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D Logeart

Publications and source records attributed to D Logeart.

46 records · Page 3Linked to original sources
PubMed1997

Fucans, sulfated polysaccharides extracted from brown seaweeds, inhibit vascular smooth muscle cell proliferation. II. Degradation and molecular weight effect.

Fucan, a sulfated polysaccharide extracted from brown seaweeds, inhibits smooth muscle cell (SMC) proliferation with a higher antiproliferative activity than heparin (Logeart et al., Eur. J. Cell Biol. 74, 1997, this issue). In order to investigate the structure-activity relationship of fucan on SMC growth, we have prepared by size exclusion chromatography fucan fractions of various molecular masses ranging from 5.5 to 556 kDa. Our experiments showed that the antiproliferative activity is dependent on the molecular weight of the polysaccharide. The molecular weight threshold indicated that about 30 saccharidic units on fucan were necessary to give the antiproliferative activity on SMCs. A kinetics study of DNA synthesis using tritiated thymidine uptake was also performed with different molecular weight fucan fractions. Although all tested fractions acted as soon as the cells enter the first cell cycle, the duration and potency of action varied. Moreover, displacement experiments of iodinated fucan revealed that the low molecular fucan fraction interacted weakly with the binding sites. Finally, gel permeation chromatography of internalized radiolabeled heparin and fucans was performed with SMCs. A rapid degradation of internalized heparin was observed, whereas only low molecular weight fucan fractions were partially degraded by SMCs. Together, these results indicate the significance of molecular weight on the antiproliferative activity of fucans on SMCs, and might help to understand their mechanism of action. In addition, the degradation experiments with internalized heparin and fucans ruled out a direct link between polysaccharide degradation and the antiproliferative effect on SMCs.

Animals↗
PubMed1996

Collagen synthesis by vascular smooth muscle cells in the presence of antiproliferative polysaccharides.

Production of various components of the extracellular matrix (ECM) modulates biological functions of the vascular tissue. This process is generally amplified in pathologic states as atherosclerosis. Atheroma originates from smooth muscle cells (SMC) which have migrated and proliferated in the vascular intima. In this study we investigated protein synthesis, collagen synthesis, and types I, III, and V collagen distribution by SMC in the presence of three families of watersoluble polysaccharides, heparin, fucans, and derivatized dextrans. We observed that fucan and derivatized dextran were able, as was heparin, to inhibit rat aortic SMC growth in culture. We then analyzed collagen modulation by measuring the incorporation of the radiolabeled precursor (3H)-proline into vascular SMC. Our results showed uncoupling of the antiproliferative capacity with collagen biosynthesis. However, fucan, the most antiproliferative polysaccharide, was also the most active in inhibiting protein and collagen synthesis. In addition, compounds that decreased total collagen synthesis preferentially increased the proportion of cell-associated collagen. Interestingly, only the antiproliferative polysaccharides inhibited significantly type V collagen biosynthesis. These new biomaterials appear to be valuable tools to study and control extracellular-matrix interactions with cells from the vascular walls.

Animals↗
PubMed1995

Hemodynamic criteria for diagnosis of right ventricular ischemia associated with inferior wall left ventricular acute myocardial infarction.

To test the diagnostic value of different hemodynamic indexes for the diagnosis of acute right ventricular (RV) ischemic dysfunction, we studied 2 groups of consecutive patients admitted for an acute left ventricular inferior wall myocardial infarction: 51 patients with (group 1) and 32 patients without (group 2) RV ischemia as determined by coronary angiography. In both groups, we analyzed by right-sided cardiac catheterization right-sided heart pressures, pulmonary capillary wedge pressure, and cardiac index. We also calculated pressure ratios (mean right atrial pressure or RV end-diastolic over pulmonary capillary wedge pressures), pulmonary vascular resistance, and RV stroke work index. We found significant differences (p < 0.01) between the 2 groups when comparing mean right atrial pressure, RV end-diastolic pressure, ratio of these 2 pressures over pulmonary capillary wedge pressure, RV stroke work index, and right atrial and RV pressure waveforms. The best combined sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were found for the right atrial M or W waveform pattern, isolated or combined with a disproportionate elevation of RV end-diastolic over pulmonary capillary wedge pressures (respectively, 92%, 94%, 90%, 87%, and 89%). Volume loading was performed in 27 patients (18 with and 9 without RV ischemia). Right heart pressures and RV stroke work index increased significantly and similarly in both groups. Cardiac index increased significantly only in patients without RV ischemia (p = 0.02). However, volume loading did not significantly modify the diagnostic value of the different hemodynamic criteria studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Derivatized dextrans modulate collagen synthesis in aortic smooth muscle cells.

The effect of specifically derivatized dextrans, with or without antiproliferative activity on smooth muscle cells (SMC), was investigated on type I and type III collagen biosynthesis and mRNA levels in post-confluent SMC cultures. Our results indicate that dextran derivatives decreased total protein and collagen synthesis independently of their antiproliferative activities. However, the most substituted dextran, the one exhibiting the strongest antiproliferative activity towards SMC, was the most active in modulating type III collagen expression. In addition, only the two dextran derivatives bearing benzylamide groups inhibited collagen excretion.

Animals↗
PubMed1995

Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart.

Troponin T, like many myofibrillar proteins, exists as multiple isoforms encoded by distinct genes or generated by splicing of the same primary RNA transcript. We have previously cloned the first human cardiac troponin T (cTnT) cDNA and showed the differential expression of cTnT in cardiac and skeletal muscle during ontogenic development. In this work we located the human cTnT gene by means of fluorescent in situ hybridization to 1q32 and, by sequencing thirteen cDNAs isolated from a human fetal heart cDNA library, identified three new isoforms resulting from specific combinations of three variable regions in human cTnT cDNA. The first variable region is a 30-bp box located at the 5' end of the cDNA, which can be excised either totally or only from the first 3 bp onwards; the second is a codon which can be completely excised; and the third is a 9-bp box in the 3' half of the cDNA, which can also be excised either totally or only from the first 3 bp. The existence of the corresponding RNAs in fetal and adult ventricles was confirmed by RNase protection studies. No accumulation of the fetal isoforms was found in failing ventricles compared with controls.

Aged↗
PubMed1993

Antiproliferative capacity of synthetic dextrans on smooth muscle cell growth: the model of derivatized dextrans as heparin-like polymers.

Proliferation of vascular smooth muscle cells (SMC) is postulated to be a key step in the pathogenesis of atherosclerosis or restenosis after vascular interventions such as angioplasty. Natural glycosaminoglycans, such as heparin and heparan sulfate, are known for their ability to inhibit SMC proliferation in vivo and in vitro. The antiproliferative activity of synthetic derivatized dextrans exhibiting heparin-like anticoagulant and anticomplement capacities have been investigated with rat aorta smooth muscle cells in culture. We report here that some derivatized dextrans grafted with benzylamide sulfonate moieties are potent antiproliferative agents for rat smooth muscle cell (SMC) in vitro. These synthetic polymers inhibit the SMC proliferation as well as heparin. The SMC growth inhibition is dose dependent, reversible and non-toxic. Highly anionic carboxylic dextrans are not capable of inhibiting the SMC growth, excluding a simple charge effect mechanism. Using fluorescent (DTAF) probes, we demonstrated that the synthetic antiproliferative polymers and heparin are internalized into the SMC. No binding or internalization was observed with native dextran devoid of antiproliferative capacity. We conclude that a suitable distribution of functional groups on the dextran backbone can simulate heparin activity in terms of antiproliferative capacity on SMC growth.

Animals↗
PubMedDate not supplied

Increasing endothelial cell permeability improves the efficiency of myocyte adenoviral vector infection.

BACKGROUND: Gene delivery to the myocardium using blood-borne adenoviral vectors is hindered by the endothelium, which represents a barrier limiting the infection rate of underlying myocytes. However, endothelial permeability may be modulated by pharmacological agents. METHODS: In the present study, we modeled the endothelial barrier in vitro using a human umbilical vein endothelial cell (HUVEC) monolayer seeded on a Transwell membrane as a support and diffusion of fluorescent dextrans as a permeability index. We used alpha-thrombin (100 nM) as a pharmacological agent known to increase endothelial permeability and tested the barrier function of the endothelial cell monolayer on adenovector-mediated luciferase gene transfer to underlying isolated cardiac myocytes. RESULTS: A confluent HUVEC monolayer represented a considerable physical barrier to dextran diffusion; it reduced the permeability of the micropore membrane alone to fluorescein isothiocyanate (FITC)-labeled dextrans of molecular weights 4, 70, 150 and 2000 kDa by approximately 54, 78, 88 and 98%, respectively. Alpha-thrombin (100 nM) increased the permeability coefficients (P(EC)) by 276, 264, 562 and 4166% for the same dextrans, respectively. A confluent HUVEC monolayer represented a major impediment to adenovector-mediated luciferase gene transfer to cardiac myocytes, largely reducing gene transfer efficiency. However thrombin induced a nine-fold increase in myocyte infection. CONCLUSION: In our model, the endothelial cell monolayer represents a major impediment to myocyte adenovector-mediated gene transfer which can be partially improved by pharmacologically increasing endothelial permeability. The Transwell model is therefore particularly useful for testing the efficiency of pharmacological agents in modulating adenovector passage through the endothelial barrier.

Adenoviridae↗
PubMedDate not supplied

[Acute myocardial infarction. Experiences of the referral network of the Beaujon and Bichat hospitals (with the collaboration of the Emergency Medical and Resuscitation Service of Beaujon)].

OBJECTIVES: Hospital management of acute myocardial infarction raises many problems in terms of medical care and organization, especially concerning the use or not of emergency corongraphy and angiography. We assessed the pertinence and consequences of a referral network operating between two cardiology units at the Beaujon and Bichat hospitals in Paris. All interventional procedures were performed at the Bichat unit. Prehospital emergency care units were integrated into the exprience and informed of indications for first line coronarography. METHODS: All cases of myocardial infarction admitted within 6 hours to the two units between 1993 to 1996 were analyzed and compared. RESULTS: Indications for referral from Beaujon to Bichat for emergency coronarography and possible angioplasy declined from 21% in 1993 to 10% in 1996. This decline was particularly noteworthy for first intention indications suggesting improved prehospital selection since the number of cases of acute myocardial infarction admitted to Beaujon remained unchanged. Certain patient characteristics differed between the two units: age (68.4 +/- 12.9 years at Beaujon versus 60.5 +/- 13.6 years at Bichat in 1996, p < 0.01) and reperfusion attempts (73% versus 90% in 1996 respectively, p < 0.01). The rate of fatal and non-fatal events were not different: 40 and 40% at Beaujon and 38 and 28% at Bichat in 1993 and 1996 respectively. CONCLUSION: These findings demonstrate that a management network can operate effectively between two hospital cardiology units and emergency care structures, allowing better patient selection for emergency coronography and possible angioplasty.

Age Factors↗