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Biomedical subjects

C Moulin

Publications and source records attributed to C Moulin.

At least 19 recordsLinked to original sources
PubMed2006

Imaging and speciation of trace elements in biological environment.

Mineral elements, often at the trace level, play a considerable role in physiology and pathology of biological systems. Metallogenomics, metalloproteomics, and metallomics are among the emerging disciplines which are critically dependent on spatially resolved concentration maps of trace elements in a cell or tissue, on information on chemical speciation, and on that on metal-binding coordination sites. The mini-review discusses recent progress in analytical techniques for element profiling on the genome scale, biological trace element imaging, and probing, identification and quantification of chemical species in the biological environment. Imaging of the element distribution in cells and tissue sections is becoming possible with sub-micrometer spatial resolution and picogram-level sensitivity owing to advances in laser ablation MS, ion beam and synchrotron radiation X-ray fluorescence microprobes. Progress in nanoflow chromatography and capillary electrophoresis coupled with element specific ICP MS and molecule-specific electrospray MS/MS and MALDI enables speciation of elements in microsamples in a complex biological environment. Laser ablation ICP MS, micro-SXRF, and micro-PIXE allow mapping of trace element distribution in 1D and 2D proteomics gels. The increasing sensitivity of EXAFS and XANES owing to the use of more intense synchrotron beams and efficient focusing optics provide information about oxidation state, fingerprint speciation of metal sites and metal-site structures.

Environmental Pollution↗
PubMed2006

An interdisciplinary approach to investigate the impact of cobalt in a human keratinocyte cell line.

Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.

Cell Line↗
PubMed2006

Use of electrospray ionization mass spectrometry for the study of Ln(III) complexation and extraction speciation with calixarene-CMPO in the fuel partitioning concept.

The calixarene-bearing CMPO groups belong to a family of extracting agents recently developed for nuclear reprocessing. These molecules exhibit specific properties to separate actinides(III) from lanthanides(III) in nitric acid solution. Speciation of two distinct calixarene-CMPO (carbamoyl phosphine oxide), substituted either in the wide rim or in the narrow rim with lanthanides (La, Eu, Yb), was undertaken. The complexation behaviour in single phase or in liquid-liquid extraction was examined with two different electrospray spectrometer source geometries. The stoichiometries of the different complexes were reported and the selectivity of these calixarenes towards lanthanides was determined. The results obtained were concordant for the two spectrometers and confirm that electrospray mass spectrometry is a useful tool to study non-covalently bonded complexes.

Journal Article↗
PubMed2006

Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations.

PURPOSE: On a routine basis we performed systematic molecular screening for FGFR3 and TP53 mutations in 121 bladder tumors. We then specifically analyzed the predictive value of the recurrence of FGFR3 and TP53 genotypes in superficial lesions. MATERIALS AND METHODS: The FGFR3 gene was analyzed by direct sequencing of exons 7, 10 and 15, whereas TP53 status was determined using the p53 functional assay in yeast. RESULTS: We identified a missense FGFR3 mutation in 66% of pTa, 26% of pT1 and 12% of pT2 tumors. Of activating FGFR3 mutations 54% and 85% were found in low G1 and intermediate G2 grade tumors, respectively, but in only 20% of high grade G3 tumors. We detected inactivating TP53 mutations in 10% of pTa, 42% of pT1 and 58% of pT2 tumors. Moreover, TP53 mutations were found only in 23% of grade G1 and 3% of grade G2 tumors but in 44% of high grade G3 tumors. When the 2 genotypes were combined, we observed that 58% of pTa tumors had the (mutant FGFR3, WT TP53) genotype, whereas 58% of invasive lesions harbored the inverse genotype (WT FGFR3, mutant TP53). The (mutant FGFR3, WT TP53) genotype and the (WT FGFR3, mutant TP53) genotype were detected in 23% and 38% of pT1G3 tumors, respectively. In the subgroup of 92 patients with superficial pTa-T1 bladder tumors we did not find that the TP53 or FGFR3 genotype alone or combined had a predictive value for tumor recurrence. CONCLUSIONS: Our data again represent solid proof for the pivotal role of FGFR3 and TP53 mutations in superficial and invasive bladder tumors, respectively. However, other molecular markers should be identified for borderline pT1G3 bladder tumors, which are probably at the crossroads of these 2 distinct molecular pathways.

Aged↗
PubMed2004

High-performance liquid chromatography with electrospray ionisation mass spectrometry and diode array detection in the identification and quantification of the degradation products of calix[4]arene crown-6 under radiolysis.

The extraction of 135Cs from high-activity liquid waste, arising from reprocessing of spent nuclear fuel, can be achieved by using calix[4]arene crown-6 compounds. The radiolytic degradation of di(n-octyloxy)calix[4]arene crown-6 (octMC6), in aliphatic or aromatic solvent in contact with 3 M nitric acid, was studied by high-performance liquid chromatography directly coupled to electrospray ionisation mass spectrometry (LC/ESI-MS). More than 50 distinct degradation products were observed, and about 30 of these were identified. These compounds can be assigned to three categories, namely, products of reactions involving radical cleavage or addition, of oxidation reactions, or of aromatic substitution reactions. The major product, corresponding to substitution by an NO2 group, was quantified by external standard calibration using a purified synthetic sample. Despite the observation of all these degradation compounds, octMC6 appears to be remarkably stable under these drastic conditions, combining hydrolysis (HNO(3) 3 M) and an extreme exposure to radiolysis (10(6) Gy). Less than 35% degradation of octMC6 was observed in aromatic solvent under these conditions.

Journal Article↗
PubMed2003

Preliminary study of the stability of calix[4]arene crown compounds under radiolysis.

The extraction of (135)Cs from high activity waste arising from reprocessing of spent fuel can be achieved by using calix[4]arene crown compounds. The radiolytic degradation of calix[4]arene crowns as well as their solvent, o-nitrophenyloctyl ether (NPOE), was studied using electrospray ionization mass spectrometry (ESI-MS) (that formed Cs(+) or Na(+) adducts) in nitric acid, as well as by chemical ionization tandem mass spectrometry (MS/MS) experiments. The structures of major degradation products were identified with MS and specifically labelled nitric acid. Although NPOE and calix[4]arene crowns alone are relatively stable, under simulated conditions resembling the real industrial processes involving radiolysis in the presence of nitric acid, several products resulting from nitration and oxidation were observed.

Journal Article↗
PubMed2001

Cloning, sequencing, tissue distribution, and heterologous expression of rat flavin-containing monooxygenase 3.

The sequence of rat FMO3 was obtained by RT-PCR and 5'/3' terminal extension. Complete cDNA was amplified, cloned, and sequenced. The cDNA encodes a protein of 531 amino acids which contains the NADPH- and FAD-binding sites and a hydrophobic carboxyl terminus characteristic of FMOs. This sequence is 81, 81, and 91% identical to sequences of human, rabbit, and mouse FMO3, respectively, and 60% identical to rat FMO1. Rat FMO3 was expressed in Escherichia coli. The recombinant protein and the native protein purified from rat liver microsomes migrated with the same mobility (56 kDa) as determined in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Recombinant rat FMO3 showed activities of methimazole S-oxidation, and NADPH oxidation associated with the N- or S-oxidation of trimethylamine and thioacetamide, in good concordance with those reported for human FMO3. When probed with rat FMO3 cDNA (bases 201 to 768), a strong signal corresponding to the 2.3-kb FMO3 transcript was detected in RNA samples from rat liver and kidney while a weak signal was observed with lung RNA samples. In contrast, the probe did not hybridize with any RNA from brain, adipose tissue, or muscle.

Amino Acid Sequence↗
PubMed2001

Application of gas chromatography-tandem mass spectrometry to the analysis of inhibition of dimerisation of tributylphosphate under radiolysis. Identification of isomeric tributylphosphate-alkylbenzene inhibitor coupling products.

Tributylphosphate (TBP), solvent used as extractant for reprocessing spent nuclear fuel, can dimerise under radiolysis. This occurs by radical radical recombination, leading to 10 isomeric dimers (TBP-TBP). These species are complexation agents and are responsible of fission product retention in the organic phase that increases the solvent degradation. In order to limit their formation two free radical inhibitors (In), isopropyl and 1,4-diisopropylbenzenes, were used. These additives reduce by about 50% the concentration of TBP-TBP dimers but this reduction is not strictly followed by TBP regeneration as mixed coupling products from TBP and inhibitor are detected. By using GC-MS-MS and selectively deuterated compounds, the identification of these different isomers (TBP-In) has been realised. From these identifications and from the analysis of the proportion of the different isomers, the major primary TBP radical generated under radiolysis was determined.

Benzene↗
PubMed2001

Molecular structure of fulvic acids by electrospray with quadrupole time-of-flight mass spectrometry.

Characterisation of the molecular structure of aquatic fulvic acids (FA) has been performed using a quadrupole time-of-flight (Q-TOF) mass spectrometer equipped with an electrospray ionisation interface. Molecular masses centred around 450 Da and sinusoidal spectral distributions have been obtained for all fulvic acids. Tandem mass spectrometry (MS/MS) experiments showed losses of 18 Da (H(2)O) and 44 Da (CO(2)), and possible molecular structures were determined for the first time to our knowledge. A methodology is reported for evaluating the average elemental composition of FA from high-resolution mass spectra by processing post-acquisition data calculations using molecular size distributions and atomic compositions of ions. The results are found to be consistent with elemental analysis data.

Benzopyrans↗
PubMed2001

Direct characterization of iodine covalently bound to fulvic acids by electrospray mass spectrometry.

Numerous studies have demonstrated that humic substances (HS) react with iodine to form iodo derivatives and thereby can control the bioavailability of radioisotopes. Unfortunately, none of these studies have provided detailed insights into product compounds and so far, to our knowledge, the direct analysis of these species by electrospray ionization (ESI) mass spectrometry has not been explored. The reactivity of iodine with fulvic acids (FA) present in HS was investigated by means of ESI coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer. ESI spectra of solutions, that were indicated by MS/MS analysis to have formed iodinated species, apparently displayed singly charged ions corresponding in m/z to hypothesized species, viz., [RI - H](-), R = (substituted FA compound). MS/MS analysis based on the diagnostic fragment ions for FA compounds and their iodo derivatives suggests that FA undergo aromatic substitutions. Furthermore, significant differences in mass profiles are observed that presumably result from extended redox reactions. The ESI-MS technique opens up new opportunities to understand the scavenging properties of HS towards radionuclides and heavy metals for environmental studies.

Benzopyrans↗
PubMed2000

Direct determination of dibutyl and monobutyl phosphate in a tributyl phosphate/nitric aqueous-phase system by electrospray mass spectrometry

Electrospray ionization mass spectrometry was tested for its potential use in the quantification of monobutyl phosphate (H2MBP) and dibutyl phosphate (HDBP), two degradation products of tributyl phosphate (TBP), the extractant used in the nuclear fuel reprocessing known as the PUREX process. Detection and quantification of these phosphate esters by electrospray in positive and negative ionization mode are reported in this study. This fast and reliable method, which does not require any preliminary sample extraction, appears to be very attractive for process control. Negative ionization mode gave abundant [M - H]- ions for both HDBP and H2MBP products. Thus, the concentration of H2MBP between 0.1 and 10 g/L in concentrated aqueous nitrate solutions can be precisely determined. Moreover, the concentration of HDBP up to 1 g/L in a TBP matrix was evaluated in this mode. For HDBP concentrations below 1 g/L, detection in the positive ionization mode appeared to be attractive. TBP and HDBP cluster detection allowed quantitative HDBP determination. Indeed, small amounts of HDBP in commercial TBP (60 mg/L) could be directly quantified using the specific [2TBP, HDBP + H]+ cluster at m/z 743.

Journal Article↗
PubMed2000

Characterization of zirconium complexes of interest in spent nuclear fuel reprocessing by electrospray ionization mass spectrometry

Liquid-liquid extraction of zirconium, one of the most important fission products, was followed using electrospray ionization mass spectrometry under conditions simulating reprocessing of nuclear spent fuel. Zr(IV) can precipitate from the organic phase after extraction by dibutylphosphoric acid (HDBP), the most common degradation product of tributylphosphate (TBP) radiolysis. Different complexes were detected with electrospray used in positive or negative ion modes, according to the extraction conditions such as the ligand/metal ratio. Stoichiometry of the Zr(IV) complexes was determined by combining isotopic labeling [H(15)NO(3)] of the aqueous phase in the extraction system and tandem mass spectrometry experiments. These results were compared with the species observed using other techniques reported in the literature. The mechanisms of ionization/desorption of these complexes are proposed depending on the organic ligand character (neutral (L) such as TBP, or acidic (HL') such as HDBP), and the ionization mode used. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

Differential regulation of uncoupling protein-1, -2 and -3 gene expression by sympathetic innervation in brown adipose tissue of thermoneutral or cold-exposed rats.

The control of uncoupling protein-1, -2 and -3 (UCP-1, UCP-2, UCP-3) mRNA levels by sympathetic innervation in rats was investigated by specific and sensitive RT-PCR assays. In rats reared at thermoneutrality (25 degrees C), unilateral surgical sympathetic denervation of interscapular brown adipose tissue (BAT) markedly reduced the UCP-1 mRNA level (-38%) as compared with the contralateral innervated BAT pad, but was without significant effect on UCP-2 and -3 mRNA levels. Cold exposure (7 days, 4 degrees C) markedly increased UCP-1 (+180%), UCP-2 (+115%) and UCP-3 (+195%) mRNA levels in interscapular BAT. Unilateral sympathetic denervation prevented the cold-induced rise in BAT UCP-1 and UCP-2 mRNAs, but not that in BAT UCP-3 mRNA. Results were confirmed by Northern blot analysis. These data indicate a differential endocrine control of UCP-1, UCP-2 and UCP-3 gene expression in rat BAT both at thermoneutrality and during prolonged cold exposure.

Adipose Tissue, Brown↗
PubMed1999

Reliability of single-lead VDD atrial sensing and pacing during exercise.

If atrial sensing ability of a single-lead VDD pacemaker is well accepted at rest, the detection quality by atrial floating electrodes remains less recognized during exercise. The aim of this study was to verify, during treadmill test and a continous telemetry, the atrial tracking performance using four different leads technologies. From November 1994 to July 1997, 21 patients (71.3 +/- 6.3 years old, 7 female, cardiopathy: 57%) were paced for isolated high degree (permanent: 13, paroxystic: 8) AV block. The implanted devices were the Vitatron Saphir/Brillant lead (13 patients), Intermedics Unity/425/04-13 lead (5 patients), Pacesetter Addvent (2 patients), and Biotronik Eikos (1 patient). The acute atrial signal amplitude was 1.66 +/- 0.75 mV. The treadmill test used the chronotropic assessment exercise protocol after pacemaker reprogramming to detect atrial undersensing (AV delay < or = 120 ms, no hysteresis, no flywheel, upper rate increase). The mean delay was 31.1 weeks (range 1-100). The testing duration was 6.1 +/- 2.3 minutes, the number of steps was 3.3 +/- 1.3 per patient, and the peak exercise rate was 135 +/- 19 beats/min. At rest, complete atrial tracking was complete in 90% of the patients, and during testing in only 23.8% of the patients, while AV synchronization > 95% was present in 57.1%, > 90% in 71.4%, and > 85% in 90.4% of patients (Vitatron 13/13, Intermedics 3/5, Biotronik 1/1, and Pacesetter 1/2). During the recovery period synchronization was always > 95%. The mean P wave amplitude at rest was 1.1 +/- 0.5 mV; during the first step, 1.04 +/- 0.61 mV; second step, 0.94 +/- 0.53 mV; third step, 0.82 +/- 0.58 mV; fourth step, 0.67 +/- 0.39 mV; and during recovery, 1.13 +/- 0.67 mV. The mean P wave decrease signal at peak of exercise is 0.21 mV (from -1.31 to +0.5). In fact, P wave variations have several patterns: a decrease was measured in 7 patients, an increase in 2 patients, and no significant change in 7 patients. Single-lead VDD P wave identification during exercise was almost accurate. However, often there was progressive lowering of atrial sensing with transient loss of AV synchrony.

Aged↗
PubMed1999

[Pheochromocytoma simulating myocardial infarct. Apropos of a case].

The authors report the case of a pheochromocytoma in a 67 year old man in whom the initial clinical presentation suggested myocardial infarction. Pheochromocytoma is usually an adrenal tumour with a very variable clinical symptomatology. It is very rare for cardiac disease to be a presenting symptom. The diagnosis was suggested by major blood pressure abnormalities occurring after starting medical treatment for infarction. Pheochromocytomas may cause serious cardiovascular disorders. The diagnosis must be suspected in the presence of atypical signs, an essential requirement to reduce the mortality of the disease.

Adrenal Gland Neoplasms↗
PubMed1998

Tissue-specific modulation of rat glucagon receptor mRNA by thyroid status.

The influence of thyroid status on glucagon receptor mRNA levels was investigated in rats using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Glucagon receptor mRNA was detected in liver, brown and white adipose tissues (BAT and WAT) and brain. In BAT and WAT, pharmacologically-induced moderate hypothyroidism resulted in a marked reduction in the relative abundance of glucagon receptor mRNA. Short-term treatment of hypothyroid rats with exogenous 3,3',5'-triiodo-L-thyronine (T3), resulting in a marked hyperthyroidism, reversed the phenomenon in BAT while the reversal was only partial in WAT. In the liver, there was no significant effect of mild hypothyroidism while there was a positive effect of hyperthyroidism. In brain, the relative tissue abundance of glucagon receptor mRNA was not affected by the large changes in plasma T3. The present results therefore indicate that thyroid status may modulate the relative abundance of glucagon receptor mRNA in a tissue-specific manner.

Adipose Tissue↗
PubMed1998

Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients.

OBJECTIVES: The present study was designed to assess whether a diuretic- or an angiotensin-converting enzyme inhibitor-based treatment can reduce arterial wall hypertrophy of a distal muscular medium-sized artery--the radial artery--and the stiffness of a proximal large elastic artery--the common carotid artery. BACKGROUND: Large-artery wall thickness and stiffness are increased during sustained essential hypertension and contribute to the increased risk of complications. Whether antihypertensive treatment can normalize the wall hypertrophy of conducting arteries has not yet been determined. METHODS: Seventy-seven elderly hypertensive patients were randomized to receive 9 months of double-blind treatment with perindopril (2 to 8 mg/day) or the diuretic combination of hydrochlorothiazide (12.5 to 50 mg/day) plus amiloride (1.25 to 5 mg/day) after a 1-month placebo washout period. If systolic blood pressure remained at >160 mm Hg after 5 months, chlorthalidone or atenolol was added, respectively. Arterial variables, including radial artery mass and common carotid artery compliance, were calculated from noninvasive measurements of internal diameter and wall thickness with the use of high resolution echo-tracking systems at baseline and after 5 and 9 months. RESULTS: During treatment, blood pressure and arterial variables changed to the same extent in both groups. After a 9-month treatment, systolic, diastolic and pulse pressures and radial artery wall thickness, mass and thickness/radius ratio decreased significantly (p < 0.01), whereas carotid compliance increased (p < 0.001). The decrease in radial artery thickness/radius ratio after a 9-month treatment was significantly related to the reduction in pulse pressure (p < 0.01), whereas the improvement in carotid compliance was related to the reduction in mean arterial pressure (p < 0.01). In healthy subjects and untreated hypertensive patients, radial artery diameter, wall thickness and thickness/radius ratio and carotid artery compliance did not change significantly during a 9-month observation period. CONCLUSIONS: These results indicate that in elderly hypertensive patients, both angiotensin-converting enzyme inhibitor- and diuretic combination-based treatments can reduce radial artery wall hypertrophy and improve carotid artery compliance.

Aged↗