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Biomedical subjects

A Leroy

Publications and source records attributed to A Leroy.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Neuropsychological testing of 5 patients with Parkinson's disease before and after neuron graft].

Five patients with idiopathic PD were followed by neuropsychological tests after brain fetal neuronal transplantation. The following tests were used in order to assess memory as well as visuospatial and frontal functions: MMSE, Mattis Scale, Wisconsin Card Sorting Test, Stroop task, word fluency tasks, 15-objects test, WAIS-R (Digit span, Arithmetic, Block design, Pictures completion, Pictures arrangement), learning of 15 words of Rey, WMS-R (Logical memory) and Visual memory of L. Israël. The same tests were performed before, then one year following the transplantation. Pooled data did not show any significant difference between pre and post-operative tests. Individual results varied among patients: 2 remained unchanged, 1 had a pathological deterioration which increased after one year, 1 had some frontal symptoms whereas the last patient improved. Our data confirm that this surgical procedure do not induce permanent neuropsychological deficits, but do not indicate at the present time any clear effect of dopamine reinnervation on cognitive functions.

Aged↗
PubMed1995

Native like structure and stability of apo AI in a n-propanol/water solution as determined by 13C NMR.

To elucidate the molecular details of the conformation of apolipoprotein AI (apo AI), we have developed an approach related to the solubilization of this protein in 30% n-propanol. We have previously reported the promotion of a native-like structure for apo AI solubilized in n-propanol, as depicted by circular dichroism, fluorescence, and limited proteolytic digestion as compared to the lipid associated form of apo AI. In the present study, we labeled the Lys residues of apo AI with 13C by reductive methylation and used 13C NMR to confirm the formation of a native-like structure of apo AI in this environment. Furthermore, by the above criteria (circular dichroism and 13C NMR) and by using urea and temperature as denaturing agents, we show that the denaturation of the native-like structure of apo AI in n-propanol is a biphasic process. These studies show that in 30% n-propanol, apo AI contains two independently folded structural domains, of markedly different stabilities that might correspond to the amino-terminal and the carboxy-terminal halves of the molecule.

1-Propanol↗
PubMed1995

Apolipoprotein A-I-containing lipoproteins and atherosclerosis.

Apolipoprotein A-I-containing lipoproteins represent a heterogeneous group of lipoparticles. Recent studies suggest that a specific subpopulation within the lipoprotein (AI) subclass may be more effective than other lipoproteins in promoting cholesterol efflux from cells and in the different steps of reverse cholesterol transport. This review describes the different apolipoprotein A-I-containing HDL subfractions, their role in reverse cholesterol transport, and their metabolic interconversions and relationship with lipoprotein-modifying enzymes.

Animals↗
PubMed1995

Cefixime penetration in human renal parenchyma.

The diffusion of cefixime, a new orally active expanded-spectrum cephalosporin, was studied in 12 patients undergoing nephrectomy after receiving 200-mg oral doses every 12 h for 2 days. The patients were divided into two groups according to the time of perioperative sampling after the last dose: 4 h (group 1) and 12 h (group 2). Preoperative blood samples were taken just before administration of the last dose of cefixime. Simultaneous blood and tissue samples were collected perioperatively at 4 h (time to peak level) and 12 h (residual level). The intrarenal concentrations of cefixime were measured by an isocratic reversed-phase high-pressure liquid chromatographic (HPLC) assay. Concentrations in serum were determined by both microbiological and HPLC assays. The mean peak levels in serum were 3.41 +/- 0.43 micrograms/ml (group 1), and the residual levels averaged 1.54 +/- 1.17 micrograms/ml (group 2). The diffusion in renal parenchyma was not significantly different in the cortexes and medullas of both groups of patients: 5.7 to 6.4 micrograms/g in group 1 and 4.6 to 4.7 micrograms/g in group 2. The decrease in cefixime concentrations was slower in tissue than in serum; the ratios of concentrations in tissue to those in serum were 3.5 to 3.6 and 1.7 to 1.9 at 4 and 12 h, respectively. The intrarenal concentrations of cefixime remained higher than the MIC for the most susceptible gram-negative bacteria during the time interval between the administration of two doses.

Administration, Oral↗
PubMed1995

Contact-dependent transfer of the galactose-specific lectin of Entamoeba histolytica to the lateral surface of enterocytes in culture.

In a study to investigate early interactions of Entamoeba histolytica with epithelial cell monolayers, we found that a monoclonal antibody (MAb), CD6, against an ameba surface antigen recognized the lateral surface of epithelial cells after coculture with trophozoites. Display of the CD6 antigen on the epithelial cells necessitated contact with active trophozoites. It was found neither at 4 degrees C, nor with prefixed trophozoites, nor with trophozoite-conditioned media, nor when a filter prevented direct contact. Monolayers exposed to amebic sonicates or detergent lysates showed random immunostaining. Access to the antigenic site was limited, as immunostaining occurred predominantly with subconfluent monolayers. CD6 epithelial cell binding was first observed after 5 min of coculture; trophozoite-mediated target cell lysis was not detected until 15 min following coculture. Epithelial cell immunostaining occurred with some other ameba-specific antibodies but not with MAbs raised against the 170-kDa subunit of the galactose-N-acetylgalactosamine (Gal/GalNAc)-specific lectin. The CD6 MAb as well as some other ameba-specific antibodies immunoprecipitated from trophozoite lysates the same bands as the MAbs against the cysteine-rich domain of the 170-kDa subunit of the Gal/GalNAc-specific lectin. Why the latter MAbs failed to stain epithelial cells in the vicinity of attached trophozoites is presently unknown. We concluded that E. histolytica trophozoites transferred the intact amebic Gal/GalNAc-specific lectin or a portion of it to the lateral surface of epithelial cells. This juxtacrine transfer preceded killing of target cells.

Animals↗
PubMed1994

Native-like structure and self-association behavior of apolipoprotein A-I in a water/n-propanol solution.

The effect of n-propanol on the secondary and tertiary structure of human apolipoprotein A-I (apoA-I), an interfacial protein, was investigated using near and far ultraviolet (UV)-circular dichroism (CD) and fluorescence spectroscopy, as well as limited proteolytic digestion with trypsin, and cross-linking with bis(sulfosuccinimidyl) suberate. The structure of apoA-I in n-propanol (30%, v/v) was compared with that in Tris buffer and in reconstituted, spherical or discoidal, high density lipoproteins (rHDL). Addition of n-propanol to apoA-I in Tris buffer induces major changes in its near and far CD spectra: alpha-helical content increases by 27% and the near UV-CD spectrum becomes very similar to that of apoA-I in rHDL particles. Fluorescence spectral, lifetime, and polarization results, and quenching by KI confirm that major structural changes occur in the N-terminal half of apoA-I as n-propanol is added: the Trp residues become more exposed to solvent than in buffer alone or in rHDL. Higher concentrations of guanidine hydrochloride or urea are required to denature apoA-I in n-propanol than in buffer alone, but a similar free energy of unfolding is observed. The N-terminus of apoA-I is relatively resistant to trypsin digestion and the C-terminus has equivalent digestion sites for apoA-I in the three states, but the kinetics of digestion are much slower in n-propanol and in rHDL compared to apoA-I in Tris buffer. Cross-linking experiments reveal that dimers of apoA-I exist in n-propanol, in contrast to dimers plus multimeric aggregates in Tris buffer. From these results we conclude that in 30% n-propanol the structure of apoA-I approaches that of 'native' lipid-bound apoA-I, in contrast to its structure in the aqueous Tris buffer.

1-Propanol↗
PubMed1994

Do turbines with servo-controlled speed improve continuous positive airway pressure generation?

Nasal continuous positive airway pressure (CPAP) devices with a servo-mechanism to control pressure have recently been developed. We evaluated six such devices and three conventional systems in terms of effectiveness in maintaining constant pressure. Machines were tested with pressure levels of 5, 10 and 15 cmH2O. Dynamic behaviour was evaluated: 1) by calculating the imposed work of breathing during simulated breath generated by a sinusoidal pump; and 2) by following the fall in pressure after a transient flow of 1 l.s-1. Quasi-static behaviour was evaluated by simulating a predetermined air leak. Under dynamic conditions, work of breathing was lowest with one conventional nasal CPAP device and three servo-controlled nasal CPAP devices; whereas, the highest levels of work of breathing were recorded with two servo-controlled nasal CPAP devices. The pressure-time response to a transient flow yielded similar results, with a significant inverse correlation between pressure values observed after 300 ms and imposed work of breathing during simulated breathing (r = -0.91). Under quasi-static conditions, microprocessor servo-controlled devices exhibited the best performance. These results suggest that microprocessor servo-controlled nasal CPAP devices are not always the best systems for maintaining constant airway pressure in dynamic situations. However, they are more effective in ensuring maintenance of the desired pressure in the event of an air leak at the mask.

Equipment Design↗
PubMed1994

The optometry game: enhancing test selection and lens prescribing skills by use of computer simulations.

The Optometry Game is a computer simulation developed to aid students in practicing test selection and lens prescription skills. Features of the simulation include a game format, digitally reproduced voices and patient pictures, and the ability of the user to customize the game for a variety of applications. Twenty optometry students evaluated the game by playing a variety of simulated patients and found it to be potentially useful in various classroom learning environments.

Computer Simulation↗
PubMed1993

Structural properties of high density lipoprotein subclasses homogeneous in protein composition and size.

We isolated native high density lipoprotein (HDL) subclasses homogeneous in size and in their protein content with the objective of investigating the differences and similarities in their apolipoprotein AI (apoA-I) structures. Defined particles were isolated from ultracentrifugally prepared HDL by immunoaffinity and gel-filtration chromatography. The isolated 88-A LpAI, 106-A LpAI, 96-A LpAI/AII particles (LpAI, particles contain only apoA-I; LpAI/AII, particles contain apoA-I and apoA-II), together with a 93-A reconstituted HDL were analyzed for purity, composition, and content of apolipoprotein molecules per particle, and were examined by far and near circular dichroism and intrinsic fluorescence spectroscopic methods, as well as by reaction kinetics with lecithin:cholesterol acyltransferase. The spectroscopic analyses indicated that the secondary structures and three-dimensional arrangements of apoA-I in all these particles are remarkably similar: their tryptophan residues are located in similar nonpolar environments and become exposed to increasing concentrations of guanidine hydrochloride in comparable denaturation steps; the 60-65% alpha-helical structures in apoA-I are denatured in similar patterns with 0-5 M denaturant concentrations. However, increasing surface lipid contents and the presence of apoA-II stabilize apoA-I on the HDL particles. The reaction kinetics with lecithin:cholesterol acyltransferase are similar and slow for the isolated HDL particles, reflecting product inhibition, and/or an apoA-I conformation that is unfavorable for the activation of the lecithin:cholesterol acyltransferase reaction.

Apolipoprotein A-I↗
PubMed1993

Caffeine decreases glial cell number and increases hyaluronan secretion in newborn rat brain cultures.

Newborn rat brain astrocytes (type 1 astrocytes, O-2A progenitor cells, and O-2A progenitor-derived cells, i.e. oligodendrocytes and type 2 astrocytes) were cultivated to investigate the effect of addition of caffeine to the culture medium on glial cell development and secretion of hyaluronan (hyaluronic acid, HA). HA is a glycosaminoglycan, secreted by type 1 astrocytes especially, which is a major component of the extracellular matrix of immature brain involved in morphogenesis and differentiation. Caffeine was added to the culture medium of primary glial cell cultures at concentrations of 102 microM (20 mg/L) or 255 microM (50 mg/L), considered therapeutic and toxic levels, respectively, in human newborns. HA was measured in the culture medium by immunoenzyme assay using sheep brain hyaluronectin, a glycoprotein that exhibits a strong affinity for HA, as probe. In primary glial cell cultures, 102 microM (20 mg/L) caffeine had no visible effect on cell number or on HA secretion. At 255 microM (50 mg/L), there was a significant reduction of cell number (i.e. type 1 astrocytes, O-2A progenitor cells, and progenitor-derived cells) and a significant increase of HA secretion per cell. These results suggest that caffeine at a high concentration in brain could have a prejudicial effect on the number of proliferating glial cells (astrocytes and oligodendrocytes) and on the composition of the extracellular matrix, which could affect myelination onset.

Animals↗
PubMed1993

[Effect of ketoprofen on the pharmacokinetics of two fluoroquinolones in males].

The influence of a non steroidal antiinflammatory drug (NSAID), ketoprofen, on the pharmacokinetics of two fluoroquinolone derivatives, pefloxacin (P) and ofloxacin (O), was studied in ten healthy adult male volunteers. The subjects were given orally for three days the quinolone alone (P: 400 mg q 12 h and O: 200 mg q 12 h), with at least a one week interval between the two quinolone studies. On day 4, the first kinetic study of pefloxacin and ofloxacin was performed. During the three following days, the quinolone was administered in association with ketoprofen (100 mg daily). Another pharmacokinetic study of P and O was performed on day 8 and the kinetic data obtained were compared to those found on day 4. During the two kinetic studies (D4 and D8), blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 et 24 h and urine was collected during the time-periods 0-4 h, 4-8 h, 8-12 h and 12 24 h. Plasma and urine concentrations of the active P and O drug were measured by microbiological assay. Ketoprofen administered for three days with the fluoroquinolone derivative induced no statistical modification in the kinetic parameters of both P and O: peak plasma levels, time to peak level, areas under the curve, apparent volume of distribution, total and renal clearances.

Adult↗
PubMed1992

Penetration of lomefloxacin into human prostatic tissue.

Serum and prostatic tissue concentrations of lomefloxacin were measured in 12 elderly patients who underwent transurethral resection of the prostate after receiving a single oral dose of 400 mg. The peak serum concentration of lomefloxacin was 2.5-10.0 micrograms/mL (mean, 5.2 +/- 1.9 micrograms/mL). During surgery, serum and tissue concentrations averaged 4.6 +/- 2.2 micrograms/mL and 6.5 +/- 2.7 micrograms/g, respectively. The ratio of tissue to serum concentrations was 1.53 +/- 0.54. The levels of lomefloxacin in serum and prostatic tissue were found to be higher than the minimum inhibitory concentration (MIC) values for most urinary tract pathogens.

Administration, Oral↗
PubMed1992

Pharmacokinetics of meropenem in subjects with renal insufficiency.

The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 micrograms.ml-1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.

Adult↗
PubMed1992

Pharmacokinetics of meropenem (ICI 194,660) and its metabolite (ICI 213,689) in healthy subjects and in patients with renal impairment.

The pharmacokinetics of meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-life of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are linearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, significantly increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 +/- 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.

Adult↗
PubMed1992

Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers.

The influence of ketoprofen (K), a non steroidal antiinflammatory drug (NSAID) on the pharmacokinetics of two fluoroquinolone derivatives: ofloxacin (O) and pefloxacin (P) was studied in ten healthy adult male volunteers. All subjects orally received every 12 h the fluoroquinolone derivative (either O or P) for three days and the combination of the quinolone and ketoprofen (once a day) during the three following days. Two pharmacokinetic studies were performed for each quinolone, on days four and eight of the treatment. Blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after dosing. Urine was collected during 4 time-periods: 0-4 h, 4-8 h, 8-12 h and 12-24 h. Plasma and urine concentrations of the active drug of O and P were measured by microbiological assay. Ketoprofen did not significantly modify the pharmacokinetic parameters of the two fluoroquinolones studied in terms of peak plasma levels, time to peak, area under the curve, elimination half-life, volume of distribution and total and renal clearances.

Administration, Oral↗
PubMed1992

Thrombin cleavage of apolipoprotein Bh of rabbit LDL: structural comparisons with human apolipoprotein B-100.

Rabbit plasma low density lipoprotein (LDL) contains one major apolipoprotein of apparent molecular weight of 320 kDa, designated apolipoprotein (apo) Bh, while another component termed apoB1 of apparent molecular weight of 220 kDa is found in chylomicrons. The fragments generated by thrombin digestion of the protein moieties of rabbit and human LDL were separated by polyacrylamide gradient gel electrophoresis and compared. As in the human species, the enzyme produced limited cleavage patterns of rabbit LDL apoB. Within the first 2 h, two fragments (Tr1 and Tr2, with apparent molecular weights 280,000 and 44,000, respectively) appeared. Longer incubations led to the production of two additional peptides, Tr3 and Tr4 (apparent molecular weights 180,000 and 96,000, respectively). Ten monoclonal antibodies, developed against rabbit LDL and designated P01 to P10, were found to react with rabbit apoB. Some also cross-reacted with human apoB. Epitope mapping, performed with these antibodies, showed that Tr3 and Tr4 were derived from the further degradation of Tr1. The rabbit is one of the most frequently used animals in atherosclerosis research. Its LDL receptor has been characterized and there exists a strain of homozygous LDL receptor-deficient rabbits referred to as WHHL rabbits. Despite this, little has been done to characterize the structure of rabbit apoB; only a short region has been sequenced and shown to be the carboxyl-terminal region, the rabbit apoB1. The molecular weight of human apoB (550,000) is much larger than rabbit apoBh. In both species, a primary and secondary thrombin cleavage occur, but the size of the fragments produced is very different between the two species. Identification of the thrombolytic fragments of the rabbit apoB have afforded the opportunity to compare the structures of both apoB species.

Animals↗
PubMed1992

[Prognostic value after 1 year of post-infarction exercise test with measurement of oxygen consumption].

A symptoms-limited exercise stress test with measurement of myocardial oxygen consumption (VO2) was carried out in 56 patients on the 44th +/- 16 days after infarction and in 48 patients on the 119th +/- 31 days. Analysis of the expired gases was performed by mass spectrography, cycle by cycle. The second test was coupled with an exercise gamma-angiography in 40 cases. The parameters on exercise were analysed in two groups at one year: group 1 asymptomatic and group 2 symptomatic (subgroup 2a with angina but no dyspnoea, subgroup 2b with dyspnoea). At the second test, the peak VO2 was lower in group 2 (19.46 +/- 5.78 ml/mn/kg) than in group 1 (24.2 +/- 6.5 ml/mn/kg) (p less than 0.008) irrespective of the symptom (angina and/or dyspnoea). The oxygen pulse was lower in group 2a with angina at one year (42.4% +/- 14.3%) compared with asymptomatic group 1 patient (58.5 +/- 12.4%) (p = 0.03). The 3 parameters: VO2, blood pressure and ejection fraction on exercise were independent. The lack of physical fitness may partially explain the absence of variation of the peak VO2 at the first test. These preliminary results should be confirmed by a multivariate analysis in a larger patient group.

Aged↗