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Biomedical subjects

P Dumoulin

Publications and source records attributed to P Dumoulin.

At least 19 recordsLinked to original sources
PubMed2001

[Systemic hypertension and sports practice. Epidemiology and therapeutics].

Hypertension, the most common cardiovascular disorder, also affects patients who want to practice a sport. Before counselling them, the physician should know the acute and chronic physiological effects of various sports. Is the activity authorised in a hypertensive? Yes, some physical activities are recommended and contribute to lower blood pressure readings. No, some other sporting activities can be dangerous and should be avoided. The choice of an antihypertensive agent should also take into account whether the hypertensive patient practices a sport, and especially if he/she participates in competitions.

Adolescent↗
PubMed2000

Functional analysis of six genes from chromosomes XIV and XV of Saccharomyces cerevisiae reveals YOR145c as an essential gene and YNL059c/ARP5 as a strain-dependent essential gene encoding nuclear proteins.

We report here basic functional analysis of strains deleted for six open reading frames (ORFs), YNL059c and YNL148c from chromosome XIV and YOR145c, YOR152c, YOR161c and YOR162c from chromosome XV of Saccharomyces cerevisiae. ORFs were replaced with the KanMX4 resistance marker using a long flanking homology PCR strategy in FY1679 and W303 diploid strains. Replacement cassettes were constructed in plasmid pUG7 and the cognate wild-type genes were recovered by gap repair. Sporulation and tetrad analysis revealed that deletion of YNL059c/ARP5 was lethal for vegetative growth in strain W303 and caused severe growth defects in strain FY1679 while YOR145c was essential for growth in both strains. Fusion of the green fluorescent protein (GFP) gene to the 3' ends of the YNL059c/ARP5 and YOR145c coding sequences created functional chimeric genes at the respective chromosomal loci. Both Arp5-GFP and Yor145-GFP localized to the nucleus, Yor145-GFP concentrating in the nucleolus. The vectors containing the deletion cassettes and the cognate wild-type genes, the oligonucleotides, and the deletant strains are available from the EUROFAN resource centre EUROSCARF (Frankfurt).

Actins↗
PubMed2000

A novel EH domain protein of Saccharomyces cerevisiae, Ede1p, involved in endocytosis.

Sequencing of the entire genome of S. cerevisiae has revealed the existence of five proteins containing EH domains. These are protein-protein interaction modules first described in mammalian Eps15, a protein that is involved in clathrin-dependent endocytosis. Two of the yeast proteins, End3p and Pan1p, are required for the internalization step of endocytosis. We report characterization of the nonessential ORF YBL047c which, like Eps15, encodes a protein with three N-terminal EH domains. Deletion of YBL047c leads to a defective fluid-phase endocytosis and to defective internalization of the pheromone (alpha)-factor and uracil permease. We therefore named YBL047c EDE1, for EH Domains and Endocytosis. Ede1p expressed as a chromosomally encoded fusion to the green fluorescent protein is localized in punctate cortical spots that only partially colocalize with actin patches. This localization is maintained when actin is depolymerized. Deletion of EDE1 impairs the diploid budding pattern, but has only a small impact on actin cytoskeleton organization, in contrast to the effects observed in pan1 cells and many end mutants impaired in proteins colocalizing with cortical actin patches. Genetic interaction was observed between EDE1 and RSP5, which encodes the ubiquitin ligase Rsp5p essential for ubiquitin-dependent endocytosis of many plasma membrane proteins, thus further emphasizing the functional link between Rsp5p and the EH domain proteins. We also observed genetic interaction between EDE1, and END3 or PAN1, suggesting that Ede1p might be part of a yeast EH network implicated in endocytosis.

Actins↗
PubMed1999

The Saccharomyces cerevisiae homologue of human Wiskott-Aldrich syndrome protein Las17p interacts with the Arp2/3 complex.

Yeast Las17 protein is homologous to the Wiskott-Aldrich Syndrome protein, which is implicated in severe immunodeficiency. Las17p/Bee1p has been shown to be important for actin patch assembly and actin polymerization. Here we show that Las17p interacts with the Arp2/3 complex. LAS17 is an allele-specific multicopy suppressor of ARP2 and ARP3 mutations; overexpression restores both actin patch organization and endocytosis defects in ARP2 temperature-sensitive (ts) cells. Six of seven ARP2 ts mutants and at least one ARP3 ts mutant are synthetically lethal with las17Delta ts confirming functional interaction with the Arp2/3 complex. Further characterization of las17Delta cells showed that receptor-mediated internalization of alpha factor by the Ste2 receptor is severely defective. The polarity of normal bipolar bud site selection is lost. Las17-gfp remains localized in cortical patches in vivo independently of polymerized actin and is required for the polarized localization of Arp2/3 as well as actin. Coimmunoprecipitation of Arp2p with Las17p indicates that Las17p interacts directly with the complex. Two hybrid results also suggest that Las17p interacts with actin, verprolin, Rvs167p and several other proteins including Src homology 3 (SH3) domain proteins, suggesting that Las17p may integrate signals from different regulatory cascades destined for the Arp2/3p complex and the actin cytoskeleton.

Actin-Related Protein 2↗
PubMed1996

Structure of the LexA repressor-DNA complex probed by affinity cleavage and affinity photo-cross-linking.

The structure of the complex of full-length Escherichia coli LexA repressor with a consensus operator DNA fragment has been probed by affinity photo-cross-linking and affinity cleavage. These methods allow the determination of approximate intermolecular distances between a given protein residue and a base or sugar moiety within the operator. In a first step unique cysteine residues were introduced in positions 7, 28, 38, or 52 of the protein. In all four cases, the original amino acid was an arginine. The four amino acids in these positions were expected to be situated on the surface of LexA interacting with DNA, as inferred from the structure of the LexA DNA binding domain [Fogh et al. (1994) EMBO J. 13, 3936-3944]. In a second step, these unique cysteine side chains of the purified proteins were chemically modified either with 4-azidophenacyl bromide or with S-(2-pyridylthio)cysteaminyl-EDTA. The first set of derivatives gives rise to UV-induced cross-linking which may be revealed by alkali/heat treatment; the second leads to direct DNA cleavage in the proximity of the derivatized amino acid. To reduce hydroxyl radical diffusion, the EDTA-iron cleavage reactions were done in the presence of high amounts of glycerol. The results indicate that amino acids 7 and 52 are near nucleotide pairs 8-12 of the operator and that amino acids 28 and 36 of LexA are near nucleotide pairs 5-8 of the operator. The results unambiguously define the orientation of the LexA DNA binding domain relative to the operator and provide support for the model of the LexA-operator complex proposed by Knegtel et al. [(1995) Proteins 21, 226-236]. Ethylation interference experiments further suggest that Arg-7 contacts the phosphate group between nucleotides 8 and 9 as predicted by the model.

Affinity Labels↗
PubMed1995

A model for the LexA repressor DNA complex.

A structural model for the interaction of the LexA repressor DNA binding domain (DBD) with operator DNA is derived by means of Monte Carlo docking. Protein-DNA complexes were generated by docking the LexA repressor DBD NMR solution structure onto both rigid and bent B-DNA structures while giving energy bonuses for contacts in agreement with experimental data. In the resulting complexes, helix III of the LexA repressor DBD is located in the major groove of the DNA and residues Asn-41, Glu-44, and Glu-45 form specific hydrogen bonds with bases of the CTGT DNA sequence. Ser-39, Ala-42, and Asn-41 are involved in a hydrophobic interaction with the methyl group of the first thymine base. Residues in the loop region connecting the two beta-sheet strands are involved in nonspecific contacts near the dyad axis of the operator. The contacts observed in the docked complexes cover the entire consensus CTGT half-site DNA operator, thus explaining the specificity of the LexA repressor for such sequences. In addition, a large number of nonspecific interactions between protein and DNA is observed. The agreement between the derived model for the LexA repressor DBD/DNA complex and experimental biochemical results is discussed.

Amino Acid Sequence↗
PubMed1993

Orientation of the LexA DNA-binding motif on operator DNA as inferred from cysteine-mediated phenyl azide crosslinking.

To address the question how the recognition helix of the LexA repressor is positioned within the major groove of operator DNA we have applied a site-specific photocrosslinking approach using a LexA mutant repressor (LexA-C52) that harbors a single cysteine side chain in position 52, close to the COOH terminus of helix 3. The LexA-C52 mutant repressor has been purified and modified site-specifically with the photoreactive azido compound 4-azidophenacyl bromide, giving rise to LexA-C52*. Here we show that LexA-C52* may be selectively photocrosslinked with two adjacent bases within each operator half-site. The crosslinked bases are located, respectively, 10 and 11 base pairs from the dyad axis of the operator. The crosslinking data imply that the LexA recognition helix is oriented opposite to what is generally observed for helix-turn-helix proteins and that this helix should form a steeper angle with respect to the plane of the base pairs than is observed for standard helix-turn-helix proteins.

Azides↗
PubMed1992

[Controlled study of the effect of dihydroergocristine on organic brain psychosyndrome].

The aim of this study was to verify long-term therapeutic efficacy and tolerance of dihydroergocristine (DHEC, CAS 17479-19-5) in a double blind placebo controlled study, in elderly patients with psychosyndrome characterized by memory and behaviour impairment. Two hundred patients, aged more than 65 years, were randomly divided into two groups of one hundred each. The first group received one 6-mg DHEC tablet daily for four months and the other group received placebo. The evaluation parameter for efficacy was the neuropsychological test SCAG (Scale of Clinical Assessment for Geriatrics), administered before and after 30, 60 and 120 days. The results showed a significant difference between DHEC and placebo with regard to total and partial scores of SCAG as well as to single items (mental alertness, recent memory, disorientation, anxiety, mood depression, emotional lability, motivation, uncooperativeness, fatigue, headache, tinnitus). After as few as thirty days of DHEC treatment the severity of mental and psychological symptoms was markedly decreased (p vs placebo < 0.01), as documented by significant positive changes of SCAG items. The four-month double blind period was followed by a two-month single blind period, during which patients of both groups received placebo. At the end of these two months, SCAG total score was unfavourably increased in patients previously administered DHEC, although scores were still significantly lower both versus baseline and versus previous placebo patients. Safety was good (placebo: one case of diarrhea; DHEC: one case of gastralgia and dizziness). Nine patients dropped out for reasons unrelated to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

[Physiological limits of variations in heart rate measured by the Holter method in 134 normal subjects].

Ambulatory 24 hour electrocardiography by the Holter method was carried out in 134 normal subjects (59 men, 75 women, mean age: 42.5 +/- 14 years). The average heart rate over 24 hours was 75 +/- 9 bpm, 82 +/- 10 bpm during the daytime and 64 +/- 8 bpm at night. Maximal and minimal momentary variations (over 5 minutes) were small during the night (+23% and -7%) and greater during the daytime (+47% and -16%). The heart rate slowed progressively over a two hour period before going to bed an increased progressively over a three hour period, reaching a peak and then slightly falling before getting up. The average heart rates of women were faster than in men (+5 bpm). The average heart rate fell with age from 30 years onwards (-0.4 bpm per year). Tobacco consumption did not seem to affect the heart rate. Supraventricular extrasystoles were observed in 68% of subjects during the day, and in 50% during the night; ventricular extrasystoles occurred in 42% of subjects by day and in 23% by night. Only 22% of subjects had no extrasystolic activity. Tobacco consumption and sex were unrelated to the incidence and frequency of extrasystoles. On the other hand, the incidence and frequency of extrasystoles were very significantly related to age.

Adolescent↗
PubMed1985

Long-term efficacy and safety of oral encainide in the treatment of chronic ventricular ectopic activity: relationship to plasma concentrations--a French multicenter trial.

To establish long-term efficacy and safety of encainide, 48 patients with chronic premature ventricular contractions (PVCs) underwent 6 months of therapy with encainide. Twenty-four-hour ambulatory ECGs were obtained at baseline for each daily dosage of 75 mg, 150 mg, and 225 mg of encainide during the in-hospital titration period and at the end of the first and sixth months during the follow-up period. There was a significant reduction in the median hourly total PVC rates from 480.6 at baseline to 2.0 at the end of the titration period with the highest dosage and to 22.1 at the last visit of the chronic dosing period. Nearly total suppression of PVCs was observed in 56% of patients at the end of the titration period and in 30% at the end of the 6-month follow-up period. The most common side effects were vertigo, vision disturbance, and headache. PR, QRS, and QTc intervals showed consistent significant increases from baseline during the various encainide trial periods. Encainide may have worsened ventricular arrhythmia in four patients who received more than 200 mg of encainide daily. Plasma concentrations of encainide and encainide metabolites showed wide interpatient variation, and no relationship was found between antiarrhythmic efficacy and plasma levels of encainide, O-demethyl-encainide, or 3-methoxy-O-demethyl-encainide.

Adolescent↗
PubMed1985

[Anti-arrhythmia effect of long-term encainide in chronic ventricular extrasystole].

The long term efficacy and tolerance of encainide were studied in 48 patients with chronic/ventricular extrasystoles (VES) treated for 6 months. Holter monitoring was performed before treatment and at each dose increment (75 mg/day; 150 mg/day and 225 mg/day) during the first week of titration, and then after 1 month and 6 months of treatment. The dose administered in the long-term study corresponded to the minimum effective dose during the titration phase (the dose which reduced the number of VES/24 hours by at least 75%). The average number of VES/hour decreased significantly from 480.6 before treatment to 2.0 at the end of the study. The frequency of episodes of ventricular tachycardia decreased significantly during treatment. The commonest side effects were vertigo, visual disturbances and headaches. Treatment was interrupted because of side-effects or inefficacy in 6 patients. The surface ECG showed significant lengthening of the PR, QRS and QTc periods and encainide appeared to have aggravated the ventricular arrhythmias of 4 patients receiving 200 mg/day. The plasma concentrations of encainide and its two principal metabolites were measured during the titration phase, at 1 month and after 6 months of treatment. 15.6 per cent of patients were slow and 84.4% of patients were rapid metabolizers. The wide individual variations of plasma concentrations and the absence of correlation between the plasma concentrations of encainide and its metabolites and the antiarrhythmic effect suggest that the compound and its metabolites play a role in the antiarrhythmic effect of the drug.

Adolescent↗
PubMed1985

[Electrophysiological effects of intravenous sotalol. Relation with plasma levels].

The object of this study was to confirm the electrophysiological effects of sotalol, a betablocker which increases the duration of the action potentials of myocardial cells, and to investigate the relationship of these effects with the doses used and plasma concentrations (PC) of the drug. 13 patients (23 to 72 years) were divided into 3 groups: Group 1 (n = 5): 0.6 mg/kg; Group 2 (n = 4): 1.2 mg/kg; and Group 3 (n = 5): 1.8 mg/kg. Measurements were performed before and 35 minutes after starting a 15 minute intravenous infusion of sotalol. At all doses, sotalol decreased the heart rate (HR), increased the corrected sinus node recovery time (CSNRT), prolonged the effective refractory periods (ERPA) and functional refractory periods (FRPA) of the right atrium. Atrioventricular conduction was depressed; prolongation of AH at an imposed rate of 100/min, prolongation of the nodal refractory periods (ERPN and FRPN), and an earlier Wenckebach point. The corrected QT interval (QTc) and ventricular refractory period (ERPV) increased. The QRS complexes and HV intervals were unchanged. Increases of CSNRT, AH, ERPN, FRPN, QTc, and ERPV were observed after the first dose (Group 1). At the dose of 1.8 mg/kg (Group 3) all parameters were modified (except the QRS and HV). All patients increased their ERPV by more than 20 p. 100. The parameters which illustrated the dose-effect relationship were the HR, ERPA, FRPN, and CSNRT. The PC of sotalol measured 60 minutes after starting the infusion were 0.58 +/- 0.23 microgram/ml (Group 1), 0.78 +/- 0.32 microgram/ml (Group 2) and 1.73 +/- 0.43 microgram/ml (Group 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Ventricular pre-excitation revealed by idioventricular rhythm and large QRS tachycardias. Apropos of an operated case].

A 15 year old boy presented with palpitations of sudden onset and termination over a two month period. The heart was clinically and radiologically normal. The electrocardiogramme showed sinus rhythm with a short PR interval (0,11 sec) and narrow QRS complexes (0,08 sec) associated with an intermittent escape accelerated idioventricular rhythm (AIVR). During an attack of palpitations a regular tachycardia (250/min) with wide QRS complexes of the same configuration as those of the AIVR (left side delay). The diagnosis of ventricular tachycardia was retained. Endocavitary electrophysiological recording demonstrated preexcitation of the right ventricle associated with accelerated nodal conduction explaining the narrow QRS complexes in sinus rhythm. The wide complex tachycardias initiated and terminated by paired ventricular stimulation were identical to the spontaneous attacks and were attributed to an antidromic reciprocating rhythm. The hypothesis of a rhythm arising from the accessory pathway is suggested. This would explain the identical configuration of the QRS complexes of the AIVR and of the antidromic reciprocating-rhythm and the disappearance of the AIVR after surgical section of the accessory pathway.

Adolescent↗
PubMed1981

[Rupture of the liver secondary to external cardiac massage in a patient with coronary disease : recovery after partial hepatectomy and aortocoronary by-pass (author's transl)].

A 55-year-old man developed ventricular fibrillation during an attack of acute Prinzmetal-type angina, and was treated by external cardiac massage and a defibrillator. Hemorrhagic shock due to laceration of the left side of the liver developed 48 hours later. A liver lobectomy was performed. The postoperative course was uneventful enabling a coronarography examination to be followed by an aortocoronary by-pass, good results being still present after one year. Complications of cardiac massage, especially those involving the liver, are discussed, as well as the treatment of traumatic liver lesions.

Coronary Artery Bypass↗
PubMed1980

[Results of valve replacement with cloth-covered Starr-Edwards ball valve prosthesis (author's transl)].

Cloth-covered Starr-Edwards prosthesis, was used to replace either the aortic valve (54 cases) or the mitral valve (71 cases), between 1968 and 1978, in an attempt to reduce the incidence of thrombo-embolic complications. Comparative studies using a silastene ball prosthesis during the same period showed that after aortic replacement, the mortality rate during the first month (12 p. cent), late deaths (actuarial survival curves), and most complications (including thrombo-embolin) were not significantly different in the two groups. Hemolysis is significantly greater after the two groups. Hemolysis is significantly greater after replacement with the metallic ball prosthesis; in one patient there was a mechanical change in the material. After mitral replacement, hospital mortality rates (6 p. cent) and the survival curves, after silastene or cloth-covered prostheses, did not differ significantly. Cloth covered mitral valve cause a significantly higher, but compensated rate of hemolysis, a metallic noise heard by 22 p. cent of the patients, and a significant reduction (about 1/5) in the incidence of thromboembolic complications.

Adult↗