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Biomedical subjects

M Dupuis

Publications and source records attributed to M Dupuis.

At least 19 recordsLinked to original sources

Perforin and its role in T lymphocyte-mediated cytolysis.

The killing mediated by cytotoxic T lymphocytes (CTL) represents an important mechanism in the immune defence against tumors and virus infections. The lytic mechanism has been proposed to consist of a polarized secretion of granule-stored molecules, occurring on effector-target cell contact. By electron microscopy, membrane deposited, pore-like lesions are detected on the target cell membrane during cytolysis by CTL. These structures resembled strikingly pores formed during complement attack. Granules of CTL isolated by nitrogen cavitation and Percoll gradient centrifugation were shown to retain cytotoxic activity. Further purification of proteins stored in these granules led to the discovery of a membranolytic protein named perforin which was capable of polymerizing into pore-like structures. In addition to this cytolytic protein, a set of serine esterases was found as well as lysosomal enzymes and proteoglycans, whose function are not yet clearly defined. The role of perforin in the cytotoxic process is currently being explored by ablating the active gene in mice.

Animals

Inhibition of lymphocyte mediated cytotoxicity by perforin antisense oligonucleotides.

The granule/perforin exocytosis model of CTL mediated cytolysis proposes that CTL, upon recognition of the specific targets, release the cytolytic, pore-forming protein perforin into the intercellular space which then mediates the cytotoxic effect. However, direct evidence for the involvement of perforin is still lacking, and indeed, recent results even seem incompatible with the model. To determine directly the role of perforin in CTL cytotoxicity, perforin antisense oligonucleotides were exogenously added during the stimulation of mouse spleen derived T cells and human peripheral blood lymphocytes (PBL), respectively. Perforin protein expression in lymphocytes was reduced by up to 65%, and cytotoxicity of stimulated T cells by as much as 69% (5.7-fold). These results provide the first experimental evidence for a crucial role of perforin in lymphocyte mediated cytotoxicity.

Animals

Antituberculous drug susceptibility testing of Mycobacterium bovis BCG strain Montréal.

Testing of Mycobacterium bovis BCG strain Montréal for susceptibility to four primary antituberculous drugs (isoniazid, ethambutol, streptomycin, and rifampin) and to one secondary drug (p-aminosalicylic acid) showed the strain to be susceptible to all five substances. Mycobacterium bovis strains ATCC 35735, which is isoniazid sensitive, and ATCC 35747, which is isoniazid resistant, were included in the test; with the exception of their respective susceptibility to isoniazid, both were inhibited by the other four drugs.

Aminosalicylic Acid

Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract.

Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. The purpose of this work was to study, under in vitro conditions, the action of Ginkgo biloba extract (Gbe) against superoxide anion (O2-.), which is directly or indirectly implicated in cell damage. Gbe appears to have both an O2-. scavenging effect and also a superoxide dismutase activity. Its antiradical effect was demonstrated by low temperature electron spin resonance and in a non-enzymatic system (phenazine methosulfate-NADH), and its enzymatic activity was shown by polarographic determination.

Animals

Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis.

In order to determine whether mammary gland differentiation, which is known to protect this organ from chemically induced carcinogenesis, can be stimulated in virgin rats by administration of a progestagenic agent, medroxyprogesterone acetate (MPA) was given to 300 Sprague-Dawley virgin rats, which at the ages of 45, 55, 65 and 75 days, groups I, II, III and IV respectively, had implanted an MPA pellet of 0.5 mg (low dose-LD) or 5.0 mg (high dose-HD). Pellets were removed after 21 days, and 21 days later five animals per group were killed for evaluation of mammary gland development. The remaining animals received 8 mg 7,12-dimethylbenz(a)-anthracene (DMBA) per 100 g body weight, and were killed after 24 weeks for evaluation of tumour incidence. Both age and treatment affected mammary gland structure and had a significant interaction in the proportion of terminal end buds (TEBs) present. The number of TEBs decreased as a function of age; treatment at both LD and HD did not modify the proportion of TEBs in groups I and III; LD decreased their percentage in group II, and both doses markedly increased TEB percentage in group IV animals. MPA LD treatment did not affect overall tumour and adenocarcinoma incidence although group IV animals developed greater incidences than their respective controls. MPA HD treated rats were 2.45 times more likely to develop tumours than their respective controls. Adenocarcinoma incidence had a significant positive correlation with the percentage of TEBs present. It was concluded that this progestagenic agent did not increase the risk of carcinoma development when administered to virgin rats at the clinical dose used for contraception. However, a 10-fold dose increase resulted in a higher tumorigenic response.

9,10-Dimethyl-1,2-benzanthracene

A clinical and sero-epidemiological study of 190 Belgian patients suffering from Lyme borreliosis.

We present a sero-epidemiological study of 190 Belgian cases of Lyme borreliosis, a multisystemic disease caused by the spirochaete Borrelia burgdorferi and transmitted by a tick bite. The whole spectrum of clinical pictures was observed in these patients, including "erythema chronicum migrans" (63%), neurological involvement (47%) and arthritis (22%), frequently in combination. Our results are compared to findings in other countries. Among the 437 Ixodes ricinus ticks collected in the Sambre and Meuse valleys around Namur, we discovered 43 ticks (9.8%) with spirochaetes in the midgut. The ecology of these arthropods explains why this infection is more prevalent in the spring and the summer. Perhaps for the same reason, the incidence ranges from low near the coast to medium in the central part and high in the wooded south-eastern part of Belgium. The main conclusions are that Lyme borreliosis is endemic in Belgium, that all the clinical pictures can be observed ant that a clear epidemiological case-definition is needed, combining clinical signs and serological results.

Adolescent

Partial purification of goat kidney beta-mannosidase.

1. Goat kidney beta-mannosidase was purified 8500-fold to a specific activity of 65,000 nmol/h per mg of protein with a 6% yield by using multiple steps including cation-exchange and anion-exchange fast protein liquid chromatography. This is the first description of a highly purified preparation from goat tissue; however, it was not homogeneous, as judged by silver-stained SDS/polyacrylamide-gel electrophoresis. 2. The enzyme exhibited microheterogeneity when analysed by isoelectric focusing (pI 5.5-6.5). 3. Purified beta-mannosidase hydrolysed the terminal beta-(1----4)-linkage of oligosaccharides that accumulate in beta-mannosidosis.

Animals

Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes.

A Ginkgo biloba extract (Gbe) containing flavonoids, among other compounds, was tested for the release of activated oxygen species (O-2, H2O2, OH.) during the stimulation of human neutrophils (PMNs) by a soluble agonist. The extract slows down O2 consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxidase, the enzyme responsible for the reduction of O2 to O-2. Consequently, superoxide anion (O-.2) and hydrogen peroxide (H2O2) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 micrograms/ml. Moreover, the hydroxyl radical generation (OH.) is very much decreased at concentrations as low as 15.6 micrograms Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severely the activity of myeloperoxidase contained in neutrophils. This enzyme, secreted into the intra and extracellular medium, catalyzes the oxidation of chloride (Cl-) by H2O2 to yield strong oxidants (HOCl, chloramines) which are implicated in inflammatory processes.

Free Radicals

[Study of a painful total hip prosthesis].

The authors propose a simple routine survey to be performed in the case of a painful total hip prosthesis which is generally able to define the diagnosis and the prognosis. X-ray films are more valuable by their repetition than by their simple analysis. Certain minor signs can help predict or detect loosening of the prosthesis or other complications, but in the great majority of cases, radiology alone is not sufficient to make the diagnosis, as the films are only able to show clear spaces around the prosthesis, without being able to definitely confirm the aetiopathogenic significance of this sign. In these cases, when the decision has not been taken to re-operate, more sophisticated investigations are required (scintigraphy, dynamic tests, arthrography), although they must be used with caution as very often the clinical findings will have the last word.

Bacteriological Techniques

Metallic elements in crude and milled chrysotile asbestos from Quebec.

Crude and milled fibers from different asbestos mines in Quebec have been analyzed for their metallic content. Crude fibers present a few metal concentrations that are characteristic for each mine. Manganese and iron can be used as discriminators, zinc and cobalt are constantly present in minute quantities, and calcium is virtually absent from crude fibers. Milled fibers are enriched in metals by factors ranging from 1.3 to greater than 15. Chromium and nickel concentrations are many times higher than in crude fibers and iron content is increased by more than 100%. Total metal content in milled fibers is mainly due to nonchrysotile material.

Asbestos

Anatomical and behavioral study of a case of asymptomatic callosal agenesis.

This paper presents radiological and behavioral observations of a case of asymptomatic congenital agenesis of the corpus callosum. CT scan data indicated that a small portion of the corpus callosum might have been preserved, although this is difficult to demonstrate with the usual criteria. Nuclear magnetic resonance showed the small preserved portion on the sagittal plane. The results of the behavioral studies agree well with already published data: the agenesis of the callosum does not induce a split-brain syndrome but does cause slight motor disturbances, an improvement of the ipsilateral paths of control, and the development of extra-callosal interhemispheric pathways.

Adolescent

[Meningoradiculitis caused by a spirochete (Borrelia burgdorferi) after arthropod bite].

Eight cases of meningoradiculitis (Garin-Bujadoux-Bannwarth's syndrome) are presented; the first case followed an "unidentified insect" bite and erythema chronicum migrans, whereas the second and third cases were not preceded by any documented insect bite or erythema; they occurred during summer in 1984 and 1985 and were characterized by cranial or radicular neuritis, lymphocytic meningitis, positive serology by immunofluorescence against Borrelia Burgdorferi and a good response to Penicillin (20 000 000 U during 14 days I.V.). Five other cases were observed in the same area as the first and second cases (Walloon Brabant) during the preceding summers; in two, serological proof of Borrelia Burgdorferi infection was obtained retrospectively. Lyme disease and Garin-Bujadoux-Bannwarth syndrome are both tick-born spirochetosis, due to two slightly different subtypes of Borrelia Burgdorferi. Their early neurological manifestations differ mainly by focalised pain on the bitten region in Garin-Bujadoux-Bannwarth's syndromes. This could be due to direct aggression of the peripheral nerve in Garin-Bujadoux-Bannwarth syndrome.

Antibodies, Bacterial