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Biomedical subjects

B Roussel

Publications and source records attributed to B Roussel.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Analysis of dot-blot technique for the detection of three autoantibodies (anti-Jo-1, anti-M2, anti-ribosome). Comparison with reference techniques].

A recently commercialized dot-blot (Cyto-Dot, BMD) offered a new method for the detection of three autoantibodies (Ab) anti-Jo-1, anti-M2, and anti-ribosomal protein although their only common point is the cytoplasmic localisation of their respective antigen. These Ab are detected by indirect immunofluorescence (IF) (anti-M2, anti-ribosomal protein), double immunodiffusion (ID) (anti-Jo-1) and western blotting (WB) (anti-M2). The aim of the study was to compare results obtained by the Cyto-Dot with those obtained by our reference technique. One hundred and seventy-seven sera were analysed, divided into four groups: group I (n = 15) with anti-Jo-1 Ab detected by ID, group II (n = 70) with anti-M2 Ab by WB, group III (n = 33) with anti-ribosomal protein Ab by IF (of which, 19 are precipitating by ID), group IV (control group, n = 59) with 31 sera of healthy individuals, six sera of patients with liver diseases resembling primary biliary cirrhosis and 22 with a particular serological profile. Cyto-Dot is very sensitive and specific for the detection of anti-Jo-1 Ab. Also, it represents a reliable method (sensitivity 0.99) for the screening of anti-M2 Ab and for the confirmation of an atypic immunofluorescence pattern. Equivalent to ID for the detection of anti-ribosomal protein Ab, the Cyto-Dot represents a good alternative technique. However, although this new diagnostic method represents a sensitive technique for the detection of the three auto-Ab, unfortunately, it can not be applied for large series.

Autoantibodies↗
PubMed1994

Effects of modafinil-induced wakefulness on glutamine synthetase regulation in the rat brain.

Changes in the level of glutamine synthetase (GS), an enzyme chiefly found in glial cells, were investigated in the brains of rats treated with modafinil, an awakening drug interfering with central catecholamine function. Two hours (waking period) and 7 h (recovery period) after intra-peritoneal injection of 128 mg/kg modafinil, a significant increase in the level of GS protein was observed by immunotitration in both the locus coeruleus (+30%) and in the frontoparietal cortex (+50%). No changes were observed with 64 mg/kg of modafinil. GS mRNA was quantified in the entire cortex by Northern blot hybridization using an oligonucleotidic GS cDNA probe. A significant increase in the GS-mRNA level (+70%) was observed in the CX of rats 2 h after injection of 128 mg/kg modafinil; the level tended to return to control values 7 h later during the recovery period. The level of glial acid fibrillary protein (GFAP), an astroglial marker, was unchanged after modafinil treatment. These changes in GS levels after modafinil treatment are discussed in terms of neuron-glia interactions in the regulation of brain metabolism during pharmacologically induced wakefulness, excluding possible stress effects.

Animals↗
PubMed1994

Thermal diffusion probe and instrument system for tissue blood flow measurements: validation in phantoms and in vivo organs.

A minimally invasive probe and instrument system for real-time measurements of temperature, thermal conductivity and tissue blood flow has been designed for research and clinical use. The essence of the probe is a thermistor, located at the tip of catheters or glass and steel needles, and operating in transient self-heated mode at constant temperature increment. Thermal conductivity and tissue blood flow are determined by use of a coupled tissue-probe thermal model. The effects of temporal baseline temperature shifts are minimized by a novel, automatic, analog compensation circuit. Very short heating periods (3 s) and cooling periods (12 s) provided near-continuous measurements (4/min). Calibration experiments performed in media of known thermal conductivity exhibit a linear response with respect to thermal conductivity. In vitro experiments performed in isolated perfused dog liver preparations are presented to evaluate this instrument system. In vivo experiments performed in cat brain, dog liver, and human tumor demonstrate the ability of this instrument system to perform physiologically valid measurements (comparison inter-subjects and intra-subjects). The minimally invasive probes (0.8 mm OD) are capable of long term measurements (several months), with minimal tissue reactions (0.3 mm around the probe).

Animals↗
PubMed1994

IgG2 subclass restriction of anti-beta 2 glycoprotein 1 antibodies in autoimmune patients.

The IgG subclass and light chain distribution of antiphospholipid antibodies (aPL) occurring in autoimmune patients were determined by means of two radioimmunoassays using either cardiolipin- or beta 2 glycoprotein 1 (beta 2GP1)-coated microtitre plates and mouse MoAbs. Of 50 sera selected for positivity of anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-beta 2GP1 antibodies and their presence was closely associated with clinical features of the antiphospholipid syndrome. Good correlations were found between ACA and anti-beta 2GP1 antibodies when considering antibody level and patterns of light chain and IgG subclass, suggesting that, overall, the same antibodies were being measured. Light chain analysis showed the polyclonal origin of these antibodies and, in most sera, a trend towards use of lambda chain. Among sera positive for anti-beta 2GP1 antibodies, IgG2 was the major subclass reactive with beta 2GP1 and cardiolipin (87% and 74% of the IgG antibody activity, respectively). In contrast, in the group of 18 sera lacking anti-beta 2GP1 antibodies, ACA were largely restricted to IgG3, with a lesser contribution by IgG1. A few selected sera from the anti-beta 2GP1-positive group were shown to contain mixtures of antibodies that required beta 2GP1 (restricted to IgG2 present in large amounts) and did not require this cofactor (restricted to IgG3 and/or IgG1 present in low amounts) for their reactivity with cardiolipin. There was no contribution of glycosylation to the epitopes recognized by anti-beta 2GP1 antibodies, even though human anti-carbohydrate antibodies are restricted to the IgG2 subclass. These findings further emphasize the intra- and interindividual heterogeneity of aPL, and should help to discriminate clinically relevant specificies.

Adolescent↗
PubMed1994

Four cases of spuriously low WBC count due to in vitro leukocyte agglutination: contribution of the hematology analyzer Coulter STKS in detecting this clinically misleading artefact.

Four spuriously lowered WBC counts due to in vitro leukoagglutination were reported from an automated cell counter (Coulter STKS). Leukocyte aggregates (3 to 50 cells), detected in the peripheral blood smears, included different cell types, normal (neutrophils, eosinophils, monocytes, lymphocytes) or abnormal (lymphoma cells). The phenomenon was associated with either a spurious leukoneutropenia or an underestimation of hyperleucocytosis. Leukoagglutination was extensively investigated in 3 cases : as shown in several reports, leukoagglutination may occur with various features, especially due to temperature and anticoagulant dependence. Our four cases reflected this variability. Furthermore, one case was found both temperature-dependent and anticoagulant-independent, a pattern not yet described in the literature. A common STKS graphic pattern was found in our 4 cases, suggesting that hematology analyzers such as Coulter STKS may be useful to detect leukoagglutination. In conclusion, each leukoneutropenia and/or each suggestive graphic pattern must be controlled by means of a blood smear examination in order to rule out the possibility of in vitro leukoagglutination.

Aged↗
PubMed1994

[Antiphospholipid and anti beta 2-glycoprotein I antibodies].

Recent studies have shown that beta 2glycoprotein I (beta 2GPI), a plasma inhibitor of coagulation with affinity for anionic phospholipids, is frequently required for the formation of the epitopes recognized by some anti-phospholipid antibodies. Six murine monoclonal antibodies directed against human beta 2GPI were compared with anti-beta 2GPI antibodies associated with systemic lupus erythematosus and primary anti-phospholipid syndrome. The beta 2GPI-dependent binding properties to neutral and anionic phospholipids were studied, as well as the target epitopes on the beta 2GPI molecule and the effect of various beta 2GPI treatments to get rid of contaminating phospholipids or to block the beta 2GPI-phospholipid interaction. The results are in favour of a direct binding of patient's antibodies to beta 2GPI, in the absence of phospholipids. Anti-beta 2GPI monoclonal antibodies, two of which inhibited beta 2GPI recognition by the antibodies from patients, possessed lupus-like anticoagulant properties, thereby constituting an interesting model for a subset (beta 2GPI-dependent) of anti-phospholipid antibodies.

Antibodies, Antiphospholipid↗
PubMed1993

Platelet activating properties of murine monoclonal antibodies to beta 2-glycoprotein I.

Previously developed murine monoclonal antibodies (MAbs) to human beta 2-glycoprotein I (beta 2 GPI), a plasma protein required for the binding of anti-phospholipid antibodies, were studied for anti-platelet reactivity and influence on platelet function. The six MAbs (IgG1 isotype) tested interacted with both intact and fixed platelets in a beta 2 GPI-dependent manner. Carbamylated beta 2 GPI was still recognized by MAbs but was unable to mediate platelet-antibody binding. MAbs induced aggregation and secretion responses of platelets in platelet-rich plasma (PRP) and whole blood, provided subthreshold concentrations of weak agonists (i.e. ADP or adrenaline) were added. When aggregation in PRP was evaluated by a counting technique instead of turbidometrically, the sole addition of MAbs led to a rapid fall in single platelets. Triggering gel-filtered platelets with MAbs together with beta 2 GPI, but not its carbamylated form, led to platelet activation after a lag time, as monitored by aggregometry, measurements of ATP and beta-thromboglobulin secretion and calcium mobilization. F(ab')2 fragments of one of the MAbs failed to activate platelets but inhibited the responses to the whole antibody. This process thus depends on MAbs binding to platelets through both Fab and Fc domains, as confirmed by the suppression of platelet responses upon pretreatment with the anti-Fc gamma RII MAb IV.3. Aggregation and secretion induced by MAbs plus beta 2 GPI did not require exogenous fibrinogen and were variably inhibited in the presence of acetyl salicylic acid, apyrase or Ca2+, depending on the concentrations used for the two proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1993

Sleep in space.

Manned space flights have shown it is possible to sleep in microgravity. However, some sleep disturbances have been reported which influence performance of the crew and safety of space flight. This paper reviews the main studies of in-flight sleep in animal and man. Most disturbances are related to phase lags due to operational requirements. Factors which can disturb in-flight sleep are analysed: environmental factors. Some of them are secondary to space flight ergonomics. Conversely, effects of microgravity on light-dark alternance are less known and lead to interesting problems of fundamental research, psychological factors, especially during long duration flights.

Aerospace Medicine↗
PubMed1993

[Study by EPR of structural modifications on liposomes induced by two metabolites of modafinil].

Awaking properties of modafinil are well known at this time, but its action mode is still hypothetic. Our contribution is limited to the study of the membrane structural modifications carried by this drug and two metabolites. By EPR spectroscopy, we have studied the two metabolites which are distinguished by acid function for the first one and sulfone function for the second one. These two metabolites have no waking properties when they are administrated to animals but one of these two metabolites has the same behaviour than modafinil on membrane action.

Benzhydryl Compounds↗
PubMed1992

Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat.

Seventeen adult cats were chronically implanted with electrodes for polygraphic recordings in order to assess the role of catecholamines in the arousal effects of oral administrations of modafinil, a presumed noradrenergic agonist, and amphetamine, a well-known catecholamine-releasing agent. Whereas both modafinil (1, 2.5 and 5 mg/kg) and amphetamine (0.25, 0.5 and 1 mg/kg) caused a significant and dose-dependent increase in wakefulness and brain temperature, amphetamine, but not modafinil, elicited marked signs of behavioral excitation. Pretreatments with alpha-methyl-DL-p-tyrosine methyl ester (50 mg/kg, i.p.), an inhibitor of catecholamine synthesis, almost completely prevented the effects of amphetamine (0.25 and 1 mg/kg), but only slightly reduced the duration of the waking effect of modafinil (2.5 and 5 mg/kg). Pretreatments with phentolamine (10 mg/kg, i.p.), prazosin (1.5 mg/kg, per os) and propranolol (5 mg/kg, i.p.), an alpha-, alpha 1- and beta-receptor antagonist, respectively, attenuated significantly the arousal effect of modafinil (1 mg/kg, the same as below) but not of amphetamine (0.25 mg/kg, the same as below). Intraperitoneal injections of haloperidol (0.5 mg/kg), a dopamine-receptor antagonist, blocked significantly the arousal of amphetamine but not of modafinil. The effects of both modafinil and amphetamine were enhanced by a pretreatment with yohimbine (1 mg/kg, i.p.), an alpha 2-receptor antagonist. These results suggest that the arousal effect of modafinil does not depend on the availability of the endogenous catecholamines but results from an enhancement of alpha 1- and beta-receptor activity and that the waking and behavioral effects of amphetamine may be mainly due to an increase in dopamine release.

Amphetamine↗
PubMed1992

Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene.

Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.

Adolescent↗
PubMed1992

Lupus-like anticoagulant properties of murine monoclonal antibodies to beta 2-glycoprotein I.

The lipid-binding inhibitor of coagulation, beta 2-glycoprotein I (beta 2GPI), has been shown to form the antigen to which some autoantibodies against anionic phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the IgG1 isotype were raised against human beta 2GPI and could be subdivided into three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3 (group A) markedly inhibited the binding of immunoglobulins from aPL-positive sera to beta 2GPI-coated wells. Using a lipid-based solid-phase radioimmunoassay, the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine, but not phosphatidylcholine, in a beta 2GPI-dependent manner. A cross-reaction between beta 2GPI from several (including bovine) species was seen with one of the MAbs (9G1). All six MAbs induced dose-dependent prolongation of the DAPTT, DRVVT, KCT and TTI clotting times of human plasma, whereas 9G1 was the sole antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory effects were observed with MAbs used in pairs provided that they did not compete with each other for beta 2GPI binding. The anticoagulant activity of the MAbs was fully neutralized by the addition of freeze-thawed platelets. The MAbs described here resemble lupus anticoagulants in several respects which makes them valuable to study the involvement of beta 2GPI in the autoimmune thrombotic pathophysiology.

Animals↗
PubMed1991

Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoprotein I as an antigen.

The requirement of plasma cofactor beta 2-glycoprotein I for binding autoantibodies against anionic phospholipids has been reported. We describe the development of an enzyme-linked immunosorbent assay (ELISA) for anti-phospholipid antibodies using highly purified beta 2-glycoprotein I for coating microtitre plates. Intra- and interassay coefficients of variation, determined with serum pools of low, medium and high positivity, ranged between 3% and 18%. 54 sera from patients with systemic lupus erythematosus and related autoimmune disorders were analyzed by this assay; the results correlated well to those obtained in an ELISA using anionic phospholipids on the solid phase (r = 0.85, P less than 0.001). The two ELISA systems showed similar sensitivities although 8/31 positive sera scored negative in the beta 2-glycoprotein I ELISA. The latter group of eight sera showed significantly higher anti-phosphatidylcholine/anti-phosphatidylserine binding ratios than the group of 23 sera which scored positive in both assays. This new assay should permit accurate measurement of most of the clinically relevant anti-phospholipid antibodies and avoid inconsistencies likely to arise from secondary interactions that characterize lipid-based ELISA.

Amino Acid Sequence↗
PubMed1991

Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity.

We have studied the effect of modafinil and amphetamine, two waking drugs, on the electrical activity of central dopaminergic and noradrenergic neurons in the rat. Modafinil (128 mg/kg, i.p.) was unable to modify the firing pattern of these neurons, while amphetamine (2 or 5 mg/kg, i.p.) consistently inhibited their activity. A pretreatment with modafinil did not change thereafter the effect of amphetamine. Contrary to amphetamine, the waking effect of modafinil does not seem to be mediated by the catecholaminergic neuron activity per se.

Animals↗