Search PubMed⌕ Search

Biomedical subjects

I C Bruce

Publications and source records attributed to I C Bruce.

At least 19 recordsLinked to original sources

Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats.

Low-frequency stimulation of the kindling site interferes with the course of kindling epileptogenesis. The present study examined the effect of unilateral low-frequency stimulation of the central piriform cortex on seizure development induced by amygdaloid kindling in rats. The ipsilateral or contralateral central piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses at 1 Hz and 50-150 muA) immediately after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or contralateral central piriform cortex significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling. The marked suppression induced by low-frequency stimulation of the central piriform cortex on either side was predominantly due to the significant retardation of progression from stage 0 to stage 1 and stage 3 to stage 4 seizures. In addition, the suppressive effect of low-frequency stimulation did not disappear when the stimulation was stopped; it could persist for at least 10 days. These findings indicate that brain areas other than the kindling focus, such as the central piriform cortex on both sides, can also be used as reasonable targets for low-frequency stimulation to retard seizure development induced by amygdaloid kindling. Secondly, like the ipsilateral central piriform cortex, the contralateral central piriform cortex may also participate in the progression and secondary generalization of focal seizures. The study suggests that unilateral low-frequency stimulation of the central piriform cortex may have a significant antiepileptogenic effect, and may be helpful for exploring effective and long-lasting therapies for human temporal lobe epilepsy.

Amygdala↗

Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke.

Previous studies indicate that the arachidonic acid-metabolizing enzymes COX-2 and 5-LOX are overexpressed during the process of colonic adenoma formation promoted by cigarette smoke. The aims of the present study were to investigate whether there exists a relationship between COX-2 and 5-LOX, and whether dual inhibition of COX-2 and 5-LOX has an anticarcinogenic effect in the colonic tumorigenesis promoted by cigarette smoke. Results showed that pretreating colon cancer cells with cigarette smoke extract (CSE) promoted colon cancer growth in the nude mouse xenograft model. Inhibition of COX-2 or 5-LOX reduced the tumor size. In the group treated with COX-2-inhibitor, the PGE2 level decreased while the LTB4 level increased. In contrast, in the 5-LOX-inhibitor treated group, the LTB4 level was reduced and the PGE2 level was unchanged. However, combined treatment with both COX-2 and 5-LOX inhibitors further inhibited the tumor growth promoted by CSE over treatment with either COX-2-inhibitor or 5-LOX-inhibitor alone. This was accompanied by the downregulation of PGE2 and LTB4. In an in vitro study, we found that the action of CSE on colon cancer cells was mediated by 5-LOX DNA demethylation. In summary, these results indicate that inhibition of COX-2 may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway during colonic tumorigenesis promoted by CSE. Suppression of 5-LOX did not induce such a shunt and produced a better response. Therefore, 5-LOX inhibitor is more effective than COX-2 inhibitor, and blocker of both COX-2 and 5-LOX may present a superior anticancer profile in cigarette smokers.

Adenocarcinoma↗

Luteolin induces vasorelaxion in rat thoracic aorta via calcium and potassium channels.

The aims of the present study were to investigate the vasoactive effects of luteolin and its mechanisms of action on the rat thoracic aorta. Luteolin (4.5-36 micromol/L) caused a concentration-dependent relaxation of endothelium-intact or endothelium-denuded aortic rings precontracted with phenylephrine (PE, 10(-6) mol/L) or a high level of K+ (6 x 10(-2) mol/L). Luteolin induced a shift of the PE concentration-response curve to the right and downward. L-NAME and propranolol did not influence the vascular effect of luteolin. However, 5-hydroxydecanoate, tetraethylammonium, BaCl2 and 4-aminopyridine significantly attenuated the vasorelaxant effect of luteolin. In Ca2+ -free medium, medium with graded concentrations of Ca2+, or K+ -free solution, luteolin reduced PE-induced contraction. It is concluded that luteolin induces endothelium-independent relaxation in rat thoracic aorta. The mechanism involves the inhibition of sarcolemmal Ca2+ channels, release from intracellular Ca2+ stores and activation of K+ channels.

Adrenergic beta-Antagonists↗

Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. METHODS: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. RESULTS: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). CONCLUSION: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

Animals↗

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes.

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.

Adenosine Triphosphatases↗

A phenomenological model for the responses of auditory-nerve fibers: I. Nonlinear tuning with compression and suppression.

A phenomenological model was developed to describe responses of high-spontaneous-rate auditory-nerve (AN) fibers, including several nonlinear response properties. Level-dependent gain (compression), bandwidth, and phase properties were implemented with a control path that varied the gain and bandwidth of tuning in the signal-path filter. By making the bandwidth of the control path broad with respect to the signal path, the wide frequency range of two-tone suppression was included. By making the control-path filter level dependent and tuned to a frequency slightly higher than the signal-path filter, other properties of two-tone suppression were also included. These properties included the asymmetrical growth of suppression above and below the characteristic frequency and the frequency offset of the suppression tuning curve with respect to the excitatory tuning curve. The implementation of this model represents a relatively simple phenomenological description of a single mechanism that underlies several important nonlinear response properties of AN fibers. The model provides a tool for studying the roles of these nonlinearities in the encoding of simple and complex sounds in the responses of populations of AN fibers.

Audiometry, Pure-Tone↗

The effects of food fragmentation index on mandibular closing angle in human mastication.

Jaw movements were recorded using a three-dimensional magnetic sensing system (Sirognathograph, Siemens) in 10 human volunteers while chewing standardized volumes of 15 food types, ranging from soft cheeses to hard nuts. The maximum horizontal amplitude inside the chewing loop (width of the loop), the height of the loop (vertical amplitude) and the closing angle made by the jaw during the late closing phase of the cycle relative to the vertical were calculated. The most highly significant correlation was between the closing angle and the square root of the ratio of two mechanical properties of the food - the toughness (R) and modulus of elasticity (E)(r = -0.85, p<0.001). The width of the chewing loop was also significantly correlated with the above combination of food properties (r = -0.75, p<0.01) whereas the vertical amplitude was not. Thus, the mechanical properties of foods appear to influence the pattern of mandibular movements in human mastication similarly to their reported effect on food breakdown rates and anterior temporalis activity during mastication.

Adult↗

A stochastic model of the electrically stimulated auditory nerve: single-pulse response.

Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.

Action Potentials↗

A stochastic model of the electrically stimulated auditory nerve: pulse-train response.

The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism. Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s. First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model. Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate, while the deterministic model predicts no variance at all.

Analysis of Variance↗

The effects of stochastic neural activity in a model predicting intensity perception with cochlear implants: low-rate stimulation.

Most models of auditory nerve response to electrical stimulation are deterministic, despite significant physiological evidence for stochastic activity. Furthermore, psychophysical models and analyses of physiological data using deterministic descriptions do not accurately predict many psychophysical phenomena. In this paper we investigate whether inclusion of stochastic activity in neural models improves such predictions. To avoid the complication of interpulse interactions and to enable the use of a simpler and faster auditory nerve model we restrict our investigation to single pulses and low-rate (< 200 pulses/s) pulse trains. We apply signal detection theory to produce direct predictions of behavioral threshold, dynamic range and intensity difference limen. Specifically, we investigate threshold versus pulse duration (the strength-duration characteristics), threshold and uncomfortable loudness (and the corresponding dynamic range) versus phase duration, the effects of electrode configuration on dynamic range and on strength-duration, threshold versus number of pulses (the temporal-integration characteristics), intensity difference limen as a function of loudness, and the effects of neural survival on these measures. For all psychophysical measures investigated, the inclusion of stochastic activity in the auditory nerve model was found to produce more accurate predictions.

Cochlear Implants↗

Food properties that influence neuromuscular activity during human mastication.

The rate of breakdown of food in mastication depends on the ratio of two mechanical properties of the food--the toughness and modulus of elasticity (Agrawal et al., 1997)--a result which can be predicted by an analysis of the energetics of fracture. The work input to produce food fragmentation is provided by the masticatory muscles, the activity levels of which depend on sensory feedback from the mouth. Here, we test the hypothesis that the activity of a representative of this musculature is modulated by the above combination of food properties. The surface electrical activity (EMG) of the anterior temporalis muscles of ten human subjects was recorded while subjects chewed standardized volumes of 15 food types. The integrated EMG in these muscles was highly significantly related to the square root of the ratio of the above two food properties. Significant correlations were found between this food property index and integrated EMG, both when data for all chews and all subjects were lumped together (r = -0.86; p < 0.0001) and when correlation coefficients between the index and EMG were plotted for each chew made by each subject. Except for two subjects in the first chew, these coefficients reached and maintained highly significant levels throughout the masticatory sequence. Thus, a clear relationship between the electrical activity of a jaw-closing muscle and the mechanical properties of food has been found for the first time.

Adult↗

Mechanical properties of foods responsible for resisting food breakdown in the human mouth.

The fragmentation of foods (breakage function) was measured in five humans on "bagged' single particles of 28 foods from three food groups. The change in the square root of the specific surface of the particles (the specific surface being the area of particle silhouettes, measured by image analysis, divided by original particle volume) produced by one bite, averaged for all participants, was inversely linearly related to the square root of the toughness of the foods divided by the square root of their Young's moduli(r = -0.86; p < 0.00001). This relation is predicted by an analysis based on food fragmentation within a limited jaw displacement. Thus, resistance to jaw movement appears to provide sensory information on the deformation fracture and fragmentation of foods. It is believed that this is the first time that a relation between the breakage of food particles by the teeth and their material properties has been found, and the finding has considerable implications for human masticatory studies, for the analysis of dentition and diet in mammals and for texture studies in food science.

Adult↗

Vagal hyperactivity in stress induced gastric ulceration in rats.

Indirect evidence suggests that stress ulceration is provoked by vagal hyperactivity. However, direct evidence of hypervagal activity during stress conditions is lacking. Experiments were designed to directly measure vagal activity under different stress conditions in rats. Starvation stress for 48 h did not change the mean amplitude of action potentials, but their frequency was significantly decreased. Restraint stress at 22 degrees C increased vagal activity, both amplitude and frequency, in the first 60 min; these responses were markedly enhanced by cold (4 degrees C) and persisted for at least 2 h. Starvation for 48 h did not induce any gastric mucosal lesions. Restraint alone produced petechiae in the gastric mucosa, but cold restraint induced severe haemorrhagic ulcers. It is concluded that cold restraint stress provokes a prolonged vagal hyperactivity, which is one of the causative factors for gastric ulceration.

Animals↗

Electromyographic assessment of non-functional masseter muscle in an awake animal model.

Non-functional activities, such as bruxism, have been implicated in the development of temporomandibular disorders (TMD). It would be of value to have an animal model in which to investigate the processes underlying such disorders. The aim of this study was to determine the electromyographic (EMG) characteristics of experimentally induced, non-functional activity in the jaw-closing muscles of awake, behaving rats and how the EMG characteristics differed from those found under normal conditions. In the same animals, chronic EMG recordings were made prior to and following the insertion of an occlusal cap, which induced non-functional activity. A characteristic EMG pattern was found only during non-functional activity. The durations and amplitudes of the EMG bursts during this activity were significantly different statistically from those found in the same animals under normal conditions.

Animals↗

A multimodal neurophysiological assessment in terminal renal failure.

A prospective multimodal neurophysiological study was conducted on 36 patients with end-stage renal failure, 16 of whom subsequently underwent renal transplantation (TR). Nerve conduction study and somatosensory evoked potentials revealed that peripheral conduction deficit, often subclinical, was the commonest abnormality, and TR resulted in substantial improvement. Visual evoked potentials demonstrated subclinical impairment, which did not improve after TR. The brainstem auditory evoked potentials were essentially normal and unaffected by TR.

Brain Stem↗

A technique for recording from single neurons in the spinal cord of the awake cat.

A means of recording activity from single neurons in the spinal cord of the awake cat over periods of several weeks is described. The method combines elements of the chronically implanted well technique used in recording from supraspinal structures, with a novel method for reversibly stabilizing the vertebral column in a detachable 'outrigger' device. Between recording sessions, the animal is therefore freely mobile, its vertebral column again flexible. This preparation allows exploration of 1 cm2 of the spinal cord to all depths, and single neurons can be held for periods of 30 min to 2 h. The activity of primary afferents, intraspinal interneurons and motoneurons can be identified and their responses quantified during limb movement by combining ancillary techniques with the stabilization method.

Animals↗

Defective utilization of sensory input as the basis for bradykinesia, rigidity and decreased movement repertoire in Parkinson's disease: a hypothesis.

From a review of the anatomical relationships and single unit activity in the components of the basal ganglia related to limb movement, it is concluded that the major outflow from basal ganglia circuits is via the motor cortex (area 4). Recent results of recording from area 4 neurons revealed that they preferentially "encode" the higher derivatives of movement, i.e. acceleration and jerk. In the parkinsonian (PK) patient and in the monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), EMG responses to imposed loads show a markedly increased gain of the "M2" component which depends upon the integrity of area 4 and which correlates with the severity of PK rigidity. The above observations are considered, along with those of others (demonstrating prolonged movement times, a decreased "repertoire" of voluntary movements fractionation of voluntary movements, inability in tracking movements without visual input, and failure to improve performance in PK's) in relation to a model of the interactions between sensory input and motor programs. Using this model, it is hypothesized that the above PK movement deficits, as well as rigidity, can be accounted for by abnormal processing of the mechanoreceptor sensory input utilized in the generation and execution of movements. The MPTP treated monkey is suggested as a model in which to directly test the hypothesis.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Postnatal dendritic development in motoneurons: evaluation by a Monte Carlo technique.

A Monte Carlo method was used to quantitate the dendritic characteristics of horseradish peroxidase-injected lumbar motoneurons (MNs) from kittens 44 to 73 days old (during the postnatal interval when motor cortical input/output linkages mature) and compared with those from adults. All of the 6 MNs analyzed were within the same range of somal sizes (40-61 micron) and dendritic domain volumes. However, two-dimensional distributions of dendritic diameter versus distance from the soma revealed that in the youngest MNs' (44 and 51 days) most dendritic processes (82 and 84%) were less than 2 micron in diameter, and had no dendrites greater than 5 micron. The adult MNs had large dendrites (20 and 24% were greater than 5 mu), while the kittens of intermediate age (66 and 73 days) exhibited both adult-like (6 and 13% greater than 5 micron) and immature (48 and 73% less than 2 micron) characteristics. "Hit probabilities" calculated from the Monte Carlo data suggest that immature MNs' dendrites may present denser targets per unit volume for ingrowing growth cones than adult MNs, and may facilitate the probability of contact with appropriate afferent axons.

Animals↗