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Biomedical subjects

A Gauthier

Publications and source records attributed to A Gauthier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes.

In this study, we report the effect of methanol, dimethyl sulfoxide (DMSO), and acetonitrile on the cytochrome P450 (P450)-mediated metabolism of several substrates in human liver microsomes: phenacetin O-deethylation for P4501A2, coumarin 7-hydroxylation for P4502A6, tolbutamide hydroxylation for P4502C8/2C9, S-mephenytoin 4'-hydroxylation for P4502C19, dextromethorphan O-demethylation for P4502D6, chlorzoxazone 6-hydroxylation for P4502E1, and testosterone 6beta-hydroxylation for P4503A4. DMSO was found to inhibit several P450-mediated reactions (2C8/2C9, 2C19, 2E1, and 3A4) even at low concentrations (0.2%). There was no measurable effect on the catalytic activity of the various P450s when methanol was present at levels </=1%, except for P4502C8/9 and 2E1. Acetonitrile did not noticeably change the catalytic activity of the P4502C8/2C9, 2C19, 2D6, and 2E1 enzymes at concentrations </=1%. It was found that the content level of the organic solvents should be kept lower than 1% because, for all three solvents, a concentration of 5% strongly affected the metabolism of the various probes. These findings should be taken into consideration when designing in vitro metabolism studies of new chemical entities.

Acetonitriles↗
PubMed1998

[Familial varices of the colon. Report of four cases].

We report four cases of ileo-colonic varices in one family. This congenital disease is uncommon with only 21 cases described in the literature. Recurrent digestive tract bleeding is the most common manifestation, but varices can be asymptomatic. Digestive endoscopy leads to the diagnosis. The diagnosis of familial colonic varices can be considered when colonic varices occur in several members of a family with no evident cause, particularly portal hypertension or venous thrombosis. No treatment is usually necessary except when major or recurrent bleeding indicates surgical resection. These malformations are classified as vascular ectasia in the subgroup of cavernous haemangiomas.

Adolescent↗
PubMed1997

Effects of aluminum exposure on behavioral parameters in the rat.

Adult rats were treated by intraperitoneal injection of aluminum gluconate for 3 months. Rats were submitted to the radial maze test to determine the influence of chronic aluminum intoxication on cognitive and noncognitive behavioral processes. Both learning abilities (working memory and reference memory) and rapidity (time spent to respond and to master a trial) were analyzed. Aluminum concentration was evaluated in the brain, serum, and liver to assess aluminum body burden. While hippocampus and neocortex showed a significant increase in aluminum concentration, aluminum treatment did never affect the animal's performance during cue learning or when the insert cues were removed. The only behavioral difference observed was a decrease in rapidity: both the total time to finish a trial and the latency to make the first choice were lengthened in aluminum-intoxicated rats.

Aluminum Compounds↗
PubMed1997

Circadian rhythm in the torque developed by elbow flexors during isometric contraction. Effect of sampling schedules.

Time-dependent changes in elbow flexion torque have been documented according to two different sampling schedules. Seven physical education students took part in the first series of experiments, and 7 other similar subjects in the second. In both sets of experiments, the subjects performed isometric contractions: maximal and submaximal at 90 degrees in the first experiments and maximal at different angular positions in the second. After a 30-minute rest period, the torque developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00 h on the day of the experiment. These subjects remained in the laboratory for 24 h. In the second series of experiments, the torque developed was measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00 h over the subsequent 6 days with only one test session per day. In this case, there was an interval of 20 h between two successive test sessions. In the first experiment, a significant time-of-day effect was observed for the torque of the elbow flexors under isometric conditions with an acrophase at 17:58 h. The 24 h normalized mean score was 92.85% with an amplitude of 7.63% of the daily mean. In the second series of experiments, there was evidence of a circadian rhythm in the torque developed by the elbow flexors at every angle position, especially at 90 degrees, the angle investigated in the first set of experiments. The peak torque was calculated to have occurred at 17:55 h. The amplitude of the rhythm was equal to 6.99% of the daily mean. There were no statistically significant differences in the characteristics of the circadian rhythm observed between the two experimental designs. We concluded that an experiment extending over several days could be employed to evaluate circadian rhythms in muscular activity reliably.

Adult↗
PubMed1997

In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse.

As domestic animals such as cat, horse, and dog increasingly become the clinical targets for drug discovery programs, the need to understand how these animals metabolize xenobiotics becomes more important. In the present study, substrates and inhibitors that were reported to be selective for particular P450 isozymes were used as probes to study in vitro metabolism in horse, dog, cat, and human liver microsomes. Seven selective catalytic activity markers for cytochrome P450-mediated reactions were measured: phenacetin O-deethylase (P4501A1/2), coumarin 7-hydroxylase (P4502A6), tolbutamide hydroxylase (P4502C8/9), S-mephenytoin 4'-hydroxylase (P4502C19), dextromethorphan O-demethylase (P4502D6), chlorzoxazone 6-hydroxylase (P4502E1), and testosterone 6beta-hydroxylase (P4503A4). Metabolic activity was found in every species with each substrate. Under the conditions of this study, it was observed that no one species was more active for any given substrate. However, rather large interspecies differences were observed. There was no marked sex difference in the way the various species metabolized the different substrates. The effect of selective P450 inhibitors on the various activities was tested with furafylline (P4501A2), mouse monoclonal antibody inhibitory to CYP2A6, sulfaphenazole (P4502C9), tranylcypromine (P4502C19), quinidine (P4502D6), diethyldithiocarbamate (P4502E1), and troleandomycin (P4503A4). In most cases, these inhibitors were effective to varying degrees against the activity seen in horse, dog, and cat liver microsomes. However, even at high concentrations, furafylline did not inhibit phenacetin O-deethylase activity in cat and troleandomycin did not affect testosterone 6beta-hydroxylase activity in horse. Sulfaphenazole was not tested in dog and cat because of the low tolbutamide hydroxylase activity. Overall, these results show that there are also large interspecies differences in the way the selective P450 inhibitors affect the in vitro metabolism of the various substrates in horse, dog, and cat liver microsomes.

Adolescent↗
PubMed1996

cDNA cloning and characterization of a 3'/5'-O-methyltransferase for partially methylated flavonols from Chrysosplenium americanum.

Enzymatic O-methylation of plant secondary metabolites is an important mechanism for the inactivation of reactive hydroxyl groups and for the modification of their solubility. A cDNA clone (pFOMT3') encoding the gene for the 3'/5'-O-methylation of partially methylated flavonols was isolated from Chrysosplenium americanum (Saxifragaceae). We used a PCR fragment obtained with degenerate oligonucleotides designed from conserved regions of various O-methyltransferases (OMTs). The pFOMT3' cDNA sequence shows about 67-85% similarity to other plant OMT sequences. The recombinant protein expresses strict specificity for positions 3'/5' (meta) of partially methylated flavonols, but does not accept quercetin or caffeic acid for further methylation. Southern blot analysis of the genomic DNA probed with an OMT sequence suggests the presence of a number of related genes in this species, consistent with the multiple enzymatic methylations involved in the biosynthesis of polymethylated flavonols in this plant.

Amino Acid Sequence↗
PubMed1996

Molecular mapping of a Yq deletion in a patient with normal stature.

The proximal long arm of the Y chromosome probably contains a gene (GCY) involved in stature determination. Recent reports have proposed the critical region extends from interval 4B to interval 5G (or 5E). In the present study, the deletion breakpoint in a male adult patient of normal height with a 46,X,del(Yq) karyotype was defined by the use of sequence-tagged site markers. The breakpoint was found between sY78 (interval 4B) and sY79 (interval 5A). The existence of a normal stature in this patient suggests that the growth determinant is proximal to sY79, therefore probably located in interval 4B or in proximal interval 5A of the Y chromosome.

Adult↗
PubMed1996

Impact of various handling and storage conditions on quantitative detection of hepatitis C virus RNA.

BACKGROUND/AIMS: Both HCV RNA viral load and HCV genotype have been described as important predicting factors determining the response to interferon in chronic hepatitis C. To investigate whether processing and storage conditions might influence the stability and could alter the concentration of the HCV RNA in serum, quantification of HCV RNA was performed by branched DNA assay. METHODS: We studied serum samples obtained from seven patients with histologically proven chronic hepatitis C. These were subjected to the following physical conditions: (1) immediate quantification, (2) storage at room temperature for 5 days, (3) storage at 4 degrees C for 5 days, (4) storage at -20 degrees C for 5 days, (5) storage at -80 degrees C for 5 days, (6) five freeze-thaw cycles, (7) blood unspun for 4 h at room temperature then centrifuged and stored at -80 degrees C for 5 days, (8) storage at 4 degrees C for 6 months, (9) storage at -20 degrees C for 6 months, (10) storage at -80 degrees C for 6 months. RESULTS: A loss of 100% HCV RNA titers was observed after storage at RT for 5 days and then storage at 4 degrees C for 6 months. A surprising decrease of HCV RNA titer (15.6%) was observed in sera stored for 5 days at -20 degrees C. Five freeze-thaw cycles resulted in a 16% decrease of the HCV RNA level. When centrifugation was performed after a 4 h delay at room temperature, a significant loss of HCV RNA titers of 29.5% was observed. Long-term stability (6 months) was observed at -80 degrees C with a slight loss of about of 10% HCV RNA titers, but a significant decrease in HCV RNA of 23% was observed at -20 degrees C. The reproducibility of the bDNA assay on five patient samples was performed eight times in duplicate and showed an average coefficient of variation of 9.1%. CONCLUSIONS: These data confirm the importance of storage and handling in measuring the amount of HCV RNA in clinical samples.

Blood Preservation↗
PubMed1996

Genetic heterogeneity between type 1a and type 1b insulin-dependent diabetes mellitus: HLA class II and TAP gene analysis.

The aim of this study was to compare the genetic susceptibility linked to the HLA Class II region genes of the Major Histocompatibility Complex in isolated insulin-dependent diabetes mellitus (1a-IDDM) and insulin-dependent diabetes mellitus associated with another autoimmune endocrinopathy (1b-IDDM). HLA genes DRB1, DQA1 and DQB1 were studied at the genomic level, as well as genes TAP1 and TAP2. One hundred and seventy-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM patients. While it appeared that common genetic traits characterize diabetes regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM. Extending the analysis of risk haplotypes DRB1*03 and DRB1*04 to TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplo-type DRB1*03 was thus characterized in 1a-IDDM patients by a lower frequency of alleles TAP1-B (13.5%) and TAP2-B (16.2%), not found in 1b-IDDM patients (33.3% for each allele). Likewise, haplotype DRB1*04 is characterized in 1b-IDDM patients by a lower frequency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in 1a-IDDM patients (22.2% and 25.9%, respectively). In total, this study showed that extending the characterization of HLA Class II haplotypes to TAP genes discriminates between the forms of diabetes restricted to a specific pancreatic affection and those reflecting a wider autoimmune disorder affecting several organs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Diurnal rhythm of the muscular performance of elbow flexors during isometric contractions.

The influence of time of day on elbow flexion torque was studied. Thirteen physical education students, 7 males and 6 females, made maximal and submaximal isometric contractions at 90 degrees of elbow flexors using a dynamometer. The torque developed was measured on each contraction. The myoelectric activity of the biceps muscle was also measured at the same time by surface electromyography (EMG) and quantified from the root mean square (RMS) activity. Torque and surface EMGs were measured at 6:00, 9:00, 12:00, 15:00, 18:00, 21:00, and 24:00 h over the same day. Oral temperature before each test session was measured on each occasion after a 30-min rest period. We observed a diurnal rhythm in elbow flexor torque with an acrophase at 18:00 h and a bathyphase at 6:00 h, in phase with the diurnal rhythm in oral temperature. However, the diurnal rhythm of temperature did not appear to have any influence on the torque. Links between neuromuscular efficiency and RMS/torque ratio were evaluated by measuring muscle activity along with torque. We also assessed variations in the level of maximal activity of the muscle under maximal voluntary contraction. Neuromuscular efficiency fluctuated during the day, with maximal and minimal efficiency at 18:00 h and 9:00 h, respectively, whereas activation level was maximal at 18:00 h and minimal at 9:00 h. The diurnal rhythm of torque was accounted for by variations in both central nervous system command and the contractile state of the muscle.

Adult↗
PubMed1996

Time-related changes of cold-stored rat liver in University of Wisconsin solution. Effect of ursodeoxycholate.

Livers of Wistar rats were stored between 0 and 36 hrs. in the University of Wisconsin preservation liquid in order to determine time-related biochemical and morphological hepatic changes. Ursodeoxycholate (100 microM) was also added in the medium to test the hepatoprotective properties of the bile salt. Biochemical assays were performed on hepatic microsomes, plasma and biliary canalicular membranes. Protein and lipid composition of the microsomal and baso-lateral plasma membranes remained stable. Protein and cholesterol content of the biliary canalicular membranes decreased, phospholipid/cholesterol ratio increased between 0 and 36 hrs.; it resulted in a leak of 5'-nucleotidase and leucine amino peptidase activity of these biliary canalicular membranes, especially up to 12 hrs. Between 0 and 36 hrs., the lipid and protein content remained stable in the plasma membranes, as well as both tested enzymatic activities. Observations under electron microscopy showed alterations and underlined fragility of the bile canaliculi, particularly after 24 hrs. preservation. Ultrastructure of sinusoidal membranes showed damaged microvilli. Endoplasmic reticulum remained unchanged, in relation to the stability of the microsomal lipidic, proteic content and hydroxymethylglutaryl-coenzyme A reductase activity, except the decreased protein content after preservation for 36 hrs without ursodeoxycholate. Ursodeoxycholate by itself did not protect against the described disturbances.

Adenosine↗
PubMed1996

Early operation for severe corrosive injury of the upper gastrointestinal tract.

OBJECTIVE: To describe our experience of treating severe corrosive burns of the upper gastrointestinal (GI) tract. DESIGN: Open study. SETTING: Teaching hospital, France. SUBJECTS: 18 patients who had swallowed an alkaline substance (caustic soda in 10 cases) and 4 who had swallowed either hydrochloric or sulphuric acid. INTERVENTIONS: Endoscopy was done a mean of 4 hours after the substance had been swallowed. 10 patients underwent oesophagogastrectomy without thoracotomy. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: 4 of the 10 patients died and 3 developed postoperative complications. Of the 12 patients treated by feeding jejunostomy 7 developed stenosis that required operation and 3 developed stenosis that responded to dilatation. None of the 12 died. CONCLUSIONS: Early oesophagoscopy allowed optimal management. Patients died if they swallowed more than 60 ml of a strong alkaline substance. When patients are treated conservatively about half will develop stenoses that require operation.

Acids↗