Search

Your search keyword '"Guglielmone, Hugo"' showing total 27 results
Start Over Author "Guglielmone, Hugo"
27 results on '"Guglielmone, Hugo"'

1. Identification and characterization of novel mutations implicated in congenital fibrinogen disorders

Author

Smith, Natalie, Bornikova, Larissa, Noetzli, Leila, Guglielmone, Hugo, Minoldo, Salvador, Backos, Donald S, Jacobson, Linda, Thornburg, Courtney D, Escobar, Miguel, White‐Adams, Tara C, Wolberg, Alisa S, Manco‐Johnson, Marilyn, and Di Paola, Jorge

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Hematology, Genetic Testing, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, afibrinogenemia, dysfibrinogenemia, fibrinogen disorders, fibrinogen mutations, molecular modeling, Cardiovascular medicine and haematology, Clinical sciences
Abstract

IntroductionFibrinogen is a complex molecule comprised of two sets of Aα, Bβ, and γ chains. Fibrinogen deficiencies can lead to the development of bleeding or thromboembolic events. The objective of this study was to perform DNA sequence analysis of patients with clinical fibrinogen abnormalities, and to perform genotype-phenotype correlations.Materials and methodsDNA from 31 patients was sequenced to evaluate disease-causing mutations in the three fibrinogen genes: FGA,FGB, and FGG. Clinical data were extracted from medical records or from consultation with referring hematologists. Fibrinogen antigen and functional (Clauss method) assays, as well as reptilase time (RT) and thrombin time (TT) were obtained for each patient. Molecular modeling was used to simulate the functional impact of specific missense variants on the overall protein structure.ResultsSeventeen mutations, including six novel mutations, were identified in the three fibrinogen genes. There was little correlation between genotype and phenotype. Molecular modeling predicted a substantial conformational change for a novel variant, FGG p.Ala289Asp, leading to a more rigid molecule in a region critical for polymerization and alignment of the fibrin monomers. This mutation is associated with both bleeding and clotting in the two affected individuals.ConclusionsRobust genotype-phenotype correlations are difficult to establish for fibrinogen disorders. Molecular modeling might represent a valuable tool for understanding the function of certain missense fibrinogen mutations but those should be followed by functional studies. It is likely that genetic and environmental modifiers account for the incomplete penetrance and variable expressivity that characterize fibrinogen disorders.

Published
2018

4. Pheno-genotyping of inherited thrombocytopenias: our experience in 50 families

Author

Heller, Paula Graciela, Goette, Nora Paula, Marin Oyarzún, Cecilia Paola, Baroni Pietto, Maria Constanza, Ayala, Daniela, Altuna, Diana R., Arrieta, Maria Elizabeth, Arbesú, Guillermo, Basqueira, Ana L., Bazack, Nora, Bonacorso, Silvina, Brodsky, Andrés, Castro Rios, Miguel, Cosentini, María L., Donato, Hugo Sebastian, Korin, Jorge D., Gomez, Silvina, Guglielmone, Hugo, Lagrotta, Pablo, Marti, Alejandra, Negro, Fernando Javier, Rapetti, María C., Rosso, Diego, Ponzinibbio, Carlos, Veber, Ernesto, Zerga, Marta Elisa, Molinas, Felisa Concepción, Savoia, Anna, Pecci, Alessandro, Marta, Rosana Fernanda, and Glembotsky, Ana Claudia

Subjects
TROMBOCITOPENIAS HEREDITARIAS, purl.org/becyt/ford/3.2 [https], purl.org/becyt/ford/3 [https], PLAQUETAS, SECUENCIACIÓN DE NUEVA GENERACIÓN
Abstract

Dada la heterogeneidad de las entidades comprendi- das en las trombocitopenias hereditarias y la escasez de marcadores distintivos, su diagnóstico constituye un verdadero desafío. El abordaje clásico se basa en la caracterización fenotípica seguida del estudio mo- lecular de genes candidatos, orientado según la sos- pecha clínica. La introducción de la secuenciación de nueva generación (NGS), que permite evaluar múltiples genes simultáneamente, constituye una al- ternativa diagnóstica de alto costo, siendo de acceso limitado en nuestro medio. Nos propusimos evaluar la utilidad del abordaje clásico en una cohorte conse- cutiva de 50 familias y describir la aplicación de NGS en un subgrupo de pacientes sin diagnóstico etioló- gico luego del enfoque clásico. Mediante el abordaje clásico se efectuó el diagnóstico en 27 (54%) familias. Posteriormente, 8 familias que quedaron sin diag- nóstico luego del algoritmo clásico, se evaluaron me- diante NGS, identificando el gen causal en 4 de ellas. Considerando ambos abordajes, el rédito diagnóstico fue 31/50 (62%) familias, con la siguiente distribu- ción: 38% desorden relacionado a MYH9, 8% síndro- me de Bernard-Soulier (4% clásico, 4% monoalélico), 4% síndrome de plaquetas grises, 4% desorden pla- quetario con predisposición a leucemia, 6% trom- bocitopenia relacionada a ANKRD26, 2% síndrome Wiskott-Aldrich. Los pacientes en los que no se pudo efectuar un diagnóstico etiológico presentaban trom- bocitopenia aislada leve, con aumento moderado del tamaño plaquetario y sangrado escaso.En conclusión, la aplicación de NGS permitió au- mentar el rédito diagnóstico, si bien sería necesa- rio ampliar la población estudiada para establecer el valor real de este abordaje en nuestro medio. Por lo tanto, el uso inicial del abordaje clásico, reserván- dose la aplicación posterior de NGS a los casos que permanecen sin diagnóstico luego de este enfoque, constituiría una alternativa útil en países con pocos recursos, apuntando a un diagnóstico adecuado que posibilite la pesquisa de complicaciones sindrómicas, oriente al tratamiento y consejo genético acertado. Diagnosis of inherited thrombocytopenias represents a true challenge owing to heterogeneity of these disorders and the absence of distinctive features in a substantial proportion of patients. Classical diagnostic approach is based on phenotypic characterization followed by molecular analysis of candidate genes guided by clinical suspicion. The introduction of next generation sequencing (NGS), that allows multiple genes analysis, is a high-cost alternative with limited access in our country. The aim of this work was to evaluate the utility of the classical approach in a consecutive cohort of 50 families and to describe the application of NGS in a subgroup of patients without an etiological diagnosis after the initial approach. Through the conventional approach, an etiologic diagnosis was made in 27 (54%) families. NGS was performed in 8 that remained without diagnosis after initial characterization, attaining a diagnosis in 4. Combining both approaches, the diagnostic yield was 31/50 (62%) families: 38% MYH9-related disorder, 8% Bernard-Soulier syndrome, 4% gray platelet syndrome, 4% familial platelet disorder with predisposition to leukemia, 6% ANKRD26-related thrombocytopenia, 2% Wiskott-Aldrich syndrome. Most patients without diagnosis had isolated macrothrombocytopenia and mild bleeding. NGS increased the diagnostic rate in this cohort, although it would be necessary to expand the population to establish its actual value in our setting. Therefore, the use of the classical approach and subsequent application of NGS in undiagnosed patients would represent a useful alternative in low-income countries, pointing out that a correct etiological diagnosis enables the detection of syndromic complications, appropriate treatment and adequate genetic counseling. Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Baroni Pietto, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Ayala, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Altuna, Diana R.. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentina Fil: Arrieta, Maria Elizabeth. Hospital Público Descentralizado Dr. Guillermo Rawson.; Argentina Fil: Arbesú, Guillermo. Hospital Dr. Humberto Notti; Argentina Fil: Basqueira, Ana L.. Hospital Privado Universitario de Cordoba.; Argentina Fil: Bazack, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Bonacorso, Silvina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Brodsky, Andrés. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Castro Rios, Miguel. No especifíca; Fil: Cosentini, María L.. Hospital Materno Infantil Doctor Hector Quintana ; Gobierno de la Provincia de Jujuy; Fil: Donato, Hugo Sebastian. Hospital Municipal del Niño de San Justo ; Municipalidad de la Matanza (buenos Aires); Fil: Korin, Jorge D.. No especifíca; Fil: Gomez, Silvina. No especifíca; Fil: Guglielmone, Hugo. Sanatorio Allende; Argentina Fil: Lagrotta, Pablo. Hospital Nacional Profesor Alejandro Posadas.; Argentina Fil: Marti, Alejandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina Fil: Negro, Fernando Javier. Sanatorio Sagrado Corazon; Argentina Fil: Rapetti, María C.. Hospital Municipal del Niño de San Justo ; Municipalidad de la Matanza (buenos Aires); Fil: Rosso, Diego. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ponzinibbio, Carlos. Hospital Italiano de La Plata; Argentina Fil: Veber, Ernesto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Zerga, Marta Elisa. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Savoia, Anna. Instituto para la Salud Materna e Infancia; Italia. Università degli Studi di Trieste; Italia Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia Fil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina

Published
2020

10. Quercetin 3, 7, 3´, 4´-Tetrasulphate from Flaveria bidentis Inhibits the Plasminogen Activator Inhibitor-1 but not the Tissue-Type Plasminogen Activator Expression in Human Normal Fibroblasts

Author

Guglielmone, Hugo, Agnese, Alicia M., Núñez Montoya, Susana Carolina, Pellizas, Claudia Gabriela, Fuentes, Marcelo, Cabrera, Jose Luis, and Donadio, Ana Carolina

Subjects
PROFIBRIONOLYTIC ACTIVITY, Otras Ciencias Químicas, SULPHATED FLAVONOIDS, FLAVERIA BIDENTIS, Ciencias Químicas, CIENCIAS NATURALES Y EXACTAS
Abstract

Sulphated flavonoids quercetin 3, 7, 3´, 4´-tetrasulphated (QTS) and quercetin 3-acetyl-7, 3´, 4´-trisulphate (ATS), obtained from Flaveria bidentis have demonstrated some antithrombotic properties. We analyzed whether both compounds affected the expression of tissue-plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the components of the fibrinolytic system. Normal human fibroblasts were pretreated with different concentrations of each sulphated flavonoid (0.1 μM to 500 μM), during 2 and 3 h followed by a 24 h incubation with phorbol myristate acetate (PMA). Results of the tPA and PAI-1 expression compared to control, showed different behaviors for the two flavonoids studied. A null inhibitory effect on the tPA expression was detected at all the concentrations for QTS and ATS. In contrast, QTS from 50 μM onwards showed a significant inhibitory effect on PAI-1 expression (p< 0.05). The profibrinolytic activity of QTS enhances its antithrombotic properties and encourages us to study these properties in animal models. Fil: Guglielmone, Hugo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Agnese, Alicia M.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia. Catedra de Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina Fil: Núñez Montoya, Susana Carolina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia. Catedra de Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina Fil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Fuentes, Marcelo. Universidad Nacional de Córdoba; Argentina Fil: Cabrera, Jose Luis. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia. Catedra de Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina Fil: Donadio, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

Published
2015

18. Mutations in LMAN1 and MCFD2 May Account for All Cases of Combined Deficiency of Factor V and Factor VIII.

Author

Zhang, Bin, primary, McGee, Beth, additional, Nichols, William C., additional, Guglielmone, Hugo, additional, Downes, Katherine, additional, Peyvandi, Flora, additional, de Bosch, Norma B., additional, Ruiz-Saez, Arlette, additional, Chatelain, Bernard, additional, Olpinski, Marian, additional, Bockenstedt, Paula, additional, Sperl, Wolfgang, additional, Kaufman, Randal J., additional, and Ginsburg, David, additional

Published
2005
Full Text
View/download PDF

22. Interaction of Human Tissue Plasminogen Activator (t-PA) with Pregnancy Zone Protein: A Comparative Study with t-PA- α2 -Macroglobulin Interaction1.

Author

Sánchez, María C., Chiabrando, Gustavo A., Guglielmone, Hugo A., Bonacci, Gustavo R., Rabinovich, Gabriel A., and Vides, Miguel A.

Subjects
PLASMINOGEN activators, PROTEOLYTIC enzymes, FIBRINOLYTIC agents, CIRCULATING anticoagulants, TISSUE plasminogen activator
Abstract

Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein strongly related to α2-macroglobulin (α2-M). Interactions of tissue plasminogen activator (t-PA) with PZP and α2-M were both investigated in vitro and the complexes were analyzed by polyacrylamide gel electrophoresis (PAGE). The results demonstrated that PZP-t-PA complex formation was evident within 1 h of incubation, whereas α2-M-t-PA complexes were formed after 18 h. Conclusions were supported by the following evidence: (i) PZP and α2-M complexes revealed changes of the mobility rate in non-denaturing PAGE, similar to those observed with a-Ms-chymotrypsin; (ii) both PZP and α2-M formed complexes of molecular size >360 kDa by SDS-PAGE, in accordance with the covalent binding of t-PA, which was previously reported for other proteinases; and (iii) PZP underwent a specific cleavage of the bait region with appearance of fragments of 85–90 kDa as judged by reducing SDS-PAGE. In contrast, the proteolytic attack on α2-M was found to occur more slowly, requiring several hours of incubation with t-PA for generation of an appreciable amount of fragments of 85–90 kDa. The appearance of free SH-groups of α-Ms was further investigated by titration with 5, 5'-dithiobis(2-nitrobenzoic acid). The maximal level of SH-groups raised was 3.9 mol/mol of PZP and 3.5 mol/mol of α2-M, indicating approximately one SH-group for each 180-kDa subunit. Finally, t-PA activity in PZP-t-PA complex was evaluated by measuring the hydrolysis of the chromogenic substrate Flavigen t-PA. Our results revealed that prolongation of the incubation period of this complex increased t-PA-mediated hydrolysis of Flavigen t-PA until a plateau was reached, approximately between 60 and 120 min. The present study suggests that PZP, by binding to t-PA, may contribute to the control of the activity of proteinases derived from fibrinolytic systems. [ABSTRACT FROM AUTHOR]

Published
1998

23. Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1or MCFD2

Author

Zhang, Bin, McGee, Beth, Yamaoka, Jennifer S., Guglielmone, Hugo, Downes, Katharine A., Minoldo, Salvador, Jarchum, Gustavo, Peyvandi, Flora, de Bosch, Norma B., Ruiz-Saez, Arlette, Chatelain, Bernard, Olpinski, Marian, Bockenstedt, Paula, Sperl, Wolfgang, Kaufman, Randal J., Nichols, William C., Tuddenham, Edward G.D., and Ginsburg, David

Abstract

Mutations in LMAN1 (ERGIC-53)or MCFD2cause combined deficiency of factor V and factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi. In this study, we analyzed 10 previously reported and 10 new F5F8D families. Mutations in the LMAN1or MCFD2genes accounted for 15 of these families, including 3 alleles resulting in no LMAN1mRNA accumulation. Combined with our previous reports, we have identified LMAN1or MCFD2mutations as the causes of F5F8D in 71 of 76 families. Among the 5 families in which no mutations were identified, 3 were due to misdiagnosis, with the remaining 2 likely carrying LMAN1or MCFD2mutations that were missed by direct sequencing. Our results suggest that mutations in LMAN1and MCFD2may account for all cases of F5F8D. Immunoprecipitation and Western blot analysis detected a low level of LMAN1-MCFD2 complex in lymphoblasts derived from patients with missense mutations in LMAN1 (C475R) or MCFD2 (I136T), suggesting that complete loss of the complex may not be required for clinically significant reduction in FV and FVIII.

Published
2006
Full Text
View/download PDF

24. Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2

Author

Zhang, Bin, McGee, Beth, Yamaoka, Jennifer S., Guglielmone, Hugo, Downes, Katharine A., Minoldo, Salvador, Jarchum, Gustavo, Peyvandi, Flora, de Bosch, Norma B., Ruiz-Saez, Arlette, Chatelain, Bernard, Olpinski, Marian, Bockenstedt, Paula, Sperl, Wolfgang, Kaufman, Randal J., Nichols, William C., Tuddenham, Edward G. D., and Ginsburg, David

Abstract

Mutations in LMAN1 (ERGIC-53) or MCFD2 cause combined deficiency of factor V and factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi. In this study, we analyzed 10 previously reported and 10 new F5F8D families. Mutations in the LMAN1 or MCFD2 genes accounted for 15 of these families, including 3 alleles resulting in no LMAN1 mRNA accumulation. Combined with our previous reports, we have identified LMAN1 or MCFD2 mutations as the causes of F5F8D in 71 of 76 families. Among the 5 families in which no mutations were identified, 3 were due to misdiagnosis, with the remaining 2 likely carrying LMAN1 or MCFD2 mutations that were missed by direct sequencing. Our results suggest that mutations in LMAN1 and MCFD2 may account for all cases of F5F8D. Immunoprecipitation and Western blot analysis detected a low level of LMAN1-MCFD2 complex in lymphoblasts derived from patients with missense mutations in LMAN1 (C475R) or MCFD2 (I136T), suggesting that complete loss of the complex may not be required for clinically significant reduction in FV and FVIII.

Published
2006
Full Text
View/download PDF

26. Lack of evidence of neoantigen formation in different batches of a double-virus inactivated factor VIII concentrate manufactured in Argentina.

Author

Guglielmone H, Farias F, Moya C, Navarro D, and Vitali MS

Subjects
Argentina, Autoantigens chemistry, Blood Coagulation Factor Inhibitors blood, Factor VIII therapeutic use, Female, Hemophilia A blood, Hemophilia A drug therapy, Humans, Male, Autoantigens analysis, Factor VIII analysis, Virus Inactivation
Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results