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M Roux

Publications and source records attributed to M Roux.

At least 37 records · Page 2Linked to original sources
PubMed1996

Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro.

Contact of various cells with extracellular matrix molecules modulates their cellular functions and phenotype. Most investigations have employed dishes coated with purified matrix constituents or plain collagen I lattices omitting the effects of other important matrix components such as proteoglycans. In this study we analyze the effect of purified glycosaminoglycans (GAGs) on human fibroblasts and human umbilical vein endothelial cells (HUVEC) embedded within collagen I/III lattices. HUVEC contracted collagen I/III gels far less efficiently than fibroblasts and addition of heparan sulfate and heparin almost completely inhibited contraction. In collagen gels HUVEC down-regulated collagenase mRNA while increasing collagen I, IV mRNA expression. Addition of heparin and heparan sulfate reversed the collagen IV mRNA induction whereas hyaluronic acid and chondroitin sulfate enhanced fibronectin and collagenase transcripts. Fibroblasts readily contracted collagen gels, and mRNA levels for fibronectin, collagenase and interleukin-6 were stimulated. Gel contraction was mostly unaffected by the different glycosaminoglycans. Fibroblasts responded to the addition of dermatan sulfate, heparan sulfate and heparin with a decrease in fibronectin, collagenase and interleukin-6 mRNA. Binding studies revealed saturable binding sites on fibroblasts and HUVEC for 35S-labelled heparin, demonstrating specificity for heparin and heparan sulfate over other GAGs in competition experiments. This study implies that glycosaminoglycans participate in cell-matrix interactions by effectively modulating the cellular phenotype via high affinity binding sites.

Animals↗
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

CCK-JMV-180 acts as an antagonist of the CCKA receptor in the human IMR-32 neuroblastoma cell line.

[125I]Cholecystokinin-8-S (CCK-8-S) bound to a single class of saturable binding sites on the human neuroblastoma cell line IMR-32 (KD = 4 +/- 1.5 nM, Bmax = 10,500 +/- 3,500 sites/cell (n = 6)). These binding sites were of the CCKA type, as demonstrated by the differential inhibition of the binding of [125I]CCK-8-S and CCK-8-S-induced 45Ca2+ efflux by the specific CCKA antagonist SR 27897 and the specific CCKB antagonist PD 134,308. CCK-JMV-180, an analogue of CCK-8-S which has been shown to activate 45Ca2+ efflux in rat cells in a manner similar to CCK-8-S, acted as a potent antagonist of CCK-8-S-induced 45Ca2+ efflux (IC50 = 50 nM) and inhibited [125I]CCK-8-S binding to IMR-32 cells (IC50 = 1.7 nM). These results show that, unlike its CCK-like effect in various animal systems, CCK-JMC-180 acts as an antagonist of CCKA receptors in the human neuroblastoma cell line IMR-32.

Calcium Radioisotopes↗
PubMed1994

Neuroprotective effects of colchicine in the gerbil model of cerebral ischaemia.

The tropolonic alkaloid colchicine significantly reduces the behavioural, electroencephalographic and histological damage seen after a 6-min occlusion of the two common carotid arteries of the Mongolian gerbil if the compound is administered at 2 or 4 mg/kg i.p. immediately upon reperfusion. A 45% increase in high-frequency ECoG activity and significant reduction of 80% in the hypermotility of the gerbils, with 63% less faults in a passive avoidance paradigm, were observed in conjunction with considerable protection of the hippocampus, after a single dose of 4 mg/kg colchicine. No adverse effects of colchicine treatment on animal movement and body weight were observable. Colchicine's possible mode of action, via inhibition of cellular transport systems, is discussed.

Animals↗
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↗
PubMed1994

[Sclerodermiform skin changes in Borrelia burgdorferi infection. Diagnostic use of polymerase chain reaction].

We report on a 61-year-old patient with sclerodermiform skin lesions of the extremities and polyneuropathy. Borrelia (B.) burgdorferi DNA was detected in lesional skin by the polymerase chain reaction. Serological testing revealed IgG antibodies to B. burgdorferi. Histology revealed an inflammatory stage of a sclerotic reaction in the lesional skin. The admixture of plasma cells and the perineural distribution of the cellular infiltrate was suggestive for a borrelia infection. Immunohistochemical staining for the B. burgdorferi flagellin (41 kDa) revealed a positive staining reaction in the epidermis of lesional skin. The improvement of both the dermatological and the neurological symptoms upon antibiotic treatment with ceftriaxone was taken as further support for the diagnosis of a. B. burgdorferi infection.

Antibodies, Bacterial↗
PubMed1994

Representation of medical concepts of the thyroid gland by physicians in anatomy and pathology.

An experimental study in cognitive psychology is described, concerning the categorization of medical concepts into specific classes, expressed by physicians specialized in anatomic pathology consultations of the thyroid gland. This study belongs to a medical computer science project, called ARISTOTLE, concerning Natural Language Processing of specialized medical reports in anatomic pathology of the thyroid gland. This research has been done for two reasons; first, to specify the characteristics of human expert categorization in an area of medical knowledge and, secondly, to validate the hierarchical organization of a prototype declarative knowledge base. In this experiment, physicians were asked to categorize 121 concepts into 10 proposed classes. These classes and concepts belong to expert knowledge represented in a conceptual graph that was constructed before the experiment. Results show variable semantic distances between concepts of a same class, and dynamic variations of these distances due to contextual representation.

Artificial Intelligence↗
PubMed1993

A soluble form of the adhesion receptor CD58 (LFA-3) is present in human body fluids.

The human adhesion receptor CD58 (LFA-3) is expressed on most human cell types. Here we report on a soluble form of CD58 (sCD58) in human serum, human urine, and culture supernatants of several cell lines. sCD58 partially purified from human serum, from supernatant of the Hodgkin cell line L428, and purified sCD58 from human urine were found to have a molecular mass of 40-70 kDa under denaturating conditions (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting). However, gel filtration of sCD58 purified from human urine gave a molecular mass of 118-166 kDa, suggesting a noncovalent homotrimer conformation or its association with other molecules. Using an enzyme-linked immunosorbent assay specific for CD58 we found that sera from patients suffering from different forms of hepatitis contained elevated sCD58 levels (n = 108). Accordingly, there was a fivefold increase of supernatant sCD58 when the hepatocellular carcinoma cell line Hep G2 was incubated with 25 ng/ml recombinant tumor necrosis factor-alpha in vitro. In contrast, sCD58 serum levels of 337 additional patients suffering from various other immunological disorders were not found to be raised. At high concentrations sCD58 binds to CD2-positive cells and inhibits rosette formation of human T cells to human erythrocytes. Thus, local release of large quantities of naturally occurring sCD58 may interfere with intercellular adhesion in vivo.

Antibodies, Monoclonal↗
PubMed1993

RP 59037 and RP 60503: anxiolytic cyclopyrrolone derivatives with low sedative potential. interaction with the gamma-aminobutyric acidA/benzodiazepine receptor complex and behavioral effects in the rodent.

This study describes the pharmacological properties of two novel cyclopyrrolone derivatives, RP 59037 [2-(7-chloro-2-naphthyridin-1,8-yl)-3-(5- methyl-2-oxohexyl)isoindolin-1-one] and RP 60503 [2-(7-chloro-2-naphthyridin-1,8-yl)isoindolin-1-yl-4- acetamidobutyrate], in the rodent. These compounds possess high affinity for the benzodiazepine binding site on the gamma-aminobutyric acidA receptor in rat cerebrocortical membranes with Ki values of 0.98 nM (RP 59037) and 1.16 nM (RP 60503). Neither compound discriminates between the putative benzodiazepine BZ1 and BZ2 binding site subtypes present in the rat cerebellum and hippocampus, respectively. Both compounds protect mice against pentylenetetrazole-induced seizures with ID50 values of 0.21 mg.kg-1 p.o. (RP 59037) and 5.96 mg.kg-1 p.o. (RP 60503). The two compounds displayed a restricted anticonvulsant profile compared to diazepam and, in this respect, resembled the pyrazoloquinoline partial agonist, CGS 9896. RP 59037 and RP 60503 were active in two rat models predictive of anxiolytic drug action, a modified Geller-Seifter conflict paradigm (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503) and the elevated plus maze (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503). Only very low activities were observed in tests of sedative or myorelaxant effects (ED50 > 50 mg.kg-1 p.o.). It is concluded that the two cyclopyrrolones possess a dissociated behavioral profile, displaying potent anxiolytic and anticonvulsant properties with little or no sedative or myorelaxant effects. Although both compounds appear to be partial agonists at their allosteric recognition site on the gamma-aminobutyric acidA receptor, RP 60503 seems to be more dissociated than RP 59037, which would be compatible with it having lower intrinsic activity. This difference is reflected in a higher receptor occupancy requirement for activity, and a smaller modulatory effect on the binding of t-[35S]butylbicyclophosphothionate.

Animals↗
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↗