Biomedical subjects

Y Boulanger

Publications and source records attributed to Y Boulanger.

At least 19 recordsLinked to original sources

PubMed2006

Monitoring the effects of mobile phone use on the brain by proton magnetic resonance spectroscopy.

PURPOSE: To determine whether extensive use of mobile phones affects brain metabolites detectable by proton magnetic resonance spectroscopy (1H MRS). MATERIALS AND METHODS: Twenty-one extensive mobile phone users (average use = 5.5 +/- 2.2 years at 2.4 +/- 1.1 hours/day) and 15 control subjects were recruited and submitted to a 1H MRS brain examination at 1.5 Tesla. Data were recorded in the most exposed right temporal and pontobulbar areas as well as in the contralateral left temporal area. The ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) to creatine/phosphocreatine (Cr) were measured. RESULTS: No statistically significant changes in the NAA/Cr, Cho/Cr and mI/Cr ratios were measured between mobile phone users and control subjects and between the exposed and contralateral temporal areas. CONCLUSION: These results indicate that extensive exposition to mobile phone radiation does not cause MRS-detectable brain metabolic changes.

Adult↗

PubMed2006

Influence of post-treatment delay on the evaluation of the response to focused ultrasound surgery of breast cancer by dynamic contrast enhanced MRI.

The assessment of the effectiveness of MRI-guided focused ultrasound surgery (MRIgFUS) of breast carcinomas can be performed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters which monitor the presence of residual tumour. The aim of this study was to evaluate the effect of the post-treatment delay on this assessment. DCE-MRI data were acquired immediately and 3-14 days after MRIgFUS treatment of 26 tumours (<7 days, n = 6; = or > ge;7 days, n = 20). The percentage of residual tumour was determined histologically on the resected mass and correlated with two DCE-MRI parameters: increase in signal intensity (ISI) and positive enhancement integral (PEI). No correlation could be found between DCE-MRI data acquired immediately after treatment and the percentage of residual tumour. Good correlation coefficients were found for data acquired several days after treatment (ISI, r = 0.749; PEI, r = 0.778). However, they were higher when the post-treatment time interval was 7 days or more (ISI, r = 0.962; PEI, r = 0.934). These results suggest that a post-treatment delay of 7 days is necessary for the accurate assessment of the presence of residual tumour by DCE-MRI parameters.

Aged↗

PubMed2002

Brain metabolic differences as a function of hemisphere, writing hand preference, and gender.

A total of 35 university-educated normal men (24 right handwriters and 11 left handwriters) and 36 age- and education-matched women (25 right handwriters and 11 left handwriters) underwent a proton magnetic resonance spectroscopy examination in seven 8 cm(3) voxels including the right and left frontal lobe tips, the right and left mid-temporal lobes, the right and left thalami, and the hypothalamus. Dependent measures were N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine/phosphocreatine (Cr) metabolite peak area ratios relative to total H(2)O. As expected, thalamic grey matter contained higher NAA ratios than telencephalic voxels (containing white and grey matter) (p < .001). The thalamic Cr/ H(2)O ratio was higher on the right, but the opposite asymmetry was observed for the temporal lobe (p < .05). Women had a higher left frontal NAA/ H(2)O ratio than men, but men had a higher hypothalamic NAA/ H(2)O ratio than women. Right-handers had a higher temporal lobe NAA/H(2)O ratio than left-handers, particularly in the left hemisphere. In addition, several significant 2- and 3-way interactions between writing hand preference, gender, and hemisphere were observed, but only in the frontal lobe.

Journal Article↗

PubMed2001

Long-term brain metabolic alterations in exogenous Cushing's syndrome as monitored by proton magnetic resonance spectroscopy.

The effects of exogenous Cushing's syndrome on the brain metabolism were investigated by proton magnetic resonance spectroscopy (MRS). Thirteen patients having been treated for 2 to 22 years with prednisone were recruited. On the average, none of the metabolites (NAA, Cr, Cho and mI) were significantly different from those of 40 normal subjects in any of the three regions studied: frontal area, thalamus and temporal area. However, the Cho/H(2)O ratios were found to decrease significantly in the thalamic area as a function of treatment period (-1.3%/year). In the frontal and temporal areas, decreases of the Cho/H(2)O ratios were measured with treatment period but they did not reach statistical significance. Effects on Cho levels can be related to those observed for patients with endogenous Cushing's syndrome and suggest an impairment at the membrane level. The Cho/H(2)O reductions were not found to be dose- or age-dependent. Other metabolite ratios did not vary with treatment period, dose or age.

Adult↗

PubMed2001

Comparison of metabolite levels and water diffusion between cortical and subcortical strokes as monitored by MRI and MRS.

UNLABELLED: Labelle M, Khiat A, Durocher A, et al. Comparison of metabolite levels and water diffusion between cortical and subcortical strokes as monitored by MRI and MRS. Invest Radiol 2001;36:155-163. RATIONALE AND OBJECTIVES: Proton magnetic resonance spectroscopy (MRS) and functional imaging techniques are increasingly recognized as useful tools for the characterization of strokes. The aim of this study was to compare cortical and subcortical (lacunar) strokes by MRS and diffusion-weighted imaging (DWI) experiments as a function of time. METHODS: Single-voxel MRS, DWI, and perfusion-weighted imaging data were recorded on patients with cortical (n = 7) or subcortical (n = 7) strokes in the acute, subacute, and chronic periods. Magnetic resonance spectra were acquired in three regions: hyperintense DWI area, adjacent area with normal DWI intensity, and contralateral area. Neurological deficits were estimated by the National Institutes of Health Stroke Scale. RESULTS: Decreases in N-acetylaspartate, choline-containing compounds, and creatine/phosphocreatine signal intensity as well as the presence of lactate were observed at all times in the hyperintense DWI area of all lesions. Small decreases were measured in the subacute and chronic phases for the adjacent area of cortical strokes but not for the adjacent area of subcortical strokes. The existence of a surrounding affected area in subcortical strokes is deduced from a combination of MRS and DWI results, possibly corresponding to the ischemic penumbra. Differences were found between the two types of lesion, especially an increased time variability of apparent diffusion coefficients in subcortical strokes. CONCLUSIONS: Magnetic resonance spectroscopy provides evidence for the existence of affected tissue outside the hyperintense DWI regions in subcortical strokes. Cortical and subcortical strokes display different DWI and MRS characteristics.

Adult↗

PubMed2000

Recovery of the brain choline level in treated Cushing's patients as monitored by proton magnetic resonance spectroscopy.

In a previous study from our group [A. Khiat, C. Bard, A. Lacroix, J. Rousseau, Y. Boulanger, Brain metabolic alterations in Cushing's syndrome as monitored by proton magnetic resonance spectroscopy, NMR Biomed. 12 (1999) 357-363], proton magnetic resonance spectroscopy (1H MRS) was used to evaluate changes in cerebral metabolites in patients with Cushing's syndrome as compared to normal subjects. Data recorded in the frontal, thalamic and temporal areas demonstrated statistically significant decreases of the Cho/Cr ratios in the frontal and thalamic areas but not in the temporal area for Cushing's syndrome patients. No statistically significant changes in the NAA/Cr ratios were measured in any of the areas studied. In this follow-up study, MRS data are reported for ten patients after correction of hypercortisolism which demonstrate a statistically significant recovery of the choline levels in the frontal and thalamic areas. No variation in the NAA, Cr and mI metabolite ratios relative to H(2)O could be measured. Results are interpreted as an inhibition of the phosphatidylcholine degrading phospholipases by glucocorticoids which disappears after correction of hypercortisolism.

Adult↗

PubMed2000

Role of phospholipase A(2) on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases.

Phospholipase A(2) catalyzes the hydrolysis of membrane glycerophospholipids leading to the production of metabolites observable by both 1H and 31P magnetic resonance spectroscopy. The signal of choline-containing compounds (Cho) observed by 1H magnetic resonance spectroscopy is constituted of metabolites of phosphatidylcholine, especially phosphocholine (PCho) and glycerophosphocholine (GPCho). The phosphomonoester (PME) and phosphodiester (PDE) signals observed by 31P magnetic resonance spectroscopy are, respectively, precursors and catabolites of phospholipids. A large number of brain diseases have been reported to cause variations in the intensity of the Cho, PME and PDE signals. Changes in the activity of phospholipase A(2) have been measured in many brain diseases. In this review, the relationships between the results of 1H and 31P magnetic resonance spectroscopy and the phospholipase A(2) assays are analyzed. In many brain diseases, the variation in the Cho signal intensity can be correlated with a stimulation or inhibition of the phospholipase A(2) activity.

Animals↗

PubMed2000

Conformational analysis of endothelin-1 analogs with indolizidinone amino acids incorporated at the C-terminus.

In light of the fact that a beta-turn conformation at the C-terminus of endothelin-1 (ET-1) could be responsible for activity at the ET(B) receptor, the incorporation of (3S, 6S, 9S)-2-oxo-3-amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acid (IAA) should provide an elegant method to establish whether a formyl group on Trp21 plays a role in stabilizing a beta-turn. Eight linear ET-1 analogs, four formylated and four nonformylated, ET-1-(Leu17-Asp18-IAA-Trp21); ET-1-(Leu17-IAA-Ile20-Trp21); ET-1-(Leu17-Asp18-Pro19-Ile20-Trp21) and ET-1-(Leu17-Asp 8-Ile19-Pro20-Trp21) have been analyzed by high-resolution nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. Two-dimensional double quantum filtered correlation spectroscopy (DQFCOSY), total correlation spectroscopy (TOCSY) and nuclear Overhausen enhancement spectroscopy (NOESY) were resolved and analyzed for each molecule. Interspatial distance constraints were derived from the intensity of the NOESY connectivities, The formation of hydrogen bonding was monitored from the temperature-dependence of the NH chemical shifts. Molecular models calculated by means of distance geometry, simulated annealing and energy minimization, suggested a global elongated structure for the formylated analogs and a folded arrangement for the nonformylated derivatives, but no hydrogen bonding was detected at the C-terminus of ET-1 analogs.

Endothelin-1↗

PubMed1999

Brain metabolic alterations in Cushing's syndrome as monitored by proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy ((1)H MRS) was used to evaluate changes in cerebral metabolites in 13 patients with Cushing's syndrome (including seven with pituitary corticotroph adenomas and six with primary adrenal disease) as compared to 40 normal subjects. Data were recorded in the frontal, thalamic and temporal areas; quantification of the MRS signals demonstrated a statistically significant decrease of the Cho/Cr ratio in the frontal and thalamic areas but not in the temporal area for patients with Cushing's syndrome. The largest decrease in Cho/Cr was measured in the thalamic area of patients with a Cushing's syndrome secondary to an adrenal disease. No statistically significant changes in the NAA/Cr ratio were measured in any of the areas studied. These results suggest that the quantification of choline levels could be helpful for monitoring the cerebral metabolite alterations in patients with hypercortisolism.

Adult↗

PubMed1999

Conformational analysis of biologically active truncated linear analogs of endothelin-1 using NMR and molecular modeling.

Some linear truncated analogs of endothelin-1 display potent agonistic activity at the ET(B) receptor, especially when the side chain of Trp21 is N-formylated. Then, the three-dimensional arrangements of six structurally reduced linear analogs, three formylated and three nonformylated, have been investigated by high resolution NMR spectroscopy and molecular modeling, in order to pinpoint the conformational features related to the biological activity. Two-dimensional double-quantum-filtered correlation spectroscopy (DQFCOSY), total correlation spectroscopy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY) were recorded and analyzed for each molecule. Interspatial distance constraints were derived from the intensity of the NOESY connectivities. The formation of hydrogen bonding was monitored from the temperature dependence of the NH chemical shifts. Molecular models calculated by means of distance geometry, simulated annealing and energy minimization, using the NMR constraints, strongly suggested a global elongated structure for the formylated analogs exhibiting biological activity, and a folded arrangement for the unformylated derivatives. Homology comparisons allowed the identification of a beta-turn-like folding of the C-terminal segment Asp18-Trp21 as a probable key-factor for activity.

Amino Acid Sequence↗

PubMed1998

Three-dimensional structure of the Y1 receptor agonist [Leu31, Pro34]NPY as determined by NMR and molecular modeling.

The solution structure of the Y1 receptor agonist, porcine [Leu31, Pro34]NPY, has been investigated by two-dimensional NMR and molecular modeling. A complete assignment of the NMR resonances was achieved and 201 inter-residue nuclear Overhauser enhancement spectroscopy (NOESY) connectivities could be identified, comprising several connectivities between the N- and C-terminal segments. A molecular model was calculated by distance geometry, simulated annealing and conjugate gradients energy minimization using the NOE constraints. The results indicate that, like NPY and other peptides of the family, [Leu31, Pro34]NPY adopts a folded hairpin structure with the terminal segments in close proximity. Analysis of the secondary chemical shifts for the CH(alpha)'s and of the temperature dependence of the NH chemical shifts combined with the NOE constraints indicates a tendency toward helix structure for the segment 18-30 and the presence of turn structure for the C-terminal segment (residues 31-36). Native NPY and [Leu31, Pro34]NPY have most of their structures in common but differ slightly in their C-terminal portion. Based on the structures of NPY and of its specific agonists, [Leu31, Pro34]NPY and NPY 13-36, conclusions can be drawn about the structural requirements for binding to the Y1 and Y2 receptor subtypes.

Animals↗

PubMed1998

Identification of the motilide pharmacophores using quantitative structure activity relationships.

Erythromycin A and some derivatives have been shown to act as agonists at the motilin receptor site (motilides) and a structural similarity between these molecules and the N-terminal fragment of motilin has been proposed. Conformational analysis and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods have been used to determine the homology between a series of erythromycin A derivatives and motilin 1-10. A total of 18 compounds has been studied to correlate the gastrointestinal motor stimulating (GMS) activity with the structure-related parameters determined by 3D-QSAR. Two models with good predictive power of the GMS activity are presented, leading to the prediction of motilin 1-10 activity. The models are consistent with the majority of the data available. The most significant parameters for GMS activity are a favorable dispersion interaction from the quaternary ammonium group of the desosamine ring. In motilin 1-10, the aromatic side chains of Phe1 and Tyr7 seem to play the same role as the quaternary ammonium group in models 1 and 2, respectively. Some hydroxyl groups of erythromycin A derivatives and hydrophobic groups of the Val2 and lle4 side chains of motilin also contribute to the GMS activity. The experimental GMS activities measured are in good agreement with the predicted values, with correlation coefficient values of 0.98 and 0.94 in models 1 and 2, respectively.

Anti-Bacterial Agents↗

PubMed1997

Solution structure of neuropeptide tyrosine 13-36, a Y2 receptor agonist, as determined by NMR.

The three-dimensional structure of neuropeptide tyrosine (NPY) 13-36, a specific Y2 receptor agonist, has been investigated by two-dimensional 1H-NMR spectroscopy in solution. Analysis of the double-quantum-filtered correlation spectroscopy (DQFCOSY), total correlation spectroscopy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY) spectra provided a complete assignment of the proton signals. The interproton connectivities observed in the NOESY spectra comprised 166 intraresidue and 95 interresidue distance ranges which were used as constraints for molecular modeling by distance geometry, simulated annealing and energy minimization. The optimal structures are characterized by a helical C-terminal fragment Leu30-Tyr36 and a wide loop from Leu17 to Ser22. The structure of NPY 13-36 is analogous to the structure of NPY under the same solvent conditions. Comparison with other reported Y2 agonists suggests that the helical Leu30-Tyr36 fragment is the most critical for activity.

Animals↗

PubMed1997

Tissue-specific regulation of fat cell lipolysis by NPY in 6-OHDA-treated rats.

The effects of neuropeptide Y (NPY), peptide YY (PYY), [Leu31, Pro34]NPY, and NPY (13-36) on adipocyte lipolysis have been studied in subcutaneous (inguinal) and visceral (parametrial) rat adipose tissues. A 48-h fasting period and chemical sympathectomy were used to evaluate the regulation of Y1 and Y2 pathways in rat adipocytes. NPY, PYY, and [Leu31, Pro34]NPY significantly inhibited fat cell lipolysis by about 25% in both tissues (p < or = 0.05). This inhibition was achieved mainly through the Y1 pathway. No significant response to NPY (13-36) was observed, suggesting a lack of involvement of the Y2 pathway in the antilipolytic effect of NPY and PYY. The 48-h fasting period led to the loss of the Y1 inhibitory effect previously observed in control rats. On the other hand, the chemical sympathectomy induced a 35% increase of fat cell lipolysis (p < or = 0.05). The latter involved the Y2 pathway as stimulated by NPY (13-36), and was observed in the parametrial tissue exclusively. These results suggest that: a) rat Y receptors reported to exhibit Gi responses can also express Gs-like responses, and b) visceral and subcutaneous adipose tissues exhibit specific regulation of fat cell lipolysis.

Adipocytes↗

PubMed1996

Structural differences between the free and bound states of the DNA-bisintercalating peptide YSPTSPSY.

The YSPTSPSY peptide is a DNA-bisintercalator that can adopt nonrandom conformations in solution. Strategies based on random conformational search and energy minimizations have been applied to generate populations of conformers characterizing YSPTSPSY. Subsequent analysis based on statistical methods and clustering allowed to determine the existence of four classes of conformers containing beta- and/or gamma-turns. NMR spectra of YSPTSPSY in solution provide evidence for such structures. Employing a Monte Carlo-based docking procedure, the YSPTSPSY peptide was docked in a DNA double-helical fragment with the sequence [d(GACGTC)]2. The peptide binds on the minor groove of DNA stacking the central CG base pairs, in a manner similar to that observed in complexes of triostin A with DNA. Upon binding, the structure of the C-terminal segment is modified into a type I beta-turn. Five intermolecular hydrogen bonds are observed, but the van der Waals interactions constitute the major stabilization factor for the complex. NMR chemical shifts, coupling constants, and NOESY connectivities are in agreement with the molecular model.

Amino Acid Sequence↗

PubMed1996

Structural comparison of alanine-substituted analogues of the calcitonin gene-related peptide 8-37. Importance of the C-terminal segment for antagonistic activity.

Replacement of specific residues of the antagonistic fragment human calcitonin gene-related peptide 8-37 (hCGRP 8-37) by alanine residues produces good antagonists to CGRP1 receptors when the replacement is made at positions 17 and 20 but a poor antagonist when the replacement is made at position 21. The solution structures of hCGRP 8-37 and of the three alanine analogues have been determined by two-dimensional 1H NMR spectroscopy and molecular modeling. Following the complete assignment of the NMR spectra, a comparison of the chemical shifts and of the temperature dependence of the amide chemical shifts showed that these parameters differed for [Ala17]-hCGRP 8-37 and [Ala20]-hCGRP 8-37 relative to hCGRP 8-37 in the N-terminal and central segments but not in the C-terminal segment (residues 31-37). In the case of [Ala21]-hCGRP 8-37, differences were observed all along the chain. Molecular modeling calculations were performed by distance geometry, simulated annealing and energy minimization using NOE distance constraints. Molecular models showed a structural homology between [Ala17]-hCGRP 8-37, [Ala20]-hCGRP 8-37 and hCGRP 8-37 in the C-terminal segment Asn31-Phe37 as well as hydrogen bonding between Val28 and Asn31. These structural similarities are not observed with [Ala21]-hCGRP 8-37. Therefore, the structure of the C-terminal segment of hCGRP 8-37 appears to be critical for antagonistic activity at CGRP1 receptors.

Alanine↗

PubMed1996

Biological and molecular analyses of structurally reduced analogues of endothelin-1.

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized through linking with an aliphatic spacer [aminocaproic acid (Aca)], segment 3-11 of ET-1 to carboxyl-terminal fragments of various lengths (16-21, 17-21,...,21). The peptides were prepared in their linear or cyclic form, and a formyl group was or was not introduced on the Trp21 side chain. Pharmacological studies were carried out with the guinea pig lung parenchyma paradigm and the rat thoracic aorta bioassay. In the rat aorta, an ET(A) receptor preparation, all of the analogues were inactive. However, in the lung parenchyma, we observed that among the linear formylated derivatives, [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(17-21)ET was a partial agonist. In this series, the presence of His16, as in [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(16-21)ET, caused a decrease in contractile activity, suggesting that the imidazole group disfavors the proper interaction of the linear molecule with the ETB receptors of the lung parenchyma. The loss of biological activity of the deformylated linear analogues strongly suggested that the formyl group played a stabilizing role in the structure of the linear molecules. Interestingly, molecular modeling studies indicated the adoption of different conformations by the formylated and the nonformylated analogues. In contrast, the stabilizing effect of the formyl group was not observed with the cyclic compounds. Furthermore, the presence of His16 favored the contractile activity of the cyclic peptides. Finally, the results demonstrated that the carboxyl-terminal residues 18-21 are required for the activity in the guinea pig lung parenchyma ETB receptors.

Animals↗

PubMed1995

Structural characterizations of neuropeptide tyrosine (NPY) and its agonist analog [Ahx5-17]NPY by NMR and molecular modeling.

The structures of human NPY and of its centrally truncated agonist analog [Ahx5-17]NPY have been investigated in DMSO-d6 by two-dimensional NMR and by molecular modeling. For both peptides, a complete resonance assignment was achieved and a large number (more than 200) of inter-residue NOE connectivities were observed, including long-range connectivities between the N- and C-terminal ends of the chain. Molecular models were calculated using NOE constraints by distance geometry, simulated annealing and conjugate gradient energy minimization. The results indicate that both peptides are folded in the center of their chain, NPY adopting the hairpin shape, whereas the central portion of [Ahx5-17]NPY is characterized by relatively large loops. In contrast to previous models, practically no alpha-helical structure exists for these peptides under our conditions, but two beta-turns are found in NPY and one in [Ahx5-17]NPY. The proximity of the terminal ends could be the determinant factor for their activity.

Amino Acid Sequence↗