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Biomedical subjects

D Chevalier

Publications and source records attributed to D Chevalier.

At least 37 records · Page 2Linked to original sources
PubMed2001

Near total laryngectomy with epiglottic reconstruction. our experience of 65 cases.

From 1980 to 1998, 65 patients whose glottic lesions were classified T1 or T2 were operated with a reconstructive anterior frontal laryngectomy with epiglottoplasty such as described by Tucker (Arch Otolaryngol Head Neck Surg 115:1341-1344). This procedure consists of resection of the two vocal cords, in some cases one arytenoid, the anterior commissure with a part of the thyroid cartilage, the anterior part of both false vocal cords, and of 1 cm of the subglottis. The epiglottis is grasped downward to close the larynx. There were no per or postoperative deaths. Our functional results confirm those reported in the previous publications. The mean time of removal of the nasogastric tube was about 12 days and the patients were generally satisfied about their residual voice. Decannulation was performed after satisfactory peroral feeding, generally about 2 weeks postoperatively. Three patients only required subsequent procedures which can be considered due to functional failures. There were four recurrences, which means a 5-year actuarial local control rate of 94%. This operation takes place as part of our surgical treatment policy of laryngeal carcinomas, considering that this surgery is like an extensive frontolateral laryngectomy. In case of an infiltrating tumor or in case of invasion to the arytenoid cartilage, we perform a supracricoid partial laryngectomy with crico-hyoido-epiglottopexy (the Majer-Piquet's procedure).

Adult↗
PubMed2001

Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacylcin synthase gene (CYP8A1).

Inheritable interindividual differences in prostacyclin production may be implicated in the pathogenesis of several human vascular diseases. Using a polymerase chain reaction/single-strand conformation polymorphism strategy, we screened for mutations in the gene encoding cytochrome P450 prostacyclin synthase (CYP8A1). DNA samples from healthy French volunteers (n = 130) of Caucasian origin were examined. Five mutations, comprising two previously reported silent mutations and three novel rare missense mutations (P38L, S118R, and R379S), were identified in the coding sequence of the gene. In the 5'-proximal region, we also found a variable number of tandem repeats (VNTR) polymorphism that consisted of four different alleles with 4-6 tandem repeats of a 9-bp unit containing a putative Spl transcriptional factor binding site. One of these (R6), a frequent allele (23.6% of alleles tested) harboring six repeats, is novel, whereas the other three are known. In vitro analysis of the effect of each VNTR allele on promoter activity of a reporter gene was performed by a transient transfection assay. Data confirmed the modulator effect of the VNTR polymorphism on reporter gene transcription. Furthermore, the data demonstrate that allele R6 has the most potent inducing effects in the A549 cell line and, after IL-6 stimulation, in human pulmonary artery endothelial cells. Overall, the data demonstrate that CYP8A1 is polymorphic in Caucasians, and that a polymorphism affecting the 5'-proximal region may result in interindividual differences in CYP8A1 transcriptional regulation in vivo. Additional factors, such as the presence of inflammatory mediators, may be required to modulate transcription of the CYP8A1 gene.

5' Untranslated Regions↗
PubMed2001

Identification of genetic variants in the human thromboxane synthase gene (CYP5A1).

Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It has been implicated in the patho-physiological process of a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and asthma. On the basis of the hypothesis that variations of the CYP5A1 gene may play an important role in human diseases, we performed a screening for variations in the human CYP5A1 gene sequence. We examined genomic DNA from 200 individuals, for mutations in the promoter region, the protein encoding sequences and the 3'-untranslated region of the CYP5A1. Eleven polymorphisms have been identified in the CYP5A1 gene including eight missense mutations R61H, D161E, N246S, L357V, Q417E, E450K, T451N and R466Q. This is the first report of genetic variants in the human CYP5A1 altering the protein sequence. The effect of these variants on the metabolic activity of CYP5A1 remains to be further evaluated.

Alleles↗
PubMed2001

Lingual thyroid. A case report.

We describe an unusual clinical case in which a non functional cervical thyroid coexisted with a functional ectopic lingual thyroid. A twenty-year-old woman was referred for hypothyroidism treated with L-thyroxin related to a basilingual tumor diagnosed 8 years previously. Oropharyngeal examination showed a spherical basilingual tumor 2.5 cm in diameter. Laboratory findings during treatment with 50 microgram of L-thyroxin daily showed: TSH 6,280 microIU/ml (N: 4,4 to 3.6), FT3 4,2 pmol/l (N: 3.3 to 5.1), and FT4 15.4 pmol/l (N: 10,5 to 25,5). Antithyroid antibodies were absent. Cervical ultrasonography showed a small hypoechogenic, heterogeneous orthotopic thyroid gland confirmed by cervical computed tomography thyroid. An I(123) scan revealed uptake above the chin on the profile, and no significant uptake is the area of the normal thyroid. The lack of iodine uptake by the cervical thyroid remains unexplained. In conclusion, this report of an ectopic thyroid location in unusual because of the coexistence of non functional cervical thyroid and of a partially functional lingual thyroid tissue. The pathogenesis of this association remains unclear.

Adult↗
PubMed2000

Two distinct forms of MAPKAP kinase-2 in adult cardiac ventricular myocytes.

Hsp27 kinase activities were studied in adult rat ventricular myocytes following sequential chromatography on Mono Q and Mono S. A basal level of activity was present following cell isolation. FPLC on Mono Q revealed three peaks of activity, peaks 'a', 'b', and 'c'. A fourth peak, 'd', was detected upon subsequent chromatography of the Mono Q flow-through on Mono S. Immunoblotting revealed that peaks 'a', 'b', and 'c' contained predominantly a 49 kDa form of MAPKAP kinase-2. Peak 'd' contained a 43 kDa form. 'In-gel' kinase assays using hsp27 indicated both forms of MAPKAP kinase-2 were active. No other bands of hsp27 kinase activity were detected. Both forms of hsp27 kinase immunoprecipitated with a MAPKAP kinase-2 antibody and have therefore been named MAPKAP kinase-2alpha (p49) and MAPKAP kinase-2beta (p43). MAPKAP kinase-2beta chromatographed on Superose 12 as a 60.7 kDa monomer whereas the behavior of MAPKAP kinase-2alpha suggested both a 65.7 kDa monomer and higher molecular mass complexes. Both activities phosphorylated hsp27 on serine residues, and two-dimensional phosphopeptide mapping indicated the same sites were phosphorylated. A tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated both MAPKAP kinase-2alpha and MAPKAP kinase-2beta activity. Inhibition of MEK activation with PD 98059 or p38alpha/beta MAP kinase activity with SB203580 blocked activation by PMA. However, whereas PD 98059 inhibited only the PMA-stimulated activation, SB203580 inhibited both PMA-stimulated and basal hsp27 phosphorylation. These data demonstrate the presence of two forms of MAPKAP kinase-2 in adult ventricular myocytes. Both forms are activated indirectly by the ERK MAP kinase pathway and directly by p38 MAP kinase but independently regulated.

Amino Acid Sequence↗
PubMed2000

Purification of myelin basic protein from bovine brain.

Myelin basic protein (MBP) is a commonly used substrate for in vitro determination of numerous protein kinase activities. Herein we describe a rapid method for isolating relatively large amounts of MBP from bovine brain with a purity greater than that currently available from commercial sources. Lipids were first extracted from the CNS tissue by homogenization in sec-butanol. Washes under neutral and mildly basic conditions were employed to remove neutral and acidic proteins from the defatted residue. MBP was subsequently extracted under acidic conditions and further purified by chromatography on CM Sephadex C-25. Potential contaminating enzyme activities were destroyed by heart treatment. This method typically yields a recovery of 1.0-1.5 mg MBP per gram of starting material with a purity of greater than 95%. The MBP prepared in this manner was suitable for determination of kinase activities by both solution and the "in gel" kinase assay systems.

Animals↗
PubMed2000

Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society.

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.

Glottis↗
PubMed2000

Composite reconstruction of hypopharynx and esophagus.

Extended surgical resection of the whole esophagus and associated hypopharynx may require composite reconstructions using a combination of pediculated and free tissue units. Twelve patients were assigned to composite reconstructions of the hypopharynx and esophagus for either metachronous carcinoma of the esophagus and head and neck (group I, n = 4), cervical anastomotic recurrence of esophageal carcinoma (group II, n = 3), or secondary reconstruction after the failure of a previous reconstruction of hypopharynx or esophagus (group III, n = 5). Pediculated tissues were the stomach (n = 10), colon (n = 1), or jejunum (n = 1). A free jejunal graft was constantly interposed between the pharynx and the mobilized organ. There were no hospital deaths. Swallowing function was restored in all patients except one who had cervical leakage as a result of partial necrosis of the free jejunal graft. Composite reconstruction permitted, even in groups I and II in which prognosis was extremely poor, prolonged survival and oral feeding, which proved beneficial in terms of the patients' quality of life.

Adult↗
PubMed2000

Molecular analysis of the N-acetyltransferase 1 gene (NAT1*) using polymerase chain reaction-restriction fragment-single strand conformation polymorphism assay.

One major interest to analyse the extent of N-acetyltransferase 1 (NAT1*) allelic variation in the human population stems to a great extent from the possible association of interindividual differences in the metabolism of aromatic amines with certain chemically induced diseases, including cancer. Considering the increasing number of mutations in the NAT1 gene that are detected, NAT1* genotyping using conventional polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) or allele-specific amplification assays has become complicated. We developed a rapid and powerful strategy allowing the full characterization of NAT1* alleles. This method, based on single-strand conformation polymorphism analysis of a unique PCR product encompassing the entire intronless NAT1*-coding region along with additional flanking segments in the 5' and 3' untranslated regions, was then applied to DNA samples from 270 individuals. Nine NAT1* allelic variants, including two novel (NAT1*28 and NAT1*29), and 15 different genotypes were identified. This approach could be advantageously used in epidemiological studies to provide more definite data on suspected associations between NAT1* genotype and certain pathological processes.

Alleles↗
PubMed1999

Molecular analysis of NOZZLE, a gene involved in pattern formation and early sporogenesis during sex organ development in Arabidopsis thaliana.

Sexual reproduction is a salient aspect of plants, and elaborate structures, such as the flowers of angiosperms, have evolved that aid in this process. Within the flower the corresponding sex organs, the anther and the ovule, form the male and female sporangia, the pollen sac and the nucellus, respectively. However, despite their central role for sexual reproduction little is known about the mechanisms that control the establishment of these important structures. Here we present the identification and molecular characterization of the NOZZLE (NZZ) gene in the flowering plant Arabidopsis thaliana. In several nzz mutants the nucellus and the pollen sac fail to form. It indicates that NZZ plays an early and central role in the development of both types of sporangia and that the mechanisms controlling these processes share a crucial factor. In addition, NZZ may have an early function during male and female sporogenesis as well. The evolutionary aspects of these findings are discussed. NZZ encodes a putative protein of unknown function. However, based on sequence analysis we speculate that NZZ is a nuclear protein and possibly a transcription factor.

Amino Acid Sequence↗
PubMed1999

Surgical treatment of T1-T2 glottic carcinomas.

Transoral laser surgery (TLS) is a safe, time and cost-effective method of treatment for early stage glottic squamous cell carcinoma. This technique is more controversial in case of local extension to other subsite or in case of limited mobility.

Carcinoma, Squamous Cell↗
PubMed1998

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

Alleles↗