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S Roux

Publications and source records attributed to S Roux.

At least 91 records · Page 5Linked to original sources
PubMed1996

Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone.

Osteoclasts (OCs), which form by fusion of hematopoietic precursor cells, are typically present in large numbers in giant cell tumors of bone (GCTBs). These tumors may, therefore, contain cells which secrete factors that stimulate recruitment and differentiation of OC precursors. Multinucleated cells resembling OCs also form in cultures of human cord blood monocytes (CBMs) stimulated by 1.25 dihydroxyvitamin D3, but these cells lack the ability to form bone resorption pits, the defining functional characteristic of mature OCs. CBMs may thus require additional stimulation to form OCs; we therefore investigated whether GCTBs are a source of such a stimulus. CBMs were stimulated in long term (21 day) culture by medium conditioned by explants of GCTBs; media collected within 15 days of explant (early-CM) and after 15 days (late-CM) were employed. We also cocultured CBMs with primary GCTB-derived stromal cells as well as immortalized bone marrow stroma-derived cells. CBMs stimulated by early-CM formed resorption pits on cortical bone slices; however, stimulation by late-CM resulted in virtually no resorption. Both early-CM and late-CM increased CBM proliferation, but not the proportion of vitronectin receptor positive or multinucleated cells. Coculture of CBMs with stromal cells of GCTBs or bone marrow did not result in bone resorption, although these stromal cells (most expressing alkaline phosphatase but progressively losing parathyroid hormone receptor expression) expressed mRNA for cytokines involved in OC differentiation, including macrophage-CSF, granulocyte-macrophage-CSF, IL-11, IL-6, and stem cell factor. Our results indicate that CBMs are capable of terminal OC differentiation in vitro, a process requiring 1,25 dihydroxyvitamin D3 as well as diffusible factor(s) which can be derived from GCTB. Stromal cells of GCTB may produce such factors in vivo, but do not support OC differentiation in vitro, possibly through phenotypic instability in culture.

Acid Phosphatase↗
PubMed1996

Reliability of multimodal evaluation of abnormal screening mammogram results.

OBJECTIVE: Our purpose was to evaluate the effectiveness and reliability of the multimodal evaluation of suspicious or equivocal screening mammogram results by use of ancillary imaging studies and needle biopsies. STUDY DESIGN: This article reports on the experience of the Breast Evaluation Center at Long Beach Memorial Medical Center between 1989 and 1993 where 43,125 screening mammograms were performed. RESULTS: A total of 2866 patients were called back for additional evaluation, which consisted of magnification views and ultrasonography. Since 1990 fine-needle biopsies have been done on selected patients and since 1992 core biopsies have been available. Needle localization excisional biopsies were performed on 344 patients, and 158 cancers were diagnosed. This represents a 46% positive predictive value. Careful follow-up was obtained on the patients seen in 1990 to attempt to determine whether any cancers developed within a year of the time the patients with abnormal screening mammogram results had been evaluated with imaging modalities but no tissue diagnosis made. One cancer may have been missed. The cost savings of this protocol are also examined. CONCLUSION: Multimodal evaluation of patients with suspicious screening mammogram results appears to be a cost effective approach with adequate sensitivity and specificity.

Biopsy, Needle↗
PubMed1996

Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma.

Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.

Adult↗
PubMed1996

Mechanism of the antiischemic effect of mibefradil, a selective T calcium channel blocker in dogs: comparison with amlodipine.

Calcium channel blockers are active in variant angina principally by preventing coronary vasospasm. However, a direct antiischemic effect may also occur. In open-chest dogs, an attack of variant angina was mimicked by a 2-min critical coronary stenosis, and the following reversible myocardial ischemia was assessed by measuring the decrease of segmental shortening. We compared the antiischemic mechanism of mibefradil, a T and L calcium channel blocker, with that of amlodipine, a pure L channel blocker. Both drugs showed a similar relationship between the decrease of the rate-pressure product and the antiischemic effect, but only mibefradil reduced heart rate. Amlodipine and mibefradil at the highest doses tested (20 and 70 micrograms/kg/min, respectively) restored 68 +/- 8 and 76 +/- 5% of segmental shortening in the ischemic area, respectively, as compared with preischemic values. Matching blood pressure (by intraaortic balloon) or heart rate (by atrial pacing) to predrug values showed that the antiischemic effect was mainly afterload-dependent for amlodipine and heart rate-dependent for mibefradil. We conclude that in variant angina, in addition to their antivasospastic effects, calcium channel blockers may be antiischemic by a direct myocardial effect associated with a decrease of the rate pressure product. Blockade of the T channel does not seem to participate in the direct antiischemic effect of mibefradil but could explain the decrease of heart rate.

Amlodipine↗
PubMed1996

Mutation of isoleucine 747 by a threonine alters the ligand responsiveness of the human glucocorticoid receptor.

Mutation of isoleucine 747 to threonine in the C-terminal part of the ligand-binding domain (LBD) of the human glucocorticoid receptor (GR) alters the ligand specificity for transactivation. Natural glucocorticoids such as cortisol or corticosterone were completely inactive with the mutant 1747T, whereas synthetic steroids like dexamethasone efficiently stimulated GR 1747T-mediated transactivation. However, the corresponding ligand dose-response curve for dexamethasone-induced transactivation was shifted to higher concentrations when compared with that obtained with the wild type GR. Neither this shift nor the inability of cortisol to activate the 1747T mutant was due to an altered in vitro ligand-binding affinity. In the canonical three-dimensional structure of nuclear receptor LBDs, isoleucine 747 is in the direct vicinity of residues that contribute to the ligand-binding pocket. Moreover, it is located in the C-terminal LBD region, which harbors the conserved core of the activation function AF-2 and undergoes a ligand-induce transconformation, required to generate the surface interacting with putative transcriptional intermediary factors/coactivators of AF-2. The phenotype of 1747T mutant is discussed in view of the possible consequences of the mutation on the various events which, according to the model, lead to a transcriptionally competent AF-2.

Amino Acid Sequence↗
PubMed1996

Effects of napsagatran (Ro 46-6240), a new synthetic thrombin inhibitor and of heparin in a canine model of coronary artery thrombosis: comparison with an ex vivo annular perfusion chamber model.

Napsagatran, a new synthetic direct thrombin inhibitor, was compared with heparin in a canine model of coronary thrombosis and concomitantly in an ex vivo perfusion chamber model. Occlusive thrombosis of the left circumflex coronary artery was induced by electrical injury. In parallel, arterial subendothelium was exposed to native blood using an annular perfusion chamber for 5, 10 and 20 min at a wall shear rate of 650/s. Dogs received saline, heparin (40 and 70 U/kg/h) or napsagatran (3 and 10 microgram/kg/min). Heparin (40 U/kg/h) and napsagatran (3 microgram/kg/min) delayed or prevented in vivo thrombotic occlusion, but only napsagatran (10 microgram/kg/min) significantly decreased the intracoronary thrombus when compared with saline. High-dose heparin (70 U/kg/h) or napsagatran (10 microgram/kg/min) decreased the platelet-rich thrombus after a 20-min chamber perfusion. Neither heparin nor napsagatran decreased the thrombus volume after a 5-min perfusion. Heparin (70 U/kg/h) and napsagatran (10 microgram/kg/min) prolonged the activated partial thromboplastin time differently (>x6 and x1.4, respectively, P<0.01), whereas the activated clotting time was prolonged equally (x2.5). Thus napsagatran in this model shows arterial antithrombotic effects similar to those of heparin. The chamber experiments suggest that neither compound affects the initiation of platelet thrombus formation. In arterial thrombosis, the activated clotting time has a higher predictive value than the activated partial thromboplastin time when a direct thrombin inhibitor is compared with heparin.

Animals↗
PubMed1996

Tumoral joint involvement in multiple myeloma and Waldenström's macroglobulinemia--report of 4 cases.

We describe 4 patients, 2 with multiple myeloma and 2 with Waldenström's macroglobulinemia, who developed arthritis due to invasion of articular and periarticular structures by malignant cells. Articular manifestations in lymphoplasmacytic disorders are most often related to metabolic or septic complications, sometimes to immunoglobulin deposits, but can also result from tumoral joint involvement.

Adult↗
PubMed1995

Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells (U937).

We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon (probe) and unlabeled amplicon (target) during hybridization. As the target quantity increased, that of the double-labeled probe decreased in accordance with the mass action law. This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers: 12-O-tetradecanoylphorbol 13-acetate (TPA) and a combination of all-trans retinoic acid (RA) and 1,25-dihydroxyvitamin D2 (VD). We observed that TPA treatment was associated with an increase in specific binding of [3H]dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment.

Base Sequence↗
PubMed1995

Activated clotting time as an appropriate test to compare heparin and direct thrombin inhibitors such as hirudin or Ro 46-6240 in experimental arterial thrombosis.

BACKGROUND: Specific thrombin inhibitors are considered to be more potent antithrombotics than heparin. However, the relation between the systemic anticoagulation generated by thrombin inhibitors and their antithrombotic effect is not well defined. In a guinea pig carotid thrombosis model, the activated clotting time (ACT), the activated partial thromboplastin time (aPTT), and thrombin-generation tests were evaluated for their ability to predict the arterial antithrombotic effect of direct thrombin inhibitors such as hirudin and Ro 46-6240 compared with heparin. METHODS AND RESULTS: Thrombosis of the carotid artery was induced by subendothelial damage in guinea pigs, and the subsequent cyclic flow variations were monitored. The effects of pretreatment with intravenous heparin, hirudin, and Ro 46-6240 were tested. After doubling the baseline aPTT, 1 IU.kg-1.min-1 heparin was inactive, whereas either hirudin or Ro 46-6240 (30 micrograms.kg-1.min-1) prevented thrombus formation by 80%. Heparin (10 IU.kg-1.min-1) induced the same antithrombotic effect but with indefinite aPTT prolongation. However, for similar prolongation of the ACT, the three compounds had equivalent antithrombotic effects. Thrombin generation was predictive of the antithrombotic effect of the thrombin inhibitors but not of heparin. CONCLUSIONS: The arterial antithrombotic effect of direct thrombin inhibitors, when compared with those of heparin, should be evaluated by the ACT and not the aPTT or thrombin-generation assays. For a "therapeutic" aPTT prolongation, thrombin inhibitors induce higher systemic anticoagulation than does heparin and thus might unduly have higher bleeding liability.

Animals↗
PubMed1995

Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research.

A large number of investigation techniques are used to establish the relationships between the clinical and biological data which are necessary for physiopathological analysis in the field of developmental disorders. It therefore seemed necessary to develop a quantified grouping system, based on developmental assessments, which could allow closer matching between clinical evaluations and biological numerical data. Two hundred and two subjects presenting developmental disorders (autistic disorder, pervasive developmental disorder not otherwise specified and mental retardation) were examined. For each child, a quantification of autistic behaviour, intellectual impairment, neurological signs and language and communication disorders was performed. A cluster analysis of these quantified data elicited four subgroups according to the scores obtained in these four different areas. We showed the value of this approach by applying it to one of the studies of monoamines routinely examined in childhood autism--dopamine and HVA, its main urinary derivative. Moreover, this method revealed a subgroup within the total population which was independent of nosographic classification and which had a particular clinical and biochemical profile. Other applications could follow, for example in the fields of neurophysiology, cerebral imaging, molecular biology and genetics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Identification of behaviour profiles with a population of autistic children using multivariate statistical methods.

The Revised Behaviour Summarized Evaluation Scale (BSE-R) was developed for the objective evaluation of autistic behaviours in order to facilitate the recording of the evolution of developmentally disabled children. Among its 29 items, 13 items that precisely describe the degree of autistic behaviours were extracted by Principal Component Analysis. We hypothesised that these relevant behaviours could differentiate autistic behaviour profiles in a population of children previously diagnosed as typically autistic. For this purpose, we used an original multivariate descriptive statistical approach, Correspondence Analysis, which can help in detecting structural relationships among variables. In a population of autistic children initially diagnosed using DSM-III-R criteria, this procedure proved effective in identifying new main dimensions of behaviours among the 13 previously defined core autistic symptoms. Cluster analysis, which followed factorial analysis, allowed the identification of three meaningful behaviour profiles separated principally on the basis of two main functions, perception and imitation, which have been always considered to be fundamentally involved in autistic syndrome. The individualisation of homogeneous subgroups of children on the basis of the behavioural evaluation provides a potentially useful starting point for further biological and therapeutic studies.

Autistic Disorder↗
PubMed1995

Comparative evaluation of acute cerebral vasospasm by the microsphere and the angiography techniques.

Experimental subarachnoid haemorrhage (SAH) induces an acute transient cerebral vasospasm. The goal of this study was to compare angiography with iterative measurements of regional cerebral blood flow (rCBF) by the microsphere technique for tracking acute cerebral vasospasm after SAH. Cerebral vasospasm was induced in anaesthetised rabbits by injecting 1 ml of fresh blood in the cisterna magna. In a first experiment, the diameter of the basilar artery was measured by repeated angiograms over 60 min. In a second experiment, rCBF was measured over 60 min by the radioactive microspheres method without and with bilateral ligation of the carotid artery. Without carotid ligation, despite a profound transient vasospasm of the basilar artery, rCBF was unchanged in the cerebellum and cerebrum and was not statistically decreased in the brain stem. However, with bilateral carotid ligation, rCBF dramatically decreased at 5 and 15 min after haemorrhage. At 30 min, despite a persistent 50% decrease in the basilar cross-sectional area, rCBF was no longer different from the control group. Thus in a model of acute vasospasm of the basilar artery, rCBF evaluation by the microsphere technique parallels the cerebral vasospasm evaluated by angiography only when both carotid arteries are ligated.

Anesthesia↗