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Biomedical subjects

P Petitjean

Publications and source records attributed to P Petitjean.

At least 19 recordsLinked to original sources
PubMed2006

Indication of a cosmological variation of the proton-electron mass ratio based on laboratory measurement and reanalysis of H2 spectra.

Based on highly accurate laboratory measurements of Lyman bands of H2 and an updated representation of the structure of the ground X 1sigma(g)+ and excited B 1sigma(u)+ and C 1pi(u) states, a new set of sensitivity coefficients K(i) is derived for all lines in the H2 spectrum, representing the dependence of their transition wavelengths on a possible variation of the proton-electron mass ratio mu = m(p)/m(e). Included are local perturbation effects between B and C levels and adiabatic corrections. The new wavelengths and K(i) factors are used to compare with a recent set of highly accurate H2 spectral lines observed in the Q 0347-383 and Q 0405-443 quasars, yielding a fractional change in the mass ratio of deltamu/mu = (2.4 +/- 0.6) x 10(-5) for a weighted fit and deltamu/mu = (2.0 +/- 0.6) x 10(-5) for an unweighted fit. This result indicates, at a 3.5sigma confidence level, that mu could have decreased in the past 12 Gyr.

Journal Article↗
PubMed2004

Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa.

OBJECTIVE: To assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short-term corticosteroids for HBV-related polyartertitis nodosa (PAN). METHODS: Ten patients (8 men, 2 women, mean +/- SD age 50.4 +/- 14.4 years) with previously untreated HBV-related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti-HBe antibody (HBeAb) seroconversion was obtained or until 2-3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV-PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months. RESULTS: One death, attributed to catheter-related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted. CONCLUSION: The strategy of short-term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV-PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV-related PAN.

Administration, Oral↗
PubMed2004

Limits on the time variation of the electromagnetic fine-structure constant in the low energy limit from absorption lines in the spectra of distant quasars.

We present the results of a detailed many-multiplet analysis performed on a new sample of Mg ii systems observed in high quality quasar spectra obtained using the Very Large Telescope. The weighted mean value of the variation in alpha derived from our analysis over the redshift range 0.4</=z</=2.3 is Deltaalpha/alpha=(-0.06+/-0.06)x10(-5). The median redshift of our sample (z approximately 1.55) corresponds to a look-back time of 9.7 Gyr in the most favored cosmological model today. This gives a 3sigma limit, -2.5 x 10(-16)</=(Deltaalpha/alphaDeltat)</=+1.2 x 10(-16) yr(-1), for the time variation of alpha, that forms the strongest constraint obtained based on high redshift quasar absorption line systems.

Journal Article↗
PubMed2003

NMR structure of the HIV-1 regulatory protein VPR.

The human immunodeficiency virus type 1 (HIV-1) genome encodes a highly conserved regulatory gene product, Vpr (96 residues, 14kDa), which is incorporated into virions. In the infected cells, Vpr, expressed late in the virus cycle, is believed to function in the early phases of HIV-1 replication, such as nuclear migration of pre-integration complex, transcription of the proviral genome, viral multiplication by blocking cells in G2 phase and regulation of apoptosis phenomenon. Vpr has a critical role in long term AIDS disease by inducing infection in non-dividing cells such as monocytes and macrophages. To gain insight into the structure-function relationships of Vpr, the (1-96)Vpr protein was synthesized with 22 labeled amino acids. Its 3D structure was analyzed in the presence of CD(3)CN and in pure water at low pH and refined by restrained simulated annealing. The structure of the protein is characterized by three well-defined alpha-helices: 17-33, 38-50 and 56-77 surrounded by flexible N and C-terminal domains. In contrast to the structure obtained in the presence of TFE, the three alpha-helices are folded around a hydrophobic core constituted of Leu, Ile, Val and aromatic residues as illustrated by numerous long range NOEs. This structure accounts for the interaction of Vpr with different targets.

Amino Acid Sequence↗
PubMed2001

[The dilemma of the last vascular access].

Age and cardio-vascular pathologies in hemodialysis patients confront us with the increasing difficulties in finding vascular access. This implies the necessity to keep in place central venous catheters (CVC) and find alternative puncturing sites. CVC malfunction in dialysis is frequently encountered (87% of cases). A variety of salvage procedures are described in the literature amongst them the "stripping" and re-canalization methods. Stripping allows withdraw fibrin strands around the CVC with a success rate of 75 to 90% and a rather low complication rate, although this may not be well documented. Re-vascularization techniques allow the placement of a CVC even across a thrombosed vessel. Success rate here is 100% in a limited series of patients. In addition to the classical access sites, like internal jugular and subclavian vein exist, alternative sites such as the external jugular, femoral or even translumbar vein.

Catheterization↗
PubMed1999

Abysmal prognosis of patients with type 2 diabetes entering dialysis.

INTRODUCTION: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis. MATERIAL AND METHODS: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84). RESULTS: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients. CONCLUSION: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.

Acute Kidney Injury↗
PubMed1999

Cardiovascular morbidity and endothelial dysfunction in chronic haemodialysis patients: is homocyst(e)ine the missing link?

BACKGROUND: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. METHODS: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. RESULTS: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. CONCLUSIONS: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

Aged↗
PubMed1998

The annealing of tRNA3Lys to human immunodeficiency virus type 1 primer binding site is critically dependent on the NCp7 zinc fingers structure.

The nucleocapsid protein NCp7 of the human immunodeficiency virus type 1 contains two zinc fingers of the CX2CX4HX4C type, flanked by several basic residues, and plays a major role in viral infectivity. Thus, NCp7 was shown to promote annealing of the tRNA3Lys to the primer binding site, a key step in reverse transcription. However, previous in vitro experiments were unable to clarify the role of the zinc fingers in this process, due to nucleic acid aggregation induced by the basic N- and C-terminal domains of NCp7. We show here that deletion of these sequences in (12-53)NCp7 strongly reduces the formation of aggregates and allows a direct visualization of the binary or ternary complexes between NCp7 and nucleic acids by gel electrophoresis. (12-53)NCp7 is able to induce hybridization of the 33P tRNA3Lys and the human immunodeficiency virus type 1 viral RNA-(77-257), which contains the primer binding site. Modification of the proximal zinc finger conformation in Cys23(12-53)NCp7 led to a large reduction in this hybridization process, while replacement of Trp37 by Leu in the distal zinc fingers resulted in a complete absence of annealing activity. These data account for the in vivo loss of viral infectivity following these mutations and emphasize the critical role of the structure of the zinc finger domain of NCp7. This could facilitate a rational approach to new antiviral agents directed toward NCp7.

Amino Acid Sequence↗
PubMed1998

Properties and growth mechanism of the ordered aggregation of a model RNA by the HIV-1 nucleocapsid protein: an electron microscopy investigation.

NCp7, the nucleocapsid protein of the human immunodeficiency virus type 1, induces an ordered aggregation of RNAs, a mechanism that is thought to be involved in the NCp7-induced promotion of nucleic acid annealing. To further investigate this aggregation the morphology and the properties of the NCp7-induced aggregates of the model RNA homoribopolymer, polyA, were investigated by electron microscopy in various conditions. In almost all the tested conditions, the aggregates were spherical and consisted of a central dense core surrounded by a less dense halo made of NCp7-covered polyA molecules. The formation of these aggregates with a narrow distribution of sizes constitutes a distinctive feature of NCp7 over other single-stranded nucleic acid binding proteins. In most conditions, at the shortest times that can be reached experimentally, all the polyA molecules were already incorporated in small aggregates, suggesting that the nucleation step and the first aggregation events took place rapidly. The aggregates then orderly grew with time by fusion of the smaller aggregates to give larger ones. The aggregate halo was important in the fusion process by initiating the bridging between the colliding aggregates. In the presence of an excess of protein, the aggregates grew rapidly but were loosely packed and dissociated easily, suggesting adverse protein-protein interactions in the aggregates obtained in these conditions. In the presence of an excess of nucleotides, the presence of both amorphous nonspherical and slowly growing spherical aggregates suggested some changes in the mechanism of aggregate growth due to an incomplete covering of polyA molecules by NCp7. Finally, we showed that in the absence of added salt, the aggregate fusions were unfavored but not the initial events giving the first aggregates, the reverse being true in the presence of high salt concentrations (> or = 300 mM).

Binding Sites↗
PubMed1998

Model of the complex formed between the H2 domain of the TATA box binding protein and the L(281-301) fragment of the human transcription factor TFIIA.

Additional interactions possibly involving the well-exposed H2 helical domain of hTBP and the acidic fragment L(281-301) of the non-conserved domain of hTFIIA have been proposed to account for the apparent discrepancies between the results of mutagenesis experiments on human proteins and the structure of the ternary complex TBP/TATA box/TFIIA established from yeast proteins by X-ray crystallography. To verify this hypothesis both peptides were synthesized and their structures studied by circular dichroism (CD), NMR and molecular modelling. These peptides exist preferentially under helical conformations in solution (30% TFE in H2O). An interaction between the two peptides was observed by fluorescence (Kapp 170 microM), CD and NMR techniques. Molecular modelling studies indicate that this complex could be stabilized by electrostatic interactions involving the glutamate Glu287 and aspartates (Asp290, Asp294, Asp297 and Asp298) of L(281-301)TFIIA and lysine residues (Lys133, Lys138 and Lys145) and arginine residues (Arg137, Arg140) of H2(TBP) in agreement with mutagenesis experiments. Similar studies could now be carried out with human proteins to demonstrate the biological relevance of this interaction.

Amino Acid Sequence↗
PubMed1998

Roles of the human immunodeficiency virus type 1 nucleocapsid protein in annealing and initiation versus elongation in reverse transcription of viral negative-strand strong-stop DNA.

To study the initiation of human immunodeficiency virus type 1 reverse transcription, we have used the viral nucleocapsid protein (NC7) to anneal tRNA3Lys primer onto viral genomic RNA and have then eliminated NC7 from this primer-template complex by digestion with proteinase K and phenol-chloroform extraction of residual protein. Our data show that saturating concentrations of NC7 resulted in the formation of an active tRNA-template complex that yielded enhanced production of full-length negative-strand strong-stop DNA [(-)ssDNA] and that this complex remained active even after the elimination of NC7. While both of the two Zn finger motifs found within NC7 were essential for efficient elongation, NC protein that contained a point mutation in the first Zn finger or that was devoid of both Zn fingers yielded primer-template complexes that could still be initiated in 1-base-extension assays. In contrast, the use of heat annealing to produce primer-template complexes resulted in proportions of full-length (-)ssDNA lower than those seen with NC protein, and the addition of NC protein to such preformed primer-template complexes was able to reverse this defect only to a marginal extent.

Capsid↗
PubMed1997

The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr.

The 96-amino acid protein Vpr functions as a regulator of cellular processes involved in human immunodeficiency virus, type 1 (HIV-1) life cycle, in particular by interrupting cells division in the G2 phase. Incorporation of Vpr in the virion was reported to be mediated by the C-terminal domain of the Pr55(Gag) polyprotein precursor, which includes NCp7, a protein involved in the genomic RNA encapsidation and p6, a protein required for particle budding. To precisely define the Gag and Vpr sequences involved in this protein-protein interaction, NCp7, p6, and Vpr as well as a series of derived peptides were synthesized using Fmoc (N-(9-fluorenyl)methoxycarbonyl) chemistry. Binding assays were carried out by Far Western experiments and by competition studies using (52-96)Vpr immobilized onto agarose beads. The results show that interaction between NCp7 and Vpr occurs in vitro by a recognition mechanism requiring the zinc fingers of NCp7 and the last 16 amino acids of Vpr. Moreover, NCp10, the equivalent of NCp7 in Moloney murine leukemia virus but not polysine inhibits Vpr-NCp7 complexation. Interestingly enough, Vpr was found to interact with Gag, NCp15, and NCp7 but not with mature p6 in vitro. In vivo mutations in NCp7 zinc fingers in an HIV-1 molecular clone led to viruses with important defects in Vpr encapsidation. Together, these results suggest that NCp7 cooperates with p6 to induce Vpr encapsidation in HIV-1 mature particles. The NCp7-Vpr complex could also be important for interaction of Vpr with cellular proteins involved in cell division.

Amino Acid Sequence↗
PubMed1997

[Kidney and nitric oxide].

Nitric oxide (NO) pathway is involved in various physiological and pathophysiological processes. NO is synthesised by NO synthase. Three isoforms, ecNOS, nNOS, iNOS have been identified to date, that are encoded by 3 distinct genes on chromosome 7, 12 and 17 respectively. L-arginine is likely involved in the control of NO synthesis. In the kidney, NO regulates glomerular hemodynamics by modulating the ultrafiltration coefficient and afferent and efferent renal arteriolar resistance. NO is further involved in the pressure-natriuresis mechanism and in the tubuloglomerular feedback. Several physiopathological models have underlined the importance of the NO in arterial hypertension and in glomerular inflammation.

Animals↗
PubMed1996

Molecular gas and dust around a radio-quiet quasar at redshift 4.69.

Galaxies are believed to have formed a large proportion of their stars in giant bursts of star formation early in their lives, but when and how this took place are still very uncertain. The presence of large amounts of dust in quasars and radio galaxies at redshifts z > 4 shows that some synthesis of heavy elements had already occurred at this time. This implies that molecular gas--the building material of stars--should also be present, as it is in galaxies at lower redshifts (z approximately = 2.5, refs 7-10). Here we report the detection of emission from dust and carbon monoxide in the radio-quiet quasar BR1202 - 0725, at redshift z = 4.69. Maps of these emissions reveal two objects, separated by a few arc seconds, which could indicated either the presence of a companion to the quasar or gravitational lensing of the quasar itself. Regardless of the precise interpretation of the maps, the detection of carbon monoxide confirms the presence of a large mass of molecular gas in one of the most distant galaxies known, and shows that conditions conducive to huge bursts of star formation existed in the very early Universe.

Astronomical Phenomena↗
PubMed1996

Persistent exercise intolerance following cardiac transplantation despite normal oxygen transport.

UNLABELLED: To define the respective roles of the periphery and central oxygen transport in the exercise limitation of heart transplanted patients (HTR), we compared 11 HTR (15.1 +/- 10.8 months after transplantation) to six age and weight matched normal controls (C), during an incremental exercise test (30 W/3 min steps; supine position), up to peak exercise level. The C stopped between 120 and 240 W (mean = 180 +/- 39 W), whereas the HTR all reached 90 W, with a significantly lower oxygen uptake (VO2), cardiac index (CI) and arterio-venous oxygen difference (AVO2D) values (respectively VO2: 16.6 +/- 2.6 vs 30.0 +/- 9.3 ml.min-1.kig-1 STPD; CI: 6.84 +/- 1.10 vs 10.55 +/- 2.86l.min-1.m-2; AVO2D: 94 +/- 13 vs 109 +/- 9 ml.l-1; all p < 0.05) but with similar lactate (LA) values (respectively 7.25 +/- 1.98 vs 7.71 +/- 1.55 mmol.l-1; p = NS). At the 90 W step which corresponds to the peak level that all the HTR reached, the C were close to their anaerobic threshold and showed similar parameters of oxygen transport (VO2: 17.4 +/- 2.0; CI: 7.50 +/- 0.41; AVO2D:90 +/- 10) but a lower lactate level (LA: 2.93 +/- 4.76; p < 0.002). At the same intermediate exercise levels VO2, CI and AVO2D were similar in both groups, while the closely matched LA and ventilation increased faster in HTR, reaching significantly higher levels as soon at the 30 W step. This evidence for an increased anaerobic exercise energy generation in HTR suggests that the periphery participates significantly in their exercise limitation, a phenomenon that might be improvable by retraining. VALUES: means+/-standard deviation.

Cardiac Output↗
PubMed1996

[Selective permeability of the glomerular filtration barrier in man].

Glomerular ultrafiltration of macromolecules is a biophysical process sharing both a diffusive and a convective component, governed by glomerular hemodynamics, through a composite structure, the glomerular filtration barrier. Studies of the fractional clearance of macromolecules have showed that transcapillary filtration of macromolecules is hindered by size, electrostatic charge and to a lesser degree by spatial conformation. Several modelizations of ultrafiltration have been developped to quantify the respective role of glomerular hemodynamic and/or membrane structural alternations as found in glomerular diseases.

Capillary Permeability↗