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PubMed1989

[Nociceptive flexion reflex. Principles and applications of the threshold determination].

The threshold for the pain flexion reflex in the lower limb can be used to determine the potency in man of analgesic drugs acting centrally. A new apparatus is, the "algometre", described. Bipolar electrical stimulation (5 stimuli of 1 ms over a period of 10 ms) is applied to the saphenous nerve just behind the external malleolus. An amplifier detects the muscle response (electromyogramme; EMG) at the muscle-tendon junction in the popliteal space; this occurs about 70-130 ms after the painful stimulus. The whole system is linked to a microcomputer. The EMG and EMG/intensity curves are displayed on a colour screen, and can be copied by a colour tracing table. The whole machine is mobile and can be moved from bed to bed. An increase in the threshold during inhalation of 50% nitrous oxide in oxygen was shown. However, the usefulness of the "algometre" in clinical practice remains to be assessed by further studies.

Electric Stimulation↗

PubMed2001

Activity-dependent development of P2X7 current and Ca2+ entry in rabbit osteoclasts.

Bone remodeling is regulated by local factors and modulated by mechanical stimuli. Mechanical stimulation can cause release of ATP, an agent that stimulates osteoclastic resorption at low concentrations and inhibits at high concentrations. We examined whether osteoclasts express P2X(7) receptors, which are activated by high concentrations of ATP and can behave as ion channels or cause the formation of membrane pores. Rabbit osteoclasts were studied using patch clamp techniques. Successive or prolonged applications of 2'- & 3'-O-(4-benzoylbenzoyl)-ATP (BzATP, a relatively potent P2X(7) agonist) or high concentrations of ATP caused the development of a slowly deactivating inward current. The underlying channel was permeable only to small cations, ruling out pore formation. Divalent cations reduced current magnitude, consistent with the presence of P2X(7) receptors, a finding confirmed in rat osteoclasts by immunocytochemistry. Successive applications of BzATP also elicited [Ca(2+)](i) elevations that required extracellular Ca(2+). The BzATP-induced current and the rise of [Ca(2+)](i) were temporally associated, and both were inhibited by PPADS, a P2X(7) antagonist. This study demonstrates that high concentrations of ATP activate P2X(7) receptors and provides the first functional evidence for an extracellular ligand-gated Ca(2+) influx pathway in osteoclasts. ATP released in response to mechanical stimuli may act through P2X(7) receptors to inhibit osteoclastic resorption.

Adenosine Triphosphate↗

PubMed1991

Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization.

This study demonstrates the induction of lysozyme mRNA expression in situ in tissue macrophages (M phi) of mice following in vivo stimulation. The resting resident tissue M phi of most tissues do not contain enough lysozyme mRNA to be detected by in situ hybridization using 35S-labeled RNA probes. Following Bacille Calmette Guerin or Plasmodium yoelli infection, however, M phi recruited to liver and spleen hybridize strongly to the lysozyme probe. Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. This response is also evoked by a noninfectious agent (intravenously injected sheep erythrocytes), and is possibly the result of an early phagocytic interaction. Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. Kupffer cells are rarely lysozyme-positive. Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations.

Animals↗

PubMed2001

Presynaptic group II mGluR inhibition of short-term depression in the medial perforant path of the dentate gyrus in vitro.

Inhibition of short-term plasticity by activation of presynaptic group II metabotropic glutamate receptors (group II mGluR) was investigated in the medial perforant path of the dentate gyrus in the hippocampus in vitro. Brief trains of stimulation (10 stimuli at 1--200 Hz) evoked short-term depression of field excitatory postsynaptic potentials (EPSPs). The steady-state level of depression, measured after 10 stimuli, was frequency dependent, increasing between 1 and 200 Hz. Activation of group II mGluR by the selective agonist LY354740 did not alter short-term depression evoked by frequencies up to 10 Hz, but did inhibit short-term depression evoked at higher frequencies in a frequency- and concentration-dependent manner. The time-averaged postsynaptic response (EPSP per unit time) was found to increase linearly with frequency up to approximately 20 Hz. At higher frequencies, the response plateaued, thereby becoming independent of frequency. Frequencies above this were differentiated only during the transient postsynaptic response that accompanies changes in firing rates. Activation of presynaptically located group II mGluR increased the frequency at which the EPSP per unit time plateaued up to 30-50 Hz.

Animals↗

PubMed2000

[Comparison of mouth pressure, twitch, after anterior magnetic stimulation against posterior magnetic stimulation in healthy subjects].

BACKGROUND: If techniques for studying respiratory muscle function are easy to use and well tolerates by patients, they can be used routinely. Measuring mouth twitches (TwM) using either bilateral anterior or posterior magnetic stimulation meets both criteria. SUBJECTS AND METHODS: We studied 16 healthy subjects. TwM was measured using bilateral anterior (TwMA) and posterior (TwMP) stimulation. Ten stimuli were applied for each technique for each subject. Five subjects repeated the test was repeated on a different day. RESULTS: The mean TwMA in healthy subjects was 21.07 +/- 4.4 cmH2O (range 13.72-30.11); the mean TwMP was 21.12 +/- 5.9 cmH2O (range 12.7-35.7) (NS). The mean difference was 2.8 +/- 2.5 cmH2O, while the ratio TwMP/PImax was 0.15 (range 0.08-0.10) and TwMA/PImax was 0.14 (range 0.07-0.15). The correlation between the two technique was 0.8. The patients who underwent testing twice had a mean TwMA of 20 cmH2O on the first day and 10.18 cmH2O on the second (NS). The coefficient of variation (CoV%) was 5.9% for TwMA and 7.2% for TwMP. CONCLUSIONS: The two techniques for measuring TwM give similar results and coefficients of variation in healthy subjects; either technique can be used. Variation from one testing day to another is low.

Adult↗

PubMed2005

Novelty-induced correlation between visual neurons and the hippocampal theta rhythm in sleep and wakefulness.

Various rhythms have been shown to affect sensory processing such as the waking-sleep cycle and the hippocampal theta waves. Changes in the firing of visual lateral geniculate nucleus neurons have been reported to be dependent on the animal's behavioral state. The lateral geniculate extracellular neuronal firing and hippocampal field activity were recorded in chronically implanted animals to analyze the relationship during quiet wakefulness and sleep associated with stimulation shifts that may introduce novelty. During wakefulness, a change in light flash stimulation pattern (stimuli frequency shift, stimuli on and off) caused an increment in the theta band power in 100% of the cases and a phase-locking of the spikes in 53% of the recorded neurons. During slow wave sleep, there were no consistent changes in the theta power notwithstanding 13% of the neurons exhibited phase-locking, i.e., novelty may induce changes in the temporal correlation of visual neuronal activity with the hippocampal theta rhythm in sleep. The present results suggest that visual processing in slow wave sleep exists, while auditory information and learning were reported during slow wave sleep in animals and newborn humans. The changes in the theta power as well as in the neuronal phase-locking amount indicate that in slow wave sleep, the ability of the hippocampus to detect/process novelty, although present, may be decreased. This is consistent with the noticeable decrease in awareness of the environment during sleep.

Animals↗

PubMed1994

Pattern of descending excitation of presumed propriospinal neurones at the onset of voluntary movement in humans.

The pattern of activation of presumed 'propriospinal' neurones was investigated in human subjects during phasic voluntary contractions of one of the following muscles: biceps, triceps, flexor carpi radialis (FCR), flexor carpi ulnaris (FCU) and extensor carpi radialis (ECR). Changes in the amplitude of the H reflex (FCR, ECR), or the tendon jerk (biceps, triceps) were used to assess the excitability of the corresponding motoneurone pools after conditioning stimulation. Conditioning stimuli were applied to the musculo-cutaneous, triceps and ulnar nerves. In most cases reflex facilitation was not observed at rest and was only disclosed at the onset of contraction. The characteristics of this facilitation (3-4 ms central delay, short duration, low threshold, depression when the afferent input was increased) are consistent with those previously attributed to 'propriospinal' excitation. It is argued that the contraction-associated facilitation was descending in origin. The descending facilitation of the 'propriospinal' system had a characteristic pattern in that the pathways selected by higher centres were those receiving the afferent feedback from the contracting muscle. These results provide further insight into the organization of human 'propriospinal' pathways: (1) it is confirmed that afferents from each muscle activate a specific subset of neurones; and (2) it is suggested that the projections of each subset are divergent, implying that individual neurones project onto diverse motor nuclei, an organization that would favour the co-ordination of multi-joint movements. Such an organization is discussed in relation to the possible role of the propriospinal system in the control of normal human upper limb movements.

Adult↗

PubMed2001

A mixed modality paradigm for recording somatosensory and auditory P50 gating.

Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.

Adult↗

PubMed1989

Electrical stimulation of bat superior colliculus influences responses of inferior collicular neurons to acoustic stimuli.

The influence of electrical stimulation of the superior colliculus (SC) on acoustically evoked responses of inferior collicular (IC) neurons was examined in 24 barbiturate-anesthetized Rufous horseshoe bats, Rhinolophus rouxi. Acoustic stimuli (50 ms, 0.5 ms rise-decay times) were delivered from a loudspeaker placed 68 cm in front of each bat and a total of 354 IC neurons were isolated. The response latencies of these neurons were mainly between 7.5 and 17.5 ms. When the ipsilateral SC was electrically stimulated, responses of 227 (64%) neurons were not affected, but responses of the remaining (127 neurons, 36%) were either inhibited (102 neurons, 29%) or facilitated (25 neurons, 7%). The degree of inhibition and the response latency of the inhibited neurons increased with the amplitude of electrical stimulation. Inhibition of a neuron's activity was also dependent upon the time interval between acoustic and electrical stimuli. The best inhibitory latency measured at maximal inhibition was between 12 and 20 ms. Conversely, facilitation shortened the response latency of IC neurons and the degree of facilitation increased with the amplitude of the acoustic stimulus. Since the SC plays an essential role in orienting an animal's responses toward sensory stimuli, our findings suggest that the SC may affect the processing of acoustic signals in the auditory system during acoustically guided orientation.

Acoustic Stimulation↗

PubMed1999

Investigating the dependence of BOLD contrast on oxidative metabolism.

Most functional magnetic resonance imaging (fMRI) studies are based on measuring the changes in the blood oxygenation level-dependent (BOLD) contrast that arise from a complex interplay between cerebral hemodynamics and oxidative metabolism. To separate these effects, we consecutively applied two different stimuli: visual stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and hypercapnia (inspiration of 5% CO2). Changes in cerebral blood flow (deltaCBF) and the effective transverse relaxation time (T2*) were measured in an interleaved manner by combining a previously described spin-labeling technique with BOLD-based fMRI. In six healthy volunteers, T2* was significantly longer during hypercapnia than during visual stimulation, whereas the corresponding deltaCBF values were the same at the given level of significance (P<0.01). This finding is explained by a significant increase in oxygen consumption under visual stimulation. The average T2* changes in the visual cortex related to cerebral hemodynamics and oxidative metabolism were 10.6+/-3.0% and -4.7+/-1.2%, respectively, resulting in a net increase of 5.9+/-2.3%. Although the hemodynamic effect is dominant, the increase in oxidative metabolism gives rise to a significant decrease in BOLD contrast. The calculated average change in the cerebral metabolic rate of oxygen (CMRO2), 4.4+/-1.1% (N = 6), is in excellent agreement with previous results obtained by positron emission tomography.

Blood Volume↗

PubMed1979

Neutral proteinases of leucocytes and the inflammatory process.

Plasminogen, the inactive precursor of plasmin, a general trypsin-like proteinase, is present at high concentration in blood and in body fluids. Most cells can recruit this proteolytic potential by secreting plasminogen activator (PA) to generate localized proteolysis in the surrounding microenvironment. PA and plasmin are serine enzymes whose pH optima match extracellular pH; further, in view of the large amount of circulating proenzyme and the broad substrate range of plasmin, the possibility that this proteolytic system can initiate a variety of proteolytic reactions or sequences should be kept in mind. PA production is precisely regulated by hormones, temporal programming, or both; and enzyme synthesis is correlated with some physiological and pathological processes requiring proteolysis. Thus PA production is coordinately regulated with ovulation, trophoblast implantation, spermatogenesis, polypeptide hormone synthesis, and some developmental phenomena; and with inflammation, tumour promotion, and neoplasia. Tissue remodelling and cell migration are common to many of these processes. Macrophage (monocyte) and polymorphonuclear leucocyte PA production is modulated by many biologically active substances. Enzyme synthesis is induced and stimulated by stimuli that recruit these cells to sites of inflammation, and it is repressed by anti-inflammatory agents, notably by glucocorticoids.

Animals↗

PubMed1995

Phenotypic and functional analysis of lymphocytes in paroxysmal nocturnal hemoglobinuria.

The hematologic disorder paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation within the Piga gene important for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. The PNH defect has been identified in all cells of the myeloerythroid lineage, but involvement of the lymphoid lineage in PNH is more controversial. We therefore analyzed lymphocytes from 22 patients with PNH to characterize phenotypically the GPI-deficient population, and to investigate the functional consequences of GPI deficiency. GPI-deficient T lymphocytes, B lymphocytes, and NK cells were identified, but at a lower percentage than granulocytes and erythrocytes. CD8+ lymphocytes were significantly more affected than CD4+ T cells, and CD45RA+ lymphocytes were significantly more affected than CD45RO+ cells. Proliferation assays demonstrated that lymphocytes from PNH patients, either unfractionated or purified GPI-deficient cells, responded normally to in vitro stimuli. When stimulated with phytohemagglutinin (PHA), naive CD45RA+ GPI-deficient T lymphocytes acquired the memory CD45RO+ phenotype. In addition, GPI-deficient T lymphocytes had a relative growth advantage as compared to normal T cells. The results demonstrate that PNH involves the lymphoid as well as the myeloerythroid lineage, and therefore arises from a totipotent bone marrow stem cell. The in vitro growth advantage of GPI-deficient lymphocytes in PNH may have important implications for the pathogenesis of some puzzling clinical aspects of PNH, including predominance of the PNH clone, defective hematopoiesis, and leukemogenesis.

Adolescent↗

PubMed1994

Long-term inositol phosphate release, but not tyrosine kinase activity, correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes.

The cascade of events within the first few minutes of T cell stimulation has been well characterized. Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems, the rate-limiting step in peripheral T cells has not been demonstrated. To model effective versus ineffective CD3-mediated stimulation in peripheral T cells, we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells: OKT3, which causes early second messenger generation but is unable to activate T cells without a second signal, and 64.1, which stimulates T cell proliferation on its own. We found that tyrosine kinase activity was similar for both mAbs over a period of hours. However, the inositol phosphate response was stronger for 64.1 than for OKT3. To tie these events to gene activation, we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation. Both stimuli induced the appearance of the NF-kappa B components (c-Rel, p65 (RelA), and p50 (NF-kappa B1)) and NF-kappa B DNA binding activity in the nucleus. However, only 64.1 induced NF-AT in the nucleus, correlating with its ability to activate T cells. Thus, NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response. On the other hand, NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3.

Antibodies, Monoclonal↗

PubMed1992

Water-flow sensitive pedal neurons in Tritonia: role in rheotaxis.

We have identified 13 pairs of neurons in the pedal ganglia of the marine nudibranch slug Tritonia diomedea that responded tonically and/or phasically to water-flow directed at the rhinophore sheaths and oral veil tips. Most of the neurons responded equally to inputs from either side of the body, but 6 pairs responded with greater intensity to ipsilateral water-flow stimuli. When stimulated intracellularly in a semi-intact, whole-animal preparation, 4 of these 6 pairs of neurons caused ipsilateral movements that may turn the animal towards that side. These observations suggest a role for these current-sensitive neurons in the previously described orientation to water-currents in Tritonia diomedea.

Action Potentials↗

PubMed1992

Widely distributed GABA-mediated afferent inhibition processes within the ventrobasal thalamus of rat and their possible relevance to pathological pain states and somatotopic plasticity.

We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventroposteromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependent on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the wide-spread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deafferentation pain is discussed.

Animals↗

PubMed1988

A comparison of the discriminatory ability and sensitivity of the trigeminal and olfactory systems to chemical stimuli in the tiger salamander.

Trigeminal receptors can respond to a wide variety of chemical stimuli, but it is unknown whether these receptors mediate discrimination between chemical stimuli matched for equal perceptual intensity. The present electrophysiological and behavioral experiments address this issue using tiger salamanders, Ambystoma tigrinum, and four compounds (amyl acetate, cyclohexanone, butanol, and d-limonene). In addition, the relative sensitivities of the trigeminal and olfactory systems to these compounds are compared. In electrophysiological cross-adaptation experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), there was complete cross adaptation such that only concentrations above the background (cross-adapting) stimulus concentration elicited responses, suggesting that chemical stimuli may stimulate trigeminal receptors nonspecifically. In behavioral experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), only animals with intact olfactory nerves could discriminate between perceptually equivalent concentrations, that is concentrations that elicited the same level of responding. Both electrophysiologically and behaviorally, the trigeminal system exhibited higher thresholds than the olfactory system. We conclude that trigeminal chemoreceptors, at least in salamanders, are unable to discriminate between these two pairs of compounds when matched for equal perceptual intensity, and that trigeminal chemoreceptors are less sensitive than olfactory receptors.

Action Potentials↗

PubMed1985

Effects of color stimulation and information on the copying performance of attention-problem adolescents.

The optimal stimulation theory proposes that hyperactive children are less tolerant of lower levels of arousal than nonhyperactive children and should thus derive greater gains from stimulation added to repetitive copying tasks than do comparisons. To test this hypothesis, 16 adolescents, rating high on attention and behavior problems, were matched on the basis of age and poor handwriting performance to 16 controls. Matched pairs were randomly assigned to treatment order (high-stimulation colored letters followed in 2 weeks by low-stimulation black letters or the reverse order) and to level of information (color added to difficult letter parts or added to randomly selected letters), counterbalanced for treatment order and level of information within each order. Errors and activity were subjected to a mixed-design analysis of covariance, with IQ the covariate. The major findings indicated that attention-problem adolescents performed better with high-stimulation task stimuli than with low, relative to the opposite performance pattern of controls. Different responding was significant for experimental but not for control children.

Achievement↗

PubMed1987

Monitoring of neuromuscular function.

Monitoring neuromuscular transmission provides valuable information to the anesthesiologist. The acquisition of relevant data contributes to a more predictable and rational approach to the use of muscle relaxants and assures improved patient care during and in the immediate postoperative period. Clinical noninvasive criteria such as the presence or absence of diplopia and or ptosis, the ability to open the eyes widely, protrude the tongue or swallow, measurement of hand grip strength or head lift or assessment of the vital capacity are limited to awake and cooperative patients. Measurement of inspiratory force and tidal volume can be evaluated in anesthetized patients breathing spontaneously. Central depressant drugs tend to depress these respiratory parameters. Accordingly, the assumption that relaxants are responsible for respiratory depression at the end of an anesthetic can only be documented when impairment of neuromuscular transmission can be demonstrated. The most reliable method of measuring neuromuscular function is to stimulate an accessible peripheral motor nerve and measurement of the evoked response of the skeletal muscle or muscles innervated by the stimulated motor nerve. The evoked muscle response depends on the pattern of motor nerve stimulation: Single twitch stimuli at a defined frequency, tetanic stimulation, posttetanic single twitch stimulation or train-of-four stimulation. The response to these different modes of stimulation can be assessed either mechanically (evoked tension response) or electrically (evoked electromyography: EMG or integrated EMG). These response criteria can be employed either individually or combined to evaluate the response to muscle relaxants and to assess the adequacy of recovery from neuromuscular blockade.

Electric Stimulation↗