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Biomedical subjects

S Roux

Publications and source records attributed to S Roux.

At least 109 records · Page 6Linked to original sources
PubMed1995

Angiotropic large cell lymphoma with mononeuritis multiplex mimicking systemic vasculitis.

Angiotropic large cell lymphoma (ALCL), the so-called malignant angioendotheliomatosis, is characterised by proliferation of tumorous cells within small vessels. Manifestations in the CNS and cutaneous lesions prevail in the clinical presentation, although any organ can be involved. The recent classification of this lymphoma as part of the large cell lymphomas has modified the therapeutic approaches employed. This should improve the prognosis of this usually fatal disease. An unusual case presenting with fever, mononeuritis multiplex, and cutaneous lesions is reported. Peripheral neuropathy without other neurological symptoms is uncommon, and, to our knowledge, such isolated mononeuritis multiplex with nerve lesions has not been previously reported in ALCL. The clinical diagnosis was a systemic necrotising vasculitis and it is considered that its differential diagnosis must include angiotropic large cell lymphoma.

Aged↗
PubMed1995

The role of endothelin in experimental cerebral vasospasm.

Endothelin (ET) may play a role in vasospasm after subarachnoid hemorrhage (SAH). The aim of our study was to test whether the systemic administration of bosentan, a nonpeptidic ET(A) and ETB receptor antagonist, could reverse vasospasm without inducing hypotension. In rabbits (single-hemorrhage model) and in dogs (double-hemorrhage model), SAH was induced; after vasospasm was established, the animals received intravenously either saline or a 30 mg/kg bolus of bosentan. The cross-sectional area of the basilar artery was analyzed by quantitative angiography. In rabbits (n = 13), bosentan reversed basilar vasospasm to the same extent as did an intravertebral injection of sodium nitroprusside. In dogs (n = 10), bosentan reversed only 52 +/- 10% of the vasospasm reversible by papaverine. Bosentan did not alter the heart rate or the arterial blood pressure in either the rabbits or the dogs. In the cerebrospinal fluid, SAH increased endothelin-1 (ET1) and big ET1 by 6 and 3.8 times, respectively; in the basilar artery, SAH increased ET1 concentration, big ET1 concentration, and ET-converting enzyme activity by 1.3, 2, and 2.7 times, respectively. In addition, a local involvement of ET was also suggested by the relaxing effect of bosentan on basilar artery rings from rabbits with SAH and not from control rabbits. Receptor binding studies performed on dog basilar arteries revealed a shift in the phenotype expression of ET receptors from the A to the B type after SAH. We conclude that ET plays a major role in SAH and that systemic ET blockade might selectively dilate spastic arteries.

Animals↗
PubMed1995

Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma.

Plasma and cerebrospinal fluid (CSF) concentrations of endothelin (ET)-1, ET-3, and big ET-1 in patients with aneurysmal rupture were measured serially for 2 weeks after the onset of aneurysmal subarachnoid hemorrhage (SAH) and compared with levels of ETs in patients without SAH and the plasma concentrations of ETs in normal volunteers. Big ET-1 was the predominant peptide present in the CSF of SAH patients. The CSF concentrations of big ET-1, ET-1, and ET-3 were significantly higher in older patients than in younger patients. In SAH patients with cerebral vasospasm (CVS) documented by transcranial Doppler sonography and clinical signs, postoperative concentrations of ETs in the CSF remained at or were increased above levels measured before surgery. In SAH patients without CVS, the concentrations of ETs in the CSF decreased with time, whereas the time course of CVS coincided with the increase in concentrations of big ET-1 and ET-1. The temporal dependence of concentrations of big ET-1 and ET-1 in SAH patients with and without CVS were significantly different. The volume of hematoma in the basal cisterns as detected by computerized tomography was predictive of the concentrations of ETs in the CSF. Plasma concentrations of ETs were not correlated with CVS. The possible role of ETs in the pathogenesis of CVS associated with SAH and the controversial data reported to date are discussed.

Adolescent↗
PubMed1995

[New therapeutic prospects in acute coronary thrombosis].

The principal new clinical approaches to the treatment of acute coronary thrombosis are reviewed. They include fibrinogen platelet receptor antagonists (anti GP IIb-IIIa) and direct thrombin inhibitors. The anti GP IIb-IIIa have been shown to be effective in unstable angina and in the prevention of acute coronary occlusion after transluminal angioplasty. Thrombin inhibitors, the leader being hirudine, also give promising results. The real clinical benefits of these agents and the risk of haemorrhage that they incur in monotherapy or in association, will only become clear when the results of large scale trials which are under way at present, become available. Other antiplatelet agents (clopidogrel, thromboxane inhibitors) are also discussed.

Acute Disease↗
PubMed1995

[Applications of luminescence reactions in life science].

Bioluminescence and chemiluminescence have emerged in the last decade as a major tool for biochemical and biological studies. Several very sensitive assays have been developed in our laboratory such as enzymatic assays, immunoassays and detection of nucleic acids. The use of a new instrumentation allowing to dimensional photon counting has permit the emergence of new investigations at the cellular level. In addition to the advantages of sensitivity and the real-time non-invasive nature of this detection system, the imaging potential of using low-light and photon counting video cameras has been particularly influential in establishing its ascendence over more traditional systems. This review provides a reflection in this field through several applications in life sciences.

Adenosine Triphosphate↗
PubMed1995

[Hirsutism. Two familial cases of 21-hydroxylase deficiency].

INTRODUCTION: One to six percent of women with hirsutism have 21-hydroxylase deficiency. Beyond these classical congenital forms, the most frequent cases present non-specific signs of hyperandrogenism. The diagnosis of the deficiency is based on 17-hydroxy-progesteron (17-OHP) assay before and after ACTH stimulation. CASE REPORT: We observed 2 sisters with a non-classical deficiency in 21-hydroxylase. Their phenotypes were very different: the elder sister had severe hirsutism and clitoromegaly and was overweight; the younger sister had more moderate hirsutism with no other signs of hyperandrogenism. Hormone patterns were also different. Both baseline and stimulated plasma 17-OHP were higher in the elder sister (47 ng/ml to 126 ng/ml and 5.2 ng/ml to 42.8 ng/ml respectively). The genotype was however identical. Both were homozygous for CYP21A duplication and short C4B and had a Val281Leu mutation on exon 7 of the CYP21B gene. DISCUSSION: This phenotypic variability in subjects with the same genotype could be explained by increased sensitivity to androgens or, more likely, to the presence of currently undetectable mutations. Genetic counselling is often requested due to the high frequency of non-classical forms and the large number of heterozygous subjects with the 21-hydroxylase trait. It is thus important to screen for 21-hydroxylase deficiency in women with hirsutism. In addition, molecular assessment of CYP21B gene should be proposed for all subjects with a non-classical form as well as family members (at least the father and mother).

17-alpha-Hydroxyprogesterone↗
PubMed1994

Specific mannose-6-phosphate receptor-independent sorting of pro-cathepsin D in breast cancer cells.

The secretion of pro-cathepsin D (pro-cath-D) in some human metastatic breast cancer cells (MCF7, MDA/MB231), contrary to normal mammary cells, is not increased by ammonium chloride treatment, indicating a mannose-6-phosphate-independent sorting to lysosomes. By studying a variety of cell lines and lysosomal enzymes, we show that secretion of newly synthesized pro-cath-D was not mediated by the 46-kDa mannose-6-phosphate receptor (MPR) and that its resistance to NH4Cl for secretion was specific to cath-D and not to other lysosomal enzymes. This resistance appeared to be correlated with the basal hypersecretion of pro-cath-D, but not with its overexpression. By contrast, pro-cath-D secretion was increased by NH4Cl in fibroblasts and nontumoral epithelial mammary cells, suggesting a specificity for cancer cells. Immunofluorescence staining showed that pro-cath-D, but neither cathepsin B nor beta-hexosaminidase, accumulated in intracytoplasmic vesicles of cells treated with ammonium chloride. In pulse--chase experiments and by subcellular fractionation on Percoll gradient, cath-D was found to be sorted into dense lysosomes whether cells were treated or not by NH4Cl. Treatment of cells with NH4Cl, however, inhibited processing and maturation of pro-cath-D, which was also observed in light vesicles in the absence of NH4Cl. Part of pro-cath-D, but not processed enzyme, was also found to be membrane associated in saponin-permeabilized cells. We conclude that in breast cancer cells, the MPR-independent pathway of pro-cath-D to lysosome is predominant compared to normal cells and other lysosomal enzymes. This alternative pathway should therefore be considered, in addition to MPR, to explain pro-cath-D sorting and activation in breast cancer cells.

Ammonium Chloride↗
PubMed1994

Effects of piracetam on indices of cognitive function in a delayed alternation task in young and aged rats.

The effects of piracetam (64, 128, and 256 mg/kg PO) on the performance of a delayed alternation in a Skinner Box were investigated. Test sessions consisted of 36 trials during which animals were first presented with a single lever (left or right) followed 5, 10, or 20 s later by two levers. A press on the lever opposite to that presented previously (nonmatching to sample) was rewarded. The number of correct responses and the reaction times to the one- and two-lever presentations were recorded. All animals received all treatments in a balanced order. Aged animals showed clear deficits on all three parameters. Piracetam was without effect on the performance of young animals but dose-dependently decreased the choice reaction times (two levers) in aged animals without affecting the other two parameters. These results suggest that piracetam does not affect short-term memory but may facilitate choice behavior in aged animals.

Aging↗
PubMed1994

[How do we read? Study of eye movement in reading].

Reading associates a perceptive time, a motor time and a cognitive time, all three phenomena being extremely interdependent. After a review of the physiological mechanisms of reading, the authors discuss, on the basis of experimentation in the normal subject, the results of a study involving electro-oculographic recording of reading.

Adult↗
PubMed1994

Experimental carotid thrombosis in the guinea pig.

The aim of our study was to develop a new carotid thrombosis model with an arterial shear rate close to that prevailing in affected arteries of patients with transient ischemic attacks (TIAs) and moderate carotid stenosis and to test various antithrombotic principles. In anaesthetized guinea pigs, carotid blood flow was monitored by a Doppler flow probe and the vessel was damaged by 2 or 3 brief pinches by a surgical forceps. The intravenous effects of aspirin (20 mg/kg), heparin (200 U/kg) and hirudin (500 micrograms/kg) or Ro 44-9883 (0.2 to 1 mg/kg), a new selective non-peptidic GP IIb-IIIa inhibitor were tested. After the damage, blood flow progressively decreased to zero and could regularly and reproducibly be restored by a mechanical shaking of the artery. The occlusive thrombus consisted mainly of platelet aggregates. The estimated shear rate in the damaged carotid artery was in the range of 1500 to 2800 s-1. The resulting cyclic flow variations (CFVs) were obtained in all the guinea pigs and were abolished in 10%, 20% and 60% of the animals treated with heparin, hirudin and aspirin, respectively. Ro 44-9883 abolished dose dependently the CFVs with 100% abolition at 1 mg/kg. Thus reproducible thrombosis without additional stenosis can be generated in the carotid artery of the guinea pig at a lower shear rate than that prevailing in the classical thrombosis models. GPIIb-IIIa blockade showed a higher curative efficacy than inhibition of the cyclooxygenase pathway or that of thrombin generation either through an antithrombin III dependent or independent mechanism.

Acetates↗
PubMed1993

Ro 44-9883, a new non-peptidic GPIIb-GPIIIa antagonist prevents platelet loss in a guinea pig model of extracorporeal circulation.

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 44-9883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 +/- 4% and 25 +/- 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 +/- 8% and 54 +/- 9%; p < 0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 +/- 8%) and only slightly decreased at 60 min (80 +/- 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

Acetates↗