Biomedical subjects

F Fournier

Publications and source records attributed to F Fournier.

At least 19 recordsLinked to original sources

PubMed2005

Investigation of the reactivity of arylamines, organo-hydrazines and tolylisocyanate towards [PW12-xMxO40]n- Keggin anions.

Reaction of K7[A,alpha-PW9Mo2O39] with Na2MoO4.2H2O in a mixture of water/dioxane/hydrochloric acid and further precipitation with (Bu4N)Br provided (Bu4N)3[A,alpha-PW9Mo3O40](3). Analogous reaction with K7-xNax[alpha-PW11O39] is an alternative to the synthesis of (Bu4N)3[alpha-PW11O39{MoVIO}]2. Multinuclear NMR and ESI mass spectrometry have been used to interpret the reaction of (Bu4N)x[alpha-PW11O39{ReO}](x=3 1; x=4 1I), (Bu4N)x[alpha-PW11O39{MoO}](x=3 2; x=4 2I) and (Bu4N)3[A,alpha-PW9Mo3O40]3 by organohydrazines, arylamines, tolylisocyanate and tetraphenylphosphine imide.

Electron Spin Resonance Spectroscopy↗

PubMed2005

Proton affinity ladder for uridine and analogs: influence of the hydroxyl group on the sugar ring conformation.

A ladder of relative proton affinities (PA) for a series of modified uridines (e.g. araU, ddU, 5BrU, 5BrdU and 5IU) was established from competitive dissociations of proton-bound heterodimers using Cooks and co-workers' kinetic method. The studied heterodimers are constituted of a modified nucleoside and either an amino acid or a nucleoside with known PA value. These non-covalent heterodimers were prepared under electrospray conditions to be selected and dissociated into the ion-trap analyzer. These results allowed our PA ladder of uridine and deoxyuridine analogs substituted at the C-5 position in the uracil ring to be extended. From this scale, it was showed that the substitution of hydrogen atom at the C-2' position in the sugar ring by a hydroxyl group involves a decrease of about 7 kJ mol(-1). The experimental values for U, 5MeU, dU, 5MedU, ddU and araU are consistent with those obtained by DFT calculations (B3P86/6-31+G//B3LYP/6-31G(.)). Several neutral and protonated conformations of these compounds were considered, in particular the ring conformation of furanose and the orientation of the base with respect to the sugar ring. These calculated results showed the influence of sugar substituent on the conformation of the neutral form of theses nucleosides. However, the most stable protonated structure is the same for all the studied nucleosides except for araU, where the position of the anti 2'-OH group imposes a specific conformation.

Carbohydrates↗

PubMed2005

Improved proton affinity measurements for proline and modified prolines using triple quadrupole and ion trap mass spectrometers.

Proton affinity (PA) of compounds such as proline, cis-3-methylproline, cis-3-ethylproline, cis-3-isopropylproline and cis-3-isopentanylproline was determined by kinetic method with amines as the reference bases. The effective temperatures determined using ion trap and triple quadrupole mass spectrometers were found to be significantly different. In the case of the triple quadrupole instruments, the effective temperature depends significantly on the collision energy. The influence of the apparent basicity (GBapp) on the effective temperature may be used to estimate the difference in protonation entropy (DeltaDeltaS degrees) between the sample and reference compounds. In case of the ion trap mass spectrometer, the variation of the effective temperature as a function of the excitation amplitude is small, so it is difficult to account for the contribution of the entropy effects to the proton affinity value. A better estimation of the PA and DeltaDeltaS degrees values for the investigated molecules is obtained by combining the GBapp and Teff data pairs that are obtained from both the mass spectrometers.

Kinetics↗

PubMed2005

Proton affinity of diastereoisomers of modified prolines using the kinetic method and density functional theory calculations: role of the cis/trans substituent on the endo/exo ring conformation.

The proton affinity (PA) of cis/trans-3-prolinoleucines and cis/trans-3-prolinoglutamic acids have been studied by the kinetic method and density functional theory (DFT) calculations. Several conformations of the neutral and the protonated modified prolines, in particular the endo and exo ring conformations, were analyzed with respect to their contribution to the PA values. When the substituent is an alkyl, both the diastereoisomers have the same PA value. However, the PA values for the diastereoisomers are different when the substituted chain contains functional groups (e.g. a carboxyl group). This variation in PA values could be attributed to the existence of intramolecular hydrogen bonds.

Algorithms↗

PubMed2003

Fluorinated matrix approach for the characterization of hydrophobic perfluoropolyethers by matrix-assisted laser desorption/ionization time-of-flight MS.

Characterization of fluorinated polymers in MALDI is often unsuccessful because commonly used matrixes, such as 2,5-dihydroxybenzoic acid, Indole acrylic acid, alpha-cyano-4-hydroxycinnamic acid, etc., do not desorb/ionize fluorinated polymers efficiently. This could be in part attributed to the unfavorable interaction between the matrix molecules and fluorinated oligomers due to differences in their hydrophobicities. Moreover, the relative cation affinity between the matrix molecules and the fluorinated oligomers may not favor the gas-phase cationization process of the fluorinated oligomers. To overcome these limitations, fluorinated derivates of benzoic acid (pentafluorobenzoic acid) and cinnamic acid (Pentafluoro cinnamic acid) were employed for the desorption/ionization of perfluoropolyethers. Presence of fluorine atoms in the matrix might improve the interaction between the matrix and perfluoroether during the crystallization or ionization step. With a pentafluorobenzoic acid matrix, intact silver cationized oligomers were desorbed, whereas with a pentafluorocinnamic acid matrix, loss of end group was observed. This loss could be rationalized by the dissociation of the silver cationized oligomers via an ion-dipole mechanism. This work shows the possibility of characterizing yet another important class of fluorinated polymer by MALDI-TOFMS.

Journal Article↗

PubMed2003

Proton affinity of proline and modified prolines using the kinetic method: role of the conformation investigated by ab initio calculations.

The proton affinities of proline, cis-3-methylproline and cis-3-ethylproline have been measured by the kinetic method using an ion trap instrument; the values obtained are 936, 940.5, and 943 kJ mol(-1), respectively. The experimental values are consistent with those obtained by high-level ab initio calculations (B3LYP/6-31+G*//B3LYP/6-31G* and B3P86/6-31+G*//B3LYP/6-31G*). Several conformations of neutral and protonated proline were considered, in particular the endo and exo ring structure and the position of the carboxyl group. These results show the importance of the position of the hydrogen atom of the carboxyl group in determining the most stable protonated proline structure.

Algorithms↗

PubMed2003

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry.

From previous studies on the reactivity of estradiol 2,3-quinone towards deoxyribonucleosides, it was demonstrated that several isomeric adducts were formed. Although adduction on steroid ring A or B has been evidenced using sequential MS(n) experiments, in some cases attachment positions are difficult to identify unambiguously. In this work, 2-hydroxyestradiol labeled with deuterium at various positions [6beta (1); 6alpha-7alpha (2); 6alpha-6beta-7alpha (3)] have been used. Isomeric adduct differentiation could be achieved using LC-ESI-MS(n). The m/z shift of the quasi-molecular ions as well as the fragmentation pathways suggested that adduction could occur on both C6 and C9 sites of the steroid B ring: Nucleophilic attack of the base on the C6 position of the steroid led to major adducts and addition of the base on the activated C9 site gave minor adducts that were found to be unstable. LC-MS(n) experiments carried out under deuterated medium provided information about some fragmentation processes by studying the m/z shift of fragment ions: (1) the loss of deoxyribose from the quasi-molecular ions took place according to a process involving a deuterium transfer from the deoxyribose alcohol function; (2) the cleavage of the steroid-base linkage involved a deuterium transfer from the hydroxy group of the catechol and likely occurred via the formation of an ion-dipole complex. The model studies conducted in this work provide new information on the fragmentation mechanisms of covalent adducts formed from estrogen quinones and deoxyguanosine, the most reactive DNA base. Besides, the first unequivocal characterization of adducts involving the steroid C9 position is shown by using deuterium labeled estrogen quinones.

Chromatography, Liquid↗

PubMed2002

Collision-induced dissociation studies of poly(vinylidene) fluoride telomers in an electrospray-ion trap mass spectrometer.

Although fluorinated polymers are widely used in different applications, they are rarely investigated by "soft ionization" techniques such as matrix-assisted laser desorption/ionization and electrospray ionization (ESI). We report here, the desorption and fragmentation of poly(vinylidene) fluoride (PVDF) telomers in an ion trap mass spectrometer coupled to an ESI source. Protonated and lithiated telomers under collision-induced dissociation resonant excitation show mainly HF losses. Fragmentation of protonated telomers can be rationalized by a double proton-transfer mechanism and that of lithiated and anionic telomers by an ion-dipole mechanism. Both mechanisms predict the formation of a stable aromatic or a linear conjugated species, respectively. For lithiated telomers, we could determine the degree of polymerization (n) from the product ion abundance in MS2 experiments. The nature of the end group plays a substantial role in orienting the fragmentation of the PVDF ions. It is interesting to note that, in MS2 experiments, Li+ and F- act as catalysts in the fragmentation of PVDF telomers. Fragmentation of the PVDF telomer backbone was not observed under any experimental conditions.

Journal Article↗

PubMed2002

Post-source decay time-of-flight study of fragmentation mechanisms of protonated synthetic polymers under matrix-assisted laser desorption/ionization conditions.

Post-source decay (PSD) of three different nylon oligomers desorbed under matrix-assisted laser desorption/ionization (MALDI) conditions was studied and their fragmentation pathways were investigated. The fragmentation of the protonated oligomers is very similar to that of peptides. The b(n)(+), y(n)(+) and z(n)(+) series of ions were observed in abundance in the PSD spectrum. The end groups and the length of the spacer in the repeating unit influence the fragmentation of the different polyamides and the relative abundances of the product ions. Competitive dehydration and deamination reactions were observed, and depend on the nature of the end groups and the repeating units. The PSD spectra are very similar to collision-induced dissociation (CID) spectra obtained under low-energy conditions, implying that the selected precursor ions possess similar average internal energies. All the peaks observed in the PSD spectrum can be rationalized by reasonable fragmentation mechanisms.

Journal Article↗

PubMed2000

Characterization of synthetic polymers by MALDI-TOF/MS: investigation into new methods of sample target preparation and consequence on mass spectrum finger print

Characterization of synthetic polymers by Matrix assisted laser desorption (MALDI) is limited by the solubility of different oligomers in a suitable solvent, and the fingerprint of the mass spectrum is affected by the properties of solvents employed (eg., pH, secondary solvents, evaporation) during sample target preparation. If solvents are not used during sample target preparation, then solvent properties should not play an important role in determining the quality of the MALDI mass spectrum. We report here two solventless approaches for sample target preparation. It was observed that Poly(ethylene glycol) 6000 (PEG) showed the same molecular mass distribution in different modes of sample target preparation. Fluorinated polymer used in these studies was affected by sample target preparation protocol and by target surface. Pyrolysis of PEG oligomers was observed in all the methods of sample target preparation. The desorbed high mass neutral oligomers fragment to give small oligomers which are then cationized by the desolvation of the cationized matrix clusters. Moreover, the origin of the matrix clusters (i.e., formed in the condensed phase or in the gas phase) determines the relative intensities of PEG oligomers cationized by sodium or potassium.

Journal Article↗

PubMed2000

Ion/molecule reactions with dimethyl ether and dimethyl-d6 ether: differentiation of four isomers contained in patchouli essential oil

In this study, we show that it is possible to differentiate four sesquiterpene isomers (C(15)H(24)) preliminarily separated by gas chromatography/mass spectrometry (GC/MS). Dimethyl ether is evaluated as a selective ionization reagent and the relative abundance of adducts formed with this reagent gas under positive chemical ionization conditions are compared and adduct ions are characterized using collision-induced dissociation. The mechanisms have been confirmed by achieving the same experiments with deuterated dimethyl ether. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1998

Biotin synthase mechanism: on the origin of sulphur.

Biotin synthase catalyses the last step of the biosynthesis of biotin in microorganisms and plants. The active protein isolated from Bacillus sphaericus and Escherichia coli contains an iron-sulphur (FeS) cluster. The native enzymes were depleted of their iron and inorganic sulphide and the resulting apoenzymes were chemically reconstituted with FeCl3 and Na2[34S] to give labelled (Fe34S) enzymes. These enzymes were functional and when assayed in vitro produced labelled biotin containing about 65% of 34S. These data strongly support the hypothesis that the sulphur of biotin is derived from the (FeS) centre of the enzyme.

Apoenzymes↗

PubMed1998

Different approaches to the identification of a cortisol isomer compound in horse urine.

A threshold concentration for cortisol in equine urine was fixed at 1.0 microgram ml-1 by the racing authorities in 1994. In some circumstances, interlaboratory discrepancies were observed and structural cortisol modification was revealed. In order to elucidate the degradation process and to prevent it, an identification study of the produced compound was carried out. The modified substrate was characterised by the same molecular weight as cortisol and a shorter retention time under the conditions used for the cortisol quantification (M.A. Popot, PhD Thesis, King's College, London, 1996). To identify this isomer, HPLC-APCI-MS and MS-MS methods were applied to the cortisol post-administration extract diluted in the mobile phase which was either a mixture of methanol-water or labelled methanol-water (CH3OD-D2O). Stereochemical effects were studied under these conditions. Deuterium-hydrogen exchange was also monitored by HPLC-APCI-MS. Considering MS and MS-MS data, the hypothesis of isomerisation at C11 giving the 11 alpha-cortisol was rejected. Isotopic labelling has allowed determination of the number of labile hydrogen atoms of the modified cortisol. Cortisol and modified cortisol have the same number of mobile hydrogens. Therefore, the hypothesis of a reduction at C20 along with an oxidation at C11 has also been rejected. Deuterium-hydrogen exchanges could be a useful tool to elucidate the structure of compounds analysed by HPLC-APCI-MS in a complex matrix such as horse urine extract.

Animals↗

PubMed1998

[Diagnosis of pervasive developmental disorders without mental retardation and its impact on obtaining social and educational services in Quebec].

Pervasive developmental disorders without mental retardation is a new clinical category including high-functioning autism, Asperger syndrome and pervasive developmental disorder non otherwise specified. Its recognition is recent and still problematic in many regards. This article reviews the historical, theoretical and clinical relations between pervasive developmental disorders without mental retardation and bordering disorders. The consequences of an inadequate diagnosis on measures of assistance for these patients is also investigated. The authors conclude on the necessity in considering, independently of the diagnosis, the description of symptoms, the intellectual level and the adaptative level in order to take the most appropriate educational and psychosocial decisions regarding pervasive developmental disorders without mental retardation.

Child↗

PubMed1997

Involvement of the Ca2+/calmodulin-dependent protein kinase II pathway in the Ca2+-mediated regulation of the capacitative Ca2+ entry in Xenopus oocytes.

Activation of the phosphoinositide transduction pathway induces capacitative Ca2+ entry in Xenopus oocytes. This can also be evoked by intracellular injection of Ins(1,4.5)P3, external application of thapsigargin and/or incubation in a Ca2+-free medium. Readmission of Ca2+ to voltage-clamped, thapsigargin-treated Xenopus oocytes triggers Ca2+-dependent Cl- current variations that reflect capacitative Ca2+ entry. Inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) by specific peptides markedly increased the amplitude of the transients, suggesting an involvement of the CaMKII pathway in the regulation of capacitative Ca2+ entry. Biochemical studies provide evidence for the activation of CaMKII in response to the development of capacitative Ca2+ entry. In effect, a CaMKII assay in vivo allows us to postulate that readmission of Ca2+ to thapsigargin-treated oocytes can induce a burst of CaMKII activity. Finally, analysis of the Cl- transient kinetics at high resolution of time suggests that CaMKII inhibition blocks the onset of the inactivation process without affecting the activation rate. We therefore postulate that CaMKII might participate in a negative feedback regulation of store-depletion-evoked Ca2+ entry in Xenopus oocytes.

Amino Acid Sequence↗

PubMed1997

Patient tolerance of transrectal ultrasound-guided biopsy of the prostate.

OBJECTIVES: To determine the acceptability by patients of ultrasound-guided prostatic biopsy without anaesthesia. PATIENTS AND METHODS: From January 1995 to January 1996, 81 patients in our department undergoing transrectal ultrasound-guided prostate biopsy were asked to assess the tolerability of the procedure using an immediate post-operative questionnaire including a 10 cm linear visual analogue scale (VAS). RESULTS: The mean VAS score was 3 (standard error 0.24) and 16% of the patients had a VAS score of > or = 5. Responses to the questionnaire showed that 6% of patients judged that the procedure should have been performed under general anaesthesia, while 19% would not agree to undergo it again without some form of anaesthesia. CONCLUSIONS: Even when anaesthesia-free, transrectal ultrasound-guided prostatic biopsy was felt to be only mildly uncomfortable by most patients, but 19% judged that it should be accompanied by some form of anaesthesia. Consequently, local anaesthetic techniques to enhance tolerance to this type of intervention without sacrificing the advantages of the current out-patient setting should be reassessed.

Aged↗

PubMed1997

[Ureterosigmoidostomy after total cystectomy in cancer. Long-term results. Apropos of 60 cases].

OBJECTIVES: Restoration of continuity of the urinary tract after total cystectomy deserves discussion even if most authors currently opt for bladder replacement or transileal cutaneous diversion. Diversion into the colon, which was used for a long time, has possibly been unjustly abandoned. METHODS: From 1974 to 1995, sixty patients (116 renal units) underwent cystectomy for cancer, followed by systematic ureterosigmoidostomy when age and local conditions allowed. The mean age of the patients (52 men and 8 women) was 60 years. They were reviewed at least every six months and surveillance consisted of annual clinical and laboratory examinations and intravenous urography for 5 years. Evaluation of the functional results and quality of life was based on the information recorded in the patients' files and on the answers to a questionnaire for the 19 patients alive without recurrence. RESULTS: The median follow-up was 80 months. Thirty seven patients have died, 23 (38.38%) of them from bladder cancer. Forty patients (66.6% had an uneventful immediate postoperative course. The major late complications were septic reflux in the upper urinary tract stenosis of the ureteric reimplantation and febrile urinary tract infections, requiring either repeat reimplantation or another diversion. Nocturnal (82%) and diurnal (85%) continence was good and 17 of the 19 patients alive with no signs of recurrence are satisfied with their lifestyle. CONCLUSION: After total cystectomy for cancer, implantation of the two ureters into the colon remains a good method of urinary diversion due to its simplicity and good tolerance sometimes at the cost of a second operation. Recent technical modifications should restore the value of this operation.

Adult↗

PubMed1996

InsP3-dependent Ca2+ oscillations linked to activation of voltage-dependent H+ conductance in Rana esculenta oocytes.

In normal medium supplemented with 10 mM tetraethylammonium chloride (TEACl), membrane depolarizations of immature Rana esculenta oocytes elicited an oscillatory outward current associated with a voltage-dependent H+ current (IH+). The voltage threshold of these oscillations was 22 +/- 5 (n = 10). The oscillations were blocked by intracellular injection of ethylene glycol-O,O'-bis-(2-acetaminoethyl)-N,N,N',N'-tetraacetic acid (EGTA), by application of 1 mM of 4-acetamido-4'-isocyanatostilbene-2,2'-disulfonic acid (SITS), by caffeine (1 mM), and by the intracellular injection of heparin, suggesting that they arose from calcium release from inositol trisphosphate (InsP3)-sensitive stores, monitored by a calcium-dependent chloride current (IClCa2+). The oscillations were independent of the external calcium concentration, and the depolarizations did not affect the InsP3 level. Ni2+, a IH+ inhibitor, blocked the oscillations. Extracellular alkalinization, which lowered the voltage threshold of IH+ and increased its amplitude, also lowered the voltage threshold of the oscillations and increased their amplitude, whereas extracellular acidification produced opposite effects. We suggest that the oscillations are linked to activation of IH+ through a pH-dependent sensitization of InsP3 receptors.

Animals↗