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Biomedical subjects

F Charbonnier

Publications and source records attributed to F Charbonnier.

14 recordsLinked to original sources
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↗
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↗
PubMed1988

Factors affecting transthoracic impedance during electrical cardioversion.

Successful cardioversion is dependent on the delivery of sufficient current. Current is determined by energy and transthoracic impedance (TTI). Our purpose was to assess factors affecting TTI in humans. Twenty-eight patients undergoing elective cardioversion were monitored up to 48 hours after shock delivery. We also studied 10 normal subjects, who did not receive shocks, for comparison. TTI declined 8% in the first hour in patients who received shocks, but also 6% in the normal subjects who wore the same pads for 1 hour but received no shocks. Twenty-four hours later, TTI returned to baseline in the nonshocked subjects but remained reduced (93% of control, p less than 0.05) in the shocked patients. There was a correlation between the total energy delivered and the decline in TTI (r = 0.69). TTI was 9% lower at end-expiration than at end-inspiration (55 +/- 3 vs 50 +/- 3 ohms, mean +/- standard error of the mean, p less than 0.01, paired t test). In the normal subjects, when a nonsalt-containing coupling agent (ultrasound coupling gel) was compared with a salt-containing gel (Redux paste), TTI was 20% higher (65 +/- 5 vs 54 +/- 4 ohms, p less than 0.01) with the nonsalt-containing gel. When no coupling agent was used, TTI was markedly higher, 160 +/- 18 ohms (p less than 0.01 vs control). After 1 hour, TTI decreased 6% in the normal subjects when salt-containing gel was used, but did not change when a nonsalt gel was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1988

Energy, current, and success in defibrillation and cardioversion: clinical studies using an automated impedance-based method of energy adjustment.

The purposes of this study were two. First, we wanted to evaluate in patients a technique for automated adjustment of selected energy for defibrillation or cardioversion based on transthoracic impedance. Second, we wanted to define the relationship of peak current and shock success in various arrhythmias. Applying a previously validated method of predicting transthoracic impedance in advance of any shock, we modified defibrillators to automatically double the operator-selected energy if the predicted impedance exceeded 70 omega. Success rates of shocks given for ventricular and atrial arrhythmias from these modified energy-adjusting defibrillators were compared with success rates for shocks given from standard defibrillators. We prospectively collected data on 347 patients who received a total of 1009 shocks. Low-energy (100 J) shocks given to high-impedance (greater than or equal to 70 omega) patients had a poor success rate; in such high-impedance patients significant improvement in shock success rate was achieved by the energy-adjusting defibrillators. For example, when 100 J shocks were selected for high-impedance patients in ventricular fibrillation the energy-adjusting defibrillators achieved a shock success rate of 75%, whereas standard defibrillators achieved a shock success rate of only 36% (p less than .01). Similar improvements were seen for ventricular tachycardia and atrial fibrillation. Thus, automated energy adjustment based on transthoracic impedance is a beneficial approach to defibrillation and cardioversion. For ventricular fibrillation, atrial fibrillation, and atrial flutter there was a clear relationship between peak current and shock success.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1988

Pediatric defibrillation: importance of paddle size in determining transthoracic impedance.

Transthoracic impedance is a major determinant of successful defibrillation or cardioversion, but no data are available concerning the range and determinants of transthoracic impedance in children. Transthoracic impedance was measured in ten ambulatory infants, 6 weeks to 9 months of age, and 37 children, 1.5 to 15 years of age, using a previously validated "test pulse" technique that measures transthoracic impedance without actually delivering a shock. We used hand-held "pediatric" (21 cm2) and "adult" (83 cm2) electrode paddles coated with either Redux paste or Redux creme. Transthoracic impedance in children was 108 +/- 24 omega (range 61 to 212 omega) using pediatric paddles. Using adult paddles lowered the transthoracic resistance by 47% to 57 +/- 11 omega (range 29 to 101 omega), P less than .05. In infants, transthoracic impedance (measured only with pediatric paddles) was 94 +/- 17 omega (range 74 to 124 omega). Using Redux paste as the coupling agent reduced transthoracic impedance by 13% (P less than .05). Transthoracic impedance was significantly but poorly related to body weight and body surface areas, but the correlations were not sufficiently high to be clinically useful. These data indicate that the larger adult electrode paddles will minimize transthoracic impedance and should be used when the child's thorax is large enough to permit electrode to chest contact over the entire paddle surface. This transition occurred at an approximate weight of 10 kg.

Adolescent↗
PubMed1985

Defibrillator electrode-chest wall coupling agents: influence on transthoracic impedance and shock success.

The purpose of this study was to determine if the difference in transthoracic impedance produced by different coupling agents affects the success of shocks for defibrillation. Three different coupling agents, Harco pads (Hewlett-Packard), Littman pads (3M) and Redux paste (Hewlett-Packard), were assessed in 10 anesthetized dogs in which ventricular fibrillation was induced by electrical stimulation of the right ventricle. Defibrillation was attempted 15 seconds later, using 50, 100 and 150 joules (selected energy). Actual delivered energy, current, impedance and the percent of the shocks that achieved defibrillation were determined for the three coupling agents. Redux paste gave significantly lower impedance and higher current than the two disposable performed coupling pads tested. Despite this, there were no significant differences in shock success among the three coupling agents. Thus, in this experimental model, over a three-fold energy range, disposable coupling pads were as effective as electrode paste for defibrillation despite the slightly higher impedance of the disposable pads.

Alcohols↗
PubMed1985

Automated impedance-based energy adjustment for defibrillation: experimental studies.

In defibrillation, current flow depends on the energy selected and the transthoracic impedance. If transthoracic impedance is high, current flow may be inadequate to defibrillate. We developed a method by which high transthoracic impedance is automatically compensated for by an increase in operator-selected energy when impedance is high. Transthoracic impedance was predicted in advance of the first shock by passing a low-level current between the defibrillator electrodes during the defibrillator charge cycle; a microprocessor monitored current flow and determined impedance. In 28 mongrel dogs we manipulated transthoracic impedance by placing glycerin-soaked gauze pads between the paddle electrodes and the chest. If the predicted impedance exceeded a preset value, the delivered energy was automatically increased by 40% or 100%. Using this impedance-based energy adjustment technique, we found significant improvements in current flow and success rate of shocks when energy was automatically increased to compensate for high transthoracic impedance. The use of transthoracic impedance as a basis for energy adjustment appears a promising technique to minimize the hazards of high electrical energy; it allows low-energy shocks in most patients while avoiding inappropriate low energies in patients with high impedance. Clinical trials are justified.

Animals↗
PubMed1984

Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.

The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.

Arrhythmias, Cardiac↗