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30 results on '"Mari, Rosella"'

3. Coagulation factor XII levels and intrinsic thrombin generation in multiple sclerosis

Author

Ziliotto, N, Baroni, M, Straudi, S, Manfredini, F, Mari, R, Menegatti, E, Voltan, R, Secchiero, P, Zamboni, P, Basaglia, N, Marchetti, G, Bernardi, F, Ziliotto, Nicole, Baroni, Marcello, Straudi, Sofia, Manfredini, Fabio, Mari, Rosella, Menegatti, Erica, Voltan, Rebecca, Secchiero, Paola, Zamboni, Paolo, Basaglia, Nino, Marchetti, Giovanna, Bernardi, Francesco, Ziliotto, N, Baroni, M, Straudi, S, Manfredini, F, Mari, R, Menegatti, E, Voltan, R, Secchiero, P, Zamboni, P, Basaglia, N, Marchetti, G, Bernardi, F, Ziliotto, Nicole, Baroni, Marcello, Straudi, Sofia, Manfredini, Fabio, Mari, Rosella, Menegatti, Erica, Voltan, Rebecca, Secchiero, Paola, Zamboni, Paolo, Basaglia, Nino, Marchetti, Giovanna, and Bernardi, Francesco

Abstract

Background: Factor XII (FXII) activation initiates the intrinsic (contact) coagulation pathway. It has been recently suggested that FXII could act as an autoimmunity mediator in multiple sclerosis (MS). FXII depositions nearby dentritic cells were detected in the central nervous system of MS patients and increased FXII activity has been reported in plasma of relapsing remitting and secondary progressive MS patients. FXII inhibition has been proposed to treat MS. Objective: To investigate in MS patients multiple FXII-related variables, including the circulating amount of protein, its pro-coagulant function, and their variation over time. To explore kinetic activation features of FXII in thrombin generation (TG). Methods: In plasma from 74 MS patients and 49 healthy subjects (HS), FXII procoagulant activity (FXII:c) and FXII protein (FXII:Ag) levels were assessed. Their ratio (FXII:ratio) values were derived. Intrinsic TG was evaluated by different triggers. Results: Higher FXII:Ag levels (p = 0.003) and lower FXII:ratio (p < 0.001) were detected in MS patients compared with HS. FXII variables were highly correlated over four time points, which supports investigation of FXII contribution to disease phenotype and progression. A significant difference over time was detected for FXII:c (p = 0.031). In patients selected for the lowest FXII:ratio, TG triggered by ellagic acid showed a trend in lower endogenous thrombin potential (ETP) in MS patients compared with HS (p = 0.042). Intrinsic triggering of TG by nucleic acid addition produced longer time parameters in patients than in HS and substantially increased ETP in MS patients (p = 0.004) and TG peak height in HS (p = 0.008). Coherently, lower FXII:ratio and longer lag time (p = 0.02) and time to peak (p = 0.007) point out a reduced response of FXII to activation in part of MS patients. Conclusion: In MS patients, factor-specific and modified global assays suggest the presence of increased FXII protein level and reduced

Published
2018

11. Factor XIII-A dynamics in acute myocardial infarction: a novel prognostic biomarker?

Author

Zeri, Giulia, primary, Orioli, Elisa, primary, Mari, Rosella, primary, Moratelli, Stefano, primary, Vigliano, Marco, primary, Marchesini, Jlenia, primary, Grossi, Maria Elena, primary, Pecoraro, Alessandro, primary, Cuneo, Antonio, primary, Ferrari, Roberto, primary, Pinotti, Mirko, primary, Serino, Luisa M., primary, Ansani, Lucia, primary, and Gemmati, Donato, additional

Published
2015
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21. Thrombotic risk in thalassemic patients

Author

Moratelli, S, DE SANCTIS, Vincenzo, Gemmati, Donato, Serino, Maria Luisa, Mari, Rosella, Gamberini, Mr, and Scapoli, Gian Luigi

Published
1998

29. An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing Multiple Human FIX Splicing Mutants.

Author

Balestra D, Scalet D, Pagani F, Rogalska ME, Mari R, Bernardi F, and Pinotti M

Abstract

In cellular models we have demonstrated that a unique U1snRNA targeting an intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1) can rescue multiple exon-skipping mutations, a relevant cause of genetic disease. Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B-causing mutations at the 5' (c.519A > G) or 3' (c.392-8T > G) splice sites of F9 exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt and mutant (hFIX-2G 5'ss and hFIX-8G 3'ss ) splicing-competent human factor IX (hFIX) cassettes resulted in the expression of hFIX transcripts lacking exon 5 in liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt context. This resulted in appreciable circulating hFIX levels (mean ± SD; hFIX-2G5'ss, 1.0 ± 0.5 µg/ml; hFIX-8G3'ss, 1.2 ± 0.3 µg/ml; and hFIXwt, 1.9 ± 0.6 µg/ml), leading to a striking shortening (from ~100 seconds of untreated mice to ~80 seconds) of FIX-dependent coagulation times, indicating a hFIX with normal specific activity. This is the first proof-of-concept in vivo that a unique ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping variants, which extends the applicability of ExSpeU1s to panels of mutations and thus cohort of patients.

Published
2016
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30. Natural and engineered carboxy-terminal variants: decreased secretion and gain-of-function result in asymptomatic coagulation factor VII deficiency.

Author

Branchini A, Rizzotto L, Mariani G, Napolitano M, Lapecorella M, Giansily-Blaizot M, Mari R, Canella A, Pinotti M, and Bernardi F

Subjects
Animals, Cattle, Child, Enzyme-Linked Immunosorbent Assay, Female, Heterozygote, Homozygote, Humans, Male, Middle Aged, Mutagenesis, Site-Directed, Prothrombin Time, Rabbits, Thromboplastin metabolism, Blood Coagulation genetics, Codon, Nonsense genetics, Factor VII genetics, Factor VII metabolism, Factor VII Deficiency genetics, Factor VII Deficiency metabolism
Abstract

We report 2 asymptomatic homozygotes for the nonsense p.R462X mutation affecting the carboxy-terminus of coagulation factor VII (FVII, 466 aminoacids). FVII levels of 3-5% and 2.7 ± 0.4% were found in prothrombin time-based and activated factor X (FXa) generation assays with human thromboplastins. Noticeably, FVII antigen levels were barely detectable (0.7 ± 0.2%) which suggested a gain-of-function effect. This effect was more pronounced with bovine thromboplastin (4.8 ± 0.9%) and disappeared with rabbit thromboplastin (0.7 ± 0.2%). This suggests that the mutation influences tissue factor/FVII interactions. Whereas the recombinant rFVII-462X variant confirmed an increase in specific activity (~400%), a panel of nonsense (p.P466X, p.F465X, p.P464X, p.A463X) and missense (p.R462A, p.R462Q, p.R462W) mutations of the FVII carboxy-terminus resulted in reduced secretion but normal specific activity. These data provide evidence for counteracting pleiotropic effects of the p.R462X mutation, which explains the asymptomatic FVII deficiency, and contributes to our understanding of the role of the highly variable carboxy-terminus of coagulation serine proteases.

Published
2012
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