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PubMed1999

The late asthmatic response is associated with baseline allergen-specific proliferative responsiveness of peripheral T lymphocytes in vitro and serum interleukin-5.

BACKGROUND: Increasing insights into the mechanism underlying the allergen-induced late asthmatic response (LAR) have been gained with implication of activated eosinophils and CD4+ T lymphocytes. However, the patient characteristics that indicate the individual capacity to develop a LAR are not well-defined. METHODS: In 22 subjects with mild to moderate house dust mite-allergic asthma, we investigated the relationship between the LAR and two other models of late-phase allergic inflammation, i.e. the allergen-specific proliferative response of peripheral blood T lymphocytes in vitro and the late cutaneous response. Non-specific bronchial responsiveness (PC20histamine), lung function (FEV1), peripheral blood eosinophil count, early phase allergic skin sensitivity, and levels of total and specific immunoglobulin E (IgE) were determined prior to bronchial allergen challenge. Serum levels of interleukin-5 (IL-5) were measured before and at several time points after allergen inhalation. RESULTS: A significant correlation was found between the magnitude of the LAR and the allergen-specific proliferative response of peripheral T lymphocytes (r = 0.44, P = 0.04) but not the late cutaneous response. Stepwise-multiple linear regression of the magnitude of the LAR on the parameters analysed at baseline, resulted in a model combining PC20 histamine, early phase allergic skin sensitivity, and the allergen-specific proliferative response of peripheral T lymphocytes (R2 = 0.84, P<0.001). No contribution of the late cutaneous response to the prediction of the LAR was found. Serum levels of IL-5 increased significantly at 6 h (P = 0.01) and 24 h (P = 0.003) after bronchial allergen challenge and correlated with the allergen-specific proliferative response of peripheral T lymphocytes in vitro (rho = 0.48, P = 0.02). CONCLUSIONS: The findings in this study point to a role of TH2-lymphocyte responses in the development of the allergen-induced LAR. In allergic asthmatic patients, allergen-specific responsiveness of peripheral T-lymphocytes in vitro may serve as a model to determine the individual capacity to develop a LAR after allergen inhalation.

Adolescent↗
PubMed1971

The peripheral vascular response to severe exercise in untethered dogs before and after complete heart block.

The peripheral vascular response to severe exercise was studied in 11 healthy conscious dogs instrumented with Doppler ultrasonic flow probes on the mesenteric, renal, and iliac arteries, and miniature pressure gauges in the aorta. The response to severe exercise was restudied in six of these dogs after recovery from a second operation producing complete heart block by the injection of formalin into the atrioventricular (AV) node. Three of these dogs also exercised while their ventricles were paced at rates of 100/min and 200/min. The untethered normal dogs ran at speeds of 15-25 miles/hr behind a mobile recording unit for a distance averaging 1.5 miles, while continuous measurements of arterial blood pressure and blood flow were telemetered and recorded on magnetic tape. Severe exercise in normal dogs increased heart rate from 84 to 259/min, arterial pressure from 89 to 140 mm Hg, flow resistance in the mesenteric and renal beds by 59 and 52% respectively, and iliac blood flow 479% above control, while mesenteric and renal blood flows remained constant and iliac resistance decreased by 73%. In dogs with complete AV block, severe exercise at speeds of 10-18 miles/hr increased heart rate from 47 to 78/min, mean arterial pressure from 81 to 89 mm Hg, iliac flow 224%, resistance in the renal bed by 273%, and mesenteric bed by 222% while it decreased blood flow in mesenteric and renal beds by 61 and 65% respectively, and iliac resistance by 62%. A similar response occurred during exercise with pacing at 100/min, but when paced at 200/min a more normal exercise response reappeared. Thus, in normal dogs the peripheral vascular response to severe exercise involved increases in heart rate, arterial pressure and visceral resistance but visceral blood flow did not decrease. In dogs with heart block, where the ability to increase heart rate is severely compromised, compensatory reduction of mesenteric and renal blood flows occurred.

Abdomen↗
PubMed1990

Brain histamine regulates pressor responses to peripheral hyperosmolality.

The role of brain histamine (HA) in the pressor response to peripheral hyperosmolality was investigated in the conscious Sprague-Dawley rat. Increased mean arterial pressure was observed during a 30-min intravenous infusion of hypertonic saline (HTS; 10 microliters.100 g body wt-1 x min-1) in vehicle-treated controls (20.1 +/- 3.8 mmHg) and in animals centrally pretreated with the specific H2-antagonist, cimetidine (15.0 +/- 3.7 mmHg). However, this pressor response was abolished in a dose-dependent manner after intracerebroventricular injection of the H1 antagonist promethazine. In other experiments, brain tissue microdissected from the supraoptic nucleus (SON), paraventricular nucleus (PVN), and posterior hypothalamic region showed significantly lower levels of total tissue HA after 60 min of intravenous HTS infusion compared with tissue taken from control animals receiving an isotonic infusion. Microdialysis in the region of the PVN or SON before and during HTS infusion showed increased extracellular concentrations of HA in the SON (24.4 +/- 10.9%) during infusion. No change in extracellular HA concentration was seen in the PVN during HTS infusion. These results support the conclusion that endogenous brain HA is involved in the pressor response to peripheral hyperosmolality.

Animals↗
PubMed1992

Cellular immune responses of peripheral blood mononuclear cells to HBV antigens during chronic and acute HBV infection.

Patients with acute self-limited and chronic HBV infection were studied to determine their in vitro cellular immune response to HBV antigens. In interferon-gamma production cultures which were evaluated as an indicator of cellular immune response, peripheral blood mononuclear cells from patients with HBeAg-positive chronic hepatitis showed elevated response to HBcAg, while those from HBeAg-positive asymptomatic carriers revealed no response to either HBcAg or HBeAg. HBeAg-stimulated interferon-gamma production was higher in anti-HBe-positive chronic hepatitis and asymptomatic carriers than that in HBeAg-positive patients. Interferon-gamma production against HBcAg was shown to be HLA class II restricted by blocking assay using monoclonal antibodies. HBsAg with or without pre-S2 did not amplify interferon-gamma production of patients with chronic hepatitis. In acute hepatitis B, both envelope and nucleocapsid antigens induced greater interferon-gamma production than in chronic HBV carriers. These results indicate that the patients with acute hepatitis responded more to HBV antigens compared with chronic HBV carriers. Furthermore, enhanced cellular immune responses, particularly to HBeAg, were observed in anti-HBe-positive patients compared to HBeAg-positive patients during chronic HBV infection, suggesting that the poor response to HBeAg in HBeAg-positive patients may account for the failure to clear HBV.

Adult↗
PubMed1993

Evaluation of prognoses of patients with gastric cancer by the responsiveness of peripheral blood lymphocyte to OK432 in vitro.

The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients. When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05). In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05). There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9%. In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001). The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis.

Cell Division↗
PubMed2001

Response of peripheral lymphocytes from patients with ossification of posterior longitudinal ligament.

The in vitro response of peripheral blood mononuclear cells or enriched CD4+ T cells from patients with ossification of the posterior longitudinal ligament to anti-CD3 monoclonal antibody has been studied. The response in both was significantly lower in patients with the continuous-type ossification than in patients with the segmental-type ossification and in healthy volunteers, and was inversely correlated with the number of vertebral bodies with ossified ligament. In patients with the segmental-type ossification, the response of peripheral blood mononuclear cells was significantly lower than that in healthy volunteers, but that of the enriched T cells was not. B cell proliferation in response to fixed Staphylococcus aureus cells was significantly lower in patients with the continuous-type ossification than in healthy volunteers but was not correlated with the number of vertebral bodies with ossified ligament. The B cell response in patients with the segmental-type ossification was not lower than that in healthy volunteers. Serum concentrations of transforming growth factor-beta1 and basic fibroblast growth factor also were higher in patients with the continuous-type ossification than in patients with the segmental-type ossification and in healthy volunteers. The findings raise the possibility that continuous-type ossification of posterior longitudinal ligament might develop differently from segmental-type ossification.

Aged↗
PubMed2005

Corticotropin-releasing hormone contributes to the peripheral inflammatory response in experimental autoimmune encephalomyelitis.

Peripheral corticotropin-releasing hormone (CRH) is thought to have proinflammatory effects. We used the model of experimental autoimmune encephalomyelitis (EAE) to study the role of CRH in an immune-mediated disease. We showed that CRH-deficient mice are resistant to EAE, with a decrease in clinical score as well as decreased cellular infiltration in the CNS. Furthermore, Ag-specific responses of primed T cells as well as anti-CD3/anti-CD28 TCR costimulation were decreased in crh(-/-) mice with decreased production of Th1 cytokines and increased production of Th2 cytokines. Wild-type mice treated in vivo with a CRH antagonist showed a decrease in IFN-gamma production by primed T cells in vitro. This effect of CRH is independent of its ability to increase corticosterone production, because adrenalectomized wild-type mice had similar disease course and severity as control mice. We found that IkappaBalpha phosphorylation induced by TCR cross-linking was decreased in crh(-/-) T cells. We conclude that peripheral CRH exerts a proinflammatory effect in EAE with a selective increase in Th1-type responses. These findings have implications for the treatment of Th1-mediated diseases such as multiple sclerosis.

Animals↗
PubMed1978

Proliferative and degenerative events in the early development of chick dorsal root ganglia. II. Responses to altered peripheral fields.

Responses of chick embryo dorsal root ganglia to early wing bud amputation were examined histologically using tritiated thymidine (3H-TdR) and autoradiography to analyze proliferation and the Feulgen procedure to visualize degenerating cells. Right wing buds were amputated at stage 15 or 16. At 4.5 to 9.5 days of incubation embryos were given a 1-hour exposure to 3H-TdR and fixed. Feulgen-stained autoradiographs were examined for percentage of cells labelled (labelling index) or degenerating (degeneration index) in lateroventral (LV) and mediodorsal (MD) regions of brachial (G14-16) and nonbrachial (G12, 13, 17) ganglia. The earliest response to amputation was a highly significant increase in degeneration indices of LV and MD regions of ipsilateral brachial ganglia at 5.5 days. Significant brachial LV responses were observed throughout the remainder of the experimental period. Two peaks occur in this response: at 5.5 days, corresponding to the peak seen in normal nonbrachial ganglia, and at 8.5 days, having no counterpart in normal development. In brachial MD regions significant degenerative responses occur at most times examined. Significant responses also occur at 7.5 and 8.5 days in MD regions of nonbrachial ganglia. The presence of MD responses in our material indicates that maturation of at least some MD neurons occurs earlier than previously thought. Significant labelling responses occur in brachial LV regions from 7.5 days on. Because other studies (Carr and Simpson, '78a) show that this time is after the end of large-scale neuronal production, this labelling response must be nonneuronal in nature. We conclude that this response is a secondary response to amputation, consequent to the greatly increased cellular degeneration. Results of experiments involving addition of limb buds at the brachial level are also presented.

Amputation, Surgical↗
PubMed1979

Lymphocyte studies in rheumatoid arthritis. III. A comparative study of the responses of peripheral blood and synovial fluid lymphocytes to phytomitogens.

The response of peripheral blood and synovial fluid lymphocytes to three non-specific mitogens has been studied. The paired samples were taken from patients with a range of inflammatory arthritides. Unstimulated synovial fluid lymphocytes (SFL) tended to have a greater uptake of tritiated thymidine than had unstimulated peripheral blood lymphocytes (PBL). This background uptake of tritiated thymidine by SFL showed a positive correlation with the response these SFL then showed to the mitogens. A significant depression was observed in the SFL response to phytohaemagglutinin when compared with the paired PBL response; this was seen in both the rheumatoid arthritis and other inflammatory joint diseases groups. SFL responses to concanavalin A and pokeweed mitogen, although depressed in individual cases, failed to show a significant depression overall. Attempts to restore the SFL response to that of the paired PBL by removal of any possible blocking substance from the cell surface either by pre-incubation of SFL in tissue culture medium or by enzyme treatment were unsuccessful. This suggested that cell surface blockers were possibly not the reason for deficient SFL reponses and that other factors were involved.

Arthritis, Rheumatoid↗
PubMed1973

Left ventricular inotropic and peripheral vasomotor responses from independent changes in pressure in the carotid sinuses and cerebral arteries in anaesthetized dogs.

1. The pressure perfusing the isolated carotid sinuses and the pressure perfusing the cerebral circulation were changed independently, and the resulting inotropic responses in the left ventricle and peripheral vasomotor responses were determined.2. Inotropic responses were assessed by measuring changes in the maximum rate of change of left ventricular pressure (dP/dt max) with heart rate and mean aortic pressure held constant. Vascular resistance changes were usually assessed by perfusing the descending thoracic aorta at constant flow and measuring changes in perfusion pressure.3. Decreases in carotid sinus pressure over the baroreceptor sensitivity range resulted in a 45% increase in dP/dt max and a 59% increase in vascular resistance.4. Unless arterial oxygen tension was abnormally low, lowering cerebral perfusion pressure to 50 mm Hg resulted in little or no inotropic and vasomotor responses. In the presence of hypoxaemia (P(a,O2) < 60 mm Hg), lowering cerebral perfusion pressure to below about 80 mm Hg resulted in marked responses.5. These experiments suggest that, unless arterial oxygen tension is abnormally low, the carotid sinus reflex and not cerebral hypotension is important in the control of the inotropic state of the heart and of vasomotor activity. With hypoxaemia, responses from cerebral hypotension may also be important.

Animals↗
PubMed1995

Effects of exercise training on endothelium-dependent peripheral vascular responsiveness.

Endurance training results in peripheral vascular adaptations in skeletal muscle which enhance perfusion and vascular flow capacity. These adaptations could result from structural modifications of the vasculature and/or alterations in the control of vascular tone. One potential mechanism through which vascular control may be modified is through adaptive changes in the intrinsic responsiveness of vascular endothelium. Experiments have demonstrated that vascular responsiveness to endothelium-dependent vasodilators are enhanced in exercise-trained animals. The enhanced endothelium-dependent relaxation appears to be mediated through elevations in the formation of endothelium-derived nitric oxide. Training also results in a decreased sensitivity to the vasoconstrictor effects of norepinephrine. This alteration appears to be due to an endothelium-dependent mechanism involving alpha 2-adrenergic receptors. One stimulus that appears to be important in initiating the adaptation of the endothelium to training is the increase in muscle blood flow and shear stress which occurs during exercise. However, other factors associated with exercise may be necessary to induce endothelial adaptations produced by endurance training. Further research is needed to determine the significance of changes in endothelium-dependent vascular responsiveness and whether this is associated with training-induced increases in muscle perfusion and vascular flow capacity.

Adaptation, Physiological↗
PubMedDate not supplied

Evaluation of lymphocyte proliferative responses to casein hydrolysate formula in cow's milk-sensitive children: response of peripheral blood mononuclear cells to hydrolysate formula.

The proliferative responses of peripheral blood mononuclear cells (PBMCs) to cow's milk proteins and a casein hydrolysate formula were investigated in 10 cow's milk-sensitive patients. The casein hydrolysate formula reduced the symptoms in seven children but not in three. The proliferative responses of PBMCs to cow's milk proteins and the formula were higher in the three patients whose symptoms were not reduced by casein hydrolysate formula. However, the proliferative responses of PBMCs to hydrolysate formula were lower than those to cow's milk proteins in patients whose symptoms were reduced by casein hydrolysate formula. These results suggest that an elimination diet with casein hydrolysate formula may not be as effective in some patients with cow's milk allergy whose PBMCs proliferate to casein hydrolysate formula.

Caseins↗
PubMed1983

Trypanosoma brucei brucei infection in goats. Response of peripheral blood lymphocytes to mitogen stimulation.

The in vitro proliferative response of peripheral blood lymphocytes from Trypanosoma b. brucei infected goats to mitogens was studied during the course of infection. An inverse correlation was observed between the number of lymphocytes and their capacity to respond to concanavalin A, phytohemagglutinin and pokeweed mitogen. Lymphocyte responsiveness to mitogens was reduced during a period of increased lymphocyte counts. During this period of time only few trypanosomes were detectable in the peripheral blood. Later in the infection, when lymphocytes decreased, mitogen responsiveness and parasitemia increased.

Animals↗
PubMed2001

Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in alopecia areata patients with a poor response to topical immunotherapy.

BACKGROUND: Topical immunotherapy with a contact allergen is effective in alopecia areata (AA). However, the mechanism of the effect is still unknown, and pretreatment prediction of the outcome of therapy in each patient remains difficult. OBJECTIVES: To predict the clinical effect of this therapy in AA patients, we investigated the relationship between clinical responses to topical immunotherapy and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to T-cell stimulants. METHODS: PBMC were taken from 67 AA patients before or during diphenylcyclopropenone immunotherapy and from 14 healthy controls, and proliferative responses to phytohaemagglutinin and staphylococcal enterotoxin B were evaluated by measuring [3H]-thymidine incorporation. RESULTS: PBMC from the AA patients with a good clinical response to immunotherapy showed a normal level of proliferation, whereas PBMC from the poor responders showed a markedly suppressed proliferative response and interleukin (IL)-2 production, but increased IL-4 production compared with the controls. CONCLUSIONS: The proliferative response of PBMC to T-cell stimulants may be one of the indicators of the clinical effect of topical immunotherapy for AA.

Adolescent↗
PubMed1993

Esmolol hydrochloride, sodium nitroprusside, and isoflurane differ in their ability to alter peripheral sympathetic responses.

To demonstrate that esmolol, sodium nitroprusside, and isoflurane differ in their abilities to alter adrenal medullary blood flow and other peripheral sympathetic responses to hypotension, 16 mongrel dogs anesthetized with pentobarbital were allocated randomly to one of four test groups and given two hypotensive stimuli, separated by 1 h, to a mean arterial blood pressure of 60 mm Hg for 10 min. The first stimulus, induced by blood loss into a pressurized bottle system, constituted the control for each animal. The second hypotensive stimulus was created by either repeat blood loss (Group 1), esmolol infusion (Group 2), sodium nitroprusside infusion (Group 3), or isoflurane administration (Group 4). Before and 10 min into hypotension, the variables of abdominal organ blood flow, adrenal medullary blood flow, arterial norepinephrine and epinephrine concentrations were measured. In the control animals (Group 1), comparable decreases in abdominal organ blood flow and similar increases in adrenal medullary blood flow, norepinephrine, and epinephrine were elicited by the first and second hypotensive stimulus. Esmolol-induced hypotension (Group 2) abolished the increase in adrenal medullary blood flow and attenuated the increase in epinephrine by 65% (P < 0.03). The decrease in abdominal organ blood flow and the increase in norepinephrine were similar to that observed during baseline hemorrhagic hypotension. In contrast, sodium nitroprusside-induced hypotension (Group 3) abolished abdominal organ vasoconstriction whereas the increases in adrenal medullary blood flow, norepinephrine, and epinephrine were comparable to baseline hemorrhagic hypotension. In fact, abdominal organ blood flow increased 2.5-fold (P < 0.001) during hypotension with SNP. Isoflurane 2%, 1.54 minimum alveolar anesthesia concentration (Group 4), abolished the increases in adrenal medullary blood flow, norepinephrine, and epinephrine observed during baseline hemorrhagic hypotension and attenuated the decrease in abdominal organ blood flow by 70% (P < 0.001). These data demonstrate that esmolol, sodium nitroprusside, and isoflurane differ radically in their ability to alter or blunt peripheral sympathetic responses to hypotension, and suggest that isoflurane is the drug most effective in blunting multiple responses of the peripheral sympathetic system.

Adrenergic beta-Antagonists↗
PubMed1989

Modulation of cerebrospinal metabolic responses to peripheral stimulation by enflurane anesthesia in rats.

Enflurane-induced modulation of cerebrospinal metabolic responses to peripheral nerve stimulation was examined in 30 rats. Local glucose utilization in the brain and lumbar spinal cord was measured using the autoradiographic 2-[C]deoxyglucose method at three anesthetic concentrations (0,5, 2, and 4%) either with or without electrical stimulation (5 mA, 0.5 ms, 10 Hz) of the unilateral sciatic nerve. Stimulation produced a 71 to 111% increase in glucose utilization in the ipsilateral dorsal horn of the spinal cord at all anesthetic concentrations examined. Stimulation also produced a 32 to 48% increase in glucose utilization in the hindlimb projectionarea of the contralateral somatosensory cortex at the two lowest concentrations (0.5 and 2%), while at 4% no stimulus-induced increase in glucose utilization was observed. The results show that there is a threshold at which enflurane suppresses the metabolic responses to peripheral stimulation in the somatosensory cortex but not in the spinal cord. If electrical stimulation of a peripheral nerve is regarded as analogous to surgical stimulation, considerable increase in the spinal cord metabolism may occur during surgery even in a deeply anesthetized subject.

Journal Article↗
PubMed1999

The extent of traumatic damage determines a graded depression of the endotoxin responsiveness of peripheral blood mononuclear cells from patients with blunt injuries.

OBJECTIVE: To study whether the endotoxin responsiveness of peripheral blood mononuclear cells correlates with the severity of injury in trauma patients. DESIGN: Prospective, observational study. SETTING: University trauma center. PATIENTS: Fifty-nine patients with blunt trauma (Injury Severity Score [ISS] 4 to 57 points). INTERVENTIONS: Standard emergency department care, surgical care, and postoperative intensive care unit treatment. MEASUREMENTS AND MAIN RESULTS: Whole blood and serum were obtained 94+/-89 (SD) mins post trauma (day 0) and during a 14-day period postinjury. Endotoxin-induced tumor necrosis factor-alpha (TNF-alpha) synthesis of peripheral blood mononuclear cells ex vivo was tested using a whole blood assay. Serum samples were assayed for TNF-alpha concentrations. A reduced capacity of whole blood to produce TNF-alpha ex vivo with endotoxin treatment was found to be closely correlated with the ISS. The capacity to produce TNF-alpha on endotoxin stimulation of whole blood from patients with an ISS > or =16 points was depressed immediately after trauma and did not reach normal values during the observation period. In patients with an ISS >22 points, maximum depression of the capacity of whole blood to produce TNF-alpha occurs within 100 mins post injury. In contrast, in patients with an ISS <22 points, maximal depression of whole blood TNF-alpha production occurs with a delay of 24 to 48 hrs after trauma. Based on pre- and postoperative values, primary surgical intervention caused a decrease of the endotoxin-stimulated TNF-alpha production of whole blood in the latter patient subgroup, as well as in the entire patient population (ISS 4 to 57) when secondary surgical treatment was necessary 5 to 13 days after trauma. CONCLUSIONS: The extent of traumatic tissue damage leads to a graded depression of immunocyte function and appears to be amplified by surgical treatment. The endotoxin responsiveness of peripheral blood mononuclear cells displays a functional marker of the anatomically defined severity of injury and gives insights into the regulation of immunocyte function after severe blunt trauma.

Adult↗