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Biomedical subjects

Michel Godin

Publications and source records attributed to Michel Godin.

16 recordsLinked to original sources
PubMed2006

A complete analysis of the laser beam deflection systems used in cantilever-based systems.

A working model has been developed which can be used to significantly increase the accuracy of cantilever deflection measurements using optical beam techniques (used in cantilever-based sensors and atomic force microscopes), while simultaneously simplifying their use. By using elementary geometric optics and standard vector analysis it is possible, without any fitted or adjustable parameters, to completely and accurately describe the relationship between the cantilever deflection and the signal measured by a position sensitive photo-detector. By arranging the geometry of the cantilever/optical beam, it is possible to tailor the detection system to make it more sensitive at different stages of the cantilever deflection or to simply linearize the relationship between the cantilever deflection and the measured detector signal. Supporting material and software has been made available for download at http://www.physics.mun.ca/beauliu_lab/papers/cantilever_analysis.htm so that the reader may take full advantage of the model presented herein with minimal effort.

Journal Article↗
PubMed2006

Monitoring of heparin and its low-molecular-weight analogs by silicon field effect.

Heparin is a highly sulfated glycosaminoglycan that is used as an important clinical anticoagulant. Monitoring and control of the heparin level in a patient's blood during and after surgery is essential, but current clinical methods are limited to indirect and off-line assays. We have developed a silicon field-effect sensor for direct detection of heparin by its intrinsic negative charge. The sensor consists of a simple microfabricated electrolyte-insulator-silicon structure encapsulated within microfluidic channels. As heparin-specific surface probes the clinical heparin antagonist protamine or the physiological partner antithrombin III were used. The dose-response curves in 10% PBS revealed a detection limit of 0.001 units/ml, which is orders of magnitude lower than clinically relevant concentrations. We also detected heparin-based drugs such as the low-molecular-weight heparin enoxaparin (Lovenox) and the synthetic pentasaccharide heparin analog fondaparinux (Arixtra), which cannot be monitored by the existing near-patient clinical methods. We demonstrated the specificity of the antithrombin III functionalized sensor for the physiologically active pentasaccharide sequence. As a validation, we showed correlation of our measurements to those from a colorimetric assay for heparin-mediated anti-Xa activity. These results demonstrate that silicon field-effect sensors could be used in the clinic for routine monitoring and maintenance of therapeutic levels of heparin and heparin-based drugs and in the laboratory for quantitation of total amount and specific epitopes of heparin and other glycosaminoglycans.

Adsorption↗
PubMed2006

[Cutaneous infection due to Mycobacterium chelonae in a hemodialysed patient].

We report a case of a hemodialysed patient who developed a cutaneous Mycobacterium chelonae infection. This infection was only localised on the left upper limb, downstream from the arteriovenous fistula. M. chelonae is an unusual human pathogen, which is present in soil, dust, and stagnant water. Various factors, especially immunosuppression can favour this sort of infection in humans. Because of the ubiquity of the mycobacterium, the source of the inoculation sometimes remains unknown. However, a great number of cases are related to nosocomial infections. The preferential localizations are cutaneous, ocular, and pulmonary. Some cases of cutaneous infections due to M. chelonae, or caused by other atypical mycobacterium, are described in renal transplantation, peritoneal dialysis and hemodialysis. In the case we describe here, the source of contamination was not identified. The outcome was favourable with clarithromycin. This treatment is still continued because of a reappearance of the lesions when treatment was discontinued.

Anti-Bacterial Agents↗
PubMed2006

Label-free microelectronic PCR quantification.

We present a robust and simple method for direct, label-free PCR product quantification using an integrated microelectronic sensor. The field-effect sensor can sequentially detect the intrinsic charge of multiple unprocessed PCR products and does not require sample processing or additional reagents in the PCR mixture. The sensor measures nucleic acid concentration in the PCR relevant range and specifically detects the PCR products over reagents such as Taq polymerase and nucleotide monomers. The sensor can monitor the product concentration at various stages of PCR and can generate a readout that resembles that of a real-time fluorescent measurement using an intercalating dye but without its potential inhibition artifacts. The device is mass-produced using standard semiconductor processes, can be reused for months, and integrates all sensing components directly on-chip. As such, our approach establishes a foundation for the direct integration of PCR-based in vitro biotechnologies with microelectronics.

Electronics↗
PubMed2005

Redox-induced surface stress of polypyrrole-based actuators.

We measure the surface stress induced by electrochemical transformations of a thin conducting polymer film. One side of a micromechanical cantilever-based sensor is covered with an electropolymerized dodecyl benzenesulfonate-doped polypyrrole (PPyDBS) film. The microcantilever serves as both the working electrode (in a conventional three-electrode cell configuration) and as the mechanical transducer for simultaneous, in situ, and real-time measurements of the current and interfacial stress changes. A compressive change in surface stress of about -2 N/m is observed when the conducting polymer is electrochemically switched between its oxidized (PPy+) and neutral (PPy0) state by cyclic voltammetry. The surface stress sensor's response during the anomalous first reductive scan is examined. The effect of long-term cycling on the mechanical transformation ability of PPy(DBS) films in both surfactant and halide-based electrolytes is also discussed. We have identified two main competing origins of surface stress acting on the PPy(DBS)/ gold-coated microcantilever: one purely mechanical due to the volume change of the conducting polymer, and a second charge-induced, owing to the interaction of anions of the supporting electrolyte with the gold surface.

Algorithms↗
PubMed2005

Pharmacokinetics of naftidrofuryl in patients with renal impairment.

Naftidrofuryl (CAS 31329-57-4) is used, mainly in elderly patients, in the treatment of various vascular disorders. The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in caucasian male and female subjects with renal impairment versus healthy volunteers. This prospective and open study was conducted in three parallel groups: Group A = healthy subjects with a Cl(CR) > 80 ml/min, Group B = uraemic patients with a 20 < or = Cl(CR) < 40 ml/min, Group C = uraemic patients with a Cl(CR) < 20 ml/min. Blood samples were taken over a period of 32 h after dosing. The mean values (+/-SD) of the pharmacokinetic parameters of naftidrofuryl for group A were as follows: tmax: 1.3 h (median), Cmax: 174 +/- 46 ng/ml, t(1/2 beta): 4.4 +/- 1.1 h, AUC(0-infinity): 1541 +/- 384 ng x h/ml; for group B: tmax: 2.5 h (median), Cmax: 239 +/- 94 ng/ml, t(1/2 beta): 5.0 +/- 1.2 h, AUC(0-infinity): 2361 +/- 751 ng x h/ml; for group C: tmax: 3.0 h (median), Cmax: 236 +/- 104 ng/ml, t(1/2 beta): 5.0 +/- 2.1 h, AUC(0-infinity): 2488 +/- 2003 ng x h/ml. The statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each group. No significant difference between each group was observed. In conclusion, renal insufficiency did not appear to influence the pharmacokinetic profile of oral naftidrofuryl.

Adult↗
PubMed2005

Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenomas.

OBJECTIVE: We aimed to investigate the expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenoma (APA) tissues in comparison with normal adrenal cortex. DESIGN AND METHODS: Total 5-HT4 receptor mRNAs were quantified by real-time quantitative polymerase chain reaction (PCR) assay, and the mRNAs encoding the 5-HT4 receptor isoforms were characterized by reverse transcription (RT)-PCR in seven normal adrenal cortices and 11 APA tissues. The distribution of 5-HT4 receptor mRNAs was investigated by in situ hybridization in both normal adrenal and APA tissues, and the presence of 5-HT in APA tissues was studied by immunohistochemistry. RESULTS: Real-time PCR analysis revealed that 5-HT4 receptor mRNA expression was 4.7-47 times higher in APA tissues than in normal glands. In situ hybridization studies showed that 5-HT4 receptor mRNAs were expressed in both zona glomerulosa and zona fasciculata/reticularis of the normal cortex and in groups of APA steroidogenic cells disseminated in the tumor tissues. Characterization of 5-HT4 receptor splice variants by RT-PCR revealed different profiles of expression in APAs versus normal adrenals. Isoforms (a) and (b) were not expressed in any APA but were present in the majority of normal adrenocortical tissues. Conversely, isoform (d) was expressed in 5/11 APAs but only in 1/7 adrenals. Immunohistochemical studies revealed the presence of 5-HT-immunoreactivity in both mast cells and clusters of steroidogenic cells in APA tissues. CONCLUSION: Our results show overexpression and different splicing of the 5-HT4 receptor in APA tissues in comparison with normal adrenocortical tissue. They also demonstrate the presence of 5-HT in both mast cells and tumor steroidogenic cells, providing evidence for a possible autocrine/paracrine activation of aldosterone secretion within adenoma tissues.

Adrenal Cortex Neoplasms↗
PubMed2004

Surface stress, kinetics, and structure of alkanethiol self-assembled monolayers.

The surface stress induced during the formation of alkanethiol self-assembled monolayers (SAMs) on gold from the vapor phase was measured using a micromechanical cantilever-based chemical sensor. Simultaneous in situ thickness measurements were carried out using ellipsometry. Ex situ scanning tunneling microscopy was performed in air to ascertain the final monolayer structure. The evolution of the surface stress induced during coverage-dependent structural phase transitions reveals features not apparent in average ellipsometric thickness measurements. These results show that both the kinetics of SAM formation and the resulting SAM structure are strongly influenced both by the surface structure of the underlying gold substrate and by the impingement rate of the alkanethiol onto the gold surface. In particular, the adsorption onto gold surfaces having large, flat grains produces high-quality self-assembled monolayers. An induced compressive surface stress of 15.9 +/- 0.6 N/m results when a c(4x2) dodecanethiol SAM forms on gold. However, the SAMs formed on small-grained gold are incomplete and an induced surface stress of only 0.51 +/- 0.02 N/m results. The progression to a fully formed SAM whose alkyl chains adopt a vertical (standing-up) orientation is clearly inhibited in the case of a small-grained gold substrate and is promoted in the case of a large-grained gold substrate.

Journal Article↗
PubMed2003

[Membranous nephropathy].

Membranous nephropathy is the most common cause of idiopathic nephrotic syndrome in adults. The frequency of secondary forms varies from 20 to 30 per cent. The principal causes appear to be systemic lupus erythematosous, drug therapy, malignancy and viral infection. The pathology includes normocellular glomeruli with subepithelial deposits on the outer surface of the glomerular basement membrane. Immunofluorescence studies reveal consistently IgG granular deposits. Prolonged high-grade proteinuria is common. Renal vein thrombosis is frequently associated. Persistent hyperlipidemia increases the risk of cardiovascular diseases. The course of idiopathic membranous nephropathy remains variable. Numerous factors affecting the prognosis of the nephropathy have been identified and should be considered for the decision of specific treatment and use of immunosuppressive therapy.

Adult↗
PubMed2003

[Virological, epidemiological and pathogenic aspects of human polyomaviruses].

VIROLOGICAL ASPECTS: Human polyomaviruses (BK virus and JC virus), together with simian polyomaviruses (SV40 virus) share 75% of genomic homology. Their in vivo and in vitro genomes vary. Molecular analyses have identified several genotypes, some of which appear related to the development of viral diseases. Genomic modifications of the regulation area might provide the BKv with a pathogenic aspect thus enhancing the induction of tubulo-interstitial nephropathies in renal transplant recipients. EPIDEMIOLOGY: Human polyomaviruses are ubiquitous and exhibit a sero-prevalence of 60 to 80% in adults. Following a primary infection via the respiratory tract in childhood, these viruses are diffused in the blood using the B-lymphocytes during their latent stage in the urogenital tract. The reactivation that occurs after several years is asymptomatic and urinary excretion of BKv is observed in 4 to 6% of immunocompetent patients. PATHOGENIC POTENTIAL: Human polyomaviruses have a cytopathogenic effect on the urothelium and epithelium of renal transplant recipients. Infection by BKv may provoke hemorrhagic cystitis or urethral stenosis. The JCv is the cause of progressive multifocal leuko-encephalitis. The BKv (and less frequently the JCv) is responsible for tubulo-interstitial nephritis possible leading to renal transplant loss. They also have an oncogenic effect and their implication in the origin of tumours is the subject of many studies.

Adult↗
PubMed2003

[Clinical aspects of human polyomaviruses in renal transplantation].

A THREAT FOR RENAL ALLOGRAFT: Human polyomavirus infections (BK virus, JC virus), known for the past 30 years, were considered as common in renal transplantation until the recently reported studies describing the responsibility of BKv (and less JCv) in the occurrence of tubulo-interstitial nephritis in around 5% of renal transplant recipients, with worsening of the renal function leading to graft failure in 10 to 45% of infected patients. Their description coincided with the use of new immunosuppressors (tacrolimus and mycophenolate mofetil) without, however, their responsibility clearly incriminated. EARLY DIAGNOSIS FOR EFFICIENT TREATMENT: The presence of cells infected by the polyomavirus ("decoy cells") in the urine and the detection of BKv or JCv DNA by PCR in the plasma and urine are viral replication markers which strongly suggest the possibility of a polyomavirus nephropathy. TWO CLINICAL VARYING FORMS: Polyomavirus infection is frequent and often asymptomatic. The diagnosis requires the detection of large nucleus "decoy cells" in fresh urine. Polyomavirus renal allograft disease is characterised by the association of decoy cells and renal failure related to a tubulo-interstitial nephropathy and the presence of DNA of the virus in the plasma. The diagnosis requires identification of intra-nuclear viral inclusions in epithelial cells using immunohistochemistry, in situ hybridisation, or electron microscopy techniques. A DIFFICULT DIAGNOSIS: Confusion between interstitial nephritis and acute cellular rejection is the major risk leading to therapeutic error. Risk factors include over-immunosuppression and/or treatment of rejection episodes which could increase viral replication as well as the emergence of mutant BKv strains at the origin of tubulo-interstitial nephritis, leading to acute and chronic dysfunction of the renal transplantation.

BK Virus↗
PubMed2003

[Therapeutic possibilities for polyomavirus infections in renal transplantation].

TO IMPROVE THERAPEUTIC MANAGEMENT: The aim is the early detection of polyomavirus infection, before the onset of tubulo-interstitial nephritic lesions, and to reduce viral replication. AT THE STAGE OF POLYOMAVIRUS INFECTION: Treatment relies on the reduction of immunosuppression. Efficacy is controlled by monitoring the decoy cells in the urine and the detection and quantification of the DNA of polyomaviruses in the plasma and urine. AT THE STAGE OF POLYOMAVIRUS DISEASE: The aim is to reduce the viral replication by further decreasing immunosuppression to stabilize renal function and avoid graft rejection. When signs of rejection and viral infection co-exist, cidofovir could be a therapeutic alternative. However, the use of cidofovir remains in the field of clinical research and requires the further development of therapeutic protocols.

Antiviral Agents↗
PubMed2002

Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies.

We have previously shown that serotonin (5-HT) stimulates aldosterone secretion from the human adrenal gland through activation of 5-HT(4) receptors. The aim of the present study was to investigate in vivo and in vitro the presence of 5-HT(4) receptors in aldosterone-producing adenomas (aldosteronomas). Eight patients with aldosteronoma received a single oral dose of placebo or cisapride (10 mg). Cisapride administration significantly increased plasma aldosterone within 120 min without any significant change in renin, cortisol, or potassium levels. In two patients, a marked decrease in the plasma aldosterone response to cisapride was observed after surgical removal of the tumor. The effects of 5-HT and selective 5-HT(4) ligands on aldosterone production from aldosteronoma tissues were studied in vitro using a perifusion system technique. 5-HT and the 5-HT(4) receptor agonist cisapride (10(-7) M, 20 min) both stimulated aldosterone secretion from aldosteronoma slices. The 5-HT- and cisapride-evoked aldosterone responses were inhibited by concomitant administration of the specific 5-HT(4) receptor antagonist GR 113808 (10(-7) M, 150 min). PCR amplification revealed the expression of 5-HT(4) receptor mRNA in 13 of 14 aldosteronomas studied. Taken together, these data show that most aldosteronomas, like normal glomerulosa cells, express a functional 5-HT(4) receptor. Our results also suggest that 5-HT, which can be locally released by intratumoral mast cells, may play a role in the pathophysiology of these tumors.

Adenoma↗
PubMedDate not supplied

Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus.

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sjögren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.

Amino Acid Sequence↗