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Biomedical subjects

I Couret

Publications and source records attributed to I Couret.

15 recordsLinked to original sources
PubMed1999

Basophil releasability in young highly trained and older athletes.

PURPOSE: Exercise-induced hypoxemia in highly trained athletes is associated with an increase in histamine release during exercise. The cells most implicated in blood histamine release are basophils. The aim of this study was to determine whether high-level endurance training induces modifications in histamine releasability from human basophils. METHODS: Seven young highly trained athletes (YA) [aged 26.1+/-1.3 yr (mean +/- SEM)] and seven master athletes (MA) (64.4+/-4.1 yr), all known to develop exercise-induced hypoxemia, were respectively compared with seven young untrained men (YC) (23.0+/-1.5 yr) and seven older untrained men (OC) (61.6+/-1.3 yr). During an incremental exhaustive exercise, blood samples for measurement of anti-IgE-induced histamine release from leukocytes were drawn at rest, VO2max, and recovery. RESULTS: Basophils from "leukocyte-rich" supernatant in YA and MA showed significantly higher histamine release induced by anti-IgE (1 microg x mL(-1) than, respectively, YC (P<0.01) and OC (P<0.05) at rest, VO2ax (P<0.01), and recovery (P<0.01). Basophils in YA and MA also showed a histamine release induced by anti-IgE that was higher at VO2max than at rest (respectively. P<0.01 and P<0.05), but this change was not found in the control groups. CONCLUSION: In conclusion, the basophils in highly trained endurance athletes, both young and older, showed higher anti-IgE-induced histamine release than those of untrained men. This effect of high-level training seemed to be potentiated by exercise.

Adult↗
PubMed1998

Interleukin-4 and interleukin-10 are chondroprotective and decrease mononuclear cell recruitment in human rheumatoid synovium in vivo.

We used the severe combined immunodeficient (SCID) mouse model to assess the effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human rheumatoid synovium and cartilage from five rheumatoid arthritis patients, obtained after joint replacement surgery, were engrafted subcutaneously to 6-8-week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL-4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor-alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4 weeks. The graft was removed and immunochemical analysis was carried out to assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation was assessed through the quantification of the erosion surface on a computerized image of the engrafted cartilage at high power view. MNC recruitment in the synovial tissue was determined by labelling blood MNC with indium-111 before their intraperitoneal injection. The activity obtained in the region of the graft were determined with a gamma camera 72 hr postinjection. The results are expressed as a percentage of initial injected activity. After 4 weeks we observed a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5% respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P < 0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10, or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These results suggest that IL-10 and IL-4 could have chondroprotective properties, and that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue efficiently.

Animals↗
PubMed1996

In vivo migration of tonsil lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: involvement of LFA-1.

Integrin-adressin binding is a critical step in lymphocte attachment to target tissues. The mucosal recognition systems (alpha E beta 7, alpha 4 beta 7, MADcam-1) have been implicated in the autoimmune process in rheumatoid arthritis. We developed a model for in vivo study of radio-labelled lymphocyte circulation and their attachment to human rheumatoid synovium. We studied the homing of tonsil lymphocytes, considered as mucosal lymphocytes, and the involvement of alpha E beta 7 integrin and LFA1 in the homing of tonsil lymphocytes. We engrafted human rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks later, we injected intraperitoneally 20 IO6 human peripheral blood or tonsil mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total body scintigram was obtained 20 h postinjection. The same protocol was performed after treatment of the MNC and mAb against LFA-1 (CD11a) or alpha E beta 7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731 +/- 8297cpm/200 pixel) versus 5982 +/- 4713cpm/200 pixel, p < 0.05). A monoclonal antibody against LFA 1 decreased the activity in the graft (4152 +/- 1287 cpm/200 pixel), p < 0.05. No significant difference in tonsil MNC attachment to rheumatoid synovial tissue was observed with a mAb against alpha E beta 7 (8057 +/- 5009 cpm/200 pixel). Our results showed an increase in radiolabelled mucosal MNC migration in synovial tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest that LFA-1 but not the alpha E beta 7 integrin is involved in tonsil MNC binding to synovial tissue in RA.

Animals↗
PubMed1996

In vivo migration of radiolabelled lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: implication of beta 2 and beta 7-integrin.

OBJECTIVE: Integrin-adressin binding is a critical step in lymphocyte attachment to target tissues. The lymphocyte function associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway has been shown to be involved in the homing of lymphocytes to arthritic joints in animal models. The mucosal recognition system [alpha E beta 7/E-cadherin, alpha 4 beta 7/mucosal vascular adressin cellular adhesion molecule 1 (MADCAM-1)] has been implicated in the autoimmune process of nonobese diabetic mice and in rheumatoid arthritis (RA). We developed a model for in vivo study of radiolabelled lymphocyte circulation and attachment to human engrafted rheumatoid synovium, and studied the involvement of LFA-1 and alpha E beta 7 integrin. METHODS: We engrafted human RA or osteoarthritis (OA) synovium subcutaneously in 6-week-old SCID/CB17 mice. Three weeks later, we injected intraperitoneally 20 x 10(6) human peripheral blood lymphocytes (PBL) labelled with 3 mCi 99mtechnetium hexamethyl propylenamine oxime. A mouse total body scintigraphy was obtained 20 h postinjection. The same protocol was performed after pretreatment of the PBL with monoclonal antibodies (Mab) against CD11a (25-3) or against alpha E beta 7 human mucosyl lymphocyte marker 1. RESULTS: PBL migrated in the rheumatoid synovial graft 20 h postinjection (activity in the region of interest of the graft: 7699 +/- 4383 cpm/200 pixel or 4.43 +/- 2.65% of initial activity) versus OA engrafted synovial tissue (1453 +/- 1137 or 0.74 +/- 0.6% of initial activity), p = 0.007. The homing to the engrafted rheumatoid synovial tissue of PBL from healthy subjects was not significantly different from the migration of PBL from patients with RA. A Mab against alpha E beta 7 significantly decreased lymphocyte attachment to rheumatoid synovial tissue (3094 +/- 3808 cpm/200 pixel or 2.65 +/- 2.4% of injected activity), p < 0.03. The same results were obtained with Mab against CD11a (5007 +/- 4190 cpm/200 pixel or 2.27 +/- 1.2%), p < 0.01. Our results show increased blood lymphocytes homing to rheumatoid synovial tissue engrafted in SCID mice versus OA tissue. CONCLUSION: The data suggest that both LFA-1 and mucosal recognition integrin alpha E beta 7 are involved in lymphocyte binding to target tissues in RA.

Animals↗
PubMed1996

Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor-alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM-1).

The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.

Animals↗
PubMed1995

The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes with single-photon emission tomography imaging in the detection and follow-up of recurrence of infective endocarditis complicating transvenous endocardial pacemaker.

In this case report we present a patient with a recurrence of subacute bacterial infectious endocarditis (IE) complicating a transvenous endocardial pacemaker. Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled granulocytes were used for diagnosis and follow-up under medical treatment only, since surgical removal of the pacemaker lead was ruled out because of the general condition of the patient. Single-photon emission tomography (SPET) imaging displayed the active lesion previously suspected on echography. At the end of antibiotic therapy, SPET indicated a favourable disease outcome whereas echocardiographic abnormalities remained nearly unchanged. The medical treatment had eradicated the IE, and the patient did well for more than 1 year thereafter.

Aged↗
PubMed1995

Radiolabelled lymphocyte migration in rheumatoid synovitis.

OBJECTIVES: To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS: After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection. RESULTS: An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours. CONCLUSIONS: The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis.

Aged↗
PubMed1994

Histamine and exercise-induced hypoxemia in highly trained athletes.

To determine whether exercise-induced hypoxemia in extreme athletes results from an increase in histamine level during maximal incremental exercise, seven young athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2 +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were compared with age-matched control groups (young controls and older controls, respectively). During maximal incremental exercise, blood samples for arterial blood gas analysis and for plasma and total histamine were drawn at rest and at 50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H) was calculated from plasma and total histamine samples. In all athletes (MA and YA groups), exercise induced an increase in %H with a concomitant decrease in arterial PO2 (PaO2); in control groups there was no change in either histamine levels or PaO2. When the data for the YA and MA groups were combined, a correlation was observed between the increase in %H and the drop in PaO2. Nevertheless, further studies are required to establish whether histamine plays a causative role in hypoxemia or is a response to injury.

Adult↗
PubMed1993

Functional characteristics of bronchial epithelium obtained by brushing from asthmatic and normal subjects.

Airways epithelial cells may be involved in the pathogenesis of asthma, but their role remains to be determined. Epithelial cells can release large amounts of 15-hydroxy-eicosatetranoic acid (15-HETE) and smaller amounts of prostaglandin E2 (PGE2) as well as fibronectin, a mediator involved in epithelial repair after injury. Epithelial cells obtained after bronchial brushing of 16 asthmatic (age 38 +/- 5 yr) and 11 normal subjects (age 36 +/- 5 yr) were studied. The percentage of epithelial cells was assessed by immunocytochemistry using an anti-cytokeratin antibody. The viability of the cells was assessed by trypan blue exclusion. The release of 15-HETE PGE2 and fibronectin was studied in resting cells and after A23187 calcium ionophore stimulation. Epithelial cells always comprised more than 86% of cells recovered, and the viability of epithelial cells was significantly (p < 0.001, Mann-Whitney U test) greater in normal subjects (54 +/- 5%) compared with asthmatic subjects (13 +/- 1%). The release of 15-HETE and fibronectin by resting epithelial cells was significantly greater in asthmatics (p < 0.05, Mann-Whitney U test) than in normal subjects. A23187 significantly (p < 0.05, Wilcoxon W test) increased the release of 15-HETE and fibronectin. There was no significant difference in the release of PGE2 by resting cells from either asthmatics or normal subjects, but challenge with A23187 induced a significant (p < 0.03, Wilcoxon W test) increase in PGE2 from cells of asthmatics but not from cells of normal subjects. This study shows that epithelial cells are activated and less viable in asthma and suggests a role for these cells in asthma.

Adult↗
PubMed1993

[Scintigraphy with radiolabeled granulocytes for the detection of peripheral septic osteoarticular sites].

Radiolabeled granulocyte scintigraphy is a recently introduced technique for detecting osteoarticular infections. Technetium-99m-labeled hexamethylpropylamineoxime (HMPAO), in use since 1986, provides excellent resolution with less radiation exposure than indium-111. Elimination of lymphocytes provides further improvements in image quality and safety, making the technique suitable for use in children. The authors prospectively studied 30 scintigraphies performed with isolated autologous 99mTc-HMPAO-labeled granulocytes to evaluate suspected osteoarticular infection. Image quality was outstanding. In peripheral sites, infection manifested as a focus of increased uptake visible in all three phases (30 min, 3 hours and 18 hours after the injection). Performance was excellent, with 11 true-positive scans, 14 true negative scans, 4 false-positive scans (including two ascribable to recent surgery), and one false-negative scan. Among the 28 evaluable cases, positive predictive value was 85%, negative predictive value was 90%, and sensitivity, specificity, and accuracy were 92%, 88%, and 89%, respectively. The only limitation to routine use of this technique is the need for in vitro granulocyte separation which is time-consuming and requires special precautions to preserve granulocyte function. Nevertheless, these data demonstrate that 99mTc-HMPAO-labeled granulocyte scintigraphy is of value for the detection of osteoarticular infections in patients without chronic inflammatory joint disease.

Acute Disease↗
PubMed1992

In vitro activation of bronchoalveolar lavage cells by house dust mite allergens.

Mast cells represent a small but important proportion of bronchoalveolar lavage cells and are directly exposed to environmental triggers including allergens. Histamine and PGD2 are mediators released during the activation of mast cells. Fourteen patients allergic to Dermatophagoides pteronyssinus were studied. After bronchoalveolar lavage the unfractionated cell pellet containing metachromatic cells was submitted to allergen challenge using three concentrations of a standardized Dermatophagoides pteronyssinus extract and one concentration of A23187 (2.5 microM). The release of histamine was measured by radioimmunoassay using a monoclonal antibody against acylated histamine and PGD2 was measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2. Histamine was released in 13/14 patients following stimulation of the cells with A23187 and 12/14 patients after stimulation with Dermatophagoides pteronyssinus extract. The release of histamine was 3.5-fold greater when cells were stimulated by the Dermatophagoides pteronyssinus extract than with A23187. PGD2 was released in 10/12 patients when cells were stimulated with A23187 and 6/14 patients in the case of Dermatophagoides pteronyssinus extract stimulation. In the latter case, the mean release was not significantly greater than baseline. For histamine, the maximum release usually occurred with the more concentrated extract whereas in the experiments where PGD2 was released, maximal generation usually occurred with the lowest concentration used. There was no correlation between the severity of asthma and the release of mediators. This study confirms the activation of metachromatic cells by allergen and shows some heterogeneity in the release of granule and membrane-derived mediators.

Adult↗
PubMed1991

Increased numbers of hypodense alveolar macrophages in patients with bronchial asthma.

Alveolar macrophages (AM) are among the cells involved in the bronchial inflammation of asthma. It has been shown that AM are a heterogeneous cell population in normal subjects. The heterogeneity of AM from 36 asthmatic patients and 23 normal subjects was studied using Percoll density fractionation. AM recovered from asthmatic patients are mainly in the lower density fractions (1.03 and 1.04 g/ml), whereas AM from normal subjects are in the higher density fractions (1.05 and 1.07 g/ml). Electron microscopic studies showed that low density AM of both asthmatic and normal subjects appear to have morphologic characteristics of activated cells by comparison with high density AM that present characteristics of quiescent cells in both asthmatic and normal subjects. The functional activity of AM fractions of asthmatic and control subjects was assessed using the release of the oxygen free radicals induced by opsonized zymosan and TxB2 generation by A23187. There was no difference between the five fractions of asthmatic or control subjects with regard to oxygen species release. The TxB2 generation was increased in the low density AM from asthmatics when compared with the same fractions of normal subjects. The hypodense cells produced less TxB2 than did cells of higher density in both asthmatic and normal subjects. The density of AM was correlated with the recent instability of the asthma but not with the severity of it. This study shows that AM from asthmatic subjects, when compared with those from control subjects, are heterogeneous, hypodense cells and that they predominate. Hypodense AM did not appear to be hyperresponsive in vitro and may have been already committed into the airways.

Adolescent↗
PubMed1990

Labeling of ethambutol with 99mTc using a new reduction procedure. Pharmacokinetic study in the mouse and rat.

Certain 99mTc-labeled derivatives of ethylene diamine substituted in NN', when labeled with 99mTc, have been proposed for studying renal excretion, and others for brain imaging. Ethambutol, a well known antituberculosis drug, possesses a structure very similar to these derivatives. We prepared a complex of [99mTc]ethambutol using hypophosphorus acid as the reducing agent. The complex was then analyzed by paper and cellulose F chromatography and by FAB mass spectrometry. A pharmacokinetic study in the mouse and rat indicated that the complex is eliminated by the kidney faster than DTPA, slower than [131I]hippuran and without significant renal retention. The [99mTc]ethambutol complex is easy to prepare and shows good stability in water at physiological pH, making it potentially useful in renal excretion studies.

Animals↗