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L Beaudoin

Publications and source records attributed to L Beaudoin.

16 recordsLinked to original sources
PubMed2001

NK T cell-induced protection against diabetes in V alpha 14-J alpha 281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen.

The onset of autoimmune diabetes is related to defective immune regulation. Recent studies have shown that NK T cells are deficient in number and function in both diabetic patients and nonobese diabetic (NOD) mice. NK T cells, which are CD1d restricted, express a TCR with an invariant V alpha 14-J alpha 281 chain and rapidly produce large amounts of cytokines. V alpha 14-J alpha 281 transgenic NOD mice have increased numbers of NK T cells and are protected against diabetes onset. In this study we analyzed where and how NK T cells interfere with the development of the anti-islet autoimmune response. NK T cells, which are usually rare in lymph nodes, are abundant in pancreatic lymph nodes and are also present in islets. IL-4 mRNA levels are increased and IFN-gamma mRNA levels decreased in islets from diabetes-free V alpha 14-J alpha 281 transgenic NOD mice; the IgG1/IgG2c ratio of autoantibodies against glutamic acid decarboxylase is also increased in these mice. Treatment with IL-12 (a pro-Th1 cytokine) or anti-IL-4 Ab abolishes the diabetes protection in V alpha 14-J alpha 281 NOD mice. The protection from diabetes conferred by NK T cells is thus associated with a Th2 shift within islets directed against autoantigen such as glutamic acid decarboxylase. Our findings also demonstrate the key role of IL-4.

Animals↗
PubMed2000

Fcalpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger's disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice.

The pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN), the most prevalent form of glomerulonephritis worldwide, involves circulating macromolecular IgA1 complexes. However, the molecular mechanism(s) of the disease remain poorly understood. We report here the presence of circulating soluble FcalphaR (CD89)-IgA complexes in patients with IgAN. Soluble CD89 was identified as a glycoprotein with a 24-kD backbone that corresponds to the expected size of CD89 extracellular domains. To demonstrate their pathogenic role, we generated transgenic (Tg) mice expressing human CD89 on macrophage/monocytes, as no CD89 homologue is found in mice. These mice spontaneously developed massive mesangial IgA deposition, glomerular and interstitial macrophage infiltration, mesangial matrix expansion, hematuria, and mild proteinuria. The molecular mechanism was shown to involve soluble CD89 released after interaction with IgA. This release was independent of CD89 association with the FcRgamma chain. The disease was induced in recombination activating gene (RAG)2(-/-) mice by injection of serum from Tg mice, and in severe combined immunodeficiency (SCID)-Tg mice by injection of patients' IgA. Depletion of soluble CD89 from serum abolished this effect. These results reveal the key role of soluble CD89 in the pathogenesis of IgAN and provide an in vivo model that will be useful for developing new treatments.

Animals↗
PubMed1999

Acute systematic and variable postural adaptations induced by an orthopaedic shoe lift in control subjects.

A small leg length inequality, either true or functional, can be implicated in the pathogenesis of numerous spinal disorders. The correction of a leg length inequality with the goal of treating a spinal pathology is often achieved with the use of a shoe lift. Little research has focused on the impact of this correction on the three-dimensional (3D) postural organisation. The goal of this study is to quantify in control subjects the 3D postural changes to the pelvis, trunk, scapular belt and head, induced by a shoe lift. The postural geometry of 20 female subjects (X = 22, sigma = 1.2) was evaluated using a motion analysis system for three randomised conditions: control, and right and left shoe lift. Acute postural adaptations were noted for all subjects, principally manifested through the tilt of the pelvis, asymmetric version of the left and right iliac bones, and a lateral shift of the pelvis and scapular belt. The difference in the version of the right and left iliac bones was positively associated with the pelvic tilt. Postural adaptations were noted to vary between subjects for rotation and postero-anterior shift of the pelvis and scapular belt. No notable differences between conditions were noted in the estimation of kyphosis and lordosis. The observed systematic and variable postural adaptations noted in the presence of a shoe lift reflects the unique constraints of the musculoskeletal system. This suggests that the global impact of a shoe lift on a patient's posture should also be considered during treatment. This study provides a basis for comparison of future research involving pathological populations.

Adaptation, Physiological↗
PubMed1999

[The ODEC (Organization for Development and Community Networks) and mental health: from networking to opening in the local community].

The Organisme de développement et d'entraide communautaire (ODEC) is a nonprofit mental health organization that was established in 1987 and offers mutual help and community development services in the Vallée-de-la-Lièvre region in the Outaouais area of Quebec. Starting with an individual accompaniment service for people living with mental health problems, ODEC has succeeded in establishing a significant mutual help network that now involves more than 100 people. This article comes out of an in-depth case study of ODEC. By analysing the major parameters of its journey over more than 10 years, it brings to the fore the impact in the mental health field of providing a network in close association with community involvement.

Community Mental Health Services↗
PubMed1998

Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes.

Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked to the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) T cells might be involved in diabetes, given their deficiency in NOD mice and the prevention of diabetes by adoptive transfer of alpha/beta double-negative thymocytes. Here, we evaluated the role of NK T cells in diabetes by using transgenic NOD mice expressing the T cell antigen receptor (TCR) alpha chain Valpha14-Jalpha281 characteristic of NK T cells. Precise identification of NK1.1(+) T cells was based on out-cross with congenic NK1.1 NOD mice. All six transgenic lines showed, to various degrees, elevated numbers of NK1.1(+) T cells, enhanced production of interleukin (IL)-4, and increased levels of serum immunoglobulin E. Only the transgenic lines with the largest numbers of NK T cells and the most vigorous burst of IL-4 production were protected from diabetes. Transfer and cotransfer experiments with transgenic splenocytes demonstrated that Valpha14-Jalpha281 transgenic NOD mice, although protected from overt diabetes, developed a diabetogenic T cell repertoire, and that NK T cells actively inhibited the pathogenic action of T cells. These results indicate that the number of NK T cells strongly influences the development of diabetes.

Animals↗
PubMed1996

Intermittent rewards raise self-stimulation thresholds.

Rats implanted with lateral hypothalamic electrodes pressed a lever to obtain 0.5 s bursts of pulses under the four combinations of fixed or variable, interval or ratio, schedules of reinforcement. Along with continuous reinforcement schedules, intervals of 1, 2, 5, and 10 s, or ratios of 2, 5, and 10 responses per stimulation were used in sessions wherein the frequency thresholds, defined as pulse frequencies that would support half-maximum rates of response, were estimated. Thresholds rose systematically under both ratio and interval schedules of reinforcement, and there was no difference between fixed and variable variations. When normalized data were plotted as a function of reinforcement density, thresholds from both interval and ratio schedules followed the same pattern, suggesting that the common factor was time between rewards. An increase in the current with a corresponding decrease in pulse frequency increased the rate at which time between rewards augmented thresholds.

Animals↗
PubMed1995

T cell activation through Thy-1 is associated with the expression of a surface protein (p100) on a subset of CD4 cells.

Thy-1 molecules, which lack a transmembrane domain, can nonetheless induce T cell activation; it has thus been suggested that a separate transmembrane molecule associated with Thy-1 is required for signal transduction. We have previously characterized a transmembrane protein with an Mr of 100,000 (p100), which is non-covalently bound to two glycosyl-phosphatidylinositol (GPI)-linked molecules, Thy-1 and ThB. p100 is selectively expressed on the T cell surface and divides peripheral CD4 cells into two subpopulations. This differential expression on CD4 cells allowed us to investigate the role of p100 in signal transduction through Thy-1 molecules. Here we report that only p100+ CD4 cells proliferate and release cytokines in response to cross-linkage of Thy-1, although both p100+ and p100- CD4 cells strongly express Thy-1 on their surfaces. Control stimulation by anti-CD3 antibodies or concanavalin A induces identical thymidine uptake by the two CD4 cell populations. Interestingly, these two populations of CD4 cells had different cytokine release profiles after activation through CD3: only p100+ CD4 cells released high amounts of IL-2 and IFN-gamma, whereas both populations released IL-4. p100 expression correlates with the induction of homotypic aggregation of T cells after Thy-1 triggering. p100 is associated with kinase activity (fyn and lck), and phosphorylated proteins of 90, 59, 57 and 33 kDa co-precipitate with Thy-1 only in p100+ CD4 cells. Altogether, these data suggest that p100 is involved in signal transduction through Thy-1. p100 expression by activated CD4 cells in vivo may be relevant to the proposed function of Thy-1 as an accessory signaling molecule in cell activation.

Animals↗
PubMed1987

In situ mechanical behavior of posterior spinal ligaments in the lumbar region. An in vitro study.

The posterior ligaments: ligamentum flavum, articular, interspinous and supraspinous ligaments of twenty five fresh cadaveric intervertebral segments, from T11-T12 to L4-L5, extracted from fourteen spines were tested in tension. A progressive dissection method was used, that is, each segment was tested after first resecting the disk with the ligaments intact and a force-elongation curve obtained. Then one ligament was cut and the test repeated, and so on. The most restrictive ligament was found to be the ligamentum flavum followed by the articular, interspinous, and supraspinous ligaments.

Aged↗
PubMedDate not supplied

Randomized trial of paroxetine in end-stage COPD.

BACKGROUND: Although the underlying pathology is initially confined to the lungs, the associated emotional responses to chronic obstructive pulmonary disease (COPD) contribute greatly to the resulting morbidity. The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms. METHODS: We conducted a 12-week, randomized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Questionnaire (CRQ), an evaluative COPD-specific quality-of-life questionnaire, was the primary outcome. RESULTS: 23 patients were randomized and 15 completed the trial (8 on Paroxetine; 7 on placebo). In the per-protocol analysis, we observed statistically and clinically significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ: emotional function (adjusted mean difference: 1.1; 95% confidence interval [CI]: 0.0 - 2.2) and mastery (difference: 1.1; CI: 0.4 - 1.8). Dyspnea and fatigue improved, but to an extent that did not reach statistical significance. In the intention-to-treat analysis, none of the differences in CRQ scores was significant. Paroxetine was not associated to any worsening of respiratory symptoms. CONCLUSIONS: The results of this small randomized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present. This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD.

Aged↗