Pharmacological characterisation of excitatory synaptic transmission in the cat red nucleus in vivo

Extracellular recordings were made from the magnocellular neurones of the red nucleus (mRN) in anaesthetised cats. A study was made of the effects of selective excitatory amino acid receptor antagonists on excitatory monosynaptic responses evoked from the sensorimotor cortex (SMC) and cerebellar interpositus nucleus (IPN). Iontophoretically applied CNQX and NBQX antagonised both SMC and IPN responses whereas, D-AP5 inhibited the SMC response but was ineffective to the IPN. At currents that selectively antagonised NMDA responses, CPPene had no effect on either SMC or IPN responses. 7-chlorokynurenate inhibited both SMC and IPN responses but required currents that antagonised both AMPA and NMDA responses and was therefore acting in a non-selective manner. Iontophoretically applied glycine was inhibitory to both agonist and synaptic responses, whilst D-serine potentiated NMDA responses but did not enhance monosynaptic responses of the SMC. However in the presence of either 7-chlorokynurenate or high currents of CNQX that reduced the SMC synaptic activation of the mRN neurones, D-serine attenuated the inhibitory action of these antagonists. It is concluded that monosynaptic responses from the SMC are mediated by both NMDA and non-NMDA receptors whereas the monosynaptic responses evoked from the IPN are mediated only by non-NMDA receptors. The lack of effect of CPPene is consistent with the postulate that two NMDA receptor subtypes are present on mRN neurones.     

Intra-individual variability in sentence completion responses.

Variability in responses to a sentence completion test over a 2 to 3 week interval, and the relationship between change in responses and relative response frequency in a group was studied. The major results were: (1) The content of the majority of responses was changed to some degree on retest. (2) Individual differences in number of responses changed on retest showed reasonable reliability. (3) Differences between sentence stems in the proportion of changed responses were consistent from group to group. (4) For each sentence stem, responses given by only one person change more frequently than those given by more than one person. (5) Positive correlations were obtained between the number of unique responses made by a subject and the number of responses he changed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

How attributional ambiguity shapes physiological and emotional responses to social rejection and acceptance.

The authors examined White and Black participants' emotional, physiological, and behavioral responses to same-race or different-race evaluators, following rejecting social feedback or accepting social feedback. As expected, in ingroup interactions, the authors observed deleterious responses to social rejection and benign responses to social acceptance. Deleterious responses included cardiovascular (CV) reactivity consistent with threat states and poorer performance, whereas benign responses included CV reactivity consistent with challenge states and better performance. In intergroup interactions, however, a more complex pattern of responses emerged. Social rejection from different-race evaluators engendered more anger and activational responses, regardless of participants' race. In contrast, social acceptance produced an asymmetrical race pattern--White participants responded more positively than did Black participants. The latter appeared vigilant and exhibited threat responses. Discussion centers on implications for attributional ambiguity theory and potential pathways from discrimination to health outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of thalamic and cortical neurons in augmenting responses and self-sustained activity: dual intracellular recordings in vivo

Progressively increasing (augmenting) responses are elicited in thalamocortical systems by repetitive stimuli at approximately 10 Hz. Repeated pulse trains at this frequency lead to a form of short-term plasticity consisting of a persistent increase in depolarizing synaptic responses as well as a prolonged decrease in inhibitory responses. In this study, we have investigated the role of thalamocortical (TC) and neocortical neurons in the initiation of thalamically and cortically evoked augmenting responses. Dual intracellular recordings in anesthetized cats show that thalamically evoked augmenting responses of neocortical neurons stem from a secondary depolarization (mean onset latency of 11 msec) that develops in association with a diminution of the early EPSP. Two nonexclusive mechanisms may underlie the increased secondary depolarization during augmentation: the rebound spike bursts initiated in simultaneously recorded TC cells, which precede by approximately 3 msec the onset of augmenting responses in cortical neurons; and low-threshold responses, uncovered by hyperpolarization in cortical neurons, which may follow EPSPs triggered by TC volleys. Thalamic stimulation proved to be more efficient than cortical stimulation at producing augmenting responses. Stronger augmenting responses in neocortical neurons were found in deeply located (<0.8 mm, layers V-VI) regular-spiking and fast rhythmic-bursting neurons than in superficial neurons. Although cortical augmenting responses are preceded by rebound spike bursts in TC cells, the duration of the self-sustained postaugmenting oscillatory activity in cortical neurons exceeds that observed in TC neurons. These results emphasize the role of interconnected TC and cortical neurons in the production of augmenting responses leading to short-term plasticity processes.     

Longitudinal studies of neutralizing antibody responses to rotavirus in stools and sera of children following severe rotavirus gastroenteritis

Rotavirus-neutralizing antibody responses in sera and stools of children hospitalized with rotavirus gastroenteritis and then monitored longitudinally were optimally detected by using local rotavirus strains. Stool responses were highest on days 5 to 8 after the onset of diarrhea. Longitudinal monitoring suggested that serum neutralizing antibody responses were a more useful measure of severely symptomatic rotavirus infection than stool responses but that stool antibody responses may be a useful measure of rotavirus immunity.     

Review of Alluvial-channel Responses to River Ice

The extent to which alluvial channels respond to ice-cover formation, presence, and breakup is not well understood. Some responses are well known and observed, such as increased flow stage or localized scour beneath the toe of an ice jam. Other responses are known in concept, such as altered bedform geometry, but are not well documented. Some potential responses are barely recognized, such as channel-thalweg adjustment. Many responses are temporal, such as the channel readjusting itself once ice is gone. A few responses may have a more enduring impact, such as a meander-loop cutoff. Most responses have not been investigated rigorously. The responses affect the full gamut of relationships between flow discharge and stage, macroturbulence structures, sediment-transport and mixing processes, and alluvial-channel stability. Of importance are the relative scales of length and time associated with ice-cover formation, presence and breakup, and a channel’s facility to respond to ice. This paper reviews alluvial-channel responses to ice formation, and raises practical engineering issues stemming from them.     

Cat carotid body chemosensory responses to non-hypoxic stimuli are inhibited by sodium nitroprusside in situ and in vitro

We studied the effects of sodium nitroprusside, a nitric oxide donor, on the chemosensory responses to cyanide and nicotine in the cat carotid body. In situ, sodium nitroprusside infusion reduced the cyanide-evoked responses in a dose-dependent manner. In vitro, Tyrode containing nitroprusside reversibly reduced the cyanide- (by 59%) and nicotine-induced (by 45%) chemosensory responses. The present results suggest that chemosensory responses induced by cyanide and nicotine are reduced by increased nitric oxide content, similarly to the hypoxic chemosensory responses.     

Pharmacological specialization of learned auditory responses in the inferior colliculus of the barn owl

Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.     

Cardiac responses to stimulation of thoracic afferents in the primate and canine

Excitatory cardiovascular responses to electrically stimulated upper thoracic sympathetic afferent nerves were observed in halothane-anesthetized mongrel dogs and monkeys. The central end of the transected ventral limb of the left ansa subclavia was stimulated before and after several types of denervation. Significant increases in right and left ventricular maximum systolic pressures, systolic and diastolic systemic blood pressures, and aortic flow were observed. The carotid sinuses were denervated bilaterally and stimulation of the ansa was repeated. The cardiovascular responses to stimulation of the ventral ansa after carotid sinus denervation were greater in magnitude than those observed prior to denervation. This carotid sinus modulation of cardiovascular responses was observed in dogs and monkeys. Cardiovascular responses to stimulation of the ventral ansa after bilateral vagotomy were significantly less than the responses observed after carotid sinus denervation prior to vagotomy. However, the responses after vagotomy were statistically identical to responses obtained while stimulating the ventral ansa when the carotid sinuses and vagi remained intact.     

Duration of serum antibody responses following vaccination and revaccination of cattle with non-living commercial Pasteurella haemolytica vaccines

This study was designed to determine the duration of serum antibody responses to Pasteurella haemolytica whole cells (WC) and leukotoxin (LKT) in weanling beef cattle vaccinated with various non-living P. haemolytica vaccines. Serum antibodies to P. haemolytica antigens were determined periodically through day 140 by enzyme-linked immunosorbent assays. At day 140, cattle were revaccinated, and antibody responses periodically determined through day 196. Three vaccines were used in two experiments (A and B), OneShot, Presponse HP/tK, and Septimune PH-K. In general, all three vaccines between 7 and 14 days induced antibody responses to WC after vaccination. Antibodies to LKT were induced with OneShot and Presponse. Revaccination at days 28 and 140 usually stimulated anamnestic responses. Serum antibodies to the various antigens remained significantly increased for up to 84 days after vaccination or revaccination. The intensity and duration of antibody responses were variable depending on the experiment and vaccines used. Vaccination with OneShot usually stimulated the greatest responses to WC. Vaccination with OneShot or Presponse resulted in equivalent primary anti-LKT responses. In experiment B, spontaneous seroconversion was found in numerous calves on day 112. Revaccination of those cattle at day 140 resulted in markedly variable antibody responses such that several groups had no increase in antibody responses.     

Immune response profile in patients with active tuberculosis in a BCG vaccinated area

Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin test responses to PPD and lymphocyte proliferative responses to crude mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens (tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in patients with pulmonary disease compared to endemic controls. However, mitogen (phytohemagglutinin)-stimulated responses were comparable in patients and controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE responses which are considered to be surrogate markers for Th2 responses were significantly higher in patients with pulmonary disease compared to healthy endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node disease showed strong Th1 responses but did not show significant responses for either polyclonal or antigen specific IgE. Thus overall suppression of T cell memory response was observed only in patients with pulmonary disease but not in patients with lymph node disease suggesting that sequestration of antigen in different compartments leads to differential activation of Th1 and Th2 responses. PPD skin test responses were highly positive in endemic controls (47% positive) and household contacts (86% positive). Furthermore, PPD positivity decreased with disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area cannot be used as a diagnostic marker for active tuberculosis particularly in advanced disease.     

Vestibular-evoked electromyographic responses in soleus: a comparison between click and galvanic stimulation

The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.     

Physiological responses of premature infants to a painful stimulus

The purpose of this study was to describe the physiological responses of premature infants to an acute tissue-damaging stimulus and to determine how severity of illness and behavioral state influenced these responses. The physiological responses (heart rate, oxygen saturation, and intracranial pressure) of a convenience sample of 124 premature infants between 32 and 34 weeks gestational age were described during four phases of a routine heel stick procedure. Analysis of the results showed a significant multivariate main effect of phase on the group of physiological responses. Behavioral state was found to influence the physiological responses, but severity of illness did not.     

Antiviral immune responses in Itk-deficient mice

Mice lacking Itk, a T-cell-specific protein tyrosine kinase, have reduced numbers of T cells and reduced responses to allogeneic major histocompatibility molecules. This study analyzed antiviral immune responses in mice deficient for Itk. Primary cytotoxic T-lymphocyte (CTL) responses were analyzed after infection with lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and vesicular stomatitis virus (VSV). Ex vivo CTL activity was consistently reduced by a factor of two to six for the different viruses. CTL responses after restimulation in vitro were similarly reduced unless exogenous cytokines were added. In the presence of interleukin-2 or concanavalin A supernatant, Itk-deficient and control mice responded similarly. Interestingly, while LCMV was completely eliminated by day 8 in both Itk-deficient and control mice, VV cleared from itk-/- mice with delayed kinetics. Antibody responses were evaluated after VSV infection. Both the T-cell-independent neutralizing immunoglobulin M (IgM) and the T-cell-dependent IgG responses were similar in Itk-deficient and control mice. Taken together, the results show that CTL responses are reduced in the absence of Itk whereas antiviral B-cell responses are not affected.     

Differential responses of pulmonary arteries and veins to histamine and 5-HT in lung explants of guinea-pigs

1. The mechanisms by which histamine and 5-HT differentially contract pulmonary arteries and veins are unclear. In lung explants from 26 guinea-pigs, we compared responses of pulmonary arteries and vein to histamine, 5-HT and KCI, and examined potential determinants for the differential responses. Lungs were filled with agarose, sectioned into approximately 1 mm thick slices, and vascular luminal areas measured by image analysis. 2. Histamine and 5-HT produced a concentration-dependent constriction in arteries and veins, greater in the latter. KCl constricted arteries and veins equally. 3. The histamine H1 antagonist chlorpheniramine (10(-4) M) abolished contractions to histamine; the H2 antagonist cimetidine enhanced maximal responses and sensitivity of arteries and veins to histamine, and diminished the differences between their maximal responses; the NO synthase inhibitor Nomega-nitro-L-arginine (L-NOARG) increased the maximal responses of arteries and veins, and the differences between their responses; indomethacin had no effect. 4. Contractions to 5-HT were abolished in arteries and markedly reduced in veins by the 5-HT2 antagonist ketanserin (10(-4) M); L-NOARG potentiated the maximal responses of arteries but not of veins; indomethacin increased the maximal responses of arteries but reduced them in veins. 5. By morphometry, arteries had a greater medial thickness and luminal diameter than veins. 6. The data suggest that in guinea-pigs, H2 receptors are responsible for the differential contractile responses of pulmonary arteries and veins to histamine, whereas endothelium-derived vasoactive substances are responsible for their differential contractile responses to 5-HT.     

The intradermal effects of the H3 receptor agonist R alpha methylhistamine in human skin

We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.     

Brain systems mediating aversive conditioning: an event-related fMRI study

We have used event-related functional magnetic resonance imaging (fMRI) to characterize neural responses associated with emotional learning. Employing a classical conditioning paradigm in which faces were conditioned by pairing with an aversive tone (US), we compared responses evoked by conditioned (CS+) and nonconditioned (CS-) stimuli. Pairing 50% of the CS+ with the US enabled us to constrain our analysis to responses evoked by a CS+ not followed by a US. Differential evoked responses, related to conditioning, were found in the anterior cingulate and the anterior insula, regions with known involvement in emotional processing. Differential responses of the amygdalae were best characterized by a time by stimulus interaction indicating a rapid adaptation of CS+-specific responses in this region.     

Complications of membrane-filtration plasma exchange

Guided by the Roy Adaptation Model of Nursing, the relationship of children's age, gender, exposure to past painful experiences, temperament, fears, and child-rearing practices to their pain responses to a venipuncture was examined. A sample of 94 children aged 8 to 12 years and their female caregivers were recruited from three outpatient clinics. During the venipuncture, children's behavioral and heart rate responses were monitored; immediately after, their subjective responses were recorded. Canonical correlation revealed two variates. In the first, age and threshold (temperamental dimension) correlated with pain quality, behavioral responses, and heart rate responses, explaining 12% of the variance. In the second, age, the temperamental dimensions of distractibility and threshold, and medical fears explained only 5.7% of the variance in pain quality and heart rate magnitude. Significant correlations between pain intensity, quality, behavioral responses, and heart rate responses support the multidimensionality of pain.     

Inhibition of HIV-1 replication by a Tat transdominant negative mutant in human peripheral blood lymphocytes from healthy donors and HIV-1-infected patients

BACKGROUND: There is increasing evidence that the T-cell reactivity to environmental allergens underlying expression of allergic disease in adulthood, develops initially during childhood. However, there is little information available on the kinetics of these early responses, or on the patterns of cytokine production during this period. OBJECTIVE: The purpose of this study was twofold: to obtain further information on the reported differences between responses to food versus inhalant allergens during early childhood, and to ascertain the age-range over which T-cell responses to inhalant allergens become polarized towards the TH2 cytokine profile, in potentially atopic children. METHODS: In vitro cytokine responses to house dust mite (HDM) and egg (OVA) were assessed by semiquantitative RT-PCR in panels of 2- and 5-year-old children and adults; lymphoproliferative responses to OVA were subjected to epitope analysis. RESULTS: At age 2 years IL-4/IL-5 responses to HDM grouped with positive atopic family history, and by age 5 years cytokine responses correlated strongly with individual SPT reactivity to HDM. In contrast, OVA responses were restricted to weak and transient IL-5 signals in the 2-year-old family history positive group. Lymphoproliferation assays performed in parallel indicate a log-scale greater postnatal expansion of T-cell reactivity to the inhalant allergen; preliminary epitope analysis of OVA responses indicate that the number of OVA epitopes recognised decrease during early childhood. CONCLUSIONS: Inhalant allergen-specific in vitro cytokine production associated with positive skin-prick test (SPT) reactions, one of the hallmarks of adult atopy, manifests in children at or before 5 years of age; additionally, cytokine responses in SPT negative 5 year-olds are restricted to IFNgamma, as per normal adults. In contrast, T-cell responses to a typical food allergen appear to be deleted during early childhood.     

Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood

An inactivated oral enterotoxigenic Escherichia coli (ETEC) vaccine against ETEC diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage fluid to CTB and CFAs were determined and compared with corresponding responses in stool extracts and serum as well as with IgA antibody-secreting cell (ASC) responses in peripheral blood. Two doses of vaccine induced significant IgA responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and in stool in 38 to 81% of them. The most frequent responses were seen against CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool correlated significantly (CTB, P < 0.01; CFA/I, P < 0. 05) with those in intestinal lavage. Intestinal lavage responses against CFAs were best reflected by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%, followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7 to 65%) analyses. CTB-specific immune responses were seen in >90% of the vaccinees in all assays.