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502 results on '"Di Sapio, A."'

201. Persistent neutralizing antibodies abolish the interferon beta bioavailability in MS patients

Author

Raija L.P. Lindberg, M. T. Giordana, E. Milano, Arianna Sala, Antonio Bertolotto, A. Di Sapio, R. Bottero, Francesca Gilli, Fabiana Marnetto, Fabio Melis, Simona Malucchi, and Marco Capobianco

Subjects
Myxovirus Resistance Proteins, Multiple Sclerosis, Biological Availability, Biology, Pharmacology, Polymerase Chain Reaction, Peripheral blood mononuclear cell, Antibodies, Pharmacokinetics, GTP-Binding Proteins, Reference Values, Gene expression, medicine, Humans, RNA, Messenger, Cytopathic effect, Interferon beta-1a, Interferon-beta, Titer, Toxicity, Immunology, Leukocytes, Mononuclear, biology.protein, Neurology (clinical), Antibody, Interferon beta-1b, medicine.drug
Abstract

Background: MxA is an antiviral protein exclusively induced by type I interferons (IFN) and some viruses, and MxA gene expression is one of the most appropriate markers for measuring the biologic activity of exogenous IFNβ.Methods: A new quantitative-competitive PCR method was used to quantify MxA mRNA in peripheral blood mononuclear cells of 99 treatment-naïve and 92 IFNβ-treated patients with MS (22 Avonex, 17 Betaferon, and 53 Rebif-22). Every 3 months, IFNβ-induced neutralizing antibodies (NAb) were evaluated in sera using a cytopathic effect assay. Three categories of patients were identified: NAb negative (NAb−), persistent NAb positive (NAb+, ≥2 consecutive positive samples), and isolated NAb+ (one positive sample).Results: Treatment-naïve patients expressed detectable MxA mRNA levels (mean = 36 ± 32 fg MxA/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH); range 1 to 160) and an upper normal threshold was established (mean + 3 SD = 132 fg MxA/pg GAPDH). IFNβ-treated patients exhibited more than 11-fold higher levels (mean = 412 ± 282 fg MxA/pg GAPDH; range 16 to 1,172). However, 17 patients did not exhibit an increase in MxA mRNA level; 15 of these 17 patients showed a concurrent Nab+ titer. Moreover, 13 were persistent NAb+. Isolated NAb+ patients did not show a decrease in bioavailability of IFNβ (n = 9; mean = 567 ± 366 fg MxA/pg GAPDH; range 83 to 1,120). In NAb− patients, bioavailability was comparable among the three different IFNβ preparations 12 hours after injection.Conclusion: During IFNβ therapy, the presence of NAb reduced or abolished bioavailability in a relevant percentage of patients. These data could be important for the early detection of patients with MS who are not responsive to IFNβ therapy.

Published
2003

202. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, Ashley H., Patsopoulos, Nikolaos A., Xifara, Dionysia K., Davis, Mary F., Kemppinen, Anu, Cotsapas, Chris, Shah, Tejas S., Spencer, Chris, Booth, David, Goris, An, Oturai, Annette, Saarela, Janna, Fontaine, Bertrand, Hemmer, Bernhard, Martin, Claes, Zipp, Frauke, DAlfonso, Sandra, Martinelli-Boneschi, Filippo, Taylor, Bruce, Harbo, Hanne F., Kockum, Ingrid, Hillert, Jan, Olsson, Tomas, Ban, Maria, Oksenberg, Jorge R., Hintzen, Rogier, F Barcellos, Lisa, Agliardi, Cristina, Alfredsson, Lars, Alizadeh, Mehdi, Anderson, Carl, Andrews, Robert, Bach Sondergaard, Helle, Baker, Amie, Band, Gavin, Baranzini, Sergio E., Barizzone, Nadia, Barrett, Jeffrey, Bellenguez, Celine, Bergamaschi, Laura, Bernardinelli, Luisa, Berthele, Achim, Biberacher, Viola, Binder, Thomas M C., Blackburn, Hannah, Bomfim, Izaura L., Brambilla, Paola, Broadley, Simon, Brochet, Bruno, Brundin, Lou, Buck, Dorothea, Butzkueven, Helmut, Caillier, Stacy J., Camu, William, Carpentier, Wassila, Cavalla, Paola, Celius, Elisabeth G., Coman, Irene, Comi, Giancarlo, Corrado, Lucia, Cosemans, Leentje, Cournu-Rebeix, Isabelle, Cree, Bruce A C., Cusi, Daniele, Damotte, Vincent, Defer, Gilles, Delgado, Silvia R., Deloukas, Panos, di Sapio, Alessia, Dilthey, Alexander T., Donnelly, Peter, Dubois, Benedicte, Duddy, Martin, Edkins, Sarah, Elovaara, Irina, Esposito, Federica, Evangelou, Nikos, Fiddes, Barnaby, Field, Judith, Franke, Andre, Freeman, Colin, Frohlich, Irene Y., Galimberti, Daniela, Gieger, Christian, Gourraud, Pierre-Antoine, Graetz, Christiane, Graham, Andrew, Grummel, Verena, Guaschino, Clara, Hadjixenofontos, Athena, Hakonarson, Hakon, Halfpenny, Christopher, Hall, Gillian, Hall, Per, Hamsten, Anders, Harley, James, Harrower, Timothy, Hawkins, Clive, Hellenthal, Garrett, Hillier, Charles, Hobart, Jeremy, Hoshi, Muni, Hunt, Sarah E., Jagodic, Maja, Jelcic, Ilijas, Jochim, Angela, Kendall, Brian, Kermode, Allan, Kilpatrick, Trevor, Koivisto, Keijo, Konidari, Ioanna, Korn, Thomas, Kronsbein, Helena, Langford, Cordelia, Larsson, Malin, Lathrop, Mark, Lebrun-Frenay, Christine, Lechner-Scott, Jeannette, Lee, Michelle H., Leone, Maurizio A., Leppa, Virpi, Liberatore, Giuseppe, Lie, Benedicte A., Lill, Christina M., Linden, Magdalena, Link, Jenny, Luessi, Felix, Lycke, Jan, Macciardi, Fabio, Mannisto, Satu, Manrique, Clara P., Martin, Roland, Martinelli, Vittorio, Mason, Deborah, Mazibrada, Gordon, McCabe, Cristin, Mero, Inger-Lise, Mescheriakova, Julia, Moutsianas, Loukas, Myhr, Kjell-Morten, Nagels, Guy, Nicholas, Richard, Nilsson, Petra, Piehl, Fredrik, Pirinen, Matti, Price, Sian E., Quach, Hong, Reunanen, Mauri, Robberecht, Wim, Robertson, Neil P., Rodegher, Mariaemma, Rog, David, Salvetti, Marco, Schnetz-Boutaud, Nathalie C., Sellebjerg, Finn, Selter, Rebecca C., Schaefer, Catherine, Shaunak, Sandip, Shen, Ling, Shields, Simon, Siffrin, Volker, Slee, Mark, Soelberg Sorensen, Per, Sorosina, Melissa, Sospedra, Mireia, Spurkland, Anne, Strange, Amy, Sundqvist, Emilie, Thijs, Vincent, Thorpe, John, Ticca, Anna, Tienari, Pentti, van Duijn, Cornelia, Visser, Elizabeth M., Vucic, Steve, Westerlind, Helga, Wiley, James S., Wilkins, Alastair, Wilson, James F., Winkelmann, Juliane, Zajicek, John, Zindler, Eva, Haines, Jonathan L., Pericak-Vance, Margaret A., Ivinson, Adrian J., Stewart, Graeme, Hafler, David, Hauser, Stephen L., Compston, Alastair, McVean, Gil, De Jager, Philip, Sawcer, Stephen J., McCauley, Jacob L., Beecham, Ashley H., Patsopoulos, Nikolaos A., Xifara, Dionysia K., Davis, Mary F., Kemppinen, Anu, Cotsapas, Chris, Shah, Tejas S., Spencer, Chris, Booth, David, Goris, An, Oturai, Annette, Saarela, Janna, Fontaine, Bertrand, Hemmer, Bernhard, Martin, Claes, Zipp, Frauke, DAlfonso, Sandra, Martinelli-Boneschi, Filippo, Taylor, Bruce, Harbo, Hanne F., Kockum, Ingrid, Hillert, Jan, Olsson, Tomas, Ban, Maria, Oksenberg, Jorge R., Hintzen, Rogier, F Barcellos, Lisa, Agliardi, Cristina, Alfredsson, Lars, Alizadeh, Mehdi, Anderson, Carl, Andrews, Robert, Bach Sondergaard, Helle, Baker, Amie, Band, Gavin, Baranzini, Sergio E., Barizzone, Nadia, Barrett, Jeffrey, Bellenguez, Celine, Bergamaschi, Laura, Bernardinelli, Luisa, Berthele, Achim, Biberacher, Viola, Binder, Thomas M C., Blackburn, Hannah, Bomfim, Izaura L., Brambilla, Paola, Broadley, Simon, Brochet, Bruno, Brundin, Lou, Buck, Dorothea, Butzkueven, Helmut, Caillier, Stacy J., Camu, William, Carpentier, Wassila, Cavalla, Paola, Celius, Elisabeth G., Coman, Irene, Comi, Giancarlo, Corrado, Lucia, Cosemans, Leentje, Cournu-Rebeix, Isabelle, Cree, Bruce A C., Cusi, Daniele, Damotte, Vincent, Defer, Gilles, Delgado, Silvia R., Deloukas, Panos, di Sapio, Alessia, Dilthey, Alexander T., Donnelly, Peter, Dubois, Benedicte, Duddy, Martin, Edkins, Sarah, Elovaara, Irina, Esposito, Federica, Evangelou, Nikos, Fiddes, Barnaby, Field, Judith, Franke, Andre, Freeman, Colin, Frohlich, Irene Y., Galimberti, Daniela, Gieger, Christian, Gourraud, Pierre-Antoine, Graetz, Christiane, Graham, Andrew, Grummel, Verena, Guaschino, Clara, Hadjixenofontos, Athena, Hakonarson, Hakon, Halfpenny, Christopher, Hall, Gillian, Hall, Per, Hamsten, Anders, Harley, James, Harrower, Timothy, Hawkins, Clive, Hellenthal, Garrett, Hillier, Charles, Hobart, Jeremy, Hoshi, Muni, Hunt, Sarah E., Jagodic, Maja, Jelcic, Ilijas, Jochim, Angela, Kendall, Brian, Kermode, Allan, Kilpatrick, Trevor, Koivisto, Keijo, Konidari, Ioanna, Korn, Thomas, Kronsbein, Helena, Langford, Cordelia, Larsson, Malin, Lathrop, Mark, Lebrun-Frenay, Christine, Lechner-Scott, Jeannette, Lee, Michelle H., Leone, Maurizio A., Leppa, Virpi, Liberatore, Giuseppe, Lie, Benedicte A., Lill, Christina M., Linden, Magdalena, Link, Jenny, Luessi, Felix, Lycke, Jan, Macciardi, Fabio, Mannisto, Satu, Manrique, Clara P., Martin, Roland, Martinelli, Vittorio, Mason, Deborah, Mazibrada, Gordon, McCabe, Cristin, Mero, Inger-Lise, Mescheriakova, Julia, Moutsianas, Loukas, Myhr, Kjell-Morten, Nagels, Guy, Nicholas, Richard, Nilsson, Petra, Piehl, Fredrik, Pirinen, Matti, Price, Sian E., Quach, Hong, Reunanen, Mauri, Robberecht, Wim, Robertson, Neil P., Rodegher, Mariaemma, Rog, David, Salvetti, Marco, Schnetz-Boutaud, Nathalie C., Sellebjerg, Finn, Selter, Rebecca C., Schaefer, Catherine, Shaunak, Sandip, Shen, Ling, Shields, Simon, Siffrin, Volker, Slee, Mark, Soelberg Sorensen, Per, Sorosina, Melissa, Sospedra, Mireia, Spurkland, Anne, Strange, Amy, Sundqvist, Emilie, Thijs, Vincent, Thorpe, John, Ticca, Anna, Tienari, Pentti, van Duijn, Cornelia, Visser, Elizabeth M., Vucic, Steve, Westerlind, Helga, Wiley, James S., Wilkins, Alastair, Wilson, James F., Winkelmann, Juliane, Zajicek, John, Zindler, Eva, Haines, Jonathan L., Pericak-Vance, Margaret A., Ivinson, Adrian J., Stewart, Graeme, Hafler, David, Hauser, Stephen L., Compston, Alastair, McVean, Gil, De Jager, Philip, Sawcer, Stephen J., and McCauley, Jacob L.

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P andlt; 1.0 x 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P andlt; 5.0 x 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals., Funding Agencies|US National Institutes of Health||Wellcome Trust||UK MS Society||UK Medical Research Council||US National MS Society||Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre||DeNDRon||Swedish Brain Foundation||Swedish Research Council||Knut and Alice Wallenberg Foundation||Swedish Heart-Lung Foundation||Foundation for Strategic Research

Published
2013
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203. Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Author

Leone, MA, Barizzone, N, Esposito, F, Lucenti, A, Harbo, HF, Goris, A, Kockum, I, Oturai, AB, Celius, EG, Mero, IL, Dubois, B, Olsson, T, Søndergaard, HB, Cusi, D, Lupoli, S, Andreassen, BK, Barcellos, L, Booth, D, Comabella, M, Compston, A, D'Alfonso, S, De Jager, P, Fontaine, B, Hafler, D, Haines, J, Hauser, SL, Hawkins, C, Hemmer, B, Hillert, J, Ivinson, A, Martin, R, Martinelli Boneschi, F, McCauley, JL, Oksenberg, J, Oturai, A, Patsopoulos, N, Pericak-Vance, M, Saarela, J, Sawcer, S, Spurkland, A, Stewart, G, Zipp, F, Myhr, KM, Guerini, FR, Naldi, P, Galimberti, D, Scarpini, E, Bergamaschi, R, Di Sapio, A, Caputo, D, Rosso, G, Cordera, S, Cavalla, P, Cavallo, R, Benedetti, MD, Salvetti, M, Capra, R, Ghezzi, A, Annovazzi, P, Coniglio, G, Liberatore, G, Rodegher, M, Moiola, L, Colombo, B, Radaelli, M, Rossi, P, Martinelli, V, Comi, G, Martinelli-Boneschi, F, Leone, MA, Barizzone, N, Esposito, F, Lucenti, A, Harbo, HF, Goris, A, Kockum, I, Oturai, AB, Celius, EG, Mero, IL, Dubois, B, Olsson, T, Søndergaard, HB, Cusi, D, Lupoli, S, Andreassen, BK, Barcellos, L, Booth, D, Comabella, M, Compston, A, D'Alfonso, S, De Jager, P, Fontaine, B, Hafler, D, Haines, J, Hauser, SL, Hawkins, C, Hemmer, B, Hillert, J, Ivinson, A, Martin, R, Martinelli Boneschi, F, McCauley, JL, Oksenberg, J, Oturai, A, Patsopoulos, N, Pericak-Vance, M, Saarela, J, Sawcer, S, Spurkland, A, Stewart, G, Zipp, F, Myhr, KM, Guerini, FR, Naldi, P, Galimberti, D, Scarpini, E, Bergamaschi, R, Di Sapio, A, Caputo, D, Rosso, G, Cordera, S, Cavalla, P, Cavallo, R, Benedetti, MD, Salvetti, M, Capra, R, Ghezzi, A, Annovazzi, P, Coniglio, G, Liberatore, G, Rodegher, M, Moiola, L, Colombo, B, Radaelli, M, Rossi, P, Martinelli, V, Comi, G, and Martinelli-Boneschi, F

Abstract

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10 -7 ) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB. © 2013 Leone et al.

Published
2013

204. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., McCauley, J.L., Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., and McCauley, J.L.

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Published
2013

205. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, Ashley H, Patsopoulos, Nikolaos A, Xifara, Dionysia K, Davis, Mary F, Kemppinen, Anu, Cotsapas, Chris, Shah, Tejas S, Spencer, Chris, Booth, David, Goris, An, Oturai, Annette, Saarela, Janna, Fontaine, Bertrand, Hemmer, Bernhard, Martin, Claes, Zipp, Frauke, D'Alfonso, Sandra, Martinelli-Boneschi, Filippo, Taylor, Bruce, Harbo, Hanne F, Kockum, Ingrid, Hillert, Jan, Olsson, Tomas, Ban, Maria, Oksenberg, Jorge R, Hintzen, Rogier, Barcellos, Lisa F, Agliardi, Cristina, Alfredsson, Lars, Alizadeh, Mehdi, Anderson, Carl, Andrews, Robert, Søndergaard, Helle Bach, Baker, Amie, Band, Gavin, Baranzini, Sergio E, Barizzone, Nadia, Barrett, Jeffrey, Bellenguez, Céline, Bergamaschi, Laura, Bernardinelli, Luisa, Berthele, Achim, Biberacher, Viola, Binder, Thomas, Blackburn, Hannah, Bomfim, Izaura L, Brambilla, Paola, Broadley, Simon, Brochet, Bruno, Brundin, Lou, Buck, Dorothea, Butzkueven, Helmut, Caillier, Stacy J, Camu, William, Carpentier, Wassila, Cavalla, Paola, Celius, Elisabeth G, Coman, Irène, Comi, Giancarlo, Corrado, Lucia, Cosemans, Leentje, Cournu-Rebeix, Isabelle, Cree, Bruce A C, Cusi, Daniele, Damotte, Vincent, Defer, Gilles, Delgado, Silvia R, Deloukas, Panos, di Sapio, Alessia, Dilthey, Alexander T, Donnelly, Peter, Dubois, Bénédicte, Duddy, Martin, Edkins, Sarah, Elovaara, Irina, Esposito, Federica, Evangelou, Nikos, Fiddes, Barnaby, Field, Judith, Franke, Andre, Freeman, Colin, Frohlich, Irene Y, Galimberti, Daniela, Gieger, Christian, Gourraud, Pierre-Antoine, Graetz, Christiane, Graham, Andrew, Grummel, Verena, Guaschino, Clara, Hadjixenofontos, Athena, Hakonarson, Hakon, Halfpenny, Christopher, Hall, Gillian, Hall, Per, Hamsten, Anders, Harley, James, Harrower, Timothy, Hawkins, Clive, Hellenthal, Garrett, Hillier, Charles, Hobart, Jeremy, Hoshi, Muni, Hunt, Sarah E, Jagodic, Maja, Jel?i?, Ilijas, Jochim, Angela, Kendall, Brian, Kermode, Allan, Kilpatrick, Trevor, Koivisto, Keijo, Konidari, Ioanna, Korn, Thomas, Kronsbein, Helena, Langford, Cordelia, Larsson, Malin, Lathrop, Mark, Lebrun-Frenay, Christine, Lechner-Scott, Jeannette, Lee, Michelle H, Leone, Maurizio A, Leppä, Virpi, Liberatore, Giuseppe, Lie, Benedicte A, Lill, Christina M, Lindén, Magdalena, Link, Jenny, Luessi, Felix, Lycke, Jan, Macciardi, Fabio, Männistö, Satu, Manrique, Clara P, Martin, Roland, Martinelli, Vittorio, Mason, Deborah, Mazibrada, Gordon, McCabe, Cristin, Mero, Inger-Lise, Mescheriakova, Julia, Moutsianas, Loukas, Myhr, Kjell-Morten, Nagels, Guy, Nicholas, Richard, Nilsson, Petra, Piehl, Fredrik, Pirinen, Matti, Price, Siân E, Quach, Hong, Reunanen, Mauri, Robberecht, Wim, Robertson, Neil P, Rodegher, Mariaemma, Rog, David, Salvetti, Marco, Schnetz-Boutaud, Nathalie C, Sellebjerg, Finn, Selter, Rebecca C, Schaefer, Catherine, Shaunak, Sandip, Shen, Ling, Shields, Simon, Siffrin, Volker, Slee, Mark, Sorensen, Per Soelberg, Sorosina, Melissa, Sospedra, Mireia, Spurkland, Anne, Strange, Amy, Sundqvist, Emilie, Thijs, Vincent, Thorpe, John, Ticca, Anna, Tienari, Pentti, van Duijn, Cornelia, Visser, Elizabeth M, Vucic, Steve, Westerlind, Helga, Wiley, James S, Wilkins, Alastair, Wilson, James, Winkelmann, Juliane, Zajicek, John, Zindler, Eva, Haines, Jonathan L, Pericak-Vance, Margaret A, Ivinson, Adrian J, Stewart, Graeme, Hafler, David, Hauser, Stephen L, Compston, Alastair, McVean, Gil, De Jager, Philip, Sawcer, Stephen J, McCauley, Jacob L, (IMSGC), International Multiple Sclerosis Genetics Consortium, Beecham, Ashley H, Patsopoulos, Nikolaos A, Xifara, Dionysia K, Davis, Mary F, Kemppinen, Anu, Cotsapas, Chris, Shah, Tejas S, Spencer, Chris, Booth, David, Goris, An, Oturai, Annette, Saarela, Janna, Fontaine, Bertrand, Hemmer, Bernhard, Martin, Claes, Zipp, Frauke, D'Alfonso, Sandra, Martinelli-Boneschi, Filippo, Taylor, Bruce, Harbo, Hanne F, Kockum, Ingrid, Hillert, Jan, Olsson, Tomas, Ban, Maria, Oksenberg, Jorge R, Hintzen, Rogier, Barcellos, Lisa F, Agliardi, Cristina, Alfredsson, Lars, Alizadeh, Mehdi, Anderson, Carl, Andrews, Robert, Søndergaard, Helle Bach, Baker, Amie, Band, Gavin, Baranzini, Sergio E, Barizzone, Nadia, Barrett, Jeffrey, Bellenguez, Céline, Bergamaschi, Laura, Bernardinelli, Luisa, Berthele, Achim, Biberacher, Viola, Binder, Thomas, Blackburn, Hannah, Bomfim, Izaura L, Brambilla, Paola, Broadley, Simon, Brochet, Bruno, Brundin, Lou, Buck, Dorothea, Butzkueven, Helmut, Caillier, Stacy J, Camu, William, Carpentier, Wassila, Cavalla, Paola, Celius, Elisabeth G, Coman, Irène, Comi, Giancarlo, Corrado, Lucia, Cosemans, Leentje, Cournu-Rebeix, Isabelle, Cree, Bruce A C, Cusi, Daniele, Damotte, Vincent, Defer, Gilles, Delgado, Silvia R, Deloukas, Panos, di Sapio, Alessia, Dilthey, Alexander T, Donnelly, Peter, Dubois, Bénédicte, Duddy, Martin, Edkins, Sarah, Elovaara, Irina, Esposito, Federica, Evangelou, Nikos, Fiddes, Barnaby, Field, Judith, Franke, Andre, Freeman, Colin, Frohlich, Irene Y, Galimberti, Daniela, Gieger, Christian, Gourraud, Pierre-Antoine, Graetz, Christiane, Graham, Andrew, Grummel, Verena, Guaschino, Clara, Hadjixenofontos, Athena, Hakonarson, Hakon, Halfpenny, Christopher, Hall, Gillian, Hall, Per, Hamsten, Anders, Harley, James, Harrower, Timothy, Hawkins, Clive, Hellenthal, Garrett, Hillier, Charles, Hobart, Jeremy, Hoshi, Muni, Hunt, Sarah E, Jagodic, Maja, Jel?i?, Ilijas, Jochim, Angela, Kendall, Brian, Kermode, Allan, Kilpatrick, Trevor, Koivisto, Keijo, Konidari, Ioanna, Korn, Thomas, Kronsbein, Helena, Langford, Cordelia, Larsson, Malin, Lathrop, Mark, Lebrun-Frenay, Christine, Lechner-Scott, Jeannette, Lee, Michelle H, Leone, Maurizio A, Leppä, Virpi, Liberatore, Giuseppe, Lie, Benedicte A, Lill, Christina M, Lindén, Magdalena, Link, Jenny, Luessi, Felix, Lycke, Jan, Macciardi, Fabio, Männistö, Satu, Manrique, Clara P, Martin, Roland, Martinelli, Vittorio, Mason, Deborah, Mazibrada, Gordon, McCabe, Cristin, Mero, Inger-Lise, Mescheriakova, Julia, Moutsianas, Loukas, Myhr, Kjell-Morten, Nagels, Guy, Nicholas, Richard, Nilsson, Petra, Piehl, Fredrik, Pirinen, Matti, Price, Siân E, Quach, Hong, Reunanen, Mauri, Robberecht, Wim, Robertson, Neil P, Rodegher, Mariaemma, Rog, David, Salvetti, Marco, Schnetz-Boutaud, Nathalie C, Sellebjerg, Finn, Selter, Rebecca C, Schaefer, Catherine, Shaunak, Sandip, Shen, Ling, Shields, Simon, Siffrin, Volker, Slee, Mark, Sorensen, Per Soelberg, Sorosina, Melissa, Sospedra, Mireia, Spurkland, Anne, Strange, Amy, Sundqvist, Emilie, Thijs, Vincent, Thorpe, John, Ticca, Anna, Tienari, Pentti, van Duijn, Cornelia, Visser, Elizabeth M, Vucic, Steve, Westerlind, Helga, Wiley, James S, Wilkins, Alastair, Wilson, James, Winkelmann, Juliane, Zajicek, John, Zindler, Eva, Haines, Jonathan L, Pericak-Vance, Margaret A, Ivinson, Adrian J, Stewart, Graeme, Hafler, David, Hauser, Stephen L, Compston, Alastair, McVean, Gil, De Jager, Philip, Sawcer, Stephen J, McCauley, Jacob L, and (IMSGC), International Multiple Sclerosis Genetics Consortium

Published
2013

206. Molecular genetic changes in a series of neuroepithelial tumors of childhood

Author

Alessia, Di Sapio, Isabella, Morra, Luca, Pradotto, Marilena, Guido, Davide, Schiffer, and Alessandro, Mauro

Subjects
Adolescent, Brain Neoplasms, DNA Mutational Analysis, Gene Amplification, Cyclin-Dependent Kinase 4, Infant, Nuclear Proteins, Proto-Oncogene Proteins c-mdm2, DNA, Neoplasm, Genes, erbB-1, Astrocytoma, Genes, p53, Polymerase Chain Reaction, Cyclin-Dependent Kinases, Child, Preschool, Proto-Oncogene Proteins, Humans, Receptors, Platelet-Derived Growth Factor, Child
Abstract

Amplification of the EGFR, mdm2, CDK4 and PDGFR A genes has been widely demonstrated in adult malignant gliomas, almost exclusively glioblastomas. To determine the role of these mutational events in pediatric astrocytic gliomas we investigated the presence of EGFR, mdm2, CDK4 and PDGFR A gene amplification in 38 childhood brain tumor biopsies, including 24 low-grade astrocytomas and 14 malignant tumors. We used differential PCR assay on DNA extracted either from paraffin embedded or frozen tissues. EGFR gene amplification was detected in 4 out of 14 malignant tumors; no low-grade astrocytoma showed amplification. Tumors with EGFR gene amplification were negative for the presence of p53 mutations, as observed in a previous study. One glioblastoma showed PDGFR A amplification, while no amplifications were observed for mdm2 and CDK4 genes. These data are in line with those obtained from studies on gliomas of adults and suggest the existence of two different subsets of malignant gliomas also in pediatric brain tumors: one carrying EGFR gene amplification, the other showing p53 mutations.

Published
2002

207. Regional variations in total and nonprotein sulfhydryl compounds in the human gastric mucosa and effects of ethanol

Author

G. Nardi, D. Taranto, Carmela Loguercio, A Grella, C. Del Vecchio Blanco, M Di Sapio, Marco Romano, Loguercio, Carmelina, Romano, Marco, DI SAPIO, M, Nardi, G, Taranto, D, Grella, A, and DEL VECCHIO BLANCO, C.

Subjects
Adult, Male, medicine.medical_specialty, digestive system, chemistry.chemical_compound, Internal medicine, Biopsy, medicine, Gastric mucosa, Distribution (pharmacology), Humans, Cysteine, Sulfhydryl Compounds, Antrum, Ethanol, medicine.diagnostic_test, Stomach, digestive, oral, and skin physiology, Gastroenterology, Proteins, Glutathione, Middle Aged, digestive system diseases, medicine.anatomical_structure, Endocrinology, chemistry, Gastric Mucosa, Female
Abstract

This study evaluated the regional distribution of sulfhydryl compounds in the human gastric mucosa and the effect of ethanol on gastric sulfhydryl tissue levels. Total sulfhydryl, glutathione, and cysteine and their oxidized forms were measured in biopsy specimens taken from the gastric body and antrum of 22 healthy volunteers. Total sulfhydryl and glutathione contents of the body of the stomach were significantly higher than those of the antrum. In contrast, cysteine concentration was higher in the gastric antrum than in the body. No difference was found in the levels of oxidized sulfhydryls between the gastric body and antrum. The effect of acute administration of ethanol on gastric sulfhydryl content was studied in nine subjects. Ethanol caused gross mucosal damage and lowered the concentration of sulfhydryl compounds in both the body and the antrum. In 10 chronic alcoholics total sulfhydryl and glutathione, but not cysteine, were markedly decreased in the gastric body but not in the antrum as compared with nonalcoholic controls. In conclusion, 1) the human gastric body contains significantly higher tissue levels of total sulfhydryls and glutathione and lower concentrations of cysteine than the antrum; 2) ethanol in a damaging concentration significantly decreases gastric tissue levels of sulfhydryl compounds; and 3) chronic ethanol intake lowers total sulfhydryl and glutathione tissue levels in the gastric body.

Published
1991

208. P141: Motor evoked potentials from multiple recording sites of the lower limbs as a monitoring tool of central motor function

Author

A. Di Sapio, Simona Malucchi, Paola Berchialla, Walter Troni, Antonio Bertolotto, Francesca Sperli, and Federica Melillo

Subjects
medicine.medical_specialty, Physical medicine and rehabilitation, Neurology, business.industry, Physiology (medical), Medicine, Neurology (clinical), business, Monitoring tool, Motor function, Sensory Systems
Published
2014
Full Text
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209. P574: Computerized static posturography: modified clinical test of sensory interaction on balance and limits of stability in multiple sclerosis patients

Author

Antonio Bertolotto, Walter Troni, Maria Malentacchi, A. Di Sapio, and Federica Melillo

Subjects
medicine.medical_specialty, business.industry, Multiple sclerosis, Posturography, Sensory interaction, Limits of stability, medicine.disease, Sensory Systems, Test (assessment), Physical medicine and rehabilitation, Neurology, Physiology (medical), medicine, Physical therapy, Neurology (clinical), business, Balance (ability)
Published
2014
Full Text
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210. Inhibitory activity of xanthine-oxidase and superoxide scavenger properties of Inga verna subsp. affinis. Its morphological and micrographic characteristics

Author

Erica Martı́nez, Alejandro Tapia, M del Carmen Cruañes, Eduardo P. Vivot, Osvaldo Di Sapio, Juan de Dios Muñoz, M Josefina Cruañes, Martha Gattuso, Guillermo Schmeda Hirschmann, and Susana Zacchino

Subjects
Pharmacology, Xanthine Oxidase, Antioxidant, Chromatography, DPPH, Superoxide, Inga, Plant Extracts, medicine.medical_treatment, Argentina, Free Radical Scavengers, Biology, Pharmacognosy, biology.organism_classification, High-performance liquid chromatography, Scavenger, chemistry.chemical_compound, Biochemistry, chemistry, Drug Discovery, medicine, Xanthine oxidase, Chromatography, High Pressure Liquid
Abstract

Hexane, dichloromethane and ethanolic extracts of Inga verna subsp. affinis were evaluated as inhibitors of xanthine-oxidase and as scavengers of the superoxide produced by the action of the enzyme. Ethanolic but not hexane and dichloromethane extracts showed inhibitory properties of xanthine-oxidase (IC 50 =27.3 μg/ml) with an additional superoxide scavenging capacity (IC 50 =12.7 μg/ml). The antioxidant potential was confirmed with the free radical 1,1-diphenyl-2-picryl hydrazyl (DPPH) assay, which showed that the ethanolic extract scavenges 50% DPPH free radicals at 11.6 μg/ml. HPLC study of the phenol content of the active extract, revealed the presence of ellagic and gallic acids as its main constituents. The main morphological and micrographic characteristics of Inga verna subsp. affinis are described in this paper too, in order to aid in its inequivocal identification since Inga spp. are noted for their morphological variation, which makes taxonomic classification very difficult.

Published
2001

211. Quality Control of Herbal Medicines with Spectrophotometry and Chemometric Techniques - Application to Baccharis L. Species Belonging to Sect - Caulopterae DC. (Asteraceae)

Author

María Victoria Rodriguez, María Laura Martínez, Adriana Cortadi, María Noel Campagna, Osvaldo Di Sapio, Marcos Derita, Susana Zacchino, Martha Gattuso, María Victoria Rodriguez, María Laura Martínez, Adriana Cortadi, María Noel Campagna, Osvaldo Di Sapio, Marcos Derita, Susana Zacchino, and Martha Gattuso

Published
2012
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213. An Italian family with Ala-47 transthyretin mutation associated with cardiomyopathy and polyneuropathy

Author

Luca Pradotto, Alessandro Mauro, Gianluigi Mancardi, A. Di Sapio, Angelo Schenone, Alberto Primavera, and Claudio Solaro

Subjects
Adult, Male, medicine.medical_specialty, Cousin, Adult, Base Sequence, genetics, Cardiomyopathies, genetics, Humans, Italy, Male, Mutation, genetics, Pedigree, Polyneuropathies, genetics/pathology, Prealbumin, genetics, Sural Nerve, pathology, Cardiomyopathy, Bioinformatics, Polyneuropathies, Sural Nerve, Internal medicine, medicine, Humans, Prealbumin, genetics, Genetics (clinical), biology, Base Sequence, business.industry, genetics/pathology, nutritional and metabolic diseases, medicine.disease, Pedigree, Transthyretin, Neurology, Italy, Heart failure, Pediatrics, Perinatology and Child Health, Mutation (genetic algorithm), Mutation, biology.protein, Cardiology, Neurology (clinical), business, Cardiomyopathies, Polyneuropathy
Abstract

We describe two Italian first cousins with familial amyloidotic polyneuropathy associated with transthyretin variant consisting of the substitution of alanine for glycine at codon 47 (TTR Ala-47), from a family with a history of cardiac failure. The 40-year-old patient presented with autonomic dysfunction and the 44-year-old cousin with congestive heart failure. Both developed sensorimotor and autonomic polyneuropathy. Since a similar clinical picture has been described in another Italian family, the cardiac involvement must be regarded as a salient and early feature of the TTR Ala-47 mutation.

Published
2000

214. No evidence for a role of rareCYP27B1functional variations in multiple sclerosis

Author

Barizzone, Nadia, primary, Pauwels, Ine, additional, Luciano, Bernadetta, additional, Franckaert, Dean, additional, Guerini, Franca Rosa, additional, Cosemans, Leentje, additional, Hilven, Kelly, additional, Salviati, Alessandro, additional, Dooley, James, additional, Danso-Abeam, Dina, additional, di Sapio, Alessia, additional, Cavalla, Paola, additional, Decallonne, Brigitte, additional, Mathieu, Chantal, additional, Liston, Adrian, additional, Leone, Maurizio, additional, Dubois, Bénédicte, additional, D'Alfonso, Sandra, additional, and Goris, An, additional

Published
2013
Full Text
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216. Parámetros micrográficos para la identificación de hojas, corteza y leño de Picrasma crenata (Vell.) Engl. (Simaroubaceae)

Author

María N. Campagna, Osvaldo Di Sapio, and Martha Gattuso

Subjects
Picrasma crenata, Simaroubaceae, micrografía, micrography, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Picrasma crenata (Vell.) Engler (Simaroubaceae) es un árbol de bajo porte conocido popularmente como "palo amargo" o "quina brava", que habita en el noreste de la Argentina, principalmente en la provincia de Misiones. En la medicina tradicional el leño se emplea en forma de infusión, como antimalárico, antipalúdico, antisifilítico y tónico; se lo utiliza también como insecticida en la elaboración de tinturas alcohólicas como sustituto de Quassia amara, para el tratamiento de la pediculosis. El objetivo de este trabajo fue realizar un estudio morfoanatómico de la corteza, el leño y las hojas de P. crenata con el fin de obtener caracteres de valor diagnóstico que permitan una correcta identificación de la especie. Se efectuaron cortes transversales y longitudinales de material fresco que fue incluido en parafina de los tres órganos de la planta, y se colorearon con Safranina-Fast Green y Violeta de Cresilo. Los resultados mostraron que: la corteza se halla constituida por 5-7 peridermis de disposición imbrincada, el floema se halla interrumpido por numerosos radios muy sinuosos y torsionados; el leño, de color blanco amarillento, tiene crecimiento semianular a anular con porosidad difusa no uniforme; las hojas son compuestas, sus folíolos oval elípticos, alternos, presentan mesófilo dorsiventral, estomas anomocíticos solo en la epidermis inferior, tricomas simples y una cavidad esquizolisígena en el parénquima central del nervio medio.

217. Caracteres morfoanatómicos y micrográficos de la corteza de Croton urucurana Baillon (Euphorbiaceae)

Author

Osvaldo A. Di Sapio and Martha A. Gattuso

Subjects
Croton urucurana, Euphorbiaceae, corteza, micrografía, morfoanatomía, bark, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Croton urucurana Baillon (Euphorbiaceae) es una especie de amplia distribución en regiones tropicales y subtropicales de las Américas. En la corteza caulinar tiene células productoras de un látex que es ampliamente utilizado en la medicina tradicional para tratar afecciones de la piel, y también como antidiarreico, antioxidante, inmunomodulador y analgésico. Numerosos estudios validan su uso etnomedicinal, pero los estudios anatómicos y ecológicos son escasos. El objetivo de este trabajo fue analizar por medio de transcorte y maceración, los caracteres morfoanatómicos y micrográficos de la corteza de C. urucurana, para su aplicación como material de referencia en el control de calidad de la droga cruda, entera o fragmentada. Se concluyó que la especie aquí estudiada puede ser identificada mediante una combinación de caracteres cualitativos, morfológicos y micrográficos.

218. Caracterización de harinas de chía (Salvia hispanica L.) comercializadas en Rosario (Santa Fe, Argentina)

Author

Carlos Périgo, Marcos Cases, Mirian Bueno, Osvaldo Di Sapio, Héctor Busilacchi, and Cecilia Severin

Subjects
Salvia hispanica L., harina de "chía, medicinal, flour of "chia, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Salvia hispanica L. (Lamiaceae) -conocida como "chía"- es una especie de interés dietario-medicinal, fuente de ácidos grasos omega-6 y omega-3, proteínas, antioxidantes y fibras solubles e insolubles. Con el objetivo de caracterizar harinas de S. hispanica que se comercializan en la ciudad de Rosario, se analizaron muestras adquiridas en diferentes comercios. Se realizó la caracterización botánica y se determinó: fibras brutas totales, humedad, cenizas, proteínas y ácidos grasos. Las muestras comercializadas como harina corresponden, en realidad, a semillas de "chía" molidas. Se comprobó que existen a la venta lotes de harina de "chía" de los que se desconoce su procedencia y procesamiento, algunos adulterados con semillas de otras especies. Los resultados de humedad y de proteínas obtenidos estuvieron dentro de los valores estipulados por el Código Alimentario Argentino 2009 pero ciertos valores de fibra bruta total y ceniza fueron inferiores. Con este relevamiento se comprobó que lo comercializado como harina de "chía" en la ciudad de Rosario es semilla molida, donde se observa una alta variación en la calidad, pues se dispone en el mercado desde productos de alta pureza hasta otros, totalmente adulterados.

220. Identificación de microestructuras y análisis arqueobotánico en sitios del Holoceno tardío de la llanura aluvial del Paraná medio

Author

Cornero Silvia, Lucía Rangone, and Osvaldo Di Sapio

Subjects
Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

La práctica de la horticultura en los pueblos costeros del Paraná fue conocida a través del relato de los cronistas del siglo XVI, como Luis Ramírez (1528) y Pedro Lopes de Souza (1531); sin embargo, debieron pasar muchos años para que se pudiera constatar la antigüedad del conocimiento de productos hortícolas alimenticios. En este sentido la arqueobotánica, como disciplina de convergencia, constituye un verdadero aporte al conocimiento de la subsistencia humana en las tierras bajas del Paraná. Se realizaron análisis de microestructuras de origen orgánico procedentes de cuatro sitios arqueológicos compatibles con la entidad arqueológica Goya Malabrigo y procedentes de los Departamentos Gral. Obligado y San Javier, de la Provincia de Santa Fe. Los fechados radiocarbónicos corresponden a dos de los sitios y los ubican en un rango cronológico de 1.680 ± 60 aprox. a 2.050 ± 50 aprox. años de antigüedad. Las muestras fueron extraídas del cálculus dental de adultos, un material calcificado que resulta de la mineralización de los depósitos acumulados en la placa dental, que permite la conservación de los restos orgánicos; del sedimento ventral de enterratorios primarios, y de adherencias conservadas en el interior de vasijas. Por diferentes técnicas se identificaron fitolitos de afinidad graminoide, células epidérmicas de Curcubitaceae, y almidón de Zea mays y Phaseolus sp., entre otras microestructuras biológicas. Hasta el momento se habían detectado, por estudios microscópicos, almidones arqueológicos adheridos a instrumentos líticos de molienda y vasijas, en la región del bajo Paraná y el Delta datados en una antigüedad cercana al último milenio. Este trabajo complementa ese antecedente y presenta la identificación de cultígenos en el norte de Santa Fe, sobre el valle aluvial del río Paraná extendiendo en el tiempo la práctica de una horticultura basada en el consumo de maíz, porotos y calabazas, que se suma a las estrategias de caza y pesca, constituyendo una economía mixta para pueblos costeros asignados a Goya Malabrigo.

221. Parámetros micrográficos para la identificación de hojas, corteza y leño de Picrasma crenata (Vell.) Engl. (Simaroubaceae)

Author

María N. Campagna, Osvaldo Di Sapio, and Martha Gattuso

Subjects
Picrasma crenata, Simaroubaceae, micrografía, micrography, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Picrasma crenata (Vell.) Engler (Simaroubaceae) es un árbol de bajo porte conocido popularmente como "palo amargo" o "quina brava", que habita en el noreste de la Argentina, principalmente en la provincia de Misiones. En la medicina tradicional el leño se emplea en forma de infusión, como antimalárico, antipalúdico, antisifilítico y tónico; se lo utiliza también como insecticida en la elaboración de tinturas alcohólicas como sustituto de Quassia amara, para el tratamiento de la pediculosis. El objetivo de este trabajo fue realizar un estudio morfoanatómico de la corteza, el leño y las hojas de P. crenata con el fin de obtener caracteres de valor diagnóstico que permitan una correcta identificación de la especie. Se efectuaron cortes transversales y longitudinales de material fresco que fue incluido en parafina de los tres órganos de la planta, y se colorearon con Safranina-Fast Green y Violeta de Cresilo. Los resultados mostraron que: la corteza se halla constituida por 5-7 peridermis de disposición imbrincada, el floema se halla interrumpido por numerosos radios muy sinuosos y torsionados; el leño, de color blanco amarillento, tiene crecimiento semianular a anular con porosidad difusa no uniforme; las hojas son compuestas, sus folíolos oval elípticos, alternos, presentan mesófilo dorsiventral, estomas anomocíticos solo en la epidermis inferior, tricomas simples y una cavidad esquizolisígena en el parénquima central del nervio medio.

222. Caracteres morfoanatómicos y micrográficos de la corteza de Croton urucurana Baillon (Euphorbiaceae)

Author

Osvaldo A. Di Sapio and Martha A. Gattuso

Subjects
Croton urucurana, Euphorbiaceae, corteza, micrografía, morfoanatomía, bark, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Croton urucurana Baillon (Euphorbiaceae) es una especie de amplia distribución en regiones tropicales y subtropicales de las Américas. En la corteza caulinar tiene células productoras de un látex que es ampliamente utilizado en la medicina tradicional para tratar afecciones de la piel, y también como antidiarreico, antioxidante, inmunomodulador y analgésico. Numerosos estudios validan su uso etnomedicinal, pero los estudios anatómicos y ecológicos son escasos. El objetivo de este trabajo fue analizar por medio de transcorte y maceración, los caracteres morfoanatómicos y micrográficos de la corteza de C. urucurana, para su aplicación como material de referencia en el control de calidad de la droga cruda, entera o fragmentada. Se concluyó que la especie aquí estudiada puede ser identificada mediante una combinación de caracteres cualitativos, morfológicos y micrográficos.

223. Caracterización de harinas de chía (Salvia hispanica L.) comercializadas en Rosario (Santa Fe, Argentina)

Author

Carlos Périgo, Marcos Cases, Mirian Bueno, Osvaldo Di Sapio, Héctor Busilacchi, and Cecilia Severin

Subjects
Salvia hispanica L., harina de "chía, medicinal, flour of "chia, Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

Salvia hispanica L. (Lamiaceae) -conocida como "chía"- es una especie de interés dietario-medicinal, fuente de ácidos grasos omega-6 y omega-3, proteínas, antioxidantes y fibras solubles e insolubles. Con el objetivo de caracterizar harinas de S. hispanica que se comercializan en la ciudad de Rosario, se analizaron muestras adquiridas en diferentes comercios. Se realizó la caracterización botánica y se determinó: fibras brutas totales, humedad, cenizas, proteínas y ácidos grasos. Las muestras comercializadas como harina corresponden, en realidad, a semillas de "chía" molidas. Se comprobó que existen a la venta lotes de harina de "chía" de los que se desconoce su procedencia y procesamiento, algunos adulterados con semillas de otras especies. Los resultados de humedad y de proteínas obtenidos estuvieron dentro de los valores estipulados por el Código Alimentario Argentino 2009 pero ciertos valores de fibra bruta total y ceniza fueron inferiores. Con este relevamiento se comprobó que lo comercializado como harina de "chía" en la ciudad de Rosario es semilla molida, donde se observa una alta variación en la calidad, pues se dispone en el mercado desde productos de alta pureza hasta otros, totalmente adulterados.

225. Identificación de microestructuras y análisis arqueobotánico en sitios del Holoceno tardío de la llanura aluvial del Paraná medio

Author

Cornero Silvia, Lucía Rangone, and Osvaldo Di Sapio

Subjects
Medicine, Therapeutics. Pharmacology, RM1-950
Abstract

La práctica de la horticultura en los pueblos costeros del Paraná fue conocida a través del relato de los cronistas del siglo XVI, como Luis Ramírez (1528) y Pedro Lopes de Souza (1531); sin embargo, debieron pasar muchos años para que se pudiera constatar la antigüedad del conocimiento de productos hortícolas alimenticios. En este sentido la arqueobotánica, como disciplina de convergencia, constituye un verdadero aporte al conocimiento de la subsistencia humana en las tierras bajas del Paraná. Se realizaron análisis de microestructuras de origen orgánico procedentes de cuatro sitios arqueológicos compatibles con la entidad arqueológica Goya Malabrigo y procedentes de los Departamentos Gral. Obligado y San Javier, de la Provincia de Santa Fe. Los fechados radiocarbónicos corresponden a dos de los sitios y los ubican en un rango cronológico de 1.680 ± 60 aprox. a 2.050 ± 50 aprox. años de antigüedad. Las muestras fueron extraídas del cálculus dental de adultos, un material calcificado que resulta de la mineralización de los depósitos acumulados en la placa dental, que permite la conservación de los restos orgánicos; del sedimento ventral de enterratorios primarios, y de adherencias conservadas en el interior de vasijas. Por diferentes técnicas se identificaron fitolitos de afinidad graminoide, células epidérmicas de Curcubitaceae, y almidón de Zea mays y Phaseolus sp., entre otras microestructuras biológicas. Hasta el momento se habían detectado, por estudios microscópicos, almidones arqueológicos adheridos a instrumentos líticos de molienda y vasijas, en la región del bajo Paraná y el Delta datados en una antigüedad cercana al último milenio. Este trabajo complementa ese antecedente y presenta la identificación de cultígenos en el norte de Santa Fe, sobre el valle aluvial del río Paraná extendiendo en el tiempo la práctica de una horticultura basada en el consumo de maíz, porotos y calabazas, que se suma a las estrategias de caza y pesca, constituyendo una economía mixta para pueblos costeros asignados a Goya Malabrigo.

227. Control of meningioma cell growth by platelet-derived growth factor (PDGF)

Author

C Mocellini, Davide Schiffer, Alessia Di Sapio, and Alessandro Mauro

Subjects
medicine.medical_specialty, Platelet-derived growth factor, Gene Expression, Biology, Tritium, Receptor, Platelet-Derived Growth Factor beta, chemistry.chemical_compound, In vivo, Neutralization Tests, Internal medicine, otorhinolaryngologic diseases, medicine, Tumor Cells, Cultured, Humans, Receptors, Platelet-Derived Growth Factor, Northern blot, Receptor, Autocrine signalling, Microscopy, Immunoelectron, neoplasms, Platelet-Derived Growth Factor, Cell growth, Antibodies, Monoclonal, Blotting, Northern, nervous system diseases, Endocrinology, Neurology, chemistry, Cell culture, Culture Media, Conditioned, Cancer research, biology.protein, Neurology (clinical), Meningioma, Platelet-derived growth factor receptor, Cell Division, Thymidine
Abstract

We have examined the possible involvement of PDGF and PDGF receptors in the growth control of five meningiomas, analyzing the biopsy specimens and the primary cultures derived from the same tumors. Light and electron microscopy demonstrated that MAbs against PDGF beta-receptors immunodecorate meningioma cells in vivo and in vitro, while those against alpha-receptors gave negative results. The effects of PDGF isoforms AA, AB, BB and of PDGF neutralizing antibodies on meningioma cultures were examined using [3H]thymidine incorporation analysis. Only with PDGF-AB and -BB a mitogenic effect was observed, while PDGF-neutralizing antibodies produced a reduction of [3H]thymidine incorporation. The production of PDGF-like growth factors by meningioma cells was tested analyzing the effects of meningioma culture-conditioned media on the growth of Swiss 3T3 cells. In all cases meningioma conditioned media stimulated the in vitro growth of 3T3 fibroblasts and this stimulatory effect was strongly reduced by PDGF-neutralizing antibodies. Furthermore, Northern blot analysis demonstrated expression of c-sis/PDGF-B and PDGF beta-receptors mRNA in all meningioma biopsies and in all the derived cultures. Our results provide strong evidence that PDGF-B chain and PDGF beta-receptors are involved in growth control mechanisms of human meningiomas through autocrine and/or paracrine mechanisms.

Published
1995

232. Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis

Author

Gilli, Francesca, primary, Lindberg, Raija L. P., additional, Valentino, Paola, additional, Marnetto, Fabiana, additional, Malucchi, Simona, additional, Sala, Arianna, additional, Capobianco, Marco, additional, di Sapio, Alessia, additional, Sperli, Francesca, additional, Kappos, Ludwig, additional, Calogero, Raffaele A., additional, and Bertolotto, Antonio, additional

Published
2010
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237. Silicones in clear formulations

Author

Goldemberg, Robert L., Tassoff, James A., and Di Sapio, Alfred J.

Subjects
Toiletries -- Composition, Cosmetics -- Composition, Silicones -- Usage, Business, Pharmaceuticals and cosmetics industries
Published
1986

238. Coexpression of PDGF and PDGF-Receptors Genes in Human Astrrocytic Gliomas

Author

Davide Schiffer, A. Bulfone, Alessandro Mauro, L. Sosso, and A. Di Sapio

Subjects
Human glioma, Nervous tissue, Paracrine mechanisms, Biology, nervous system diseases, medicine.anatomical_structure, medicine, biology.protein, Cancer research, Growth stimulation, Autocrine signalling, Receptor, neoplasms, Gene, Platelet-derived growth factor receptor
Abstract

The expression of gene sequences related to PDGF A and B chains and of PDGF B-type receptor in human glioma biopsies was analyzed. The major part of astrocytic gliomas expressed transcripts for these genes at higher levels than found in peritumoral and in normal nervous tissue specimens. Our results are in agreement with the hypothesis of an autocrine growth stimulation in astrocytic gliomas, mediated by PDGF and PDGF receptors. Moreover, PDGF may be involved in paracrine mechanisms responsible for endothelial hyperplasias in malignant gliomas.

Published
1991
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241. Serum and cerebrospinal fluid neurofilament light chains measured by SIMOA™, Ella™, and Lumipulse™ in multiple sclerosis naïve patients.

Author

Vecchio, D, Puricelli, C, Malucchi, Virgilio, E, Martire, S, Perga, S, Passarelli, F, Valentino, Di Sapio, A, Cantello, R, Dianzani, U, and Comi, C

Abstract

•Neurofilament light chains (NfL) require ultrasensitive techniques to be measured in the serum, and different platforms are available: Ella™, Lumipulse™, and SIMOA™.•In newly diagnosed relapsing-remitting multiple sclerosis (MS) patients CSF and serum NfL absolute levels strongly correlated between assays, although being more elevated with Ella™.•SIMOA™ and Lumipulse™ showed high agreement for serum and CSF values.

Published
2023
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246. Inhibitory activity of xanthine-oxidase and superoxide scavenger properties of Inga verna subsp. affinis. Its morphological and micrographic characteristics

Author

Vivot, Eduardo, primary, de Dios Muñoz, Juan, additional, del Carmen Cruañes, M, additional, Josefina Cruañes, M, additional, Tapia, Alejandro, additional, Schmeda Hirschmann, Guillermo, additional, Martı́nez, Erica, additional, Di Sapio, Osvaldo, additional, Gattuso, Martha, additional, and Zacchino, Susana, additional

Published
2001
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