Biomedical subjects

A Gauthier

Publications and source records attributed to A Gauthier.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.

OBJECTIVES: To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). PATIENTS AND METHODS: In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. RESULTS: Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean +/- SD) increased significantly both in the etidronate group (+2.1% +/- 0.7%/year) and in the alendronate group (+5.3% +/- 0.9%/year). The increase was significantly greater with alendronate (P< 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% +/- 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+ 1.2% +/- 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). CONCLUSION: Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Aged↗

PubMed2001

UCP3 and its putative function: consistencies and controversies.

The physiological function of uncoupling protein 3 (UCP3) is as yet unknown. Based on its 57% homology to UCP1 whose physiologic function is uncoupling and thermogenesis, UCP3 was attributed with the function of mitochondrial uncoupling through proton-leak reactions. UCP3 is expressed selectively in muscle, a tissue in which it has been estimated that proton leak accounts for approx. 50% of resting energy metabolism. Genetic linkage, association and variant studies suggest a role for UCP3 in obesity and/or diabetes. Studies of the heterologous expression of UCP3 in yeast provide support for the idea that UCP3 can uncouple mitochondrial oxidative phosphorylation, but the physiological relevance of these results is questionable. In vitro studies of mitochondria from Ucp3(-/-) mice provide support, but there are no changes in resting metabolic rate (RMR) of mice. In vivo studies demonstrate increased ATP synthesis, but estimates of substrate oxidation rate indicate no change. Mice that greatly overexpress Ucp3 in muscle have increased RMR. Inconsistent with the function of uncoupling are the observations that fasting results in increased expression of UCP3, but no change in muscle proton leak. Moreover, fasting decreases energy expenditure in muscle. Expression patterns for Ucp3 and lipid-metabolism genes support a physiological role in fatty acid oxidation. Overall, findings support a role for Ucp3 in fatty acid metabolism that may have implications for obesity and/or Type II diabetes.

Animals↗

PubMed2001

Enterohaemorrhagic and enteropathogenic Escherichia coli use a different Tir-based mechanism for pedestal formation.

Enterohaemorrhagic Escherichia coli (EHEC) adheres to the host intestinal epithelium, resulting in the formation of actin pedestals beneath adhering bacteria. EHEC and a related pathogen, enteropathogenic E. coli (EPEC), insert a bacterial receptor, Tir, into the host plasma membrane, which is required for pedestal formation. An important difference between EPEC and EHEC Tir is that EPEC but not EHEC Tir is tyrosine phosphorylated once delivered into the host. In this study, we assessed the role of Tir tyrosine phosphorylation in pedestal formation by EPEC and EHEC. In EPEC, pedestal formation is absolutely dependent on Tir tyrosine phosphorylation and is not complemented by EHEC Tir. The protein sequence surrounding EPEC Tir tyrosine 474 is critical for Tir tyrosine phosphorylation and pedestal formation by EPEC. In contrast, Tir tyrosine phosphorylation is not required for pedestal formation by EHEC. EHEC forms pedestals with both wild-type EPEC Tir and the non-tyrosine-phosphorylatable EPEC Tir Y474F. Pedestal formation by EHEC requires the type III delivery of additional EHEC factors into the host cell. These findings highlight differences in the mechanisms of pedestal formation by these closely related pathogens and indicate that EPEC and EHEC modulate different signalling pathways to affect the host actin cytoskeleton.

Amino Acid Sequence↗

PubMed2001

Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells.

Enteropathogenic Escherichia coli (EPEC) is an extracellular bacterial pathogen that infects the human intestinal epithelium and is a major cause of infantile diarrhea in developing countries. EPEC belongs to the group of attaching and effacing (A/E) pathogens. It uses a type III secretion system to deliver proteins into the host cell that mediate signal transduction events in host cells. We used gene array technology to study epithelial cell responses to EPEC infection at the level of gene expression. We found that EPEC induces the expression of several genes in infected HeLa cells by a lipopolysaccharide (LPS)-independent mechanism, including cytokines and early growth response factor 1 (Egr-1). The transcription factor Egr-1 is an immediate-early-induced gene that is activated in most cell types in response to stress. EPEC-induced upregulation of egr-1 is mediated by the activation of the MEK/extracellular signal-regulated kinase signal transduction pathway and is dependent on the type III secretion system. egr-1 is also induced during infection of mice by the A/E pathogen Citrobacter rodentium, suggesting that both Egr-1 and the activation of this mitogen-activated protein kinase signal transduction pathway may play a role in disease.

Animals↗

PubMed2000

[Central nervous system demyelinating disease following hepatitis B vaccination with GenHevac B. Review of ten years of spontaneous notifications (1989-1998)].

OBJECTIVES: To describe and analyze spontaneous reports of central nervous system (CNS) demyelinating disease including multiple sclerosis, following vaccination with GenHevac B vaccine, from 1989 to December 31, 1998. METHODS: Descriptive analysis of adverse event reports in the vaccinated population, including the number of cases of CNS demyelinating disease, their frequencies, their dates of onset in relation to dates of report and their distribution according to age, sex and the number of injections. A Kaplan-Meier curve was used to analyze the time period between the last dose of vaccine and the onset of CNS demyelinating disease. RESULTS: Overall, 187 cases of CNS demyelinating disease were spontaneously reported, (0.54 reports per 100,000 doses of GenHevac B distributed). The average time period between the occurring date of onset of the disease and its subsequent report was 24 months. The average age of onset was 31.7 years old and 73% of cases were women. The time between the last dose of vaccine and the onset of disease was regularly distributed from 1 day to 5 years (median: 60 days). CONCLUSION: These results, together with available clinical, epidemiological data regarding multiple sclerosis, do not suggest a causal relationship between CNS demyelinating disease and vaccination with GenHevac B.

Adult↗

PubMed2000

Absence of hepatitis C genome in semen of infected men by polymerase chain reaction, branched DNA and in situ hybridization.

BACKGROUND/AIMS: The presence or absence of hepatitis C virus (HCV) RNA in the semen of infected man remains controversial, mainly due to technical difficulties associated with nucleic acid detection. The aims of this study were to assess the presence of HCV RNA in spermatozoa and in seminal fluid using different polymerase chain reaction (PCR)- and non-PCR-dependent methods and, in the case of HCV presence, to correlate this detection with the viraemia. METHODS: Serum and semen from 25 chronically infected hepatitis C patients were studied. The semen was separated into spermatozoa and seminal fluid and HCV RNA was analysed in the two fractions using RT-PCR and branched DNA. The presence of HCV RNA in pelleted cells was also assessed using in situ hybridization. RESULTS: All three approaches failed to demonstrate HCV RNA in semen. The presence of an inhibitor of the PCR was demonstrated in seminal fluid but not in spermatoza. CONCLUSION: Our results confirmed the lack of detection of HCV RNA in semen by PCR- and non-PCR-dependent techniques and support the view that viral contamination in semen remains, if present, at a very low level. Nevertheless, epidemiological studies are required to definitively assess the absence of sexual transmission of HCV

Adolescent↗

PubMed2000

Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats.

BACKGROUND & AIMS: Corticotropin-releasing factor (CRF) exerts its action through CRF receptors 1 and 2 (CRF-R1 and CRF-R2). CRF has preferential affinity for CRF-R1, whereas urocortin displays high affinity for both. We investigated changes in colonic motor function after intraperitoneal (IP) injection of CRF-related peptides. METHODS: Colonic motility was recorded in vivo in conscious rats equipped with electrodes chronically implanted in the cecum and proximal colon or in vitro in distal colon; fecal output was monitored in naive rats. RESULTS: Rat CRF, rat urocortin, and amphibian sauvagine (10 microg/kg, IP) induced a new pattern of cecocolonic myoelectric activity characterized by clustered spike bursts of long duration; the percentage of occurrence was highest after CRF. The rank order of potency to increase fecal pellet output after IP peptide injection (0.3-10 microg/kg, IP) was CRF > urocortin = sauvagine. The CRF-R1/R2 antagonist astressin (33 microg/kg, IP) and the CRF-R1 antagonist CP-154,526 (20 mg/kg, subcutaneously) inhibited IP CRF-induced changes in cecocolonic myoelectric activity and IP CRF- and water avoidance stress-induced fecal output. In vitro, CRF injected into the inferior mesenteric artery increased distal colonic myoelectric activity compared with saline injection. CONCLUSIONS: These results demonstrate that CRF acts peripherally to stimulate colonic motility and that CRF-R1 is primarily involved in mediating IP CRF/urocortin- and water avoidance stress-induced colonic motor response.

Animals↗

PubMed2000

Objective assessment of the contribution of each diagnostic test and of the ordering sequence in jaundice caused by pancreatobiliary carcinoma.

BACKGROUND: Computer-assisted diagnostic systems are not substantially more accurate than the clinician in the differential diagnosis of jaundice but may help in optimal selection and sequencing of tests. The present study aimed to assess with an electronic diagnostic tool the pattern of ordering tests and the diagnostic contribution and related financial cost of each test in jaundiced patients with pancreatobiliary carcinoma, in an effort to make the clinician's diagnostic behaviour more efficient and economical. METHODS: Clinical and diagnostic test data were prospectively gathered from 356 jaundiced patients with pancreatobiliary carcinoma and entered in a Bayesian diagnostic programme. The test results were added to the existing diagnostic evidence, and the programme calculated the diagnostic contribution of each test. RESULTS: A total of 1804 diagnostic tests were ordered. Quantitative assessment of the diagnostic contribution of each test showed that percutaneous transhepatic cholangiography and computed tomography were associated with the highest provision of information. The most cost-effective tests were ultrasonography and liver function tests. CONCLUSIONS: It is possible to determine objectively the diagnostic contribution of each test in establishing the diagnosis of pancreatobiliary carcinoma. The observed physician behaviour in ordering the various diagnostic tests might be improved with regard to its efficacy and its cost-effectiveness profile.

Bayes Theorem↗

PubMed2000

Circadian rhythms in human muscular efficiency: continuous physical exercise versus continuous rest. A crossover study.

This study deals with the influence of time of day on neuromuscular efficiency in competitive cyclists during continuous exercise versus continuous rest. Knee extension torque was measured in ultradistance cyclists over a 24h period (13:00 to 13:00 the next day) in the laboratory. The subjects were requested to maintain a constant speed (set at 70% of their maximal aerobic speed obtained during a preliminary test) on their own bicycles, which were equipped with cyclosimulators. Every 4h, torque developed and myoelectric activity were estimated during maximal isometric voluntary contractions of knee extensors using an isokinetic dynamometer. Mesenteric temperature was monitored by telemetry. The same measures were also recorded while the subjects were resting awake until 13:00 the next day. During activity, torque changed within the 24h period (p < .005), with an acrophase at 19:10 and an amplitude of 7.8% around the mean of 70.7%. At rest, a circadian rhythm was observed in knee extensor torque (p < .05), with an acrophase at 19:30 and an amplitude of 6% around the mean of 92.3%. Despite the standardized conditions, the results showed that isometric maximal strength varied with time of day during both a submaximal exercise and at rest without prior exercise. The sine waves representing these two rhythms were correlated significantly. Although at rest the diurnal rhythm followed muscular activity (i.e., neurophysiological factors), during exercise, this rhythm was thought to stem more from fluctuations in the contractile state of muscle.

Adult↗

PubMed2000

Mechanical fractionation reveals structural requirements for enteropathogenic Escherichia coli Tir insertion into host membranes.

Enteropathogenic Escherichia coli (EPEC) inserts its receptor for intimate adherence (Tir) into host cell membranes by using a type III secretion system. Detergents are frequently used to fractionate infected host cells to investigate bacterial protein delivery into mammalian cells. In this study, we found that the Triton X-100-soluble membrane fraction from EPEC-infected HeLa cells was contaminated with bacterial proteins. We therefore applied a mechanical method of cell lysis and ultracentrifugation to fractionate infected HeLa cells to investigate the biology and biochemistry of Tir delivery and translocation. This method demonstrates that the translocation of Tir into the host cell membrane requires its transmembrane domains, but not tyrosine phosphorylation or binding to Tir's ligand, intimin.

Bacterial Proteins↗

PubMed2000

Relative efficacy of sildenafil compared to other treatment options for erectile dysfunction.

OBJECTIVE: We examined and compared the efficacy of sildenafil in patients previously using other agents or devices for erectile dysfunction (ED) treatment. METHODS: We identified 47 patients with organic ED who had tried other therapies (intracavernosal injection therapy [ICIT], intraurethral prostaglandin suppositories [IPS], vacuum erection devices [VEDs], or yohimbine) before using sildenafil. Comparisons of the efficacy of sildenafil to the previously used agent or device were assessed by telephone questionnaire. Responses were compared using nonparametric Wilcoxon rank sum and analysis of variance testing. RESULTS: Sildenafil therapy was no more effective than ICIT or VEDs but was more effective than IPS. No significant difference occurred in response to sildenafil with age. Of 22 patients achieving erections adequate for intercourse with their previous therapy, 14 (63%) achieved equal or improved erections with sildenafil. Of the remaining 18 patients who had erections inadequate for intercourse with previous therapy, 5 (27%) had adequate erections with sildenafil. CONCLUSIONS: Oral sildenafil therapy provides results comparable to those of other available ED treatment modalities. A trial of this drug in this patient population is warranted.

Adult↗

PubMed2000

[Circadian fluctuations in the muscular efficiency of athletes: with sleep versus sleep deprivation].

The influence of time of day on muscular performance was studied. From part of the results of two different studies (EAS et EPS), the effects of sleep deprivation were appreciated. Seven times over the 24-h period, developed torque and myoelectric activity were estimated during maximal isometric voluntary contractions using an isokinetic dynamometer: elbow flexion for EAS in standardised sleep, and knee extension for EPS in complete sleep deprivation. The results showed nycthemeral changes in torque in both conditions (p < 0.005), with maximal values recorded at the beginning of night. Although during sleep deprivation (EPS) the rhythm followed neurophysiological factors, during EAS, this rhythm was accounted for by the variations in the contractile state of muscle.

Adult↗

PubMed1999

Enteropathogenic Escherichia coli: a pathogen that inserts its own receptor into host cells.

Enteropathogenic Escherichia coli (EPEC) is a major cause of infant diarrhea, killing hundreds of thousands of children per year worldwide. Intimate attachment to the host cell leading to the formation of actin-rich pedestals beneath the adhering bacteria is an essential feature of EPEC pathogenesis. EPEC attaches to host cells via the outer membrane adhesin, intimin. It was recently shown that EPEC inserts its own receptor for intimate adherence, Tir (translocated intimin receptor) into the host cell membrane. The focus of this review is on the discovery and characterization of this novel receptor, and our current understanding of its role in pedestal formation. Gram-negative bacterial secretion systems, including type III secretion systems, are reviewed and discussed in the context of Tir delivery into the host cell membrane. The relationship and relevance of in vitro models compared to the actual in vivo situation is essential to understanding disease. We have critically reviewed the use of animal models in studying EPEC infection. Elucidating the function of Tir will contribute to our understanding of how EPEC mediates disease.

Adhesins, Bacterial↗

PubMed1999

Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) attaches intimately to mammalian cells via a bacterial outer membrane adhesion molecule, intimin, and its receptor in the host cell membrane, Tir. Tir is a bacterial protein translocated into the host cell membrane and tyrosine phosphorylated after insertion. Tir-intimin binding induces organized actin polymerization beneath the adherent bacteria, resulting in the formation of pedestal-like structures. A series of Tir deletion derivatives were constructed to analyse which Tir domains are involved in intimin binding. We have localized the intimin-binding domain (IBD) of Tir using a yeast two-hybrid system and a gel-overlay approach to a region of 109 amino acids that is predicted to be exposed on the surface of the plasma membrane. A truncated Tir protein lacking this domain was translocated to the host cell membrane and tyrosine phosphorylated, but failed to bind intimin or to induce either actin polymerization or Tir accumulation beneath the bacteria. These results indicate that only a small region of Tir is needed to bind intimin and support the predicted topology for Tir, with both N- and C-terminal regions in the mammalian cell cytosol. They also confirm that Tir-intimin interactions are needed for cytoskeletal organization. We have also identified N-terminal regions involved in Tir stability and Tir secretion to the media.

Actins↗

PubMed1999

Comparison of mobile lithotripters at one institution: healthtronics lithotron, Dornier MFL-5000, and Dornier Doli.

BACKGROUND AND PURPOSE: Extracorporeal shockwave lithotripsy (SWL) has replaced most surgical and endourologic procedures for upper urinary tract stone disease. Our institution contracted with mobile lithotripter companies to provide SWL. We reviewed the outcomes of 50 patients treated on each machine with regard to efficacy, complications, and retreatment rates. PATIENTS AND METHODS: One hundred fifty patients over 21 years of age were treated at Ochsner Foundation Hospital from April 1995 through June 1998. All stones were in either the kidney or the upper ureter, and all were <20 mm. Three mobile lithotripters-the Dornier MFL-5000 (4/95-9/96), the Dornier Doli (9/96-11/97), and the HealthTronics Lithotron (12/97-4/98)-were each used to treat 50 patients. Conscious monitored intravenous sedation was used in all patients. Post-treatment evaluations were made at 2 weeks, 1 month, and 3 months. RESULTS: A successful outcome (stone free or fragments <4 mm) was achieved in 72% (MLF-5000), 68% (Doli), and 80% (Lithotron) of patients (P = 0.39). Treatments that were followed by retreatments or other further procedures (ureteroscopy or percutaneous nephrolithotomy) were counted as failures. The retreatment rate was 10%, 22%, and 10%, respectively. There were three significant complications with the Doli unit: two large perirenal hematomas (4%) and one delayed splenic rupture in a patient with a history of pelvic surgery that necessitated transfusions and urgent splenectomy. The minor complication rates with all three lithotripters were similar to those reported in the literature. The three-month efficiency quotients were 0.55 for the Lithotron and MFL-5000 and 0.41 for the Doli. CONCLUSIONS: Statistically equivalent success rates were achieved with all three machines. The electromagnetic unit (Doli) had higher rates of retreatment and significant complications than the electrohydraulic lithotripters (MFL-5000, Lithotron).

Adult↗

PubMed1999

[Why we prefer the thin layer technique to conventional Pap smears. A double-blind study of 473 specimens].

The study evaluated the feasibility of a thinlayer technique on a routine basis for cervical smears and compared 473 ThinPrep preparations to the matched conventional Papsmears. The interpretation was double-blind and performed according to the Bethesda system. A consensus was established in discordant cases. The technique was easily mastered by gynecologists and technicians. Main advantages of the thinlayer technique were: a low number (1%) of unsatisfactory samples; a constant quality; homogeneity of cell distribution; the disappearance of problems of interpretation due to fixation or smear artifacts, red cells, polymorphs; a more precise interpretation, a firmer diagnosis; less visual fatigue; a shorter time of interpretation; the possibility of preparing more slides and performing special techniques on the same specimen. Main disadvantages were a higher cost and a necessary period of learning for cytologists.

Adult↗

PubMed1998

Protein translocation: delivering virulence into the host cell.

A wide variety of plant and human bacterial pathogens use a specialized 'type III' protein secretion system to deliver virulence factors into host cells. Appendage-like surface structures have recently been identified on several bacterial pathogens and there are indications that these may be conduits for virulence factor delivery.

Animals↗

PubMed1998

Characterization of two cDNA clones which encode O-methyltransferases for the methylation of both flavonoid and phenylpropanoid compounds.

Enzymatic O-methylation of phenylpropanoid and flavonoid compounds is believed to be catalyzed by distinct classes of O-methyltransferases [EC 2.1.1.6x]. The O-methylated derivatives of phenylpropanoids and flavonoids play an important role in lignification and as antimicrobial compounds, respectively. Two cDNA clones, OMT1 and OMT2, which differ in three amino acid residues were isolated and characterized from the semiaquatic freshwater weed Chrysosplenium americanum (Saxifragaceae). These two novel cDNA clones encode enzymes which catalyze the 3'-O-methylation of the flavonoid aglycones luteolin and quercetin, although they also catalyze the efficient 3/5-O-methylation of the phenylpropanoids caffeic and 5-hydroxyferulic acids, respectively. Both recombinant proteins were partially purified from an Escherichia coli expression system and their kinetic parameters were compared using two flavonoids and two phenylpropanoids as substrates. Although both gene products methylate caffeic acid and 5-hydroxyferulic acid to a similar extent, they exhibit a threefold higher affinity for and a four- to sixfold increase in turnover of flavonoid compounds. The gene product of OMT1 accepts the flavonoid substrates luteolin and quercetin for methylation at a higher rate than that of OMT2, as indicated by a two- to threefold increase in its Vmax values and turnover ratios. The fact that C. americanum accumulates a variety of highly methylated flavonols and exhibits little lignification suggests that these two flavonoid OMT clones have retained their ability to O-methylate phenylpropanoids as well. These results are discussed in relation to differences in the amino acid sequences of these two clones, as well as with other O-methyltransferases, and the evolutionary divergence of these genes in plants.

Amino Acid Sequence↗