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L Cantin

Publications and source records attributed to L Cantin.

15 recordsLinked to original sources
PubMed2001

Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.

The first crystallographic structure of human type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD3, AKR1C2), an enzyme playing a critical role in steroid hormone metabolism, has been determined in complex with testosterone and NADP at 1.25-A resolution. The enzyme's 17beta-HSD activity was studied in comparison with its 3alpha-HSD activity. The enzyme catalyzes the inactivation of dihydrotestosterone into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) as well as the transformation of androstenedione into testosterone. Using our homogeneous and highly active enzyme preparation, we have obtained 150-fold higher 3alpha-HSD specificity as compared with the former reports in the literature. Although the rat and the human 3alpha-HSDs share 81% sequence homology, our structure reveals significantly different geometries of the active sites. Substitution of the Ser(222) by a histidine in the human enzyme may compel the steroid to adopt a different binding to that previously described for the rat (Bennett, M. J., Albert, R. H., Jez, J. M., Ma, H., Penning, T. M., and Lewis, M. (1997) Structure 5, 799-T812). Furthermore, we showed that the affinity for the cofactor is higher in the human 3alpha-HSD3 than the rat enzyme due to the presence of additional hydrogen bonds on the adenine moiety and that the cofactor is present under its reduced form in the active site in our preparation.

17-Hydroxysteroid Dehydrogenases↗
PubMed2001

Crystallization and preliminary X-ray crystallographic analysis of the human type 3 3 alpha-hydroxysteroid dehydrogenase at 1.8 A resolution.

In androgen-sensitive target tissues, 3 alpha-hydroxysteroid dehydrogenase regulates the androgen receptor (AR) activity by catalyzing the inactivation of 5 alpha-dihydrotestosterone (the most natural potent androgen) to 5 alpha-androstane-3 alpha,17 beta-diol. In this report, the crystallization of a human prostatic type 3 3 alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily, is described. Two different crystal forms of the complex between the human type 3 3 alpha-HSD, NADP(+) and testosterone have been obtained using PEG as precipitant. Crystal form I, which diffracts to 1.6 A, belongs to the monoclinic space group P2(1), with unit-cell parameters a = 55.07, b = 87.15, c = 76.88 A, beta = 107.37 degrees and two subunits in the asymmetric unit. A complete data set has been collected at 1.8 A. Crystal form II, which diffracts to 2.6 A, belongs to the rhombohedral space group R32, with unit-cell parameters a = b = 143.59, c = 205.86 A, alpha = beta = 90, gamma = 120 degrees and two subunits in the asymmetric unit.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Familial intracranial aneurysms: recurrence risk and accidental aggregation study.

BACKGROUND: The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings. RESULTS: The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0-2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD +/- 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA. CONCLUSION: These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.

Adult↗
PubMed1996

Assessing the stability of cystatin/cysteine proteinase complexes using mildly-denaturing gelatin-polyacrylamide gel electrophoresis.

A method for assessing the stability of cystatin/cysteine proteinase complexes using mildly-denaturing gelatin-polyacrylamide gel electrophoresis (gelatin-PAGE) is described. As suggested by the use of well-known cystatins (human stefins A and B, and oryzacystatins I and II) and the plant cysteine proteinase papain, the ability of cystatin/cysteine proteinase complexes to remain stable during electrophoresis is associated with the degree of affinity between the enzyme and the inhibitor (and inversely associated with the Ki values), at least with the disulfide bond-lacking cystatins. Complexes with Ki values > or = 10(-8) M (weak interactions) are partly or completely dissociated under the conditions used, while those with lower Ki values (strong interactions) remain stable. As shown by the differential effects of two plant cystatins, oryzacystatins I and II, against a cysteine proteinase present in crude (complex) extracts from a plant pest -- the two-spotted spider mite (Tetranychus urticae Koch), the gelatin-PAGE procedure is suitable for studying the ability of cystatins to form highly stable complexes with cysteine proteinases, without the need for prior purification steps. Considering the well-recognized potential of proteinase inhibitors for pest and pathogen control, this analytical approach will be useful for rapidly assessing the respective potential of various cystatins for protection of plants, animals, and humans.

Animals↗
PubMed1996

Identification of stable plant cystatin/nematode proteinase complexes using mildly denaturing gelatin/polyacrylamide gel electrophoresis.

The biochemical interactions between two cystatins from rice seeds, oryzacystatin I (OCI) and oryzacystatin II (OCII), and the cysteine proteinases from three plant parasitic nematodes, Meloidogyne hapla, M. incognita and M. javanica, were assessed using standard protease assays and mildly denaturing gelatin/polyacrylamide gel electrophoresis (gelatin/PAGE). Activity detected in extracts of preparasitic second-stage larvae (J2) from M. hapla was optimal at pH 5.5 and was inhibited in vitro by the cysteine proteinase inhibitors trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane, hen egg cystatin, OCI, and OCII. As demonstrated by class-specific activity staining, all the activity measured between pH 3.5 and pH 7.5 was accounted for by a major proteinase form, Mhp1, and two minor forms, Mhp2 and Mhp3. Mhps were also detected in extracts and excretions of parasitic J2 and adult females, indicating their continuous expression throughout development of M. hapla, and their possible involvement in the extracellular degradation of proteins. Interestingly, the two plant cysteine proteinase inhibitors OCI and OCII showed different degrees of affinity for the major proteinase form, Mhp1. Both inhibitors almost completely inactivated this proteinase in native conditions but, unlike OCII, OCI conserved a high affinity for Mhp1 during mildly denaturing gelatin/PAGE, showing the differential stabilities of the OCI/Mhp1 and OCII/Mhp1 complexes. In contrast to Mhp1, the major cysteine proteinases detected in the two closely related species M. incognita and M. javanica were strongly inhibited by OCII, while the inhibition of OCI was partly prevented during electrophoresis. This species-related efficiency of plant cystatins against nematode cysteine proteinases could have practical implications when planning their use to control nematodes of the genus Meloidogyne.

Animals↗
PubMed1996

Epidemiological study of reptured intracranial aneurysms in the Saguenay-Lac-Saint-Jean region (Quebec, Canada).

BACKGROUND: Using a population-based register of the Saguenay-Lac-Saint-Jean region (Quebec, Canada), the genealogical reconstruction of 533 individuals with intracranial aneurysm (IA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: As part of an ongoing project to assess a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present study was to determine whether age-specific rates of reputed cerebral aneurysms were higher than in other populations. DESIGN: A retrospective study of cases of proven ruptured IAs which were hospitalized during the 1973 to 1992 period was conducted. Age-adjusted rates were computed and compared to those reported in the Helsinki population. RESULTS: We identified 412 cases of ruptured aneurysms. The age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women), which is similar to the incidence rates reported in other studies. Although the mean age at time of rupture was younger (46.6 years +/- 13.8) than usually reported, no increase in age-specific incidence rates was detected. CONCLUSIONS: The results of this epidemiological study neither support nor reject the hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population.

Adolescent↗
PubMed1996

A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada).

The genealogies of 533 individuals with an intracranial aneurysm (IA) born in the Saguenay-Lac-Saint-Jean region, a geographically isolated area located in northeastern Quebec, were reconstructed using a population-based register. A control group consisting of three individuals of the same sex and born on the same day and in the same municipality than the IA patients was created; the genealogies of the 1599 controls were also reconstructed. The coefficients of inbreeding and kinship were calculated. Familial aggregation, i.e. the presence of IA in two or more first- to third-degree relatives, was also sought. The mean inbreeding coefficient was lower in the IA group than in the control group (7.92 x 10(-4) versus 10.04 x 10(-4)). The mean kinship coefficient was higher in the IA group than in the control group (2.17 x 10(-4) versus 1.55 x 10(-4)). Forty-eight IA patients (9.0%) were first-degree relatives compared to only 1.9% of the control individuals. The proportion of individuals showing familial aggregation was higher in the IA group than in the control group (29.8% and 18.6% respectively). These results strongly suggest that some IA are genetically determined in this population.

Consanguinity↗
PubMed1995

Carboxy-terminal truncation of oryzacystatin II by oryzacystatin-insensitive insect digestive proteinases.

The biochemical interactions between digestive proteinases of the Coleoptera pest black vine weevil (Otiorynchus sulcatus) and two plant cysteine proteinase inhibitors, oryzacystatin I (OCI) and oryzacystatin II (OCII), were assessed using gelatin-polyacrylamide gel electrophoresis, OCI-affinity chromatography, and recombinant forms of the two plant inhibitors. The insect proteinases were resolved in gelatin-containing polyacrylamide gels as five major bands, only three of them being totally or partially inactivated by OCI and OCII. The maximal inhibitory effect of both OCs at pH 5.0 was estimated at 40% and the inhibition was stable with time despite the presence of OC-insensitive proteases, indicating the stability of the OCI and OCII effects. After removing OC-sensitive proteinases from the insect crude extract by OCI-affinity chromatography, the effects of the insect cystatin-insensitive proteases on the structural integrity of the free OCs were analyzed. While OCI remained stable, OCII was subjected to limited proteolysis leading to its gradual transformation into a approximately 10.5-kDa unstable intermediate, OCIIi. As shown by the degradation pattern of a glutathione S-transferase (GST)/OCII fusion protein, the appearance of OCIIi resulted from the C-terminal truncation of OCII. Either free or linked to GST, OCIIi was as active against papain and human cathepsin H as OCII, and the initial specificities of the inhibitor for these two cysteine proteinases were conserved after cleavage. Although these observations indicate the high conformational stability of OCII near its active (inhibitory) site, they also suggest a general conformational destabilization of this inhibitor following its initial cleavage, subsequently leading to its complete hydrolysis. This apparent susceptibility of OCII to proteolytic cleavage by the insect proteinases could have major implications when planning the use of this plant cystatin for insect pest control.

Animals↗
PubMed1988

[The treatment of the psychotic.].

It is becoming more and more common that people take for granted the idea that psychoanalysis can do nothing for psychotics. Nonetheless, it is Freud who took the "senseless" products of Man that are dreams, lapsus', symptoms, deliria, hallucinations, and who "reinstated" them in the realm of humanity. But it may also be what many hold against him. Supported by over six years of working with psychotic s in a Centre de traitement psychanalytique in Québec, the author can prove the existence of an apropriate treatment for psychosis. The psychotic who enters the analytical field begins reacting to the analyst's "calling" aimed at having him speak up. The cure for psychotics follows a logicical path and must respect certain conditions ; the author attempts to describe the process, from the "calling" of transference to the object created through which the psychotic can relate socially.

English Abstract↗
PubMed1986

[For a new clinical approach to psychosis : the " 388 "].

The history of the last thirty years of North-American psychiatry points up the difficulties encountered in the treatment of psychotic patients in a hospital setting but also in the maintaining of their social integration. In a search for solutions, and taking into account the needs observed at the Robert-Giffard Hospital in Quebec, a group of professionals of GIFRIC decided to open, in the center of town, a Psychoanalytical Center for psychotics. Operating since 1982, the "388" is arming at a social réintégration of the psychotic patients in order to read a more satisfying life according to their possibilities of co-existence with others. It is an outside of the hospital structure which permits the treatment of the crisis as well as providing longterm care. The care and services given are based on a psychoanalytical frame. This paper describes the clientele, the services offered, the treatment, the patients' evolution and the problems that arise from the evaluation of such a new structure.

English Abstract↗
PubMed1985

An approach to the provision of nutrition services in a cancer treatment centre.

Nutritional care of the cancer patient has been the subject of extensive publications in recent years. Its importance, although generally recognized, has not led to universal availability of nutrition services to cancer patients and their families. Nutritional care can be supportive or palliative and must be coordinated with the care provided by other members of the multidisciplinary team. This article presents some of the important factors involved in the implementation of nutrition programs in a cancer treatment centre. The need for enthusiastic, competent, and human delivery of nutritional care is emphasized.

Cancer Care Facilities↗
PubMed1982

[Group experience : risks and stakes.].

This article presents an experience of an interdisciplinary group crossed by three principal axes : the psychoanalytical field, the socio-cultural and political field, and human sciences research. This adventure led researchers and intervening persons from twenty disciplines to realize projects which are the forms and the means of reappropriation of their own subjective history by their intervention in certain sectors of development of their region. These projects pair research and intervention in the areas of mental health, art and culture. The members of the group give themselves the means to guarantee the viability of these projects in a position of relative independence in relation to traditional institutions.

English Abstract↗