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Biomedical subjects

Y Denizot

Publications and source records attributed to Y Denizot.

At least 73 records · Page 4Linked to original sources
PubMed1996

Human bone marrow fibroblasts--an overview of their characterization, proliferation and inflammatory mediator production.

Bone marrow fibroblasts regulate hematopoiesis by interacting directly (cell-to-cell contact) with hematopoietic cells and by secreting regulatory molecules (such as GM-CSF, M-CSF, IL6 and LIF) that modulate hematopoiesis either in a positive or a negative manner. Several cytokines (such as bFGF, EGF, PDGF and TGF-beta) affect the growth of human marrow fibroblasts in vitro. Further in vivo studies are still required to clarify the role of marrow fibroblasts and their interactions with hematopoietic progenitors during myelofibrosis and leukemic diseases.

Bone Marrow↗
PubMed1996

PAF and haematopoiesis: IX. Platelet-activating factor increases DNA synthesis in human bone marrow cells.

Platelet-activating factor (PAF) is present in human bone marrow leading us to investigate its effect on human bone marrow cell proliferation. While PAF (0.1 microM to 1 nM) stimulates the incorporation of [3H]thymidine by freshly isolated adherent human bone marrow cells, PAF has no effect on non adherent cells. A non-metabolizable PAF agonist is more potent than PAF to stimulate thymidine incorporation in adherent cells. The precise role of PAF in human haematopoiesis in vivo remains to be clarified.

Bone Marrow↗
PubMed1996

Regulation of platelet-activating factor production in gastric epithelial cells.

The authors have previously reported that platelet-activating factor (PAF), a phospholipid mediator with potent proinflammatory activities, is produced in the gastric mucosa and stimulates gastric acid secretion in humans and animals. In the present study they used the human gastric tumour cells HGT1 (clone 6) to examine whether PAF production is regulated by neuromediators. PAF was extracted by ethanol and assayed by the washed platelet aggregation test. HGT1 cells produced PAF spontaneously (110 +/- 20 pg 10(6) cells). The addition of vasoactive intestinal peptide (VIP; 10(-9) to 10(-7) mol L(-1)) or of histamine (10(-5) to 10(-3) mol L(-1)) increased PAF production by three- to fivefold, while the addition of carbachol (10(-7) to 10(-4) mol L(-1)) increased PAF production up to sevenfold. PAF production was also increased up to 10- to 13-fold, in a dose- and time-dependent manner, by the addition of calcium and two- to threefold by the addition of phorbol myristate acetate (PMA; 10(-7) to 10(-5) mol L(-1)). However, the addition of dibutyryl cyclic AMP (dBcAMP; 10(-6) to 10(-4) mol L(-1) was without any effect. This is the first report showing PAF production by gastric epithelial cells in response to histamine, VIP and carbachol. Furthermore, the findings are consistent with a central role of calcium in this production. The results of this study, together with those of previous studies from the authors' laboratory, support the hypothesis that PAF is a physiological mediator of gastric acid secretion.

Animals↗
PubMed1996

PAF and hematopoiesis. VIII. Biosynthesis and metabolism of PAF by human bone marrow stromal cells.

Human bone marrow stromal cells were studied for their ability to synthesize and to metabolize platelet-activating factor (PAF), a lipidic compound with potent immunoregulatory properties. When stimulated with 2 microM calcium ionophore for 60 minutes, cultures of stromal cells increased their PAF production (3.52 +/- 0.91 ng/1 x 10(6) cells) compared with controls (0.82 +/- 0.13 ng/1 x 10(6) cells). Addition of exogenous lyso PAF (100 nM) and acetyl-CoA (100 microM) during calcium ionophore stimulation did not change the PAF production. The synthesis of PAF was not influenced by the concentration of albumin in the incubation buffer. The PAF from stromal cells exhibited a hexadecyl chain at the sn-1 position of the molecule, as determined by reverse-phase HPLC. While stromal cells contained low amounts of PAF acetylhydrolase activity and did not secrete it in the culture medium, they metabolized exogenous PAF with 1-alkyl-2-acyl-glycero-phosphocholine and neutral lipids as the major metabolic products. The present results are the first to demonstrate the synthesis and metabolism of PAF by human bone marrow stromal cells. These data suggest that they might be a source of the PAF found in the human bone marrow and/or might be important in the regulation of its levels. The role of PAF on the proliferation and functions of human hematopoietic cells deserves investigation.

Bone Marrow↗
PubMed1995

PAF and haematopoiesis: III. Presence and metabolism of platelet-activating factor in human bone marrow.

Platelet-activating factor (PAF) is a phospholipid compound with major immunoregulatory activities. The present study shows that human bone marrow contains 576 +/- 39 pg PAF/ml (n = 35). Bone marrow-derived PAF exhibits the same biophysical and biological properties that synthetic PAF. PAF concentrations in bone marrow are correlated with the granulocyte (r = 0.4, P = 0.02) but not with the lymphocyte (r = 0.24, P = 0.17) and the monocyte (r = 0.12, P = 0.48) counts. In bone marrow PAF is inactivated by a plasma PAF acetylhydrolase activity (48.0 +/- 2.3 nmol/min per ml, n = 34). Experiments with [3H]PAF indicate that human bone marrow cells actively metabolize this potent molecule by the deacetylation-transacylation pathway. Results of this investigation indicate the permanent presence of significant amounts of PAF in bone marrow suggesting its putative involvement in the processes of bone marrow cell proliferation and maturation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

PAF and haematopoiesis. IV. Modifications of spleen and thymus PAF contents after a single dose of the chemotherapeutic drug 5-fluorouracil in mice.

The spleen and thymus of mice were examined for the presence of PAF after injection of 5-fluorouracil (5-FU) (200 mg/kg). A significant increase of the spleen (P = 0.005) and thymus (P < 0.05) PAF concentrations was noted 48 h after 5-FU infusion. PAF levels in thymus are similar to those of controls from days 4 to 14. By contrast, spleen PAF significantly decreased (0.005 < P < 0.03) from days 7 to 14. Conversely, the 5-FU administration did not modify the spleen and plasma acetylhydrolase activity, suggesting that the variations of PAF levels in thymus and spleen were mainly due to differences of local PAF production. Thus, the chemotherapeutic drug 5-FU modulates in vivo PAF production in haematopoietic organs of mice. Considering the effects of PAF in the processes of B- and T-cell proliferation and functions, these results could be of importance for the role of PAF during human cancer therapy and haematopoiesis in vivo.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Effects of a paf-receptor antagonist on hemodynamics during and after cardiopulmonary bypass.

OBJECTIVES: To assess after cardiopulmonary bypass (CPB) the role of paf-acether (paf), a phospholipid mediator whose injection in animal mimics the hemodynamics observed after CPB. DESIGN: Prospective double-blind randomized study. SETTING: Single institutional university hospital. PARTICIPANTS: 18 patients scheduled to undergo coronary artery bypass graft. INTERVENTIONS: 18 patients randomly received a placebo (n = 8) or 120 mg BN52021 (n = 10), a paf-receptor antagonist injected twice just before vascular cannulation and before cross-clamp release. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were performed with a pulmonary artery and a radial artery catheter before and after the first injection of BN52021 or placebo, at the end of CPB, 1, 15, and 30 minutes after protamine infusion, then 6 hours and 24 hours postoperatively. BN52021 infusion, did not affect hemodynamic parameters. After CPB, the pulmonary artery pressures, the cardiac index, and the pulmonary artery occlusion pressures were statistically the same between groups. By contrast, the pulmonary vascular resistances (1.5 +/- 0.5 IU v 4.5 +/- 0.6 IU, p < 0.05), the right ventricular systolic work index (5.3 +/- 0.91 g m m-2 v 9.37 +/- 1.02 g m m-2, p < 0.05) and the transpulmonary gradient (4.7 +/- 1.1 mmHg v 12.0 +/- 1.2 mmHg, p < 0.05) were lower in the BN52021 group as compared with the placebo group. After protamine infusion, these differences between groups disappeared. CONCLUSION: Because the inotropic and vasodilator therapy and the volume loading were the same between groups, this study suggests that pretreatment with a paf-receptor antagonist improves post-CPB pulmonary resistance. Nevertheless, this beneficial effect is transient without consequences on left ventricular function indices.

Blood Pressure↗
PubMed1994

PAF and hematopoiesis. II. Elevated levels of plasma paf acetylhydrolase after rapid infusion of 5-fluorouracil in cancer patients.

Blood platelet-activating factor (PAF) levels are regulated by a plasma PAF acetylhydrolase. We investigated its levels in cancer patients during the course of a 5-day 5-fluorouracil (5-FU) treatment. PAF acetylhydrolase increased in nine patients with daily bolus infusion of 0.4 g 5-FU per m2 of body surface (81.7 +/- 8.7 nmol PAF/min/ml vs. 66.6 +/- 7.0; P < 0.001 for day 5 as compared to day 1). By contrast PAF acetylhydrolase did not change in seven patients with continuous infusion of 5-FU. The meaning of these results is discussed in respect of the immunoregulatory role of PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

Stimulated human gastric tumor cells (HGT) fail to synthesize eicosanoids.

HGT cells are a human gastric tumor cell line. Preliminary data have shown that HGT cells incorporate exogenous arachidonic acid (AA) in their membrane lipids. However, we found that HGT cells are unable to produce significant amounts of AA metabolites after stimulation with calcium ionophore A23187. Furthermore, no lipoxygenase activity was detected in crude HGT cell extracts by employing an assay monitoring the in vitro utilization of linoleic acid. The meaning of these results is discussed in respect of the role of eicosanoids during cell proliferation.

Calcimycin↗
PubMed1994

The decreased transfer of arachidonic acid from triglycerides to phospholipids during proliferation of a human gastric tumor (HGT) cell line is not linked to modification of membrane fluidity.

Prelabeling-chase experiments with [14C]arachidonic acid in human cancer gastric cells (HGT) indicated a preferential incorporation of arachidonic acid into triglycerides followed by a transfer to phospholipids. This phenomenon was quicker using cells in log phase growth than in quiescent phase and was not linked to modification of HGT membrane fluidity assessed by the fluorescence polarization of the 1,6-diphenyl hexatriene probe. By contrast, growing cells in a medium enriched with oleic or linoleic acids increase plasma membrane fluidity. The importance of the site of arachidonic incorporation in HGT lipid is discussed.

Arachidonic Acid↗