PubMed Health⌕ Search

Biomedical subjects

M Seigneur

Publications and source records attributed to M Seigneur.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of the antioxidants selenium and beta-carotene on HIV-related endothelium dysfunction.

Patients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-seropositive subjects with 100 microg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers. The non-supplemented patients experienced increases in von Willebrand factor and soluble thrombomodulin (both p <0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene. Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.

Antioxidants↗
PubMed1997

[Assay of plasma thrombomodulin in systemic diseases].

Membrane thrombomodulin (TM) is a very efficient natural anti-thrombin glycoprotein with anticoagulant properties expressed on endothelial cell surface. Circulating plasmatic thrombomodulin (TMp) detected by enzyme immunoassay in plasma is considered as a cell marker of endothelial injury. The TMp levels are increased in many conditions (diabetes mellitus, atheromatous disease...). In cases of collagen vascular diseases, where vascular endothelium damage is suspected, TMp is increased particularly in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). It is noteworthy that the TMp level is correlated with disease activity. Since TMp is a non specific marker of endothelial damage, it may be of interest as a useful marker for the supervision of these diseases. Further studies are needed on larger series. TMp level change during spontaneous evolution or under treatment will help determine wether TMp is a predictor and prognostic marker of these systemic diseases.

Acute Disease↗
PubMed1997

Circulating endothelial cell markers in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease.

We examined the relationship between specific endothelial cell markers soluble E-selectin, von Willebrand factor and soluble thrombomodulin and the location or extent of atherosclerosis by analysing plasma samples from 200 patients with symptomatic peripheral vascular disease and 213 age- and sex-matched asymptomatic control subjects. Using ELISAS, we found increased von Willebrand factor and thrombomodulin (both P < 0.0001) in the patients relative to the control subjects, but no significant change in soluble E-selectin. Soluble thrombomodulin was increased in patients with disease at one locus (i.e. of the carotid or iliac/femoral arteries), with an additional significant increase in patients with disease at multiple loci (i.e. any combination of carotid, coronary or iliac/femoral artery disease). No marker differentiated carotid artery disease from iliac/femoral artery disease. We conclude that von Willebrand factor is a marker of generalized atherosclerosis, but that soluble thrombomodulin is related to the extent of disease. Further research into these endothelial cell products are warranted to explore their diagnostic and/or prognostic potential.

ABO Blood-Group System↗
PubMed1997

uvrD mutations enhance tandem repeat deletion in the Escherichia coli chromosome via SOS induction of the RecF recombination pathway.

It has previously been shown that recombination between tandem repeats is not significantly affected by a recA mutation in Escherichia coli. Here, we describe the activation of a RecA-dependent recombination pathway in a hyper-recombination mutant. In order to analyse how tandem repeat deletion may proceed, we searched for mutants that affect this process. Three hyper-recombination clones were characterized and shown to be mutated in the uvrD gene. Two of the mutations were identified as opal mutations at codons 130 and 438. A uvrD::Tn5 mutation was used to investigate the mechanism of deletion formation in these mutants. The uvrD-mediated stimulation of deletion was abolished by a lexAind3 mutation or by inactivation of either the recA, recF, recQ or ruvA genes. We conclude that (i) this stimulation requires SOS induction and (ii) tandem repeat recombination in uvrD mutants occurs via the RecF pathway. In uvrD+ cells, constitutive expression of SOS genes is not sufficient to stimulate deletion formation. This suggests that the RecF recombination pathway activated by SOS induction is antagonized by the UvrD protein. Paradoxically, we observed that the overproduction of UvrD from a plasmid also stimulates tandem repeat deletion. However, this stimulation is RecA independent, as is deletion in a wild-type strain. We propose that the presence of an excess of the UvrD helicase favours replication slippage. This work suggests that the UvrD helicase controls a balance between different routes of tandem repeat deletion.

Adenosine Triphosphatases↗
PubMed1997

Blocking rolling circle replication with a UV lesion creates a deletion hotspot.

UV light irradiation increases genetic instability by causing mutations and deletions. The mechanism of UV-induced rearrangements was investigated making use of deletion-prone plasmids. Chimeric plasmids carrying pBR322 and M13 replication origins undergo deletions that join the M13 replication origin to a random nucleotide. A restriction fragment was UV irradiated, introduced into such a hybrid plasmid and deletions formed at the M13 origin were analysed. In most of the deletant molecules, the M13 replication nick site was linked to a nucleotide in the irradiated fragment, showing that UV lesions are deletion hotspots. These deletions were independent of the UvrABC excision repair proteins, suggesting that the deletogenic structure is the lesion itself and not a repair intermediate. They were not found in the absence of M13 replication, indicating that they result from the encounter of the M13 replication fork with the UV lesion. Furthermore, UV-induced deletions occurred independently of pBR322 replication. We conclude that, in contrast to pBR322 replication forks, M13 replication forks blocked by UV lesions are deletion prone. We propose that the deletion-prone properties of a UV-arrested polymerase depend on the associated helicase.

Adenosine Triphosphatases↗
PubMed1997

Soluble adhesion molecules and endothelial cell damage in HIV infected patients.

Endothelial damage is present in HIV infection but our understanding of markers and mechanisms is incomplete. We found increased levels of markers of endothelial cell damage such as von Willebrand factor (vWf), soluble thrombomodulin (sTM) and adhesion molecule E-selectin in 90 subjects seropositive for HIV relative to healthy controls. sTM was strongly raised in those patients with the lowest CD4+ cell count (p < 0.001), but levels of vWf increased at each incremental fall in CD4+ cell count and the two indices correlated significantly (r = -0.485, p < 0.001). vWf correlated strongly with levels of the inflammatory cytokines tumor necrosis factor (TNF-alpha) and alpha interferon (IFN-alpha) but sTM correlated only weakly with IFN-alpha. We suggest that increased vWf is largely the result of inflammatory stimulus of the endothelium but that sTM is found only in those patients with more severe disease, and so truly represents endothelial damage.

Adolescent↗
PubMed1996

Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis.

OBJECTIVES: To test the hypothesis that endothelial cell damage and hypoxia are related to the activity of neutrophil elastase in patients with peripheral atherosclerosis. DESIGN: A cross-sectional serological study in a tertiary referral, University Hospital. MATERIALS: Venous blood was obtained from 22 patients with peripheral vascular disease and an equal number of age and sex matched controls. METHODS: Neutrophil elastase and two markers of endothelial cell damage (von Willebrand factor and soluble thrombomodulin) were measured in plasma by ELISA. Hypoxia was measured by percutaneous oxygen (by oximeter) at the dorsum of the foot. RESULTS: Patients had higher von Willebrand factor, higher soluble thrombomodulin and higher elastase but lower percutaneous oxygen (all p < 0.001). In the patient's group, there were significant inverse correlates between von Willebrand factor and percutaneous oxygen (p = 0.004) and between soluble thrombomodulin and percutaneous oxygen (p = 0.011) while elastase correlated positively with soluble thrombomodulin (p = 0.023). CONCLUSIONS: Our data support the hypothesis that release of elastase from activated neutrophils relates to endothelial cell damage. This may contribute to hypoxia and may result in the deterioration in clinically assessed atherosclerosis.

Arteriosclerosis↗
PubMed1996

Endothelium activation related increase of soluble intercellular adhesion molecule-1 in human schistosomiasis. Lack of correlation with serology.

Soluble intercellular adhesion molecule-1 (sICAM-1) level was measured in sera from 41 patients with Schistosoma mansoni schistosomiasis and compared with the sICAM-1 level in 41 healthy subjects. A significant increase in serum sICAM-1 was observed in patients with schistosomiasis compared with control subjects. As they were inhabitants of the French Antilles, the patients were, however, not settled in a malaria endemic zone, allowing this cause of sICAM-1 enhancement to be eliminated. No correlation was found between the level of sICAM-1 and the schistosomiasis serological titre. Such results favour the hypothesis of an activation of vascular endothelial cells due to egg deposition.

Endothelium, Vascular↗
PubMed1996

Influence of hypoxia and hypoxia-reoxygenation on endothelial P-selectin expression.

P-selectin is an endothelial adhesion molecule involved in the initial step of the neutrophil recruitment. We investigated the effect of hypoxia (95% N2, 5% CO2) and of hypoxia-reoxygenation (95% air, 5% CO2) on the expression of P-selectin by human umbilical vein endothelial cells (HUVEC). P-selectin expression was detected by immunolabelling and quantified by flow cytometric analysis. Our data indicate that hypoxia induces an increase in P-selectin expression with a maximum reached after 90 minutes. A hypoxic exposure of 90 minutes results in a highly significant increase compared to normoxia (p < 0.001, n = 13). Furthermore, when a reoxygenation period follows 90 minutes of hypoxia, the initially elevated levels of P-selectin are dramatically enhanced with a maximum obtained after 60 minutes of reoxygenation.

Cell Hypoxia↗
PubMed1996

Effect of buflomedil on the neutrophil-endothelial cell interaction under inflammatory and hypoxia conditions.

In hypoxia/ischaemia and ischaemia/reperfusion, human neutrophils are likely to play an important role in the development of endothelial cell damage in the microcirculation. Buflomedil hypochloride improves the capillary perfusion in such related situations, evoking a possible effect upon neutrophils. Using in vitro models of cell adhesion, buflomedil decreased 100% of histamine related neutrophil adhesion (flow system) and partially inhibited adhesion after IL-1-4 hours (flow and stable systems). Hypoxia induced neutrophil adhesion (4 hours) was also reduced by buflomedil, which decreased the expression of P-selectin at the surface of endothelial cells. As adenosine (NECA) exhibited the same results in hypoxia and theophylline inhibited them, such results support an action of buflomedil presumably via the A2 receptor.

Adenosine↗
PubMed1996

Vascular endothelial lesion in patients undergoing bone marrow transplantation.

Changes in endothelial cell activity are likely to play a role in the thrombotic complications of bone marrow transplantation (BMT) such as the development of veno-occlusive disease. Accordingly, we measured established plasma endothelial cell markers von Willebrand factor (vWf), soluble thrombomodulin (sTM), soluble ICAM-1 (sICAM-1), and possible inducers of these molecules, TNF alpha and elastase, in the plasma of 25 patients, 1 week before as well as 1 and 3 weeks after BMT. Compared to healthy age and sex-matched controls, patients exhibited increased vWf and sTM. One week after transplantation, there were significant increases in vWf and sICAM-1, with a significant fall in elastases. Three weeks after the transplantation, sICAM-1 and, to a lesser extent, vWf increased still further, whereas elastases were unchanged. There were no significant changes in sTM and in TNF alpha through the serial study. Our data suggest that before conditioning, vascular endothelium is damaged by both injury and activation, as seen by the variations of vWf and sTM. After transplantation, the enhancement of this damage seems to be more specifically related to activation, since we observed a strong subsequent increase in vWf and markedly in sICAM-1.

Adolescent↗
PubMed1996

Soluble P selectin in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease and its risk factors.

Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in the plasma of patients with atherosclerosis, but its relationship to the anatomical location of symptomatic disease or extent of symptomatic disease is unknown. The influence of the risk factors for atherosclerosis on soluble P-selectin is also unclear. To clarify these questions we analysed plasma samples from 170 patients with symptomatic peripheral vascular disease and 119 asymptomatic controls who were, as a group, age- and sex-matched. Soluble P-selectin (ELISA) was increased in 83 patients with symptomatic disease of the iliac and/or femoral arteries alone (P < 0.05, ANOVA) but not in 37 patients with symptomatic carotid artery disease alone compared with controls. Soluble P-selectin was equally raised in 120 patients with disease at one arterial site and in 50 patients with disease at two or more arterial sites (both P < 0.05) compared with controls. Smoking and atherosclerosis were both independent predictors of raised soluble P-selectin. We conclude that increased soluble P-selectin may have value as a marker of peripheral vascular disease of the iliac and/or femoral arteries in group comparisons only, as the poor discrimination and wide variation of data make comparisons at the individual level difficult.

Aged↗
PubMed1995

Influence of pentoxifylline on membrane thrombomodulin levels in endothelial cells submitted to hypoxic conditions.

Thrombomodulin (TM) expression at the surface of endothelial cells is upregulated by cAMP analogues, whereas hypoxic conditions induce a decrease in this expression. Pentoxifylline (PTX) enhances the intracellular levels of cAMP in human umbilical vein endothelial cells (HUVECs). We therefore investigated the influence of this drug on TM expression in cells submitted to hypoxia. TM expression was quantified at the surface of HUVECs in the presence or absence of PTX during 18 h of incubation. Membrane TM was immunolabeled with a fluorescent monoclonal antibody and the expression was quantified by flow cytometric analysis. Our preliminary data revealed that PTX at 0.01 microM significantly increased TM expression levels compared with cells in hypoxia without the drug. Therefore, at this low dose PTX appears able to counterbalance the procoagulant effect of hypoxia.

Cell Membrane↗
PubMed1995

Asymptomatic atherosclerosis in HIV-positive patients: A case-control ultrasound study.

Atherosclerosis has been reported in some HIV-positive subjects without any known risk factor. The purpose of the present study was to investigate cervical arteries, abdominal aorta and femoral arteries by B-mode ultrasonography and doppler in 30 HIV-positive subjects matched to 18 controls for sex, age, tobacco consumption and arterial hypertension. Although no haemodynamically or clinically relevant lesions were found, plaques occurred more often in patients than in controls (11 patients, 36.7% vs. 2, 11.1%; P = 0.05). Compared to the HIV-positive patients without plaques, those with plaques had a tendency to have decreased lower HDL cholesterol, higher tobacco consumption and lower CD4-cell count (77 +/- 85/mm3 vs. 220 +/- 202/mm3). The patients with plaques (but not those without plaques) had lower HDL cholesterol than controls (P = 0.03). Asymptomatic atherosclerosis seems to be more frequent in HIV-positive patients and is associated to lower HDL cholesterol.

Adult↗