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1.
Pfisterer Matthias; Kaiser Christoph; Brunner-La-Rocca Hanspeter 《European heart journal》2007,28(15):1913
We thank Agostini Pierfranco and colleagues for their interestin our analysis of the 相似文献
2.
Hinney A Antwerpen B Geller F Schäfer H Siegfried W Goldschmidt H Remschmidt H Ziegler A Hebebrand J 《Molecular genetics and metabolism》2002,76(2):152-156
In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association. 相似文献
3.
Illes Z Stern JN Keskin DB Reddy J Brosnan CF Waldner H Santambrogio L Kuchroo VK Strominger JL 《European journal of immunology》2005,35(12):3683-3693
The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-gamma, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length gammabeta and alphabeta subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVbeta2+ MPB85-99-specific transgenic and hVbeta2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVbeta2- endogenous T cells. 相似文献
4.
Kathrin Mühlemann Christine Franzini Christoph Aebi Christoph Berger David Nadal Jody St?helin Hanspeter Gnehm Klara Posfay-Barbe Alain Gervaix Hugo Sax Ulrich Heininger Jan Bonhoeffer Gerhard Eich Christian Kind Christiane Petignat Pietro Scalfaro 《Infection control and hospital epidemiology》2004,25(9):765-771
OBJECTIVE: To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. DESIGN: Prevalence survey and evaluation of a new comorbidity index. SETTING: Seven Swiss pediatric hospitals. PATIENTS: Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. RESULTS: Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS: This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospitals. 相似文献
5.
Christine Zimmermann Marlies Rawiel Claudine Blaser Martina Kaufmann Hanspeter Pircher 《European journal of immunology》1996,26(12):2903-2910
The role of Fas in the homeostatic regulation of CD8+ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) αβ transgenes specific for the LCMV glycoprotein peptide aa 33–41 in the context of H-2Db were used. Five main results emerged: first, development of lymphadenopathy and of CD4−CD8− double-negative B220+ T cells in lpr mice was not inhibited by the αβ TCR transgenes; second, tolerance induction and peripheral deletion of CD8+ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8+ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8+ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4−CD8− double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8+ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas. 相似文献
6.
Feeding myelin oligodendrocyte glycoprotein (MOG) followed by immunization results in induction of oral tolerance evidenced by the amelioration of experimental autoimmune encephalomyelitis (EAE). Oral tolerization is characterized by the suppression of Th1 responses and up-regulation of Th2 responses and TGF-beta. To identify the costimulatory molecules and cell types involved in cytokine-mediated suppression we examined wild type mice and mice deficient for either CD86 (CD86-/-) or B cells (muMT). Oral tolerance was found in CD86-/- mice evidenced by amelioration of disease severity, decreased proliferative responses and IFN-gamma production and increased IL-4. TGF-beta was not up-regulated in CD86-/- or muMT mice but was increased in wild type mice. Analysis of the gut associated lymphoid tissue (GALT) of different mouse strains (C57BL/6 and PLJxSJL F1) fed distinct myelin antigens (MOG and myelin basic protein, MBP) showed that TGF-beta was increased in wild type mice of both strains by 3 days post-immunization and further increased with time. In contrast, no up-regulation of TGF-beta was found in the GALT of CD86-/- or muMT mice. These results demonstrate that CD86 is not required for oral tolerization and that both CD86 and B cells are important for the up-regulation of TGF-beta following oral antigen. 相似文献
7.
Wai-Ping Fung-Leung Valerie A. Wallace Dawn Gray William C. Sha Hanspeter Pircher Hung-Sia Teh Dennis Y. Loh Tak W. Mak 《European journal of immunology》1993,23(1):212-216
During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8+ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule. 相似文献
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