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3. Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project

Author

Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., Ferroni, E., Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., and Ferroni, E.

Subjects
Male, medicine.medical_specialty, Population, Postmarketing surveillance, Rate ratio, REGISTRIES, Retrospective Studie, Internal medicine, BIOSIMILARS, medicine, Adalimumab, Humans, Pharmacology (medical), Original Research Article, education, Adverse effect, ANTI-TNF THERAPY, RHEUMATOID-ARTHRITIS, RISK, PHARMACOVIGILANCE, BIOSIMILARS, EXPERIENCE, REGISTRIES, PSORIASIS, MEDICINES, ACCESS, Biosimilar Pharmaceuticals, Retrospective Studies, RISK, Delivery of Health Care, Female, Infliximab, Italy, SARS-CoV-2, COVID-19, Pharmacology, education.field_of_study, PSORIASIS, business.industry, Biosimilar, ANTI-TNF THERAPY, General Medicine, medicine.disease, RHEUMATOID-ARTHRITIS, PHARMACOVIGILANCE, MEDICINES, EXPERIENCE, Immune-mediated inflammatory diseases, ACCESS, business, Human, Biosimilar Pharmaceutical, Biotechnology, medicine.drug
Abstract

Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

Published
2021

4. Analysis of fatal adverse drug events recorded in several Italian emergency departments (the MEREAFaPS study)

Author

Pagani, S., Lombardi, N., Crescioli, G., Vighi, G. V., Spada, G., Romoli, I., Andreetta, P., Capuano, A., Marrazzo, E., Marra, A., Leoni, O., Vannacci, A., Venegoni, M., Vighi, G. D., Bettoni, D., Blandizzi, C., Bonaiuti, R., Borsi, V., Cecchi, E., Convertino, I., Del Lungo, M., Di Mauro, C., Farina, G., Ferraro, S., Fucile, A., Galfrascoli, E., Geninatti, E., Giovannetti, L., Leonardi, L., Liccardo, R., Monina, G., Mugelli, A., Parrilli, M., Rafaniello, C., Rossi, F., Rostan, S., Ruocco, M., Sironi, M., Sportiello, L., Tuccori, M., Pagani, S., Lombardi, N., Crescioli, G., Vighi, G. V., Spada, G., Romoli, I., Andreetta, P., Capuano, A., Marrazzo, E., Marra, A., Leoni, O., Vannacci, A., Venegoni, M., Vighi, G. D., Bettoni, D., Blandizzi, C., Bonaiuti, R., Borsi, V., Cecchi, E., Convertino, I., Del Lungo, M., Di Mauro, C., Farina, G., Ferraro, S., Fucile, A., Galfrascoli, E., Geninatti, E., Giovannetti, L., Leonardi, L., Liccardo, R., Monina, G., Mugelli, A., Parrilli, M., Rafaniello, C., Rossi, F., Rostan, S., Ruocco, M., Sironi, M., Sportiello, L., and Tuccori, M.

Subjects
Drug, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, media_common.quotation_subject, Adverse drug reaction, 030204 cardiovascular system & hematology, 03 medical and health sciences, Appropriateness of drug use, Pharmacovigilance, 0302 clinical medicine, Older patients, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Drug safety, media_common, Aged, Medication error, business.industry, Public health, Anticoagulants, Mean age, medicine.disease, Italy, Concomitant, Emergency medicine, Emergency Medicine, Female, business, Emergency Service, Hospital, Algorithms, Platelet Aggregation Inhibitors
Abstract

Fatal Adverse Events (FADEs) are a major public health problem, and some FADEs could be preventable. The aim of the present study is to describe the frequency, the drugs involved and the preventability in the FADEs collected through the MEREAFaPS Study between 2012 and 2018. All cases including the outcome “death” have been examined. We excluded cases with vaccine-related ADEs, overdose or suicide, and ADEs occurred during the hospitalisation. Two trained assessors evaluated all cases fulfilling the inclusion criteria. ADEs’ preventability was evaluated applying the Schumock and Thornton algorithm. During the study period, we observed 429 cases of death, 92 of which were excluded. The remaining 337 cases involved 187 women and 150 men, with a mean age of 79 and of 77years, respectively. For each report, the suspected drugs and concomitant ones were 1.26 and 4.20, respectively. Anticoagulants and antiplatelet agents account for more than 40% of FADE cases and the most frequent reactions are haemorrhages (37.5%). The 25% of the FADEs were preventable. This study confirms that FADEs are still a relevant clinical occurrence, and are often caused by widely used old drugs associated with adverse events. The death of one in four patients was preventable. Further efforts should be done to improve the appropriateness of the therapy, especially in older patients who are treated with anticoagulants.

Published
2021

12. The role of Trichoderma spp. and silica gel in plant defence mechanisms and insect response in vineyard.

Author

Parrilli, M., Sommaggio, D., Tassini, C., Di Marco, S., Osti, F., Ferrari, R., Metruccio, E., Masetti, A., and Burgio, G.

Subjects
*SILICA gel, *TRICHODERMA, *JASMONIC acid, *VINEYARDS, *CHALCID wasps, *VITIS vinifera, *JASMONATE
Abstract

Several elicitors, stimulating induced resistance mechanisms, have potential in preventing or mitigating pathogen infections. Some of these compounds, triggering the production of jasmonic acid (JA), a precursor of herbivore-induced plant volatiles, could also play a central role in indirect resistance to pest species, by improving beneficial arthropod performance, and necrotrophic pathogens. In the current work, Trichoderma gamsii / T. asperellum and silica gel treatments – alone and in combination – were studied to evaluate the plant defence mechanism on grapevines (Vitis vinifera L.) by laboratory and field trials. JA production level was measured before and after Plasmopara viticola infection on potted vines. JA production induced by silica gel was higher than that caused by Trichoderma before infection. In Trichoderma -treated plants, JA production increased after P. viticola inoculation. In vineyard field trials, Mymaridae (Hymenoptera: Chalcidoidea) showed higher captures in transparent sticky traps on silica gel-treated plants, in comparison with control. On the other hand, no significant attraction was detected for Ichneumonoidea and other Chalcidoidea in silica gel and T. gamsii / T. asperellum -treated plants. The potential effects of elicitors are discussed, in the frame of attract and reward strategy. [ABSTRACT FROM AUTHOR]

Published
2019
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13. Program and abstracts for the 2011 Meeting of the Society for Glycobiology

Author

Hollingsworth, MT, Hart, GW, Paulson, JC, Stansell, E, Canis, K, Huang, IC, Panico, M, Morris, H, Haslam, S, Farzan, M, Dell, A, Desrosiers, R, von Itzstein, M, Matroscovich, M, Luther, KB, Hülsmeier, AJ, Schegg, B, Hennet, T, Nycholat, C, McBride, R, Ekiert, D, Xu, R, Peng, W, Razi, N, Gilbert, M, Wakarchuk, W, Wilson, IA, Gahlay, G, Geisler, C, Aumiller, JJ, Moremen, K, Steel, J, Labaer, J, Jarvis, DL, Drickamer, K, Taylor, M, Nizet, V, Rabinovich, G, Lewis, C, Cobb, B, Kawasaki, N, Rademacher, C, Chen, W, Vela, J, Maricic, I, Crocker, P, Kumar, V, Kronenberg, M, Paulson, J, Glenn, K, Mallinger, A, Wen, H, Srivastava, L, Tundup, S, Harn, D, Menon, AK, Yamaguchi, Y, Mkhikian, H, Grigorian, A, Li, C, Chen, HL, Newton, B, Zhou, RW, Beeton, C, Torossian, S, Tatarian, GG, Lee, SU, Lau, K, Walker, E, Siminovitch, KA, Chandy, KG, Yu, Z, Dennis, JW, Demetriou, M, Pandey, MS, Baggenstoss, BA, Washburn, JL, Weigel, PH, Chen, CI, Keusch, JJ, Klein, D, Hofsteenge, J, Gut, H, Szymanski, C, Feldman, M, Schaffer, C, Gao, Y, Strum, S, Liu, B, Schutzbach, JS, Druzhinina, TN, Utkina, NS, Torgov, VI, Szarek, WA, Wang, L, Brockhausen, I, Hitchen, P, Peyfoon, E, Meyer, B, Albers, SV, Chen, C, Newburg, DS, Jin, C, Dinglasan, RD, Beverley, SM, Guo, H, Novozhilova, N, Hickerson, S, Elnaiem, DE, Sacks, D, Turco, SJ, McKay, D, Castro, E, Takahashi, H, Straus, AH, Stalnaker, SH, Live, D, Boons, GJ, Wells, L, Stuart, R, Aoki, K, Boccuto, L, Zhang, Q, Wang, H, Bartel, F, Fan, X, Saul, R, Chaubey, A, Yang, X, Steet, R, Schwartz, C, Tiemeyer, M, Pierce, M, Kraushaar, DC, Condac, E, Nakato, H, Nishihara, S, Sasaki, N, Hirano, K, Nasirikenari, M, Collins, CC, Lau, JT, Devarapu, SK, Jeyaweerasinkam, S, Albiez, RS, Kiessling, L, Gu, J, Clark, GF, Gagneux, P, Ulm, C, Mahavadi, P, Müller, S, Rinné, S, Geyer, H, Gerardy-Schahn, R, Mühlenhoff, M, Günther, A, Geyer, R, Galuska, SP, Shibata, T, Sugihara, K, Nakayama, J, Fukuda, M, Fukuda, MN, Ishikawa, A, Terao, M, Kimura, A, Kato, A, Katayama, I, Taniguchi, N, Miyoshi, E, Aderem, A, Yoneyama, T, Angata, K, Bao, X, Chanda, S, Lowe, J, Sonon, R, Ishihara, M, Talabnin, K, Wang, Z, Black, I, Naran, R, Heiss, C, Azadi, P, Hurum, D, Rohrer, J, Balland, A, Valliere-Douglass, J, Kodama, P, Mujacic, M, Eakin, C, Brady, L, Wang, WC, Wallace, A, Treuheit, M, Reddy, P, Schuman, B, Fisher, S, Borisova, S, Coates, L, Langan, P, Evans, S, Yang, SJ, Zhang, H, Hizal, DB, Tian, Y, Sarkaria, V, Betenbaugh, M, Lütteke, T, Agravat, S, Cholleti, S, Morris, T, Saltz, J, Song, X, Cummings, R, Smith, D, Hofhine, T, Nishida, C, Mialy, R, Sophie, D, Sebastien, F, Patricia, C, Eric, S, Stephane, H, Mokros, D, Joosten, RP, Dominik, A, Vriend, G, Nguyen, LD, Martinez, J, Hinderlich, S, Reissig, HU, Reutter, W, Fan, H, Saenger, W, Moniot, S, Asada, H, Nakahara, T, Miura, Y, Stevenson, T, Yamazaki, T, De Castro, C, Burr, T, Lanzetta, R, Molinaro, A, Parrilli, M, Sule, S, Gerken, TA, Revpredo, L, Thome, J, Cardenas, G, Almeida, I, Leung, MY, Yan, S, Paschinger, K, Bleuler-Martinez, S, Jantsch, V, Wilson, I, Yoshimura, Y, Adlercreutz, D, Mannerstedt, K, Wakarchuk, WW, Dovichi, NJ, Hindsgaul, O, Palcic, MM, Chandrasekaran, A, Bharadwaj, R, Deng, K, Adams, P, Singh, A, Datta, A, Konasani, V, Imamura, A, Lowry, T, Scaman, C, Zhao, Y, Zhou, YD, Yang, K, Zhang, XL, Leymarie, N, Hartshorn, K, White, M, Cafarella, T, Seaton, B, Rynkiewicz, M, Zaia, J, Acosta-Blanco, I, Ortega-Francisco, S, Dionisio-Vicuña, M, Hernandez-Flores, M, Fuentes-Romero, L, Newburg, D, Soto-Ramirez, LE, Ruiz-Palacios, G, Viveros-Rogel, M, Tong, C, Li, W, Kong, L, Qu, M, Jin, Q, Lukyanov, P, Zhang, W, Chicalovets, I, Molchanova, V, Wu, AM, Liu, JH, Yang, WH, Nussbaum, C, Grewal, PK, Sperandio, M, Marth, JD, Yu, R, Usuki, S, Wu, HC, O'Brien, D, Piskarev, V, Ramadugu, SK, Kashyap, HK, Ghirlanda, G, Margulis, C, Brewer, C, Gomery, K, Müller-Loennies, S, Brooks, CL, Brade, L, Kosma, P, Di Padova, F, Brade, H, Evans, SV, Asakawa, K, Kawakami, K, Kushi, Y, Suzuki, Y, Nozaki, H, Itonori, S, Malik, S, Lebeer, S, Petrova, M, Balzarini, J, Vanderleyden, J, Naito-Matsui, Y, Takematsu, H, Murata, K, Kozutsumi, Y, Subedi, GP, Satoh, T, Hanashima, S, Ikeda, A, Nakada, H, Sato, R, Mizuno, M, Yuasa, N, Fujita-Yamaguchi, Y, Vlahakis, J, Nair, DG, Wang, Y, Allingham, J, Anastassiades, T, Strachan, H, Johnson, D, Orlando, R, Harenberg, J, Haji-Ghassemi, O, Mackenzie, R, Lacerda, T, Toledo, M, Straus, A, Takahashi, HK, Woodrum, B, Ruben, M, O'Keefe, B, Samli, KN, Yang, L, Woods, RJ, Jones, MB, Maxwell, J, Song, EH, Manganiello, M, Chow, YH, Convertine, AJ, Schnapp, LM, Stayton, PS, Ratner, DM, Yegorova, S, Rodriguez, MC, Minond, D, Jiménez-Barbero, J, Calle, L, Ardá, A, Gabius, HJ, André, S, Martinez-Mayorga, K, Yongye, AB, Cudic, M, Ali, MF, Chachadi, VB, Cheng, PW, Kiwamoto, T, Na, HJ, Brummet, M, Finn, MG, Hong, V, Polonskaya, Z, Bovin, NV, Hudson, S, Bochner, B, Gallogly, S, Krüger, A, Hanley, S, Gerlach, J, Hogan, M, Ward, C, Joshi, L, Griffin, M, Demarco, C, Deveny, R, Aggeler, R, Hart, C, Nyberg, T, Agnew, B, Akçay, G, Ramphal, J, Calabretta, P, Nguyen, AD, Kumar, K, Eggers, D, Terrill, R, d'Alarcao, M, Ito, Y, Vela, JL, Matsumura, F, Hoshino, H, Lee, H, Kobayashi, M, Borén, T, Jin, R, Seeberger, PH, Pitteloud, JP, Cudic, P, Von Muhlinen, N, Thurston, T, von Muhlinen, N, Wandel, M, Akutsu, M, Foeglein, AÁ, Komander, D, Randow, F, Maupin, K, Liden, D, Haab, B, Dam, TK, Brown, RK, Wiltzius, M, Jokinen, M, Andre, S, Kaltner, H, Bullen, J, Balsbaugh, J, Neumann, D, Hardie, G, Shabanowitz, J, Hunt, D, Hart, G, Mi, R, Ding, X, Van Die, I, Chapman, AB, Cummings, RD, Ju, T, Aryal, R, Ashley, J, Feng, X, Hanover, JA, Wang, P, Keembiyehetty, C, Ghosh, S, Bond, M, Krause, M, Love, D, Radhakrishnan, P, Grandgenet, PM, Mohr, AM, Bunt, SK, Yu, F, Hollingsworth, MA, Ethen, C, Machacek, M, Prather, B, Wu, Z, Kotu, V, Zhao, P, Zhang, D, van der Wel, H, Johnson, JM, West, CM, Abdulkhalek, S, Amith, SR, Jayanth, P, Guo, M, Szewczuk, M, Ohtsubo, K, Chen, M, Olefsky, J, Marth, J, Zapater, J, Foley, D, Colley, K, Kawashima, N, Fujitani, N, Tsuji, D, Itoh, K, Shinohara, Y, Nakayama, K, Zhang, L, Ten Hagen, K, Koren, S, Yehezkel, G, Cohen, L, Kliger, A, Khalaila, I, Finkelstein, E, Parker, R, Kohler, J, Sacoman, J, Badish, L, Hollingsworth, R, Tian, E, Hoffman, M, Hou, X, Tashima, Y, Stanley, P, Kizuka, Y, Kitazume, S, Yoshida, M, Kunze, A, Nasir, W, Bally, M, Hook, F, Larson, G, Mahan, A, Alter, G, Zeidan, Q, Copeland, R, Pokrovskaya, I, Willett, R, Smith, R, Morelle, W, Kudlyk, T, Lupashin, V, Vasudevan, D, Takeuchi, H, Majerus, E, Haltiwanger, RS, Boufala, S, Lee, YA, Min, D, Kim, SH, Shin, MH, Gesteira, T, Pol-Fachin, L, Coulson-Thomas, VJ, Verli, H, Nader, H, Liu, X, Yang, P, Thoden, J, Holden, H, Tytgat, H, Sánchez-Rodríguez, A, Schoofs, G, Verhoeven, T, De Keersmaecker, S, Marchal, K, Ventura, V, Sarah, N, Joann, P, Ding, Y, Jarrell, K, Cook, MC, Gibeault, S, Filippenko, V, Ye, Q, Wang, J, Kunkel, JP, Arteaga-Cabello, FJ, Arciniega-Fuentes, MT, McCoy, J, Ruiz-Palacios, GM, Francoleon, D, Loo, RO, Loo, J, Ytterberg, AJ, Kim, U, Gunsalus, R, Costello, C, Soares, R, Assis, R, Ibraim, I, Noronha, F, De Godoy, AP, Bale, MS, Xu, Y, Brown, K, Blader, I, West, C, Chen, S, Ye, X, Xue, C, Li, G, Yu, G, Yin, L, Chai, W, Gutierrez-Magdaleno, G, Tan, C, Wu, D, Li, Q, Hu, H, Ye, M, Liu, D, Mink, W, Kaese, P, Fujiwara, M, Uchimura, K, Sakai, Y, Nakada, T, Mabashi-Asazuma, H, Toth, AM, Scott, DW, Chacko, BK, Patel, RP, Batista, F, Mercer, N, Ramakrishnan, B, Pasek, M, Boeggeman, E, Verdi, L, Qasba, PK, Tran, D, Lim, JM, Liu, M, Mo, KF, Kirby, P, Yu, X, Lin, C, Costello, CE, Akama, TO, Nakamura, T, Huang, Y, Shi, X, Han, L, Yu, SH, Zhang, Z, Knappe, S, Till, S, Nadia, I, Catarello, J, Quinn, C, Julia, N, Ray, J, Tran, T, Scheiflinger, F, Szabo, C, Dockal, M, Niimi, S, Hosono, T, Michikawa, M, Kannagi, R, Takashima, S, Amano, J, Nakamura, N, Kaneda, E, Nakayama, Y, Kurosaka, A, Takada, W, Matsushita, T, Hinou, H, Nishimura, S, Igarashi, K, Abe, H, Mothere, M, Leonhard-Melief, C, Johnson, H, Nagy, T, Nairn, A, Rosa, MD, Porterfield, M, Kulik, M, Dalton, S, Pierce, JM, Hansen, SF, McAndrew, R, Degiovanni, A, McInerney, P, Pereira, JH, Hadi, M, Scheller, HV, Barb, A, Prestegard, J, Zhang, S, Jiang, J, Tharmalingam, T, Pluta, K, McGettigan, P, Gough, R, Struwe, W, Fitzpatrick, E, Gallagher, ME, Rudd, PM, Karlsson, NG, Carrington, SD, Katoh, T, Panin, V, Gelfenbeyn, K, Freire-de-Lima, L, Handa, K, Hakomori, SI, Bielik, AM, McLeod, E, Landry, D, Mendoza, V, Guthrie, EP, Mao, Y, Wang, X, Moremen, KW, Meng, L, Ramiah, AP, Gao, Z, Johnson, R, Xiang, Y, Rosa, MDEL, Wu, SC, Gilbert, HJ, Karaveg, K, Chen, L, Wang, BC, Mast, S, Sun, B, Fulton, S, Kimzey, M, Pourkaveh, S, Minalla, A, Haxo, T, Wegstein, J, Murray, AK, Nichols, RL, Giannini, S, Grozovsky, R, Begonja, AJ, Hoffmeister, KM, Suzuki-Anekoji, M, Suzuki, A, Yu, SY, Khoo, KH, van Alphen, L, Fodor, C, Wenzel, C, Ashmus, R, Miller, W, Stahl, M, Stintzi, A, Lowary, T, Wiederschain, G, Saba, J, Zumwalt, A, Meitei, NS, Apte, A, Viner, R, Gandy, M, Debowski, A, Stubbs, K, Witzenman, H, Pandey, D, Repnikova, E, Nakamura, M, Islam, R, Kc, N, Caster, C, Chaubard, JL, Krishnamurthy, C, Hsieh-Wilson, L, Pranskevich, J, Rangarajan, J, Guttman, A, Szabo, Z, Karger, B, Chapman, J, Chavaroche, A, Bionda, N, Fields, G, Jacob, F, Tse, BW, Guertler, R, Nixdorf, S, Hacker, NF, Heinzelmann-Schwarz, V, Yang, F, Kohler, JJ, Losfeld, ME, Ng, B, Freeze, HH, He, P, Wondimu, A, Liu, Y, Zhang, Y, Su, Y, Ladisch, S, Grewal, P, Mann, C, Ditto, D, Lardone, R, Le, D, Varki, N, Kulinich, A, Kostjuk, O, Maslak, G, Pismenetskaya, I, Shevtsova, A, Takeishi, S, Okudo, K, Moriwaki, K, Terao, N, Kamada, Y, Kuroda, S, Li, Y, Peiris, D, Markiv, A, Dwek, M, Adamczyk, B, Thanabalasingham, G, Huffman, J, Kattla, J, Novokmet, M, Rudan, I, Gloyn, A, Hayward, C, Reynolds, R, Hansen, T, Klimes, I, Njolstad, P, Wilson, J, Hastie, N, Campbell, H, McCarthy, M, Rudd, P, Owen, K, Lauc, G, Wright, A, Goletz, S, Stahn, R, Danielczyk, A, Baumeister, H, Hillemann, A, Löffler, A, Stöckl, L, Jahn, D, Bahrke, S, Flechner, A, Schlangstedt, M, Karsten, U, Goletz, C, Mikolajczyk, S, Ulsemer, P, Gao, N, Cline, A, Flanagan-Steet, H, Sadler, KC, Lehrman, MA, Coulson-Thomas, YM, Gesteira, TF, Mader, AM, Waisberg, J, Pinhal, MA, Friedl, A, Toma, L, Nader, HB, Mbua, EN, Johnson, S, Wolfert, M, Dimitrievska, S, Huizing, M, Niklason, L, Perdivara, I, Petrovich, R, Tokar, EJ, Waalkes, M, Fraser, P, Tomer, K, Chu, J, Rosa, S, Mir, A, Lehrman, M, Sadler, K, Lauer, M, Hascall, V, Calabro, A, Cheng, G, Swaidani, S, Abaddi, A, Aronica, M, Yuzwa, S, Shan, X, Macauley, M, Clark, T, Skorobogatko, Y, Vosseller, K, Vocadlo, D, Banerjee, A, Baksi, K, Banerjee, D, Melcher, R, Kraus, I, Moeller, D, Demmig, S, Rogoll, D, Kudlich, T, Scheppach, W, Scheurlen, M, Hasilik, A, Steirer, L, Lee, J, Moe, G, Troy, FA, Wang, F, Xia, B, Wang, B, Yi, S, Yu, H, Suzuki, M, Kobayashi, T, Sato, Y, Zhou, H, Briscoe, A, Lee, R, Wolfert, MA, Matsumoto, Y, Hamamura, K, Yoshida, T, Akita, K, Okajima, T, Furukawa, K, Urano, T, Ruhaak, LR, Miyamoto, S, and Lebrilla, CB

Subjects
Embryogenesis, Cancer screening, Cancer research, medicine, Cell migration, Neural cell adhesion molecule, Biology, medicine.disease, Biochemistry, Metastasis
Abstract

Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.

Published
2016

14. 'Structural characterization of the Lipid A from the LPS of the haloalkalophilic bacterium Halomonas pantelleriensis' in its current form for publication in the Extremophiles

Author

Carillo S., Pieretti G., Casillo A., Lindner B., Romano I., Nicolaus B., Parrilli M., Giuliano M., Cammarota M., Lanzetta R., and Corsaro MM.

Subjects
lipopolisaccaride, lipids (amino acids, peptides, and proteins)
Abstract

Halomonas pantelleriensis is a Gram-negative haloalkaliphilic bacterium isolated from the sand of the volcanic Venus mirror lake, closed to seashore in the Pantelleria island in the south of Italy. It is able to optimally grow in media containing 3-15% (w/v) total salt and at pH between 9-10. To survive in these harsh conditions the bug has developed several strategies that probably concern the bacteria outer membrane, a barrier regulating the exchange with the environment. In such a context the lipopolysaccharides (LPSs), which are among the major constituent of the Gram-negative outer membrane, are thought to contribute to the restrictive membrane permeability properties. The structure of the lipid A family derived from the lipopolysaccharide of Halomonas pantelleriensis is reported herein. The lipid A was obtained from the purified LPS by mild acid hydrolysis. The lipid A, which contains different number of fatty acids residues, and its partially deacylated derivatives were completely characterized by means of ESI FT-ICR mass spectrometry and chemical analysis. A comparison with the lipid A structure of the phylogenetic proximal Halomonas magadiensis is also reported.

Published
2016

20. [The new complexity: new dynamics in clusters and districts]

Author

Parrilli, M Davide

Subjects
ddc:330
Abstract

Recently, service clusters have been identified, such as in the case of the logistics and transportation cluster in the Basque Country (e.g. transportation of people and ware, intelligent transport services, etc.) or that of port activities (warehousing services, loading-unloading of goods, shipping service, etc.). Simultaneously, several multi-sector clusters around a specific client are rising. It is the case of the child cluster in France or in Catalunya that includes much more than traditional clusters focused on a final homogeneous product; in fact this includes the production of toys, kids clothes, health products and furniture for children, among others, which belonged to separate sectors and clusters before. In addition to identifying new types of clusters that strengthen the visibility and work of their firms , the great majority of these clusters and districts, e.g. in the Basque Country, have become more ‘complex' in depth (division and specialization of labor) and extension to a variety of activities that were quite separated from one another, though can now come together with the objective to respond to the new demand of local and global society. For instance, the demand for new renewable sources of energy promotes a change in sectoral/entrepreneurial attitudes, for which such diversified sectors as oil refinery, wind, maritime and solar energy, find representation in the same cluster association and recognize themselves as part of one 'complex' cluster that gains in visibility and scale of operations for global agents such as large industries, large scale construction projects, among others. The identification and the activity of such clusters and districts, sometimes associated in a specific locality, in other occasions to a wider territory, exhibit the growing awareness of the strengths and diversities of the territorial production fabric and the importance businesses and agents attribute to identifying themselves as such in order to develop joint initiatives that can generate important economies of scale and scope that help competing in the new globalized economy, particularly when these local production systems strive to open their way in global production networks and in international markets.

Published
2011

32. Structural elucidation of a novel core oligosaccharide backbone of the lipopolysaccharide from the new bacterial species Agrobacterium larrymoorei

Author

Molinaro A., De Castro C., Lanzetta R., Parrilli M., Raio A., and Zoina A.

Subjects
core oligosaccharide, phytopatogenic bacteria, lipids (amino acids, peptides, and proteins), R-form LPS, Agrobacterium larrymoorei
Abstract

Agrobacterium larrymoorei is a Gram negative phytopatogenic bacterium which produces tumors on Ficus benjamina plants and differs from other agrobacteria both genetically and biochemically. The lipopolysaccharide (LPS) plays an important role in the pathogenesis of agrobacteria. Depending on the saccharide size, there are two kinds of LPS deriving from smooth and rough bacteria (S-LPS and R-LPS). A. larrymoorei produces only an R-form LPS, a lipooligosaccharide and in this article the first core structure was elucidated for an Agrobacterium species. This core is unusual since it lacks heptose residues and phosphate groups. A similar structure was found in Rhizobium spp., that are a group of bacteria that taxonomically are very close to agrobacteria.

Published
2003

33. Structural determination of lipid A of the lipopolysaccharide from Pseudomonas reactans

Author

Silipo A., Lanzetta R., Garozzo D., Lo Cantore P., Iacobellis N.S., Molinaro A., Parrilli M., Evidente A., A., Silipo, R., Lanzetta, D., Garozzo, P., LO CANTORE, N. S., Iacobelli, A., Molinaro, M., Parrilli, and Evidente, Antonio

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

'The chemical structure of lipid A from the lipopolysaccharide of the mushroom-associated bacterium Pseudomonas reactans, a pathogen of cultivated mushroom, was elucidated by compositional analysis and spectroscopic methods (MALDI-TOF and two-dimensional NMR). The sugar backbone was composed of the beta-(1'-->6)-linked d-glucosamine disaccharide 1-phosphate. The lipid A fraction showed remarkable heterogeneity with respect to the fatty acid and phosphate composition. The major species are hexacylated and pentacylated lipid A, bearing the (R)-3-hydroxydodecanoic acid [C12:0 (3OH)] in amide linkage and a (R)-3- hydroxydecanoic [C10:0 (3OH)] in ester linkage while the secondary fatty acids are present as C12:0 and/or C12:0 (2-OH). A nonstoichiometric phosphate substitution at position C-4' of the distal 2-deoxy-2-amino- glucose was detected. Interestingly, the pentacyl lipid A is lacking a primary fatty acid, namely the C10:0 (3-OH) at position C-3'. The potential biological meaning of this peculiar lipid A is also discussed.

Published
2002

35. Enfermedad Vascular de Dieulafoy como una Emergencia Quirúrgica: Revisión

Author

Fernandez, L, Parrilli, M, Tenia, JC, Da Silva, M, Bracho, N, Alvarez, G, and Cedeño, JG

Subjects
Dieulafoy’s illness, Enfermedad de dieulafoy, Vascular ectasy, Hemorragia digestiva superior, Ectasia vascular, Upper gastrointestinal bleeding
Abstract

Se presenta un caso de enfermedad de Dieulafoy en una paciente de 51 años quien presentó hemorragia digestiva superior profusa, con deterioro hemodinámico. Se realizó intervención quirúrgica encontrándose lesión fúndica, sangrante, compatible con la enfermedad de Dieulafoy y situs abdominalis inversus, falleciendo en el postoperatorio inmediato. Esta enfermedad poco frecuente es causa de hemorragia digestiva superior y se diagnostica por endoscopia o en el curso de una laparatomia, observándose arteria de mediano calibre sangrante en las porciones altas del estómago. El tratamiento suele ser quirúrgico pero recientemente la endoscopia superior ha tomado la pauta diagnóstica y terapéutica. Se hacen consideraciones teórico-analíticas de tan inusual patología. A case of Dieulafoy’s illness in a female 51 years old presenting an important upper gastrointestinal bleeding with haemodinamic failure is reported. Emergency laparatomy was performed and it showed hemorrhagic fundus lesion. Diagnosis was made by histopathology studies; situs inversus of abdominal organs was also seen. The patient died in inmediate postoperative period. This unusual illness causes upper gastrointestinal tract bleeding and its diagnosis is performed either by endoscopy or laparatomy, showing bleeding in a middle caliber artery of upper stomach. The traditional treatment has been abdominal surgery, but recently, upper endoscopy has become an alternative for diagnosis and therapeutic procedures. Theorical and analytic considerations of this rare disease are made in relation with the present case.

Published
2000

37. Innate Immunity: Plant Recognition of Bacterial MAMPs

Author

Erbs, Gitte, Jensen, Tina Tandrup, Dow, J. M., Molinaro, A., Parrilli, M., Cooper, R. M., Newman, Mari-Anne, Erbs, Gitte, Jensen, Tina Tandrup, Dow, J. M., Molinaro, A., Parrilli, M., Cooper, R. M., and Newman, Mari-Anne

Published
2008

49. First structural characterization of Burkholderia vietnamiensis lipooligosaccharide from cystic fibrosis-associated lung transplantation strains

Author

Ierano, T., primary, Silipo, A., additional, Sturiale, L., additional, Garozzo, D., additional, Bryant, C., additional, Lanzetta, R., additional, Parrilli, M., additional, Aldridge, C., additional, Gould, F K., additional, Corris, P. A, additional, Khan, C M A., additional, De Soyza, A., additional, and Molinaro, A., additional

Published
2009
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