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Biomedical subjects

C Gauthier

Publications and source records attributed to C Gauthier.

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

XAFS and X-MCD spectroscopies with undulator gap scan.

The first experimental applications of the undulator gap-scan technique in X-ray absorption spectroscopy are reported. The key advantage of this method is that during EXAFS scans the undulator is permanently tuned to the maximum of its emission peak in order to maximize the photon statistics. In X-MCD or spin-polarized EXAFS studies with a helical undulator of the Helios type, the polarization rate can also be kept almost constant over a wide energy range.

Journal Article↗
PubMed1998

Cross-contamination potential of saliva ejectors used in dentistry.

It has been postulated that evacuation systems used in dentistry could be a source of cross-contamination between patients through backflow of bacteria dislodged from the saliva ejector tubings. The bacterial microflora associated with these systems was characterized using transmission electron microscopy (TEM) and microbiological cultures. The potential for backflow was investigated by a study of pressure differentials in evacuation system tubing and by the presence of bacteria in backflow samples. Evacuation lines were coated with microbial biofilms in which microcolonies of Gram-positive cocci and Gram-negative bacilli predominated, embedded in an extensive polysaccharide matrix. Most bacteria were metabolically active. Occasionally, buccal material such as collagen, fibrin and eukaryotic cell debris was observed. In other experiments, flow reversal was detected several times during saliva ejector use though each of these events was brief (less than 0.1 s). Aspiration of saliva, or occlusion of the mouthpiece opening by the oral mucosa, were the major factors leading to backflow episodes. Bacteria associated with backflow were found in almost 25% assays, with counts ranging from 1-300 cfu/occurrence. The majority of the bacteria isolated from biofilm or backflow samples were staphylococci, micrococci and non-fermentive Gram-negative rods. Pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus were also isolated from backflow fluids. No oral streptococci could be recovered from biofilms in the tubing beyond 15 min from the last saliva ejector use however, suggesting that these species did not survive in the biofilms. These data suggest, although without direct proof of cross-contamination, the possible existence of an infectious risk associated with oral evacuation systems, as potential pathogens may be shed from tubing biofilms following backflow. Even if the risk of cross-contamination between patients is considered to be low, the necessity for regular disinfection of these systems must be stressed, since biofilms can serve as a reservoir for pathogens or harbor potentially infectious material.

Bacterial Infections↗
PubMed1998

Biofilms, infectious agents, and dental unit waterlines: a review.

Aquatic biofilms, which are widespread not only in nature but also in medical and dental devices, can be the source of serious nosocomial infections. In these hardy microbial communities, pathogens like nontuberculous mycobacteria, Pseudomonas aeruginosa, Legionella pneumophila, and other bacteria not only survive but proliferate and lie in wait for susceptible hosts. Not only are these organisms intrinsically resistant to high temperatures and biocides, but the biofilms they inhabit enhance their resistance. This should be of concern to infection control practitioners. The bacterial colonization of dental unit waterlines can be used as a model to investigate the problem of waterborne biofilms in health care settings.

Bacterial Infections↗
PubMed1998

Differential expression, abundance, and regulation of Na+-phosphate cotransporter genes in murine kidney.

Three classes of high-affinity Na+-Pi cotransporters are expressed in mammalian kidney. These include Npt1 (type I), Npt2 (type II), and the cellular receptors for gibbon ape leukemia virus (Glvr-1) and amphotropic murine retrovirus (Ram-1) (type III). We defined the tissue distribution as well as the relative renal abundance of Npt1, Npt2, Glvr-1, and Ram-1 mRNAs and examined the effects of low-Pi diet, the Hyp mutation, and growth hormone (GH) on their renal expression by ribonuclease protection assay. In normal mouse kidney, Npt1, Npt2, Glvr-1, and Ram-1 accounted for 15 +/- 1.0, 84 +/- 1.0, 0.5 +/- 0.2, and 0.5 +/- 0.3% of total Na+-Pi cotransporter mRNAs, respectively. Evidence was obtained for low-abundance Npt1 mRNA expression in liver and Npt2 mRNA expression in intestine, whereas Glvr-1 and Ram-1 mRNAs were also detected in bone, intestine, heart, and liver. Npt2 mRNA was localized to proximal tubules in the renal outer cortex, whereas Glvr-1 transcripts were detected throughout the kidney by in situ hybridization. The Hyp mutation elicited a significant reduction in renal Npt1 and Npt2 mRNAs (78 +/- 8 and 57 +/- 3% of normal, respectively), whereas neither low-Pi diet nor GH influenced the renal abundance of Npt1 and Npt2 transcripts. Renal Glvr-1 mRNA expression was significantly increased in Hyp mice and GH-treated mice (145 +/- 6 and 165 +/- 5% of control, respectively), whereas the renal abundance of Ram-1 transcript was unaffected by either the Hyp mutation, low-Pi diet, or GH treatment. In summary, we demonstrate that Npt2 is the predominant Na+-Pi cotransporter in mouse kidney, that Npt2 and Glvr-1 have distinct patterns of renal expression, and that the Hyp mutation modulates the renal expression of Npt1, Npt2, and Glvr-1 mRNAs. Our results suggest that increased renal Glvr-1 mRNA may contribute to GH stimulation of renal Na+-Pi cotransport.

Animals↗
PubMed1998

Na+ -phosphate cotransport in mouse distal convoluted tubule cells: evidence for Glvr-1 and Ram-1 gene expression.

While there is considerable evidence for phosphate (Pi) reabsorption in the distal tubule, Pi transport and its regulation have not been well characterized in this segment of the nephron. In the present study, we examined Na+-dependent Pi transport in immortalized mouse distal convoluted tubule (MDCT) cells. Pi uptake by MDCT cells is Na+-dependent and, under initial rate conditions, is inhibited by phosphonoformic acid (41 +/- 3% of control), a competitive inhibitor of Na+-Pi cotransport. The transport system has a high affinity for Pi (Km = 0.46 mM) and is stimulated by lowering the extracellular pH from 7.4 to 6.4 and inhibited by raising the pH from 7.4 to 8.4. Exposure to Pi-free medium for 21 h increased Na+-Pi cotransport from 2.1 to 5.5 nmol/mg of protein/5 minutes (p < 0.05) while parathyroid hormone, forskolin, and phorbol 12-myristate 13-acetate failed to alter Pi uptake in MDCT cells. Reverse transcriptase polymerase chain reaction of MDCT cell RNA provided evidence for the expression of the Npt1 but not the Npt2 Na+-Pi cotransporter gene. However, preincubation of MDCT cells with Npt1 antisense oligonucleotide led to only 20% inhibition of Na+-Pi cotransport, suggesting that other Na+-Pi cotransporters are operative in MDCT cells. Indeed, we showed, by ribonuclease protection assay, that MDCT cells express the ubiquitous cell surface receptors for gibbon ape leukemia virus (Glvr-1) and amphoteric murine retrovirus (Ram-1) that also function as Na+-Pi cotransporters. In summary, we demonstrate that the pH dependence and regulation of Na+-Pi cotransport in MDCT cells is distinct from that in the proximal tubule and suggest that different gene products mediate Na+-Pi cotransport in the proximal and distal segments of the nephron.

Animals↗
PubMed1998

Contact lens induced peripheral ulcers during hydrogel contact lens wear.

PURPOSE: Ulcerative keratitis is the most serious adverse response associated with contact lens wear. However, some reports of microbial keratitis in the literature may refer to a less severe form of corneal ulceration, which we have termed contact lens induced peripheral ulcers (CLPU). METHODS: We present details of 11 cases of CLPU which occurred in clinical trials at our research unit. RESULTS: CLPU episodes are characterized by a single, small (< 2 mm diameter) circular lesion in the corneal mid-periphery or periphery, involving a focal loss of the full thickness of the epithelium associated with subepithelial stromal infiltrates. Patient symptoms may include ocular irritation, pain, photophobia, and lacrimation. They are usually associated with the use of hydrogel extended wear contact lenses. The lesions are self-limiting, typically healing within 7 days without treatment. After resolution, a small circular scar remains, which does not affect vision because of its peripheral location. The etiology of CLPU is unclear. In our studies, the incidence of CLPU was similar in conventional (2.9% per patient year) and disposable (2.0% per patient year) hydrogel extended wear, but lower during intermittent extended wear (1.6% per patient year); only one case occurred during daily wear (< 0.5% per patient year). CONCLUSIONS: A conservative approach to patient management of all suspected cases of corneal ulceration is encouraged. However, we suggest that future reports of ulcerative keratitis associated with various lens types and wearing schedules should differentiate between potentially devastating microbial keratitis and the relatively innocuous peripheral ulceration described in this paper.

Adult↗
PubMed1997

Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice.

PEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, was recently identified as the candidate gene for X-linked hypophosphatemia. In the present study, we cloned mouse and human Pex/PEX cDNAs encoding part of the 5' untranslated region, the protein coding region, and the entire 3' untranslated region, determined the tissue distribution of Pex/PEX mRNA, and characterized the Pex mutation in the murine Hyp homologue of the human disease. Using the reverse transcriptase/polymerase chain reaction (RT/PCR) and ribonuclease protection assays, we found that Pex/PEX mRNA is expressed predominantly in human fetal and adult mouse calvaria and long bone. With RNA from Hyp mouse bone, an RT/PCR product was generated with 5' but not 3' Pex primer pairs and a protected Pex mRNA fragment was detected with 5' but not 3' Pex riboprobes by ribonuclease protection assay. Analysis of the RT/PCR product derived from Hyp bone RNA revealed an aberrant Pex transcript with retention of intron sequence downstream from nucleotide 1302 of the Pex cDNA. Pex mRNA was not detected on Northern blots of poly (A)+ RNA from Hyp bone, while a low-abundance Pex transcript of approximately 7 kb was apparent in normal bone. Southern analysis of genomic DNA from Hyp mice revealed the absence of hybridizing bands with cDNA probes from the 3' region of the Pex cDNA. We conclude that Pex/PEX is a low-abundance transcript that is expressed predominantly in bone of mice and humans and that a large deletion in the 3' region of the Pex gene is present in the murine Hyp homologue of X-linked hypophosphatemia.

Amino Acid Sequence↗
PubMed1997

Glycolysis inhibition by palmitate in renal cells cultured in a two-chamber system.

A major shortcoming of renal proximal tubular cells (RPTC) in culture is the gradual modification of their energy metabolism from the oxidative type to the glycolytic type. To test the possible reduction of glycolysis by naturally occurring long-chain fatty acids, RPTC were cultured in a two-chamber system, with albumin-bound palmitate (0.4 mM) added to the basolateral chamber after confluency. Twenty-four hours of contact with palmitate decreased glycolysis by 38% provided that carnitine was present; lactate production was decreased by 38%, and the decrease in glycolysis resulted from a similar decrease of basolateral and apical net uptake of glucose. In contrast to the previously described effect of the nonphysiological oxidative substrate heptanoate, palmitate promoted a long-term decrease in lactate production and sustained excellent cellular growth. After 4 days of contact, decreased glycolysis was maintained even in the absence of carnitine and resulted from a decrease of basolateral uptake only, suggestive of long-term regulation different from the earlier effects. Thus, although cultured RPTC lost their oxidative phenotype, they exhibited a type of regulation (Randle effect) that is found in the oxidative-type but not in the glycolytic-type tissues, therefore unmasking a regulative capacity barely detectable in fresh RPTC. Low PO2 (50 mmHg in the apical chamber) could be a major cause of elevated glycolysis and could hinder the effects of palmitate.

Animals↗
PubMed1997

Advantages of a two-chamber culture system to test drug nephrotoxicity: the example of cephaloridine.

Rabbit renal proximal tubular cells, cultured to confluency on a permeable collagen film in a two-chamber system, were exposed for 72 h to various concentrations of the nephrotoxic antibiotic, cephaloridine (CLD). A decrease in cellular proteins, leakage of lactate dehydrogenase and morphological changes appeared at CLD concentrations of 0.1, 1.0, and 0.5 mg/ml, respectively. The permeability of the monolayer to Lucifer yellow (LY), a dye that does not cross cell membranes, was increased by 1 or 2 mg/ml but not by lower concentrations of CLD. The large basolateral/apical glucose concentration gradient established by the cells was decreased by CLD. However, the fact that, at the CLD concentration of 1 mg/ml, LY totally equilibrated by diffusion across the monolayer, whereas the injured monolayer was still able to maintain a detectable glucose gradient, shows that damage caused by CLD to the diffusion barrier prevails over that affecting glucose uptake. Consistent with the data in the literature concerning the mechanism of CLD accumulation in renal cells, our results show that CLD was more toxic when it was added at the basolateral than at the apical side of the cultured cells. These results illustrate the advantages of using a two-chamber system of cell culture in nephrotoxicity studies.

Animals↗
PubMed1996

Functional beta3-adrenoceptor in the human heart.

Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of beta3-adrenoceptor agonists with an order of potency: BRL 37344 > SR 58611 approximately CL 316243 > CGP 12177. The dose-response curve to BRL 37344-decreasing myocardial contractility was not modified by pretreatment with nadolol, but was shifted to the right by bupranolol, a nonselective beta-adrenoceptor antagonist. Beta3-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential. Beta3-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) beta3-adrenoceptors are present and functional in the human heart; and (b) these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure.

Action Potentials↗
PubMed1996

What ethicists talk about when they talk about managed care.

Defining the values at stake as we move into managed care is an awesome--yet necessary--endeavor. To help sort things out, the Society for Health and Human Values brought together health care ethicists and medical humanists to discuss how human values are being incorporated into health care reform. Here's an excerpt from that conversation.

Ethicists↗
PubMed1996

Advantages and limitations of the use of isolated kidney tubules in pharmacotoxicology.

Among the cellular models used in in vitro renal pharmacotoxicology, isolated kidney tubules, used as suspensions mainly of proximal tubules, offer important advantages. They can be prepared in large amounts under nonsterile conditions within 1-2 h; thus, it is possible to employ a great number of experimental conditions simultaneously and to obtain rapidly many experimental results. Kidney tubules can be prepared from the kidney of many animal species and also from the human kidney; given the very limited availability of healthy human renal tissue, it is therefore possible to choose the most appropriate species for the study of a particular problem encountered in man. Kidney tubules can be used for screening and prevention of nephrotoxic effects and to identify their mechanisms as well as to study the renal metabolism of xenobiotics. When compared with cultured renal cell, a major advantage of kidney tubules is that they remain differentiated. The main limitations of the use of kidney tubules in pharmacotoxicology are (1) the necessity to prepare them as soon as the renal tissue sample is obtained; (2) their limited viability, which is restricted to 2-3 h; (3) the inability to expose them chronically to a potential nephrotoxic drug; (4) the inability to study transepithelial transport; and (5) the uncertainty in the extrapolation to man of the results obtained using animal kidney tubules. These advantages and limitations of the use of human and animal kidney tubules in pharmacotoxicology are illustrated mainly by the results of experiments performed with valproate, an antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules, unlike cultured renal cells, retain key metabolic properties is also shown to be of the utmost importance in detecting certain nephrotoxic effects.

Animals↗
PubMed1996

[Neurologic manifestations of Mycoplasma pneumoniae infections].

BACKGROUND: Some neurological manifestations associated with Mycoplasma pneumoniae infection have been reported, such as meningoencephalitis, cerebellitis, aseptic meningitis, polyradiculopathy, transverse myelitis, cranial nerve palsies and myositis. CASE REPORT: Case 1. A 10 year-old boy had an acute pneumonia that was subsequently proven to be due to Mycoplasma pneumoniae infection. This infection was resistant to macrolid administration for 1 week requiring the administration of vibramycin instead. At that time, the patient developed an aseptic meningitis syndrome and a severe cerebellitis. He completely recovered within a few days. Case 2. A boy was admitted because he suffered from polyradiculopathy that had appeared during an acute episode of pneumonia. The neurological involvement extended to cranial nerves, then subsequently completely disappeared. Seroimmunological studies confirmed the Myoplasma pneumoniae infection. CONCLUSION: The mechanism of these classical but rare neurological manifestations remains unclear.

Child↗
PubMed1996

alpha1-adrenergic stimulation induces early afterdepolarizations in ferret Purkinje fibers.

The aim of this study was to evaluate whether alpha1-adrenergic stimulation, which prolongs repolarization, could induce early afterdepolarizations (EADs) in ferret Purkinje fibers. We used standard microelectrodes to study the effects of phenylephrine 10(-6)M in the presence of metoprolol 1.5 x 10(-6)M, on action potentials (AP) recorded from isolated ferret Purkinje fibers superfused with normal Tyrode's solution. Phenylephrine induced a time-dependent prolongation of the AP duration at 60 and 90% of full repolarization (APD60, APD90) from 223 +/- 8 and 269 +/- 9 ms, respectively, during control to 279 +/- 11 and 329 +/- 12 ms after 1-h superfusion (n = 29; p < 0.05 vs. control for both parameters) and 334 +/- 13 and 385 +/- 15 ms after 4 h (n = 29, p < 0.05 vs. control and 1-h superfusion for both parameters) without changing the other parameters. About one third of the fibers studied developed EADs that could be either phase 2 or phase 3 EADs. The alpha1-adrenoceptor antagonist WB 4101 (10(-7)M) limited the AP prolongation and prevented the occurrence of EADs. On the other hand, the alpha1-adrenoceptor alkylating agent chloroethylclonidine (10(-7)M) had no effect. The calcium chelator BAPTA [1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid] (2 x 10(-3)M) did not prevent the induction of EADs by phenylephrine, although it suppressed the twitch tension, showing that it did chelate the intracellular calcium. Our results show that alpha1-adrenergic stimulation prolongs repolarization in ferret Purkinje fibers and can induce EADs. This effect is mainly mediated by the WB 4101-sensitive alpha1-adrenoceptors (alpha1A- and/or alpha1C-adrenoceptors) and does not depend on intracellular calcium. alpha1-Adrenergic stimulation may have arrhythmogenic effects in patients with long QT syndrome (LQTS).

Animals↗
PubMed1996

Progesterone and estradiol inhibit CFTR-mediated ion transport by pancreatic epithelial cells.

The cystic fibrosis (CF), gene product, CF transmembrane conductance regulator (CFTR), is responsible for adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- transport in epithelial cells, and mutant CFTR accounts for the pathology in the CF pancreas. We have previously shown that both isolated rabbit pancreatic acini and the human pancreatic duct cell line PANC-1 possess a cAMP-activated Cl- conductance identified as CFTR. We report here that preincubation in either of the female hormones progesterone or beta-estradiol inhibits activation by cAMP, but not by Ca2+ ionophore, of PANC-1 cell volume reduction under isotonic conditions. cAMP-activated cell volume reduction is sensitive to antisense, but not sense, CFTR oligodeoxynucleotide. Furthermore, progesterone inhibits cAMP-activated Cl- efflux from rabbit acinar cells. Moreover preincubation with progesterone, but not beta-estradiol, reduces CFTR mRNA and protein levels as measured using polymerase chain reaction amplification of reverse-transcribed acinar RNA and Western blots of protein from acinar membranes. We conclude that female hormones inhibit CFTR functional activity in pancreatic epithelial cells by different mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Electrophysiologic characteristics of cells spanning the left ventricular wall of human heart: evidence for presence of M cells.

OBJECTIVES: The present work was designed to provide an initial characterization of M cells in the normal human heart. BACKGROUND: Recent studies have uncovered a unique population of cells in the midmyocardial region of the canine ventricle. These cells, named M cells, were found to possess electrophysiologic features and a pharmacologic responsiveness different from those of other myocardial cells. Although well characterized in the dog, their presence or absence in the human heart is unknown. METHODS: Standard microelectrode techniques were used to map slices of ventricular free wall obtained from normal human hearts (n = 4). Preparations were paced at cycle lengths ranging from 1 to 10 s. RESULTS: We identified three cell subtypes: endocardial, subepicardial (M cells) and epicardial cells. The principal features differentiating M cells from the other cell subtypes were their longer action potential duration, more accentuated action potential duration rate relations and greater maximal rate of increase in action potential upstroke (Vmax). Our findings suggest that M cells represent approximately 30% of the cellular mass of the left ventricular wall. Concordance between changes in their repolarization and changes in QTU interval provide support for the role of M cells in the generation of the electrocardiographic (ECG) U wave. CONCLUSIONS: This study provides evidence for the existence of M cells in the human heart that contribute to heterogeneity of repolarization within the ventricular wall. Our findings provide strong support for the hypothesis that M cells contribute importantly to the manifestation of the U wave on the ECG.

Action Potentials↗