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PubMed1994

Modality-dependent modulation of conduction by impulse activity in functionally characterized single cutaneous afferents in the rat.

Cutaneous afferents exhibit changes in excitability after impulse activity that are correlated with functional modality but are independent of axonal diameter, as studied in 39 cold fibers and 51 nociceptors of the rat. Latency of conducted impulses was used to indicate changes in axonal excitability caused by electrical stimulation. Stimuli were applied both at fixed frequencies and at the time intervals of impulses previously recorded during response to natural stimulation. Latency increased following both these forms of electrical stimulation, as well as after natural stimulation of the receptive fields. The latency increase was correlated with the number of impulses and the frequency of the preceding discharge in all of 4 nociceptors and 13 cold fibers studied for this feature. Increase of latency by electrical or natural stimulation led to reduced responsiveness to natural stimulation. The magnitude and time course of latency changes were correlated with fiber modality. In 32 nociceptors the latency increased continuously with time during a stimulus train, whereas in 21 cold fibers there was only an initial increase in latency over the first few seconds, after which the latency remained at a plateau even as the firing response continued. Paralleling this slowing, impulse failure occurred more frequently during repetitive stimulation in both A delta and C nociceptors than in velocity-matched cold fibers of either class. Based on the magnitude of latency increases during stimulus trains at different frequencies, two distinct patterns were discerned in A nociceptors: "Type II" fibers slowed significantly more than "Type I" or cold fibers. The results support the hypotheses (1) that the pattern of latency changes during activity are signatures for the modality in a given fiber; and (2) that endogenous, activity-dependent processes of the axon contribute to adaptation and encoding in cutaneous sensory afferents.

Afferent Pathways↗

PubMed1996

Peripherally obtained electrophysiological responses to olfactory stimulation in man: electro-olfactograms exhibit a smaller degree of desensitization compared with subjective intensity estimates.

After chemical stimulation of the human olfactory epithelium it is possible to record a negative response (electro-olfactogram, EOG) which is interpreted as the summated receptor potentials of the olfactory nerve. The aim of the present investigation was to test the EOG's changes in relation to pairs of stimuli. Stimulation was performed with vanillin (0.8 ppm) regarded to exclusively excite fibers of the olfactory nerve. Ten healthy volunteers participated in the experiments. Pairs of stimuli were applied at different interstimulus intervals ISIs (2-8 s). EOG could be recorded in 6 out of 10 subjects. After olfactory stimulation the responses' peak amplitude was found to range from 0.15 to 1.8 mV. When pairs of olfactory stimuli were applied responses obtained at an ISI of 8 s were clearly separated whereas at an ISI of 2 s responses were superimposed on each other. As with an ISI of 8 s, the amplitude produced by the second stimulus was nearly as great as the first responses' amplitude (decrease by approximately 20%). In contrast, intensity estimates obtained in an additional experiment (n = 10) decreased by 40-60%. Based on the present data peripheral encoding in the olfactory system appears to be less subject to desensitization compared to the decrease of intensity estimates.

Adult↗

PubMed1994

Mechanics of caloric stimulation in a case with a plug in the horizontal semicircular canal.

Horizontal eye movements were recorded by electronystagmography in a subject with a plug of granulation tissue in the unilateral horizontal semicircular canal by the room temperature air caloric stimulation. Stimuli were sequentially presented to both ears with the subject supine and prone, keeping the horizontal canal vertical. Caloric stimuli presented to the unplugged ear resulted in a vestibular nystagmus whose slow phase eye velocity (SPEV) was always directed toward the stimulated side when the subject was supine and toward the opposite side when he was prone. In contrast, calorics presented to the horizontal canal plugged ear showed that SPEV was always directed toward the stimulated side, irrespective of whether the subject was supine or prone. Results were consistent with consensus that the caloric responses noted in the horizontal canal plugged ear reflected horizontal canal afferent activity which may correspond to direct effect of temperature on end organs or afferents. The findings imply that a caloric mechanism exists which is independent of the conventionally accepted one involving concection currents within the canal.

Aged↗

PubMed2002

Central stimulants as discriminative stimuli. Asymmetric generalization between (-)ephedrine and S(+)methamphetamine.

Central stimulants readily serve as training stimuli in drug discrimination studies and typically substitute for one another in tests of stimulus generalization regardless of which is used as training drug. We have previously found that, although substitution occurs between (+)amphetamine and (-)ephedrine, substitution did not occur upon administration of S(+)methamphetamine to (-)ephedrine-trained animals. In the present investigation, rats were trained to discriminate S(+)methamphetamine (1 mg/kg) from saline vehicle and tests of stimulus generalization were performed with several stimulants, including (-)ephedrine. The S(+)methamphetamine stimulus (ED(50)=0.06 mg/kg) generalized to R(-)methamphetamine (ED(50)=1.61 mg/kg), S(+)amphetamine (ED(50)=0.28 mg/kg), S(-)methcathinone (ED(50)=0.21 mg/kg), methylphenidate (ED(50)=0.28 mg/kg), cocaine (ED(50)=3.68 mg/kg) and (-)ephedrine (ED(50)=13.1 mg/kg). Hence, stimulus generalization between S(+)methamphetamine and (-)ephedrine is apparently asymmetrical. In a companion study, R(-)methamphetamine was administered to rats trained to discriminate (-)ephedrine (4 mg/kg); substitution occurred and R(-)methamphetamine (ED(50)=0.92 mg/kg) was found to be nearly equipotent with (-)ephedrine (ED(50)=0.8 mg/kg). Although the exact basis for the observed results are unclear, they are discussed in terms of the different effects of (-)ephedrine and the methamphetamine optical isomers on neurotransmitter release and reuptake.

Animals↗

PubMedDate not supplied

Cumulative dose-response curves for gallamine: effect of altered resting thumb tension and mode of stimulation.

Neuromuscular blockade studies often use the thumb adductor twitch response to ulna nerve stimulation. Two factors that may influence the results are the resting muscle tension (initial fiber length) and the pattern of the stimulus wave form. This study was undertaken to improve understanding of the effect of these factors and lead to better controlled study conditions and more consistent data. During nitrous oxide-barbiturate-narcotic anesthesia in 10 normal adult patients, as the resting thumb tension was increased from 50 to 200 g, the evoked thumb adductor twitch response (Grass stimulator, 0.25 Hz) was augmented by 28%. There was only a 2.5% increase in the evoked (developed) tension when the resting tension was further increased from 200 to 300 g. Developed tension at 50 g was significantly (p less than 0.001) less than at the other resting tensions. The developed tension at 100 g was also significantly (p less than 0.05) less than at resting tensions of 200 or 300 g. Cumulative dose-response curves for gallamine in nine patients were not significantly altered by increasing resting tension from 50 to 200 g. Biphasic (Block-Aide monitor) or single square wave (Grass stimulator) stimuli wave forms in nine normal adult patients yielded gallamine dose-response curves that were not statistically different. The muscle response to biphasic stimulation during a non-depolarizing blockade was not affected by the average muscle refractory period. Because of the significantly lower developed tension at resting tension settings of 50 to 100 g, a practical consideration during neuromuscular function studies would be to have the resting thumb tension adjusted and rechecked for each patient and kept within the 200-300-g range to ensure maximum uniform developed tension. The type of stimulus wave form selected will not affect results as long as it is used consistently throughout the study.

Adjuvants, Anesthesia↗

PubMed1987

Spatial organization of human perioral reflexes.

Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.

Adult↗

PubMedDate not supplied

[Transcranial magnetic stimulation of the facial nerve: evaluation of a new method in neurophysiological study of Bell's palsy].

Transcranial magnetic stimulation is a new technique used to stimulate brain areas as well as peripheral nerves in healthy, waking persons. To date this technique has appeared safe. The aim of the present study was to assess the clinical application of this method in patients with Bell's palsy. Electromyographic responses were elicited by electrical and magnetic transcranial stimulation of the facial nerve in 26 patients affected by Bell's palsy. Electrical stimulation: stimuli of 0.1 ms duration, and up to 15 V, were delivered through surface electrodes set 2.5 cm apart over the facial nerve at the stylomastoid foramen. Magnetic stimulation: the coil was placed tangent to the parieto-occipital surface of the scalp. The stimulus intensity was then increased stepwise until a supramaximal response was obtained. Recording: the focal recording electrode was placed ipsilateral to the side stimulated over the superior orbicularis oculi; the reference electrode was placed over the nasal bone. The patients were tested with two neurophysiological determinations: the first 15-30 days from the onset of the palsy; the second 30-60 days after the first. A clinical follow-up was performed six months after the second determination. The results indicate that, contrary to traditional electroneurography, transcranial magnetic stimulation is not able to supply useful neurophysiological indications in patients with Bell's palsy. Although the absence of compound muscle action potential upon stimulation of the side with the lesion did demonstrate some impediment to conduction, it did not have any prognostic value since it was also present in patients who were clinically well at the time of the second check-up.

Adult↗

PubMed1992

Relevance of stimulus duration for activation of motor and sensory fibers: implications for the study of H-reflexes and magnetic stimulation.

Electric stimuli with durations of 0.5-1.0 msec are optimal for studies of H-reflexes. It is more difficult to obtain H-reflexes with shorter duration stimuli or with magnetic stimulation. In order to understand this behavior, we studied the excitation thresholds for motor and sensory fibers in the ulnar, median and tibial nerves using both electric and magnetic stimulation. For short duration electrical stimuli (0.1 msec) the threshold for motor fibers is lower than for sensory fibers. For longer duration electric stimuli (1.0 msec) the threshold for sensory fibers is lower. For magnetic stimulation the threshold for motor fibers is much lower than for sensory fibers. Thus, stimulus duration is a critical parameter for sensory fiber excitation, and current magnetic stimulators are not optimal.

Adult↗

PubMed1997

Regulation of the interleukin-2 CD28-responsive element by NF-ATp and various NF-kappaB/Rel transcription factors.

The CD28 costimulatory signal enhances antigen-mediated induction of interleukin-2 (IL-2) gene transcription through activation of an enhancer termed the CD28-responsive element (CD28RE). Although various nuclear proteins have been shown to bind to CD28RE, their in vivo functions in the regulation of this enhancer remain elusive. In this report, we show that CD28RE binds distinct transcription factors in cells treated with different mitogenic stimuli. Stimulation of the T-cell receptor (TCR) complex in the absence of a CD28 costimulatory signal induces a member of the nuclear factor of the activated T cells, NF-ATp; however, this treatment fails to activate the CD28RE enhancer activity. Significant activation of CD28RE was detected when the cells were treated with both the TCR stimulators and an anti-CD28 monoclonal antibody (anti-CD28), which induces the NF-kappaB/Rel enhancer binding proteins in addition to NF-ATp. The costimulatory activity of anti-CD28 can be further enhanced by a phorbol ester. Kinetic analyses demonstrate that activation of endogenous IL-2 gene transcription is correlated with the binding of CD28RE by NF-ATp and different NF-kappaB/Rel species. Transient-transfection studies reveal that expression of either NF-ATp or the p50-RelA NF-kappaB heterodimer leads to the potent transactivation of both the CD28RE enhancer and the intact IL-2 promoter in mitogen-stimulated cells. Remarkably, coexpression of these two families of enhancer-binding proteins in Jurkat T cells results in the transactivation of the CD28RE enhancer even in the absence of any cellular stimuli. Together, these results suggest that activation of IL-2 gene transcription by the TCR- and CD28-mediated signals involves the interaction of CD28RE with NF-ATp and various NF-kappaB/Rel transcription factors.

CD28 Antigens↗

PubMed1996

Deficient CD4+ T cell proliferation in the class 1 MHC-restricted 2C TCR-transgenic mouse.

A comparative study of immune function and marker expression of CD4+ T cells from MHC class 1-restricted 2C TCR-transgenic (2C+) and control transgene-negative littermate (2C-) mice was performed. While 2C+CD4+ T cells resembled memory T cells on the basis of CD44highCD45RBlow expression, the majority of 2C-CD4+ T cells were of the CD44lowCD45RBhigh naive phenotype. Slightly lower levels of TCR-beta and CD3 were found on 2C+CD4+ T cell than 2C-CD4+ T cells. Vigorous proliferation by 2C-CD4+ T cells was observed upon stimulation with 1) anti-CD3 mAb presented through the FcR of macrophages; 2) immobilized (plate-bound) anti-CD3 + anti-CD28 mAbs; and 3) PMA + ionomycin. In marked contrast, all three mitogenic stimuli stimulated highly deficient proliferative responses by 2C+CD4+ T cells. However, significant IL-2 production was detected both in anti-CD3 and in PMA + ionomycin-stimulated cultures of 2C+CD4+ T cells. While intracellular calcium in 2C-CD4+ T cells rapidly increased following anti-CD3 addition, no such increase was observed for similarly stimulated 2C+CD4+ T cells. Anti-CD28, PMA, and coculture with 2C-CD4+ T cells each failed to significantly correct the deficient 2C+CD4+ T cells proliferation as induced by anti-CD3. In addition, IL-2, IL-4, and IL-7 supplements also failed to reverse the deficient proliferation of 2C+CD4+ T cells despite expression of IL-2R component alpha-, beta-chains and the gamma-chain common also to IL-4R and IL-7R. Thymus CD4+8- T cells from the 2C-transgenic mouse were similarly deficient in proliferation as spleen CD4+ T cells. A small subpopulation of CD4+ T cell from the 2C-transgenic mouse expressed the transgenic TCR alpha:beta heterodimer as detected by the 1B2 anti-2C clonotypic mAb; both 1B2+ and 1B2- subpopulations proliferated poorly in response to anti-CD3 and to PMA + ionomycin. These results raise the possibility that TCR engagement with MHC class 1 molecules during early intrathymic development can result in the emergence of CD4+ T cells characterized by unusual marker expression and function.

Animals↗

PubMed2005

Amplitude-dependency of response of SI cortex to flutter stimulation.

BACKGROUND: It is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear. RESULTS: Optical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions. CONCLUSION: Increasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population.

Animals↗

PubMed2001

Secretory phospholipase A2 mediates cooperative prostaglandin generation by growth factor and cytokine independently of preceding cytosolic phospholipase A2 expression in rat gastric epithelial cells.

Transforming growth factor (TGF)-alpha and interleukin (IL)-1beta are responsible for the healing of gastric lesions through, in part, prostaglandin (PG) generation. We examined the contribution of cytosolic and secretory phospholipase A(2)s (cPLA(2) and sPLA(2)) to the PG generation by rat gastric epithelial cells in response to both stimuli. Stimulation with TGF-alpha for 24 h increased cPLA(2) and cyclooxygenase (COX)-2 markedly, PGE(2) slightly, and type IIA sPLA(2) and COX-1 not at all, whereas IL-1beta increased sPLA(2) only. Both stimuli synergistically increased PGE(2), sPLA(2), and the two COXs but not cPLA(2). The onset of the PGE(2) generation paralleled the sPLA(2) release but was apparently preceded by increases in cPLA(2) and the two COXs. The increase in PGE(2) was impaired by inhibitors for sPLA(2) and COX-2 but not COX-1. cPLA(2) inhibitors suppressed PGE(2) generation by TGF-alpha alone but not augmentation of PGE(2) generation or sPLA(2) release by IL-1beta in combination with TGF-alpha. Furthermore, despite an increase in cPLA(2) including its phosphorylated form (phosphoserine), -induced arachidonic acid liberation was impaired in the TGF-alpha/IL-1beta-stimulated cells, in which p11, a putative cPLA(2) inhibitory molecule, was also increased and co-immunoprecipitated with cPLA(2). These results suggest that synergistic stimulation of sPLA(2) and COX-2 expression by TGF-alpha and IL-1beta results in an increase in PGE(2). Presumably, the preceding cPLA(2) expression is not involved in the PGE(2) generation, because of impairment of its hydrolytic activity in the stimulated cells.

Animals↗

PubMed1979

Neurohumoral regulation of blood flow to bones and marrow.

We used labeled microspheres to measure bone and marrow blood flow under control conditions and during several interventions. In dogs, blood flow to compact cortical bone (femoral diaphysis) was 2 +/- 0.1 ml.min-1. 100 g-1, and in hematopoietic marrow (femur), flow was 24 +/- 5 ml.min-1. 100 g-1. Hematopoietic cancellous bones (sternum, ilium) received substantial blood flow. We estimate that as much as 11% of cardiac output is directed to the skeleton. Bone and marrow vessels were responsive to several stimuli. During exercise, vascular resistance in bone increased two- to fourfold, in contrast to profound vasodilation in adjacent skeletal muscle. Hemmorrhage also increased bone vascular resistance. Bone and marrow vessels responded to humoral stimuli: norepinephrine increased vascular resistance and adenosine decreased resistance. Bone vessels also responded to neural stimuli: stimulation of carotid baroreceptors decreased vascular resistance, and activation of sympathetic pathways by baroreceptor deafferentation in cats increased vascular resistance. These studies indicate that bone and marrow vessels respond actively to physiological stresses and to several humoral and neurogenic stimuli

Animals↗

PubMed1988

Effects of electrolytic lesions of the superior olivary complex and trapezoid body on brainstem auditory-evoked potentials in the guinea pig. I. Vertex-tragus recordings.

Brainstem auditory-evoked potentials (BAEP) were recorded between vertex and tragus in 22 guinea pigs, after destruction of the contralateral ear in order to produce monaural stimulation. Stimuli employed were 100 dB SPL clicks and tone bursts. Normative recordings showed five positive peaks, P1-P5 and four negative peaks, N1-N4. Electrolytic lesions were then made to the superior olivary complex (SOC) ipsilateral to the stimulation (6 animals), contralateral to the stimulation (8 animals), and trapezoid body (TB) (8 animals). In each group a statistical analysis of the results (amplitudes and latencies) was made (paired t test). After lesions to the ipsilateral SOC, there was an increase in the amplitude of P1 and a decrease in P3. After lesions to the contralateral SOC, there was a larger decrease in P3, which disappeared in 2 guinea pigs which had a large lesion involving many TB fibers. After TB lesions, there was a decrease in the P2-N2 composite wave, disappearance of P3, a decrease in P4, and an increase in the latency of P1 and P1-P2 and P2-P4 intervals. After ipsilateral SOC lesions, which certainly involved the uncrossed olivocochlear efferent tract, the increase in P1 suggested a disinhibition of the efferent fibers. The large decrease or the loss of P3 after TB lesions and SOC lesions involving many TB fibers suggested that P3 could be generated by the contralateral part of the TB fibers, in the vicinity of the contralateral SOC. These data are in agreement with the predominance of fiber tracts in the generation of BAEP.

Animals↗

PubMed2002

Summation in autoshaping is affected by the similarity of the visual stimuli to the stimulation they replace.

Pigeons received autoshaping with 2 stimuli, A and B, presented in adjacent regions on a television screen. Conditioning with each stimulus was therefore accompanied by stimulation that was displaced from the screen whenever the other stimulus was presented. Test trials with AB revealed stronger responding if this displaced stimulation was similar to, rather than different from, A and B. For a further experiment the training just described included trials with A and B accompanied by an additional, similar, stimulus. Responding during test trials with AB was stronger if the additional trials signaled the presence rather than the absence of food. The results are explained with a configural theory of conditioning.

Animals↗

PubMed1987

Mechanisms mediating the brain stem control of somatosensory transmission in the dorsal horn of the cat's spinal cord: an intracellular analysis.

The effect of brainstem stimulation was studied on neurones recorded intracellularly in the superficial and deeper laminae of the lumbosacral dorsal horn of the spinal cord in anaesthetised cats. Stimulation in the nucleus locus coeruleus (LC) produced a hyperpolarization in 4/13 multireceptive neurones and produced a biphasic action consisting of a hyperpolarization which was followed by a depolarization in 3/13 neurones. These actions were produced irrespective of whether the multireceptive neurone was located in the superficial or deeper laminae of the dorsal horn. Stimulation failed to produced postsynaptic potentials in the remaining 6/13 multireceptive neurones. The amplitude of hyperpolarization was increased by the passage of depolarising pulses through the recording microelectrode and decreased by hyperpolarizing pulses. Stimulation in other brainstem areas such as, the lateral (FTL), paralemniscal (FTP) and central (FTC) divisions of the tegmental field and the nuclei raphe magnus (NRM) and reticularis magnocellularis (RMc) also hyperpolarized neurones in the dorsal horn. The polarity of hyperpolarization evoked from some brainstem areas (FTP, FTC, RMc) could be reversed to depolarisation by the passive diffusion of ions from the recording microelectrode containing 3M-KCl. Brainstem (LC, NRM, FTP, FTL) stimulation generated long lasting (700 ms) hyperpolarization on 4/4 selectively nocireceptive neurones of lamina I. There was, however, no effect on the activity of 5/5 neurones recorded in laminae I/II which in addition to receiving excitatory cutaneous inputs were inhibited by heat stimuli. Stimulation in LC also produced dorsal root potentials (DRPs) and reduced the amplitude of simultaneously recorded excitatory postsynaptic potentials (EPSPs) generated by the activation of primary afferent fibres in 3 multireceptive neurones. It is concluded that inhibition of nociceptive transmission in the spinal cord from LC and other brainstem areas may involve both pre- and postsynaptic mechanisms.

Action Potentials↗

PubMed2005

The saltation illusion demonstrates integrative processing of spatiotemporal information in thermoceptive and nociceptive networks.

In sensory saltation, first reported by Geldard and Sherrick (Science 178:178-179, 1972), a stimulus is displaced towards a second one following closely in time and space as a function of the delay between the stimuli. The distance between stimulus locations is restricted by the extension of sensory fields in the primary somatosensory cortex. Saltation is assumed to reflect dynamic changes in these cortical representations. The present study demonstrates for the first time saltation in thermoceptive and nociceptive pathways with CO(2) laser stimulation. Stimuli were presented to the dorsal forearms of 18 healthy subjects at two intensities. Saltation patterns consisted of a reference stimulus S0 near the wrist, the first test stimulus S1 at the reference location after a fixed onset delay of 1,000 ms, and a second test stimulus S2 at a location 105 mm distant from reference after a variable onset delay of 60-516 ms. Perceived positions were indicated by the subjects without skin contact with a 3D tracker. As expected, subjects mislocalized S1 towards S2. Mean S1 displacement was 51+/-36 mm. Decreasing delays between S1 and S2 resulted in increasing displacements, independent of intensity. However, since no clear-cut discrimination of thermal versus nociceptive activation could be achieved definite conclusions about differences between the two modalities cannot be drawn. In addition, effects of body site on the saltation characteristics were observed. The saltation paradigm constitutes a promising approach to the functional analysis of spatiotemporal dynamics in thermoceptive and nociceptive networks to supplement brain-mapping approaches to cortical sensory fields.

Adult↗

PubMed1994

Characterization of the human neutrophil C1q receptor and functional effects of free ligand on activated neutrophils.

The partial characterization and expression of the C1q receptor (C1q-R) in relation to other complement receptors present on the surface of neutrophils has been examined, as well as the effects of free C1q on cell function. A polyclonal anti-C1q-R antibody recognizes a 68-kD neutrophil surface protein. C1q-R expression was not upregulated upon warming, priming, or exposure to FMLP, but decreased after exposure to phorbol myristate acetate (PMA), because of shedding of the receptor into the extracellular medium, as detected by enzyme-linked immunosorbent assay. CR3 and CR1 expression was upregulated from intracellular pools after cell stimulation by PMA. No evidence of intracellular pools of C1q-R was found, as assessed by immunoblotting of subcellular fractions. But C1q-R appeared to be expressed early in cell differentiation, was detected on undifferentiated HL-60 cells, and like CR3 expression, increased upon 5 days differentiation towards a neutrophil lineage. However, C1q-R expression decreased upon additional culture, whereas CR3 expression continued to increase. A large variation in the percentage of peripheral cells expressing C1q receptors in donors was observed, ranging from 13% to 100%, contrasting with CR3 receptors that exhibited less variability. Interactions between free monomeric C1q and neutrophils were also studied. Incubation of stimulated neutrophils with 10 to 100 micrograms/mL C1q resulted in a further increase in CR3 expression and adherence to albumin-coated surfaces. Staphylococci opsonized with low quantities of C1q (0.1 to 1 microgram/mL) mediated a moderate and sustained respiratory burst in neutrophils, whereas a burst of similar magnitude was generated only with free C1q at concentrations 10- to 100-fold higher. Stimulation was only partially inhibited if cells were first treated with anti-C1q-R antibody, suggesting other C1q binding proteins may be present on the cell surface. In summary, neutrophil C1q receptor is approximately 68-kD, exhibits varying expression on different subjects, and is not upregulated from intracellular stores on exposure to soluble stimuli. Stimulated, but not resting, neutrophils selectively respond to raised levels of free C1q, resulting in altered cell function and enhanced CR3 receptor expression. These studies thus suggest complex roles for C1q in neutrophil function.

Antibodies↗