The GRMD dog (Golden Retriever Muscular Dystrophy) is the best clinically relevant DMD animal model. In the present study we evaluated some newly identified circulating miRNA biomarkers for muscular ...dystrophy in the GRMD model. Additionally we screened systematically for new candidate circulating miRNA biomarkers. We confirmed the dysregulation of the previously described dystromiRs, miR-1, miR-133 miR-206 and miR-378, and identified a new candidate miRNA that might be classified in the same dystromiR group. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy. The first are miRNAs associated with cardiac pathology. The second are miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region. Finally we have confirmed a dysregulation of the miRNAs associated with cardiac pathology also in a small cohort of DMD patients. Given the strong interspecies conservation of miRNAs and our preliminary data in DMD patients, these newly identified dysregulated miRNAs in GRMD are strong candidate biomarkers for DMD.
Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD ...animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.
Gene transfer into hCD34+ hematopoietic stem/progenitor cells (HSCs) using human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) has several promising therapeutic applications. ...Yet, efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist such as fibronectin fragments and cationic compounds, but all present limitations. In this study, we describe a new transduction enhancer called Vectofusin-1, which is a short cationic peptide, active on several LV pseudotypes. Vectofusin-1 is used as a soluble additive to safely increase the frequency of transduced HSCs and to augment the level of transduction to one or two copies of vector per cell in a vector dose-dependent manner. Vectofusin-1 acts at the entry step by promoting the adhesion and the fusion between viral and cellular membranes. Vectofusin-1 is therefore a promising additive that could significantly ameliorate hCD34+ cell-based gene therapy.
A total of 188 acne patients (113 male and 75 female) with a mean age of 25 years (range 15-42 years) were treated with isotretinoin in doses ranging from 0.5 to 1 mg/kg. The study lasted 9 years. ...The treatment was not terminated until 2 months after total healing. The patients were then re-examined at regular intervals. In the event of a recurrence greater than grade 2 (pre-nodular threshold grade), they underwent a new course of treatment. At the end of the study, three groups were distinguished: (1) immediate, long-term, stable remissions following one single course of isotretinoin (111 patients with an average follow-up period of 27 months); (2) stable remissions following 2 or 3 courses of isotretinoin (54 patients with an average follow-up period of 16 months); (3) immediate partial remissions or partial remissions following several courses of treatment in 23 patients who continued to present with at least grade 3 acne. There was no significant statistical difference between the first two groups with respect to the age and sex of the patients and the grade and prior duration of the acne. The third group differed from the other two in having a greater proportion of patients with microcystic acne (p < 0.05) and women with endocrinological problems ((p < 0.001).
Using a low temperature scanning tunneling microscope (STM) we have imaged isolated O-related features on the unreconstructed surface between (2x1)-O regions on Cu{110}. On the assumption that these ...are individual O atoms, they appear to occupy mostly hollow sites in the troughs. We suggest that such adatoms constitute an active form of O known to participate readily in deprotonation reactions on copper surfaces.
Using a low temperature scanning tunneling microscope (STM) we have imaged isolated oxygen-related features on the unreconstructed surface between (2 × 1)-O regions on Cu{110}. On the assumption that ...these are individual oxygen atoms, they appear to occupy mostly hollow sites in the troughs. We suggest that such adatoms constitute an active form of oxygen known to participate readily in deprotonation reactions on copper surfaces.
Bullous drug eruption caused by Introna Andry, P; Weber-Buisset, M J; Fraitag, S ...
Annales de dermatologie et de vénéréologie,
1993, Letnik:
120, Številka:
11
Journal Article
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