Influenza in Canada--1998-1999 season.
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Biomedical subjects
Publications and source records attributed to L Pelletier.
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Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. The genetic loci that contribute to mononuclear cell infiltration of the central nervous system and clinical manifestations of EAE in the rat were investigated in the F2 progeny of the highly susceptible Lewis and resistant Brown Norway strains. The data confirmed that the Lewis allele of a MHC-linked gene is necessary, but not sufficient, to confer EAE susceptibility in the F2 progeny. Subsequent analyses were thus restricted to the subset of the F2 animals with EAE-predisposing MHC genotypes. A genome-wide scan approach was performed using 103 microsatellite markers covering 85% of the genome. Two non-MHC regions were identified, one near the centromere of chromosome 4 and the other on the long arm of chromosome 10, that significantly contributed to the disease. In addition, three regions on chromosomes 9, 13, and 17 were suggestive for linkage. Congenic mapping is now needed to reduce the support intervals encoding the loci of interest to sizes amenable to physical mapping and to eventually demonstrate the involvement of some of the candidate genes of immunologic importance localized in these regions.
The authors report the case of a 9-month-old infant presenting with obstructive jaundice. Preoperative investigation findings showed distension of the extrahepatic biliary tract. Urine analysis result was positive for cytomegalovirus. At laparotomy, a 1-cm round mass was found within the head of the pancreas, near its upper border and in the course of the common bile duct. Findings on frozen sections could not rule out a malignant process and an hepaticoduodenostomy was constructed. Final diagnosis was juvenile xanthogranuloma. An association between cytomegalovirus and juvenile xanthogranuloma has been reported previously in the literature.
The main purpose of this study was to compare psychological and social problems among chronically ill school-aged children to those observed in a group of healthy children of the same age. On the basis of the data collected, it was also possible to compare self-perception and social functioning problems between the 2 groups of children, as well as to identify the contributing factors explaining the observed differences in psychosocial adaptation between these 2 groups. Three measures were used to assess psychological and social problems. Mental health problems were measured by the Dominique (Valla, Bergeron, Bérubé, Gaudet, & Saint-Georges, 1994). Self-Perception and Social Functioning were assessed by the Self-Perception Profile (Harter, 1985) and the Rating Scale of Child's Actual Behavior (Harter, 1985). Information on characteristics of the child and his or her family was also collected. Sixty children aged 6 to 11 and diagnosed as having juvenile diabetes or asthma, 59 control children, and the children's parents participated in this study. A chi-square test and multivariate analysis of variance were used to compare the 2 groups of children. Results indicate that children with diabetes and asthma do not present more psychological and social problems than other children of the same age. Results also suggest that age is the only variable indicating a higher proportion of mental health problems among chronically ill children. Results are discussed and compared to those of previous studies from which the conceptual frame-work of this study was developed.
Transcription factors belonging to the nuclear factor of activated T cells (NFAT) family regulate the expression of cytokine genes and other inducible genes during the immune response. The functions of NFAT proteins are directly controlled by the calcium- and calmodulin-dependent phosphatase calcineurin. Here we show that the binding of calcineurin to NFAT is substantially increased when calcineurin is activated with calmodulin and calcium. FK506.FKBP12 drug-immunophilin complexes inhibited the interaction of NFAT with activated calcineurin much more effectively than they inhibited the interaction with inactive calcineurin, suggesting that part of the interaction with activated calcineurin involved the enzyme active site. We have previously shown that NFAT is targeted to inactive calcineurin at a region distinct from the calcineurin active site (Aramburu, J., Garcia-Cozar, F. J., Raghavan, A., Okamura, H., Rao, A., and Hogan, P. G. (1998) Mol. Cell 1, 627-637); this region is also involved in NFAT binding to activated calcineurin, since binding is inhibited by an NFAT peptide spanning the calcineurin docking site on NFAT. The interacting surfaces are located on the catalytic domain of the calcineurin A chain and on an 86-amino acid fragment of the NFAT regulatory domain. NFAT binding to the calcineurin catalytic domain was inhibited by the calcineurin autoinhibitory domain and the RII substrate peptide, which bind in the calcineurin active site, as well as by the NFAT docking site peptide, which binds to a region of calcineurin distinct from the active site. We propose that, in resting cells, NFAT is targeted to a region of the calcineurin catalytic domain that does not overlap the calcineurin active site. Upon cell activation, displacement of the autoinhibitory domain by calmodulin binding allows NFAT to bind additionally to the calcineurin active site, thus positioning NFAT for immediate dephosphorylation at functional phosphoserine residues.
A range of vaccination policy options for improving the control of measles in Canada is investigated using a mathematical model to simulate transmission of the disease. Results suggest that a catch up campaign giving a second dose of vaccine to children aged up to 18 years would have an immediate impact on transmission, which could be maintained by the introduction of a routine second dose at either 18 months or 5 years of age. Introducing a routine second dose of vaccine without a catch up campaign would allow continued endemic transmission of measles among older children for at least 10-15 years.
BACKGROUND: Several studies have suggested that measuring interstitial pH and pO2, may be useful to monitor ischemia throughout cardioplegic arrest during cardiac surgery. METHODS: To evaluate the levels of myocardial tissue pH and pO2 that correlate with significant ischemia, 7 dogs underwent cold blood cardioplegic arrest and subsequent incremental episodes of 5, 10, 20 and 40 min of ischemia interrupted by cardioplegic infusion over 10-min periods. RESULTS: Myocardial tissue pH and pO2 were monitored with probes implanted in the anterior and lateral walls of the left ventricle. The release of CK, troponine T and lactate was measured before and after each episode of ischemic arrest. Tissue pH decreased from 7.08+/-0.15 to 7.03+/-0.15 (p>0.05), 7.21+/-0.15 to 7.07+/-0.11 (p>0.05), 7.17+/-0.15 to 6.82+/-0.14 (p<0.05) and 7.0+/-0.18 to 6.63+/-0.08 (p<0.05) after 5, 10, 20 and 40 min of ischemic arrest. Tissue pO2 decreased from 74+/-10 to 38+/-11 mmHg (p<0.05), 83+/-16 to 18+/-4 mmHg (p<0.05), 9+/-22 to 14+/-5 mmHg (p<0.05) and 64+/-24 to 16+/-10 mmHg (p<0.05) after 5, 10, 20 and 40 min of ischemic arrest. CK, troponine T and lactate serum levels increased significantly only following 40 min of ischemic arrest. Myocardial temperature decreased to an average minimum of 14+/-1 degrees C during cardioplegic infusion. CONCLUSIONS: A myocardial tissue pH lower than 7.04 (90% CI, upper limit of 6.82+/-0.14) and a tissue pO2 lower than 22 mmHg (90% CI, upper limit of 14+/-5 mmHg) correlate with anaerobic metabolism and myocardial ischemia during cold cardioplegic arrest.
Mercuric chloride (HgCl2) induces T helper 2 (Th2) autoreactive anti-class II T cells in Brown Norway rats. These cells produce interleukin (IL)-4 and induce a B cell polyclonal activation that is responsible for autoimmune disease. In Brown Norway rats, HgCl2 triggers early IL-4 mRNA expression both in vivo and in vitro by T cells, which may explain why autoreactive anti-class II T cells acquire a Th2 phenotype. The aim of this study was to explore the transduction pathways by which this chemical operates. By using two murine T cell hybridomas that express IL-4 mRNA upon stimulation with HgCl2, we demonstrate that: 1) HgCl2 acts at the transcriptional level without requiring de novo protein synthesis; 2) HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels; 3) calcium/calcineurin-dependent pathway and protein kinase C activation are both implicated in HgCl2-induced IL-4 gene expression; and 4) HgCl2 can activate directly protein kinase C, which might be one of the main intracellular target for HgCl2. These data are in agreement with an effect of HgCl2 which is independent of antigen-specific recognition. It may explain the T cell polyclonal activation in the mercury model and the expansion of pathogenic autoreactive anti-class II Th2 cells in this context.
Autoreactive anti-MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW x BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-gamma and TGF-beta, and the protective effect is TGF-beta dependent since protection is abrogated by anti-TGF-beta treatment. These results identify regulatory, TGF-beta-producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.
It is now currently thought that Th1 autoreactive cells may induce organ specific autoimmune disease and in these situations Th2 cells are considered as regulatory cells. However, in other situations Th2 cells may be pathogenic. Thus, some chemicals (HgCl2, gold salts or D-penicillamine) may induce Th2-mediated systemic autoimmune disorders in susceptible Brown-Norway (BN) rats. In contrast, HgCl2 induces non antigen specific immunosuppression in Lewis (LEW) rats and protects this strain against organ-specific autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). Anti-self MHC class II T cells have been detected in both susceptible and resistant strains upon exposure with these chemicals. Autoreactive T cell lines that recognize self MHC class II molecules have been derived from gold salt-injected BN rats (BNAu lines) and from HgCl2-injected LEW rats (LEWHg lines). BNAu T cell lines produced IL-4 and transferred antibody-mediated autoimmunity in BN rats deprived of CD8+ cells. In contrast, HgCl2 protects susceptible rats from Th1-mediated autoimmunity, (autoimmune uveoretinitis). LEWHg lines produced IL-2, IFN-gamma and TGF-beta and were able to protect LEW rats against cell-mediated autoimmunity (EAE) and (LEW x BN)F1 hybrids from antibody-mediated, HgCl2-induced autoimmunity. Several points will be discussed: the specificity of these autoreactive T cells, the mechanisms by which chemicals may induce these cells and the mechanisms by which the immune system maintains or reestablishes self tolerance in rats exposed to these agents.
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Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a polyclonal B cell activation that was suspected to be due to the emergence of anti-self major histocompatibility complex (MHC) class II T cells. In the present study, six anti-self MHC class II T cell lines have been derived from six gold salt-treated rats by repeated stimulations with normal syngeneic MHC class II-bearing cells. The T cell lines proliferated in the presence of self MHC class II-positive B cell-enriched or B cell-depleted cells and the proliferation was inhibited by preincubating stimulator cells with an anti-IA monoclonal antibody. The T cell lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-gamma and could, therefore, be considered as T helper type 2 (Th2) and Th0 cells, respectively. They triggered normal syngeneic B cells to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti-DNA and anti-laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti-laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear cell infiltration. An anti-ovalbumin T cell line that produced IL-4 and low amounts of IFN-gamma was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 cell lines to induce antibody-mediated autoimmunity. They also show that CD8+ cells play a crucial role in the control of such autoreactive cells. Finally, this work suggests that Th2 cells could initiate cell-mediated reactions either directly or indirectly.
In-Ceram material is a relatively new all-ceramic restorative material with improved properties that require research. The clinical selection of restorative materials is based on a number of parameters such as esthetics, fit, and strength. This study determined the flexural strength of In-Ceram system components and compared the core material with conventional feldspathic ceramics and with Dicor all-ceramic restorative material. Four-point flexural strength values of bend bars of each ceramic were 18.39 +/- 5.00 MPa for In-Ceram sintered alumina, 76.53 +/- 15.23 MPa for In-Ceram infusion glass, and 236.15 +/- 21.94 MPa for In-Ceram infused alumina core. Flexural strength of self-glazed feldspathic porcelain was 69.74 +/- 5.47 MPa, as-cast Dicor ceramic 71.48 +/- 7.17 MPa, and polished Dicor ceramic was 107.78 +/- 8.45 MPa.
Using data from the Survey of Old Age Security and Canadian Pension Plan Retirement Recipients conducted by Health and Welfare Canada in 1987, this article estimates the relationship between sociodemographic characteristics and institutionalization of elderly persons in Canada. Region of residence was introduced in our model as a proxy for system effects. Logistic regression showed that age, marital status, health, family income, and region of residence all have a significant effect on institutionalization. We look at policies specific to different provinces to elaborate some hypotheses on how they affect the likelihood of residing in an institution. When trying to estimate the future needs and costs of institutional housing, this study shows the importance of considering not only the number of persons aged 65 years and over, but also expected changes in their sociodemographic characteristics and in the policies concerning long-term care services.
BACKGROUND: Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulonephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulopathy and vascular granular Ig deposits. Lewis (LEW) rats are resistant. METHODS: The genetic requirements governing the appearance of these manifestations were studied in congenic rats, and in F1 hybrids injected with ATPS. RESULTS: Non-MHC-linked genes from the BN strain were absolutely required for all the traits to be observed. The RT1n (BN) or RT1(1) (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT1(1) alleles were associated with the highest response. However, granular Ig deposits were only observed in RT1n rats. The high serum IgE concentration and the antilaminin Ab level were associated with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits. CONCLUSIONS: This study shows that susceptibility to ATPS was mainly dependent upon non-MHC-linked BN genes and that the involvement of MHC-linked genes differed depending upon the character considered. There is an epistatic effect between the various genes.
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