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Biomedical subjects

F Charbonnier

Publications and source records attributed to F Charbonnier.

At least 37 records · Page 2Linked to original sources
PubMed1996

Current-based transthoracic defibrillation.

This study examines in a prospective, multicenter trial the feasibility and advantage of current-based, transthoracic defibrillation. Current-based, damped, sinusoidal waveform shocks of 18, 25, 30, 35, or 40 amperes (A) were administered beginning with 25 A for polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) or 18 A for monomorphic VT; success rates were compared with those of energy-based shocks beginning at 200 J for VF/polymorphic VT and 100 J for VT. The current-based shocks were delivered from custom-modified defibrillators that determined impedance in advance of any shock using a "test-pulse" technique; the capacitor then charged to the exact energy necessary to deliver the operator-selected current against the impedance determined by the defibrillator. Three hundred sixty-two patients received > 1 shock for VF, polymorphic VT, or monomorphic VT: 569 current- based shocks and 420 energy-based shocks. Current-based shocks of 35/40 A achieved success rates of up to 74% for VF/polymorphic VT; 30 A shocks terminated 88% of monomorphic VT episodes. Energy-based shocks of 300 J terminated 72% of VF/polymorphic VT; 200-J shocks terminated 89% of monomorphic VT. We could not demonstrate a significant increase in the success rate of current-based shocks over energy-based shocks for patients with high transthoracic impedance; this may be due to inadequate sample size. Thus, current-based defibrillation is clinically feasible and effective. A larger study will be needed to test whether current-based defibrillation is superior to energy-based defibrillation.

Electric Countershock↗
PubMed1996

Association study between schizophrenia and monoamine oxidase A and B DNA polymorphisms.

Monoamine oxidases (MAO) A and B, which are encoded by two distinct genes located on the human X chromosome, are both involved in the oxidative metabolism of dopamine. Decreased levels of platelet MAO-B activity has been reported in patients with schizophrenia and genetic variation in MAO activity had been proposed as a significant factor in the etiology of this disease. We carried out an association study using two intragenic polymorphisms within the MAO-A and MAO-B genes in 110 schizophrenic patients and 87 control subjects. For each polymorphic marker, no significant difference in allelic frequencies was observed between patients and controls. Nevertheless, a trend toward an association between allele 1 of the MAO-B gene and paranoid schizophrenia was found. Our results do not support the hypothesis that inherited variants of MAO genes might play a major role in a genetic predisposition to schizophrenia. Since several previous reports found a low MAO-B platelet activity in patients with paranoid schizophrenia, the identification of polymorphisms related to enzyme activity would be useful.

Adolescent↗
PubMed1996

Structure and cellular distribution of mouse brain testican. Association with the postsynaptic area of hippocampus pyramidal cells.

The complete deduced primary structure of mouse brain testican has been established from cDNA cloning. The cDNA encodes a polypeptide of 442 amino acids belonging to the proteoglycan family. The mouse brain testican core protein is 95% identical to its human testicular counterpart. In situ hybridization investigations revealed that mouse testican mRNA is mainly present in a subpopulation of pyramidal neurons localized in the CA3 area of the hippocampus. An immunocytochemical approach, with antibodies directed against an overexpressed chimeric antigen, produced in bacterial systems, showed that testican is associated with the postsynaptic region of these pyramidal neurons. Testican includes several putative functional domains related to extracellular or pericellular proteins associated with binding and/or regulatory functions. On the basis of its structural organization and its occurrence in postsynaptic areas, this proteoglycan might contribute to various neuronal mechanisms in the central nervous system.

Amino Acid Sequence↗
PubMed1996

No founder effect in three novel Alzheimer's disease families with APP 717 Val-->Ile mutation. Clerget-darpoux. French Alzheimer's Disease Study Group.

We sequenced exons 16 and 17 of the APP (amyloid precursor protein) gene in 18 unrelated French Alzheimer's disease (AD) patients. These patients had an onset before the age of 60 and belonged to families with autosomal dominant transmission of the disease. We detected the APP 717 Val-->Ile mutation in three out of 18 (16.6%) families. In these three families, all affected subjects had the APOE 3/3 genotype, but their ages of onset ranged from 38 to 60 years, indicating that factors other than the APOE genotype influence age of onset. Analysis of two polymorphic loci adjacent to the APP gene showed that at least two independent mutational events had occurred within these pedigrees, in spite of their origin in the same region of France.

Adult↗
PubMed1995

Alternative splicing of MLH1 messenger RNA in human normal cells.

The hMLH1 protein, composed of 756 amino acids, is the human homologue of the bacterial DNA mismatch repair protein MutL, and germ line mutations of the hMLH1 gene have been identified in kindreds with hereditary nonpolyposis colorectal cancer. We have detected three alternatively spliced forms of hMLH1 mRNA in normal lymphocytes and tissues. One of the spliced forms lacks the coding region of hMLH1 from codons 227 to 295 and the two other transcripts are predicted to encode two truncated proteins retaining the 264 and 226 N-terminal amino acids of hMLH1, respectively. The biological significance of this alternative splicing remains to be established.

Adaptor Proteins, Signal Transducing↗
PubMed1995

A simple p53 functional assay for screening cell lines, blood, and tumors.

Mutations in the p53 gene are implicated in the pathogenesis of half of all human tumors. We have developed a simple functional assay for p53 mutation in which human p53 expressed in Saccharomyces cerevisiae activates transcription of the ADE2 gene. Consequently, yeast colonies containing wild-type p53 are white and colonies containing mutant p53 are red. Since this assay tests the critical biological function of p53, it can distinguish inactivating mutations from functionally silent mutations. By combining this approach with gap repair techniques in which unpurified p53 reverse transcription-PCR products are cloned by homologous recombination in vivo it is possible to screen large numbers of samples and multiple clones per sample for biologically important mutations. This means that mutations can be detected in tumor specimens contaminated with large amounts of normal tissue. In addition, the assay detects temperature-sensitive mutants, which give pink colonies. We show here that this form of p53 functional assay can be used rapidly to detect germline mutations in blood samples, somatic mutations in tumors, and mutations in cell lines.

Adolescent↗
PubMed1995

The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease.

The major component of the vascular and plaque amyloid deposits in Alzheimer disease is the amyloid beta peptide (A beta). A second intrinsic component of amyloid, the NAC (non-A beta component of amyloid) peptide, has recently been identified, and its precursor protein was named NACP. A computer homology search allowed us to establish that the human NACP gene was homologous to the rat synuclein gene. We mapped the NACP/synuclein gene to chromosome 4 and cloned three alternatively spliced transcripts in lymphocytes derived from a normal subject. We analyzed by RT-PCR and direct sequencing the entire coding region of the NACP/synuclein gene in a group of patients with familial early onset Alzheimer disease. No mutation was found in 26 unrelated patients. Further studies are required to investigate the implication of the NACP/synuclein gene in Alzheimer disease.

Age of Onset↗
PubMed1995

Speculations on the origin of life and thermophily: review of available information on reverse gyrase suggests that hyperthermophilic procaryotes are not so primitive.

All present-day hyperthermophiles studied so far (either Bacteria or Archaea) contain a unique DNA topoisomerase, reverse gyrase, which probably helps to stabilize genomic DNA at high temperature. Herein the data relating this enzyme is reviewed and discussed from the perspective of the nature of the last detectable common ancestor and the origin of life. The sequence of the gene encoding reverse gyrase from an archaeon, Sulfolobus acidocaldarius, suggests that this enzyme contains both a helicase and a topoisomerase domains (Confalonieri et al., Proc. Natl. Acad. Sci., 1993, 90, 4735). Accordingly, it has been proposed that reversed gyrase originated by the fusion of DNA helicase and DNA topoisomerase genes. If reverse gyrase is essential for life at high temperature, its composite structure suggests that DNA helicases and topoisomerases appeared independently and first evolved in a mesophilic world. Such scenario contradicts the hypothesis that a direct link connects present day hyperthermophiles to a hot origin of life. We discuss different patterns for the early cellular evolution in which reverse gyrase appeared either before the emergence of the last common ancestor of Archaea, Bacteria and Eucarya, or in a lineage common to the two procaryotic domains. The later scenario could explain why all today hyperthermophiles are procaryotes.

Archaea↗
PubMed1995

Mutations of the presenilin I gene in families with early-onset Alzheimer's disease.

We analyzed 12 families with autosomal dominant early-onset Alzheimer' s disease (EOAD)for mutations in the coding region of the presenilin I (PSNLI) gene corresponding to the AD3 locus on chromosome 14q24.3. A total of eight missense mutations at codons 82, 115, 139, 163, 231, 264, 392, and 410 including six novel mutations, were identified in eight families. Cosegregation of the mutations with EOAD was confirmed in three families, one including 36 affected individuals. This study underlines the great allelic heterogeneity and the large distribution of the mutations within the PSNLI coding region. Our results support the notion that PSNLI is the major gene involved in autosomal dominant EOAD.

Age of Onset↗
PubMed1995

Co-segregation of thrombosis with the factor V Q506 mutation in an extended family with resistance to activated protein C.

The activated protein C (APC) resistance phenotype results from a mutation at one of the cleavage sites of factor V by APC (Q506). We describe a large family with an APC resistance phenotype and without any other detectable coagulation defect, including eight subjects who had developed deep venous thrombosis (mean age of the first thrombosis episode 29 years; range 17-55 years). The factor V Q506 mutation was detected in the seven patients with thrombosis who could be tested and in 13 asymptomatic subjects (mean age 17 years; range 5-33 years). The APC resistance was detectable in only 10 heterozygotes among the 19 tested. These data suggest that, in affected families, the risk for the factor V Q506 mutation carriers to develop thrombosis may be very high and that factor V genotyping must be performed in patients with thrombosis even without any detectable APC resistance phenotype.

Adult↗
PubMed1994

Effects of salt and temperature on plasmid topology in the halophilic archaeon Haloferax volcanii.

We report here the effect of environmental parameters, salinity, temperature, and an intercalating drug on plasmid topology in the halophilic archaeon Haloferax volcanii. We first studied the topological state of the plasmid pHV11 in media of different salt compositions and concentrations. The superhelical density of plasmid PHV11 varies in a way that depends on the kind of salt and on the concentrations of individual salts. With respect to growth temperature, the plasmid linking number increased at higher temperature in a linear way, contrary to what has been reported for Escherichia coli, in which the plasmid linking number decreased at higher temperature. These results suggest that some of the mechanisms that control DNA supercoiling in halophilic Archaea may be different from those described for E. coli. However, homeostatic control of DNA supercoiling seems to occur in haloarchaea, as in Bacteria, since we found that relaxation of DNA by chloroquine triggers an increase in negative supercoiling.

Archaea↗
PubMed1994

Comparison of plasmid DNA topology among mesophilic and thermophilic eubacteria and archaebacteria.

Several plasmid DNAs have been isolated from mesophilic and thermophilic archaebacteria. Their superhelical densities were estimated at their host strain's optimal growth temperature, and in some representative strains, the presence of reverse gyrase activity (positive DNA supercoiling) was investigated. We show here that these plasmids can be grouped in two clusters with respect to their topological state. The group I plasmids have a highly negatively supercoiled DNA and belong to the mesophilic archaebacteria and all types of eubacteria. The group II plasmids have DNA which is close to the relaxed state and belong exclusively to the thermophilic archaebacteria. All archaebacteria containing a relaxed plasmid, with the exception of the moderately thermophilic methanogen Methanobacterium thermoautotrophicum Marburg, also exhibit reverse gyrase activity. These findings show that extrachromosomal DNAs with very different topological states coexist in the archaebacterial domain.

Archaea↗
PubMed1992

Transthoracic defibrillation: effect of sternotomy on chest impedance.

The purpose of this study was to determine the effect of sternotomy on transthoracic impedance, a major determinant of current flow and defibrillation success. Transthoracic impedance was determined by using a validated test-pulse technique that does not require actual shocks. Seventeen patients undergoing median sternotomy were studied prospectively. Transthoracic impedance was determined before operation, 3 to 5 days after operation and (in eight patients) greater than or equal to 1 month after operation. When measured using paddle electrodes placed in the standard apex-right parasternal defibrillating position, transthoracic impedance declined after sternotomy in all patients, from 77 +/- 18 to 59 +/- 17 omega (p less than 0.01); smaller declines were demonstrated by using other electrode positions. Transthoracic impedance remained below the preoperative level in the eight patients who underwent a second set of measurements at least 1 month after operation. Six normal subjects not undergoing sternotomy underwent serial transthoracic impedance measurements at least 5 days apart; mean transthoracic impedance did not change. It is concluded that transthoracic impedance declines after sternotomy. At any operator-selected energy level a higher current flow will result after sternotomy; this may facilitate postoperative defibrillation.

Cardiography, Impedance↗
PubMed1992

Evidence that a plasmid from a hyperthermophilic archaebacterium is relaxed at physiological temperatures.

A plasmid of 3.45 kb (pGT5) was recently discovered in a strain of hyperthermophilic archaebacterium which was isolated from samples collected in a deep-sea hydrothermal vent. This strain (GE5) grows within a temperature range of 68 to 101.5 degrees C, and we show here that it contains a strong ATP-dependent reverse gyrase activity (positive DNA supercoiling). By comparison with eubacterial plasmids of known superhelical densities, we estimated the superhelical density of the archaebacterial plasmid pGT5 to be -0.026 at 25 degrees C. The equation which relates the change of the rotation angle of the DNA double helix with temperature was validated at 95 degrees C, the optimal growth temperature of the GE5 strain. Considering these new data, the superhelical density of plasmid pGT5 was calculated to be -0.006 at the physiological temperature of 95 degrees C, which is close to the relaxed state. This finding shows that the DNA topology of a plasmid isolated from a hyperthermophilic archaebacterium containing reverse gyrase activity is strikingly different from that of typical eubacterial plasmids.

Archaea↗
PubMed1990

Transthoracic defibrillation using sequential and simultaneous dual shock pathways: experimental studies.

Dual pathway sequential DC shocks reduce energy requirements for internal defibrillation. Our purpose was to determine if dual pathway shocks similarly reduce energy requirements or improve shock success in transthoracic (external) defibrillation. We studied 39 closed-chest anesthetized mongrel dogs. The dual pathways used were left chest to right chest and left chest to posterior. In eight dogs we also assessed dual shock pathways oriented orthogonally, left lower chest to right upper chest and left upper chest to right lower chest. Four different dual pathway groups were studied: group 1: simultaneous shocks, sinusoidal waveform; group 2: sequential shocks, sinusoidal waveform, 100-msec shock separation, orthogonal shock pathways; group 3: sequential shocks, sinusoidal waveform, 100 msec shock separation; and group 4: sequential shocks, rectangular waveform (sequential shocks: 2 pulses, 2.5 msec each, 0.1-msec separation; single shock: 1 pulse, 5 msec). Shocks were given at 50 (J) joules, 100 J and 150 J and curves of energy versus success compared for dual pathway shocks versus single shocks. We found that the highest mean success rates (96 +/- SD 9%) were achieved by simultaneous sinusoidal waveform dual pathway shocks at 100 J; this was identical to results achieved by the single pathway sinusoidal waveform comparison shocks at 100 J. Sequential dual pathway sinusoidal shocks separated by 100 msec achieved a mean success rate of 79 +/- 31% at 150 J; the comparison single pathway mean success rate was similar: 81 +/- 22% at 150 J. Thus, dual pathway sequential or simultaneous transthoracic shocks did not demonstrate clear superiority over single pathway shocks.

Animals↗
PubMed1989

Mechanisms responsible for decline in transthoracic impedance after DC shocks.

To test the hypothesis that tissue hyperemia and edema in the current pathway cause a decrease in transthoracic impedance (TTI) following direct current (DC) shock, the thoracic-skin and skeletal blood flow and blood volume were measured in anesthetized dogs after three 100-J shocks. TTI declined 11% (P less than 0.01) after DC shocks. Blood flow increased 10-fold in skeletal muscle from 0.9 +/- 0.2 to 11.3 +/- 2.6 (SE) ml.100 g-1.min-1 (P less than 0.05). Blood flow did not change outside the current pathway. Blood volume increased in skin in the current pathway from 7.6 +/- 1.5 ml/100 g preshock to 17.5 +/- 2.0 ml/100 g (P less than 0.01) at 60 min after shock; skeletal muscle blood volume did not change. We also determined postshock tissue weight before and after 72 h of drying at 70 degrees C. The percentage decline from wet weight after drying was 68.4 +/- 3.4% in the current pathway vs. 64 +/- 3.8% outside the pathway (P less than 0.05), indicating the tissue in the current pathway was more edematous. Finally, hindlimb edema was induced by deliberate overperfusion. As hindlimb circumference (edema) increased, impedance declined. We conclude that increases in tissue blood flow or tissue blood volume or tissue edema contribute to the decline in transthoracic impedance after DC shock.

Animals↗