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Results for “peripheral response”

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PubMed2002

Peripheral inflammatory response in Alzheimer's disease and multiinfarct dementia.

Whether peripheral inflammatory molecules can be considered markers of dementia is still an open issue. We have investigated the presence of circulating cytokines and the ability of blood cells to release them in response to an inflammatory stimulus in patients with different types of dementia and in age-matched controls. A significant increase in circulating interleukin-1beta in moderate Alzheimer and in multiinfarct (145 and 224 times control concentration, respectively) dementia and in circulating tumor necrosis factor-alpha concentration in multiinfarct dementia patient group (156%) were found. Tumor necrosis factor-alpha and interleukin-6 released from blood cells after exposure to lipopolysaccharide were significantly reduced in moderate Alzheimer (60%, both cytokines) and multiinfarct patients (71 and 50%, respectively), while interleukin-10 was decreased only in multiinfarct patients (61%). The results show that patients with Alzheimer disease or multiinfarct dementia have an upregulation of circulating cytokines and a downregulation of cytokines released by blood cells.

Alzheimer Disease↗

PubMed2006

Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells.

beta-Defensins are a family of small cationic peptides involved in the innate response to microbial infection. Although their role in microbial killing is well established, the mechanisms through which this occurs remain largely undefined. Here, using protein array technology, we describe a role for human beta-defensins in the induction of an inflammatory cytokine response by human peripheral blood mononuclear cells (PBMCs). Human beta-defensins 1, 2, and 3 were examined for induction of an array of cytokines and chemokines. Some cytokines, such as interleukin 8 (IL-8) and monocyte chemoattractant protein 1, were up-regulated by all three defensins, while others, such as IL-6 and IL-10, were induced more selectively. It was notable that each defensin induced a unique pattern of cytokines. This report documents, for the first time, an analysis of the composite cytokine response of human PBMCs to beta-defensins. The induction or up-regulation of a number of cytokines involved in the adaptive immune response suggests a possible role for these defensins in linking innate and acquired immunity.

Cells, Cultured↗

PubMed1978

In vitro responses of peripheral blood and spleen lymphoid cells to mitogens and antigens in childhood Hodgkin's disease.

Over the past 5 years, parameters of immunological function have been determined in all children with biopsy-proven Hodgkin's disease in the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center. This report summarizes the in vitro responses of lymphocytes to stimulation by mitogens and antigens (between January 1975 and December 1976) in 33 of these previously untreated patients. In nine of these patients, responses of the splenic lymphocytes were studied concomitantly with the responses of peripheral blood lymphocytes. Peripheral blood from normal children and adults was used as the control. Our results have demonstrated no significant differences between the responses of normal children and adult controls. The absolute necessity for concomitant studies of the controls and the patients was shown. The value of examining multiple concentrations of a single mitogen was also well defined. In the children with Hodgkin's disease, there was a consistent failure of the peripheral blood lymphocytes to respond to the lower concentration dose of phytohemagglutinin. However, this abnormality was not found in the splenic lymphocytes.

Adolescent↗

PubMed2005

The response of peripheral blood neutrophils unstimulated and stimulated by prodigiosan to smoking.

UNLABELLED: Alterations of neutrophils function by tobacco products may play a central role in the pathogenesis of periodontal diseases and several smoking related systemic diseases. The aim of the study was to assess a response of peripheral blood neutrophils unstimulated and stimulated by prodigiosan to smoking. MATERIALS AND METHODS: The study included 17 smoking men that addressed for treatment of various odontological problems to out patient department of Kaunas University Clinic. The subjects were 22-43 years of age and systemic diseases free. All subjects answered to questions about smoking habits. To assess the response of neutrophils (unstimulated and stimulated by prodigiosan) to smoking the chemiluminescence and nitroblue tetrazolium test were used to measure their oxidative metabolism. RESULTS: After smoking both neutrophils unstimulated and stimulated with prodigiosan showed considerable extracellular chemiluminescence responses, but the first one reached maximal value in 45 min, while the second one in 15 min after smoking. There was no total (intra and extracellular) chemiluminescence response of neutrophils unstimulated and stimulated by prodigiosan to smoking. Neutrophils exposed to smoking showed a significant increase in their nitroblue tetrazolium reduction. CONCLUSION: Both stimulated by prodigiosan and unstimulated peripheral blood neutrophils release reactive oxygen species extracellulary which may alter the pathogenic processes in periodontal and other systemic diseases.

Adjuvants, Immunologic↗

PubMed1993

Response of peripheral nerve to cyclic compression in a laboratory rat model.

Repetitive cyclic loading of a nerve has been proposed as a pathogenic factor in the development of occupational compression neuropathies. Little is known about the basic response of peripheral nerve to cyclic compression. We investigated the hypothesis that cyclic compression is more detrimental to nerve function than constant compression. We measured the amplitudes and velocities of distally evoked action potentials in the presence of constant or cyclic compression of the tibial nerve in rats. Seven groups were subjected to constant or cyclic compression for 6 h by a computer controlled, hydraulically activated compression chamber. Nerves were compressed with 0 (control group), 30, 60, or 90 mm Hg of constant pressure or 0-30, 20-50, or 30-60 mm Hg of cyclic compression for approximately 20,000 compression cycles. Action potentials were recorded every 15 min. The effects of cyclic compression on nerve conduction were equivalent to the effects of constant compression at the average applied pressure. Cyclic loading itself does not appear to be an important pathogenic factor in the development of nerve conduction block.

Action Potentials↗

PubMed1995

Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals.

Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic asthmatic patients with normal spirometric values, and to be correlated with airways hyperresponsiveness to methacholine. We investigated whether Rp in asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in response to cool, dry air. Using a wedged bronchoscope technique, we challenged an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22 degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and eight normal subjects. Baseline Rp and Rp following challenge were measured with saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min; median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07] cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03 to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We conclude that the peripheral airways of asthmatic individuals with EIB are responsive to cool, dry air, and may play an important role in EIB.

Airway Resistance↗

PubMed1995

[The studies on the effect of proliferative response of peripheral blood lymphocyte of healthy persons by preparations of M. vaccea].

This paper present that preparations of M. vaccea, which included suspensions of live bacilli, irradiation-killed bacilli and high temperature killed bacilli, for the effect on lymphocyte proliferative response of peripheral blood in healthy persons were compared by 3H-TdR incorporation method. CPM of control was 448 +/- 131, CPM adding suspensions of live M. vaccea, irradiation-killed bacilli and high temperature killed bacilli were 1037 +/- 194, 2299 +/- 140, 1819 +/- 528, 994 +/- 186, respectively. Stimulative index of all four preparations were more than 2.0, specially suspensions of live and irradiation killed M. vaccea is more effective than BCG and high temperature killed M. vaccea, which were 5.13, 4.06, respectively. In another experiment, suspensions of live, irradiation-killed and high temperature killed M. vaccea plus rIL-2 were found more effective than rIL-2 alone. CPM of them were 9544 +/- 1727, 8530 +/- 714, 8230 +/- 1035, and 3721 +/- 1336, respectively, but BCG was 6904 +/- 1218. The results show that preparations of M. vaccea tested have distinctly promotive effect for proliferative response of lymphocyte in vitro. The addition of rIL-2 to suspendions of live M. vaccea, irradiation killed and high temperature killed M. vaccea cooperatively increased the effects of proliferative response mentioned above.

BCG Vaccine↗

PubMed1980

Proliferative responses of peripheral blood lymphocytes to polyclonal activation: a comparison of young and elderly individuals.

Associated with human aging is a decline in immune activity, of both the cell-mediated and humoral types. In vivo, autoantibodies increase with aging and antibody responses to flagellin are decreased in the elderly as compared to the young. These abnormalities may be due to defects in helper or suppressor T cells, or innate defects in B cells. In vitro, the proliferative response of B cells to pokeweed mitogen (PWM) is dependent upon T cells. We studied the proliferative response of peripheral blood mononuclear cells (MNC) to polyclonal activation with PWM in young and elderly normal individuals and found that the number of IgA- and IgM-bearing B cells produced was increased in elderly subjects. This difference was statistically significant for IgA-bearing cells when MNC were placed with 5 and 15 microliter of PWM for 5 days and with 15 microliter of PWM for 6 days. Statistically significant increases in IgM-bearing cells were seen when MNC were plased with 5 microliter of PWM for 5 days and 5 and 10 microliter of PWM for 7 days. The differences in numbers of IgG-bearing cells were less consistent. Significant increases were seen when MNC were cultured with 10 microliter of PWM for 5 days and 5 microliter of PWM for 6 days. Our results suggest that in elderly normal individuals numbers of immunoglobulin-bearing cells are increased after polyclonal activation of MNC. This increase in immunoglobulin-bearing B cells associated with reports of in vivo humoral abnormalities suggests that there is loss of regulation of T cells on B cells in normal elderly individuals.

Adult↗

PubMed2003

Proliferative response of peripheral blood lymphocytes to mitogens in the owl monkey Aotus nancymae.

The new world primate Aotus sp. has been recommended by the World Health Organization as a model for evaluation of malaria vaccine candidates, given its susceptibility to experimental infection with the human malaria parasites Plasmodium falciparum and P. vivax. The present study examined the in vitro proliferative response of peripheral blood mononuclear cells (PBMCs) isolated from Aotus monkeys, utilizing a wide range of mitogens. Results presented herein demonstrate that the in vitro proliferative response of PBMCs from the Aotus sp. is quite variable from monkey to monkey for each of the mitogens assessed. PBMCs from the Aotus monkey exhibited a delayed kinetic proliferative response and, particularly, a different sensitivity to proliferation in response to various concentrations of Phytohemagglutinin-P and favin lectins, the phorbol ester Phorbol myristate acetate and the calcium ionophore ionomycin. Altogether, our findings are consistent with the conclusion that the in vitro proliferative response of PBMCs from the Aotus differ in their activation requirements compared with PBMCs from humans.

Animals↗

PubMed2003

Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides.

OBJECTIVES: Increased levels of hypomethylated CpG-containing DNA in sera from patients with systemic lupus erythematosus (SLE) may contribute to the initiation and/or perpetuation of the disease. This study characterizes the in vitro response of peripheral blood mononuclear cells (PBMC) from SLE patients to CpG DNA. METHODS: Secretion of cytokines and IgM, cell proliferation and up-regulation of co-stimulatory molecules were evaluated in PBMC from SLE patients (n=24) and normal controls (n=24) after stimulation with synthetic oligodeoxynucleotides (ODN) containing CpG motifs. RESULTS: Up-regulation of co-stimulatory molecules and the secretion of interferon-alpha and interleukin-6 (IL-6) in response to CpG ODN was significantly reduced in monocytes and dendritic cells from SLE patients. Secretion of interferon-gamma by natural killer (NK) cells was also reduced. In contrast, the IgM and IL-10 response of B cells to CpG ODN was normal. CONCLUSION: Monocytes, dendritic cells and NK cells from SLE patients respond abnormally to CpG ODN stimulation, which may contribute to the cytokine imbalance observed in SLE.

Aged↗

PubMed1998

A T cell activation antigen, Ly6C, induced on CD4+ Th1 cells mediates an inhibitory signal for secretion of IL-2 and proliferation in peripheral immune responses.

A T cell activation antigen, Ly6C, is considered to be involved in the autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains largely unknown. We prepared a rat anti-mouse Ly6C monoclonal antibody (mAb) (S14) that inhibits the proliferation of peripheral T cells stimulated with anti-CD3 mAb in vitro. S14 mAb, the specificity of which is confirmed by a cDNA transfectant, recognizes Ly6C antigen preferentially expressed on a part of CD8+ T cells in peripheral lymphoid organs. The immunohistochemical analysis demonstrates that Ly6C appears on CD8+ T cells in the conventional T cell-associated area of BALB/c but not of nonobese diabetic (NOD) mice, confirming the absence of Ly6C+ T cells in NOD mice. Addition of soluble S14 mAb to the culture does not influence the proliferation of T cells in vitro; however, the S14 mAb coated on the plate clearly inhibits the proliferation and IL-2 production of anti-CD3-stimulated peripheral T cells. The T cells are arrested at the transitional stage from G0/G1 to S+G2/M phases, but they are not induced to undergo apoptotic changes in vitro. This inhibitory signal provided through the Ly6C molecule inhibited IL-2 secretion in a subpopulation of the activated CD4+ T cells. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the cytokine secretion from Th1 clones is preferentially inhibited. These results suggest that Ly6C mediates an inhibitory signal for secretion of cytokines from Th1 CD4+ T cells, potentially causing the inhibition of immune response in peripheral lymphoid tissues.

Animals↗

PubMed1990

Effects of food on the central and peripheral haemodynamic response to upright exercise in normal volunteers.

The central and peripheral haemodynamic effects of a modest meal were investigated in healthy volunteers at rest and in response to submaximal exercise. The meal increased heart rate, cardiac output, oxygen consumption, carbon dioxide production, and minute ventilation at rest and during exercise. The effects of food were additive to those induced by the exercise. Food had no effect on limb blood flow and lowered total systemic vascular resistance suggesting that there were no compensatory changes in regional blood flow to help redirect blood to the gut. An increase in cardiac output, and therefore myocardial work, is the predominant cardiovascular response to eating and this may help explain the postprandial deterioration in symptoms of some patients with cardiovascular disorders.

Adult↗

PubMed2001

Blunted peripheral vasodilatory response is a hallmark of progressive deterioration in mild to moderate congestive heart failure.

BACKGROUND: Several reports have shown that dilatory response to acetylcholine (ACh) and nitroprusside (SNP) is blunted in the limb vasculature in patients with congestive heart failure (CHF). However, it is not yet known whether this vascular dysfunction is related to clinical outcome. We have examined the relationship between peripheral vasodilatory response and prognosis of CHF. METHODS AND RESULTS: A total of 46 patients with mild to moderate CHF were enrolled (mean age 56 years). Changes in forearm blood flow (FBF) during intra-arterial infusion of ACh and SNP were determined by plethysmography. FBF changes above baseline for each dose were cumulated and used as an index of endothelium-dependent (ACh) response and endothelium-independent (SNP) response, respectively. During the follow-up period (mean 32 months), 9 patients were admitted to the hospital for treatment of worsening refractory CHF, and 6 patients died suddenly or developed life-threatening arrhythmia. By Kaplan-Meier analysis, when all cardiac events were included, no significant differences were observed between any levels of vascular response in terms of prognosis. However, when deterioration events were analyzed separately, patients with SNP responses below the median (7.4 mL/min/dL) had significantly higher rates of hospital admission caused by worsening CHF than those with above the median responses (P <.05). This relationship was not found between ACh response and clinical outcome. By Cox multivariate analysis, blunted vasodilatory response to SNP was a significant predictor of worsening CHF (chi(2) = 3.95; P <.05). CONCLUSION: This study has shown that patients with mild to moderate CHF showing a blunted vascular response to SNP rather than ACh were admitted to the hospital more frequently because of deterioration of CHF. This finding suggests that changes in vascular smooth muscle and/or vascular structure in the peripheral vasculature may be a critical element in the worsening of CHF.

Acetylcholine↗

PubMed2000

Effects of the depletion of CD8(+) T cells and monocytes on the proliferative responses of peripheral blood leucocytes from Trypanosoma evansi-infected sheep.

Sheep peripheral blood mononuclear cells and those depleted of CD8(+) T cells and/or monocytes were stimulated with polyclonal mitogens and specific antigens, and analysed by means of cell proliferation assay procedure to examine whether these cell populations are involved in Trypanosoma evansi-induced immunosuppression. The removal of CD8(+) T cells failed to normalize the proliferative responses of peripheral blood mononuclear cells from infected sheep to concanavalin A stimulation while the depletion of monocytes resulted in full and enhanced response, showing that macrophages are mainly responsible for the suppression. Although the depletion of CD8(+) T cells, monocytes or both restored the responses of the cells to lipopolysaccharide stimulation, the responsiveness of the undepleted cells to this mitogen was significantly higher from day 24 post infection (p<0.01). The results were discussed in relation to current known mechanisms of depressed lymphocyte proliferation in tsetse-transmitted African trypanosome infections.

Animals↗

PubMed1995

Responsiveness of peripheral blood mononuclear cells from normal and atopic donors to microbial superantigens.

Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus strains secreting exotoxins such as the staphylococcal enterotoxin B (SEB) and A (SEA). Nonetheless the role of SEB and SEA in AD is yet unknown. We analyzed the responsiveness of peripheral blood mononuclear cells (PBMCs) and isolated T cells from donors with AD and from normal donors to SEB and SEA. PBMCs as well as T cells from normal donors showed a significantly enhanced proliferation after stimulation with enterotoxin B, whereas the 3H-thymidine uptake of the T lymphocytes from patients with AD was markedly suppressed. Furthermore, we show that IFN-gamma mRNA and protein and mRNA for both chains of IL-12 (p35 and p40) are produced in human PBMCs from normal donors upon stimulation with SEB and SEA. In contrast to normal donors T cells from donors with AD predominantly express mRNA for IL-4, IL-5, and only diminished levels for IFN-gamma and IL-12 upon stimulation with SEB and SEA. Furthermore, in contrast to normal donors, PBMCs from donors with AD spontaneously produce high levels of IgE and express increased levels of CD23, the low-affinity receptor for IgE. Nonetheless, the superantigens by themselves, from 0.1 fg up to 1 microgram/10(6) cells, induced neither IgE secretion nor CD23 expression on PBMCs. Moreover, the addition of superantigens to IL-4-treated PBMC cultures diminished or totally suppressed the IL-4-induced IgE synthesis and CD23 expression. No differences were observed between PBMCs from normal donors of donors with AD. Both PBMCs isolated from normal and atopic donors produced high levels of soluble IL-4-receptor (up to 210 +/- 90 pg/ml). Addition of soluble IL-4-receptor to PBMC cultures downregulated the IL-4-induced IgE synthesis and CD23 expression in unstimulated as well as in SEB-stimulated PBMCs from normal donors and donors with AD. Our results suggest that superantigen-producing staphylococcal strains on the skin of patients with AD may modulate and/or amplify allergic inflammation.

Base Sequence↗

PubMed1985

Adrenalectomy reduces peripheral neural responses to gustatory stimuli in the rat.

In the rat, sodium need leads to an increase in sodium intake, which depends on salt taste sensitivity. The adrenalectomized rat, because of excessive body sodium loss, has been an important animal model for studying the physiological mechanisms underlying salt ingestion. In order to investigate the mediation by peripheral taste responsivity of changes in salt intake, multiunit responses of the chorda tympani nerve to various concentrations of sodium chloride, potassium chloride, lithium chloride, hydrochloric acid, and quinine hydrochloride were recorded from adrenalectomized and control rats. In order to control for a generalized decrease in sensory sensitivity, recordings from the auriculotemporal nerve to tactile stimulation of the pinna were also performed. There were no group differences in amplitude of the integrated neural responses to tactile stimulation. The largest decrease in gustatory responsivity occurred for suprathreshold concentrations of sodium chloride and lithium chloride. The data are discussed with reference to possible mechanisms underlying this neural alteration and to the role that reductions in salt taste responsivity play in mediating increases in salt intake.

Adrenal Glands↗

PubMed1984

Mitogen-induced hyperproliferation response of peripheral blood mononuclear cells from patients with severe generalized periodontitis: lack of correlation with proportions of T cells and T-cell subsets.

Severe generalized periodontitis (SGP) is a localized inflammatory disease which differs clinically from common periodontitis in that it leads to remarkable extensive alveolar bone loss in relatively young adults. There is evidence that B-cell responses to bacterial substances may play a major role in the pathogenesis of this disease. In the present report, we show that a B-cell mitogen from Actinomyces viscosus (AVIS) bacteria provokes a hyperproliferation response of peripheral blood mononuclear cells (PBMNC) from these patients. In addition, AVIS-stimulated PBMNC from SGP patients proliferate for longer periods in culture than do PBMNC from control subjects. There were, however, no differences between patients and controls in the numbers of immunoglobulin-secreting cells in these cultures as determined by an indirect plaque-forming cell assay. The possibility that differences in numerical proportions of regulatory T-cell subsets may play a role in the mitogen-induced hyperproliferation phenomenon is examined. PBMNC were stained with fluorescein isothiocyanate-conjugated monoclonal antibodies OKT3, OKT4, and OKT8 in order to identify, respectively, total T cells, helper/inducer, and suppressor/cytotoxic subsets. Flow cytometric analysis of such specifically stained cell preparations from 14 control subjects and 14 SGP patients did not reveal any significant differences between the proportions of total T cells or T-cell subsets of the two groups. Furthermore, there were no statistically significant correlations between the magnitude of proliferation responses and the proportions of total T cells or either of the T-cell subsets.

Adult↗

PubMed2006

Medullary monoamines and NMDA-receptor regulation of cardiovascular responses during peripheral nociceptive stimuli.

We have previously reported that AMPA-receptor blockade within the rostral ventrolateral medulla (RVLM) attenuates cardiovascular responses and extracellular concentrations of glutamate during mechanical, but not during thermal stimulation [Gray, T., Lewis III, E., Maher, T.J., Ally, A., 2001. AMPA-receptor blockade within the RVLM modulates cardiovascular responses via glutamate during peripheral stimuli. Pharmacol. Res. 43, 47-54]. In this study, we examined the role of NMDA-receptor blockade within the RVLM on cardiovascular responses and release of biogenic monoamines (serotonin [5HT], dopamine [DA], and norepinephrine [NE]) during both mechanical and thermal nociception using anesthetized Sprague-Dawley rats. Both mechanical and thermal stimulation have been shown to activate peripheral Adelta and C-fiber polymodal nociceptors. Noxious mechanical stimuli were induced by applying a pinch to alternate hindpaw for 5s while the noxious thermal stimuli involved immersion of the metatarsus of alternate hindpaw in a water bath at a temperature of 52 degrees C for 5 s. Mechanical stimulation increased mean arterial pressure (MAP), heart rate (HR), extracellular fluid 5HT, and DA concentrations (n=10). However, extracellular levels of NE were decreased within the RVLM. Furthermore, NMDA-receptor blockade with a competitive antagonist, AP-7 (200 nM), within the RVLM attenuated the cardiovascular responses and changes in 5HT and DA, but had no effect on NE levels. The thermal stimulation elicited similar increases in MAP and HR, however, extracellular levels of 5HT or DA did not change. Concentrations of NE were decreased during a thermal stimulation similar to the levels observed following mechanical stimuli. In contrast to mechanical stimuli, bilateral administration of AP-7 (200-1 mM) into the RVLM had no effect on cardiovascular responses, 5HT, DA or NE concentrations during a thermal stimulation. These results show that NMDA receptors within the RVLM most likely play a role in modulating cardiovascular responses by altering 5HT and DA concentrations within the RVLM during mechanical but not thermal nociception. Overall, the present study delineates the NMDA-receptor mediated central integrative mechanisms within the RVLM that coordinate processing of sensory impulses arising from peripheral noxious stimulation.

Afferent Pathways↗