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Publications and source records attributed to C Blanchet.
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OBJECTIVES: The objectives of this study were to examine the profile of relative concentrations in plasma phospholipids of n-3 fatty acids among peri- and postmenopausal Inuit women living in Greenland and to verify their relationships with ischemic heart disease risk factors and more particularly, with concentrations of plasma triacylglycerols. STUDY DESIGN: This study was part of a survey conducted in 2000, which aimed to assess the prevalence of osteoporosis and the associated risk factors among peri- and postmenopausal Greenland Inuit women. METHODS: The study population consisted of 153 women aged 49-69 years (mean +/- SD: 55.3 +/- 4.4 y) randomly selected. Data were obtained through an interview (questionnaire on lifestyle habits, medical history etc) and a clinical session (physiologic and anthropologic measurements). Plasma samples were used to measure the fatty acid composition of plasma phospholipids. RESULTS: The mean body mass index of women was 27.9 +/- 6.1. Seventy-five percent were smokers and 9% were currently on hormone replacement therapy. Relative concentrations of total n-3 fatty acids were very high (13.8%, 95% CI: 13.1-14.6), with docosahexanoic and eicosapentanoic acids accounting for 4.7% and 7.2%, respectively. The ratio of n-3:n-6 fatty acids was 0.67. n-3 fatty acids were inversely correlated to triacylglycerols. CONCLUSION: These data show that peri- and post-menopausal Greenland Inuit women have very high plasma concentrations of n-3 fatty acids that protect them from ischemic heart disease.
The purpose of this study was to assess the magnitude of the relationship between leisure physical activity and bone status as measured either by an Achilles ultrasound bone densitometer (QUS) or dual-energy X-ray absorptiometry (DXA) in postmenopausal women. We studied 1162 French Canadian postmenopausal women, aged 33-84 years (mean age 58 years), for QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI)] measured at the right calcaneus, and bone mineral density (BMD) measured at the lumbar spine and femoral neck. Multivariate regression analyses revealed that leisure physical activity level was an independent predictor of the heel QUS parameters and of femoral neck BMD. No such association was observed for BMD of the lumbar spine. Heel QUS parameters (BUA, SOS, SI) and femoral neck BMD adjusted for interfering covariables showed a statistically significant difference between sedentary (less than three sessions/month) and active women (three or more sessions/week) (P < or = 0.001). Furthermore, after adjusting each heel QUS parameters for the mean lumbar spine BMD value, the association observed between leisure physical activity and QUS remained significant. These results suggest that regular leisure physical activity could influence QUS parameters, independently of BMD, and that quantitative ultrasound could be a suitable outcome measure in exercise studies in postmenopausal women.
INTRODUCTION: Diagnosis of anorexia nervosa is readily evoked in young girls who associate decreased food intake and weight loss. Among the differential diagnoses of anorexia, it is important to underline the preponderant place occupied by Crohn's disease. OBSERVATIONS: We report three cases of young 18 to 25 year-old girls, initially treated for anorexia nervosa in a psychiatric department. Diagnosis of Crohn's disease was made within 5 to 13 years. The clinical and biological characteristics are reported for each case. COMMENTS: In view of the frequency of digestive disorders concomitant to eating disorders, the distinction between anorexia and digestive disease is particularly delicate. It requires appropriate somatic and biological assessment that, when confronted with clinical and/or biological atypia, may query the initial diagnosis of anorexia.
We examined the potential expression and function of alpha7 nicotinic acetylcholine receptors (nAChRs) in leukocytes. RT-PCR with alpha7 specific primers revealed the presence of the receptor mRNA in leukocytes. Immunoblotting and immunofluorescence experiments demonstrated the expression of a protein that is recognized by alpha7 specific antibodies. However, nicotine and acetylcholine (ACh) failed to elicit current in leukocytes. Binding experiments with alpha-bungarotoxin rhodamine conjugated were negative, illustrating the absence of a high-affinity binding site. RT-PCR analysis revealed the selective expression of the dupalpha7 mRNA. These data indicate that leukocytes express in their membrane the dupalpha7 protein but its physiological role remains to be identified.
MATERIALS & METHODS: We present a retrospective study of 95 patients with recurrence of oropharyngeal carcinoma after exclusive radiotherapy. The treatment consisted in a salvage composite resection in all cases. RESULTS & DISCUSSION: Since the use of muscular flaps, the post-operative complications have been relatively minimised but the carcinologic results were disappointing: only 20% of patients were alive free of disease at 5 years. The main prognostic factors for overall survival were the stage rT of the relapse, the histologic invasion of the nodes and the quality of the resection. The anatomic site of relapse did not influence the survival. CONCLUSION: Our serie confirms the high frequency of second primary tumors in oropharyngeal cancers. Rigorous selection of patients for exclusive radiotherapy is mandatory to decrease the number of relapses and might avoid salvage surgery.
Cochlear outer hair cells (OHCs) express nicotinic acetylcholine receptors (nAChRs) whose calcium permeability allow the activation of co-localized Ca(2+)-sensitive K+ channels (SK-type). The large organic cation tetraethylammonium (TEA) is known to block at millimolar concentration voltage-gated and Ca(2+)-activated K+ currents in OHCs. In the present study, we show that extracellular TEA blocked much more efficiently, at micromolar concentrations, ACh-evoked K+ currents in isolated guinea pig OHCs. The dose-inhibition curve indicated an IC(50) of 60 microM, a value two orders of magnitude lower than the one reported on SK or BK channels. The site of the blocking action was on the extracellular side of the plasma membrane since 10 mM intracellular TEA did not prevent or change the characteristics of the ACh-evoked K+ current. The block of this K+ current in OHCs was mainly explained by a direct action of TEA at the nAChRs. Indeed, we demonstrated that extracellular TEA inhibited directly the ionotropic cation current flowing through the nAChRs (IC(50)=30 microM). This study demonstrated for the first time that extracellular TEA is an effective blocker of the OHCs' nAChRs.
GABA(B) (gamma-aminobutyric acid type B) receptors are important for keeping neuronal excitability under control. Cloned GABA(B) receptors do not show the expected pharmacological diversity of native receptors and it is unknown whether they contribute to pre- as well as postsynaptic functions. Here, we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable, exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. These behavioral findings are paralleled by a loss of all biochemical and electrophysiological GABA(B) responses in null mutant mice. This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes.
The isocitrate dehydrogenase kinase/phosphatase (IDHK/P) of E. coli is a bifunctional enzyme responsible for the reversible phosphorylation of isocitrate dehydrogenase (IDH) on a seryl residue. As such, it belongs to the serine/threonine protein kinase family. However, only a very limited homology with the well-characterized eukaryotic members of that family was identified so far in its primary structure. In this report, a new region of amino acids including three putative residues involved in the kinase activity of IDHK/P was identified by sequence comparison with eukaryotic protein kinases. In IDHK/P, these residues are Asp-371, Asn-377, and Asp-403. Their counterpart eukaryotic residues have been shown to be involved in either catalysis (former residue) or magnesium binding (the two latter residues). Site-directed mutagenesis was performed on these three IDHK/P residues, and also on the Glu-439 residue equivalent to that of the Ala-Pro-Glu motif found in the eukaryotic protein kinases. Mutations of Asp-371 into either Ala, Glu, or Gln residues drastically lowered the yield and the quality of the purification. Nevertheless, the recovered mutant enzymes were barely able to phosphorylate IDH either in vitro or after expression in an aceK (-) mutant strain. In contrast, mutation of either Asn-377, Asp-403, or Glu-439 into an Ala residue altered neither the yield of purification nor the maximal phosphorylating capacity of the enzyme. However, when IDH was phosphorylated in the presence of increasing concentrations of magnesium ions, the two former mutants displayed a much lower affinity for this cation, with a K(m) value of 0.6 or 0.8 mM, respectively, as compared to 0.1 mM for the wild-type enzyme. On the other hand, the Glu439Ala mutant has an affinity for magnesium essentially unaffected. Therefore, and in contrast to the current opinion, our results suggest that the catalytic mechanism of IDHK/P exhibits some similarities with that found in the eukaryotic members of the protein kinase family.
Programs devoted to the analysis of protein sequences exist either as stand-alone programs or as Web servers. However, stand-alone programs can hardly accommodate for the analysis that involves comparisons on databanks, which require regular updates. Moreover, Web servers cannot be as efficient as stand-alone programs when dealing with real-time graphic display. We describe here a stand-alone software program called ANTHEPROT, which is intended to perform protein sequence analysis with a high integration level and clients/server capabilities. It is an interactive program with a graphical user interface that allows handling of protein sequence and data in a very interactive and convenient manner. It provides many methods and tools, which are integrated into a graphical user interface. ANTHEPROT is available for Windows-based systems. It is able to connect to a Web server in order to perform large-scale sequence comparison on up-to-date databanks. ANTHEPROT is freely available to academic users and may be downloaded at http://pbil.ibcp.fr/ANTHEPROT.
ABC (ATP-binding cassette) transporters and helicases are large superfamilies of seemingly unrelated proteins, whose functions depend on the energy provided by ATP hydrolysis. Comparison of the 3D structures of their nucleotide-binding domains reveals that, besides two well-characterized ATP-binding signatures, the folds of their nucleotide-binding sites are similar. Furthermore, there are striking similarities in the positioning of residues thought to be important for ATP binding or hydrolysis. Interestingly, structures have recently been obtained for two ABC proteins that are not involved in transport activities, but that have a function related to DNA modification. These ABC proteins, which contain a nucleotide-binding site akin to those of typical ABC transporters, might constitute the missing link between the two superfamilies.
BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.
BACKGROUND: Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. OBJECTIVES: The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. DESIGN: The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. RESULTS: Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. CONCLUSIONS: Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.
Molecular modeling of proteins is confronted with the problem of finding homologous proteins, especially when few identities remain after the process of molecular evolution. Using even the most recent methods based on sequence identity detection, structural relationships are still difficult to establish with high reliability. As protein structures are more conserved than sequences, we investigated the possibility of using protein secondary structure comparison (observed or predicted structures) to discriminate between related and unrelated proteins sequences in the range of 10%-30% sequence identity. Pairwise comparison of secondary structures have been measured using the structural overlap (Sov) parameter. In this article, we show that if the secondary structures likeness is >50%, most of the pairs are structurally related. Taking into account the secondary structures of proteins that have been detected by BLAST, FASTA, or SSEARCH in the noisy region (with high E: value), we show that distantly related protein sequences (even with <20% identity) can be still identified. This strategy can be used to identify three-dimensional templates in homology modeling by finding unexpected related proteins and to select proteins for experimental investigation in a structural genomic approach, as well as for genome annotation.
INTRODUCTION: Thyroglossal duct cyst (TGDcs) is the most common malformation of the neck. The risk of infection and malignant transformation impose its treatment. OBJECTIVES: The purpose of our study were: 1) to specify some points about the symptomatology and preoperative evaluation necessary for TGDcs diagnosis; 2) to analyse the factors who can explain an unsuccessful surgical treatment. PATIENTS AND METHODS: Our study is based on a retrospective review of cases and a review of the literature. From 1981 to 2000, 99 children with a mean age of five years were treated for a TGDcs with a surgical procedure in the Grenoble University Hospital. 3 excision and 96 Sistrunck's procedure were performed. In all cases a histological study was made. RESULTS: Ultrasonography was the most frequent preoperative evaluation. We have had 7 complications: 3 haematoma, 2 abscess and 2 desunited scar. 6 children have had recurrent disease. Among these 6 children, 3 have had an excision and 3 a Sistrunck's procedure. No case of malignant transformation was reported. CONCLUSION: Ultrasonography is the first preoperative evaluation to obtain before surgical treatment of a TGDcs. Sistrunck's procedure is the best surgical treatment with a value of recurrence from 1% to 10%. Areas of surgical failure included breaking of cyst during the dissection, inadequate hyoïd bone resection, an anatomical variation with many ductuli in the base of tongue, inadequate muscles of tongue resection.
PURPOSE OF THE STUDY: The purpose of our study was to determine the position and value of ultrasound scan of the liver in the initial check-up of patients treated for a squamous cell carcinoma of the upper respiratory and digestive tract. MATERIAL AND METHODS: Our study is based on a retrospective review of 267 patients (249 males and 18 females) managed in the E.N.T. Department of Grenoble universitary hospital from 1993 to 1995 for a upper respiratory and digestive tract malignant tumor. No patient has been previously treated. The site of the primary tumor was: the oropharynx (108 cases), the hypopharynx (88 cases), the oral cavity (44 cases), the larynx (20 cases), the rhinopharynx (6 cases) and the cervical oesophagus (1 case). Endoscopic procedure with biopsy was performed for all the patients. Histologic examination revealed an invasive squamous cell carcinoma in all the cases. The complete check up included a ultrasound scan of the liver and a chest X-ray for all the patients. RESULTS: Ultrasound scan of the liver revealed one or several metastases in 4 cases (1.5%). The primary tumor was hypopharyngeal in 3 cases (2 stages III, 1 stage IV) and oropharyngeal in 1 case (stage III). In three cases, carcinoma was poorly differentiated. Ultrasound scan of the liver was doubtful for 8 patients (3%). The primary tumor was oropharyngeal in 6 cases (1 stage I, 3 stages III, 2 stages IV), laryngeal in 1 case (stage III) and hypopharyngeal in case (stage IV). In six cases carcinoma was well differentiated. All the complementary examinations concluded to a benign liver disease, with a mean diagnosis delay of 4 weeks for the 8 patients. The mean follow-up duration of the 8 patients was 22 months (range 9 to 42 months). None presented any metastases during the follow up. CONCLUSION: Our results compared with those of the literature revealed that ultrasound scan of the liver is a few specific examination which may be recommended for hypopharyngeal tumors, or for a large cervical adenopathy (N2 or N3), a poor differentiated tumor wherever the site of the primary tumor is.
Aminoglycoside antibiotics such as gentamicin are known to block the medial olivocochlear efferent system. In order to determine whether this inhibition takes place at the postsynaptic cholinergic receptors in outer hair cells (OHCs), we studied the effects of these polycationic molecules on cholinergic currents evoked in isolated guinea-pig OHCs. The cholinergic response of OHCs involves nicotinic-like receptors (nAChRs) permeable to Ca2+ ions that activate nearby Ca2+-sensitive K+ channels (KCa(ACh) channels). The extracellular application of gentamicin and neomycin reversibly blocked ACh-evoked K+ current (IK(ACh)) with IC50 values of 5.5 and 3.2 microM, respectively. The results showed that the blocking mechanism of IK(ACh) was due to inhibition of Ca2+ influx via nAChRs. Our study also provides interesting insights into the functional coupling between nAChRs and KCa(ACh) channels in OHCs. By directly recording the cation current flowing through nAChRs (In(ACh)) using an intracellular solution containing 10 mM BAPTA, we measured an EC50 near 110 microM for ACh-evoked In(ACh). This EC50 for ACh is one order of magnitude higher than that measured indirectly on IK(ACh). This reveals a rather low affinity of ACh for its receptor but a very efficient coupling between nAChRs and KCa(ACh) channels. We also show that a high external Ca2+ concentration reverts the gentamicin inhibition of IK(ACh) and that gentamicin directly alters the cation current flowing through the nAChRs of OHCs. We propose that gentamicin acts as a non-competitive cholinergic blocker by displacing Ca2+ from specific binding sites at the nAChRs. This block of the nAChRs at the level of the postsynaptic membrane in OHCs could explain the inhibitory effect of gentamicin reported on the crossed medial olivocochlear efferent system in vivo.
Acetylcholine can stimulate the release of vasopressin. In organ-cultured hypothalamo-neurohypophyseal systems, acetylcholine enhanced vasopressin release by acting in or near the supraoptic nucleus Extracellular recordings suggested that acetylcholine can increase supraoptic neuron excitability. These effects could be mimicked, in part, by nicotine or blocked by nicotinic antagonists, suggesting that they might be mediated by nicotinic acetylcholine receptors. Autoradiography indicated that alpha-bungarotoxin binding sites are present in the supraoptic nucleus; however, neither acetylcholine nor nicotine binding sites could be detected. Thus, the existence, let alone the nature, of nicotinic receptors in the supraoptic nucleus has so far remained elusive. The present work attempts to determine: (i) whether functional nicotinic receptors are present in this nucleus; (ii) whether they are located on neurosecretory magnocellular cells or at presynaptic sites; (iii) what their pharmacological and biophysical properties are; (iv) whether they influence the activity of all or only part of supraoptic neurons. Whole-cell recordings were performed in hypothalamic slices or in acutely dissociated supraoptic neurons and the effect of nicotinic agonists was tested under voltage-clamp conditions. Autoradiography was done in coronal hypothalamic sections, using [3H]epibatidine and [125I]alpha-bungarotoxin as ligands. Our results indicate that supraoptic neurons possess functional nicotinic receptors containing the alpha7 subunit.