Search PubMed⌕ Search

Biomedical subjects

J Duchateau

Publications and source records attributed to J Duchateau.

At least 55 records · Page 3Linked to original sources
PubMed1997

Dose-response relationship to inhaled endotoxin in normal subjects.

Exposure to endotoxin and to its purified derivative lipopolysaccharide (LPS) is related to several occupational pulmonary diseases and to severe domestic asthma. An inhalation of a given dose of pure LPS produces both a systemic and a bronchial inflammatory response. Information on the dose-response relationship to inhaled LPS in normal subjects is a prerequisite to define the safety threshold of exposure. In the present study, the clinical and inflammatory responses to rising doses of inhaled LPS was evaluated. Nine normal volunteers were challenged weekly by inhalation with saline, 0.5, 5, and 50 microg LPS (Escherichia coli). The response determinators are the clinical symptoms, fever, FEV1, blood polymorphonuclear neutrophils (PMNs) with their level of activation (measured by luminol enhanced-chemiluminescence), and both the blood and the urine concentrations of the C-reactive protein (CRP). To assess the bronchial inflammatory response, an induced sputum was obtained 6 h after each dose of LPS, and the total and differential cell counts as well as the MPO, ECP, and TNF-alpha concentrations were measured. Compared with the saline, an inhalation of 0.5 microg LPS induces a significant decrease in the PMN luminol-enhanced chemiluminescence (p < 0.01), which could reflect a process of margination and/or extravascular sequestration of activated PMN. Inhalation of 5 microg LPS is associated with a significant rise in blood CRP (p < 0.01) and PMNs (p < 0.001) and in sputum PMNs (p < 0.05), monocytes (p < 0.05), and MPO (p < 0.05). Inhalation of 50 microg LPS was characterized by a significant increase in temperature (p < 0.01), blood PMNs (p < 0.001), blood and urine CRP (p < 0.01 and < 0.01), and sputum PMNs (p < 0.001), monocytes (p < 0.05), lymphocytes (p < 0.05), MPO (p < 0.01), TNF-alpha (p < 0.01), and ECP (p < 0.01) while five subjects develop symptoms. In normal subjects, the response to inhaled LPS is dose-related, the most sensitive markers of LPS-induced inflammation being the blood PMNs count with their level of activation, the blood CRP concentration, and the sputum PMNs count. The no-response threshold to an acute inhalation of LPS is less than 0.5 microg.

Administration, Inhalation↗
PubMed1997

Mite allergy is associated with a specific profile of IgG epitopes recognized on antigen p1 of Dermatophagoides pteronyssinus.

BACKGROUND: Immune response to inhaled antigens differs in allergic patients and healthy individuals, mostly in the quality of T cell help provided (i.e. Th2 or Th1 dominant subset). However, while different in many functional aspects, both groups of T cells shared the capacity to support the synthesis of antigen-specific immunoglobulin G (IgG) antibodies detected in different amounts in the serum of atopic and healthy individuals. OBJECTIVE: The present study investigates whether these IgG responses display similar or different epitopic dominance in the mite sensitization model. METHODS: Antibody specificity was evaluated by comparing the IgG binding to native Der p1 (nDer p1) and its products of pepsin hydrolysis (dDer p1) in 56 mite-allergic patients and 148 healthy individuals, including 24 mite-sensitized individuals in a solid enzyme linked immunosorbent assay (ELISA). Antibody specificity was also studied in competitive ELISA using streptavidin biotin technology. RESULTS: Mite-allergic sera showed a higher degree of binding to nDer p1 than to dDer p1, whereas control sera and mite-sensitized sera bound at a similar level to the two forms of the antigen. Allergic sera and control sera, including mite-sensitized sera, showed distinct capacities to prevent the binding to nDer p1 of pooled IgG from each group as well as murine monoclonal antibodies specific to Der p1. CONCLUSION: The IgG response to Der p1 of mite-allergic patients differs from that of healthy controls and mite-sensitized subjects, not only in its increased titres but also in its consistant pattern of modified specificity, displaying a marked preference for conformational epitopes. Cross-competition experiments confirm the clinically associated, restricted specificity, allowing almost complete discrimination between groups, particularly between mite-sensitized and mite-allergic subjects, which is currently impossible with routinely available assays.

Adult↗
PubMed1996

Fine tuning of epitopic dominance induced by lung cancer on the IgG response to bovine betalactoglobulin: towards a paraneoplastic immune marker.

BACKGROUND: Investigating the humoral immune response to mucosal antigens in patients with lung cancer, we have documented a preferential immunoglobulin G (IgG) binding to cryptic epitopes unmasked by the proteolysis of bovine beta-lactoglobulin (BLG). In contrast, IgG from healthy controls and patients with chronic bronchitis (COPD) bind preferentially to continuous epitopes presented on both native (n) and denaturated (d) forms of this antigen. The present study further characterized the differences in the epitope profiles recognized on BLG. METHODS: The capacity of individual sera from 65 lung cancer patients, tested before and after cancer removal for the patients with early stage lung carcinoma, 65 healthy controls, and 52 patients with COPD, to prevent the binding of pooled IgG fractions from each population as well as murine monoclonal antibodies (MoAb), specific for BLG, to solid phase bound antigen was evaluated in enzyme-linked immunoadsorbent assay using streptavidin-biotin technology. Some of these experiments were also performed with sera from 42 patients diagnosed with other cancers. RESULTS: Compared with control sera and sera from patients with other solid tumors, lung cancer patient sera showed distinct capacities to prevent the binding of murine MoAb as well as human pooled IgG fractions to n- and d-BLG. The inhibition capacities of lung cancer sera changed as soon as five weeks after cancer removal. CONCLUSIONS: The results indicate that the difference in epitope specificity exhibited by lung cancer sera is not restricted to cryptic epitopes, but also affects continuous and discontinuous epitopes, accessible only on the native antigen. A high level of binding discrimination between antibodies from the study populations is also observed at the level of the epitope. This deviation in the epitope specificity of antibodies changes soon after cancer removal, suggesting a tumor-dependent disturbance. Also documented in the Dermatophagoides pteronyssinus model, it opens the way to a new class of paraneoplastic immune markers for this malignancy, with, at first glance, a high specificity level.

Adenocarcinoma↗
PubMed1996

Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children.

BACKGROUND: The serine protease inhibitor aprotinin inhibits trypsin, kallikrein, and plasmin and enhances the complement hemolytic activity of the first complement component C1. We tested whether low-dose aprotinin influences the inflammatory reaction related to cardiopulmonary bypass. METHODS: In an open, randomized study, 25 children undergoing cardiac operations were investigated prospectively. The treated group comprised 11 patients receiving low-dose aprotinin (20,000 kIU/kg [2.8 mg/kg]), and the control group included 14 patients. Complement activation, cytokine production, and leukocyte stimulation were analyzed before, during, and after cardiopulmonary bypass. RESULTS: In all children, significant C3 conversion and C5a generation, interleukin-6 synthesis, and myeloperoxidase, eosinophil cationic protein, and histamine liberation occurred in relation to cardiopulmonary bypass. This was not influenced by aprotinin treatment. In contrast, neutrophil kinetic studies at the end of cardiopulmonary bypass showed a significantly lower increase in the aprotinin as compared with the control group. CONCLUSIONS: Our results suggest that low-dose aprotinin has little influence on the inflammatory reaction induced by cardiopulmonary bypass. Aprotinin affects neutrophil mobilization but not white blood cell degranulation related to cardiopulmonary bypass, and has no influence on complement activation and interleukin-6 synthesis.

Analysis of Variance↗
PubMed1996

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.

Acute-Phase Reaction↗
PubMed1996

Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations.

To evaluate cytokine balance related to cardiopulmonary bypass, we prospectively investigated 11 infants undergoing cardiac operations for congenital heart disease. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and the antiinflammatory cytokine interleukin-10 were measured at multiple time points before, during, and after bypass. Tumor necrosis factor-alpha and interleukin-8 values were within normal range before the operation. These values increased significantly during bypass, reaching their peaks after protamine administration (tumor necrosis factor-alpha, 133.6 +/- 124.9 pg/ml; mean +/- standard deviation; p<0.005) and 2 hours after termination of the procedure (interleukin-8, 92.1 +/- 44.1 pg/ml; p < 0.01). Tumor necrosis factor-alpha and interleukin-8 equaled normal prebypass values from the first postoperative day on. Interleukin-10 levels were within normal range before the operation and were already significantly increased 10 minutes after initiation of bypass (interleukin 10, 39.4 +/- 34.3 pg/ml; p<0.05). These levels remained elevated throughout the procedure but returned to normal after protamine administration. A second significant release of interleukin-10 occurred from the early postoperative period on, reaching its peak 24 hours after termination of cardiopulmonary bypass (interleukin-10, 351.6 +/- 304.0 pg/ml; p < 0.01). Interleukin-10 values were normal on the second postoperative day in all patients. Interleukin-10 kinetics showed an inverse pattern compared with tumor necrosis factor-alpha and interleukin-8. This difference suggests an interplay between proinflammatory and antiinflammatory cytokines released during and after cardiopulmonary bypass. Interleukin-10 levels measured 4 and 24 hours after bypass strongly correlated with the degree of hypothermia during bypass (Spearman's correlation coefficient, -0.77 [p < 0.01] and -0.89 [p < 0.0005], respectively); these levels did not correlate with duration of bypass and aortic crossclamping, however. This result suggests that besides immunologically mediated production of interleukin-10, hypothermia itself could modulate interleukin-10 production. In conclusion, this study demonstrates interleukin-10 production, in addition to interleukin-8 and tumor necrosis factor-alpha synthesis, in response to cardiopulmonary bypass in infants. Interleukin-10 could play a protective role by down-regulating proinflammatory cytokine release during and after cardiopulmonary bypass.

Anesthesia, General↗
PubMed1996

Effect of sodium nitroprusside on complement activation induced by cardiopulmonary bypass: a clinical and experimental study.

Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside--a nitrovasodilator releasing nitric oxide--for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p <0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p <0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 +/- 0.8 mmol/L and 14.0 +/- 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 o 0.3 mmol/L for the classic pathway. the zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release.

Cardiopulmonary Bypass↗
PubMed1996

Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias.

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.

Adolescent↗
PubMed1996

Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men.

BACKGROUND: Interleukin (IL)-10 is a potent antiinflammatory cytokine inhibiting the release of tumor necrosis factor--alpha (TNF-alpha) and IL-8 by activated macrophages and polymorphonuclear leukocytes. Cardiopulmonary bypass (CPB) represents a unique situation where an inflammatory reaction is predictably induced. The present study examined the influence of CPB on the release of TNF-alpha, IL-1 beta, IL-8, and IL-10 and also defined the effects of pretreatment with corticosteroids on the release of these cytokines. METHODS: The study included 22 patients undergoing coronary artery bypass graft operations, including eight control patients and seven patients who received dexamethasone, and seven patients who received methylprednisolone 4 hours before the operation. Cytokines were measured with the enzyme-linked immunosorbent assay technique before treatment, before anesthesia induction, immediately before heparin administration, before aorta declamping, 10 minutes and 90 minutes after aorta declamping, and 4 hours after the end of CPB. RESULTS: In the control patients the TNF-alpha levels and especially the IL-8 levels increased during CPB and reached their maximal levels 4 hours after CPB. IL-10 levels rose moderately and transiently, reaching peak values 90 minutes after aorta declamping. Notably, administration of corticosteroids prevented IL-8 release but increased IL-10 levels, which were tenfold higher than in the control group 90 minutes after aorta declamping (dexamethasone, 271 +/- 128 pg/ml; methylprednisolone, 312 +/- 213 pg/ml; control, 17 +/- 12 pg/ml, p < 0.05). IL-1 beta was not detected in any group of patients. CONCLUSIONS: The present data indicate that IL-10 is released together with proinflammatory cytokines during and after CPB and that pretreatment with corticosteroids markedly enhances this release. The release of IL-10 may play an important role in the antiinflammatory effects of corticosteroids.

Aged↗
PubMed1996

Improvement of quality of life by treatment with cetirizine in patients with perennial allergic rhinitis as determined by a French version of the SF-36 questionnaire.

BACKGROUND AND AIM: Perennial allergic rhinitis impairs social life, but it is not known whether quality of life may be improved when patients are treated with an H1-blocker. A randomized, double-blind, placebo-controlled study was carried out with cetirizine to assess the effect of this drug on quality of life. METHODS: Two hundred seventy-four patients with perennial allergic rhinitis were tested. Quality of life was measured by using the Medical Outcome Study Short-Form Health Survey (SF-36) questionnaire. After a 2-week run-in period, cetirizine, 10 mg once daily, (136 patients) or placebo (138 patients) was given for the next 6 weeks. The SF-36 questionnaire was administered after the run-in period (at the start of treatment) and after 1 and 6 weeks of treatment. Symptom-medication scores were measured daily during the study. RESULTS: After the run-in period (baseline), there were no significant differences between the cetirizine and placebo groups in terms of symptoms or quality-of-life scores. After 6 weeks of treatment, percentage of days without rhinitis or with only mild rhinitis symptoms was significantly greater in the cetirizine group in comparison with the placebo group (p < 0.0001, Mann-Whitney U test). All of the nine quality-of-life dimensions were significantly improved (from p = 0.01 to p < 0.0001, Mann-Whitney U test) after 1 and 6 weeks of cetirizine treatment compared with placebo. There was no improvement in the placebo group. CONCLUSIONS: This study is the first to demonstrate that an H1-blocker, cetirizine, can improve quality of life for patients with perennial allergic rhinitis.

Adolescent↗
PubMed1996

Significance of very low retinol levels during severe protein-energy malnutrition.

In developing countries, severe vitamin A deficiency is associated with increased child mortality. In Kivu, Zaïre, child mortality rate is approximately 50 per 1000 per year and protein calorie malnutrition is endemic. To evaluate vitamin A status in this population, we measured plasma retinol levels in 28 severely malnourished hospitalized children (plasma albumin level below 3 g/dl), and in 153 outpatients (mean plasma albumin level: 3.19 +/- 0.7 g/dl) as controls. Sixty percent of inpatients and 37 percent of out-patients had retinol levels below 10 micrograms/dl (P = 0.02) suggesting a high prevalence of severe vitamin A deficiency in this population. We found that plasma retinol levels were correlated with low retinol binding protein plasma levels (r = 0.77). We conclude that although vitamin A deficiency probably exists in this malnourished population, low retinol levels could at least partly be related to decreased levels of its carrier protein.

Biomarkers↗
PubMed1996

Severity of asthma is related to endotoxin in house dust.

In sensitized subjects, exposure to the mite allergen appears to be only one of several factors leading to asthma. We hypothesized that in association with allergen exposure, endotoxin, a proinflammatory agent present in house dust (HD), influences the severity of asthma. Using a cross-sectional study design, we investigated a group of 69 consecutive dust mite (HDM)-sensitized subjects defined as having rhinitis (n = 20) or asthma (n = 49); the latter were evaluated functionally and clinically by three different scores and by their need for daily medication. Concentrations of Dermatophagoides pteronyssinus p I allergen (Der p I) (by two-site monoclonal antibody enzyme-linked immunosorbent assay [ELISA]), guanine (by high-pressure liquid chromatography [HPLC]), and endotoxin (by modified Limulus. amebocyte lysate assay) were measured in HD collected in duplicate from the mattresses and floors in each subject's home. The concentrations of Der p I and of guanine in HD collected from mattresses were significantly higher in asthmatic subjects than in those with rhinitis (p < 0.05 and < 0.04, respectively). In subjects (n = 37) exposed to a high level of HDM allergen (i.e., Der p I > or = 10 micrograms/g HD and/or guanine > or = 0.10 mg/100 mg HD), the severity of asthma was unrelated to mite allergen concentration in HD. On the contrary, the severity of asthma was related to concomitant exposure to endotoxin in HD, since the concentration of HD endotoxin was significantly and inversely correlated with FEV1 (p < 0.05), FEV1/FVC (p < 0.02), daily need for oral (p < 0.01) and inhaled (p < 0.01) corticosteroids, daily need for beta 2 agonists (p < 0.001) and xanthines (p < 0.01), and clinical scores such as the modified Aas score (p < 0.01). In HDM-sensitized subjects exposed to a high level of allergen, the concentration of endotoxin measured in HD is an important determinant of asthma severity.

Adult↗
PubMed1996

[Post-gastroplasty plastic surgery].

Gastric volume modification by surgery (gastroplasty, gastric banding ...) is intended to improve health in patients presenting morbid obesity. However, consecutive cutaneous sequellae are always ungrateful and often particularly disabling. The treatment of these sequellae often necessitates plastic surgery correction. We present a series of 21 patients whose cutaneous sequellae secondary to gastroplasty were operated on after a mean loss of 42% of body mass index. Sixty-three anatomical sites were treated in 27 operative sessions without any general complication. The number of operative sessions was limited using a simultaneous multiple surgical team approach, which is particularly adapted to this type of patients. The local complications (11 cases) were minor (delays of healing, hematoma, seroma, abscess). Even though the final aesthetic appearance depended greatly on the preoperative situation, all the patients were satisfied with the results obtained.

Abdomen↗
PubMed1995

Lung cancer-related changing profile of B-cell epitopes recognized on mucosal antigens: the Der p1 model.

BACKGROUND: The natural immunoglobulin G (IgG) response towards antigens presented at the mucosal level in patients with lung cancer, the most frequent mucosal malignancy in humans was studied. Compared with healthy control subjects, patients with lung cancer display lower IgG antibody titers toward antigen p1 of the house dust mite, Dermatophagoides pteronyssinus (Der p1), chronically presented to the respiratory mucosa. The present study further characterizes this defect in terms of antibody specificity. METHODS: Antibody specificity was studied by comparing the IgG binding to native Der p1 (nDer p1) and its products of pepsin hydrolysis (dDer p1) in a solid phase enzyme-linked immunosorbent assay (ELISA) in 148 patients with lung carcinoma, 148 healthy control subjects, and 50 patients with chronic bronchitis. Antibody specificity was also evaluated before and after (5 +/- 1 weeks) surgical excision of the tumor in competition ELISA using streptavidin-biotin technology. RESULTS: Lung cancer sera had a higher degree of binding to dDer p1 compared with nDer p1, whereas control group sera bound similarly to the two forms of the antigen. Lung cancer sera and control group sera showed distinct capacities to prevent the binding of pooled IgG from each group to nDer p1. The inhibition capacity displayed by cancer sera is changed 5 weeks after cancer removal. CONCLUSION: These results, somewhat similar to those observed for bovine betalactoglobulin, document the recognition of a different set of epitopes on Der p1 and more generally on mucosal antigens by lung cancer IgG compared with the IgG from control patients. This distinct profile of epitope specificity changes partially soon after cancer removal, suggesting a tumor-dependent disturbance and opens the way to a new class of markers in lung cancer. Furthermore, this study documents a surprising but striking influence of the clinical status on the choice of B-cell immunodominant epitopes in mucosal responses.

Adult↗
PubMed1995

Blood inflammatory response to inhaled endotoxin in normal subjects.

Previously we have reported that in asthmatics an inhalation of 20 micrograms lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non-atopic subjects were challenged by inhalation of a solution containing 20 micrograms LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by the changes in forced expiratory volume in one second (FEV1), in specific conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced-chemiluminescence (luminol-CL, as a marker of the PMN degree of activation), C-reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis factor-alpha (TNF-alpha) and adrenocorticotropic hormone (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge associated with an increase in the level of luminol-CL (P < 0.001). This rise in luminol-CL level was significant at 120 min (P < 0.05) before any change in the PMN count. After 24 and 48 h the acute-phase protein CRP raised significantly (P < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the TNF alpha detectable level was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Bed rest induces neural and contractile adaptations in triceps surae.

The electromechanical adaptations of the triceps surae muscle were examined in one subject confined to bed for 5 wk due to strong orthostatic headaches. The torque produced by the triceps surae and the electromyographic (EMG) activities of the slow soleus (Sol) and fast lateral gastrocnemius (LG) were studied in response to voluntary and electrically induced contractions. Bed rest caused a 46% decrease in the maximal voluntary contraction (MVC) torque. This loss of strength was associated with a deficit of 33% in central activation and 19% in the estimated muscle force-generating capacity. The EMG activity during MVC was found to be reduced in both muscles, but to a greater extent in the LG (-51%) than in the Sol (-32%). The decrease in amplitude of the maximal M wave (Mmax) recorded in response to supramaximal electrical stimulation was greater in Sol (-28%) than in LG (-12%). After bed rest, the twitch time to peak torque was slightly prolonged (+9%) and the maximal rate of tension development (dT/dt) was reduced by 31% in electrically induced and 24% in voluntary contractions. Although muscle fatigability during a 60-s sustained MVC was not affected by the bed rest period, the relative contributions of the two muscles differed from control. These results indicate that muscular adaptations were more prominent in Sol while neural adaptations were more significant in LG. Furthermore, the neural changes almost completely recovered within 2 wk, whereas the contractile alterations required at least 5 times longer to return to the control values.

Action Potentials↗
PubMed1994

Are similar inflammatory factors involved in strenuous exercise and sepsis?

An increasing body of data suggest that strenuous exercise triggers an inflammatory response having some similarity with those occurring in sepsis. Indices of this inflammatory response to exercise (IRE) especially include leukocytosis, release of inflammatory mediators and acute phase reactants, tissue damage, priming of various white blood cell lines, production of free radicals; activation of complement, coagulation and fibrinolytic cascades. Inflammatory responses to strenuous exercise and sepsis could in part be due to the release of endotoxin in blood as common triggering factor, but it seems that tissue damage and/or contact system activation are more important triggering mechanisms in exercising subjects. While the magnitude and duration of cellular and humoral changes associated with IRE are quite different from those observed in sepsis, recent human studies suggested that chronic and/or excessive IRE could have adverse effects. Among the possible consequences of acute and chronic IRE are delayed onset muscular soreness and loss of force, cardiovascular complications, intravascular hemolysis, hypoferraemia and increased susceptibility to infection.

Blood Coagulation↗