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F Dupuis

Publications and source records attributed to F Dupuis.

At least 19 recordsLinked to original sources
PubMed2002

Structural features of prions explored by sequence analysis I. Sequence data.

Animal prion proteins (PrPs) form at the sequence level a very homogenous and 'closed' family. Therefore, few of their structural and functional features can be gleaned from sequence comparison as is now possible on a wide scale for other protein families. To detect putatively related proteins (at the structural and/or functional level), we used a battery of sequence analysis tools. This analysis resulted in (i) the identification of a putative 'prion-like' domain within the envelope of foamy retroviruses, (ii) the detection of putative similarities between prions and an interferon-inducible membrane protein, and (iii) the proposal that of the TATA-box-binding protein is a structural scaffold, which might allow understanding of a key event leading to the structural conversion from PrP(C) (normal cellular prion structure) towards PrP(Sc) (pathogenic structure).

Amino Acid Sequence↗
PubMed2002

Structural features of prions explored by sequence analysis. II. A PrP(Sc) model.

Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which the beta strand content increases and that of the a helix decreases. However, the structure of the pathogenous form PrP(Sc), occurring after conformational conversion of the normal cellular form PrP(C), is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrP(C) structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrP(Sc). In the present analysis, we detail the schematic construction of PrP(Sc) monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore may provide further insights into the structurally and functionally elusive PrP protein. Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions.

Amino Acid Sequence↗
PubMed2001

Cerebral arteriolar structure and function in pinealectomized rats.

We examined cerebral arteriolar structure and autoregulation of cerebral blood flow (CBF) in control (n = 8), sham-operated (n = 8), pinealectomized (n = 10), and pinealectomized plus melatonin-treated (0.51 +/- 0.01 mg x kg(-1) x day(-1) in drinking water, n = 9) young Wistar rats. The lower limit of CBF autoregulation (LLCBF) was determined by measurement of CBF (in arbitrary units, laser Doppler) during stepwise hypotensive hemorrhage; the arteriolar internal diameter (ID; in microm, cranial window) was also measured. Measurements of ID were repeated during a second stepwise hypotension after smooth muscle cell deactivation (67 mmol/l EDTA). The cross-sectional area (CSA) was measured by histometry. CSA and EDTA-induced vasodilatation decreased after pinealectomy (517 +/- 21 vs. 819 +/- 40 microm(2) in sham and 829 +/- 55 microm(2) in control, P < 0.05, and 81 +/- 4 vs. 102 +/- 5 microm in sham and 104 +/- 4 microm in control, P < 0.05, respectively) and were restored by melatonin (924 +/- 39 microm(2) and 102 +/- 5 microm, respectively). These results suggest that melatonin deprival makes the arteriolar wall thinner and stiffer. However, these changes had little effect on LLCBF. In conclusion, pinealectomy of young rats induces atrophy and decreases distensibility of the cerebral arteriolar wall; these effects are prevented by melatonin. They do not modify LLCBF.

Animals↗
PubMed2000

Concussions in athletes produce brain dysfunction as revealed by event-related potentials.

We have used event-related potentials (ERP) to assess cerebral activity following mild traumatic brain injuries in 20 college athletes practising contact sports. Concussion victims showed a striking decrease in P300 amplitude, an effect presumed to reflect alterations in attentional-cognitive processes. Moreover, the degree of impairment was strongly related to the severity of post-concussion symptoms. Our data suggest that concussions cause objectively measurable changes in the electrophysiological markers of brain activity and hence in the functions of the structures from which they originate. ERPs may thus constitute a reliable method to accurately monitor the clinical course and recovery of head injuries in athletes.

Adult↗
PubMed2000

Effects of lipoxygenase metabolites of arachidonic acid on the growth of human blood CD34(+) progenitors.

The influence of lipoxygenase metabolites of arachidonic acid on proliferation and differentiation of CD34(+) cells was studied. Their effects on the CFU-GM and BFU-E progenitors were investigated by culture of CD34(+) cells in liquid or semisolid medium. Only 12-HETE (1 microM) stimulated the [(3)H]thymidine as well as BrdU incorporation and increased the number of cell divisions (PKH2 tracking). Addition of 12-HETE and 15-HETE but not of LXA(4), LXB(4), LTB(4), and LTC(4) to liquid cultures of CD34(+) cells for 3 and 8 days reduced in a time-dependent manner the number of CFU-GM and BFU-E. Both HETEs also increased the percentage of glycophorin A(+) cells while they reduced the percentage of CD34(-)/CD33(+) cells after 3 and 5 days of liquid cultures. These results show that HETE treatment stimulates proliferation and accelerates the differentiation of CD34(+) cells, mostly toward the erythroid lineage.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2000

[Cerebral magnetic resonance imaging (MRI) in the diagnosis of leptomeningeal carcinomatosis in melanoma patients].

OBJECTIVE: Meningeal involvement is frequent in metastatic melanoma, approximately 30% in autopsy series. Functional signs may be misleading and the neurological examination may be normal. Certain diagnosis requires identification of tumor cells in the cerebrospinal fluid. CSF cytology is however sometimes negative and magnetic resonance imaging (MRI) with gadolinium injection may provide the diagnosis. The aim of this retrospective study was to assess the role of imaging in the diagnosis of leptomeningeal carcinomatosis. PATIENTS AND METHODS: The diagnosis of leptomeningeal carcinomatosis was made in 8 patients between 1992 and 1998. All had signs of neurological function impairment, but the neurology examination was abnormal in only 2. RESULTS: Cytology examination of the cerebrospinal fluid provided the diagnosis of leptomeningeal carcinomatosis in 5 patients. One out of 5 brain CT scans were positive, showing meningeal enhancement confirmed by brain MRI. The spinal tap was not contributive in 2 cases and was not done in 1. In these three cases, the brain CT did not provide any diagnostic element while the brain MRI with gadolinium injection confirmed the diagnosis of leptomeningeal carcinomatosis. DISCUSSION: Forty-one percent of patients with autopsy proven leptomeningeal carcinomatosis have a normal ante mortem spinal tap. Brain MRI with gadolinium injection has better sensitivity than brain CT scan. All patients with nonspecific neurological signs and a normal spinal tap should be explored with a brain MRI.

Adolescent↗
PubMed1998

In vivo modifications of AcSDKP metabolism and haematopoiesis in mice treated with 5-fluorouracil and Goralatide.

BACKGROUND: The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), a physiological inhibitor of the proliferation of haematopoietic stem cells, is degraded by the angiotensin-I-converting enzyme (ACE). Whereas synthetic AcSDKP (Goralatide) protects normal mice from the haematological toxicity of chemotherapy, it has a lower beneficial effect in humans. This discrepancy could be dependent on Goralatide administration schedules, as well as on the endogenous concentrations of AcSDKP and ACE, which vary during chemotherapy. METHODS: We investigated the effect of one myelotoxic dose of 5-fluorouracil (5-FU, 200 mg kg-1) administered without or with Goralatide on blood, bone marrow (BM) and spleen AcSDKP concentrations, ACE activity, nucleated cell counts and survival of the primitive haematopoietic progenitors high proliferative potential colony-forming cells (HPP-CFCs). RESULTS: The 5-FU treatment dramatically decreased the BM concentrations of AcSDKP by 73% and increased the ACE activity in plasma by 50% during the period of active BM regeneration. Repeated injections of Goralatide from 24 h before to 36 h after the i.p. injection of 5-FU spared BM HPP-CFCs. As an injection of 10 mg of Goralatide induced a short peak of plasma AcSDKP without modifying its BM concentrations, we suggest that its protective effect on HPP-CFCs could be mediated by its interference with other plasma molecules targeting to the BM. CONCLUSION: By improving our knowledge of the biology of AcSDKP in vivo during chemotherapy, our results could help to better define the therapeutic use of Goralatide.

Animals↗
PubMed1998

Effect of platelet-activating factor on the growth of human erythroid and myeloid CD34+ progenitors.

We have assessed the effect of platelet-activating factor (PAF), a biologically active phospholipid present in the human marrow, on the growth of human marrow and blood CD34+ progenitors. While the metabolization rate of PAF by CD34+ cells is low (weak acetylhydrolase and acylation processes) it is readily catabolized by the acetylhydrolase activity present in the growth medium (10% fetal calf serum + 10% 5637-conditioned medium). Treatment of marrow CD34+ cells with the non-metabolizable PAF agonist C-PAF (1 nM to 100 nM) immediately before semi-solid culture significantly (P < 0.01) decreased the number of BFU-E but not of CFU-GM colonies. Treatment of marrow or blood CD34+ cells with C-PAF (10-100 nM) for 3 days in liquid medium before semi-solid culture significantly (P < 0.01) decreased the number of BFU-E and CFU-GM colonies. Treatment of blood CD34+ cells with the two PAF receptor antagonists CV 3988 and BN 52021 (1 microM) had no significant effect on the number of BFU-E and CFU-GM colonies suggesting no role of endogenous PAF in these processes. These results show that exogenous PAF downregulates human erythropoiesis and myelopoiesis, a result that might be of importance during inflammatory states.

Antigens, CD34↗
PubMed1998

Effects of lipoxygenase metabolites of arachidonic acid on the growth of human mononuclear marrow cells and marrow stromal cell cultures.

The effects of various lipoxygenase metabolites of arachidonic acid (AA) were investigated on the growth of freshly isolated human bone marrow mononuclear cells and marrow stromal cell cultures. LTB4, LXA4, LXB4, 12-HETE and 15-HETE (1 microM) decreased [3H]-thymidine incorporation on marrow stromal cell cultures without affecting cell number. Only 12-HETE showed a dose-response effect on [3H]-thymidine incorporation. While LTB4 (1 microM) decreased thymidine incorporation on marrow mononuclear cells, LTC4, LXA4, LXB4, 12-HETE and 15-HETE had no effect. The lipoxygenase inhibitor NDGA had no effect on both cell types suggesting no role of endogenous lipoxygenase metabolites on cell growth. These results suggest no important role of lipoxygenase metabolites of AA on the proliferation of human marrow mononuclear cells and marrow stromal cell cultures.

Arachidonic Acid↗
PubMed1997

Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line.

The human immature K562 erythroid cell line was studied for its capacity to produce and to metabolize the phospholipid molecule platelet-activating factor (PAF). K562 cells produced PAF under calcium ionophore stimulation. Lyso PAF and acetyl-CoA (the acetate donor molecule for the acetylation of lyso PAF into PAF) had no effect on the amounts of PAF produced by ionophore-stimulated cells. The metabolism of PAF and lyso PAF by K562 cells was compared to that of freshly-isolated human bone marrow erythroblasts and blood erythrocytes. K562 cells rapidly metabolized [3H]PAF and [3H]lyso PAF with 1-alkyl analogue of phosphatidylcholine as the major metabolic product. In contrast, blood erythrocytes did not. PAF acetylhydrolase activity levels in K562 cells and bone marrow erythroblasts were similar and higher than in blood erythrocytes. PAF (1-100 nM) stimulated [3H]thymidine incorporation in K562 cells grown in low serum concentration, a non-metabolizable PAF agonist being more potent than PAF to stimulate thymidine incorporation. PAF receptor mRNA was detected in K562 cells by polymerase chain reaction on reverse transcripts. The present study demonstrates that K562 cells produce and metabolize PAF and underlines the putative role of erythroid precursors in the modulation of bone marrow PAF concentrations. The effect of PAF on the growth of K562 cells might be mediated through PAF receptors suggesting a potential role of PAF on the proliferation and functions of human erythroid marrow precursors.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Production and metabolism of platelet-activating factor by human bone marrow cells.

Platelet-activating factor (PAF) is a phospholipid mediator of inflammation present in the human bone marrow. Freshly isolated human mononuclear bone marrow cells and marrow stromal cell cultures produced PAF under calcium ionophore (2 microM) and LPS (10 micrograms/ml) stimulation. By contrast, M-CSF (1000 U/ml), GM-CSF (100 ng/ml), IL1, IL3, IL6 and stem cell factor (10 ng/ml) did not stimulate PAF production. Marrow stromal cells produced 50-fold more PAF than freshly isolated mononuclear marrow cells, suggesting that stromal cells might be the major source of the human marrow-derived PAF. Mononuclear marrow cells and stromal cell cultures metabolized PAF with 1-alkyl-2-acyl-glycerophosphocholine as the major metabolic product. PMSF and p-BPB decreased the catabolism of PAF by freshly isolated marrow cells, but not by stromal cell cultures. While stromal cells rather than haematopoietic progenitors might be a major source of the human bone-marrow-derived PAF, both cell types metabolize it, suggesting their putative role in the regulation of PAF concentration in the human bone marrow.

Bone Marrow↗
PubMed1997

Presence and metabolism of lyso platelet-activating factor in human bone marrow.

Lyso platelet-activating factor (PAF) is the precursor of PAF, an inflammatory phospholipid molecule present in human bone marrow. The present study shows that in healthy volunteers lyso PAF concentrations are significantly lower (P = 0.0001, Mann-Whitney U-test) in bone marrow plasma (594 +/- 67 ng/ml, n = 47) than in blood plasma (1448 +/- 99 ng/ml, n = 31). Marrow plasma lyso PAF concentrations are similar in patients with lymphoid and nonlymphoid malignancies as compared with controls. Freshly isolated mononuclear marrow cells and cultures of marrow stromal cells contain lyso PAF. Experiments with [3H]lyso PAF indicate that human mononuclear bone marrow cells and marrow stromal cells actively acylate lyso PAF into a 1-alkyl analogue of phosphatidylcholine. Results of this investigation indicate: (1) that lyso PAF is present in human marrow cells and plasma; and (2) that marrow cells and stromal cells metabolize it, thus suggesting their role in the regulation of lyso PAF amounts in human bone marrow.

Aged↗
PubMed1997

Effects of lipidic mediators on the growth of human myeloid and erythroid marrow progenitors.

Freshly isolated human marrow mononuclear cells produce lipidic compounds such as PAF and leukotrienes. These lipidic molecules act on human marrow myelopoiesis and erythropoiesis by modulating the growth of committed progenitors (CFU-GM and BFU-E) in vitro. Nanomolar concentrations of leukotriene B4 and C4 stimulate the growth of human marrow CFU-GM. In contrast, micromolar concentrations of lipoxygenase inhibitors (NDGA and BW755C) decrease their growth suggesting a role for endogenous lipoxygenase metabolites in this process. Micromolar concentrations of prostaglandin E2 up-regulate and down-regulate the growth of marrow BFU-E and CFU-GM, respectively. In contrast, the other cyclooxygenase metabolites have no effect. Recent studies indicate that nanomolar concentrations of PAF decrease the growth of CFU-GM and BFU-E from purified marrow CD34+ cells. Together these results indicate that lipidic mediators act on human myelopoiesis and erythropoiesis. However at this time the mechanisms and molecular signals mediating the effects of lipidic molecules on human marrow cells are unexplored.

Bone Marrow↗
PubMed1997

Platelet-activating factor and antagonists modulate DNA synthesis in human bone marrow stromal cell cultures.

Platelet-activating factor (PAF) is present in the human bone marrow. We have investigated the effect of PAF and antagonists (BN 52,021 and CV 3988) on the growth of human marrow stromal cells. PAF (1 microM) stimulates and PAF antagonists (0.1-1 microM) inhibit [3H]thymidine incorporation in cells grown in 5% serum. The catabolism of PAF by stromal cells was inhibited by CV 3988 suggesting the presence of specific PAF receptor on cells. PAF and antagonists (0.1 nM-10 microM) had no effect on cells cultured in high serum concentration (20%) or in low serum concentration (1%) with 0.5 ng/ml of basic fibroblast growth factor (bFGF). This study indicates for the first time that PAF modulates the serum-induced but not the bFGF-induced growth of marrow stromal cells. The interactions between PAF and stromal cells during inflammatory marrow events such as myelofibrosis deserve to be assessed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

PAF and haematopoiesis XII: macrophage colony-stimulating factor (M-CSF) decreases platelet-activating factor (PAF) acetylhydrolase production in macrophagic J774 cells.

Platelet-activating factor (PAF) is a phospholipid mediator with major immunoregulatory activities. Macrophages produce PAF acetylhydrolase activity, which regulates blood PAF concentrations. Macrophage colony-stimulating factor (M-CSF) is involved in the differentiation and functions of cells from the monocytic/macrophagic lineage. We found that murine macrophagic J774 cells metabolized PAF with lyso PAF as the major metabolite product. As in mouse plasma, the metabolism of PAF by J774 cells was not inhibited by PMSF, p-BPB, DTNB and quinacrine, M-CSF (100-5000 U/ml) significantly decreased PAF acetylhydrolase activity of the J774 cell without exhibiting a significant effect on cell growth. Elevated concentrations of M-CSF are found in blood and tissues during inflammatory states. It could be suggested that a decreased PAF catabolism by tissue macrophages in response to M-CSF may induce local elevated PAF concentrations, thus amplifying the inflammatory response.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

PAF and haematopoiesis. X. Macrophage colony-stimulating factor and granulocyte macrophage colony-stimulating factor enhance platelet-activating factor acetylhydrolase production by human blood-derived macrophages.

Platelet-activating factor (PAF), a phospholipid autacoid with potent regulatory functions, is synthesized by stimulated monocytes. Macrophages are a source of the plasma acetylhydrolase activity (AHA) which regulates PAF concentrations. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are involved in the differentiation and functions of cells from the monocytic/macrophagic lineage. This work reports that M-CSF and GM-CSF stimulated AHA production by human blood monocyte-derived macrophages in a time- and dose-dependent manner. After 7 days of culture without serum, a 6- and 4-fold increase was found in cells treated with M-CSF (1000 U/ml) and GM-CSF (50 ng/ml), respectively. M-CSF (up to 1000 U/ml) and GM-CSF (up to 10 ng/ml) did not induce PAF production by human blood monocytes. While GM-CSF (10 ng/ml) and interleukin-1 (10 U/ml) stimulated M-CSF production from monocyte-derived macrophages, PAF did not. These results indicate that M-CSF and GM-CSF enhance AHA production by human blood-derived macrophages cultured in low serum concentrations. Clearly the effects of growth factors on AHA production in vivo deserve to be assessed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗