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Biomedical subjects

M Gauthier

Publications and source records attributed to M Gauthier.

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

Escherichia coli cytotoxic necrotizing factor 1 effaces microvilli and decreases transmigration of polymorphonuclear leukocytes in intestinal T84 epithelial cell monolayers.

Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like protein from pathogenic Escherichia coli strains, induces an actin cytoskeleton reorganization consisting of the formation of prominent stress fibers by permanent activation of the small GTP-binding protein Rho. Since p21Rho regulates tight-junction permeability and perijunctional actin reorganization in epithelial intestinal cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez, P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we used polarized T84 epithelial intestinal cell monolayers to examine whether CNF1 could affect microvillus structure, transepithelial resistance, and polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with CNF1 did not influence transepithelial resistance, suggesting that barrier function and surface polarity were not affected by the toxin. However, CNF1 effaced intestinal cell microvilli and induced a strong decrease of PMN transepithelial migration in either the luminal-to-basolateral or the basolateral-to-luminal direction. CNF1 could thus be a virulence factor exhibiting a new type of combined activity consisting of effacing of microvilli and occlusion of the epithelial barrier to PMNs. Attenuated transepithelial migration of PMNs could result in the enhanced growth and protection of luminal bacteria.

Bacterial Toxins↗
PubMed1997

Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine.

Pathogenic Escherichia coli are responsible for a variety of diseases, including diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the virulence factors produced by uropathogenic (CNF1) or enteropathogenic (CNF2) E. coli strains that cause diseases in humans and animals, respectively. CNFs induce an increase in the content of actin stress fibres and focal contacts in cultured cells. Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho and indirect evidence indicates that CNF1 might constitutively activate Rho. Here we show that CNF1 catalyses the deamidation of a glutamine residue at position 63 of Rho, turning it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the reorganization of actin stress fibres. To our knowledge, CNF1 is the first example of a bacterial toxin acting by deamidation of a specific target protein.

Actins↗
PubMed1997

Reactivation of C1-inhibitor polymers by denaturation and gel-filtration chromatography.

C1-inhibitor is a proteinase inhibitor in the serpin family. It is an important inhibitor of complement C1, plasma kallikrein, and factor XIIa, and as such is involved in regulating inflammatory pathways. Studies on the plasma-derived protein are hampered by the relative ease with which the protein converts to an inactive state on storage, under mild denaturing conditions, or by incubating in some unfavorable buffers. This inactivation is caused by formation of soluble polymers which can be visualized on native electrophoresis. In order to facilitate studies on both the plasma-derived protein and recombinant variants planned for the future, it was necessary to devise a method for the rapid reactivation of the polymers in high yield. It was found that nonionic detergents did not dissociate the polymers, but they were readily dissociated in 0.1% SDS. Treatment with 0.1% SDS followed by rapid removal of the SDS and refolding on an FPLC Superose 6 column allowed for recovery of about 15% of the protein in the active monomeric form. Eighty-five percent eluted as a range of higher order polymers. Using 8 M urea as the denaturant a 25% yield of active monomer was recovered. However, with 6 M guanidine hydrochloride as the denaturant, the yield of active monomer was almost 50%. The remaining material was not present as a range of polymeric species but was probably a dimer. Therefore this method is a useful technique to facilitate studies on C1-inhibitor. Moreover, the ability to produce monomer, dimer, and polymer forms of C1-inhibitor is useful for studies investigating the conformational changes which have occurred in the different forms.

Chromatography, Gel↗
PubMed1997

Acquired carnitine abnormalities in critically ill children.

UNLABELLED: In order to characterize the role of carnitine during metabolic stress, we prospectively determined carnitine profiles in plasma and urine on admission, days 2, 5, 10 and 15, among 28 critically ill children free of any known conditions associated with secondary carnitine deficiency. More than 25% of plasma and 50% of urinary carnitine measurements were abnormal; 96% (27/28) of patients displayed on at least one occasion an abnormal [< -2 SD or > +2 SD] carnitine value in plasma. Three children had extremely low [< 10 micromol/l] free carnitine (FC) levels in plasma. Plasma esterified and FC levels on admission were not related to the risk of mortality [PRISM score], to muscle lysis [CK values], and to the caloric intake. Levels of FC and esterified carnitine in plasma were unrelated to those measured in urine. CONCLUSION: Abnormal plasma and urine carnitine measurements are frequently found in critically ill children; the biological significance of these perturbations remains unclear. Caution must be exercised before concluding that an abnormal carnitine value is indicative of an underlying hereditary metabolic disorder in this population.

Adolescent↗
PubMed1997

The bionic glove: an electrical stimulator garment that provides controlled grasp and hand opening in quadriplegia.

OBJECTIVE: This report describes the operation of the Bionic Glove, a new functional electrical stimulation (FES) device designed to improve the function of the paralyzed hand after spinal cord injury (SCI) or stroke. DESIGN: Signals from a sensor in the glove detecting voluntary wrist movement are used to control FES of muscles either to produce hand-grasp or to open the hand. When the glove is donned, conductive areas on its inside surface automatically make contact with self-adhesive electrodes on the skin. SETTING AND PATIENTS: This report concerns nine people with SCI who have used the device in their daily lives for up to a year or more. Measurements were made at clinics in Edmonton, Miami, and Chicago as part of a multicenter clinical trial. OUTCOME MEASURES AND RESULTS: The mean peak force of tenodesis grasp in the nine subjects increased from 2.6N (passive) to 11.3N (glove active). Active force was significantly greater than passive grasp force even when muscles were fatigued after repetitive grasp-release cycles. Most manual tasks improved significantly with the use of the glove, as judged by the number of tasks completed in a minute or the subjects' qualitative ratings of task difficulty. CONCLUSION: The Bionic Glove can provide significant improvement of hand function in people with C6-C7 SCI.

Adult↗
PubMed1997

Evaluation of zolpidem, triazolam, and placebo as hypnotic drugs the night before surgery.

STUDY OBJECTIVE: To compare the hypnotic effects of a bedtime dose of zolpidem, triazolam, and placebo. DESIGN: "Double-blind, randomized, placebo- and active-controlled, parallel-group" trial. SETTING: Six Canadian hospitals. PATIENTS: 357 patients (aged 19 to 71 years) hospitalized the night before a surgical procedure. INTERVENTIONS: At bedtime, each patient received either zolpidem 10 mg, triazolam 0.25 mg, or placebo, and was allowed to sleep for a maximum of 8 hours. MEASUREMENTS: Outcome measures were subjective in nature and included a morning questionnaire, visual analog scales, and observation forms by study personnel. All continuous variables were analyzed by analysis of variance. All categorical data were compared using the Cochran-Mantel-Haenszel (CMH) test, and the percentage of patients asleep was compared using a CMH chi-square analysis. When significant overall treatment effects were observed, pairwise comparisons were undertaken. Compared with the placebo group, the following parameters were significantly (p < 0.001) different in the zolpidem and triazolam groups: sleep latency was shorter, total sleep time was longer, patients fell asleep more easily, and the number of patients awake 2 hours after drug administration was lower. There were no differences between any groups in next-morning somnolence or ability to concentrate. Both drugs were well tolerated, with adverse event incidence rates nearly identical to placebo. CONCLUSIONS: In patients suffering from transient insomnia, a single dose of zolpidem 10 mg was as effective as triazolam 0.25 mg, and both were more effective than placebo and were well tolerated.

Adult↗
PubMed1997

Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains.

Cytotoxic necrotizing factor type 1 (CNF1) induces, in epithelial cells, the development of stress fibres via the GTPase Rho pathway. We showed that CNF1 is able to modify Rho both in vitro and in vivo. Recombinant N-terminal 33kDa (CNF1Nter) and C-terminal 14.8-31.5 kDa (CNF1Cter) regions of the CNF1 protein allowed us to demonstrate that the N-terminal region contains the cell-binding domain of the toxin and that the C-terminal region is responsible for its catalytic activity. CNF1Nter lowered the activity of CNF1 when provided to cells before the toxin whereas CNF1Cter had no effect on CNF1 cell toxicity. CNF1Cter was sufficient to induce a typical CNF1 phenotype when microinjected into African green monkey kidney cells (Vero cells), and was able to modify Rho as previously reported for CNF1. The C-terminal domain lost its catalytic activity when deleted of various subdomains, suggesting a scattered distribution of catalytic-site amino acids. Elucidation of the CNF1 functional organization and analysis of amino acid homologies between CNFs (CNF1, CNF2), Pasteurella multocida toxin (PMT) and dermonecrotic toxin of Bordetella pertussis (DNT) allowed us to postulate that CNFs and DNT act on Rho via the same enzymatic activity located in their C-terminus, and that CNFs and PMT probably bind to analogous cell receptors.

Amino Acid Sequence↗
PubMed1997

Replacement of isoleucine-47 by threonine in the HPr protein of Streptococcus salivarius abrogates the preferential metabolism of glucose and fructose over lactose and melibiose but does not prevent the phosphorylation of HPr on serine-46.

Phosphorylation of HPr on a serine residue at position 46 (Ser-46) by an ATP-dependent protein kinase has been reported in several Gram-positive bacteria, and the resulting intermediate, HPr(Ser-P), has been shown to mediate inducer exclusion in lactococci and lactobacilli and catabolite repression in Bacillus subtilis and Bacillus megaterium. We report here the phenotypic properties of an isogenic spontaneous mutant (G22.4) of Streptococcus salivarius ATCC 25975, in which a missense mutation results in the replacement of isoleucine at position 47 (Ile-47) by threonine (Thr) in HPr. This substitution did not prevent the phosphorylation of HPr on Ser-46, nor did it impede the phosphorylation of HPr on His-15 by EI or the transfer of the phosphoryl group from HPr(His-P) to other PTS proteins. However, the 147T substitution did perturb, in glucose-grown but not in galactose-grown cells, the cellular equilibrium between the various forms of HPr, resulting in an increase in the amount of free HPr at the expense of HPr(His-P)(Ser-P); the levels of HPr(His-P) and HPr(Ser-P) were not affected. Growth on melibiose was virtually identical for the wild-type and mutant strains, whereas the generation time of the mutant on the other sugars tested (glucose, fructose, mannose, lactose and galactose) increased 1.2- to 1.5-fold. The preferential metabolism of PTS sugars (glucose and fructose) over non-PTS sugars (lactose and melibiose) that is observed in wild-type cells was abolished in cells of mutant G22.4. Moreover, alpha- and beta-galactosidases were derepressed in glucose- and fructose-grown cells of the mutant. The data suggest that HPr regulates the preferential metabolism of PTS sugars over the non-PTS sugars, lactose and melibiose, through the repression of the pertinent catabolic genes. This HPr-dependent repression, however, seems to occur solely when cells are growing on a PTS sugar.

Adenosine Triphosphate↗
PubMed1997

Iontophoretic administration of 2% lidocaine HCl and 1:100,000 epinephrine in humans.

OBJECTIVE: The primary objective was to evaluate the clinical safety and effectiveness of the iontophoretic administration of lidocaine HCl 2% and epinephrine 1:100,000 to induce local dermal anesthesia before intravenous (i.v.) cannulation. DESIGN: Section I: Open, nonblinded. Section II: Randomized, double-blind, placebo-controlled. SETTING: Section I: Healthy adult volunteers. Section II: Patients presenting for scheduled outpatient eye surgery. PATIENTS: Section I: Seven healthy adult volunteers. Section II: Forty-four patients requiring i.v. cannulation before scheduled eye surgery. INTERVENTIONS: Section I: Volunteers received iontophoresis of lidocaine HCl 2% with epinephrine 1:100,000 for a total delivery current of 40 mA min. Section II: Patients received iontophoresis for a total delivery current of 40 mA min of lidocaine HCl 2% with epinephrine 1:100,000 (active) or saline (control) immediately before intravenous cannulation with a 20-gauge i.v. catheter. MAJOR OUTCOME MEASURES: Section I: Venous blood plasma lidocaine levels, adverse events associated with iontophoresis. Section II: Patient and investigator assessment of analgesia, patient acceptance of iontophoresis, adverse events associated with iontophoresis. RESULTS: Section I: No detectable levels of lidocaine were identified in any blood plasma sample. Adverse effects were minimal and transitory. Section II: Pain was decreased following lidocaine iontophoresis in comparison with controls, as determined by the patients and investigators. Iontophoresis was well accepted by the patients. Adverse effects were minimal and transitory. CONCLUSIONS: Iontophoresis of lidocaine 2% with 1:100,000 epinephrine for short delivery times does not lead to delivery of clinically important systemic levels of lidocaine in healthy adults. Iontophoresis of lidocaine 2% with 1:100,000 epinephrine provides adequate skin anesthesia for placement of peripheral small-gauge i.v. catheters.

Adult↗
PubMed1997

Nosocomial pneumonia and tracheitis in a pediatric intensive care unit: a prospective study.

We conducted a prospective study in the multidisciplinary pediatric intensive care unit (pediatric ICU) of a tertiary-care university hospital in order to determine the incidence, risk markers, risk factors, and complications related to bacterial nosocomial pneumonia (BNP) and tracheitis (BNT) in children. A cohort of 1,114 consecutive admissions to the pediatric ICU was enrolled over a 56-wk period; 154 cases were excluded mostly (75%) because they already had a respiratory infection at entry. The final sample included 960 admissions (831 patients). Diagnosis of BNP or BNT was based on Centers for Disease Control of Atlanta criteria using a consensus method involving three experts, who also attributed complications to BNP and BNT. A total of 29 BNP and BNT (3.0%; 95% CI: 1.1 to 4.1%) were diagnosed (BNP: 1.2%, 95% CI: 0.7 to 1.9%; BNT: 1.8%, 95% CI: 0.8 to 2.6%). Three factors were retained by multivariate analysis as independent risk factors or markers for BNP (immunodeficiency, immunosuppression, and neuromuscular blockade), and two for BNT (head trauma and respiratory failure). Gram-negative bacteria and Staphylococcus aureus were the microorganisms most frequently found in the tracheal aspirates. Prescription of antibiotics was commonly attributable to BNP (75%) and BNT (59%). Death, as well as multiple organ system failure, resulted from BNP in 8% of cases, but never from BNT. In BNT, the reintubation rate was 24%. Nosocomial bacterial respiratory infections are rare in critically ill children. However, BNP causes significant complications, and more attention should be focused on BNT in the critically ill child.

Child, Preschool↗
PubMed1996

Mecamylamine-induced impairment of acquisition and retrieval of olfactory conditioning in the honeybee.

Mecamylamine, a nicotinic receptor antagonist, was injected into the honeybee brain haemolymph. The effects of the drug were investigated on Pavlovian conditioning of the proboscis extension reflex. The conditioned response was acquired after a one-trial learning session, consisting of an olfactory-conditioned stimulus combined with a gustatory antennal unconditioned stimulus. The drug was injected at different times before or after the learning session in order to dissociate its effects on acquisition, consolidation and retrieval processes. The performance was evaluated in short-delayed recall tasks. To control potential effects on sensory-motor activity, the effects of the drug were also investigated on sensory processes (through olfactory and gustatory functions) and on motor processes of proboscis extension. The results of conditioning experiments showed that pretrial injection induced a decrease of retention performance 1 h after the learning trial. Mecamylamine injected 20 min after the learning session induced a time-dependent impairment of retention performance, as has been shown by the performance level registered from 10 to 80 min after injection. A 5-min post-trial injection had no effect on retention performance. Control experiments did not reveal any effect of mecamylamine on the response reflex of proboscis extension and on responsiveness to olfactory stimuli (geraniol, lavender and vanillin). The absence of effects on sensory perception combined with the amnestic effect induced by pre- or late post-trial injections lead us to conclude that mecamylamine specially impaired acquisition and retrieval processes. The involvement of nicotinic-like receptors in these processes is discussed.

Animals↗
PubMed1996

Epidemiology of sepsis and multiple organ dysfunction syndrome in children.

STUDY OBJECTIVES: To determine the cumulated incidence and the density of incidence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS) in critically ill children; to distinguish patients with primary from those with secondary MODS. DESIGN: Prospective cohort study. SETTING: Pediatric ICU of a university hospital. PATIENTS: One thousand fifty-eight consecutive hospital admissions. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: SIRS occurred in 82% (n=869) of hospital admissions, 23% (n=245) had sepsis, 4% (n=46) had severe sepsis, 2% (n=25) had septic shock; 16% (n=168) had primary MODS and 2% (n=23) had secondary MODS; 6% (n=68) of the study population died. The pediatric risk of mortality (PRISM) scores on the first day of admission to pediatric ICU were as follows: 3.9 +/- 3.6 (no SIRS), 7.0 +/- 7.0 (SIRS), 9.5 +/- 8.3 (sepsis), 8.8 +/- 7.8 (severe sepsis), 21.8 +/- 15.8 (septic shock); differences among groups (p=0.0001), all orthogonal comparisons, were significant (p<0.05), except for patients with severe sepsis. The observed mortality for the whole study population was also different according to the underlying diagnostic category (p=0.0001; p<0.05 for patients with SIRS and those with septic shock, compared with all groups). Among, patients with MODS, the difference in mortality between groups did not reach significance (p=0.057). Children with secondary MODS had a longer duration of organ dysfunction (p<0.0001), a longer stay in pediatric ICU after MODS diagnosis (p<0.0001), and a higher risk of mortality (odds ratio, 6.5 [2.7 to 15.9], p<0.0001) than patients with primary MODS. CONCLUSIONS: SIRS and sepsis occur frequently in critically ill children. The presence of SIRS, sepsis, or septic shock is associated with a distinct risk of mortality among critically ill children admitted to the pediatric ICU; more data are needed concerning children with MODS. Secondary MODS is much less common than primary MODS, but it is associated with an increased morbidity and mortality; we speculate that distinct pathophysiologic mechanisms are involved in these two conditions.

Adolescent↗
PubMed1996

[Surgical health care patterns and cancer cost: two studies using population registry data].

The goal of the first study was to analyze the surgical health care patterns for operated cases colorectal cancer. The role of surgery was analyzed for 732 cases diagnosed between 1988 and 1991 and recorded by the Doubs Cancer Registry, France. Young patients were more inclined to surgery than the older patients: 41% before 65 years and 27% after 65 (p < 0.02). Age was the only variable related to the type of activity of the surgeon (public or private sector): 65.9% of patients younger than 65 years were treated by a private surgeon but only 56.6% of patients older than 65 (p < 0.02). The goal of the second study was to analyze direct costs induced by cancer from the point of view of the "Mutualité Sociale Agricole", the rural branch of the French Social Security. A 3-year follow-up was the minimum required to be able to isolate costs in function of the different clinical steps of the disease. This study was performed on 24 breast cancers, 16 lung cancers, 22 prostatic cancers and 36 colorectal cancers diagnosed between 1988 and 1991 in patients insured by the Doubs MSA (the rural branch of the French Social Security). The average cost of a cancer varied from 53,800 FF to 82,600 FF, according to cancer site. Transportation costs represented from 7% to 15% of the total cost. These two studies outline the usefulness of cancers registries as a tool for health authorities looking for a better efficiency of the health care system.

Aged↗
PubMed1995

Small-subunit rRNA sequences and whole DNA relatedness concur for the reassignment of Pasteurella piscicida (Snieszko et al.) Janssen and Surgalla to the genus Photobacterium as Photobacterium damsela subsp. piscicida comb. nov.

The taxonomic status of Pasteurella piscicida (strain NCIMB 2058T [T = type strain] and a strain isolated from the environment) was investigated by performing phylogenetic analyses of small-subunit rRNA sequences, DNA-DNA hybridization analyses, and biochemical characterization analyses. The results of the phylogenetic analyses and the levels of DNA-DNA complementarity demonstrated conclusively that Pasteurella piscicida is extremely closely related to Photobacterium damsela ATCC 33539T. Since the two taxa exhibited a level of DNA-DNA relatedness of 80%, they are members of the same species. The high level of DNA relatedness and the presence of specific morphological and biochemical characteristics support the hypothesis that two subspecies should be recognized. On the basis of its phylogenetic position, we concluded that Pasteurella piscicida should be renamed Photobacterium damsela subsp. piscicida comb. nov.

Base Sequence↗
PubMed1995

Phylogenetic analysis of the genera Alteromonas, Shewanella, and Moritella using genes coding for small-subunit rRNA sequences and division of the genus Alteromonas into two genera, Alteromonas (emended) and Pseudoalteromonas gen. nov., and proposal of twelve new species combinations.

Small-subunit ribosomal DNA sequences were determined for 17 strains belonging to the genera Alteromonas, Shewanella, Vibrio, and Pseudomonas, and these sequences were analyzed by phylogenetic methods. The resulting data confirmed the existence of the genera Shewanella and Moritella, but suggested that the genus Alteromonas should be split into two genera. We propose that a new genus, the genus Pseudoalteromonas, should be created to accommodate 11 species that were previously Alteromonas species, including Pseudoalteromonas atlantica comb. nov., Pseudoalteromonas aurantia comb. nov., Pseudoalteromonas carrageenovoa comb. nov., Pseudoalteromonas citrea comb. nov., Pseudoalteromonas denitrificans comb. nov., Pseudoalteromonas espejiana comb. nov., Pseudoalteromonas haloplanktis comb. nov. (with two subspecies, Pseudoalteromonas haloplanktis subsp. haloplanktis comb. nov. and Pseudoalteromonas haloplanktis subsp. tetraodonis comb. nov.), Pseudoalteromonas luteoviolacea comb. nov., Pseudoalteromonas nigrifaciens comb. nov., Pseudoalteromonas rubra comb. nov., and Pseudoalteromonas undina comb, nov., and one species that previously was placed in the genus Pseudomonas, Pseudoalteromonas piscicida comb. nov. We propose that P. haloplanktis (type strain, ATCC 14393) should be the type species of the genus Pseudoalteromonas. At this time the emended genus Alteromonas is restricted to a single species, Alteromonas macleodii.

Base Sequence↗