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Biomedical subjects

M Roux

Publications and source records attributed to M Roux.

At least 19 recordsLinked to original sources
PubMed1995

A model for medical knowledge representation application to the analysis of descriptive pathology reports.

A new knowledge-representation system is presented, designed for medical knowledge-based applications and in particular for the analysis of descriptive medical reports. Knowledge is represented at two levels. A definitional level uses a concept-type hierarchy, a relation-type hierarchy, and a set of schematic graphs to define the concepts used and the relations between them, as well as different types of cardinality restrictions on these relations. A set of compositional hierarchies using the classic "has-part" relation as well as a new set-inclusion relation allows concept composition to be precisely defined. An assertional level allows the creation and manipulation of empirical data, in the form of graphs using the concepts, relations, and constraints defined at the definition level. The use of cardinality constraints in graph unification is considered in the context of descriptive medical discourse analysis.

Artificial Intelligence↗
PubMed1994

Fragmentation of phospholipid bilayers by myelin basic protein.

Human myelin basic protein (MBP) is shown to disrupt multilamellar phosphatidylcholine bilayers into small lipoprotein particles in a manner similar to the cytolytic peptide melittin (Dufourc, E. J., Smith, I. C. P., & Dufourcq, J. (1986) Biochemistry 25, 6448-6455). This bilayer fragmentation, as monitored by 31P nuclear magnetic resonance, is temperature-dependent and completely inhibited by the presence of small amounts of negatively charged phosphatidylserine. The stabilizing property of phosphatidylserine is lost with the neutralization of its negative charges upon membrane binding of cationic species such as calcium ions. No MBP-induced fragmentation is observed with bilayers of negative or zwitterionic lipid mixtures which mimic the myelin lipid composition. The membrane fragmentation observed in vitro in the presence of MBP could play a role in vivo in demyelinating diseases.

Calcium↗
PubMed1994

Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease.

Several small studies have indicated an impaired cell mediated immune response as a possible cause for the delayed elimination of the bacteria in Whipple's disease. A specific defect, however, has not been defined. We examined the expression of cell surface molecules and mitogenic responses of peripheral blood mononuclear cells in 27 patients with Whipple's disease at different disease stages by indirect immunofluorescence and by measurement of [3H]thymidine incorporation, respectively. E-rosette formation and cutaneous reaction to seven recall antigens were determined. Matched healthy donors served as controls. We found a significantly reduced number of cells expressing the complement receptor 3 alpha-chain (= CD11b) in all patients. In florid disease, the number of activated cells (in particular CD58 positive cells) was increased and CD4/CD8 ratios were diminished. Proliferation to phytohemagglutinin and to sheep red blood cells was reduced at all stages of the disease. Serum of control persons reversed this decreased responsiveness especially in patients with active disease. Skin reaction was hypoergic in all patients. Determination of CD58 positive cells increased in patients with active disease may be useful to define the activity of the disease and the duration necessary for treatment. Transient inhibiting serum activities may impair the CD2/CD58 interaction. The reduction of cells expressing CD11b, the decreased proliferation, and the cutaneous hypoergy indicate a persisting defect of cell mediated immunity in vivo and in vitro. These defects may contribute to the impaired ability of patients with Whipple's disease to eliminate bacteria.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemia.

Riluzole (2 amino 6-trifluoromethoxybenzothiazole), when administered at 4 and 8 mg/kg i.p., 0.5, 4.5, 24 and 28 h after the initiation of ischaemia, significantly reduced the prevalence of slow wave, and increased the proportion of higher frequency activity seen in the quantified electrocorticogram (ECoG), during the weeks that followed a 6 min bilateral occlusion of the common carotid arteries in the Mongolian gerbil. In focal ischaemia, provoked in Fischer rats following the occlusion of the middle cerebral artery, administration of riluzole (8 mg/kg) at 30 min and 24.5 h post occlusion significantly reduced the volume of infarcted cortex. These activities of riluzole could be related to its inhibition of sodium channel activity, which in turn inhibits glutamate release.

Animals↗
PubMed1992

Structural and functional epitopes of the human adhesion receptor CD58 (LFA-3).

CD58 (LFA-3), a heavily glycosylated protein of 40-70 kDa, is expressed on a broad range of hematopoietic and non-hematopoietic cells. It serves as a physiological ligand of the CD2 receptor, present on T cells and natural killer cells, and plays, thus, an important role in lymphocyte adhesion and T cell activation through CD2. Whereas several epitopes and their respective function are known for CD2, a similarly detailed characterization of CD58 is still lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against recombinant human CD58 and describe here the identification of six structurally and/or functionally distinct epitopes on the CD58 molecule. All epitopes were found to be present in equal numbers on a wide range of CD58+ cells, none of them being differentially up-regulated following cell activation or malignant transformation. Two of these epitopes represent functionally relevant sites, involved in binding of CD58 to CD2 and T cell activation via CD2. One further epitope appears to be selectively involved in CD58-mediated activation, whereas the other three displayed no functional effects. The new mAb allow for the first time the detection of CD58 in enzyme-linked immunosorbent assays and immunofluorescence while bound to its receptor CD2 in human serum or on freshly isolated blood cells. Finally, one mAb was found to specifically cross-react with T11TS, the equivalent of CD58 in sheep.

Animals↗
PubMed1992

A simple vacuum transfer device for nucleic acids.

We present a new vacuum device intended for transferring nucleic acids from agarose gels onto hybridization membranes. The apparatus is drawn so that plastic sheets serve as substitutes for the elaborate, but cumbersome and unnecessary, locking systems mounted on all the commercial blotters. This substitution results in (1) a much more easy and rapid set-up of the transfer and (2) a very simple framework allowing the possibility of low-cost manufacturing.

Blotting, Northern↗
PubMed1991

Natural inhibitors of T-cell activation in Hodgkin's disease.

Secondary immunodeficiency is frequently observed in Hodgkin's disease (HD) and is due in part to impaired T-cell function. Using monoclonal antibodies that bind to triggering molecules of human T lymphocytes (CD3/Ti antigen receptor; CD2 E-rosette receptor) and exert functional effects on T-cell activation, we have investigated in vitro immune responses of circulating lymphocytes from patients with HD in progression (n = 9) and in remission (n = 14). In patients with progressive HD, a severe dysfunction of the alternative CD2-mediated T-cell activation pathway was detected (49.3 +/- 14.2 v 9.4 +/- 5.1 cpm x 10(-3), in controls, P less than .01; n = 9) that parallels the reduced capacity of T lymphocytes to form rosettes with sheep red blood cells. Diminished alternative pathway activation in HD is not only due to a defect at the cellular level but also due to soluble mediators in the patients' plasma. Plasma from patients in progression markedly reduces CD2 mediated activation (P less than .01). These activities interfere, at least in part, with CD2/CD58 interactions and, therefore, reduce T-lymphocyte triggering through this amplifier mechanism.

Adult↗
PubMed1991

GTP hydrolysis mechanisms in ras p21 and in the ras-GAP complex studied by fluorescence measurements on tryptophan mutants.

We have substituted leucine 56 or tyrosine 64 of p21 ras with a tryptophan. The intrinsic fluorescence of this tryptophan was used as an internal conformational probe for time-resolved biochemical studies of the ras protein. The slow intrinsic GTPase, GDP/GTP exchange induced by the SDC25 "exchange factor", and the fast GTP hydrolysis induced by GAP were studied. Tryptophan fluorescence of mutated ras is very sensitive to magnesium binding, GDP/GTP exchange, and GTP hydrolysis (changes in tyrosine fluorescence of wild-type ras are also observed but with a lower sensitivity). Nucleotide affinities, exchange kinetics, and intrinsic GTPase rates of the mutated ras could be measured by this method and were found to be close to those of wild-type ras. The SDC25 gene product enhances GDP/GTP exchange in both mutants. In both mutants, a slow fluorescence change follows the binding of GTP gamma S; its kinetics are close to those of the intrinsic GTPase, suggesting that a slow conformational change precedes the GTPase and is the rate-limiting step, as proposed by Neal et al. (1990) (Proc. Natl. Acad. Sci. U.S.A. 87, 3562-3565). GAP interacts with both mutant ras proteins and accelerates the GTPase of (L56W)ras but not that of (Y64W)ras, suggesting a role for tyrosine 64 in GAP-induced GTP hydrolysis. However, GAP does not accelerate the slow conformational change following GTP gamma S binding in either of the mutated ras proteins. This suggests that the fast GAP-induced catalysis of GTP hydrolysis that is observed with (L56W)ras bypasses the slow conformational change associated with the intrinsic GTPase and therefore might proceed by a different mechanism.

Amino Acid Sequence↗
PubMed1991

31P-NMR study of pig intestinal brush-border membrane structure: effect of zinc and cadmium ions.

31P-NMR experiments on intact pig small intestine brush-border membrane vesicles (BBMV) and detergent-solubilized membranes gave direct insights into the organization of the phospholipids (PL) and their interaction with zinc and cadmium ions. Various endogenous PL were identified from well resolved BBM micelle spectra. These experiments revealed a strong interaction of Zn2+ and Cd2+ with the negatively charged phosphatidylinositol and phosphatidylserine. In BBM micelles, a progressive time-dependent PL degradation occurred in the absence of ions and indicated the presence of active phospholipases. The presence of zinc inhibited the degradation process whereas cadmium had the opposite influence. 31P spectra of BBMV were carefully characterized. Neither zinc nor cadmium affected the PL bilayer structural organization. A degradation of PL, monitored by the increase of the inorganic phosphate (Pi) signal, also occurred in vesicles but to a lesser extent than in micelles. A 2/3 internal, 1/3 external PL asymmetry was observed in the absence and presence of ions.

Animals↗
PubMed1991

Calcium binding by phosphatidylserine headgroups. Deuterium NMR study.

The binding of calcium to headgroup deuterated 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphoserine (POPS) was investigated by using deuterium magnetic resonance in pure POPS membranes and in mixed 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC)/POPS 5:1 (m:m) bilayers. Addition of CaCl2 to pure POPS bilayers led to two component spectra attributed, respectively, to liquid-crystallin POPS (less than 15 kHz) and POPS molecules in the calcium-induced dehydrated phase (cochleate) (approximately 120 kHz). The liquid-crystalline component has nearly disappeared at a Ca2+ to POPS ratio of 0.5, indicating that, under such conditions, most of the POPS molecules are in the precipitated cochleate phase. After dilution of the POPS molecules in zwitterionic POPC membranes (POPC/POPS 5:1 m:m), single component spectra characteristic of POPS in the liquid-crystalline state were observed in the presence of Molar concentrations of calcium ions (Ca2+ to POPS ratio greater than 50), showing that the amount of dehydrated cochleate PS-Ca2+ phase, if any, was low (less than 5%) under such conditions. Deuterium NMR data obtained in the 15-50 degrees C temperature range with the mixed PC/PS membranes, either in the absence or the presence of Ca2+ ions, indicate that the serine headgroup undergoes a temperature-induced conformational change, independent of the presence of Ca2+. This is discussed in relation to other headgroup perturbations such as that observed upon change of the membrane surface charge density.

Calcium↗
PubMed1991

Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.

1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.

Adrenergic beta-Antagonists↗
PubMed1990

Ca2+, Mg2+, Li+, Na+, and K+ distributions in the headgroup region of binary membranes of phosphatidylcholine and phosphatidylserine as seen by deuterium NMR.

The binding of calcium, magnesium, lithium, potassium, and sodium to membrane bilayers of 5 to 1 (M/M) 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1-palmitoyl- 2-oleoylphosphatidylserine (POPS) was investigated by using deuterium nuclear magnetic resonance (2H NMR). Both lipids were deuteriated on their polar headgroups, and spectra were obtained at 25 degrees C in the liquid-crystalline phase as a function of salt concentration. The spectra obtained with calcium were correlated with 45CaCl2 binding studies to determine the effective membrane-bound calcium at low calcium binding, up to 0.78 calcium per POPS. Deuterium quadrupolar splittings of both POPC and POPS headgroups were shown to be very sensitive to calcium binding. The behavior of these two headgroups over a wide range of CaCl2 concentrations suggests that Ca2+ binding occurs in at least two steps, the first step being achieved with 0.5 M CaCl2, with a stoichiometry of 0.5 Ca2+ per POPS. Correlations of the deuterium Ca2+ binding data with related data obtained after incorporation of a cationic integral peptide showed that the effects of these two cationic molecules of the POPS headgroup are qualitatively similar, and provided further support for two-step Ca2+ binding to the POPC/POPS 5:1 membranes. The corresponding data obtained with magnesium, lithium, and potassium indicate that these cations interact with both the choline and serine headgroups. The amplitudes of headgroup perturbations could be partly correlated to the relative affinities of the metallic cations for the lipid membrane. The two-step binding described with Ca2+ appears to be relevant to the Mg2+ data, and in certain limits to the Li+ data. The data were interpreted in terms of conformational changes of the lipid headgroups induced by an electric field due to the charges of the membrane-bound metallic cations. A conformational change of the serine headgroup induced by the membrane-bound charges is proposed. We propose that the metallic cations can be differentiated on the basis of their respective spatial distribution functions relative to the choline and serine headgroups. According to this interpretation, the divalent cations Ca2+ and Mg2+ are more deeply buried in the membrane than monovalent Na+ and K+, the case of Li+ being intermediate of the latter two. This conclusion is discussed in relation to fundamental theories of the spatial distribution of ions near the interface between water and smooth charged solid surfaces.

Binding Sites↗
PubMed1990

Autoradiographic localization of [3H]oestradiol in epididymis, seminal vesicles and prostate of the fetal guinea-pig.

The selective uptake and localization of radioactivity in the fetal male reproductive organs (epididymis, seminal vesicles and prostate) of the guinea-pig (50-60 days of gestation) after in-vivo and in-situ subcutaneous injection of [3H]oestradiol was investigated by autoradiography. In 50-day-old fetuses, the different areas of the epididymis showed selective retention of radioactivity in the nuclei of peritubular and stromal cells surrounding the epididymal duct; no retention was observed in the epididymal epithelium. A similar distribution of silver grains was observed in the 60-day-old fetus. Seminal vesicles and prostate sections from both 50- and 60-day-old fetuses showed concentration and retention of radioactivity only in stromal cells, whereas the epithelium did not exhibit silver grains. In all the tissues studied, the nuclear labelling was abolished after injection of [3H]oestradiol plus a 100-fold excess of non-labelled oestradiol. As the mesenchyme surrounding the epithelia of the epididymis, seminal vesicles and prostate were labelled selectively with [3H]oestradiol, it is suggested that during fetal life of the guinea-pig the mesenchymal stroma of these fetal male reproductive organs may be considered as a target tissue for oestrogen.

Animals↗
PubMed1990

[Evaluation of the placebo effect on blood pressure profile during exercise in patients with mild uncomplicated hypertension].

UNLABELLED: The administration of placebo (pharmacologically inactive substance) is justified in clinical trials of antihypertensive drugs, in order to avoid the inclusion of placebo-responders. The evaluation of antihypertensive treatments during exercise is an interesting end point, since aerobic exercising is part of antihypertensive treatment. The aims of this study are to determine the placebo impact on blood pressure, heart rate and catecholamine secretion profiles during exercise testing. METHOD: 10 untreated essential mild to moderate hypertensives participated to a single blind study comprising two successive submaximal exercise testings (85% of maximal theoretical heart rate), separated by a single oral administration of placebo. Blood pressure and heart rate were measured after 10 minutes of resting position and at the end of each effort step (2 mm, 20 Watts), both before and after placebo. Blood samples (5 ml) were collected at rest and during maximal exercise before and after placebo, in order to determine the effect of placebo on circulating catecholamines. RESULTS: there was no significant variations between the "control" and exercise testings after placebo, neither on blood pressure or heart rate profiles, nor in values of circulating catecholamines [Noradrenaline at rest: 1.88 +/- 0.96, exercise: 6.43 +/- 1.93 nm/l before placebo, 1.65 +/- 0.83 nm/l and 5.71 +/- 2.12 nm/l after placebo respectively (NS)]. CONCLUSION: the placebo, which effect is generally determined on blood pressure at rest by sphygmomanometry, seems devoid of any activity on blood pressure, heart rate or catecholamine profile during exercise, in essential moderate hypertensives. Thus, antihypertensive treatments at exercise can be evaluated by comparison to baseline cardiovascular parameters without placebo groups.

Adult↗
PubMed1989

Conformational changes of phospholipid headgroups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance.

Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction of a cationic amphiphilic peptide with pure DMPC membranes and with mixed bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS). The choline and serine headgroups were selectively deuteriated at the alpha and beta positions. The amphiphilic peptide, with 20 leucine residues in the hydrophobic core and two cationic hydrophilic lysine residues at each end, spanned the lipid bilayer. Although 2H NMR experiments using DMPC with perdeuteriated fatty acyl chains showed that the average order parameter of the hydrophobic region was not significantly modified by the incorporation of the amphiphilic peptide, for either DMPC or DMPC/DMPS (5:1) bilayers, large perturbations of the quadrupolar splittings of the choline and serine headgroups were observed. The results obtained with the DMPC headgroup suggest that the incorporation of the cationic peptide in both DMPC and DMPC/DMPS (5:1) bilayers leads to a structural perturbation directly related to the net charge on the membrane surface. The magnitude of the observed effect seems to be similar to those observed previously with other cationic molecules [Seelig, J., MacDonald, P.M., & Scherer, P.G. (1987) Biochemistry 26, 7535-7541]. Two of the three quadrupolar splittings of the PS headgroup exhibited large variations in the presence of the amphiphilic peptide, while the third one remained unchanged. Our data have led us to propose a model describing the influence of membrane surface charges on headgroup conformation. In this model, the surface charge is represented as a uniform charge distribution. The electric field due to the charges produces a torque which rotates the polar headgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗