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Biomedical subjects

C Vincent

Publications and source records attributed to C Vincent.

At least 127 records · Page 7Linked to original sources
PubMed1998

Evaluation of the capacity of dendritic cells derived from cord blood CD34+ precursors to present haptens to unsensitized autologous T cells in vitro.

Langerhans cells play a key role in contact hypersensitivity reactions. The application of haptens on the skin leads to many modifications of these cells, including the increase of major histocompatibility complex II expression, allogeneic stimulation potency, and migration towards lymph nodes to activate T cells. Moreover, it has been shown that Langerhans cells cultured in vitro are able to prime naive T cells in response to hapten contact. From CD34+ progenitors present in cord blood, we generated dendritic cells of which some presented the phenotypic markers of Langerhans cells. We show that these cells are able to sensitize syngeneic naive (CD45RA+) T cells to haptens such as trinitrophenyl conjugate of trinitrobenzene sulfonic acid (TNP) and fluoroscein isothiocyanate. The response to TNP is higher than to fluoroscein isothiocyanate, whereas sodium dodecyl sulfate, an irritant molecule used as a control, never caused this effect. Phenotypic analysis of cellular suspensions and experiments of cell sorting lead to the conclusion that only CD1a+ cells are able to induce a primary response of syngeneic T cells to TNP or fluoroscein isothiocyanate. Furthermore, we have shown a close relationship between the differentiation state of dendritic cells and their ability to prime T lymphocytes. Dendritic cells are able to present haptens in an efficient manner between day 10 and 14 of culturing CD34+ progenitors, whereas they were efficient in presenting alloantigens from day 6 until after day 20. This dissociation suggests the need of an active metabolic process for hapten presentation in the direct treatment of dendritic cells with haptens. This model of hapten presentation was used for a panel of fragrance molecules and other molecules considered as weaker haptens than TNP and fluoroscein isothiocyanate.

Antigens, CD1↗
PubMed1998

Kinetics of 131I-beta2 microglobulin in hemodialysis patients: assessment using total body counting.

The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 microCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled beta2-M excretion by an extrarenal route was nearly nonexistent. The 131I-beta2-M half-life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153+/-33 mg/L of beta2-M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing beta2-M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of 131I-beta2-M binding on the membranes, expressed as beta2-M equivalents, were 0, 16, 54, 58, and 59 mg/m2 for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the beta2-M breakdown and removal in hemodialysis patients. Intact beta2-M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the beta2-M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance beta2-M generation.

Acrylic Resins↗
PubMed1998

Two domains in vertebral development: antagonistic regulation by SHH and BMP4 proteins.

It has previously been shown that the notochord grafted laterally to the neural tube enhances the differentiation of the vertebral cartilage at the expense of the derivatives of the dermomyotome. In contrast, the dorsomedial graft of a notochord inhibits cartilage differentiation of the dorsal part of the vertebra carrying the spinous process. Cartilage differentiation is preceded by the expression of transcription factors of the Pax family (Pax1/Pax9) in the ventrolateral domain and of the Msx family in the dorsal domain. The proliferation and differentiation of Msx-expressing cells in the dorsal precartilaginous domain of the vertebra are stimulated by BMP4, which acts upstream of Msx genes. It has previously been shown that the SHH protein arising from the notochord (and floor plate) is necessary for the survival and further development of Pax1/Pax9-expressing sclerotomal cells. We show here that SHH acts antagonistically to BMP4. SHH-producing cells grafted dorsally to the neural tube at E2 inhibit expression of Bmp4 and Msx genes and also inhibits the differentiation of the spinous process. We present a model that accounts for cartilage differentiation in the vertebra.

Animals↗
PubMed1998

Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis.

OBJECTIVE: We previously reported that so-called antikeratin antibodies (AKA) and antiperinuclear factor (APF) recognize epitope(s) present on human epidermal filaggrin. In the present study, we developed a new diagnostic test for rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies (AFA) by immunoblotting. METHODS: We tested 670 serum samples, including 190 RA. AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium. Diagnostic values of the tests were compared. RESULTS: Each test resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99. Although the tests were strongly correlated, their association allowed the diagnosis of more than 60% of RA samples, with the same specificity. CONCLUSION: Immunoblot detection of AFA, a simple and standardizable test, may be an alternative or complement to conventional IIF detection of AKA.

Adolescent↗
PubMed1998

[Shouldice steel wire repair and under local anesthesia: prospective evaluation of postoperative comfort].

This study evaluates postoperative comfort of patients who have undergone inguinal hernia operations by Shouldice technique. The low analgesic consumption, the out patient management of 77% of patients, the resumption of normal activity after one week and a satisfaction index of nearly 100%, are the main results of this study. For the authors, this comfort is another argument in favour of the use of this technique.

Activities of Daily Living↗
PubMed1997

Characterization of a bacterial gene encoding an autophosphorylating protein tyrosine kinase.

Acinetobacter johnsonii harbors a protein tyrosine kinase activity that is able to catalyze autophosphorylation, like a number of eukaryotic tyrosine kinases. A biochemical and genetic analysis of this enzyme was performed. Maximum phosphorylation in vitro was obtained by incubating the kinase for 2 min at pH 7.0 in the presence of 5 mM magnesium chloride. In contrast to eukaryotic enzymes, no inhibitory effect of genistein and no phosphorylation of synthetic substrates such as poly (Glu80 Tyr20) or angiotensin II were observed. The analysis of the bacterial kinase by two-dimensional gel electrophoresis revealed the presence of at least five isoforms, all phosphorylated exclusively at tyrosine, which supports the concept that autophosphorylation occurs at multiple sites within the protein. The cloning and nucleotide sequencing of the gene encoding this kinase were achieved, which represents the first molecular characterization of a gene of this type in bacteria. An open reading frame of 2199 nucleotides encoding a protein of 82,373 Da was detected. The analysis of the deduced amino acid sequence suggested a possible involvement of the enzyme in cell recognition and bacterial pathogenicity. In addition, the cloning and sequencing of the region immediately upstream of the gene encoding the kinase revealed a novel open reading frame of 426 nucleotides encoding a phosphotyrosine protein phosphatase of 16,217 Da, which indicates that autophosphorylation on tyrosine is a physiologically reversible reaction.

Acinetobacter↗
PubMed1997

Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase.

In this paper, we report the cDNA sequence and deduced primary sequence for human cytosolic seryl-tRNA synthetase, and its expression in Escherichia coli. Two human brain cDNA clones of different origin, containing overlapping fragments coding for human seryl-tRNA synthetase were sequenced: HFBDN14 (fetal brain clone); and IB48 (infant brain clone). For both clones the 5' region of the cDNA was missing. This 5' region was obtained via PCR methods using a human brain 5' RACE-Ready cDNA library. The complete cDNA sequence allowed us to define primers to isolate and characterize the intron/exon structure of the serS gene, consisting of 10 introns and 11 exons. The introns' sizes range from 283 bp to more than 3000 bp and the size of the exons from 71 bp to 222 bp. The availability of the gene structure of the human enzyme could help to clarify some aspects of the molecular evolution of class-II aminoacyl-tRNA synthetases. The human seryl-tRNA synthetase has been expressed in E. coli, purified (95% pure as determined by SDS/PAGE) and kinetic parameters have been measured for its substrate tRNA. The human seryl-tRNA synthetase sequence (514 amino acid residues) shows significant sequence identity with seryl-tRNA synthetases from E. coli (25%), Saccharomyces cerevisiae (40%), Arabidopsis thaliana (41%) and Caenorhabditis elegans (60%). The partial sequences from published mammalian seryl-tRNA synthetases are very similar to the human enzyme (94% and 92% identity for mouse and Chinese hamster seryl-tRNA synthetase, respectively). Human seryl-tRNA synthetase, similar to several other class-I and class-II human aminoacyl-tRNA synthetases, is clearly related to its bacterial counterparts, independent of an additional C-terminal domain and a N-terminal insertion identified in the human enzyme. In functional studies, the enzyme aminoacylates calf liver tRNA and prokaryotic E. coli tRNA.

Amino Acid Sequence↗
PubMed1997

Inflorescence commitment and architecture in Arabidopsis.

Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species, terminal flower 1 in Arabidopsis and centroradialis in Antirrhinum, inflorescences that are normally indeterminate are converted to a determinate architecture. The Antirrhinum gene CENTRORADIALIS (CEN) and the Arabidopsis gene TERMINAL FLOWER 1 (TFL1) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike CEN, TFL1 is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity.

Amino Acid Sequence↗
PubMed1997

Anatomic basis for auditory brainstem implant.

Profound bilateral retrocochlear deafness cannot respond to a cochlear implant. For such patients only electrical stimulation of the cochlear nucleus complex can achieve, at best, a partial restoration of hearing. Based on the experience of the W.F. House group at the House Ear Institute in Los Angeles, we have developed an implantable device with many surface electrodes. A personal study has enabled us to establish the main relationships of the nucleus with the aim of inserting the device in contact with it, and to verify its effectiveness in the region. Histological study of anatomic specimens has shown the presence of spheroid neurone, considered to be the secondary neurone of the auditory pathway, at the level of the area of implantation.

Brain Stem↗
PubMed1997

A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family.

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Adult↗
PubMed1997

A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21.

Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by congenital hearing loss combined with retinitis pigmentosa. This dual sensorineural deficiency is transmitted in an autosomal recessive mode. Usher syndrome type I (USH1) is the most severe form. Four loci responsible for USH1 (USH1A, 1B, 1C and 1D) have previously been mapped, among which only the USH1B gene has been cloned. Using homozygosity mapping in a consanguineous family from Morocco, we identified a novel locus for USH1, USH1E, mapping to chromosome band 21q21. The delimited 15 cM interval is flanked by the loci D21S1905 and D21S1913. Subsequent segregation analysis of two families affected by USH1, in which the A, B, C and D loci had been excluded, also excluded the involvement of the USH1E locus, therefore indicating the existence of at least one more locus for USH1.

Child↗
PubMed1997

Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. We report here on the complete genomic structure of EYA1. This gene consists of 16 coding exons and extends over 156 kb. It encodes various alternatively spliced transcripts differing only in their 5' regions. Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified. Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon. This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations. To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.

Amino Acid Sequence↗
PubMed1997

Characterization of a temperature-sensitive Escherichia coli mutant and revertants with altered seryl-tRNA synthetase activity.

A mutation in the structural gene coding for seryl-tRNA synthetase in temperature-sensitive Escherichia coli K28 has been reported to alter the level of enzyme expression at high temperature (R. J. Hill and W. Konigsberg, J. Bacteriol. 141:1163-1169, 1980). We identified this mutation as a C-->T transition in the first base of codon 386, resulting in a replacement of histidine by tyrosine. The steady-state levels of serS mRNA in K28 and in the wild-type strains are very similar. Pulse-chase labeling experiments show a difference in protein stability, but not one important enough to account for the temperature sensitivity of K28. The main reason for the temperature sensitivity of K28 appears to be the low level of specific activity of the mutant synthetase at nonpermissive temperature, not a decreased expression level. Spontaneous temperature-resistant revertants were selected which were found to have about a fivefold-higher level of SerRS than the K28 strain. We identified the mutation responsible for the reversion as being upstream from the -10 sequence in the promoter region. The steady-state levels of serS mRNA in the revertants are significantly higher than that in the parental strain.

Cloning, Molecular↗
PubMed1997

Impact of litigation on senior clinicians: implications for risk management.

OBJECTIVES: To investigate the impact of litigation on consultants and senior registrars and to establish their views on methods of reducing adverse events and litigation. DESIGN: Postal survey. SETTING: Acute hospitals in the North Thames (West) Regional Health Authority. SUBJECTS: 1011 consultants and senior registrars in acute hospitals. MAIN MEASURES: Perceived causes and effects of adverse events; views on methods of reducing litigation and adverse events. RESULTS: 769 (76%) doctors responded. 288 (37%) had been involved in litigation at some point during their career; 213 surgeons (49%) and 75 (23%) doctors in the medical specialties. Anger, distress, and feeling personally attacked were common responses to litigation. Clinicians' views on reducing litigation emphasised the need for change at the clinical level. Supervision of junior staff, workload, and training in communication skills were to the fore. CONCLUSIONS: The high frequency of doctors who have experienced litigation and the emotional responses described indicate that clinicians require support at several levels. At a personal level, support can be offered to clinicians going through the litigation process or after an adverse event. Also, managerial support is needed by offering financial and practical help in correcting the factors that have been consistently identified as producing high risk situations to minimise the possibility of a reoccurrence. Accidents in medicine are, by their very nature, costly in human and financial terms and the root causes must be tackled. Recommendations are made for clinicians and risk management teams.

Attitude of Health Personnel↗
PubMed1997

Risk factors for long-term mental and psychosomatic distress in Latvian Chernobyl liquidators.

Epidemiologic studies on the health effects of the Chernobyl disaster have focused largely on physical health, whereas the psychological consequences have received little attention. The authors have assessed the associations of various exposure variables with mental and psychosomatic distress in a sample of 1412 Latvian liquidators drawn from the State Latvian Chernobyl Clean-up Workers Registry. The outcome was a mixed mental-psychosomatic disorder occurring during 1986 to 1995. Comparisons among subgroups of the cohort classified according to exposure type or level were based on the proportional hazards model. Length of work (> or = 28 days) in a 10-km radius from the reactor (relative risk [RR] = 1.39, 95% confidence interval [CI] 1.14-1.70), work (> 1 time) on the damaged reactor roof (RR = 1.46, 95% CI 1.02-2.09), forest work (RR = 1.41, 95% CI 1.19-1.68), fresh fruit consumption (> or = 1 time/day) (RR = 1.72, 95% CI 1.12-2.65) are risk factors for mixed mental-psychosomatic disorder. Construction of the sarcophagus (RR = 1.82, 95% CI 0.89-3.72) is also associated with this outcome, although nonsignificantly. Distinguishing stress-related from radiation-induced effects in this data set was difficult and these findings should provide a basis for later hypothesis testing in other cohorts.

Adult↗
PubMed1997

[Results of hearing preservation in surgery of vestibular schwannoma. Value of combined retrosigmoid and middle fossa approaches].

We report our experience of hearing preservation in acoustic neurinoma surgery, using combined retrosigmoid and middle fossa approaches. Fifty neurinomas operated on between 1987 and 1994 were included in this retrospective study. Hearing preservation surgery was performed for patients with grade II or grade III tumors (mean average tumor diameter: 14.4 mm), presenting with normal or serviceable pre-operative hearing (pure tonal average decrease less than 50 dB, speech discrimination score better than 50%). Isolated middle fossa approach was used in 3 cases, isolated retrosigmoid approach in 2 cases. The 45 other cases were operated on using both routes during the same procedure. Total removal of the tumor with anatomic facial preservation was performed in all cases. No death occurred. The facial function assessed 3 months after surgery was good in 84% of cases (House-Brackmann grades I or II). The mean follow-up was 42 months. Post-operative hearing was measurable in 48% of cases and serviceable in 30% of cases. The size of the tumor and the level of preoperative hearing appear to be the most important predictive criteria for successful hearing preservation.

Adolescent↗