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Biomedical subjects

C Petit

Publications and source records attributed to C Petit.

At least 19 recordsLinked to original sources
PubMed2006

Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats.

Recent epidemiological studies suggest that high meat intake is associated with promotion of colon cancer linked with haem-iron intake. We previously reported that dietary haem, in the form of either haemoglobin or meat, promotes precancerous lesions in the colon of rats given a low-calcium diet. The mechanism of promotion by haem is not known, but is associated with increased lipid peroxidation in faecal water and strong cytotoxic activity of faecal water on a cancerous mouse colonic epithelial cell line. To better understand the involvement of faecal water components of haem-fed rats in colon-cancer promotion, we explored the effect of faecal water on normal [adenomatous polyposis coli (Apc)+/+] or premalignant cells (Apc-/+). Further, we tested if this effect was correlated to lipoperoxidation and 4-hydroxynonenal (HNE). We show here for the first time that heterozygote Apc mutation represents a strong selective advantage, via resistance to apoptosis induction (caspase 3 pathway), for colonic cells exposed to a haem-iron-induced lipoperoxidation. The fact that HNE treatment of the cells provoked the same effects as the faecal water of rats fed the haem-rich diet suggests that this compound triggers apoptosis in those cells. We propose that this mechanism could be involved in the promotion of colon carcinogenesis by haem in vivo.

Animals↗
PubMed2006

Evidence of a high proportion of premature unbalanced separation of sister chromatids in the first polar bodies of women of advanced age.

BACKGROUND: Maternal ageing is the only aetiological factor unequivocally linked to aneuploidy. Two mechanisms seem to explain these abnormalities in oocytes: non-disjunction and premature unbalanced separation of sister chromatids (PSSC). Previous studies of unfertilized oocytes argue for a major role of PSSC in the aetiology of aneuploidy for women of advanced age, but in vitro ageing of the oocytes could influence the results. METHODS: Owing to the high prevalence of aneuploidy in women of advanced age, chromosomal screening of the first polar body just before ICSI was offered to women (from 38 years of age) included in an assisted reproduction programme. RESULTS: Among 141 oocytes from 29 women (mean age 40 years and 2 months), 43 (30.5%) were abnormal. Sixty-five abnormalities were found and PSSC was involved in 80% of cases. CONCLUSION: These results are in accordance with previous studies and confirm, in 'fresh' oocytes, the major role of PSSC in the aetiology of aneuploidy in women of advanced age.

Adult↗
PubMed2005

Results of cochlear implantation in two children with mutations in the OTOF gene.

OBJECTIVE: The purpose of the study is to present the results of cochlear implantation in case of deafness involving mutations in the OTOF gene. This form of deafness is characterized by the presence of transient evoked otoacoustic emissions (TEOAE). In cases of profound deafness with preserved TEOAE, two main etiologies should be considered: either an auditory neuropathy (a retrocochlear lesion) or an endocochlear lesion. It is essential to differentiate these two entities with regards to therapy and screening. PATIENTS: We report two children who presented with profound prelingual deafness, confirmed by the absence of detectable responses to auditory evoked potentials (AEP), associated with the presence of bilateral TEOAE. Genetic testing revealed mutations in OTOF, confirming DFNB9 deafness. Both patients have been successfully implanted (with a follow-up of 18 and 36 months, respectively). MAIN OUTCOME MEASURES: Clinical (oral production, closed and open-set words and sentences list, meaningful auditory integration scale), audiometric evaluation (TEOAE, AEP) before and after implantation, and neural response telemetry (NRT). RESULTS: Both patients present a good quality of clinical responses and electrophysiological tests after implantation, indicating satisfactory functioning of the auditory nerve. This confirms the endocochlear origin of DFNB9 and suggests that these mutations in OTOF lead to functional alteration of inner hair cells. CONCLUSION: In the absence of a context of neurological syndrome, the combination of absent AEP and positive TEOAE should lead to a genetic screening for mutations in OTOF, in order to undertake the appropriate management.

Audiometry↗
PubMed2005

Seven-nanometer hexagonal close packed cobalt nanocrystals for high-temperature magnetic applications through a novel annealing process.

Seven-nanometer cobalt nanocrystals are synthesized by colloidal chemistry. Gentle annealing induces a direct structural transition from a low crystalline state to the hexagonal close packed (hcp) phase without changing the size, size distribution, and the lauric acid passivating layer. The hcp structured nanocrystals can be easily redispersed in solvent for further application and processing. We found that the magnetization at saturation and the magnetic anisotropy are strongly modified through the annealing process. Monolayer self-assembly of the hcp cobalt nanocrystals is obtained, and due to the dipolar interaction, ferromagnetic behavior close to room temperature has been observed. This work demonstrates a novel approach for obtaining small size hcp structured cobalt magnetic nanocrystals for many technological applications.

Journal Article↗
PubMed2005

Closed-loop experimental validation of the spatially filtered Shack-Hartmann concept.

An experimental validation of the spatially filtered Shack-Hartmann concept (F-SH) is presented that allows aliasing effects to be decreased. This effect is studied by use of an adaptive optical testbed with a focal plane pinhole in front of the wave-front sensor. First, the ability to close the loop on turbulence is demonstrated. Then the performance gain conferred by the device is quantified and compared with end-to-end simulation results. Another property of the F-SH concept, i.e., the reduction of the waffle modes, is highlighted.

Journal Article↗
PubMed2005

Oxetane locked thymidine in the Dickerson-Drew dodecamer causes local base pairing distortions -- an NMR structure and hydration study.

The introduction of a North-type sugar conformation constrained oxetane T block, 1-(1',3'-O-anhydro-beta-D-psicofuranosyl) thymine, at the T(7) position of the self-complementary Dickerson-Drew dodecamer, d[(5'-C(1)G(2)C(3)G(4)A(5)A(6)T(7)T(8)C(9)G(10)C(11)G(12)-3')](2), considerably perturbs the conformation of the four central base pairs, reducing the stability of the structure. UV spectroscopy and 1D NMR display a drop in melting temperature of approximately 10 degrees C per modification for the T(7) oxetane modified duplex, where the T(7) block has been introduced in both strands, compared to the native Dickerson-Drew dodecamer. The three dimensional structure has been determined by NMR spectroscopy and has subsequently been compared with the results of 2.4 ns MD simulations of the native and the T(7) oxetane modified duplexes. The modified T(7) residue is found to maintain its constrained sugar- and the related glycosyl torsion conformations in the duplex, resulting in staggered and stretched T(7).A(6) and A(6).T(7) non-linear base pairs. The stacking is less perturbed, but there is an increased roll between the two central residues compared to the native counterpart, which is compensated by tilts of the neighboring base steps. The one dimensional melting profile of base protons of the T(7) and T(8) residues reveals that the introduction of the North-type sugar constrained thymine destabilizes the core of the modified duplex, promoting melting to start simultaneously from the center as well as from the ends. Temperature dependent hydration studies by NMR demonstrate that the central T(7).A(6)/A(6).T(7) base pairs of the T(7) oxetane modified Dickerson-Drew dodecamer have at least one order of magnitude higher water exchange rates (correlated to the opening rate of the base pair) than the corresponding base pairs in the native duplex.

Base Composition↗
PubMed2005

Zinc tolerance and hyperaccumulation in F1 and F2 offspring from intra and interecotype crosses of Thlaspi caerulescens.

The relationship between zinc (Zn) tolerance and hyperaccumulation in Thlaspi caerulescens was investigated from F1 and F2 crosses within and among metallicolous and nonmetallicolous Mediterranean populations. F1 offspring were grown on increasingly Zn-enriched soils to test Zn enrichment effects, and many families of F2 offspring were grown on a Zn-rich soil. Tolerance of F1 offspring depended on stress intensity. Tolerance of interecotype crosses was intermediate between that of the intraecotype crosses. No difference in Zn accumulation appeared among the F1 offspring from the three crosses involving metallicolous parents. Otherwise, none of these offspring exceeded the Zn hyperaccumulation threshold (10,000 mg kg(-1)), unlike the nonmetallicolous ones. The latter also showed the highest mortality. In some F2 families from interecotype crosses, hyperaccumulation values exceeded 15,000 mg kg(-1) in nontolerant offspring, whereas tolerant offspring displayed lower values (c. 10,000 mg kg(-1)). There was no difference between tolerant and nontolerant offspring when they showed low hyperaccumulation. Therefore, the relationship between tolerance and hyperaccumulation in F1 and F2 crosses depended on the hyperaccumulation level of plants.

Crosses, Genetic↗
PubMed2004

History and environmental impact of mining activity in Celtic Aeduan territory recorded in a peat bog (Morvan, France).

The present study aims to document historical mining and smelting activities by means of geochemical and pollen analyses performed in a peat bog core collected around the Bibracte oppidum (Morvan, France), the largest settlement of the great Aeduan Celtic tribe (ca. 180 B.C. to 25 A.D.). The anthropogenic Pb profile indicates local mining operations starting from the Late Bronze Age, ca. cal. 1300 B.C. Lead inputs peaked at the height of Aeduan civilization and then decreased after the Roman conquest of Gaul, when the site was abandoned. Other phases of mining are recognized from the 11th century to modern times. They have all led to modifications in plant cover, probably related in part to forest clearances necessary to supply energy for mining and smelting. Zn, Sb, Cd, and Cu distributions may result from diffusional and biological processes or from the influence of groundwater and underlying mineral soil, precluding their interpretation for historical reconstruction. The abundance of mineral resources, in addition to the strategic location, might explain why early settlers founded the city of Bibracte at that particular place. About 20% of the anthropogenic lead record was accumulated before our era and about 50% before the 18th century, which constitutes a troublesome heritage. Any attempts to develop control strategies in accumulating environments should take into account past human activities in order to not overestimate the impact of contemporary pollution.

Archaeology↗
PubMed2004

Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma.

BACKGROUND AND PURPOSE: This study correlates the treated volume, the GTV and the CTV at the time of intracavitary brachytherapy (BT) with the histopathological findings obtained by surgery (S) in 33 patients (pts) with cervix carcinoma. PATIENTS AND METHODS: Sixteen pts (group I), FIGO stage IB1 (1), IB2 (4), IIB (10), IIIB (1), received external beam radiotherapy (EBT) with a total dose of 45 Gy in 5 weeks and concomitant CISPLATIN 40 mg/m(2) weekly, followed by BT up to a total dose of 15 Gy. S was performed 6-8 weeks thereafter. Seventeen pts (group II), FIGO IA2 (1), IB1 (14), IIB (2), were treated by BT alone with a total dose of 60 Gy and S after 6-8 weeks. All pts had a MRI examination after BT with a moulded applicator in situ for exact delineation of GTV, CTV and critical organs and a 3D dosimetry directly from MRI data. RESULTS: In group I (EBT + BT + S), the histopathological findings showed complete tumour sterilization (CR) in 56% of pts. Residual disease (RD) was found in 43%. Dosimetric data showed in pts with CR a larger mean treated volume (213 vs. 166 cm(3)) and a better mean coverage of the GTV and the CTV by the reference isodose (99 and 91%) as in pts with RD (85 and 77%). In group II (BT + S), CR was found in 52%, RD in 41%. Dosimetric data showed a larger mean treated volume (154 vs. 109 cm(3)) for pts with RD and a mean coverage of the GTV and the CTV by the reference isodose of 97 and 84% vs. 89 and 80% for pts with CR. CONCLUSIONS: An incomplete coverage of the GTV and/or the CTV by the reference isodose is an important risk factor for RD at the time of surgery. Furthermore, for pts who received BT alone, tumour size seemed to be a limiting factor for an accurate coverage of the CTV by the reference isodose.

Adult↗
PubMed2004

Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.

Sensorineural hearing defect and goiter are common features of Pendred's syndrome. The clinical diagnosis of Pendred's syndrome remains difficult because of the lack of sensitivity and specificity of the thyroid signs. The identification of PDS as the causative gene allowed molecular screening and enabled a re-evaluation of the syndrome to identify potential diagnostic characteristics. This report presents the clinical and genotypic findings of 30 French families, for whom a diagnosis of Pendred's syndrome had been made. Twenty-seven families had at least one mutated allele. Twenty-eight different mutations were identified, 11 of which had never been previously reported. The main clinical characteristics were: early hearing loss, fluctuation in terms of during deafness evolution, and the presence of an enlarged vestibular aqueduct.

Adolescent↗
PubMed2004

Refined mapping of the autosomal recessive non-syndromic deafness locus DFNB13 using eight novel microsatellite markers.

The locus for a type of an autosomal recessive non-syndromic deafness (ARND), DFNB13, was previously mapped to a 17-cm interval of chromosome 7q34-36. We identified two consanguineous Tunisian families with severe to profound ARND. Linkage analyses with microsatellites surrounding the previously identified loci detected linkage with markers corresponding to the DFNB13 locus in both families. Haplotype analyses assigned this locus to a 3.2-Mb region between markers D7S2468 and D7S2473. In order to refine this interval, we identified nine dinucleotide repeats in the 7q34 region. To investigate the polymorphism of these repeats, a population study of 74 unrelated individuals from different regions of Tunisia was carried out. Our results demonstrated that eight of the nine repeats are polymorphic. The average number of alleles at these informative loci was 9.12 with a polymorphism information content of 0.71. Little evidence for linkage disequilibrium between some marker pairs was found. Haplotype analysis using these microsatellites refined the DFNB13 interval to an area of 2.2 Mb between the D7S5377 and D7S2473. In order to identify the DFNB13 gene, we sequenced and eliminated three candidate genes. Other known and predicted genes are being screened for deafness-causing mutations.

Case-Control Studies↗
PubMed2004

Improving glycaemic control of patients with Type 2 diabetes in a primary care setting: a French application of the Staged Diabetes Management programme.

AIMS: To assess the impact of a French adaptation of the Staged Diabetes Management (SDM) programme on glycaemic control of people with Type 2 diabetes in primary care. Secondary endpoints were blood pressure, blood lipids, healthcare costs and quality of life. METHODS: Prospective, randomized controlled study, of 1 years' duration. General practitioners (GPs) were recruited in four separate districts of a French region. They enrolled consecutive patients with Type 2 diabetes. GPs in the intervention group were educated in the SDM programme. GPs in the control group were asked to provide usual care. Healthcare costs were collected by medical departments of the Health Insurance systems. Quality of life was assessed with the Duke Health Profile. RESULTS: Three hundred and forty patients enrolled by 57 GPs completed the study, 192 in the intervention group and 148 in the control group. Patients in the intervention group were managed more adequately in accordance with the guidelines (P < 0.05 for nine out of 10 items). HbA(1c) decreased by 0.31% in the intervention group and increased by 0.56% in the control group, resulting in a difference of 0.87% by the end of the study (P = 0.001). Blood pressure and blood lipids did not differ between groups. Occurrence of major complications was low and identical in both groups. Incremental costs during the study in the intervention group were 35 euros per patient per month, and this was not significantly different in comparison with the control group. Quality of life was not affected by the intervention. CONCLUSIONS: Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.

Blood Glucose↗
PubMed2003

Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness.

Connexins are the protein subunits of gap junction channels that allow a direct signaling pathway between networks of cells. The specific role of connexin channels in the homeostasis of different organs has been validated by the association of mutations in several human connexins with a variety of genetic diseases. Several connexins are present in the mammalian cochlea and at least four of them have been proposed as genes causing sensorineural hearing loss. We have started our functional analysis by selecting nine mutations in Cx26 that are associated with non-syndromic recessive deafness (DFNB1). We have observed that both human Cx26 wild-type (HCx26wt) and the F83L polymorphism, found in unaffected controls, generated electrical conductance between paired Xenopus oocytes, which was several orders of magnitude greater than that measured in water-injected controls. In contrast, most recessive Cx26 mutations (identified in DFNB1 patients) resulted in a simple loss of channel activity. In addition, the V37I mutation, originally identified as a polymorphism in heterozygous unaffected individuals, was devoid of function and thus may be pathologically significant. Unexpectedly, we have found that the recessive mutation V84L retained functional activity in both paired Xenopus oocytes and transfected HeLa cells. Furthermore, both the magnitude of macroscopic junctional conductance and its voltage-gating properties were indistinguishable from those of HCx26wt. The identification of functional differences of disease causing mutations may lead to define which permeation or gating properties of Cx26 are necessary for normal auditory function in humans and will be instrumental in identifying the molecular steps leading to DFNB1.

Animals↗
PubMed2003

[Brachytherapy in cervix cancers: development of techniques and concepts].

Brachytherapy plays an important role in the treatment of patients with cervical carcinoma. Technical modalities have evolved during the last years and have benefited from imaging modalities development, specially MRI. Imaging modalities contribute to a better knowledge of tumoral extension and critical organs. Ultrasound during brachytherapy has led to the almost complete eradication of uterine perforation. In the future, a more systematic use of systems allowing optimization may induce a better dose distribution in the tumor as well as in the critical organs. Recent data provided information in favor of a better analysis in the relative role of dose-rate, total dose and treated volume and their influence on the local control and complication incidence. Concomitant radiochemotherapy represents a standard in the treatment of patients with tumoral size exceeding 4 cm. Some questions still remain: is concomitant chemotherapy of benefit during brachytherapy? Is there any place for complementary surgery, specially in patients with complete response after external irradiation with concomitant chemotherapy and brachytherapy? In order to answer the former question, a phase III randomized trial is going to start, with the Fédération Nationale des Centres de Lutte Contre le Cancer as a promoter.

Antineoplastic Agents↗
PubMed2003

Mapping a gene for 46,XY gonadal dysgenesis by linkage analysis.

46,XY gonadal dysgenesis was transmitted as an autosomal-dominant trait in a large family with multiple affected members. Expressivity of the trait was highly variable, ranging from pure to partial gonadal dysgenesis associated with normal female genitalia or sexual ambiguity, to mild hypospadias in otherwise normal males. The phenotypic features of this trait appeared to be confined to the genitourinary system. Multipoint parametric analysis using markers D5S664, D5S633, and D5D2102 yielded an LOD score of 4.47, assuming sex-limited, autosomal-dominant inheritance with a penetrance of 0.6. Because mutation in testis-determining genes leads to gonadal dysgenesis in 46,XY individuals, we postulate that the gene mapped by this study normally plays a role in gonadal differentiation.

Chromosome Mapping↗