during the experiment, reaching 8.0+/-0.5% (mean+/-S.E.M.) above pre-injection control values 165 min after drug administration. Signal increases remained high at the experiment end (3 h post sulpiride administration). Sulpiride (30 mg/kg i.v.) had a similar effect in the frontal cortex, increasing signal 5.2+/-1.8% above control values by 174 min; its effects were, however, more variable between rats, and were not statistically significant. Sulpiride (3 mg/kg i.v.) had no significant effect upon BOLD signal intensity in any brain region. No dose of sulpiride resulted in any significant BOLD signal changes in the striatum or cerebellum. These data are supportive of the notion that sulpiride causes an increase in frontal dopaminergic function by antagonism of presynaptically located dopamine D(2) receptors in this brain region, consistent with its therapeutic action. Furthermore, the utility of BOLD contrast fMRI as a means of detecting changes in neuronal activity contingent upon the administration of a psychoactive pharmacological agent has been demonstrated.

Animals↗
PubMed2001

The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association.

The neurofibromatosis 2 protein product merlin, named for its relatedness to the ezrin, radixin and moesin (ERM) family of proteins, is a tumour suppressor whose absence results in the occurrence of multiple tumours of the nervous system, particularly schwannomas and meningiomas. Merlin's similarity to ERMs suggests that it might share functions, acting as a link between cytoskeletal components and the cell membrane. The N-terminus of merlin has strong sequence identity to the N-terminal actin-binding region of ezrin; here we describe in detail the merlin-actin interaction. Employing standard actin co-sedimentation assays, we have determined that merlin isoform 2 binds F-actin with an apparent binding constant of 3.6 microM and a stoichiometry of 1 mol of merlin per 11.5 mol of actin in filaments at saturation. Further, solid-phase binding assays reveal that merlin isoforms 1 and 2 bind actin filaments differentially, suggesting that the intramolecular interactions in isoform 1 might hinder its ability to bind actin. However, merlin does not bind G-actin. Studies of actin filament dynamics show that merlin slows filament disassembly with no influence on the assembly rate, indicating that merlin binds along actin filament lengths. This conclusion is supported by electron microscopy, which demonstrates that merlin binds periodically along cytoskeletal actin filaments. Comparison of these findings with those reported for ERM proteins reveal a distinct role for merlin in actin filament dynamics.

Actins↗
PubMed2001

Caspase mRNA expression in a rat model of focal cerebral ischemia.

Proteins of the caspase family are involved in the signalling pathway that ultimately leads to programmed cell death (apoptosis), which has been reported to occur in some experimental models of stroke. In a previous paper we used quantitative reverse transcription and polymerase chain reaction (RT-PCR) to characterise changes in the mRNA expression of one member of this family, caspase-3, in a rat model of permanent focal ischemia. Here we have used this technique to study the expression of a further three caspases which are involved in different aspects of caspase signalling. Caspase-8, involved in Fas-mediated apoptosis, was upregulated in the cortex of ischemic rats. Caspase-11, which leads to the synthesis of the functional form of the cytokine interleukin-1 beta, also showed increased expression, but with a different temporal profile from caspase-8. In contrast, caspase-9, which forms part of the pathway signalling through the mitochondria, showed a decrease in expression. The expression of a further four caspases (1, 2, 6 and 7) has also been characterised in a simpler experiment. These caspases all showed distinctive patterns of expression following the induction of ischemia. These data lead us to conclude that caspase expression as a whole is under very strict transcriptional control in this model. Certain elements of caspase signalling, such as the Fas-induced pathway and the events upstream of IL-1 beta processing, are upregulated, while others are not. This may be due to some form of genetic program activated in response to ischemia in the brain and may highlight which biological pathways are modulated.

Animals↗
PubMed2001

Cortical spreading depression and migraine: new insights from imaging?

The possibility that spreading depression (SD) of cortical activity, a phenomenon observed in all vertebrates, causes the aura of migraine remains an open question in spite of nearly half a century of investigation. SD is also thought to be associated with the progressive neuronal injury observed during cerebral ischaemia. Thus, the ability to detect and investigate SD in humans might prove clinically significant. Animal studies of cortical spreading depression (CSD) have benefited greatly from the advent of relatively non-invasive imaging techniques. The use of these new imaging techniques for clinical studies will accelerate progress in this area of neurobiology.

Animals↗
PubMed2001

Mapping of brain activation in response to pharmacological agents using fMRI in the rat.

Functional MRI (fMRI) was used to investigate the effects of psychotropic compound activity in the rat brain in vivo. The effects of dizocilpine (MK-801) an N-methyl-D-aspartate receptor antagonist and m-chlorophenylpiperazine (mCPP), a 5-HT(2b/2c)-receptor agonist on rat brain activity were investigated over a time interval of about 1 h and the results were compared to published glucose utilisation and cerebral blood flow data. Signal magnitude increases were observed predominantly in limbic regions following MK-801 administration (0.5 mg/kg i.v) whereas signal decreases were restricted to neocortical areas; a characteristic, time dependent pattern of regional changes evolved from the thalamic nuclei to cortical regions. In contrast, mCPP (25 mg/kg i.p) produced gradual signal intensity increases in limbic and motor regions with signal decreases restricted to the visual, parietal and motor cortices. The results from both compounds show remarkable similarity with autoradiographic measurements of cerebral blood flow and glucose uptake. These experiments suggest that the spatio-temporal capabilities of fMRI may be applied to the in vivo investigation of psychoactive compound activity with potential for clinical applications.

Animals↗
PubMed2001

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging.

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T1-weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T1-weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

Animals↗
PubMed2001

Excision of a giant hydatid cyst of the lung under thoracic epidural anaesthesia.

We present a patient with a large pulmonary hydatid cyst compressing underlying lung, with previous pulmonary tuberculosis, who presented in respiratory failure. After institution of thoracic epidural anaesthesia employing 0.25% bupivacaine, 1% lignocaine and fentanyl, the patient was placed in the sitting position and the hydatid cyst excised and drained after a limited rib resection. An air leak persisted until the 16th postoperative day. A marked improvement in symptoms as well as in spirometly and arterial blood gases occurred, and the patient was discharged on the 20th day. Thoracic epidural anaesthesia may be a safer method than general anaesthesia for removal of a hydatid cyst in a patient with severe respiratory compromise.

Adjuvants, Anesthesia↗
PubMed2001

Reliability and sensitivity of joint space measurements in hand radiographs using computerized image analysis.

OBJECTIVE: To establish the sensitivity and reliability of proximal interphalangeal (PIP) and metacarpophalangeal (MCP) mean joint space measurements using standard clinical radiographs of healthy subjects, in order to determine the limits at which a change in radiographic joint space could indicate a change in actual joint size. METHODS: Repeat hand radiographs of healthy subjects were taken using standard techniques at 3-5 day intervals with the hands flat (5 posteroanterior radiographs in 8 subjects) or in 6 different flexed positions on a single occasion (8 subjects). The mean joint space was determined using custom soft ware and was validated manually. Measurement reproducibility within subjects, within films, and between hand positions was assessed by analysis of variance. RESULTS: In repeat radiographs taken in the standard clinical position, the precision of individual join space measurements indicates that changes > 0.11 mm (approximately 7%) would represent an actual physical change in joint space width (with 95% probability). Averaging measurements across fingers for a single subject decreases the detectable change to 0.05 mm (approximately 3%). With increasing flexure, radiographic joint space tended to increase in MCP and decrease in PIP. CONCLUSION: Mean finger joint space measured from standard clinical radiographs is a reliable and sensitive measurement in healthy subjects even with some change in hand position. Work is required to establish whether the joint space change measured from serial radiographs of patients with arthritis over a period of 6-12 mo exceeds the detectable limits of change derived in this study.

Adult↗
PubMed2000

A quantitative analysis of cortical spreading depression events in the feline brain characterized with diffusion-weighted MRI.

Cortical spreading depression (CSD) in the gyrencephalic cat brain was detected with diffusion-weighted echoplanar (DWEP) magnetic resonance imaging (4-8/min for 1-2 hours) using a horizontal imaging plane through the suprasylvian (SG) and marginal gyri. A t-statistic mapping technique allowed a quantitative characterization of the passage of events through single-image pixels (0.15 mm(2)), thus providing a resolution unavailable to previous studies in which time-dependent changes instead were derived from averaging data over relatively large ROIs. Using the enhanced analysis, CSD events initiated by KCl could be quantified for the first time as primary or secondary according to their spatial and temporal features. Primary events covered 26.2 +/- 9.9 mm(2)of cortical surface (mean +/- SD, n = 7 experiments) and propagated rapidly (3.5 +/- 0.65 mm * min(-1)) with a hemispherical geometry. In contrast, the subsequent secondary events were multiple, spatially restricted (covering 7.6 +/- 4.6 mm(2), P < 0.005), slower in propagation (2.6 +/- 0.41 mm * min(-1), P < 0.012), and often confined to the originating gyrus (26 out of 59 events). However, both event types were associated with significantly reduced apparent diffusion coefficients (ADCs; from 800 to approximately 660 x 10(-6) mm(2)* s(-1), P < 0.05) that were similar for both primary (21 +/- 5.1%) and secondary waves (18 +/- 7. 7%) and that had similar durations (full width at half-maximal height: 86 +/- 17 vs. 79 +/- 20 seconds, respectively). These findings associate CSD for the first time with two categories of ADC disturbance that are similar in amplitude and duration but that differ in spatial extent, velocity, and extensiveness of spread.

Animals↗
PubMed2000

Pharmacological magnetic resonance imaging: a new application for functional MRI.

Various methods, including functional magnetic resonance imaging (fMRI), have recently been developed to allow investigators to study functional activity in the living brain. Such techniques are now being used to investigate regionally specific brain activity associated with the administration of CNS-active drugs. fMRI in particular is increasingly recognized as being a relatively non-invasive way to perform pharmacological investigations in experimental animals, healthy human volunteers, and individuals with CNS disease. This use of fMRI, dubbed 'pharmacological MRI' or 'phMRI', holds the promise of providing relatively straightforward pharmacodynamic assays and can be used to establish brain-penetrability parameters, or dose-ranging information for novel therapeutic compounds.

Anesthetics↗
PubMed2000

Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo EPI.

Graded asymmetric spin echo-echo planar imaging (ASE-EPI) was used to measure transient alterations in cerebral oxygenation resulting from 60 seconds of anoxia in alpha-chloralose anaesthetised rats. The anoxic period induced a transient fall ( approximately 1 min) in signal intensity followed by a prolonged signal overshoot consistent with an autoregulatory response to oxygen deprivation. The magnitude of signal response, integrated over the entire brain, increased linearly with the echo asymmetry (t(ge)). However, that increase in sensitivity was offset by a reduced signal to noise ratio and quality of the image data. The responses of four regions of interest within the brain to the anoxic stimulus, and the effect of increasing the echo asymmetry, were compared. A comparable magnitude of signal decrease was observed in all brain regions except the superficial cortex that included pial vessels. As t(ge) was incremented differences in signal attenuation between regions became more pronounced. The signal overshoot observed upon restoration of normal breathing gases showed similar trends, producing similar normalised vascular responses for all regions of interest studied. Different regions of interest showed comparable time courses of the signal overshoot suggesting that similar autoregulatory vascular mechanisms operate in all brain regions. These findings additionally show that the use of graded ASE-EPI produced a characteristic profile of maximum signal change measured during and following the anoxic period for each brain region. They suggest that the shape of this profile was determined by the local vasculature within each region of interest; this feature could be exploited in activation studies to eliminate regions with significant signal changes originating from large draining vessels. Finally, the consistent physiological response observed, when the overshoot was compared to the magnitude of the signal drop, demonstrated that modification of the spin echo offset parameter did not mask or detrimentally alter the signal change resulting from the underlying physiological perturbation.

Animals↗
PubMed2000

Porphyrias.

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Acute Disease↗
PubMed2000

The effects on increasing cardiac output with adrenaline or isoprenaline on arterial haemoglobin oxygen saturation and shunt during one-lung ventilation.

Theoretically, if the cardiac output were increased in the presence of a given intrapulmonary shunt, the arterial haemoglobin oxygen saturation (SaO2) should improve as the venous oxygen extraction per ml of blood decreases. To test this hypothesis, eight pigs were subjected to one-lung ventilation and adrenaline and isoprenaline infusions used to increase the cardiac output. The mixed venous oxygen, shunt fraction and oxygen consumption were measured. With both adrenaline and isoprenaline, although there was a small rise in mixed venous oxygen content, there was a fall in SaO2. With adrenaline, the mean shunt rose from 48% to 65%, the mean oxygen consumption rose from 126 ml/min to 134 ml/min and the mean SaO2 fell from 86.9% to 82.5%. With isoprenaline, the mean shunt rose from 45% to 59%, the mean oxygen consumption rose from 121 ml/min to 137 ml/min and the mean SaO2 fell from 89.5% to 84.7%. It is concluded that potential improvement in SaO2, which might occur from a catecholamine-induced increase in mixed venous oxygen content during one-lung ventilation, is more than offset by increased shunting and oxygen consumption which reduce SaO2.

Adrenergic beta-Agonists↗
PubMed2000

Can insertion length for a double-lumen endobronchial tube be predicted?

It has been suggested that the appropriate length of insertion for double-lumen tubes can be estimated by external measurement. This study examined the accuracy of external measurement in estimating the actual length of insertion required in 130 patients. It also examined the relationship between the length inserted and the patient's height in 126 patients and their weight in 125 patients. Although there was a fair correlation between the measured external length and the final inserted length (r = 0.61), the 95% confidence intervals of slope and intercept allowed a large variation and the prediction was too wide to be clinically useful. Height was reasonably well correlated with the final length (r = 0.51) but an equally wide 95% confidence interval rendered it of little clinical value. There was no correlation between weight and final tube length. It is concluded that external measurement alone is not adequate to predict a clinically acceptable position of the double-lumen tube.

Adolescent↗