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Biomedical subjects

D Fournier

Publications and source records attributed to D Fournier.

At least 109 records · Page 6Linked to original sources
PubMed1992

Catalytic properties of cholinesterases: importance of tyrosine 109 in Drosophila protein.

Tyrosine 109 in the acetylcholinesterase sequence of Drosophila melanogaster corresponds to an aspartate in vertebrate cholinesterases. Mutation of this amino acid to a glycine in the human butyrylcholinesterase gives rise to the 'atypic' phenotype characterized by a reduced activity for charged compounds. We investigated the importance of tyrosine 109 in the Drosophila sequence by in vitro mutagenesis and its expression in the Xenopus oocyte. We show here that tyrosine 109 contributes to the conformation of the active site and the charge of the residue at position 109 is important for catalytic properties. Sensitivity of the enzyme to organophosphorus and carbamate compounds is modified depending on residues present in position 109, therefore this amino acid is a potential site of resistance for insects to insecticides.

Acetylcholinesterase↗
PubMed1992

A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation.

We describe a new variant of Glanzmann's thrombasthenia (variant Strasbourg I). The patient (M.S.) showed an absence of platelet aggregation to ADP, thrombin, and collagen, and a decreased clot retraction. Platelet fibrinogen was approximately 20% of normal levels. ADP-stimulated platelets bound markedly reduced amounts of soluble fibrinogen and platelet adhesion to surface-bound fibrinogen was defective. Normal to subnormal amounts of glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) complexes, the platelet fibrinogen receptor, were revealed by SDS-PAGE, crossed immunoelectrophoresis, and antibody binding. However, the complexes were unusually sensitive to dissociation with EDTA at room temperature. Furthermore, flow cytometry showed that the platelets failed to bind the activation-dependent monoclonal antibody, PAC-1, after stimulation. In contrast, an RGDS-containing peptide induced significant binding of the anti-ligand-induced binding site antibody, D3GP3, suggesting the presence of a functional RGD binding domain on the patient's GPIIb-IIIa complex. Sequence analysis was performed after polymerase chain reaction amplification of selected patient's GPIIIa exons, and of the patient's platelet GPIIb and GPIIIa mRNAs. A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution. The defect has been inherited from the parents who are heterozygous for the same mutation. This substitution points to an essential amino acid in a region of GPIIIa involved in the binding of fibrinogen and influencing the Ca(2+)-dependent stability of the GPIIb-IIIa complex.

Adult↗
PubMed1991

In vivo bidirectional modulatory effect of benzodiazepine receptor ligands on GABAergic transmission evaluated by positron emission tomography in non-human primates.

The central type benzodiazepine receptor (BDZr), an allosteric modulatory site of the GABAA receptor-anion channel, has been shown in vitro to respond to drugs with positive efficacy (agonists), zero efficacy (competitive antagonists) and drugs with negative efficacy (inverse agonists). However, this general concept of the function of BDZr drugs has rarely been assessed in intact living brain. We report here in on a non-invasive in vivo assessment of the intrinsic efficacies of BDZr drugs in the brain of non-human primates. We have performed an in vivo simultaneous determination of fractional BDZr occupancy and the resulting pharmacological efficacies of the full agonist diazepam, the partial agonist bretazenil, the antagonist flumazenil (Ro15-1788), the partial inverse agonist Ro15-4513 and the full inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM). Positron emission tomography (PET) was used to estimate fractional BDZr occupancy measured as the in vivo displacement in the brain of the positron emitter radioligand, [11C]flumazenil. Simultaneously, the proconvulsant or anticonvulsant efficacies of the BDZr drugs were measured as their abilities to facilitate or counteract the central effects of an infusion of pentylenetetrazol, a non-competitive GABA antagonist acting on the picrotoxin site of the receptor complex. This was measured using electroencephalographic recording (EEG). Our results show that, in vivo, the fractional receptor occupancy by a given drug is perfectly correlated with its resulting graded pharmacological effects, as predicted from the competitive drug receptor interaction theory. Furthermore, the slope of the relationship between fractional receptor occupancies and the resulting pharmacological effects (an index of intrinsic efficacy) strictly depends on the BDZr ligand considered. Diazepam displayed a strong positive intrinsic efficacy, and, in contrast, beta-CCM a marked negative one. Between these two extremes, the partially active drugs bretazenil and Ro15-4513, which required a large fractional receptor occupancy to produce significant anti- or proconvulsant effects, respectively, displayed only a weak intrinsic efficacy. Flumazenil did not produce any significant pharmacological effect. We observed that the in vivo intrinsic efficacies of diazepam, flumazenil and beta-CCM correlate with their intrinsic efficacies as measured by their modulatory effects on the GABA-dependent membrane chloride conductance in vitro. Thus, the intrinsic efficacies measured using PET and EEG are likely to reflect the different in vivo abilities of BDZr drugs to induce or stabilize the GABAA-benzodiazepine chloride channel in a given conformation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Acquired mural (dural) arteriovenous shunts of the vein of Galen. Report of 4 cases.

4 patients with acquired arteriovenous shunts located in the wall of an ectatic vein of Galen (VG) are reported. They represent so-called VG dural arterio-venous malformations (DAVM). These shunts involve the vasa vasorum normally present in the VG wall. Physiopathology, clinical signs and age groups are usually the same as those encountered in other DAVMs; conversely they are totally different from the other mural shunts of the VG, detected in the pediatric population (true VG arteriovenous malformations), and leading to different clinical symptoms. Venous approach in these VG DAVMs is almost always contraindicated unless secondary occlusion of VG afferent has spontaneously excluded the pouch from the cerebral venous circulation.

Adult↗
PubMed1991

Small angle x-ray diffraction studies on the topography of cannabinoids in synaptic plasma membranes.

In a previous publication, we have described in detail how we used small angle x-ray diffraction to determine the topography of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) in dimyristoylphosphatidylcholine (DMPC) bilayers, and to deduce the conformation of the THC side chain by using the iodo-analog (5'-I-delta 8-THC) in the model membrane. We have now extended our studies to synaptic plasma membrane systems where the cannabinoids are believed to exert part of their pharmacological effects. Synaptic plasma membranes (SPM) were isolated from fresh bovine brains and delta 8-THC was incorporated into the membranes. By comparing the electron density profiles of drug free and drug-containing SPM preparations, we observed an electron density increase due to the presence of delta 8-THC in a region centered at 9.2 A from the terminal methyl groups of the membrane bilayer. In an attempt to dissect the effects of different membrane components on the topography of delta 8-THC, we carried out parallel experiments using membrane preparations from the synaptosomal membrane total lipid extract (TLX) as well as from bovine brain phosphatidyl choline extract (PCX) containing 30 mole percent cholesterol (Chol). Our results regarding the topography of delta 8-THC and 5'-I-delta 8-THC in these lipid membranes show that the TLX bilayer simulates the natural membrane environment very closely whereas in the PCX/Chol bilayer delta 8-THC resides at a location approximately 4 A closer to the membrane interface, similar to that found in our previous study using DMPC model membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases.

The authors report the results of treatment in 49 consecutive patients with brain arteriovenous malformations (AVM's) who underwent therapeutic embolization with liquid adhesive agents between 1984 and 1988 at the Toronto Western Hospital. Thirty-three patients had no other treatment and were followed up with angiography at 2 years and clinically from 2 to 6 years. Of the other 16 patients, 10 had adjunctive radiosurgery and six underwent surgical resection following embolization. Seven (14%) of the 49 patients had a morphological cure effected by embolization as evidenced on their 2-year follow-up angiograms: these have remained clinically stable. Twelve patients developed neurological deficits after embolization; eight (16% of the series) were transient and four (8%) were permanent. Two patients (4%) had a delayed hemorrhage after incomplete obliteration of their malformations. Endovascular treatment resulted in clinical improvement in 15 (33%) of the other 46 patients. None of the patients who initially presented with hemorrhage had a rebleed following embolization. It is concluded that endovascular treatment with liquid embolic material can be an integral part of the multidisciplinary treatment protocol for patients with brain AVM's.

Cerebral Angiography↗
PubMed1991

[Indications for bone autografts and allografts in cranioplasties. Apropos of a series of 51 cases, 30 of them with follow-up].

Based on a series of 51 cranioplasties performed between 1978 and 1988 with follow-up of 30 cases, the authors define the respective indications for bone autografts and allografts. The various donor sites of autografts are reviewed, particularly in relation to the history of their use. Similarly, the history of the use of allografts is also reviewed and the various methods of sterilisation are considered. The authors review all of the literature on this subject and compare their results with those of other authors.

Adolescent↗
PubMed1991

[Calcificated necrotic inflammatory granuloma after intradiscal injection of triamcinolone hexacetonide].

Recently, it has been demonstrated that symptomatic epidural calcifications represent a complication of intradiscal injection of triamcinolone hexacetonide (Hexatrione). Out of our three cases, pathological examination showed lesions of necrosis with granulomatous inflammatory reaction and bone metaplasia. Necrosis seems to be the primary cause of calcifications so we propose to call the lesion inflammatory and necrotic granuloma. The incidence of these granulomas is unknown. They are unpredictable and appear with a mean range of a year following the intradiscal injection. The treatment is surgery if they become symptomatic.

Anti-Inflammatory Agents↗
PubMed1991

Tuberculosis and HIV.

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Acquired Immunodeficiency Syndrome↗
PubMed1991

[MRI of the liver].

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Budd-Chiari Syndrome↗
PubMed1990

Studies on the interaction of platelet glycoprotein IIb-IIIa and glycoprotein IV with fibrinogen and thrombospondin: a new immunochemical approach.

We have designed a new binding assay based on crossed immunoelectrophoresis that allowed us to test for the relative capacities of platelet membrane glycoprotein IIb-IIIa (GP IIb-IIIa), and glycoprotein IV (GP IV) to bind purified Arg-Gly-Asp (RGD)-containing adhesive proteins. Preformed immune complexes were made by reacting a platelet lysate with murine monoclonal antibodies to GP IV (OKM5 and FA6-152) or to GP IIb-IIIa (AP-2). Upon two-dimensional electrophoretic separation in agarose gels and immunoprecipitation by a polyclonal antibody to mouse IgG, the immobilized complexes containing the desired antigen were further probed with purified 125I-labeled TSP or fibrinogen. Under these conditions, immobilized GP IV was found to specifically bind TSP, whereas it was unreactive with fibrinogen. By contrast, immobilized GP IIb-IIIa demonstrated fibrinogen binding capacity but did not demonstrate any reactivity toward TSP. These observations suggest that the overall structure of the adhesive protein may determine the accessibility of the RGD sequence to its binding site on GP IIb-IIIa.

Amino Acid Sequence↗
PubMed1990

Topographic anatomy of the lumbar lateral vertebral groove. Anatomical basis of the surgical approach to extra foraminal herniated disc.

The study of numerous dissections, sections and X-rays of the lumbar spine has enabled us to clarify the connections of the lumbar spinal nerves at their emergence from the intervertebral foramen and in the lateral vertebral groove. This work naturally leads to the study of the extra foraminal herniated disc by an extra isthmian approach or to percutaneous surgery of thoracolumbar discs.

Humans↗
PubMed1990

Revascularization of brain arteriovenous malformations after embolization with bucrylate.

Between 1984 and 1988, 52 brain arteriovenous malformations (AVMs) were embolized in the Radiology Department of the Toronto Western Hospital. 9 were localized in the occipital lobe. There was angiographic follow-up ranging from one to four years. Two embolized AVMs, both occipital, showed revascularisation at 6 months and two years respectively. In one case the embolization had resulted in a complete obliteration of the AVM. In the other, the nidus was reduced by 95%. It is suggested that the occipital lobe, because of its rich vascularity, is more prone than other parts of the brain to produce intense collateralization leading indirectly to resupply of embolized AVMs. Existence of these collaterals may also explain the rarity of visual defects in occipital AVMs. These cases confirm the need for post therapeutic angiographic controls to assess the stability of the results obtained.

Adult↗