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Concolino P Mello E Patrosso MC Penco S Zuppi C Capoluongo E 《Metabolism: clinical and experimental》2012,61(4):519-524
More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21-hydroxylase gene (CYP21A2) mutations. The CYP21A2 gene is located in the human leukocyte antigen (HLA) class III region on the short arm of chromosome 6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98% homologous in its coding sequence with CYP21A2. Most CYP21A2 mutations result from intergenic recombinations between CYP21A2 and the closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for only 5% to 10% of 21-hydroxylase deficiency alleles. However, detection of these rare and spontaneous mutations has continued to expand worldwide. We identified 2 novel CYP21A2 missense mutations (p.H282N and p.Y191H) in 2 Italian patients with simple-virilizing and nonclassic CAH forms. Functional analysis of these CYP21A2 mutations was performed. Functional in vitro assay for mutagenized CYP21A2 enzymes was performed in transiently transfected mammalian cells to test the residual enzyme activity and the apparent kinetic values. The residual activities obtained allowed us to classify the p.H282N and p.Y191H variants as simple-virilizing and nonclassic CAH associated mutations, respectively. These results correlate with the rate of severity of the patients' disease. This finding provides a further contribution for assisting in the diagnosis of CAH patients. 相似文献
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Wang F Kohan AB Kindel TL Corbin KL Nunemaker CS Obici S Woods SC Davidson WS Tso P 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(24):9641-9646
Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca(2+) influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV(-/-) mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV(-/-) mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes. 相似文献
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Paranhos LR Benedicto EN Nunes MF Kairalla SA Siqueira DF Torres FC 《International journal of orthodontics (Milwaukee, Wis.)》2012,23(1):31-37
The aim of this study was to analyze a possible correlation of different cephalometric measurements to define facial type and to evaluate the best measurement for diagnosis. The sample consisted of 95 lateral cephalograms of caucasian patients with normal occlusion, aged between 15 years and two months and 21 years and four months, of which 54 were male and 41 female. The facial types were divided into dolichofacial, mesofacial and brachyfacial, according to the standards stated by different authors, and a relationship among them was investigated using the Kappa and Total agreement methods. The highest agreement found was between FMA and SN.GoGn; the lowest was between SN. Gn and VERT index. According to literature review and the interpretation of the results, SN.GoGn appears to be the best measurement to define facial type. 相似文献
86.
Vanessa Galli Simone Simionatto Silvana Beutinger Marchioro Gustavo Henrique Ferrero Klabunde Fabricio Rochedo Concei??o Odir Ant?nio Dellagostin 《Clinical and Vaccine Immunology : CVI》2013,20(9):1370-1376
Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (EP), which is a respiratory disease responsible for huge economic losses in the pig industry worldwide. The commercially available vaccines provide only partial protection and are expensive. Thus, the development of alternatives for the prophylaxis of EP is critical for improving pig health. The use of multiple antigens in the same immunization may represent a promising alternative. In the present study, seven secreted proteins of M. hyopneumoniae were cloned, expressed in Escherichia coli, and evaluated for antigenicity using serum from naturally and experimentally infected pigs. In addition, the immunogenicity of the seven recombinant proteins delivered individually or in protein cocktail vaccines was evaluated in mice. In Western blot assays and enzyme-linked immunosorbent assays, most of the recombinant proteins evaluated were recognized by convalescent-phase serum from the animals, indicating that they are expressed during the infectious process. The recombinant proteins were also immunogenic, and most induced a mixed IgG1/IgG2a humoral immune response. The use of these proteins in a cocktail vaccine formulation enhanced the immune response compared to their use as antigens delivered individually, providing evidence of the efficacy of the multiple-antigen administration strategy for the induction of an immune response against M. hyopneumoniae. 相似文献
87.
Simone Baldovino Davide Montin Silvana Martino Savino Sciascia Elisa Menegatti Dario Roccatello 《Autoimmunity reviews》2013,12(8):796-801
Common variable immunodeficiency is a collection of diseases characterized by primary hypogammaglobulinemia. The causes of CVID are extremely heterogeneous and may affect virtually every pathway linked to B cell development and function. Clinical manifestations of CVID mainly include recurrent bacterial infections, but autoimmune, gastrointestinal, lymphoproliferative, granulomatous, and malignant disorders have also been frequently reported as associated conditions. We aimed to focus on the state of the art of the relationship between infections, inflammation and autoimmunity in CVID. 相似文献
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Juliana Marotti Pedro Tortamano Silvana Cai Martha Simões Ribeiro João Eduardo Miranda Franco Tomie Toyota de Campos 《Lasers in medical science》2013,28(1):303-309
Several implant surface debridement methods have been reported for the treatment of peri-implantitis, however, some of them can damage the implant surface or promote bacterial resistance. Photodynamic therapy (PDT) is a new treatment option for peri-implantitis. The aim of this in vitro study was to analyze implant surface decontamination by means of PDT. Sixty implants were equally distributed (n?=?10) into four groups and two subgroups. In group G1 there was no decontamination, while in G2 decontamination was performed with chlorhexidine. G3 (PDT???laser?+?dye) and G4 (laser, without dye) were divided into two subgroups each; with PDT performed for 3 min in G3a and G4a, and for 5 min in G3b and G4b. After 5 min in contact with methylene blue dye (G3), the implants were irradiated (G3 and G4) with a low-level laser (GaAlAs, 660 nm, 30 mW) for 3 or 5 min (7.2 and 12 J). After the dilutions, culture media were kept in an anaerobic atmosphere for 1 week, and then colony forming units were counted. There was a significant difference (p?<?0.001) between G1 and the other groups, and between G4 in comparison with G2 and G3. Better decontamination was obtained in G2 and G3, with no statistically significant difference between them. The results of this study suggest that photodynamic therapy can be considered an efficient method for reducing bacteria on implant surfaces, whereas laser irradiation without dye was less efficient than PDT. 相似文献