排序方式: 共有37条查询结果,搜索用时 31 毫秒
1.
Roberto Cilia MD Sara Tunesi PhD Giorgio Marotta MD Emanuele Cereda MD Chiara Siri PsyD Silvana Tesei MD Anna L. Zecchinelli MD Margherita Canesi MD Claudio B. Mariani MD Nicoletta Meucci MD Giorgio Sacilotto MD Michela Zini MD Michela Barichella MD Corrado Magnani MD Stefano Duga PhD Rosanna Asselta PhD Giulia Soldà PhD Agostino Seresini BSc Manuela Seia BSc Gianni Pezzoli MD Stefano Goldwurm MD PhD 《Annals of neurology》2016,80(5):662-673
2.
Degiorgio D Colombo C Seia M Porcaro L Costantino L Zazzeron L Bordo D Coviello DA 《European journal of human genetics : EJHG》2007,15(12):1230-1238
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal-recessive disorder due to mutations in the ATP-binding cassette, subfamily B, member 4 gene (ABCB4). ABCB4 is the liver-specific membrane transporter of phosphatidylcholine, a major and exclusive component of mammalian bile. The disease is characterized by early onset of cholestasis with high serum gamma-glutamyltranspeptidase activity, which progresses into cirrhosis and liver failure before adulthood. Presently, about 20 distinct ABCB4 mutations associated to PFIC3 have been described. We report the molecular characterization of 68 PFIC3 index cases enrolled in a multicenter study, which represents the largest cohort of PFIC3 patients screened for ABCB4 mutations to date. We observed 31 mutated ABCB4 alleles in 18 index cases with 29 distinct mutations, 25 of which are novel. Despite the lack of structural information on the ABCB4 protein, the elucidation of the three-dimensional structure of bacterial homolog allows the three-dimensional model of ABCB4 to be built by homology modeling and the position of the mutated amino-acids in the protein tertiary structure to be located. In a significant fraction of the cases reported in this study, the mutation should result in substantial impairment of ABCB4 floppase activity. The results of this study provide evidence of the broad allelic heterogeneity of the disease, with causative mutations spread along 14 of the 27 coding exons, but with higher prevalence on exon 17 that, as recently shown for the closely related paralogous ABCB1 gene, could contain an evolutionary marker for mammalian ABCB4 genes in the seventh transmembrane segment. 相似文献
3.
4.
5.
6.
7.
M. Grassi F. Capello L. Bertolino Z. Seia M. Pippione 《Clinical and experimental dermatology》2009,34(8):910-914
Background. Lupus erythematosus (LE) and dermatomyositis (DM) are interface dermatitis, histologically characterized by formation of colloid bodies and a CD4+ CD8+ lymphocyte infiltrate. Colloid bodies are examples of intraepidermal apoptosis. Granzyme (Gr)B, synthesized by activated cytotoxic lymphocytes, is a serine protease able to prime apoptosis. GrB+ lymphocytes have been previously found in infiltrates in skin lesions from other types of interface dermatitis. Aim. To evaluate, on histological skin specimens from patients with LE and DM, GrB expression as a mediator of keratinocyte apoptosis in lymphocyte infiltrate. Methods. In total, 22 patients with cutaneous LE [9 with discoid lupus erythematosus (DLE), 9 with subacute lupus erythematosus (SCLE) and 4 with systemic lupus erythematosus (SLE)] and 20 patients with DM were studied. Skin specimens underwent immunohistochemical staining with antibodies to CD3, CD4, CD8 and GrB. Results. Immunohistochemical study with GrB was positive in 17 of the 22 patients with LE but only 2 of the 20 patients with DM. In LE, in systemic and subacute forms of LE, the median obtained was < 10 (+) whereas in the chronic forms, the median was 10–50% (++). Patients with DM were negative for GrB. Conclusions. In LE, a correlation between GrB+ lymphocyte and the presence of DLE form was found, but in DM, GrB is poorly expressed. GrB labels a subpopulation of effector cells involved in ongoing cytotoxic action and should be considered as a specific marker showing the extent of the direct local cytotoxic damage. GrB could play a role in the induction of skin apoptosis mechanisms in LE. 相似文献
8.
9.
10.