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PubMed1987

Role of chemotactic factor inactivator in modulating alveolar macrophage-derived neutrophil chemotactic activity.

The stimulated alveolar macrophage is a potent source of neutrophil chemotactic activity. The release of this chemotactic activity can be inhibited by pretreating alveolar macrophages with anti-C5 antibody. We hypothesized that C5a, a fragment cleaved from C5 when C5 is activated, might activate the alveolar macrophage to release neutrophil chemotactic activity and that chemotactic factor inactivator, a serum inhibitor of C5a, could decrease this release. Activated complement components including C5a were found to stimulate guinea pig macrophages to release chemotactic activity into their culture supernatants at levels that were significantly higher than the chemotactic activity of C5a alone (P less than 0.001). Chemotactic factor inactivator was found to cause a marked reduction in the chemotactic activity released by macrophages stimulated with phagocytic and nonphagocytic stimuli (P less than 0.001, all comparisons). These data indicate that C5a can stimulate alveolar macrophages to release chemotactic activity in vitro, and that chemotactic factor inactivator may play a role in modulating this process.

Aminopeptidases↗

PubMed1984

The effect of captopril treatment on potassium-induced stimulation of aldosterone production in vitro.

Potassium and angiotensin (AII) show interdependence as stimuli of aldosterone production. However, potassium stimulates in vitro in the absence of AII. In the present study we examined for a contribution by AII to the in vitro stimulatory potential of potassium, an AII effect mediated on the adrenal before killing of the animal. Captopril, an angiotensin converting-enzyme inhibitor, was administered orally and by sc injection for 3 days so as to decrease levels of AII. Aldosterone secretory responses by adrenal capsules to graded increments in potassium were measured subsequently using a perifusion system. It was found that captopril pretreatment significantly reduced the magnitude of aldosterone secretory response to increments in potassium of 0.5 to 6.0 mM, from a baseline potassium concentration of 3.5 mM. Responses to the lowest increment in potassium, 0.5 and 1.0 mM, were virtually abolished by captopril treatment. The results suggest that AII sensitizes the adrenal glomerulosa such that very small changes in potassium concentration can affect aldosterone production.

Adrenal Glands↗

PubMed1979

Tertiary esophageal contractions evoked by acoustical stimuli.

"Spontaneous" tertiary esophageal contractions occur in a high proportion of healthy subjects. This study was carried out to investigate whether such contractions can be elicited by acoustical stimuli, to determine the threshold intensity at which contractions occur, and to find out how many of a sequence of equiintense tones at such a threshold intensity evoke contractile responses. Esophageal pressures were recorded 5, 10, and 15 cm above the lower esophageal sphincter, and swallowing was recorded by an electromyogram of the mylo-hyoid muscles. The results are summarized as follows: (a) All of 22 subjects exposed to 1000 Hz tones of intensities between 70 and 125 dBA responded with teritary contractions; their mean threshold intensity was 86.8 dBA +/- 3.0 SEM. Intensities that were 5 to 20 dBA higher were necessary to evoke contractions also in response to a second tone of a given intensity. (b) In 36 to 40 subjects exposed to 40 1000 Hz, 90 dBA tones tertiary contractions occurred in response to 47.2% of stimuli presented. (c) On repetitive stimulation, there was a significant decrease in number and amplitude of esophageal responses with an increasing number of stimuli. It is concluded that the esophagus takes part in the response system of the healthy organism to environmental stimuli.

Acoustic Stimulation↗

PubMed1995

Comparison of the responses to moving texture patterns of simple and complex cells in the cat's area 17.

1. Whether complex (C) cells are the only truly texture-sensitive units in the cat's primary visual cortex remains controversial. In view of the strong physiological significance of having putatively only one class of cells sensitive to visual noise in the striate cortex, we reinvestigated this issue. Sensitivities of simple (S) and C cells to noise were quantitatively studied and compared in order to clearly document the response properties of cells in the striate cortex to visual noise and to establish whether one can unequivocally segregate S from C cells on the basis of those specific properties. 2. Receptive fields were stimulated with all relevant stimuli, i.e., drifting sine-wave gratings, electronically generated noise pattern of 256 x 256 elements (ratio 1:1 of dark and light elements), and flashing and moving bars (both bright and dark). 3. A total of 60 S cells out of 85 (70.6%) and 90 C cells out of 101 (81.8%) responded to the motion of visual noise. Responses of most C cells were sustained, i.e., their discharge rate was maintained at a constant level throughout presentation of the stimulus. On the other hand, responses of the majority of S cells were characterized by several bursts of discharges. On average, optimal firing rates were greater for gratings than for noise. 4. For practically all cells, responses to noise varied as a function of direction of motion. The mean direction bandwidths were, respectively, 43 +/- 24 degrees and 48 +/- 23 degrees (mean +/- SD) for S and C cells. In both groups, neurons were more broadly tuned for the direction of noise than that of gratings (t-test, P < 0.001). We rarely observed bimodal tuning curves for noise, with each peak lying on either side of the orientation curve. These results could be expected if one considers texture stimuli not in the space domain (as dot patterns) but in the frequency domain, i.e., patterns containing all spatial frequencies and orientations. 5. In general, the direction indexes of S and C cells were similar whether they were stimulated by drifting noise or gratings. S cells had a slight tendency to be more direction selective for noise than for gratings. 6. For all S and C cells tested, responses to noise varied as a function of drift velocity. The mean optimal velocity was 12.9 and 10.2 degrees/s for S and C cells, respectively (t-test, P > 0.05). Most cells were band-pass with mean bandwidths of 2.2 and 2.7 octaves for S and C cells, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1976

[Effect of arpenal on the EMG-potentials of the anterior tibial muscle in cats during acute phosdrine poisoning].

The authors examined the changes in the nerve-muscular conductivit occuring after acute poisoning with phosdrine and treatment with arpenal and oximic reacytivators of HE-toxogonine and TMB-4 on 20 cats, anesthethised with urethane and atropine protection under the conditions of artificinal respiration. They found that there was a total nerve-muscular block cessation of the mediation in the myoneural synaptic zones, characterized by complete cessation also of the induced electrical responses after single and serial stimuli, during acute intoxications with phosdrine, used in lethal doses of 300 mg/kg intramuscularly. After treatment with H-cholinolitics (arpenal) there was a quick recovery of the muscle contractions as well as of the evoked myopotentials after stimulation with single electric stimuli. In contrast to the oximnic reactivators of He (toxogonine, TMB-4) during serial electric stimuli (10,20 and 30 per second after treatment with arpenal there was a quick contraction only after the first stimulus, after which a progresive weakening of the induced electric myopotentials followed till the appearence of a total nerve-muscular block. This phenomenon was explained by the lack of reactivating properties of H-cholinolitics to HE, inhibited by FOV.

Acute Disease↗

PubMed2000

Single unit responses of human cutaneous mechanoreceptors to air-puff stimulation.

OBJECTIVE: To investigate responsiveness of human cutaneous mechanoreceptor to selective tactile stimuli produced by brief air-puff stimulation. METHODS: Using percutaneous microneurography, activities of single sensory units innervating glabrous skin of the hand were recorded, and air-puff stimuli with a short rise time (0.5 ms), generated by a high-speed air control system, were applied to the receptive field. Receptor activation time was estimated as the latency difference between electrically and air-puff evoked responses. RESULTS: Thirty units were analyzed: all 4 kinds of mechanoreceptors of human glabrous skin (fast adapting type 1 [FA I, n=7], fast adapting type 2 [FA II, n=4], slowly adapting 1 [SA I, n=5] and slowly adapting 2 [SA II, n=14]) were activated by air-puff stimulation. Estimated receptor activation times were 0.6-6.2 ms (mean 2.2 ms). FA II units occasionally responded twice or more to a single air-puff stimulus. CONCLUSIONS: Brief air-puffs can activate all 4 human cutaneous mechanoreceptors, and the receptor transduction time is estimated as approximately 2.0 ms. Properties of human mechanoreceptors can be studied using air-puff stimulation and microneurography.

Adult↗

PubMed1983

Effects of stimulation of the mediodorsal nucleus and its projection cortex on heart rate in the rabbit.

Electrical stimulation of prefrontal cortex in anesthetized rabbits evoked small (less than 10%) changes in heart rate. In contrast, stimulation of the thalamic mediodorsal nucleus (MD) elicited decreases in heart rate proportional to the stimulating current. The maximal peak reductions in heart rate evoked by higher current intensities were 85% from prestimulus levels. The bradycardiac response had a short latency after stimulus onset (less than 1 s, peak within 5 s), and the heart rate usually returned to baseline within 30 s after stimulation. Vagal cholinergic innervation of the heart was suggested as the final effector pathway since bilateral vagotomy or administration of atropine (sulfate or methyl nitrate, 0.15-0.4 mg/kg, i.v.) virtually abolished the rapid bradycardiac responses. Administration of a beta-adrenergic receptor blocker (propranolol, 3 mg/kg, i.v.) was without effect on the heart rate response. The effective medial thalamic area for evoking a response was localized to MD, the thalamic midline nuclei between both MDs and a region continuous with, but posterior to MD (e.g. parafascicular nucleus). A descending effector pathway from the thalamus was implicated since complete bilateral ablation of prefrontal cortex did not reduce the stimulus-produced bradycardia evoked from MD. Similar large bradycardiac responses were obtained in an unanesthetized preparation to both MD stimulation and to sensory stimuli, suggesting a possible physiological correlate for these intracranially-evoked heart rate changes.

Animals↗

PubMed1994

Multiple defects of T helper cell function in newly diagnosed patients with Hodgkin's disease.

T helper cell (TH) function, as assessed by interleukin-2 (IL-2) production and [3H]thymidine incorporation, was studied in 47 newly diagnosed untreated patients with Hodgkin's disease (HD) and 34 healthy controls. Three different stimuli were used to stimulate in vitro peripheral blood mononuclear cells (PBMC): influenza A vaccine (FLU), HLA alloantigens (ALLO) and phytohaemagglutinin (PHA). Four different patterns of TH function were observed in HD patients: (1) IL-2 production in response to all of the stimuli (40%); (2) IL-2 production in response to ALLO and PHA but not to FLU (26%); (3) IL-2 production in response to PHA alone (19%); and (4) failure to respond by IL-2 production to any of the three of the stimuli (15%). Thus, defective in vitro TH function was detected in the majority of these patients (60%). Defective TH function was observed in none of the 34 controls. Severely compromised TH function (patterns 3 and 4) tended to be associated with more advanced clinical presentation and more compromised haematological parameters (P < 0.05). The IL-2 production assay was more sensitive than the proliferative assay as only 30% of the HD patients failed to proliferate in response to FLU, and none failed to proliferate in response to either ALLO or PHA; this assay can detect subtle, multiple patterns of immune dysregulation in untreated HD patients. Our results suggest that HD is associated with a fundamental dysregulation in TH function, illustrate the complexity of such dysregulation, and raise the possibility that HD progression will be associated with a type-1-type-2 switch in immunoregulatory cytokine production.

Adolescent↗

PubMedDate not supplied

[Effect of narcotics on impulse conduction in the afferent pathways of visceral nerves].

In tests set up on cats immobilized with pyraxolone and anatruxonium the effect of non-inhalation narcotics on the evoked potentials of the cortex and subcortical structures with visceral and also somatic, acoustic and photo-stimulation was studied. With stimuli of different modality sodium ethaminal was found to inhibit evoked potentials of the cerebral hemispheres, diencephalon and midbrain cortex. Hexabarbital sodium suppressed biopotentials in specific, associative and non- specific brain structures in the event of visceral and somatic stimulation. Viadril enhanced the amplitude of potentials in all types of stimulation Urethan inhibited potentials in specific pathways of visceral and somatic nerves as well as in associative and non-specific brain structures following visceral, somatic and acoustic stimulation, with the amplitude of potentials to photostimulation then increasing.

Animals↗

PubMed2003

Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits.

OBJECTIVE: To compare 3 types of noxious stimuli applied to various anatomic areas of anesthetized dogs and rabbits for determination of the minimum alveolar concentration (MAC). ANIMALS: 10 dogs and 10 rabbits. PROCEDURE: Dogs were anesthetized with isoflurane and halothane in a randomized order. Rabbits were anesthetized with isoflurane. The MAC was determined by skin incision on the lateral aspect of the chest; clamping of the tail, paw of the forelimb, and paw of the hind limb; and application of electrical current to the oral mucosa (dogs only), forelimb, and hind limb. The MAC was the end-tidal concentration midway between the value permitting and preventing purposeful movement in response to noxious stimuli. RESULTS: In dogs, mean +/- SEM MAC for isoflurane was 1.27 +/- 0.05% for clamping stimuli, 1.36 +/- 0.04% for oral electrical stimulation, 1.35 +/- 0.04% for electrical stimulation to the limbs, and 1.01 +/- 0.07% for surgical incision. The MAC for halothane was 0.97 +/- 0.03% for tail clamping, 0.96 +/- 0.03% for clamping of the limbs, 1.04 +/- 0.03% for electrical stimulation, and 0.75 +/- 0.06% for surgical incision. In rabbits, MAC for isoflurane was 2.08 +/- 0.02% for clamping stimuli, 2.04 +/- 0.02% for electrical stimulation, and 0.90 +/- 0.02% for surgical incision. The MAC for surgical incision was significantly lower than values for the other methods in both species. CONCLUSIONS AND CLINICAL RELEVANCE: Use of electrical current and clamping techniques resulted in similar MAC values. Surgical incision underestimated MAC values in dogs and rabbits.

Anesthesia, Inhalation↗

PubMed1980

Firing characteristics of neurons mediating optokinetic responses to rat's vestibular neurons.

1) The responses of single units in the pretectum (Pt) and in the n. reticularis tegmenti pontis (NRTP) to constant velocity horizontal rotation (0.25--60 deg/s) of a large-field visual pattern were studied in immobilized, non-anesthetized DA-HAN rats. In addition, responses of Pt and NRTP neurons to pure vestibular stimuli (rotation in the dark) were studied. 2) Pt neurons showed seven response types to optokinetic stimulation (Table 1). The most frequent response (48%) consisted of a very rapid increase in firing to steady state on temporonasal motion stimulation of the contralateral eye; nasotemporal stimuli yielded no change in resting rate as did stimulation of the ipsilateral eye. The response maximum occurred at a retinal slip velocity of 1 deg/s. None of the Pt units tested responded to pure vestibular stimuli. 3) NRTP neurons - as Pt units - most frequently (43%) increased their discharge rate on temporonasal stimulation of the contralateral eye and maintained a constant resting rate during nasotemporal motion. Peak response amplitudes also occurred with retinal slip velocites of 1 deg/s. Contrary to the fast time-to-peak of the responses of Pt neurons NRTP units showed a slow rise in frequency of firing to peak response levels. 4) NRTP neurons responded to pure vestibular stimuli (horizontal angular acceleration in the dark). The vestibular responses were synergistic with those evoked in the same neurons by optokinetic stimuli. Thus, the most frequently encountered type of optokinetic response (s. above) showed a type II vestibular response. 5) Comp]arison of OKN and Vn optokinetic responses with those of Pt and NRTP suggests that the unidirectional-selective Pt and NRTP neurons are important links in the central optokinetic path. In addition, the NRTP may represent the site at which the retinal slip signal and the eye velocity signal converge. This convergence has been postulated in models of the system [12].

Animals↗

PubMed1982

The visually evoked potential in humans with amblyopia: pseudorandom modulation of uniform field and sine-wave gratings.

The visually evoked potential was recorded in response to pseudorandom modulation of a uniform field and sine-wave gratings in humans with naturally occurring amblyopia. Analysis in the frequency domain showed similar temporal tuning when the nonamblyopic and amblyopic eye were stimulated with a uniform field and with spatial stimuli. Although most observers showed some reduction in the cortical response to stimulation of the amblyopic eye with uniform field modulation, all observers showed reductions in the response obtained for stimulation of the amblyopic eye with spatial stimuli. This decrease in the cortical response to stimulation of the amblyopic eye for sine-wave gratings was present at either the low and middle temporal frequencies or over the range of temporal frequencies tested, and was greater than that observed in those amblyopes who also showed reductions with uniform field modulation. Latency measures in the time domain showed increases in the response of the early components when the amblyopic eye was stimulated with a uniform field and with sine-wave gratings above 2 c/deg. These electrophysiological results confirm the results obtained psychophysically which suggest that although amblyopia is primarily a spatial anomaly, the response is influenced by the temporal attributes of the stimulus as well.

Adolescent↗

PubMed1989

Thoracic stimulation and prolactin secretion.

Although galactorrhea and/or enhanced prolactin (PRL) secretion have been reported with a variety of thoracic stimuli, the effect of thoracic stimulation on dynamic prolactin secretion is not clear. A 49-year-old woman with ventilatory muscle weakness from polio presented with galactorrhea, and intermittent hyperprolactinemia but regular menses. The galactorrhea was noted following the use of a new, tight fitting cuirass (thoracic apparatus which assists ventilation). To determine if the new, "tight" cuirass elicited enhanced PRL secretion, and to assess more extensively the effect of such thoracic stimulation on PRL secretion, serum PRL was measured during brief and prolonged stimulation, sleep, and pharmacological manipulation of PRL. Basal PRL was normal (less than 25 ng/ml) and increased during brief stimulation (1 hour) with the "tight" (137%) and "loose" cuirass (140%). Although the absolute increments were similar, the "tight" cuirass elicited an earlier PRL peak than the "loose" cuirass and the PRL began to decrease while the "tight" cuirass was still functioning. Several hours of thoracic stimulation resulted in a transient rise in PRL and a fall to normal, prestimulatory levels despite persistent stimulation. During this stimulation, PRL did not rise after sleep nor after insulin-induced hypoglycemia despite normal cortisol and GH increments, but the PRL response after TRH was exaggerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMedDate not supplied

[Is it possible to train Achatina fulica using visual stimulation?].

The conditioned behavior to visual stimuli was obtained in Achatina fulica mollusk on the basis of its negative phototaxis. Directional moving of snails toward black cards was accompanied by the negative unconditioned stimulation (electric current). Learning was expressed in a statistically significant decrease in locomotor activity of animals and decrease in the rate of preference of sections with black cards. Learning developed within two daily training sessions with 30 trials in each of them. Learning traces were observed as defensive behavior at least during a month after reinforcement elimination.

Animals↗

PubMed2001

Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells.

Chronic hepatitis C virus (HCV) infection frequently develops into liver disease and is accompanied by extra-hepatic autoimmune manifestations. The tetraspanin CD81 is a putative HCV receptor as it binds the E2 envelope glycoprotein of HCV and bona fide HCV particles. Here we show that HCV E2 binding to CD81 on human cells in vitro lowers the threshold for IL-2 receptor alpha expression and IL-2 production, resulting in strongly increased T cell proliferation. HCV E2-induced co-stimulation also enhances the production of IFN-gamma and IL-4 and causes increased TCR down-regulation. This suggests that binding of HCV particles to CD81 on T cells in vivo may lead to activation by otherwise suboptimal stimuli. Therefore, co-stimulation of autoreactive T cells by HCV may contribute to liver damage and autoimmune phenomena observed in HCV infection.

Antigens, CD↗

PubMed1998

Detection, cDNA cloning and sequencing of canine interleukin 12.

In canine peripheral blood mononuclear cells (PBMC) the mRNAs coding for both subunits of canine interleukin 12 (IL-12) were identified using reverse transcription polymerase chain reaction (RT-PCR). Stimulation of canine PBMC with Staphylococcus aureus strain Cowan plus Concanavalin A for 5 h resulted in significant mRNA synthesis. Likewise, inactivated vaccinia virus induced IL-12 mRNA synthesis, however with different kinetics. The complete nucleotide sequence for both IL-12 subunits was determined using rapid amplification of cDNA ends (RACE)-PCR and cloning of amplified specific cDNAs. Computer-aided amino acid (aa) sequence comparison of both canine IL-12 subunits revealed more than 80% identity with the amino acid sequences of six other mammalian species. Closest relationship was found to human, porcine, bovine and cervine IL-12. However, no reactivity was found with antibodies directed against human IL-12, when supernatants of stimulated canine PBMC were tested. Supernatants of canine PBMC stimulated for IL-12 release also induced interferon gamma (IFN-gamma) mRNA as detectable by RT-PCR; however, it was not clear whether IFN-gamma mRNA synthesis was due to an IL-12 specific effect or other stimuli. As to the stimulating effect of IL-12 on canine IFN-gamma mRNA synthesis, recombinant human IL-12 was found to be a good inducer. Since IL-12 is regarded a major regulatory molecule of T-cell-mediated immune response and cell growth our work on the cloning and sequencing of this cytokine from dogs lays the basis for future investigations on the biological and possible therapeutic role of canine IL-12.

Amino Acid Sequence↗

PubMed1999

Patterns of hyperalgesia in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a triad of sensory, motor and autonomic dysfunctions, with long-standing pain and temperature differences of the affected and contralateral limb as predominant symptoms. The pathogenesis of the disorder still remains unclear. Among the main hypotheses of an underlying pathophysiology we find inflammatory processes and dysfunction of the sympathetic nervous system. Whether the main site of dysfunction is found centrally or peripherally is not known. With psychophysical methods we studied patterns of hyperalgesia to obtain a better understanding of the neuropathic pain component in CRPS. Forty patients in an acute phase of CRPS and a median duration of the disease of 10 weeks, were included in the study. Hyperalgesia to heat was tested with a thermode providing feedback-controlled temperature increases. Two forms of mechanical hyperalgesia were examined: phasic mechanical stimuli by using a custom-made impact stimulator for the determination of individual pain thresholds, tonic mechanical stimuli were applied using a pinch-device. Additionally a 'wind-up' paradigm was used to study a pain phenomenon of presumed central origin: a defined impact stimulus was given once and five times in repetition. A subpopulation of patients was reevaluated for mechanical hyperalgesia after i.v. injection of 500 mg acetyl-salicylic acid. Hyperalgesia to heat was insignificant. We found, however, a marked mechanical hyperalgesia to phasic impact stimuli (P < 0.005), whereas, static stimulation (squeezing skin folds) results were insignificant again. Wind-up related pain was also significantly enhanced in the affected limb (P < 0.02). The anti-inflammatory agent had no effect. These results indicate a non-inflammatory pathogenesis in CRPS presumably central in origin.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1990

Transmitter characteristics of small mesenteric arteries from the rat.

We have studied the neurogenic response of small mesenteric arteries from the rat to evaluate the involvement of possible co-transmitters under various modes of stimulation. Segments of small branches of the mesenteric artery were mounted in a myograph and the intramural nerves were activated with transmural electrical stimulation. A single stimulation of the nerves caused a contraction that was reduced by only 20% in the presence of adrenergic blocking agents (prazosin or phenoxybenzamine), whereas the steady-state response to continuous nerve stimulation of high frequency was reduced by 90-95%. In contrast, all responses to applied noradrenaline in doses up to at least 1 mM were eliminated by phenoxybenzamine treatment. The stable ATP analogue, alpha,beta-methylene ATP, reduced the response to a single nerve stimulation by 70%, but reduced the contraction caused by continuous high-frequency nerve stimulation by only 10%. None of these agents affected the response to applied neuropeptide Y (NPY). The response of relaxed vessels to nerve stimulation was totally blocked by the combination of an adrenoceptor-blocking agent and alpha,beta-methylene ATP, although even in this situation a further neurogenic response could be revealed in vessels precontracted with vasopressin. Responses to either single stimuli or brief burst stimulations were potentiated after high-frequency stimulation. Both the adrenergic and non-adrenergic components were enhanced to roughly the same extent. Also the potentiated response was eliminated by the combined application of prazosin and alpha,beta-methylene ATP. The non-adrenergic transmitter in the sympathetic nerves of small arteries thus appears to be the dominant transmitter during low-frequency nerve stimulation, causing rapid but phasic activation. Noradrenaline is the most important transmitter for higher frequencies, exerting slower but sustained contractions. The post-stimulatory potentiation affects both the adrenergic and the non-adrenergic part of the neurogenic response.

Adenosine Triphosphate↗