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Biomedical subjects

S Laurent

Publications and source records attributed to S Laurent.

At least 19 recordsLinked to original sources
PubMed2001

Rab3a controls exocytosis in cholecystokinin-secreting cells.

The expression of rab3A and rab3D isoforms in the enteroendocrine, cholecystokinin-secreting, cell lines STC-1 and GLUTag is here demonstrated. In contrast, rab3B is undetectable in these two cell lines, and rab3C is only slightly expressed in GLUTag cells. Using a transient co-transfection system with human growth hormone as reporter protein, we show that overexpression of the GTPase-deficient mutant rab3AQ81L, but not rab3DQ81L, significantly decreases human growth hormone secretory responses to various agonists in STC-1 cells. These results indicate that endocrine cell lines of intestinal origin express rab3A and rab3D proteins, but the GTP-bound form of rab3A only acts as a negative modulator in the control of cholecystokinin secretion from STC-1 cells.

Animals↗
PubMed2001

Slow clearance gadolinium-based extracellular and intravascular contrast media for three-dimensional MR angiography.

The objective of this study was to assess two new slow-clearance contrast media with extracellular and intravascular distribution for magnetic resonance angiography (MRA). Extracellular Gd-DTPA-BC(2)glucA and intravascular Gd(DO3A)(3)-lys(16) were developed within the European Biomed2 MACE Program and compared with two reference compounds, intravascular CMD-A2-Gd-DOTA and extracellular GdDOTA, in 12 rats. Pre- and post-contrast three-dimensional MR (TR/TE = 5 msec/2.2 msec; isotropic voxel size 0.86 mm(3)) was acquired for 2 hours. Signal-to-noise enhancement (DeltaSNR) was calculated. Two minutes after injection, all contrast media provided strong vascular signal enhancement. The DeltaSNR for Gd-DTPA-BC(2)glucA, Gd(DO3A)(3)-lys(16), CMD-A2-Gd-DOTA, and GdDOTA were 13.0 +/- 1.8, 25.0 +/- 3.2, 25.0 +/- 4.0, and 18.0 +/- 3.4, respectively. Gd-DTPA-BC(2)glucA, Gd(DO3A)(3)-lys(16), and CMD-A2-Gd-DOTA cleared slowly from the circulation, whereas GdDOTA cleared rapidly. Vascular DeltaSNR at 2 hours were 2.9 +/- 0.6, 25.0 +/- 3.2, 25.0 +/- 4.0, and 0.4 +/- 1.0. Gd(DO3A)(3)-lys(16) provided strong vascular and minor background enhancement, and thus may be useful for MRA or perfusion imaging. Gd-DTPA-BC(2)glucA produces persistent enhancement of extracellular water, and thus may allow quantification of extracellular distribution volume and assessment of myocardial viability.

Animals↗
PubMed2001

Deuterium NMR study of the MP-2269: albumin interaction--a step forward to the dynamics of non-covalent binding.

MP-2269, the Gd(III) complex of 4-pentylbicyclo[2.2.2]octane-1-carboxyl-di-L-aspartyl-lysine-derived-DTPA, is a small Gd-agent that binds non-covalently to serum albumin in vivo to assume the enhanced relaxivities associated with macromolecular agents, (due in part to increased rotational correlation time, tau(R)). To further explore the fundamental parameters that govern the dynamics of water proton relaxation enhancement by this prototypical albumin-binding agent, the rotational correlation time (tau(R)) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using 2H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the alpha-position of the carbonyl groups. 2H-NMR studies were conducted at 7.05T (46 MHz) and 310 degrees K on a Bruker NMR spectrometer. Spectral deconvolution permitted calculation of transverse relaxation rates, 1/T(2), from the NMR linewidths and subsequently, tau(R). The results yielded a tau(R) of the albumin bound complex of approximately 8 ns. This value is intermediate between those earlier estimated by 17O-NMR ( approximately 1 ns) and 1H-NMRD ( approximately 20-50 ns) and significantly shorter than that of albumin. The 2H-NMR study results also indicate that the exchange between free and albumin-bound forms of the La(III) analog is slow (exchange lifetimes >1 ms). This slow exchange does not affect the water residence lifetimes (tau(M) 140-280 ns).

Contrast Media↗
PubMed2001

Albumin-bound MRI contrast agents: the dilemma of the rotational correlation time.

Human serum albumin (HSA) binds numerous molecules, among which are suitably designed MRI contrast agents. The rotational tumbling of the protein is thus one of the parameters likely to affect the in vivo relaxivity of these agents. Literature unveils discrepancies about the value of the rotational correlation time (tau(R)) of HSA. In the present work, the tau(R) of this protein has been determined by studying the deuterium relaxation rate of small molecules known for their strong binding to HSA (warfarin and 4-hydroxycoumarin). Values of approx. 20-22 ns are obtained at 310 K in a 4% HSA solution and are in good agreement with the theoretical predictions.

4-Hydroxycoumarins↗
PubMed2001

Stereospecific binding of MRI contrast agents to human serum albumin: the case of Gd-(S)-EOB-DTPA (Eovist) and its (R) isomer.

The water proton relaxation rate enhancement of the hepatospecific Gd-(S)-EOB-DTPA (Eovist) and of its (R) isomer in aqueous solutions free of protein, in serum and in 4% human serum albumin solution, are compared. In the absence of proteins, both compounds exhibit, as expected, the same proton relaxivity, as measured by the nuclear magnetic relaxation dispersion (NMRD) profiles. In serum and albumin solution, non-covalent binding of the paramagnetic complexes to macromolecules is observed. Both isomers are likely to bind to the same site of human serum albumin, but the affinity of the (S) isomer is larger than for the (R) isomer.

Contrast Media↗
PubMed2001

Mechanical properties and structure of carotid arteries in mice lacking desmin.

OBJECTIVE: Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS: To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves of the common carotid artery (CCA) in homozygous (Des -/-), heterozygous (Des +/-) and wild-type (Des +/+) mice. To evaluate the mechanical strength, we have measured the in vitro intraluminal pressure producing the rupture of the carotid artery wall. The structure analysis of the arterial wall was based on histology and electronic microscopy. RESULTS: A lower distensibility and an increase of arterial wall viscosity were observed in Des -/- compared with Des +/+. Arterial thickness of Des -/- was similar to those of Des +/+, without changes in elastin and collagen contents. Electron microscopy revealed that the perimeter of cellular fingerlike-projections was smaller in Des -/-, indicating that the cells have lost part of their connections to the extracellular matrix. The rupture pressure was significantly lower in Des -/- (1500+/-200 mmHg) compared with Des +/+ (2100+/-80 mmHg) indicating a lower mechanical strength of the vascular wall. No significant difference was found between Des +/- and Des +/+. CONCLUSION: The desmin is essential to maintain proper viscoelastic properties, structure and mechanical strength of the vascular wall.

Analysis of Variance↗
PubMed2001

Expression of presumed specific early and late factors associated with liver regeneration in different rat surgical models.

Experiments performed on the portal branch ligation (PBL) model indicate that early changes observed after surgery are not related to the regenerative process because they also occur in atrophying lobes. To further confirm the lack of specificity of the early events and to exclude the influence of circulatory factors released by proliferating lobes on their occurrence, we investigated this response after sham operation (SO) and portacaval shunt (PCS), a model characterized by liver atrophy. We also attempted to determine expression of later events associated specifically with regeneration, ie, expression of p53 or c-Ha-ras, or inhibition of proliferation, ie, interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) after partial (PH) and temporary partial (TPH) hepatectomy, SO and PCS. Nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) DNA binding were assessed by electrophoretic mobility shift assay (EMSA), interleukin-6 (IL-6) mRNA by reverse transcription-polymerase chain reaction (RT-PCR), c-myc and c-jun mRNAs by Northern blot analysis at 0.5 and 2 hours, p53 and c-Ha-ras mRNAs by Northern blot analysis at 8 and 24 hours, and IL-1beta and TGF-beta1 by RT-PCR at 24 hours. The early response including an increase of NF-kappaB, STAT3, IL-6, and immediate-early genes expression was present after PH, PCS, and SO. In SO, slight differences were observed in comparison with PH: no NF-kappaB p65/p50 DNA binding was observed, only three of six SO rats were positive for IL-6, and immediate-early genes induction showed differences in the intensity of the response. At later times, p53 mRNA increased at 8 hours after PH and TPH, c-Ha-ras mRNA at 24 hours after PH, and IL-1beta mRNA at 24 hours after PCS. Early events are not specifically associated with the reduction of liver mass or with the regenerative process, are not predictive of future cell fate, and are most likely related to surgical stress. p53 and c-Ha-ras induction is closely associated with cell cycle progression whereas IL-1beta, but not TGF-beta1, appears to be one of the negative growth regulators that might play an important role in atrophy.

Animals↗
PubMed2001

Stability of MRI paramagnetic contrast media: a proton relaxometric protocol for transmetallation assessment.

RATIONALE AND OBJECTIVES: The suitability of paramagnetic complexes as magnetic resonance contrast agents depends on various factors such as their relaxivity, stability, selectivity, and the inertness toward transmetallation by endogenous ions. The transmetallation of a series of 18 gadolinium complexes by the Zn2+ ion was studied in vitro by proton relaxometry. METHODS: Transmetallation was analyzed through the evolution of the paramagnetic longitudinal relaxation rate of water protons at 37 degrees C in pH = 7 phosphate buffer solutions containing 2.5 mmol/L of the gadolinium complexes and 2.5 mmol/L zinc chloride. The measurements were performed at 0.47 T over a period of at least 3 days. RESULTS: The results confirm the high stability of macrocyclic systems and a high sensitivity of Gd-diethylenetriamine-pentaacetic acid (DTPA) derivatives to transmetallation by Zn2+ ions. The decreasing order of stability with respect to metal exchange is as follows: Gd-macrocyclics > Gd-C-functionalized DTPA > Gd-DTPA > primary and secondary Gd-DTPA bisamides. The ternary bisamide analyzed in this study [Gd-DTPA-1,11-bisbismethylamino-1,11-dioxo-3,6,9-triaza-3,6,9-tris(carboxymethyl)undecane] is more stable than the parent compound Gd-DTPA. CONCLUSIONS: A simple relaxometric protocol has been successfully developed to study the in vitro transmetallation process of gadolinium complexes. The importance of the functionalization and substitution of the DTPA-like complexes is clearly shown.

Chromatography, High Pressure Liquid↗
PubMed2001

Detection of avian oncogenic Marek's disease herpesvirus DNA in human sera.

The avian herpesvirus Marek's disease virus (MDV) has a worldwide distribution and is responsible for T-lymphoma in chickens. The question as to whether MDV poses a public health hazard to humans was first raised when the virus was isolated in 1967. However, no irrefutable results have been obtained in immunological and virological studies. We used a nested-PCR to detect MDV DNA in human serum samples. A total of 202 serum samples from individuals exposed and not exposed to poultry was tested by nested-PCR for a target sequence located in the MDV gD gene. The assay system was specific and sensitive, making it possible to detect a single copy of the target sequence. Forty-one (20%) of the 202 serum samples tested positive for MDV DNA. The prevalence of MDV DNA was not significantly different in the group exposed to poultry and the group not exposed to poultry. There was also no difference due to age or sex. Alignment of the 41 gD sequences amplified from human sera with eight gD sequences amplified from MDV-infected chicken sera showed a maximum nucleotide divergence of 1.65%. However, four 'hot-spot' mutation sites were identified, defining four groups. Interestingly, two groups contained only human MDV-gD sequences. The status of the MDV genome detected in human blood is discussed.

Adult↗
PubMed2001

Effects of acupuncture on radial artery hemodynamics: controlled trials in sensitized and naive subjects.

Palpation of the radial pulses is an important technique in traditional Chinese medicine. Two double-blind randomized trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitized subjects) and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform were measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-min acupuncture period. In sensitized patients, arterial diameter significantly increased during real acupuncture, compared with the sham group (+7.5 +/- 2.8 vs. -2.9 +/- 2.7%, respectively; P < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time course of blood pressure, radial artery distensibility, and pressure waveform. Our results demonstrate that real acupuncture is associated with an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.

Acupuncture Therapy↗
PubMed2001

Fenestrations of the carotid internal elastic lamina and structural adaptation in stroke-prone spontaneously hypertensive rats.

Our aim was to determine the structural factors that determine the mechanical adaptation of the carotid arterial wall in stroke-prone hypertensive rats (SHRSP). Distensibility-pressure and elastic modulus-stress curves assessed by in vivo echo-tracking measurements indicated a reduction in arterial stiffness in 13-week-old SHRSP compared with Wistar-Kyoto rats (WKY). Elastin and collagen contents determined biochemically were not different between SHRSP and WKY. Confocal microscopy showed that the mean area of fenestrations and fraction of area occupied by fenestrations of the internal elastic lamina (IEL) were smaller in SHRSP than in WKY, which indicated a reduction in stress-concentration effects within the IEL. Immunohistologic staining of EIIIA fibronectin isoform and total fibronectin (also as determined by Western blot) was greater in SHRSP, which suggested increased cell-matrix interactions. We suggest that these structural modifications of the vascular wall play a synergistic role in the mechanical adaptation to a high level of stress in SHRSP.

Animals↗
PubMed2001

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.

Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.

Adult↗
PubMed2001

Community assessment in a vertically integrated health care system.

OBJECTIVES: In this report, the authors present a representative case of the implementation of community assessment and the subsequent application of findings by a large, vertically integrated health care system. METHODS: Geographic information systems technology was used to access and analyze secondary data for a geographically defined community. Primary data included a community survey and asset maps. RESULTS: In this case presentation, information has been collected on demographics, prevalent health problems, access to health care, citizens' perceptions, and community assets. The assessment has been used to plan services for a new health center and to engage community members in health promotion interventions. CONCLUSIONS: Geographically focused assessments help target specific community needs and promote community participation. This project provides a practical application for integrating aspects of medicine and public health.

Community Health Services↗
PubMed2001

[Reversible hypokinetic cardiomyopathy revealing severe hypocalcemia].

Dilated cardiomyopathy may be primary or secondary. Although some causes are well known, such as toxic substances (alcohol, chemotherapy...) or viral infections, biochemical abnormalities are much less common. The authors report the case of a 58 year old woman with no previous history admitted to hospital for an inaugural episode of cardiac failure. The ECG showed sinus tachycardia with a long QT interval (560 mm) and a dilated hypokinetic cardiomyopathy with a left ventricular ejection fraction of 20%. The aetiological investigation showed severe hypocalcaemia (0.66 mmol/L) related to primary hypoparathyroidism. This is an important cause to remember because its treatment leads to correction of the cardiac disease, usually within weeks.

Calcifediol↗
PubMed2000

Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment.

BACKGROUND: Local pulse pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean blood pressure (BP). The present study was designed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. METHODS AND RESULTS: Ninety-eight essential hypertensive patients were randomized to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high-resolution echo-tracking systems. PP was measured locally with applanation tonometry and independently of mean BP. After 9 months of treatment, mean BP, carotid PP, and intimal-medial thickness (IMT) decreased significantly, with no difference between the 2 groups. The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. CONCLUSIONS: The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.

Adult↗
PubMed2000

[Auditing of drug use practices in anesthesia].

OBJECTIVES: Internal pharmaceutical practice guidelines were produced in a department of anaesthesia of a University hospital in 1995, after a preliminary evaluation showing controversial and expensive practices. After approval, these recommendations were circulated to all members of the department. Phase I of this study was started 18 months later, to evaluate the compliance of anaesthetists with these guidelines. STUDY DESIGN: Prospective survey. METHOD: An audit was performed by a research assistant pharmacist, previously trained, who compared anaesthetic agents and fresh gas flows used during anaesthetics with those recommended in the internal guidelines. RESULTS: Implementation of guidelines was observed in more than 90% of cases for all agents studied, except for non-depolarizing neuromuscular relaxants. Relaxants of intermediate duration were used in 52% of cases with an expected surgery duration of more than 90 min, in opposition to the guidelines stating that pancuronium should have been administered in such circumstances. These results were presented and discussed. Slight changes in the guidelines (especially concerning monitoring of neuromuscular blockade) were made and evaluated again, using the same method (Phase II). A small but significant improvement was seen with induction agents (use of propofol in non-approved situations: 5 versus 0%, P = 0.03), while a non significant trend toward better implementation of guidelines was seen with non-depolarizing agents (use of pancuronium in surgery of expected duration > 90 min: phase I vs phase II = 47 vs 52%, NS; use of pancuronium in surgery of expected duration < 90 min: phase I vs phase II = 3.5 vs 0%, NS). CONCLUSION: This study suggests that implementation of internal guidelines is easy when clinical indications of the agents are not controversial.

Anesthetics↗