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At least 145 records · Page 8Linked to original sources
PubMed2002

Effects of ketanserin and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30-500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we report the effects of the serotonin (5-HT)2 receptor antagonist ketanserin and the D2 dopamine receptor blocking antipsychotic drug haloperidol on these responses. Fifteen males (aged 18-35 years) participated in four sessions at 7-day intervals, in which they received ketanserin 20 mg, ketanserin 40 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 3 h after ingestion of haloperidol or 1 h after ingestion of ketanserin. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials), and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Ketanserin 40 mg significantly reduced the amplitude of the EMG response and both doses of ketanserin significantly suppressed prepulse inhibition of the response; haloperidol had no effect on EMG response amplitude or prepulse inhibition. Neither drug affected N1/P2 amplitude or prepulse inhibition of this response. Ketanserin, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Haloperidol, but not ketanserin, elevated serum prolactin level. These results confirm that prepulse inhibition of the startle response and of the N1/P2 complex have different pharmacological sensitivities. The ability of ketanserin to attenuate the startle response may reflect its sedative action, as other drugs with sedative properties have also been found to attenuate the startle response in man. The ability of ketanserin to suppress prepulse inhibition of the startle response is consistent with previous evidence for the involvement of 5-HTergic mechanisms in the regulation of prepulse inhibition in man.

Acoustic Stimulation↗
PubMed1962

On the discriminative control of concurrent responses: the relations among response frequency, latency, and topography in auditory generalization.

Human subjects were used in a study of auditory generalization following multiple-response discrimination training. The relations observed among stimulus intensity, response probability, and response latency were invariant with respect to whether the two vocal responses conditioned were topographically discrete, as in one experiment, or topographically continuous, as in another. The major findings were:1. The probabilities associated with a specific response were maximal over several stimulus values at the extreme ends of the continuum, then dropped sharply at stimuli intermediate to the initial S(D)'s as the probability of the alternative response increased.2. Overall response latency was inversely related to the relative frequency of the two responses at each stimulus value. When the two responses were most nearly equal in probability, latencies were maximal; when one response had close to unit or zero probability, latencies were minimal.3. Analysis of the latencies of the two responses, taken separately, revealed: (a) an increase in latency as the difference between the test stimulus and the initial S(D) increased; (b) a sharp discontinuity in the latency gradient and reversal in trend at intermediate stimulus intensities; and (c) at a given stimulus value, latencies associated with the stochastically dominant response were consistently shorter than those of the nondominant response.4. No changes in response topography (fundamental frequency) were correlated with the characteristic changes in probability and latency during stimulus generalization.

Discrimination Learning↗
PubMed1980

Variation in the suppression or enhancement of responses related to drug habits as a function of stimulus classes and competing response categories.

Male prisoners who were opiate addicts (N = 47) were given three Process Association Tests of Addiction containing stimuli which evoked responses characteristic of three levels of drug habits: beginning and ending stage of addiction, intermediate stage of addiction, and an advanced level of addiction. Each test required subjects to associate 278 word stimuli with one of five options which were randomly selected from among 20 options covering the stages of addiction, steps in drug taking, and drug effects. The purpose of the study was to determine whether responses to particular options suppressed or enhanced responses to other options. A strong interaction was found between the classes of stimuli and the response options which produced suppression or enhancement. This interaction made it possible to develop a suppression scale to measure the effect of each class of stimulus. Popular responses most frequently suppressed responses of other options. Thus, when the stimuli were clean, responses of "to be clean" and "to live a normal life," which are sensitive indicators of the beginning or ending stages of addiction , suppressed responses of other stages. The response of "to be high," a prime indicator of an intermediate habit, suppressed responses of other options when the stimuli were drug names. Responses of "to be hooked" and "to fix," which are specific indicators of a strong habit, and "to be high," which is a nonspecific indicator of a strong habit, suppressed responses of many other options. In the development of new association tests the analysis of suppression could provide a basis for selectively varying option groupings in order to increase or decrease the frequently of certain responses.

Adult↗
PubMed2004

Response preparation and stimulus-response congruence to fractionating reaction time of upper and lower limbs.

We measured the fractionating reaction time for upper and lower limbs of 18 young men, using an electromyogram to clarify the interaction of response preparation and stimulus-response congruence on premotor and motor time. The reaction time was divided into two periods with respect to the onset of the electromyogram, premotor and motor components. Manipulating the probability of the Go versus NoGo signals varied three different amounts of response preparation. Prior to the imperative stimulus, precue information about the position of a stimulus was presented. In the stimulus-response congruent task, subjects were required to release a key on the same side of the body using either an upper or lower limb in response to an imperative Go stimulus. In the stimulus-response incongruent task, subjects were required to act in a reverse manner. Subjects were not supposed to respond to the NoGo stimulus. The premotor time of the upper and lower limb responses was affected by the respective effects of response preparation and stimulus-response congruence. The motor time of the upper and lower limb responses increased as the probability of the Go signal decreased but not in relation to stimulus-response congruence. These results suggest that response preparation affects not only information processing time but also peripheral motor activity due to motor programming, and that the stimulus-response congruence effect on motor time disappears when information about the position of the imperative stimulus is precued.

Adolescent↗
PubMed1975

Cells involved in the immune response. XXIX Establishment of optimal conditions for the primary and secondary immune responses by rabbit lymphoid cells in vitro.

Attempts were made to initiate the primary and secondary humoral immune responses to sheep red blood cells (SRBC) in vitro as determined by the hemolytic plaque-forming cell (PFC) response, with cell suspensions prepared from a variety of lymphoid organs of the rabbit- thymus, bone marrow, spleen, appendix, sacculus rotundus, Peyer's patches, popliteal lymph node and circulating leukocytes. A number of different media and gaseous phases were utilized in order to establish the optimal conditions for the immune response in vitro. The induction of a secondary PFC response was consistently obtained with 'memory' spleen cells obtained from rabbits 3-6 months following intravenous immunization with SRBC but not with cells of any of the other lymphoid organs, and this response probably represents the activity of memory cells which reside in the rabbit spleen. A primary response was observed only with 'normal' spleen cells, and the medium which faciliated the response was different from that which facilitated the induction of the secondary response in vitro. It was also observed, using a medium in which normal spleen cells were incapable of generating PFC', that mixed cultures of normal spleen and normal appendix or bone marrow cells could give a marked PFC reponse in vitro. Whether the PFC response to SRBCs obtained with the lymphoid cells of normal, unimmunized rabbits represent a true primary response, a secondary response, or a response of a different nature as a consequence of continuous subthreshold immunization of the rabbit with enteric microorganisms which cross-react with the antigen, remains to be determined. However, out initial successes with cultures consisting of cells of at least two distinct lymphoid organs in cases where the cells of any one of these organs could not respond, suggest that interaction of at least two functionally distinct cells is required and that the repsonse observed in vitro is probably a primary immune response.

Animals↗
PubMed2002

Response time as a discriminator between true- and false-positive responses in suprathreshold perimetry.

PURPOSE: To report on differences between the latency distributions of responses to stimuli and to false-positive catch trials in suprathreshold perimetry. To describe an algorithm for defining response time windows and to report on its performance in discriminating between true- and false-positive responses on the basis of response time (RT). METHODS: A sample of 435 largely inexperienced patients underwent suprathreshold visual field examination on a perimeter that was modified to record RTs. Data were analyzed from 60,500 responses to suprathreshold stimuli and from 523 false-positive responses to catch trials. RESULTS: False-positive responses had much more variable latencies than responses to suprathreshold stimuli. An algorithm defining RT windows on the basis of z-transformed individual latency samples correctly identified more than 70% of false-positive responses to catch trials, whereas fewer than 3% of responses to suprathreshold stimuli were classified as false-positive responses. CONCLUSIONS: Latency analysis can be used to detect a substantial proportion of false-positive responses in suprathreshold perimetry. Rejection of such responses may increase the reliability of visual field screening by reducing variability and bias in a small but clinically important proportion of patients.

Adolescent↗
PubMed1985

Signal transduction and ligand-receptor dynamics in the human neutrophil. Transient responses and occupancy-response relations at the formyl peptide receptor.

The responses of neutrophils to formyl peptides are initiated and in many cases achieve a maximal level prior to equilibrium receptor occupancy. In order to begin to understand the linkage between receptor occupancy and cell response we have used a pulsed binding procedure to analyze: 1) the number of receptors contributing to three potential signalling events and six functional responses and 2) the evolution of these responses once ligand binding is interrupted. We find that the half-optimal elevations of the potential signals are produced by less than 1% occupancy (Ca2+) or 1-3% occupancy (cAMP, membrane depolarization). In contrast, actin polymerization and a rapid light scatter response are elicited by less than 0.1% occupancy. Half-optimal elastase release and degranulation require approximately 3% occupancy. While half-optimal O2- production and aggregation require approximately 30% occupancy, the half-optimal rate of O2- production requires less than 10% occupancy. To resolve the apparent lack of correlation between the responses and the signals we examined their time courses following the pulse of stimulation. At least four responses and one signal are transient and decay while occupied receptors remain on the membrane surface. These include the Quin 2-Ca2+ signal, actin polymerization, the light scatter response, O2- generation, and aggregation. Ca2+ elevation is correlated with the responses in that: 1) each of these responses is transient unless new receptors are occupied; 2) occupancy of nearly all of the receptors contributes to the time course of these responses; 3) when binding is interrupted, the responses decay with a half-time of 15 s, following a latency of approximately 10 s or less (except for disaggregation where latency is 30-40 s). We discuss evidence in support of the hypothesis that transient cell responses arise from transient receptor activation.

Actins↗
PubMed2002

Alprazolam, a benzodiazepine, does not modify the ACTH and cortisol response to hCRH and AVP, but blunts the cortisol response to ACTH in humans.

Alprazolam (AL), a benzodiazepine which activates gamma-amino butyrric acid (GABA)-ergic receptors, exerts a clear inhibitory effect on the activity of the hypothalamo-pituitary-adrenal (HPA) axis and is able to markedly reduce the ACTH response to metyrapone-induced inhibition of glucocorticoid feedback. It has been suggested that its inhibitory action could be regulated by CRH or AVP mediated mechanisms. However, the effect of benzodiazepines on the HPA response to CRH or AVP is contradictory. It has been shown that benzodiazepines have specific receptors on the adrenal gland but it is unclear if they mediate biological effects in humans. In order to further clarify the mechanisms underlying the inhibitory effect of benzodiazepine on HPA axis in humans, we studied the effect of AL (0.02 mg/kg po at -90 min) or placebo in 7 healthy young volunteers (7 female, age: 26-34 yr; wt: 50-58 kg, BMI 20-22 kg/m2) on: 1) the ACTH and cortisol responses to hCRH (2.0 microg/kg iv at 0 min) or AVP (0.17 U/kg im at 0 min); 2) the cortisol, aldosterone and DHEA responses to ACTH 1-24 (0.06 and 250 microg iv at 0 and 60 min, respectively). After placebo, the ACTH and cortisol responses to hCRH (peaks, mean+/-SE: 29.8+/-4.4 pg/ml and 199.3+/-19.6 microg/l) were similar to those recorded after AVP (31.7+/-6.5 pg/ml and 164.8+/-18.0 microg/l); the cortisol response to 0.06 microg ACTH (190.4+/-11.8 microg/l) was similar to that recorded after hCRH and AVP but lower (p<0.01) than that after 250 microg ACTH (260.6+/-17.4 microg/l). AL did not modify the ACTH response to both hCRH (42.5+/-7.1 pg/ml) and AVP (33.3+/-2.7 pg/ml), which even showed a trend toward increase. AL also failed to significantly modify the cortisol response to both hCRH (156.3+/-12.7 microg/l) and AVP (119.4+/-14.5 microg/l), which, on the other hand, showed a trend toward decrease. The cortisol peaks after 0.06 microg ACTH were significantly reduced (p<0.02) by AL pre-treatment (115.0+/-7.7 microg/l) which, in turn, did not modify the cortisol response to the subsequent ACTH bolus (214.7+/-16.6 microg/l). The DHEA and aldosterone responses to all the ACTH doses were not significantly modified by AL. In conclusion, these data show that the HPA response to AVP as well as to hCRH is refractory to the inhibitory effect of AL which, in turn, blunts the cortisol response to low ACTH dose. These findings suggest that both CRH- and AVP-mediated mechanisms could underlie the CNS-mediated inhibitory effect of AL on HPA axis; in the meantime, these results suggest that benzodiazepines could also act on adrenal gland by blunting the sensitivity of the fasciculata zone to ACTH.

Adrenocorticotropic Hormone↗
PubMed1997

Antibody response to Actinobacillus pleuropneumoniae antigens after vaccination of pigs bred for high and low immune response.

To enhance inherent general resistance to infectious diseases an indirect strategy of selective breeding for multiple immune response traits representing both antibody and cell-mediated immune response has been pursued over several generations in pigs. High and low response lines differ significantly not only in response to antigens included in the estimated breeding values upon which the selection was based, but also to other antigens. To test whether or not the lines also differed in antibody response to vaccination, high and low response pigs were given a commercial Actinobacillus pleuropneumoniae vaccine, and their serum antibody to three constituent antigens, carbohydrates (CHO) 1 and 5 and lipopolysaccharide (LPS) 1 was measured by enzyme immunoassay. The high line had significantly (P < or = 0.05) more antibody to all antigens except at day 28 to CHO antigen 5. The frequency of non-response to vaccination was also less in the high response pigs to CHO antigen 1 (P < or = 0.01) and to the LPS antigen (P < or = 0.06) but not to the CHO antigen 5. Based upon these observation it is concluded that the high immune response pigs are more responsive to the commercial vaccine than are the low response pigs and that the strategy of altering population immune response by multi-trait selective breeding may be useful in facilitating vaccine-based health management programs for livestock.

Actinobacillus pleuropneumoniae↗
PubMed1997

Lack of correlation between bronchoconstrictor response and bronchodilator response in a population-based study.

Bronchodilator and bronchoconstrictor responsiveness have been considered physiological opposites in patients with obstructive airways disease. Provocation challenges have been replaced by bronchodilator tests in the assessment of cases of severe airways obstruction. The aim of this study was to examine the relationship between bronchoconstrictor and bronchodilator responsiveness, and their supposed interchangeability, in a general population. From the Vlagtwedde-Vlaardingen follow-up study, 101 adults were recruited (mean (SD) age 55 (11) yrs, 67 males and 34 females, and 31 were smokers). All completed a questionnaire on airways symptoms. Bronchoconstrictor and bronchodilator responsiveness were assessed with cumulative dose-response curves, using histamine and terbutaline, respectively. Thus, it was possible to relate histamine sensitivity of the airways (the concentration of histamine, at which forced expiratory volume in one second (FEV1) falls by 10% (PC10)) to the maximal bronchodilator response (delta FEV1) and the sensitivity to the bronchodilator (cumulative dose of inhaled terbutaline at which FEV1 increases by 10% (RD10)). Subjects with a bronchoconstrictor response (PC10 < or = 16 mg x mL(-1); n=38) had more respiratory symptoms than those without (n=63) (40 versus 21%) and also lower baseline FEV1 values (90 versus 96% predicted), but had comparable bronchodilator responsiveness. Subjects with a bronchodilator response (delta FEV1 > or = 9% of the predicted value; n=13) did not differ from those without (n=88) for all parameters, including symptoms, allergy and pulmonary function. In those with a bronchoconstrictor response, there was a weak but significant correlation between the PC10 and RD10 (rho=-0.32), but not between PC10 and delta FEV1. This study suggests that bronchoconstrictor and bronchodilator responsiveness are not highly correlated, even in subjects with airways obstruction. Symptoms were associated with the presence of a bronchoconstrictor, but not a bronchodilator, response. We conclude that bronchoconstrictor and bronchodilator responsiveness are two different phenotypic markers that are not interchangeable in epidemiological studies.

Administration, Inhalation↗
PubMedDate not supplied

[Validation of a scale for responsibility (Salkovskis Responsibility Scale)].

Appraisal of inflated responsibility for harm is the cornerstone of Salkovskis's cognitive theory for obsessive compulsive disorder. The aim of our study is to present the validation study of the French translation of the R scale. The present study compared 50 subjects with obsessive compulsive disorder, 37 patients suffering from social phobia and 183 control subjects on a responsibility questionnaire (R scale). The cognitive hypothesis of Obsessive Compulsive Disorder (OCD) specifies two levels of responsibility-related cognitions: responsibility assumptions (attitudes) and responsibility appraisals (interpretations). The R scale evaluates the responsibility assumptions. Such attitudes should reflect the more generalized tendency to assume responsibility in a given situation, particularly situations involving intrusions and doubts. It is possible that such assumptions may be less specific to OCD. The inclusion of social phobia subjects in the present study allows evaluation of the specificity of any findings to OCD. Patients were diagnosed and classified according DSM IV criteria. The control subjects were taken in the general population. No formal interview was conducted. The three groups were compared for sex, age and educational level. Before treatment, all the participants filled in the Responsibility Scale of Salkovskis (27 items), the Beck Depression Inventory (21 items), the Beck Anxiety Inventory and the Bouvard's Obsessive Compulsive Thoughts Checklist. The results indicate that the two anxious groups scored significantly higher than the control group on Beck Depression and Anxiety Inventories but no significant difference was observed between the two anxious groups. OCD patients scored significantly higher than both social phobic patients and control subjects on the Obsessive Compulsive Thoughts Checklist (OCTC). The social phobic group scored this checklist significantly higher than the control group. In sum, the three groups were different on obsessive compulsive thoughts. On the washing subscale of the Obsessive Compulsive Thoughts Checklist, the OCD patients differed significantly from the control group and the social phobia patients. No difference was observed between the social phobia subjects and the control group. On the two other subscales of the OCTC, the checking and the responsibility scales, the three groups were different: OCD patients scored significantly higher than both social phobic patients and control subjects; the social phobic patients scored higher than the control group. Results support the reliability (test retest) and the internal consistency of the questionnaire. Patients with obsessive compulsive disorder (OCD) and social phobia subjects had significantly elevated score on the total scale compared to control subjects. However social phobia patients did not differ from patients with OCD. So, the responsibility for harm, evaluated by the R-scale seems not to be specific of OCD. This finding does not support the results of two studies (28, 30). But these two studies compared OCD patients with an anxious group including panic disorder with agoraphobia, generalized anxiety disorder and social phobia. The correlations with a measure of OCD symptoms were higher than the correlations with anxiety and depression. Finally, the factor structure was only studied on the control group. The exploratory factor analysis indicates that the R scale is a two-dimensional scale, reflecting a need to prevent risks and the belief that one has power to harm. The first dimension is less specific to the pathology than the second. Only patients with OCD had significantly elevated score on the "need to prevent risks" compared to the non-clinical group. The two anxious groups differed on "the belief that one has power to harm" from the non-clinical group but social phobia patients did not differ from patients with OCD. In sum, the two subscales of the R scale did not discriminate OCD patients and social phobic subjects. Further research is needed to replicate the present findings and to confirm the two dimensions of the R scale. Overall, the results are consistent with the hypothesis that responsibility beliefs are important in the experience of obsessional problems. However, responsibility assumptions such as the belief that one has the power to harm are shared with social phobia.

Adult↗
PubMed1976

The immune response to dextran in BALB/c mice. I. Modification of "thymus-independent" response by the T cell mitogen concanavalin A.

Normal and congenitally athymic mice respond to immunization with dextran, thus indicating that the response is thymus independent. Athymic mice have lower plaque-forming cell (PFC) response than normal mice 3 days after immunization, but similar PFC response as normal mice by 5 days. Seven to 10 days after immunization, athymic mice maintain a high level of PFC response whereas the PFC response declines sharply in normal mice. Concanavalin A (Con A), added at initiation of in vitro culture, enhances the response of spleen cells from primed normal mice. Treatment with methyl-alpha-D-mannoside (MAM), a competitive inhibitor of binding of Con A, immediately after addition of Con A, abolishes the enhancement. Treatment with MAM, 3 to 6 hr after Con A addition, partially blocks the enhancement. The enhancing effect is dependent on the dose of Con A and the duration of in vivo priming before in vitro culture. Con A does not enhance the in vitro PFC response of cells from primed athymic mice. Supernatants from Con A-treated non-primed normal spleen cell cultures enhance the PFC response of "nude" cells, thereby indicating that enhancement by Con A is mediated through a soluble T cell product(s) with no apparent antigen specificity. Hydroxyurea, an inhibitor of DNA synthesis, blocks the enhancement by Con A of cells primed for 1 to 3 days. Release of hydroxyurea block after 19 hr incubation does not restore the PFC response, thereby indicating the responding anti-dextran PFC precursor cells are engaging actively in DNA synthesis. PFC response of primed cells taken at the peak of anti-dextran response (day 5) shows that they are less susceptible to the hydroxyurea block. Con A enhances the PFC response of cells primed for 5 days even in the absence of DNA synthesis.

Animals↗
PubMed2002

Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients.

The prolactin (PRL) increases in plasma, induced by the electrical stimulus during electroconvulsive therapy (ECT), is a consistent finding that can be studied in order to obtain information about its actions on the brain neurotransmitter systems, the most probable candidates being the serotonergic and the dopaminergic system. Central serotonergic and dopaminergic responsivity may also be assessed using neuroendocrine challenge tests. In this study, we measured the PRL responses during the first ECT of a therapeutic course in 15 male depressive patients, of mean age 49.2 +/- 14.5 (range 22 to 68 years), and score in the HDRS of 29 +/- 8 (range 18 to 43 points). Before the ECT course, we assessed the central serotonergic and dopaminergic responsivities, by measuring the PRL responses to the administration of the serotonin uptake inhibitor clomipramine (CMI) intravenously, and, two days later, the PRL responses dopamine receptor blocker haloperidol (HAL), administered intramuscularly. The CMI and HAL tests were also performed in 15 healthy male subjects. The PRL responses to CMI of the patients were blunted compared to healthy controls, while the PRL responses to HAL were not significantly different from controls. Searching for correlations among the maximal PRL responses to the three stimuli in the patient's group, we found that the PRL responses to ECT were significantly correlated to the PRL responses to i. m. HAL (r = 0.8205, N = 15, p < 0.001) and not to the PRL responses to i. v. CMI (r = 0.1713, n. s.). It is suggested that the rises in PRL during ECT reflect the responsivity of the hypothalamus-pituitary dopaminergic system, and seem to be the result of a transient decrease in the inhibitory dopaminergic input of the hypothalamus to the pituitary lactotrophs, caused by the electrical stimulus and the subsequent seizure.

Adult↗
PubMed1985

Immune responses to T-dependent and T-independent antigens during visceral leishmaniasis in mice: evidence for altered T-cell regulation of immune responses to non-parasite antigens.

Antibody responses to T-dependent and T-"independent" antigens were studied in disease-susceptible (BALB/c and C57BL/10) and disease-resistant (A/J) mice infected with Leishmania donovani chagasi. Disease-susceptible mice but not disease-resistant mice showed a transient decrease in PFC responses to TNP on a T-dependent carrier (BGG) during the period of 4-8 weeks after infection. Infected disease-susceptible animals also showed increased responses to TNP on a type II T-independent carrier (Ficoll), which persisted until at least 14 weeks after infection. The increased responses were associated with a significant increase in anti-TNP antibody of the IgG2b subclass. When T-enriched spleen cells from infected mice and B-enriched spleen cells from uninfected mice were transferred to irradiated recipients immunized with TNP-Ficoll, increased anti-TNP PFC were observed over numbers seen in irradiated recipients which received both B and T cells from uninfected mice. Increased responses to TNP-Ficoll were also induced by prior administration of soluble leishmania extract in CFA. Infected mice immunized with TNP-LPS, a T-independent type I antigen, also had increased anti-TNP antibody responses, but had normal anti-LPS antibody responses. The elevated antibody production which occurred in response to the T-"independent" antigens could not be attributed to the relatively low polyclonal response which occurred in both disease-resistant and disease-susceptible mice infected with L. donovani chagasi. The observations are consistent with leishmania induced, transient alterations in some T-cell functions including response to haptens on T-dependent carriers, and a lack of down regulation of T-"independent" responses. Subtle lesions in immunoregulation may be important correlates of successful protozoal infection and may be responsible for some of the immunologic manifestations of the disease.

Animals↗
PubMed1992

Cyclic AMP modulation of human B cell proliferative responses: role of cAMP-dependent protein kinases in enhancing B cell responses to phorbol diesters and ionomycin.

The ability of cyclic AMP (cAMP) to modulate human B cell proliferative responses and the possible role of cAMP-dependent kinases (PKA) in cAMP modulation of proliferative responses were investigated. The addition of dibutyl cAMP (Bt2 cAMP) or the cAMP-elevating agent forskolin to B cells stimulated by crosslinking surface immunoglobulins (sIg) resulted in a concentration-dependent inhibition of proliferative responses. By contrast, Bt2 cAMP or forskolin enhanced the proliferative responses of B cells after direct stimulation by phorbol myristate acetate (PMA) and the calcium ionophore ionomycin. The inhibition and enhancement of B cell proliferative responses by Bt2 cAMP were observed at different incubation intervals and were not due to temporal shifts of optimal responses. Also, Bt2 cAMP caused only small changes in B cell RNA synthesis compared to modulation of proliferative responses. Exposure of B cells to Bt2 cAMP rapidly activated PKA. Blocking Bt2 cAMP activation of PKA with the kinase inhibitor HA1004 prevented Bt2 cAMP enhancement of B cell responses after direct stimulation by PMA and ionomycin. In reciprocal experiments, the kinase inhibitor H7 resulted in some inhibition of PKC activation but did not inhibit Bt2 cAMP activation of PKA or Bt2 cAMP enhancement of proliferative responses. Other experiments demonstrated that B cells treated with Bt2 cAMP had selective increases in the de novo phosphorylations of two endogenous substrates which reflected PKA activation. Furthermore, concentrations of HA1004 or H8 which inhibited Bt2 cAMP enhancement of proliferative responses also inhibited PKA phosphorylations of these substrates whereas H7 did not. Thus, elevations of cAMP can enhance or inhibit human B cell proliferative responses to different stimuli and the activation of PKA is important for cAMP enhancement of certain responses.

Amino Acid Sequence↗
PubMed1986

Late bronchial response and increase in methacholine hyperresponsiveness after exercise and distilled water challenge in atopic subjects with asthma with dual asthmatic response to allergen inhalation.

We investigated the occurrence of late asthmatic response and increased methacholine responsiveness after exercise and ultrasonically nebulized distilled water (UNDW) inhalation in 12 subjects with asthma with dual asthmatic response and increased responsiveness after allergen challenge. On 3 separate days, allergen, exercise, and UNDW challenges were performed 2 hours after methacholine. FEV1 was measured for 8 hours to detect any delayed change in airway caliber. If there were a further significant reduction in FEV1 after the recovery from the immediate bronchoconstriction, methacholine challenge was performed again when FEV1 had returned to baseline. Reproducibility of any observed late response to exercise and UNDW was also investigated by repeating these challenges on 2 subsequent days. After allergen inhalation only nine subjects had an early asthmatic response, whereas all the tested subjects demonstrated a late reaction and increased methacholine responsiveness. Ten subjects had an immediate response to exercise, and this was followed by a late response in only four patients. Nine subjects demonstrated early response to UNDW inhalation, and five subjects also had a late reaction. These late responses were associated with an increase in methacholine responsiveness in a subset of the tested subjects. Late-phase reactions to exercise and UNDW were not reproducible.

Administration, Inhalation↗
PubMed1994

Immune response in healthy volunteers vaccinated with BCG plus killed leishmanial promastigotes: antibody responses to mycobacterial and leishmanial antigens.

Antibody (IgG) responses to mycobacterial (BCG; PPD; Mycobacterium leprae soluble antigen, MLSA) and leishmanial (Leishmania mexicana LV4) antigens were measured in 208 initially PPD and leishmanin skin-test negative volunteers divided into four vaccine groups as follows: 68 received BCG plus killed promastigotes (group A), 47 received BCG alone (group B), 47 received killed promastigotes alone (group C), and 46 formed the diluent control (placebo, group D). Three vaccine doses were administered at 8-12 week intervals. Vaccinees were bled immediately prior to each vaccination, and again at 3- and 12-month follow-up. Skin tests were performed prevaccination, and again at the 3- and 12-month follow-up. Anti-BCG, anti-PPD and anti-MLSA IgG levels increased significantly in groups A and B receiving BCG. The presence of leishmanial antigen (with BCG) in the inoculum suppressed the IgG response to Mycobacterium tuberculosis/Mycobacterium bovis-related (PPD and BCG), but not M. leprae-related (MLSA)-related, antigens. A small but significant increase (relative to prevaccination level) in response to MLSA, but not to BCG or PPD was observed in the non-BCG-vaccinated groups. The background level of response to mycobacterial and leishmanial antigens was higher in the Venezuelan vaccinees than in non-endemic (British) volunteers. Responses to leishmanial antigen were not enhanced in the two vaccine groups receiving killed promastigotes (with/without BCG) compared with the BCG alone and placebo groups. Instead, all vaccine groups showed a pattern of response consistent with either (i) a response to the skin-test antigen or, more likely, (ii) seasonal endemic exposure to leishmanial antigen. Interestingly, this endemic response to leishmanial antigen was enhanced in the vaccine groups receiving BCG, despite the fact that group B received no leishmanial antigen in the vaccine inoculum. When prevaccination IgG levels (mean + 3 standard deviations) were used to determine a negative cut-off, a low percentage (< 38%) of vaccinees converted to responder status for either anti-mycobacterial or anti-leishmanial responses, and those who did would be classified as 'low-responder' status compared with titres observed in severe forms of disease. Hence, although there was evidence for a background endemic response to both leishmanial and mycobacterial antigens, there was no evidence that vaccination per se led to a potentially disease exacerbatory level of TH2-associated antibody response especially with respect to the anti-leishmanial response.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2005

Preparing not to move: does no-response priming affect advance movement preparation processes in a response priming task?

The response-priming paradigm is frequently employed to study motor control by means of behavioural as well as psychophysiological methods. In this paradigm, response performance is studied under various preparation conditions, but in all cases participants are generally primed for action. This setting neglects an essential ability of the motor system in everyday situations, i.e. the efficient execution of a movement with and without warning. In this context the present experiment assessed the behavioural effects of a modified response-priming paradigm, in which participants were asked to execute movements when primed for action, and when the prime predicted that no response would be required. Thirty volunteers participated the experiment, which tested whether the insertion of no-response trials would affect the validity effect, and assessed the differences between invalid trials and reactions performed subsequent to no-response primes. The data showed that the validity effect is not modulated by the added no-response condition, which suggests that movement preparation mechanisms can be studied with this particular task. In addition, responses in invalid trials were substantially different from responses executed after no-response primes. These results are interpreted in relation to psychophysiological evidence on advance movement preparation. It is proposed that the performance differences between response- and no-response priming conditions may be due to different preactivations of motor regions evoked by the prime stimuli, a hypothesis to be addressed with psychophysiological measures in the future.

Adolescent↗