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M Menard

Publications and source records attributed to M Menard.

At least 19 recordsLinked to original sources

Novel mimics of sialyl Lewis X: design, synthesis and biological activity of a series of 2- and 3-malonate substituted galactoconjugates.

A series of potent inhibitors of P-selectin as potential anti-inflammatory agents is reported. These compounds are derivatives of galactocerebrosides bearing a malonate side chain in positions 2 and 3 of the galactose moiety. Based on the binding mode of sialyl Lewis X, the two acidic groups of the malonate are designed to form ionic interactions with two important lysines in the active site of P-selectin, Lys113 and Lys111. On the other hand, the 4- and 6-hydroxy groups on the galactose ring are arranged to chelate the calcium ion in the P-selectin active site. The synthesis and the biological activity of this series of compounds are described. Lead compounds having a greater potency than sialyl Lewis X are identified.

Animals↗

Telecytology.

Explore the source record for details and available documents.

Animals↗

Analyzing pacemaker leads: application of a form of energy.

In the province of Ontario, analyzing of pacemaker leads is a delegated controlled act. This article describes the certification/recertification process for analyzing of pacemaker leads at the Hamilton Health Sciences Corporation.

Certification↗

[Idiopathic sub-glottal stenosis in the adult].

Idiopathic subglottic stenosis is a rare condition. The records of five patients with idiopathic subglottic stenosis treated between 1989 and 1998 were reviewed. All were female and had similar clinical and histopathologic features. Endoscopic dilatation or/and radial CO2 laser and dilatation were successful in maintaining the airway of all five patients without tracheotomy. The pathogenesis of idiopathic subglottic stenosis is strictly speculative, for this reason we advocate a conservative approach.

Adult↗

Estrogen withdrawal-induced human breast cancer tumour regression in nude mice is prevented by Bcl-2.

We recently showed that estrogen induces expression of the anti-apoptotic protein, Bcl-2 in MCF-7 human breast cancer cells. Since estrogen-dependent breast tumours can regress following estrogen withdrawal, we hypothesized that stable Bcl-2 expression would prevent estrogen-withdrawal induced regression of MCF-7 tumours. We therefore established tumours in ovariectomized female nude mice implanted with an estrogen-release pellet using untransfected MCF-7 cells or MCF-7 cells stably transfected with a Bcl-2 cDNA sense or antisense expression vector. All tumours grew at similar rates indicating that Bcl-2 levels have no effect on tumour formation. After removal of the estrogen pellet, Bcl-2 antisense tumours and untransfected MCF-7 tumours regressed means of 49% and 52%, respectively, after estrogen pellet removal whereas Bcl-2 sense tumours were significantly stabilized. Regressing tumours displayed characteristics of apoptotic cells. These results show that Bcl-2 can prevent hormone-dependent breast tumour regression and are consistent with the notion that decreased Bcl-2 levels following estrogen withdrawal renders hormone-dependent breast tumour cells sensitive to apoptotic regression.

Animals↗

Deregulated expression of the retinoid X receptor alpha prevents muscle differentiation in P19 embryonal carcinoma cells.

We have studied the expression of the retinoid X receptor (RXR) family of receptors during the DMSO-induced differentiation of P19 murine embryonal carcinoma cells into mesoderm and muscle. RXR-alpha protein is weakly detectable in untreated P19 cells and in a mutant line of P19 cells (D3) that are resistant to DMSO-induced differentiation but begins to increase by day 3 and continues to rise gradually thereafter, whereas RXR-gamma protein is readily detected in P19 cells and decreases over the course of differentiation. Protein expression is uncoupled from mRNA levels, because DMSO induces a rapid, aggregation-independent, transient increase in RXR-alpha mRNA that diminishes by day 3 of differentiation. Thus, the expression of RXR-alpha protein is prevented at early times during DMSO-induced differentiation. Stable P19 cell clones that constitutively express RXR-alpha protein [P19(RXR-alpha)] are resistant to DMSO-induced differentiation associated with increased levels of oligonucleosomal-length DNA fragmentation. Loss of RXR-alpha expression after multiple passages results in a reversion to a DMSO-responsive phenotype. Id1 transcripts are present in P19 cells and are transiently decreased on day 2 of DMSO differentiation but remain elevated in DMSO-treated P19(RXR-alpha) and in P19 cells treated simultaneously with retinoic acid and DMSO. The mRNA for the mesoderm inducer protein Brachyury T was also deregulated in P19(RXR-alpha) cells and D3 cells compared with that of wild-type P19 cells. Together, these results show that expression of the RXR-alpha mRNA and protein in P19 cells is tightly regulated during the mesodermal/muscle differentiation of P19 cells, and that ectopic expression of the RXR-alpha protein prevents differentiation associated with increased cell death, prolonged expression of Brachyury T, and constitutive expression of Id1.

Administration, Topical↗

Sulfated galactocerebrosides as potential antiinflammatory agents.

Native sulfatides, as well as many sulfated glycolipids, have been shown to avidly bind to the selectin receptors. In vivo, native sulfatides significantly block activity in selectin-dependent inflammatory responses. The fact that nonsulfated galactocerebrosides did not inhibit selectin-mediated adhesion identified a critical role for the anionic sulfate residue. We therefore initiated a program to evaluate the activity of position isomers. This study showed a binding selectivity for the positions 2 and 3 of the sulfate group on the carbohydrate ring as well as enhanced activity for the disulfated analogs. Furthermore, it was discovered that the attachment of lipophilic substituents on the carbohydrate ring was tolerated, consistent with the presence of a lipophilic pocket in the binding activity. This resulted in compounds with a 6-fold increased potency.

Animals↗

[Trans-facial approaches of cancers of the ethmoid].

Lateral rhinotomy, midface degloving approach and medial maxillectomy are described. Lateral rhinotomy allows for a wide surgical approach, complete tumor removal with safe margins and satisfying cosmetic result. Lateral rhinotomy with medial maxillectomy is recommended for surgical resection of ethmoid sinus carcinoma. This surgical approach allows for a simultaneous neurosurgical subfrontal approach.

Ethmoid Sinus↗

[Malignant tumors of the ethmoid region. Neurosurgical techniques].

We describe the main neurosurgical approaches in use for removing cancers of the ethmoid region: a) the classical subfrontal procedure usually combined with a transfacial approach, b) the sub-fronto-orbito-nasal approach (SFON) now performed in a majority of procedures as long as the tumor does not present with a large intra-cranial and/or maxillary extension. The advantages and drawbacks of both techniques are discussed. The progressive simplification of techniques for anterior cranial base reconstruction is explained and warranted.

Ethmoid Bone↗

[Malignant ethmoid-sphenoidal tumors. 130 cases. Retrospective study].

We report on 130 ethmoidal cancers. 96 (74%) were adenocarcinomas (ADKE). 110 were operated upon between 1984 and 1996: 9.1% T1 + T2, 27.7% T3, 36.2% T4a, 27% T4b. Neoadjuvant chemotherapy was administered in 93 patients (76 ADKE). Combined surgical route was performed 103 times, sub-fronto-orbito-nasal (SFON) route 7 times. Post-operative radiotherapy was performed in 36 patients. Complete clinical and radiological response to chemotherapy was noted in 21.5% of cases (23% of ADKE). Post-operative mortality concerned one patient who died from a pulmonary embolism during the third post-operative week. Morbidity included: 3 transient clinical rhinorrheas, 5 meningitis (one of which was responsible for heavy psycho-intellectual disability), 4 deep suppurations associated with osteitis of the bone flap and two superficial suppurations. 44 patients had a local recurrence (10 ADKE). No recurrence appeared in complete chemoresponders. Systematic preservation of intra-orbital contents did not increase the risk of local failure. Eleven patients (4 ADKE) developed cervical nodes and/or systemic metastasis. Death occurred after a mean of three months following the diagnosis of metastasis. Survival rate was: 60% at 3 years, 51.5% at 5 years, 32.5% at 10 years. ADKE survival rate was: 55% at 3 years, 51.5% at 5 years, 23% at 10 years. Survival ws related to tumoral extension: 75% at 5 and 10 years for T3, 45% at 5 years and 38% at 10 years for T4a, 40% at 3 years and null at 5 years for T4b, 5 and 10 years survival rate of complete chemoresponders are 100% whatever the tumour. Prognosis remained poor for epidermoid carcinomas (survival rate: 36% at 3 years, 0% at 5 years) and for melanomas (mean survival: 19.6 months). Post-operative radiotherapy should be indicated for large tumors T3, T4a and T4b).

Adenocarcinoma↗

BMS-190394, a selectin inhibitor, prevents rat cutaneous inflammatory reactions.

Selectin binding is the first step in extravasation of leukocytes through the endothelium. Infiltration of leukocytes is a hallmark of an inflammatory response. Blockade of selectin-dependent adhesion, therefore, represents a specific mechanism-based anti-inflammatory strategy. We have used the natural product sulfatide, one of the selectin ligands, as a template to design a novel selectin antagonist. BMS-190394, a structural analog of sulfatide, is an inhibitor of cell binding to P-, E- and L-selectin-Ig fusion proteins. BMS-190394 also inhibits binding mediated by native P-selectin expressed on the surface of activated platelets. Pharmacokinetic analysis of BMS-190394 showed that the compound remained in circulation with a T1/2 of 7 hr, long enough to inhibit the development of an acute inflammatory response. The in vitro activity and pharmacokinetic profile of this selectin-blocking compound led to the determination of its in vivo anti-inflammatory activity. BMS-190394 was a potent inhibitor of the dermal immune complex-induced reverse passive Arthus reaction in rats when delivered by the i.v. or i.p. route. The ED50 of the compound in the reverse passive Arthus reaction compares favorably to that for dexamethasone. BMS-190394 was also an effective inhibitor of the delayed-type hypersensitivity reaction in the rat. Compared with previous reports of the use of antibodies and complex oligosaccharides to inhibit the activity of the selectins, this low-molecular-weight inhibitor of the selectins presents a novel class of anti-inflammatory agents.

Animals↗

Experimental infection of the raccoon (Procyon lotor) with Borrelia burgdorferi.

The reservoir competence of the raccoon (Procyon lotor) for the Lyme disease spirochete (Borrelia burgdorferi) was evaluated in the laboratory during September 1991 to April 1993. Five raccoons were exposed to spirochete-infected (JD1 and Wisconsin 210 Wise strains) Ixodes scapularis nymphs (20/raccoon). A second feeding of spirochete-infected (Wisconsin 210 Wise strain) nymphs (20/raccoon) was performed with four of the original raccoons. Xenodiagnosis with cohorts of I. scapularis larvae (300/cohort) or nymphs (150/cohort) that were periodically placed on each animal was used to detect infection. We examined 1943 engorged ticks by a indirect immunofluorescence monoclonal antibody assay, but no spirochetes were detected. After exposure to spirochete-infected ticks, blood samples were collected at approximately weekly intervals and ear-skin biopsy samples were taken from each animal every third week. These tissues were placed in Barbour-Stoenner-Kelly media. Spirochetes were isolated in cultures of skin (wk 3, 5, 9, 81, and 83) and blood (wk 5, 8, 9, 11, and 12) of one raccoon and the skin (wk 28 and 31) of another raccoon. Antibody response of each animal was monitored through enzyme-linked immunosorbent assays and immunoblotting of blood serum against B. burgdorferi proteins. Except for one animal, raccoons did not have an antibody response until they were fed upon by a second cohort of infected I. scapularis nymphs. Based on Western blot analyses, raccoons exposed to B. burgdorferi via tick bite responded to the 31- (OspA) and 34-KDa (OspB) antigens. Response to other antigens varied among raccoons. Based on our results raccoons may be inefficient reservoirs for B. burgdorferi. Although some raccoons can become infected with B. burgdorferi, they may not transfer the infection to attached ticks.

Animals↗

[Clinical study of a mivacurium-propofol combination for laparoscopic surgery in children].

Coelioscopic surgery in children is today in constant progress and requires pharmacological agents which provide excellent surgical conditions for variable and unpredictable durations. The mivacurium-propofol association was clinically studied in this context in 30 ASA I patients aged from 6 to 16 years and appeared safe, efficient and easy to use. The orbicularis oculi and pollicis adductor stimulation allows simple and adapted neuromuscular blockade monitoring. Double-burst stimulation at the ulnar nerve improves the detection of a residual curarization.

Age Factors↗