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Biomedical subjects

E Lebrun

Publications and source records attributed to E Lebrun.

At least 19 recordsLinked to original sources
PubMed2002

Rupture of infected superficial femoral artery aneurysm. A case report.

A case of misdiagnosed infected superficial femoral artery aneurysm is presented. It was initially misdiagnosed as thrombophlebitis. Surgical excision and repair with a saphenous vein interposition graft was performed. The diagnosis of this disease is difficult because there is a lack of signs and symptoms. Staphylococcus aureus and enterobacter are the two most common organisms responsible for infected peripheral aneurysms. Surgery is the standard treatment: ligation, drainage and resection with or without arterial reconstruction depending upon the aneurysm localization.

Aged↗
PubMed2001

Homonuclear (1)H-NMR assignment and structural characterization of human immunodeficiency virus type 1 Tat Mal protein.

The transacting transcriptional activator (Tat) is a viral protein essential for activation of the human immunodeficiency virus (HIV) genes, and it plays an important role in HIV induced immunodeficiency. We report the NMR structural characterization of the active Tat Mal variant that belongs to a highly virulent D-subtype HIV type-1 (HIV-1) strain (Mal) found mainly in Africa. A full Tat Mal protein (87 residues) is synthesized. This synthetic protein is active in a transactivation assay with HeLa cells infected with the HIV long terminal repeated noncoding sequences of the HIV-1 provirus (LTR) lac Z gene. Homonuclear (1)H-NMR spectra allows the sequential assignment of the Tat Mal spin systems. Simulating annealing generates 20 conformers with similar folding. The geometry of the mean structure is optimized with energy minimization to obtain a final structure. As the European variant (Tat Bru) the N-terminal region of Tat Mal constitutes the core, and there is a hydrophobic pocket composed of the conserved Trp 11 interacting with several aromatic residues. The two functional regions of Tat (basic and the cysteine-rich regions) are well exposed to the solvent. A short alpha-helix is observed in region V adjacent to the basic region. This alpha helix induces local structural variations compared to the NMR structure of Tat Bru, and it brings the cysteine-rich and basic regions closer. This study suggests that similar folding exists among Tat variants.

Africa↗
PubMed2001

Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia.

Deletion of the 13q14 chromosomal region is frequent in B cell chronic lymphocytic leukemia (B-CLL) and is believed to inactivate a tumor supressor gene (TSG) next to RB1. We studied microsatellite markers spanning the 13q14 chromosomal region in 138 children with acute lymphoblastic leukemia (ALL). Allelic loss was demonstrated in six cases (4.3%). Deletion did not include RB1 in two cases. In five patients, the deleted region overlapped that described in B-CLL. A sixth patient harbored a smaller deletion, slightly more telomeric than minimal deleted regions reported in B-CLL. Apparent differences in the delineation of the minimal deleted region could be due to the fact that the putative TSG is a very large gene, with some deletions affecting only a part of it. Our present findings suggest that at least some of its exons lie within a region of less than 100 kb more telomeric that previously thought.

Adolescent↗
PubMed2001

An activation-independent role of transcription factors in insulator function.

Chromatin insulators are defined as transcriptionally neutral elements that prevent negative or positive influence from extending across chromatin to a promoter. Here we show that yeast subtelomeric anti-silencing regions behave as boundaries to telomere-driven silencing and also allow discontinuous propagation of silent chromatin. These two facets of insulator activity, boundary and silencing discontinuity, can be recapitulated by tethering various transcription activation domains to tandem sites on DNA. Importantly, we show that these insulator activities do not involve direct transcriptional activation of the reporter promoter. These findings predict that certain promoters behave as insulators and partition genomes in functionally independent domains.

Animals↗
PubMed2001

Protosilencers in Saccharomyces cerevisiae subtelomeric regions.

Saccharomyces cerevisiae subtelomeric repeats contain silencing elements such as the core X sequence, which is present at all chromosome ends. When transplaced at HML, core X can enhance the action of a distant silencer without acting as a silencer on its own, thus fulfilling the functional definition of a protosilencer. Here we show that an ACS motif and an Abf1p-binding site participate in the silencing capacity of core X and that their effects are additive. In addition, in a variety of settings, core X was found to bring about substantial gene repression only when a low level of silencing was already detectable in its absence. Adjoining an X-STAR sequence, which naturally abuts core X in subtelomeric regions, did not improve the silencing capacity of core X. We propose that protosilencers play a major role in a variety of silencing phenomena, as is the case for core X, which acts as a silencing relay, prolonging silencing propagation away from telomeres.

Base Sequence↗
PubMed2000

Early evolution of cytochrome bc complexes.

Primary structures, functional characteristics and phylogenetic relationships of subunits of cytochrome bc complexes from phylogenetically diverse bacterial and archaeal species were analysed. A single case of lateral gene transfer, i.e. the import of an epsilon-proteobacterial cytochrome bc(1) complex into Aquificales, was identified. For the enzyme in the remainder of the species studied, the obtained phylogenies were globally in line with small subunit rRNA trees. The distribution of a few key phylogenetic markers, such as contiguousness of cytochrome b, nature of the c-type subunit or spacing between b-heme ligands, are discussed. A localised modification of previous tree topologies is proposed on the basis of the obtained data. The comparison of extant enzymes furthermore allowed us to define the minimal functional and evolutionary core of the enzyme. The data furthermore suggest that the ancestral enzyme was put together from subunits that previously had played a role in other electron transfer chains.

Amino Acid Sequence↗
PubMed2000

1H-13C nuclear magnetic resonance assignment and structural characterization of HIV-1 Tat protein.

Tat is a viral protein essential for activation of the HIV genes and plays an important role in the HIV-induced immunodeficiency. We chemically synthesized a Tat protein (86 residues) with its six glycines C alpha labelled with 13C. This synthetic protein has the full Tat activity. Heteronuclear nuclear magnetic resonance (NMR) spectra and NOE back-calculation made possible the sequential assignment of the 86 spin systems. Consequently, 915 NMR restraints were identified and 272 of them turned out to be long range ([i-j] > 4), providing structural information on the whole Tat protein. The poor spectral dispersion of Tat NMR spectra does not allow an accurate structure to be determined as for other proteins studied by 2D NMR. Nevertheless, we were able to determine the folding for Tat protein at a 1-mM protein concentration in a 100 mM, pH 4.5 phosphate buffer. The two main Tat functional regions, the basic region and the cysteine-rich region, are well exposed to solvent while a part of the N-terminal region and the C-terminal region constitute the core of Tat Bru. The basic region adopts an extended structure while the cysteine-rich region is made up of two loops. Resolution of this structure was determinant to develop a drug design approach against Tat. The chemical synthesis of the drugs allowed the specific binding and the inhibition of Tat to be verified.

Amino Acid Sequence↗
PubMed1999

In vitro evaluation of B-CLL cells apoptotic responses to irradiation.

Defective apoptosis is a mechanism which could possibly explain B chronic lymphocytic leukemia (B-CLL) cell accumulation. Differences in evolution and prognosis of B-CLL patients may be due to heterogeneity in apoptotic cell death. We studied the apoptotic response to in vitro gamma radiation of blood mononuclear cells from 18 untreated B-CLL patients. In cells irradiated with 2, 4 or 8 Gy and then cultured for 20 hours, the percentage of trypan blue excluding (viable) cells was not modified (>92%). An apoptotic response to irradiation was detected in the majority of the patients, but the individual percentage of apoptotic cells varied widely (8 to 81% after 8 Gy irradiation) in individual cases. The flow cytometric analysis of nick-end DNA labeling demonstrated a dose effect of irradiation, particularly in patients with an apoptotic response of over 20%. In the future, a valuable clue to the selection of irradiation regimens for B-CLL patients may be the investigation of correlations between in vitro radiation-induced apoptosis and the in vivo response to radiation therapy.

Aged↗
PubMed1998

Surgical trauma does not decrease resistance to infection.

OBJECTIVE: To investigate the effect on survival of two operations done at various intervals before the induction of monobacterial or multibacterial peritonitis in rats. DESIGN: Laboratory study. SETTING: Teaching hospital, Belgium. MATERIAL: Inbred male white wistar R/A rats. INTERVENTIONS: Posterolateral laparotomy, hindleg amputation, or control (anaesthetic only) (n=90 animals in each group), followed by induction of Escherichia coli or Staphylococcus aureus peritonitis at 1, 7 or 14 days. Further groups of rats were similarly operated on (50 in each group), but peritonitis was induced by caecal ligation and puncture. MAIN OUTCOME MEASURE: Survival 7 days after induction of peritonitis. RESULTS: Of the rats in which E. coli was used to induce peritonitis 27/28 (96%), 29/29 (100%), and 21/30 (70%) had survived 7 days after induction of peritonitis in the group that underwent posterolateral laparotomy, compared with 18/30 (60%), 20/28 (71%), and 18/28 (64%) in the control group; p 0.001, 0.002, and 0.78, respectively. The figures for hindleg amputation were 21/27 (78%), 23/27 (85%), and 17/30 (57%). The corresponding figures for S. aureus peritonitis were for posterolateral laparotomy 28/30 (93%), 20/30 (67%), and 24/29 (83%) compared with controls 21/30 (70%), 9/30 (30%), and 20/29 (69%); p 0.04, 0.009, and 0.75, respectively. The figures for hindleg amputation were 21/30 (70%), 12/30 (40%), and 23/30 (77%). Similar results were obtained with peritonitis induced by caecal ligation and puncture. CONCLUSIONS: Although surgical trauma may depress various aspects of the immune response in rats, it does not decrease their resistance to intraperitoneal microbial infections. The previous opening of the peritoneal cavity seemed to improve survival in our model.

Animals↗
PubMed1996

Influence of age, lead axis, frequency of arrhythmic episodes, and atrial dimensions on P wave triggered SAECG in patients with lone paroxysmal atrial fibrillation.

Signal-averaged P wave of 42 patients with lone paroxysmal atrial fibrillation (PAF) and 29 normal subjects (N) were recorded, using three orthogonal leads and analyzed in the time and frequency (entire P wave or a 100-ms segment ranging from 75 ms before to 25 ms after the end of P wave) domains. PAFs were divided into a group of 12 having > or = 2 attacks a month (HF) and a group of 30 having < or = 2 attacks a year (LF). Statistically significant differences were absent with regard to ages of PAF and N; ages of HF, LF, and N at the time of signal-averaged ECG; ages of HF and LF at the time of the first arrhythmic episode; and elapsed times from the first episode. Length of P wave and some frequency-domain parameters were found to be significantly correlated with age. PAF showed a significantly longer duration of P wave in the frontal plane using the time-domain analysis. Frequency analysis was found to be useful in evaluating the influence of attack frequency. HF showed significantly higher values of some frequency-domain parameters than LF and N, while the three groups did not differ for time-domain analysis. P wave duration and frequency content of the three orthogonal leads proved to be significantly different in PAF and N. Right and left atrial echocardiographic dimensions proved to be higher (even if within normal limits) in HF than in LF and N. Results suggest that frequency analysis should be performed on the entire P wave.

Age Factors↗
PubMed1995

Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF-beta isoforms.

We have previously shown that TGF-beta 1 exerts a bifunctional effect on RAC proliferation. Added to quiescent cultures, it inhibits the entry of G0/G1 cells into S phase whereas in S phase synchronized populations, it stimulates the DNA replication rate with a delayed G2 + M phase and a subsequent transient increase of cell number. As TGF-beta 2 and beta 3 isoforms are also expressed in bone and cartilage tissues, it was of interest to study their effect on RAC proliferation, in comparison to that of TGF-beta 1. Using cell counting and tritiated thymidine incorporation, we found that all the TGF-beta s used here induced an increase of RAC proliferation rate occurring between 24 and 48 h of exposure. TGF-beta 2 appeared as the most efficient form as judged from the maximum of thymidine labelling. However, TGF-beta 3 induced an increase of cell number slightly higher than both TGF-beta 1 and TGF-beta 2 (+30% versus 20% for TGF-beta 1 and beta 2). TGF-beta 2 and beta 3 were able to stimulate the DNA replication rate as previously demonstrated for TGF-beta 1. However, the effect occurred later for TGF-beta 2 and beta 3 (12 h) than for TGF-beta 1 (6 h). This was confirmed by flow cytometric analysis of DNA content. In addition, immunodetection by flow cytometry demonstrated that all TGF-beta isoforms enhanced endogenous expression of TGF-beta-related peptides. The effect was shown to be associated with the cell cycle S phase and was greater for TGF-beta 3 than for TGF-beta 1 and beta 2. These findings suggest that TGF-beta s could act on RAC functions via autocrine and paracrine ways. Taken together, these data indicate that TGF-beta s may modulate proliferation of articular chondrocytes and therefore could play a role in the activation of these cells in the early stages of osteoarthritis.

Animals↗
PubMed1994

[Children in parental separation. Review of the literature].

The authors present a synthesis of the studies published in the literature since 1980 concerning the psychological consequences of parental separation on children. The risk of psychological disturbances varies according to the age and the sex of the child, and to the different parental attitudes. Pediatricians have an important role in preventing psychological consequences of parental separation on children by giving information to the parents and helping the children to understand and accept the event. In addition early recognition of psychological disturbances is important in order to offer a specialized support to the child.

Adolescent↗
PubMed1993

Rabbit articular chondrocytes (RAC) express distinct transforming growth factor-beta receptor phenotypes as a function of cell cycle phases.

We previously showed that TGF-beta 1 exerted a bifunctional effect on the proliferation of cultured rabbit articular cells (RAC), depending on the serum level present in the medium. Slowly proliferating cells (2% fetal calf serum, FCS) were growth-inhibited by TGF-beta 1, whereas actively dividing cells (10% FCS) exhibited a transient growth increase in response to the factor. Here we demonstrate that both of these cycling populations of RAC display two distinct systems of high-affinity binding sites for TGF-beta 1. However, a significant increase (60%) in the number of the highest affinity receptors was observed in the 2% FCS-treated cells compared to those cultured in 10% FCS (in 2% FCS: Kd1 = 295 +/- 78 pM, 1899 +/- 99 sites/cell; Kd2 = 1106 +/- 61 pM, 9935 +/- 940 sites/cell; in 10% FCS:Kd1 = 287 +/- 10 pM, 1054 +/- 65 sites/cell; Kd2 = 1128 +/- 101 pM, 8257 +/- 61 sites/cell). This finding was correlated with the greater number of G0/G1 cells in the population cultured in 2% FCS (70%) compared to that exposed to 10% FCS (55%). The data was further confirmed using cells synchronized in late G1/early S phase (> 80% of S phase). This cell population exhibited a single class of TGF-beta 1 high-affinity binding sites (Kd = 1140 +/- 85 pM, 6836 +/- 1787 sites/cell). In contrast, cells synchronized in G0/G1 (> 80% of cells in G0/G1) expressed one binding system of Kd = 402 +/- 59 pM (940 +/- 56 sites/cell). These results clearly demonstrate that cultured RAC express different TGF-beta 1 receptor systems as a function of the cell cycle.

Animals↗
PubMed1992

TGF-beta-induced G2/M delay in proliferating rabbit articular chondrocytes is associated with an enhancement of replication rate and a cAMP decrease: possible involvement of pertussis toxin-sensitive pathway.

This study was undertaken to gain more insight into the mechanism whereby TGF-beta influences the cell cycle progression of cultured rabbit articular chondrocytes. Using proliferating chondrocytes in fetal calf serum-containing medium, we have previously shown that TGF-beta induced a recruitment of cells at the end of the S phase (G2/M) observed 24 h after addition. The delayed cells may then be released, producing a proliferative effect at 48 h, provided a substantial amount of FCS (10%) is present in the medium. Otherwise, in low level of serum (2% FCS, for example), only inhibition of cell proliferation is observed. In chondrocytes synchronized in S phase by a thymidine block, we investigated here the time-course incorporation of [3H]-thymidine into DNA, the cell cycle traverse by flow cytofluorometric study of DNA content, the expression of PCNA (Proliferating Cell Nuclear Antigen), and cAMP levels. The data demonstrate that TGF-beta provoked a decrease of cAMP content (0.5-1 h) followed by an enhancement of the DNA synthesis rate (4 h) which was detectable through cytofluorometric analysis and [3H]-thymidine labeling and correlated with the PCNA expression. In contrast, addition of cAMP analogues to the cultures resulted in an inhibition of replication rate. We also showed that pertussis toxin produced a decrease of the DNA synthesis rate, in a transient manner and only in the presence of TGF-beta. All these results suggest that TGF-beta may accelerate the replication process of cyclized chondrocytes, making then accumulate at the G2/M boundary, via a mechanism that could involve the adenylate cyclase activity and a Gi-protein. The factor might be responsible for producing a pool of cells having already replicated their DNA and therefore capable of re-entering the cell cycle without delay. This cell population could serve as a tissue reserve able to induce a mitosis wave when necessary--for example, in the repair of tissue damage.

Adenylate Cyclase Toxin↗
PubMed1992

Flow cytometric detection of transforming growth factor-beta expression in rabbit articular chondrocytes (RAC) in culture--association with S-phase traverse.

We have previously shown that TGF-beta 1 decreased the entry of G0/G1-synchronized rabbit articular chondrocytes (RAC) into S-phase, whereas it enhanced the proliferation rate of actively dividing cells (asynchronous or S-phase-synchronized cells). The growth proliferative effect was accompanied by both increased DNA replication rate and G2/M delay. Since TGF-beta mRNA has been detected in chondrocytes, it was of interest to study the expression of the factor in correlation with the cell cycle of RAC. Using cytofluorometric analysis of both DNA content and TGF-beta protein level, we demonstrated that S-phase-synchronized RAC constitutively expressed TGF-beta, whereas G0/G1-synchronized cells only display very low levels of the factor. The data showed that the expression of TGF-beta is correlated with S-phase traverse since it increases with the percentage of cells in S-phase (less than 27% in G0/G1 to 70% in S-phase-synchronized cells). Moreover, exposure of RAC to TGF-beta 1 (1 ng/ml) for 24 h increased the percentage of positive cells, independently of the number of cells in S-phase, indicating that the factor may up-regulate its own expression. All together, these data suggest that TGF-beta could play a role in initiating the proliferation of articular chondrocytes during the early events of osteoarthritis and might take a part in the repair of cartilage matrix.

Animals↗
PubMed1990

Inhibition of bovine dihydrofolate reductase and enhancement of methotrexate sensitivity by N4-(2-acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone.

N4-(2-Acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone (AATSC) belongs to a series of molecules known to have broad antimicrobial inhibitory activity. These molecules contain the 2-acetoxyethoxy moiety which could conceivably take up a conformation analogous to that of the ribosyl group. Moreover, the thiosemicarbazone moiety, when in the presence of a suitable enzymatic site, could mimic the triazine group, which is found in a number of antifolate drugs. AATSC, which has both bacterial inhibitory activity and water solubility, was accordingly evaluated for its antifolate activity against the bovine liver dihydrofolate reductase. AATSC is shown to be a fully uncompetitive inhibitor of that enzyme. Furthermore, AATSC enhances the activity of methotrexate. Such a potentiation could be useful for therapeutic purposes.

Animals↗