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In the present study, we have tested the sera of sixty five diabetic patients treated with insulin, researching the action of some physiologic and therapeutic factors (sex, age, insulin dose and time of treatment), to production of anti-insulin antibodies. Our results have shown that an important percentage of diabetic patients treated by porcine insulin produce antibodies: 72% of studied patients, concerning chiefly all the women and patients under-fourty years old. However our results have not pointed out any relation between the administered insulin dose versus the anti-insulin antibodies production, in spite of the early production of these antibodies in a great part of the patients. 相似文献
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Mayada Achour Marc Mousli Mahmoud Alhosin Abdulkhaleg Ibrahim Jean Peluso Christian D. Muller Valérie B. Schini-Kerth Ali Hamiche Sirano Dhe-Paganon Christian Bronner 《Biochemical and biophysical research communications》2013,430(1):208-212
Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) contributes to silencing of tumor suppressor genes by recruiting DNA methyltransferase 1 (DNMT1) to their hemi-methylated promoters. Conversely, demethylation of these promoters has been ascribed to the natural anti-cancer drug, epigallocatechin-3-gallate (EGCG). The aim of the present study was to investigate whether the UHRF1/DNMT1 pair is an important target of EGCG action. Here, we show that EGCG down-regulates UHRF1 and DNMT1 expression in Jurkat cells, with subsequent up-regulation of p73 and p16INK4A genes. The down-regulation of UHRF1 is dependent upon the generation of reactive oxygen species by EGCG. Up-regulation of p16INK4A is strongly correlated with decreased promoter binding by UHRF1. UHRF1 over-expression counteracted EGCG-induced G1-arrested cells, apoptosis, and up-regulation of p16INK4A and p73. Mutants of the Set and Ring Associated (SRA) domain of UHRF1 were unable to down-regulate p16INK4A and p73, either in the presence or absence of EGCG. Our results show that down-regulation of UHRF1 is upstream to many cellular events, including G1 cell arrest, up-regulation of tumor suppressor genes and apoptosis. 相似文献
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Tim Schulte Jonas L?fling Cecilia Mikaelsson Alexey Kikhney Karina Hentrich Aurora Diamante Christine Ebel Staffan Normark Dmitri Svergun Birgitta Henriques-Normark Adnane Achour 《Open biology》2014,4(1)
Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187–385) determined to 2.0 Å resolution. BR187–385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10. 相似文献
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7C8 is a mouse monoclonal antibody specific for the third hypervariable region (V3) of the human immunodeficiency virus type 2 (HIV-2)-associated protein gp125. The three-dimensional crystal structure of the Fab fragment of 7C8, determined to 2.7 Å resolution, reveals a deep and narrow antigen-binding cleft with architecture appropriate for an elongated epitope. The highly hydrophobic cleft is bordered on one side by the negatively charged second complementarity determining region (CDR2) and the unusually long positively charged CDR3 of the heavy chain and, on the other side, by the CDR1 of the light chain. Analysis of 7C8 in complex with molecular models of monomeric and trimeric gp125 highlights the importance of a conserved stretch of residues FHSQ that is localized centrally on the V3 region of gp125. Furthermore, modeling also indicates that the Fab fragment neutralizes the virus by sterically impairing subsequent engagement of the gp125 trimer with the co-receptor on the target cell. 相似文献
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Michaëlsson J Achour A Rölle A Kärre K 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(12):7327-7334
NK cell recognition of targets is strongly affected by MHC class I specific receptors. The recently published structure of the inhibitory receptor Ly49A in complex with H-2Dd revealed two distinct sites of interaction in the crystal. One of these involves the alpha1, alpha2, alpha3, and beta2-microglobulin (beta2m) domains of the MHC class I complex. The data from the structure, together with discrepancies in earlier studies using MHC class I tetramers, prompted us to study the role of the beta2m subunit in MHC class I-Ly49 interactions. Here we provide, to our knowledge, the first direct evidence that residues in the beta2m subunit affect binding of MHC class I molecules to Ly49 receptors. A change from murine beta2m to human beta2m in three different MHC class I molecules, H-2Db, H-2Kb, and H-2Dd, resulted in a loss of binding to the receptors Ly49A and Ly49C. Analysis of the amino acids involved in the binding of Ly49A to H-2Dd in the published crystal structure, and differing between the mouse and the human beta2m, suggests the cluster formed by residues Lys3, Thr4, Thr28, and Gln29, as a potentially important domain for the Ly49A-H-2Dd interaction. Another possibility is that the change of beta2m indirectly affects the conformation of distal parts of the MHC class I molecule, including the alpha1 and alpha2 domains of the heavy chain. 相似文献
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Anis Raddaoui Alexandra S. Sim?es Rekaya Baaboura Sofia Félix Wafa Achour Tarek Ben Othman Mohamed Béjaoui Raquel Sá-Le?o Assia Ben Hassen 《PloS one》2015,10(10)
BackgroundPneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, antimicrobial resistance and clonality of Streptococcus pneumoniae isolated from neutropenic patients in Tunisia.MethodsFifty-nine S. pneumoniae were isolated from infection (n = 31) and colonization (n = 28) sites of patients (children and adults) attending the National Centre of Bone Marrow Transplantation in Tunis between 2005–2011. All isolates were characterized by serotype, antimicrobial resistance pattern and multilocus sequence typing (MLST).ResultsThe majority (66.1%) of the isolates belonged to five serotypes all included in PCVs: 6B, 9V, 14, 19F and 23F. The potential coverage of the 10-valent and 13-valent PCV was of 71.2% and 76.3% respectively. Resistance rates were very high and 69.5% of the isolates were multidrug resistant: non-susceptibility rates to penicillin, amoxicillin and cefotaxime were 66.1%, 40.7% and 27.1%, respectively; resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole, were 69.5%, 61.0%, 37.3%, 22.0% and 67.8%, respectively. The most frequent serotypes had STs characteristic of multidrug resistant international clones known to be highly successful and important causes of pneumococcal infection: Spain 23F-ST81, France 9V/14-ST156, Spain 6B-ST90, 19F-ST320, and Portugal 19F-ST177.ConclusionsThe majority of S. pneumoniae strains recovered from immunocompromised patients in Tunisia are representatives of multidrug resistant pandemic clones that express serotypes targeted by PCVs. To contain the burden of pneumococcal disease and improve treatment choices among Tunisian immunocompromised patients PCVs should be offered to all of them. 相似文献
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Sarcolectin (SCL) is a tissue growth factor found in various human or animal tissues, functioning in balance with interferons (IFNs) that can inhibit growth and affect cell differentiation. Like somatotropin, SCL is found in the pituitary gland. In humans, the SCL gene is located on chromosome 12 (q12-q13) and expressed as a 55 kDa protein consisting of 469 amino-acids. After a single activation of peripheral blood mononuclear cells (PBMC) obtained from more than 30 individuals, highly significant cell proliferation was found to peak after 7 days in culture. The presence of adherent cells was necessary for cell proliferation. SCL induced over-expression of alpha-IL-2 receptor (CD25) leading to proliferation of CD3+/CD4+/CD45RO+ T cells. Thus in PBMC, SCL induced CD4+ T cell growth and expression of inflammatory cytokine genes, including TNF-alpha, IL-1beta, IL-6 and IL-8. IFNs are also produced following activation as a feedback response which is maintained for about 20 days. 相似文献
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Thilo C Berglund P Applequist SE Yewdell JW Ljunggren HG Achour A 《The Journal of biological chemistry》2006,281(13):8950-8957
Human cytomegalovirus encodes several proteins that interfere with expression of major histocompatibility complex (MHC) class I molecules on the surface of infected cells. The unique short protein 2 (US2) binds to many MHC class I allomorphs in the endoplasmic reticulum, preventing cell surface expression of the class I molecule in question. The molecular interactions underlying US2 binding to MHC class I molecules and its allele specificity have not been fully clarified. In the present study, we first compared the sequences and the structures of US2 retained versus non-retained human leukocyte antigen (HLA) class I allomorphs to identify MHC residues of potential importance for US2 binding. On the basis of this analysis, 18 individual HLA-A2 mutants were generated and the ability of full-length US2 to bind wild-type and mutated HLA-A2 complexes was assessed. We demonstrate that Arg181 plays a critical role in US2-mediated inhibition of HLA-A2 cell surface expression. The structural comparison of all known crystal structures of HLA-A2 either alone, or in complex with T cell receptor or the CD8 co-receptor, indicates that binding of US2 to HLA-A2 results in a unique, large conformational change of the side chain of Arg181. However, although the presence of Arg181 seems to be a prerequisite for US2 binding to HLA-A2, it is not sufficient for binding to all MHC class I alleles. 相似文献