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PubMedDate not supplied

Amygdalar neuronal responses to peripheral nociceptive stimuli in rats.

Amygdala plays a very important role in the mediation of pain. In the present study the behaviour of the amygdalar neurons in response to various peripheral noxious stimuli was observed. Noxious mechanical, thermal, electrical, chemical and the non-noxious stimuli (touch) were applied individually to the animal and then the neuronal responses to these stimuli were recorded. Our results showed that the majority of amygdalar units recorded from medial, lateral and basolateral nuclei, responded to different peripheral noxious (thermal, electrical, chemical mechanical) and non-noxious stimuli by excitation. However few neurons decreased their activity on stimulation. Some of these neurons also exhibited after discharge following application of higher intensity of noxious stimuli.

Action Potentials↗

PubMed1993

Proliferative responses of peripheral blood lymphocytes of mice and humans stimulated with recombinant interleukin 2.

In vitro proliferative responses of human and murine peripheral blood lymphocytes (PBL) were studied. The cells were stimulated with recombinant interleukin 2 (IL-2) or with a mixture of phorbol-13-myristate-12-acetate with either IL-2 or calcium ionophores. Proliferation of human PBL could be induced by doses of human IL-2 or phorbol that were much lower than those required to produce responses of murine cells. However, the magnitude of the responses of human PBL was definitely lower than that of the responses of murine PBL. Murine IL-2 did not induce proliferation of human PBL, but it synergized with phorbol. The responses of murine PBL reflected the previously described strain differences in responses of spleen cells that were shown to be under complex polygenic control. The proliferation of murine spleen cells could be induced with human, as well as murine IL-2, and both species of IL-2 synergized with phorbol. While no clear-cut low and high responders could be identified among normal healthy human subjects, 2 individuals produced consistently low responses to IL-2 and 1 individual displayed low responses to phorbol and calcium ionophore A23187. Available data suggest, but do not allow a firm conclusion, that proliferative responses of human PBL are under genetic control, perhaps as complex as that reported for mice.

Animals↗

PubMed1995

Physical conditioning in rats influences the central and peripheral catecholamine responses to sustained exercise.

We have investigated the effect of treadmill running in rats (25m.min-1 using a 3% gradient; for 1 h or 2 h) on the cortical extracellular concentrations of noradrenaline (NA) and its main metabolites-3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol- and the plasma adrenaline (A) and NA concentrations in relation to prior physical conditioning (1 or 2-h running.day-1 for 12 days). Cortical microdialysates and peripheral blood were collected during 1-h resting, 1-h or 2-h running and for 1 h after exercise. Catecholamines and their metabolites were quantitated using high performance liquid chromatography with electrochemical detection. Treadmill running stimulated concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e. NA turnover and release. The effect extended into the recovery period even more as the duration of the run increased. Prior physical conditioning greatly influenced the central and peripheral catecholamine responses: the 1-h trained rats experienced the 2-h run as a stressful new event eliciting great long-lasting catecholamine responses, whereas the 2-h trained rats exhibited a progressive sustained catecholamine increase with an earlier onset of the central NA release. The data are discussed in relation to the psychological and intellectual effects of exercise and physical fitness in humans. In addition, the positive correlation found between the central noradrenergic activation and peripheral A secretion confirmed and extended our previous observations in exercising men and gave support to the hypothesis that the elevation of circulating A can be a relevant factor mediating--directly or indirectly--the exercise-induced central effects.

Animals↗

PubMed1986

Enhanced peripheral vasoconstrictor response and increased thromboxane A2 synthesis after the cold pressor test in patients with angina at rest.

Peripheral vascular resistance (PVR) and thromboxane A2(TxA2) synthesis after the cold pressor test were investigated in different subsets of patients with angina (10 with stable effort angina, 36 with resting angina [24 in an active phase and 12 in an inactive phase], and five with Prinzmetal's variant angina) and in 41 control subjects of equivalent age and risk factors. Left ventricular end-diastolic pressure, ejection fraction, extent of coronary angiographic lesions, and baseline PVR were not significantly different among the various patient groups. In all patient groups, except those with variant angina, the cold pressor test resulted in a higher increase in PVR than in the control subjects (p less than .001 for all groups). In patients with variant angina the vasoconstrictor response was increased only in proximity (about 1 hr) to ischemic attacks. In patients with active resting angina the vasoconstrictor response was on the average four times longer than that in patients with effort angina and with inactive resting angina (p less than .001). This exaggerated vasoconstrictor response was associated with elevated TxA2 resting levels in plasma and with increased TxA2 synthesis after the cold pressor test. A linear relationship was found between the area of the vascular response and the area of TxA2 production after the cold pressor test in patients with active resting angina (r = .87, p less than .001). The increased TxA2 synthesis and the inappropriate increase of peripheral vascular response to sympathetic stimulation revert back to normal in the inactive phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed2000

Foveal attention modulates responses to peripheral stimuli.

When attending to a visual object, peripheral stimuli must be monitored for appropriate redirection of attention and gaze. Earlier work has revealed precentral and posterior parietal activation when attention has been directed to peripheral vision. We wanted to find out whether similar cortical areas are active when stimuli are presented in nonattended regions of the visual field. The timing and distribution of neuromagnetic responses to a peripheral luminance stimulus were studied in human subjects with and without attention to fixation. Cortical current distribution was analyzed with a minimum L1-norm estimate. Attention enhanced responses 100-160 ms after the stimulus onset in the right precentral cortex, close to the known location of the right frontal eye field. In subjects whose right precentral region was not distinctly active before 160 ms, focused attention commonly enhanced right inferior parietal responses between 180 and 240 ms, whereas in the subjects with clear earlier precentral response no parietal enhancement was detected. In control studies both attended and nonattended stimuli in the peripheral visual field evoked the right precentral response, whereas during auditory attention the visual stimuli failed to evoke such response. These results show that during focused visual attention the right precentral cortex is sensitive to stimuli in all parts of the visual field. A rapid response suggests bypassing of elaborate analysis of stimulus features, possibly to encode target location for a saccade or redirection of attention. In addition, load for frontal and parietal nodi of the attentional network seem to vary between individuals.

Adult↗

PubMedDate not supplied

[Proliferative response of peripheral blood mononuclear cells to the recombinant allergen BtM of the Blomia tropicalis housedust mite].

Allergic diseases are triggered when individuals genetically predisposed to developing an allergy (atopy) are exposed to sensitizing allergens. These allergens are captured and processed by antigen-presenting cells (APC) which presents them to T lymphocytes. Some of these allergens have a significant influence on the development of this type of disease and cause most of the symptoms in allergic individuals around the world. They are found in the feces of house dust mites, which have diverse and varied origin in several species, for example the Blomia tropicalis (Bt) mite. In Cartagena (Colombia), this highly prevalent mite has been a central object of study by the Institute of Immunological Research of the University of Cartagena, where several of its allergens have been cloned, sequenced and expressed as recombinant allergens. Moreover, their capacity to bind to IgE and the frequency of this process has been studied. The aim of the present study was to analyze the lymphoproliferative response of peripheral blood mononuclear cells (PBMC) in healthy and allergic individuals to one of the recombinant allergens of B. tropicalis, BtM. This response was studied in PBMC from six patients with allergy to Bt (positive cutaneous test to Bt extract), using a cellular proliferation technique, with incorporation of 3H thymidine at days 3 and 6 days of culture, and at three different concentrations of BtM. Notable among the results was the high proliferation produced by cells from patient JF018 at 3 days of stimulus (41.7 IE), with the lowest concentration of protein (100 microg/mL). Moreover, in all the experiments this concentration was the cause of most of the cell proliferation. In addition, some response to control LAC012 against glutathione-S-transferase (GST) was induced. In conclusion, the results of the present study demonstrate that the recombinant allergen BtM is able to induce a cellular response in the PBMC of patients allergic to Bt. Moreover, it is able to induce a response similar to that produced by natural allergens, because its pattern of response is similar to that shown by cells stimulated with Bt extract. These results also show that a process of anergy can be produced in cells when excess antigen is present. In some individuals (both allergic and nonallergic), GST is able to cause a proliferative response, indicating its sensitizing potential in these individuals.

Allergens↗

PubMed1983

Antigen-specific proliferation responses of peripheral blood lymphocytes to Trichomonas vaginalis antigen in patients with Trichomonas vaginitis.

This report describes the development of an assay system which overcomes the difficulty of detecting immune responses of patients with Trichomonas vaginitis by making use of peripheral blood leukocytes obtained from such patients. When peripheral blood leukocytes from the patient were stimulated in microcultures with the soluble antigen extracted from Trichomonas vaginalis, significant degrees of proliferation ensued, as measured by the incorporation of [methyl-3H]thymidine 4 to 5 days after initiation. The antigen-induced proliferation response of peripheral blood leukocytes is specific for T. vaginalis antigen. The T. vaginalis-specific [methyl-3H]thymidine incorporation is mediated by Leu-1-positive cells, namely, T lymphocytes, in the peripheral blood leukocyte population. This assay system should prove useful for the analysis of the immune response to the protozoa in patients with Trichomonas vaginitis.

Antigens↗

PubMed1986

Blastogenic responses of peripheral blood leukocytes from owl monkeys experimentally infected with Leishmania braziliensis panamensis.

The relationship of the progression and regression of cutaneous lesions of 6 owl monkeys (Aotus trivirgatus) to the responses of their peripheral blood leukocytes (PBL) in vitro to mitogens and to leishmanial antigens, as well as their delayed skin test responses (DTH) in vivo to leishmanin antigen, were studied after primary and challenge infections with Leishmania braziliensis panamensis (WR 128 or WR 539). All 6 infected monkeys developed primary and satellite cutaneous leishmanial lesions which were measured for up to 30 weeks in 3 of the monkeys and up to 52 weeks in the other 3 monkeys. Two owl monkeys which had recovered from cutaneous leishmaniasis demonstrated acquired resistance when challenged with an intradermal inoculation of L. b. panamensis (WR 128). Reactivity of PBL from infected owl monkeys to PHA, Con A, and PWM was similar during primary and challenge infections to that observed prior to infection. Reactivity to leishmanial antigens was detected at 20 to 28 weeks post-infection (PI), became statistically significant after 28 weeks and remained elevated up to 52 weeks PI and after challenge infections. During primary infections DTH responses to leishmanin antigen were detected as early as 8 weeks PI, and continued up to 27 weeks PI. After challenge infections DTH reactivity was positive at 25 and 37 weeks, the only times the response was evaluated. The immunological responses of owl monkeys to L. b. panamensis were similar in many respects to those observed in humans with localized cutaneous leishmaniasis. This nonhuman primate model should be useful for future studies involving the immunology and chemotherapy of cutaneous leishmaniasis.

Animals↗

PubMed2001

Normal proliferative responses of peripheral blood mononuclear cells to streptococcal preparation OK-432 in patients with pustulosis palmaris et plantaris constitute a distinct feature from the reduced responses observed in those with psoriasis vulgaris, pustular psoriasis, and acrodermatitis continua of Hallopeau.

It was previously reported that peripheral blood mononuclear cells (PBMC) from the patients with psoriasis vulgaris (PV) showed a reduced proliferative response in vitro to the stimulation of a lyophilized preparation of penicillin-treated low virulence Su-strain of Streptococcus pyogenes group 3, OK-432. In this study, at first it was examined whether OK-432 acts as a superantigen. By analyzing the usage of Vbeta T-cell receptor (TCR) of proliferating T cells stimulated with OK-432, it was found that OK-432 stimulated preferentially Vbeta2 TCR-bearing T cells. Next, to find differences in in vitro responses of PBMC among various types of sterile pustular dermatoses such as pustulosis palmaris et plantaris (PPP), acrodermatitis continua of Hallopeau (AC), and generalized pustular psoriasis (GPP), the proliferative responses of PBMC obtained from these patients under the stimulation of OK-432 were compared. When the PBMC was stimulated with interleukin (IL)-2, no significant difference was found in their proliferative responses among those obtained from the patients with these sterile pustular dermatoses, PV or healthy controls. However, like those from PV patients, PBMC from AC and GPP patients showed significantly smaller responses to OK-432 than those from the healthy controls. In contrast, the proliferative responses of PBMC from the patients with PPP to OK-432 was comparable to those from healthy controls. These results, in addition to its unique clinical and histopathological characteristics, suggest that PPP has a different pathogenetic background from that underlying PV, AC, or GPP.

Acrodermatitis↗

PubMed1999

Peripheral hormonal responses to D-fenfluramine as a probe of central serotonergic function in humans.

We tested the hypothesis that D-fenfluramine (DFEN)-elicited cortisol (CORT) release in humans may be mediated by a direct effect on the adrenal gland by pretreating subjects with dexamethasone (DEX), to prevent release of ACTH from the pituitary, followed by a DFEN challenge test. Eight healthy subjects (four males; four female) (mean age = 38.1 +/- 8.4 years (SD)] were studied > 1 week apart (same phase of menstrual cycle) and testing order was randomised. On the with-DEX day (DEX+), subjects took 2 mg DEX orally at 10 p.m.; 30 mg DFEN was then given orally at 9 a.m. and samples were taken at 0-5 h for PRL and CORT. Peak hormone responses (delta values) were calculated by subtracting baseline values from the maximum levels post-DFEN administration. Peak and baseline hormonal values were compared between the two test conditions; DFEN-induced CORT and PRL responses were compared across all time points, with and without DEX. There was no significant difference in delta PRL between the two test conditions (DEX- and DEX+), but delta CORT values were significantly reduced after DEX: mean delta CORT DEX- = 68.4 +/- 26.3 nmol/l; DEX+ = 0.0 nmol/l (all blunted) (df 7,1; P = 0.03). The completely blunted peripheral cortisol response indicates that DFEN cortisol responses are of central origin only.

Adrenocorticotropic Hormone↗

PubMed1991

Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis.

The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 +/- 11% versus 6 +/- 18%, p less than 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 +/- 5% versus -42 +/- 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 +/- 30% versus 108 +/- 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 +/- 4% versus 1 +/- 4%, p less than 0.05) and nitroprusside (19 +/- 4% versus 5 +/- 4%, p less than 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 +/- 1% versus -1 +/- 5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1991

In vitro response of peripheral blood mononuclear cells to phytohemagglutinin and interleukin-2.

The serological determination of class II antigens is still a mandatory test prior to allotransplantation. It is known that these antigens are normally expressed on B lymphocytes and monocytes. The B lymphocytes that constitute 10% to 15% of total blood lymphocytes are the cells currently used for HLA-DR typing. To avoid HLA-DR typing difficulties, or even impossibilities that are frequently encountered among some patient groups, we studied the response of peripheral blood mononuclear cells--as an alternative source of cells for class II antigen typing--to in vitro mitogen and interleukin-2 activation and propagation. Although the patients included in this study were selected having previously known HLA-DR typing difficulties, all could be adequately typed by this method.

B-Lymphocytes↗

PubMed1980

Therapy of primary hypothyroidism with L-triiodothyronine: discordant cardiac and pituitary responses.

Cardiac systolic time intervals were studied in ten patients with primary hypothyroidism before and during therapy with increasing doses of oral L-triiodothyronine (L-T3). Therapy was increased sequentially from 10, 20, 25 to 50 microgram of L-T3 daily on a monthly basis. On L-T3, 20 to 25 microgram/day, cardiac systolic time intervals and other peripheral responses to thyroid hormone including serum cholesterol concentration, serum creatine phosphokinase (CPK) activity, and basal metabolic rate had normalized. However, serum thyrotrophin (TSH) levels and peak TSH responses to thyrotrophin-releasing hormone (TRH) remained elevated on these doses of L-T3. As the dose of L-T3 was increased from 20 to 50 microgram/day, mean basal serum TSH levels decreased from 55 to 16 microunits/ml, and the peak TSH response to TRH decreased from 243 to 58 microunits/ml (P less than 0.001) while systolic time intervals did not decrease further. Changing to L-thyroxine (L-T4) therapy at this point resulted in further suppression of TSH secretion, without significantly altering systolic time intervals or the other peripheral responses to thyroid hormone. These data suggest (a) that some biological responses to thyroid hormone were normalized on lower doses of L-T3 than were required to normalize TSH secretion, and (b) that higher doses of L-T3 or substituting L-T4 therapy could suppress TSH secretion further without altering the other peripheral responses to thyroid hormone.

Adult↗

PubMed1979

Influence of sex and age on febrile responses to peripheral and central administration of pyrogens in the rabbit.

1. Intravenous injections of leucocytic pyrogen in doses of 15, 30 and 60 mul./kg caused febrile reactions in male rabbits that were related to age of the animal: rabbits under 2 yr of age developed fevers that were related to dose of pyrogen, while rabbits 2-3 yr old showed large febrile responses which were not dose-related.2. Female rabbits of comparable ages generally showed smaller febrile reactions to I.V. leucocytic pyrogen, and still older females (3-5 yr) developed fever only after the largest dose.3. Dose-related febrile responses to 2.5, 5 and 10 mul. leucocytic pyrogen given intracerebroventricularly (I.C.V.) were greater in male rabbits 1-3 yr old than in females of comparable age. Female rabbits 3-5 yr old showed dose-related fevers that were smaller than those of younger animals of both sexes.4. There were no major differences in response to 125, 250 and 500 ng PGE(2), given I.C.V., between male and female rabbits under 2 yr of age. Females 2-3 yr of age had greater responses to PGE(2) than males of comparable age whilst the oldest females showed smaller responses.5. It is concluded that the febrile response of the rabbit to peripheral and central leucocytic pyrogen varies with both age and sex. Differences in sensitivity of central fever controls to endogenous pyrogen in animals of different ages and sexes may account for the different responses to peripheral pyrogen.

Aging↗

PubMed2006

Modulated hemodynamic response to clonidine in bile duct-ligated rats: the role of nitric oxide.

Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(omega)-nitro-L-arginine methyl ester (L-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 microg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P<0.001) and hypotension (P<0.05), which were corrected by chronic naltrexone but not L-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P<0.01). Acute L-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P<0.05). However, the difference between the two groups was preserved (P<0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P<0.001). Chronic L-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P<0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities.

Animals↗

PubMed2003

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies.

Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

Adolescent↗

PubMed1993

Late asthmatic response causes peripheral airway hyperresponsiveness in dogs treated with metopirone.

To determine if late asthmatic response (LAR) is associated with hyperresponsiveness of airway smooth muscle itself, we performed antigen challenge in dogs treated with Metopirone. We studied the contractile response to acetylcholine (ACh) in isolated bronchial and bronchiolar segments 8 h after either saline inhalation (the control group) or antigen challenge in dogs demonstrating immediate asthmatic response (IAR) alone and in dogs demonstrating both IAR and LAR. Airway responses to Ascaris suum antigen were assessed by changes in respiratory resistance measured with the forced oscillation technique at 3 Hz. Concentration-response curves of bronchial preparations to ACh did not differ significantly among three groups consisting of the control, IAR and LAR. However, the contractile response of bronchiolar preparations to ACh was significantly greater in the LAR group when compared to the control and IAR groups at the concentrations of ACh ranging from 10(-6) to 3 x 10(-4) M (p < 0.01). SQ 29548, a receptor antagonist of thromboxane A2 and prostaglandin D2 (PGD2), inhibited LAR-induced hyperresponsiveness to ACh in a concentration-dependent fashion. The bronchiolar preparations obtained from dogs showing LAR contained a significantly higher amount of PGD2 than those obtained from dogs showing IAR alone (p < 0.01, n = 6). These results suggest that LAR is associated with hyperresponsiveness of peripheral airway smooth muscle to ACh, and this augmented response to ACh mediates via PGD2 released during LAR.

Acetylcholine↗

PubMed2002

The enzyme indoleamine 2,3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen.

The essential amino-acid, L-tryptophan, is the precursor of serotonin. Its availability in the brain is controlled by indoleamine 2,3-dioxygenase (IDO). This enzyme is inducible by cytokines such as interferon-gamma (IFN-gamma) and is the first and rate-limiting enzyme of the catabolism pathway of tryptophan. Since induction of IDO has been proposed to mediate the influence of cytokines on mood in patients with various somatic disorders, the present study aimed at analyzing the relationships between changes in brain IDO activity and serum IFN-gamma levels in response to peripheral immune stimulation by lipopolysaccharide (LPS) and superantigen in mice. Each of these treatments induced an increase in serum IFN-gamma at 6 h post-treatment followed 24 h later by a two-fold increase in IDO activity in the brain. These results support the involvement of peripheral IFN-gamma in the control of L-tryptophan catabolism in the brain.

Animals↗