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Analysis of electrodermal evidence for a paramedullary afferent tract in patients with a transection of the thoracic spinal cord.

An effort was made to corroborate earlier reports that the central nervous system rostral to a functionally complete transection of the human spinal cord remains responsive to noxious stimulation of sites below the level of the transection. Nine patients were studied who had sustained a functionally complete transection of the thoracic spinal cord between T5 and T11 spinal segments. Noxious electrocutaneous stimulation or intense pressure was applied to a lower extremity while electrodermal activity was recorded concurrently from contralateral palmar sites which were shown to be under normal suprasegmental control. While electrodermal responses were occasionally recorded in the post-stimulus intervals, there was no tendency for these responses to exceed the number or amplitude of responses recorded during stimulus-free control periods. These results were interpreted as suggesting that the few responses observed during the post-stimulus intervals were not evoked by stimulation of the lower extremities and were instead representative of spontaneous electrodermal activity or were related to uncontrolled auditory or visual stimuli accompanying lower extremity stimulation. Additional results highlighted the importance of controlling accessory auditory and visual cues occurring in conjunction with lower extremity stimuli. In some patients with a transection above the sympathetic outflow to the lower extremities, it was shown that electrodermal responses from the plantar aspect of each foot could be elicited reliably by lower extremity stimuli. These results confirmed previously reported evidence that the functionally isolated human spinal cord can reflexly mediate electrodermal responses.

Adolescent↗

Physiological phenotyping of cholecystokinin-responsive rat taste receptor cells.

The recent discovery that subsets of rat taste receptor cells (TRCs) express the peptide cholecystokinin (CCK) and that subsets of TRCs respond to CCK with altered potassium currents or elevated intracellular calcium via CCK-A receptor has lead to the hypothesis that CCK may play a novel signaling role within the taste bud, perhaps modifying tastant responses by co-transmission with a classic transmitter. To better understand this phenomenon, CCK-responsive TRCs were characterized for sensitivity to two bitter stimuli, quinine or caffeine, or to the neurotransmitter ACh using a ratiometric procedure with the calcium sensitive dye fura-2. In characterizing TRC responses to quinine, it was observed that quinine-induced elevations of intracellular calcium were not due to endogenous fluorescence of the quinine molecule. Most (60-70%) CCK-responsive cells were also sensitive to either bitter stimuli or to cholinergic stimulation. These data suggest that TRCs expressing CCK-receptors also express receptors to bitter stimuli and/or muscarinic receptors. They further support the notion of a putative modulatory role of CCK with convergence of multiple inputs occurring at the level of intracellular calcium.

Animals↗

The effect of hand position and pattern motion on temporal order judgments.

Subjects made temporal order judgments (TOJs) of tactile stimuli presented to the fingerpads. The subjects judged which one of two locations had been stimulated first. The tactile stimuli were patterns that simulated movement across the fingerpads. Although irrelevant to the task, the direction of movement of the patterns biased the TOJs. If the pattern at one location moved in the direction of the second location, the subjects tended to judge the first location as leading the second location. If the pattern moved in the opposite direction, that location was judged as trailing. In a series of experiments, the effect of the spatial position of the hands and fingers on TOJs and the perception of the direction of pattern movement were examined. Changing the position of the hands so that the patterns no longer moved directly toward each other reduced or eliminated the effect of motion on TOJs. In a variation of Aristotle's illusion, the moving patterns were presented to crossed and uncrossed fingers. The results indicated that, contrary to Aristotle's illusion, the subjects processed the moving patterns relative to an environmental framework, rather than to the local direction of motion on the fingerpads. Presenting the patterns to crossed hands produced results similar to those obtained with crossed fingers: The subjects processed the patterns according to an environmental framework.

Discrimination, Psychological↗

[Comparative investigation of somatosensory spinal and cortical evoked potentials in children (author's transl)].

Somatosensory spinal (spinEP) and primary cortical evoked responses (ssEP) to median and tibial nerve stimulation (at forefinger, wrist, and ankle respectively) were investigated by means of summation techniques in 23 normal children aged 6 to 14 years. Amplitude recovery functions of cervical spinEP were tested by paired stimuli and short tetanic stimulation at the wrist; spinEP amplitudes were unchanged for stimulus intervals down to 5 ms. The amplitudes of the cervical spinEP after strong stimuli to the finger were only a quarter as great as those obtained by stimulation of the wrist at motor threshold strength. In one patient with the Brown-Séquard syndrome cervical spinEP were absent for stimuli on the side of position sense impairment, but were unaffected for stimuli on the side of dissociated sensory loss. The normal latencies of spinEP (to the onset of the negative potential) and ssEP (to first negative peak) are presented as functions of body height. The difference between these two latencies yielded a central latency from the lower cervical spinal cord of about 9--10 ms. The spinal afferent conduction velocity, calculated from the difference between the lumbar and cervical latencies after tibial nerve stimulation at the ankle, was found to be 74m/s.

Adolescent↗

Two forms of sensitization of the local bending reflex of the medicinal leech.

Sensitization of the local bending reflex of the medicinal leech Hirudo medicinalis was studied in a semi-intact preparation in which behavioral and electrophysiological recordings were made simultaneously. 1. Sensitization of local bending could be produced in two ways: by repeated stimulation of the mechanoreceptor sensitive to pressure (the P cell), and by stimulation of the mechanoreceptor sensitive to noxious stimuli (the N cell). 2. Both forms of sensitization produced a central neuronal change, measured as an increase in the number of stimulus-evoked action potentials in cell 3 (an excitor of dorsal longitudinal muscles). 3. Intracellular stimulation of serotonin-containing neurons 21 and 61 mimicked the sensitizing stimuli, but stimulation of the Retzius cell, which also contains serotonin, did not. 4. Stimulation of the Leydig cell, which releases octopamine, decreased the strength of local bending.

Action Potentials↗

The augmentation effects of secretin on the insulin responses to known stimuli: specificity for glucose.

Secretin stimulates insulin release directly and augments insulin responses when administered prior to an insulinogenic stimulus. The magnitude and specificity of this augmentation effect of secretin pretreatment was evaluated in normal subjects to pulses of the following stimuli: 5 g glucose (n = 6), 1 g arginine (n = 8), 2 microgram isoproterenol (n = 6), 0.5 g tolbutamide (n = 5) and 0.5 mg glucagon (n = 6). Secretin was administered either as a 15 U pulse with a 3 U/min infusion for 25 min or as 4-150 U pulses. A period of 30 min elapsed after either the cessation of the infusion or the final 150 U pulse. In all studies, the acute insulin responses immediately following secretin were observed and had returned to baseline levels prior to the administration of any insulinogenic stimulus. Secretin only augmented the acute insulin responses to 5 g glucose pulses (pre-secretin glucose; 28 +/- 20 muU/ml, mean +/- SD; post-secretin glucose pulse: 45 +/- 37 muU/ml, P less than 0.5), an increase of 56 +/- 21% (P less than .005). A highly linear relationship was noted (r = .98, P less than .01) between the acute insulin response to glucose before and after secretin suggesting that the insulin response to the control glucose pulse is a major determinant of the glucose stimulated response after secretin. Secretin pretreatment did not augment the insulin responses to arginine, isoproterenol, tolbutamide and glucagon. The specificity of secretin for augmenting glucose stimulated insulin release suggets a possible role for secretin in carbohydrate metabolism.

Adult↗

Rapid off-response and retinal receptor diseases.

A method was described to record the electroretinogram (ERG) in response to off- and on-stimuli, using Ganzfeld light stimulation. The rapid off-response representing the cone response was recorded with the off-stimuli with the light-dark ratio of 10:1 to maintain a constant photopic condition of 1.6 X 10(3) trolands (Zero log unit). The amplitude of the rapid off-response to completely extinguishing the background light was Vo and the amplitude elicited by intermediate intensities of off-stimuli was V. Vo-V was thought to represent the state of the receptor hyperpolarization, and it was correlated with the stimulus intensity (I) by Log (Vo-V) = nLog I + C; n averaged 0.84 +/- 0.15 in 12 normal subjects, and C was a constant. The scotopic b-wave was recorded by on-stimuli with the light-dark ratio of 1:100 and with the intensity less than -2.0 log units. The cone threshold was calculated using the criterion amplitude of the rapid off-response of 10 microvolts. The rod threshold was likewise computed with the criterion amplitude of the scotopic b-wave of 50 microvolts. The cone and rod sensitivities were determined in 5 patients with progressive cone (-rod) dystrophy and in 8 patients with central pigmentary retinal dystrophy. The cone sensitivity was markedly reduced in the former and the rod sensitivity was highly affected in the latter conditions. Separate evaluations of the cone and rod functions by the present technique will be clinically useful.

Adult↗

Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli.

The effect of sensory stimulation on discharge in norepinephrine-containing locus coeruleus (NE-LC) neurons was studied in unanesthetized behaving rats. Single unit and multiple unit extracellular recordings demonstrated consistent patterns of response. (1) Short latency (15-to 50-msec), transient, biphasic changes in discharge were elicited predictably by non-noxious auditory, visual, and somatosensory stimuli; individual recordings typically exhibited polysensory responsiveness. (2) Sensory-evoked field potentials (FPs) were synchronized with unit responses simultaneously recorded from the same electrodes. (3) The magnitudes of sensory-evoked response varied as a function of vigilance, so that the largest responses occurred for stimuli which awakened animals and the least responsiveness was exhibited during uninterrupted sleep. (4) Sensory responsiveness decreased during grooming and sweet water consumption, similar to the results for sleep. (5) Characteristic response properties were topographically homogeneous throughout the NE-LC. (6) Discharge was synchronized markedly among neurons in multiple unit populations during phasic robust responses. These results are interpreted in light of the preceding report (Aston-Jones, G., and F.E. Bloom (1981) J. Neurosci. 1: 876-886) and studies of the postsynaptic effects of NE to indicate that the NE-LC system may function more in phasic processes than in modulation of the tonic arousal level. We propose that pronouced NE-LC discharge may enhance activity within target cell systems primarily concerned with processing salient external stimuli and suppress cental nervous system activity related more to tonic, vegetative functions. Thus, the NE-LC system may bias global behavioral orientation between stimuli in the external versus internal environments.

Animals↗

Variables affecting production of monocyte chemotactic factor 1 from human leukocytes stimulated with Cryptococcus neoformans.

The chemokine monocyte chemoattractant protein 1 (MCP-1) is produced predominantly by mononuclear phagocytes and stimulates recruitment into infected tissues of blood monocytes and T cells. These cell types are thought to be critical to host defenses against infections due to Cryptococcus neoformans, a major cause of disease in persons with AIDS and other disorders of cell-mediated immunity. Accordingly, in the present study, we examined the conditions under which human monocytes and bronchoalveolar macrophages (BAM) are stimulated by C. neoformans to produce MCP-1. C. neoformans was a potent inducer of MCP-1 release from monocytes, with levels of chemokine secreted similar to that seen following stimulation with lipopolysaccharide (LPS). BAM, in contrast, were stimulated by LPS, but not by C. neoformans, to secrete MCP-1. A peak in MCP-1 mRNA was seen 8 h following cryptococcal stimulation of monocytes. Nine strains of C. neoformans stimulated monocytes to release MCP-1, and there was only modest variation between strains. However, when an individual strain was used, the capacity of C. neoformans to stimulate monocyte MCP-1 release did vary, depending upon the conditions used to grow the fungal stimuli. Finally, C. neoformans stimulated comparable quantities of MCP-1 release in monocytes from donors with and without human immunodeficiency virus infection. These data establish C. neoformans as a potent stimulator of MCP-1 in monocytes, but not in BAM. The failure of C. neoformans to stimulate MCP-1 in BAM, if occurring in vivo, could result in a diminished cell-mediated inflammatory response following inhalation of airborne fungi.

Chemokine CCL2↗

Activation of human cerebral and cerebellar cortex by auditory stimulation at 40 Hz.

We used functional brain imaging with positron emission tomography (PET)-H2 15O to study a remarkable neurophysiological finding in the normal brain. Auditory stimulation at various frequencies in the gamma range elicits a steady-state scalp electroencephalographic (EEG) response that peaks in amplitude at 40 Hz, with smaller amplitudes at lower and higher stimulation frequencies. We confirmed this finding in 28 healthy subjects, each studied with monaural trains of stimuli at 12 different stimulation rates (12, 20, 30, 32, 35, 37.5, 40, 42.5, 45, 47.5, 50, and 60 Hz). There is disagreement as to whether the peak in the amplitude of the EEG response at 40 Hz corresponds simply to a superimposition of middle latency auditory evoked potentials, neuronal synchronization, or increased cortical synaptic activity at this stimulation frequency. To clarify this issue, we measured regional cerebral blood flow (rCBF) with PET-H2 15O in nine normal subjects at rest and during auditory stimulation at four different frequencies (12, 32, 40, and 47 Hz) and analyzed the results with statistical parametric mapping. The behavior of the rCBF response was similar to the steady-state EEG response, reaching a peak at 40 Hz. This finding suggests that the steady-state amplitude peak is related to increased cortical synaptic activity. Additionally, we found that, compared with other stimulation frequencies, 40 Hz selectively activated the auditory region of the pontocerebellum, a brain structure with important roles in cortical inhibition and timing.

Acoustic Stimulation↗

Effects of interleukin-10 on human peripheral blood mononuclear cell responses to Cryptococcus neoformans, Candida albicans, and lipopolysaccharide.

Deactivation of mononuclear phagocytes is critical to limit the inflammatory response but can be detrimental in the face of progressive infection. We compared the effects of the deactivating cytokine interleukin 10 (IL-10) on human peripheral blood mononuclear cell (PBMC) responses to lipopolysaccharide (LPS), Cryptococcus neoformans, and Candida albicans. IL-10 effected dose-dependent inhibition of tumor necrosis factor alpha (TNF-alpha) release in PBMC stimulated by LPS and C. neoformans, with significant inhibition seen with 0.1 U/ml and greater than 90% inhibition noted with 10 U/ml. In contrast, even at doses as high as 100 U/ml, IL-10 inhibited TNF-alpha release in response to C. albicans by only 50%. IL-10 profoundly inhibited release of IL-1beta from PBMC stimulated by all three stimuli. TNF-alpha mRNA and release was inhibited even if IL-10 was added up to 8 h after cryptococcal stimulation. In contrast, inhibition of IL-1 beta mRNA was of lesser magnitude and occurred only when IL-10 was added within 2 h of cryptococcal stimulation. IL-10 inhibited translocation of NF-kappaB in response to LPS but not the fungal stimuli. All three stimuli induced IL-10 production in PBMC, although over 10-fold less IL-10 was released in response to C. neoformans compared with LPS and C. albicans. Thus, while IL-10 has deactivating effects on PBMC responses to all three stimuli, disparate stimulus- and response-specific patterns of deactivation are seen. Inhibition by IL-10 of proinflammatory cytokine release appears to occur at the level of gene transcription for TNF-alpha and both transcriptionally and posttranscriptionally for IL-1beta.

Candida albicans↗