Biomedical subjects

P Morin

Publications and source records attributed to P Morin.

At least 37 records · Page 2Linked to original sources

PubMed2000

Determination at ppb level of an anti-human immunodeficiency virus nucleoside drug by capillary electrophoresis-electrospray ionization tandem mass spectrometry.

Capillary electrophoresis coupled with tandem mass spectrometry was used to indirectly separate and quantify the active metabolite of the anti-human immunodeficiency virus (anti-HIV) didanosine drug. The influence of several parameters (pH and ionic strength of volatile formic acid-ammonia buffer) upon electroosmotic flow, electrophoretic mobility and peak efficiency of several nucleosides (A, dA, ddA, C) has been studied. This paper illustrates the current importance in CE-MS technique as a complementary or substituted method to the known HPLC-radioimmunoassay or HPLC-UV method to measure levels of anti-HIV drugs. The limit of detection for 2',3'-dideoxyadenosine by this method is 2 microg 1(-1) in a formic acid-ammonia buffer (pH 2.5, 10 mM ionic strength). This methodology could be used to perform simultaneous detection of two or more anti-HIV nucleosides, such as stavudine or didanosine in combination therapy.

Anti-HIV Agents↗

PubMed2000

Enhancement of second-migrating enantiomer peak symmetry of basic drugs by using dual-cyclodextrin system in capillary electrophoresis.

Today, chiral separations of cationic drugs by capillary electrophoresis are generally carried out by adding negatively charged cyclodextrins (CDs) to the running buffer while anionic or neutral drug separations require the use of dual-CD systems (mixtures of neutral and charged CDs). Chiral separation of some basic drugs (idazoxan, efaroxan, milnacipran) has been studied by using mixtures of sulfated-beta-CD (S-beta-CD) and hydroxypropyl-gamma-CD (HP-gamma-CD). The influence of the following parameters (nature and concentration of neutral CD, concentration of S-gamma-CD) on many separation factors (electrophoretic mobility, selectivity, efficiency, asymmetry factor, resolution) demonstrated that dual-CD systems are useful for chiral separation of basic drugs in order to improve the symmetry of the second-migrating enantiomer. Indeed, the neutral CD reduces the extent of electromigration dispersion by mobility tuning. Finally, the 0.5 mg/mL S-beta-CD/5 mg/mL HP-gamma-CD dual system has allowed the chiral separation of idazoxan, efaroxan and milnacipran enantiomers in less than 9 min.

Cyclodextrins↗

PubMed2000

The spatial distribution and resolution of coaxial backscattered electrons in SEM, calculated by monte carlo simulations

We simulate, within a sample, the trajectories of the backscattered electrons detected in a scanning electron microscopy with a particular detection geometry. Thus we obtain the depth and lateral distributions, according to the adjustable parameter values, of the detected electrons. Finally, the scanline profile across a chemical edge is drawn. The conditions corresponding to the best lateral resolution are established; we obtain an ultimate resolution of the same order as the beam diameter.

Journal Article↗

PubMed2000

Charge effect in point projection images of carbon fibres

Nanometre-sized carbon fibres across holes have been observed in a lensless point projection field-emission microscope operating between 100 and 300 eV. At sufficiently high magnification fringe patterns appear; with the help of simulations we show that they are strongly dependent on the charge density of the fibres. These patterns are characterized by an odd number of fringes with a central fringe that becomes very bright as the charge increases. Average diameter and linear charge density have been obtained with remarkable precision from analysis of fringes. Charge distribution from the middle to the edge of fibres has been investigated as well as narrowings at localized places on the fringe pattern. From these two examples, the limits of the models used for the simulations and those of the data acquisition system are discussed. Finally, this work emphasizes the fact that the fringe pattern masks the actual form of the fibre and that it is necessary to take account of the charge effect to interpret this diffraction pattern.

Journal Article↗

PubMed2000

Identification of the bacteriologicalcontamination of a water treatment line used for haemodialysis and its disinfection.

Renal haemodialysis care units in hospitals use enormous amounts of potable water for the functioning of 'artificial kidneys'. In order to avoid complications with patients' blood this water has to be specially treated. However, the treatment line itself can induce problems due to a high concentration of bacteria in the water. A high bacterial load, as well as bacterial toxins, can provoke immunological reactions in the patients. This paper shows that a granular activated carbon (GAC) filter is a source of bacterial contamination of the water due to the presence of a biofilm on the medium's surface. The majority of the bacteria released are Gram-negative. Because sloughing events in the biofilm can lead to dangerously high concentrations of bacteria and endotoxin levels in water, it is important to control this phenomenon. In treatment lines, GAC filters are regularly chlorinated. Our pilot experiment studied the disinfection of the filter with sodium hypochlorite and peracetic acid. Our results show that both disinfectants have a weak and transient effect on the biomass in the filter. It appears that chemical treatment of the filter is not the ideal solution to the bacteriological threat. Moreover, disinfection of the GAC filter transiently increases the contamination of the water. Alternative solutions to the use of chemical disinfection procedures are discussed.

Biofilms↗

PubMed2000

Safety and immunogenicity of a five-dose series of inactivated Mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis.

Five doses of inactivated Mycobacterium vaccae vaccine were administered intradermally to 22 human immunodeficiency virus (HIV)-infected patients (11 bacille Calmette-Guérin [BCG]-positive and 11 BCG-negative) in Zambia whose CD4 lymphocyte counts were >/=200 cells/mm(3). HIV viral load and lymphocyte proliferation responses were compared for vaccine recipients and 22 HIV-infected control patients (11 BCG-positive and 11 BCG-negative). Immunization was safe and well tolerated in all patients, and induration at the vaccine site decreased from dose 1 to dose 5. A transient decrease in HIV viral load was observed in BCG-positive vaccine recipients after dose 3 but not after subsequent doses. Median lymphocyte stimulation indices to M. vaccae were 6.0 in vaccine recipients and 2.3 in control patients (P<.001). Stimulation indices were >/=3.0 in 19 vaccine recipients (86%) and 7 control patients (32%; P=.001). A 5-dose series of vaccination with inactivated M. vaccae is safe in HIV-infected patients and induces lymphocyte proliferation responses to the vaccine antigen. M. vaccae vaccine is a candidate for the prevention of tuberculosis in HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1999

Liquid chromatography analysis of phosphonic acids on porous graphitic carbon stationary phase with evaporative light-scattering and mass spectrometry detection.

The analysis of several phosphonic acids has been investigated by liquid chromatography (LC), using porous graphitic carbon as stationary phase with mass spectrometry (MS) or evaporative light-scattering detection (ELSD). In both detection modes (MS and ELSD), the mobile phase must be volatile and, due to the porous graphitic carbon (PGC) properties, should promote electronic interactions. Among the various hydrogeno- and perfluorocarboxylic acids tested, trifluoroacetic acid (0.1%, v/v) was selected as electronic competitor for solute retention. The baseline resolution of a phosphonic acids mixture required a trifluoroacetic-acetonitrile gradient elution. This methodology was then applied to the identification of phosphonic acids in a spiked tap water sample. Quantitative analyses are successfully achieved with a good correlation coefficient.

Carbon↗

PubMed1999

Randomised trial of intradermal Mycobacterium vaccae or intradermal hepatitis B immunisation in children with HIV infection.

This study assessed the safety of inactivated Mycobacterium vaccae as a candidate vaccine to prevent disseminated mycobacterial disease in children with HIV infection. 35 children ages 1-8 with CD4 counts > or =300/mm3 in New Hampshire, Boston and Chicago were randomised in a 2:1 schedule to receive a 3-dose series of intradermal M. vaccae vaccine (MV) or hepatitis B vaccine (HBV) at 2-month intervals. Immunisation was safe and well tolerated; 2-day median vaccine site in duration was 5 mm in MV recipients and 0 mm in HBV recipients (p < 0.001). There were no significantly different changes in viral load or CD4 count between the two vaccine groups. No PPD skin test conversions occurred after immunisation. MV is safe and well tolerated and deserves further evaluation as a vaccine to prevent mycobacterial disease in HIV-infected children.

Administration, Cutaneous↗

PubMed1999

Comparison of sulfobutylether- and sulfated-beta-cyclodextrins as additives for the chiral separation of basic spirobenzopyrans by capillary electrophoresis.

Three charged substituted beta-cyclodextrins (beta-CDs), sulfobutylether-beta-(SBE-beta-CD), degree of substitution (DS) 4 and 7), and sulfated-beta-(S-beta-CD) cyclodextrins, were compared as chiral additives in capillary electrophoresis for the enantiomeric separation of basic spirobenzopyran derivatives (pKa 9.9) which differ from each other by an N-alkyl group. The number of sulfobutylether groups attached to the cyclodextrin moiety significantly influences the enantioseparation of the basic drugs. SBE-beta-CD (DS 7) which is more strongly bound to cationic analyte than SBE-beta-CD (DS 4.6), requires smaller concentrations to achieve the same resolution. Besides, better enantioresolutions were obtained with S-beta-CD rather than with SBE-beta-CDs though higher concentrations are required, which led to high current values. However, both pairs of enantiomers cannot be resolved using S-beta-CD while SBE-beta-CDs make it possible to resolve simultaneous enantioseparation of such solutes slightly differing in hydrophobicity. This supports the hypothesis that hydrophobic interactions (outside of the CD cavity) between the butyl group attached to SBE-beta-CD and the N-alkyl group of spirobenzopyran play a role in the enantioseparation. On the other hand, the sulfate group of S-beta-CD was directly attached to the CD moiety which means that the S-beta-CD-drug complexation mechanism arises through the combination of electrostatic and hydrophobic (inside the CD cavity) interactions. Finally, enantiomers of spirobenzopyran drugs were satisfactorily resolved by CE using a 20 mg/mL S-beta-CD concentration (resolution 4.0), 7 mg/mL SBE-beta-CD DS 4 (resolution 1.3), or 5 mg/mL SBE-beta-CD DS 7 (resolution 3.3) added to the phosphate buffer (pH 2.6, 50 mM ionic strength).

Anions↗

PubMed1999

Linkage of inflammatory bowel disease to human chromosome 6p.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD.

Alleles↗

PubMed1998

Identification of phosphonic acids by capillary electrophoresis-ionspray mass spectrometry.

The identification of alkylphosphonic acids in spiked tap water has been investigated by on-line capillary electrophoresis-UV spectrometry-mass spectrometry (CE-UV-MS) in negative-ion mode. The 5 mM sorbic acid-ammonia electrolyte (pH 6.5) allows simultaneous indirect UV and MS (ionspray) detection. Several parameters (electrolyte pH, make-up chemical composition and make-up flow-rate) have been optimized and 5 mg/l limit of detection has been reached for these analytes in selected ion monitoring MS detection. MS-MS detection has also been investigated to reach a low detection limit (100 micrograms/l) for alkyl alkylphosphonic acids in spiked tap water. The mass spectra of these compounds exhibit a very abundant negative ion, [M-H]- (MS) with characteristic fragmentation (MS-MS) of acids and monoesters. Quantitative analysis achieved with CE-UV shows good correlation coefficients and allows accurate quantification of the analytes.

Electrophoresis, Capillary↗

PubMed1998

Spectroscopic Techniques using Synchrotron Radiation and Free-Electron and Conventional Lasers.

Considerable progress in the investigation of the electronic and vibrational properties of atoms, molecules, materials, surfaces and interfaces has been achieved by combining different photon sources of complementary characteristics. In this paper some experimental results obtained recently at LURE by using two synchronized sources, such as the IR free-electron laser (FEL) CLIO, the VUV storage ring FEL, synchrotron radiation and table lasers, are presented. Using CLIO synchronized with a YAG laser allows the investigation of the vibrational properties of adsorbed species by the non-linear optical technique of visible-IR sum (difference) frequency generation, as shown for the adsorption of hydrogen on platinum in the electrochemical environment. The second result reported here relates to the study of the intersubband stimulated emission in GaAs/GaAlAs quantum wells by pump-probe experiments using the two-colour configuration of CLIO. The combination of a mode-locked Ar(+) laser and synchrotron radiation has been used for investigations in a pump-probe arrangement of the ionization of Xe atoms via the resonant state Xe* 5p(5)5d [3/2](1). The final example is a time-resolved core-level spectroscopy study of photoexcited Si(111) 2 x 1 surfaces by using a combination of the naturally synchronized UV storage ring laser and synchrotron radiation.

Journal Article↗

PubMed1998

Investigation of micelles and anionic cyclodextrins as pseudostationary phases for the capillary electrophoresis separation of oligosaccharides derivatized with 2-amino-benzamide.

Oligomers of glucose and oligosaccharides released from glycoproteins were derivatized with 2-aminobenzamide. As this fluorophore imparts no charge to the oligosaccharides, several strategies were investigated to achieve capillary electrophoresis (CE) separation of both neutral and charged derivatized glycans. Micellar electrokinetic capillary chromatography (MEKC) with the addition of anionic surfactants was evaluated as a first approach: sodium dodecyl sulfate (SDS) produced the best separation of the oligoglucose fragments, where the migration was inversely related to their degree of polymerization. To demonstrate the applicability of this method for complex carbohydrate analysis, oligosaccharide mixtures derived from ribonuclease B (RNase B) and alpha-acid glycoprotein (alpha-AGP) were analyzed. A satisfactory separation for the high-mannose structures found in RNase B could be obtained, whereas charged oligosaccharides from alpha-AGP were poorly resolved. Cyclodextrin-modified CE was chosen as the second approach: the effect of the addition of sulfobutylether-beta-cyclodextrin (SBE-beta-CD) or sulfobutylether-gamma-cyclodextrin (SBE-gamma-CD) on the electrophoretic mobilities and resolution of neutral and charged oligosaccharides was then studied. Selectivity of sialylated structures could be further improved by using anionic cyclodextrins (CDs) instead of micelles. However, this latter approach failed to baseline-resolve the different high-mannose structures of RNase B. A successful separation of the complex mixture of oligosaccharides from alphaalpha-AGP was obtained with the addition of 4% of SBE-gamma-CD and triethylamine (TEA) in a phosphate buffer, pH 6.7.

Anions↗

PubMed1998

Cellular immune responses to mycobacteria in healthy and human immunodeficiency virus-positive subjects in the United States after a five-dose schedule of Mycobacterium vaccae vaccine.

The safety and immunogenicity of heat-killed Mycobacterium vaccae vaccine were investigated in a pilot study assessing the feasibility of immunization to prevent mycobacterial disease in patients with human immunodeficiency virus (HIV) infection. Fifteen (seven healthy and eight HIV-positive subjects) received five doses of M. vaccae vaccine. Lymphocyte proliferation assays (LPAs) were performed using Mycobacterium avium sensitin (MAS) and M. vaccae sonicate (MVS). Vaccine was well tolerated in all 15 subjects with minimal induration at the vaccine site. LPAs for four of seven healthy vaccines were positive for MAS after immunization. Median responses to MAS and MVS that were determined by LPAs were consistently higher for the eight HIV-positive vaccinees than for the seven healthy controls. A five-dose series of M. vaccae vaccine is safe for both healthy and HIV-positive subjects and deserves further evaluation as a vaccine to prevent HIV-associated mycobacterial disease.

Bacterial Vaccines↗

PubMed1998

Oral analogue scale as an outcome measure after displaced intra-articular calcaneal fractures.

Functional outcome measures of displaced intra-articular calcaneal fractures have been documented using general health surveys (SF36) and disease-specific health surveys (Visual Analogue Scale). A simple oral analogue scale (OAS) was collected on 115 patients with 124 displaced intra-articular calcaneal fractures at 2 years or more after fractures. There was a high correlation (r = 0.72, P < 0.0001) between the verbal OAS and the written Visual Analogue Scale. We believe that the OAS may assist in follow-up outcome assessment and management in this difficult trauma patient population. Outcomes may be accomplished verbally rather than in written form.

Calcaneus↗

PubMed1998

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13.

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Adult↗

PubMed1997

Abnormal sulfate metabolism in vitamin D-deficient rats.

To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO4 cotransporter were evaluated in vitamin D-deficient (D-D-) rats and in D-D- rats rendered normocalcemic by either vitamin D or calcium/lactose supplementation. D-D- rats had significantly lower plasma sulfate levels than control animals (0.93+/-0.01 and 1.15+/-0.05 mM, respectively, P < 0.05), and fractional sulfate renal excretion was approximately threefold higher comparing D-D- and control rats. A decrease in renal cortical brush border membrane Na-SO4 cotransport activity, associated with a parallel decrease in both renal Na-SO4 cotransport protein and mRNA content (78+/-3 and 73+/-3% decreases, respectively, compared with control values), was also observed in D-D- rats. Vitamin D supplementation resulted in a return to normal of plasma sulfate, fractional sulfate excretion, and both renal Na-SO4 cotransport mRNA and protein. In contrast, renal sulfate excretion and renal Na-SO4 cotransport activity, protein abundance, and mRNA remained decreased in vitamin D-depleted rats fed a diet supplemented with lactose and calcium, despite that these rats were normocalcemic, and had significantly lower levels of parathyroid hormone and 25(OH)- and 1,25(OH)2-vitamin D levels than the vitamin D-supplemented groups. These results demonstrate that vitamin D modulates renal Na-SO4 sulfate cotransport and sulfate homeostasis. The ability of vitamin D status to regulate Na-SO4 cotransport appears to be a direct effect, and is not mediated by the effects of vitamin D on plasma calcium or parathyroid hormone levels. Because sulfate is required for synthesis of essential matrix components, abnormal sulfate metabolism in vitamin D-deficient animals may contribute to producing some of the abnormalities observed in rickets and osteomalacia.

Animals↗

PubMed1997

Immunization of healthy adult subjects in the United States with inactivated Mycobacterium vaccae administered in a three-dose series.

Heat-killed Mycobacterium vaccae vaccine was administered in a three-dose intradermal schedule to 10 healthy adult volunteers at 0, 2, and 10 months. Local and systemic side effects were monitored and vaccine site reactions were measured and photographed at visits 2 days, 14 days, and 2 months after each dose. Reactions to skin tests with purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) and titers of antibody to arabinose lipoarabinomannin were determined at baseline and after each dose of vaccine. Lymphocyte proliferation responses to MAS were determined after the final dose of vaccine. Immunization was safe and well tolerated, with maximal induration (range, 6-25 mm) at 2 days. PPD skin test conversions did not occur. Seven subjects completed the three-dose schedule; preexisting immunologic responses to mycobacteria were boosted in three, and a new response was elicited in one. M. vaccae vaccine is safe and induces measurable immunologic responses to mycobacterial antigens in some healthy adults.

Adult↗