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3. Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Author

Podlekareva, D. N., Panteleev, A. M., Grint, D., Post, F. A., Miro, J. M., Bruyand, M., Furrer, H., Obel, N., Girardi, E., Vasilenko, A., Losso, M. H., Arenas-Pinto, A., Cayla, J., Rakhmanova, A., Zeltina, I., Werlinrud, A. M., Lundgren, J. D., Mocroft, A., Kirk, O., Toibaro, J. J., Warley, E., Tamayo, N., Cristina Ortiz, M., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Skrahina, E., Skrahin, A., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., d'Arminio Monforte, A., Riekstina, V., Aldins, P., Duiculescu, D., Malashenkov, E., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes, J. L., Martinez-Lacasa, X., Falco, V., Imaz, A., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Miller, R., Chentsova, N., Podlekareva, D., Kjaer, J., and Duiculesku, D.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Tuberculosis, Anti-HIV Agents, Antitubercular Agents, Argentina, HIV Infections, Rate ratio, Cohort Studies, symbols.namesake, Cause of Death, Coinfection, Europe, Female, Humans, Multivariate Analysis, Internal medicine, medicine, Poisson regression, Cause of death, business.industry, Mortality rate, medicine.disease, 3. Good health, Surgery, Cohort, symbols, business, Cohort study
Abstract

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (3 months, 3-12 months or12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died3 months, 3-12 months or12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Published
2014

4. Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

Author

Podlekareva, D. N., Grint, D., Post, F. A., Mocroft, A., Panteleev, A. M., Miller, R. F., Miro, J. M., Bruyand, M., Furrer, H., Riekstina, V., Girardi, E., Losso, M. H., Cayla, J. A., Malashenkov, E. A., Obel, N., Skrahina, A. M., Lundgren, J. D., Kirk, O., Chentsova, N., Duiculesku, D., Toibaro, J. J., Warley, E., Tamayo, N., Ortiz, M. C., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Vasilenko, A., Skrahina, E., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., Aldins, P., Zeltina, I., Duiculescu, D., Rakhmanova, A., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes Mutua de Terrassa, J. L., Martinez-Lacasa, X., Imaz, V. F., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Arenas-Pinto, A., Kjaer, J., and Ellefson, M.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, TB-HIV co-infection, Health care index score, Outcome of TB-HIV patients, TB-HIV health care utilisation, AIDS-Related Opportunistic Infections, Cause of Death, Coinfection, Delivery of Health Care, Female, Follow-Up Studies, Global Health, HIV Seropositivity, Humans, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Health care, medicine, 030212 general & internal medicine, Cause of death, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Regimen, Infectious Diseases, Risk assessment, business
Abstract

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

Published
2013

6. ISS-NIA ITALIAN COHORT: NEW ANTI-HIV INHIBITORS IN PATIENTS EXPERIENCED TO IP, NRTI, NNRTI

Author

Bucciardini, R., Floridia, M., Weimer, Le, Fragola, V., Massella, M., Baroncelli, S., Pirillo, Mf, Galluzzo, Cm, Donnini, S., Mirra, M., Di Gregorio, M., Lucattini, S., Fucili, L., Baldelli, F., Francisci, D., Martinelli, L., Bastianelli, S., Pastore, G., Ladisa, N., Volpe, A., Vullo, V., D Ettore, G., Ceccarelli, G., Andreoni, M., Sarmati, L., Delle Rose, D., Montano, M., Tozzi, V., Libertone, R., Pucillo, L., Narciso, P., Bellagamba, R., Tommasi, C., Petrosillo, N., Cicalini, S., Sighinolfi, L., Daniela Segala, Armignacco, O., Preziosi, R., Ferrari, C., Antoni, Ad, Cavalli, A., Parruti, G., Sozio, F., Cosentino, L., Dionisio, D., Vivarelli, A., Manconi, Pe, Ortu, F., Di Martino, Ml, Chiodo, F., Biagelti, C., Borderi, M., Boni, P., Del Gobbo, R., Paggi, Am, Silvestri, C., Scalise, G., Giacometti, A., Cirioni, O., Mura, Ms, Mannazzu, M., Coinu, G., Bellissima, P., Bonfante, S., Neri, D., Guaraldi, G., and Beghetto, B.

Subjects
antiretroviral therapy, HIV, COHORT STUDY, NO
Published
2009

9. Phenomenological analysis of the dynamics of cryoaggregation by light-scattering spectrometry.

Author

Giardina, Bruno, Di Stasio, Enrico, Di Stasio, E., Bizzarri, P., Bove, M., Casato, M., Fiorilli, M., Galtieri, A., Pucillo, L. P., Di Stasio, Enrico (ORCID:0000-0003-1047-4261), Giardina, Bruno, Di Stasio, Enrico, Di Stasio, E., Bizzarri, P., Bove, M., Casato, M., Fiorilli, M., Galtieri, A., Pucillo, L. P., and Di Stasio, Enrico (ORCID:0000-0003-1047-4261)

Abstract

Cryoglobulins are proteins that precipitate at temperatures below 37 degreesC. Coldinduced precipitation of proteins may occur in vivo secondary to several important diseases, and lead to pathological manifestations involving different organs. Cryoprecipitation may be observed in vitro by exposing serum samples, supposed to contain cryoglobulins, to low temperatures, but this needs several days to occur. Proteinprotein interactions leading to cryoprecipitation are still poorly understood and the knowledge of the underlying mechanism may be relevant to the understanding of the onset of pathological manifestations. Using lightscattering spectrometry, we studied cryoprecipitation occurring in vitro at different temperatures and cryoglobulin concentrations. We describe the kinetics of the coldinduced precipitation of mixed cryoglobulins, measured as increase in turbidity. The plots obtained demonstrate that the cryoprecipitation did not occur as a singlestep reaction, but consisted of four distinct phases where both temperature and cryoglobulin concentration affected the immune complexes formation. Light scatter spectrometry may provide a simple, sensitive and rapid method for the detection of cryoglobulins

Published
2003

13. Formalin-treated bacteria as selective B cell mitogens: Results in primary and acquired immunodeficiencies

Author

Sirianni, M. C., Pucillo, L. P., MASSIMO FIORILLI, Aiuti, F., Banck, G., and Forsgren, A.

Subjects
Adult, Male, B-Lymphocytes, Adolescent, Bacteria, Immunologic Deficiency Syndromes, Infant, Lymphocyte Activation, Leukemia, Lymphoid, Child, Preschool, Formaldehyde, Humans, Female, Mitogens, Child, Cell Division, Research Article
Abstract

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

15. Lymphocyte distribution and intrahepatic compartmentalization during HCV infection: a main role for MHC-unrestricted T cells

Author

Chiara Agrati, Nisii, C., Oliva, A., D Offizi, G., Montesano, C., Pucillo, L. P., and Poccia, F.

Subjects
Settore MED/04 - Patologia Generale, gamma-delta, T-Cell, Hepatitis C, Lymphocyte Subsets, Liver, T-Lymphocyte Subsets, Antigen, Receptors, Natural, Cytokines, Animals, Killer Cells, Humans, Inflammation Mediators, Receptors, Antigen, T-Cell, gamma-delta, Killer Cells, Natural

16. Marked increase in etravirine and saquinavir plasma concentrations during atovaquone/proguanil prophylaxis

Author

Ivanovic Jelena, Gallo Anna L, D'Avolio Antonio, Tempestilli Massimo, Bellagamba Rita, Tommasi Chiara, Nicastri Emanuele, Pucillo Leopoldo P, and Narciso Pasquale

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract The case of a 32-year-old Caucasian female with multi-drug resistant HIV-1 subtype B infection treated with a salvage regimen including maraviroc, raltegravir, etravirine and unboosted saquinavir who started atovaquone/proguanil prophylaxis, is reported. The potential interactions between atovaquone/proguanil and these anti-retroviral drugs are investigated. Pharmacokinetic analyses documented a marked increase in etravirine and saquinavir plasma concentrations (+55% and +274%, respectively), but not in raltegravir and maraviroc plasma concentrations. The evidence that atovaquone/proguanil significantly interacts with etravirine and saquinavir, but not with raltegravir and maraviroc, suggests that the mechanism of interaction is related to cytochrome P450.

Published
2011
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17. Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload

Author

Leopoldo Paolo Pucillo, Andrea Baiocchini, Carmine Mancone, Franca Del Nonno, Marco Tripodi, Vera van Noort, Tonino Alonzi, Claudia Montaldo, Nicolina Rotiroti, Giuseppe Ippolito, Laura Amicone, Alice Conigliaro, Angela Maria Cozzolino, Cecilia Battistelli, Simone Mattei, Montaldo, C., Mattei, S., Baiocchini, A., Rotiroti, N., Nonno, F., Pucillo, L., Cozzolino, A., Battistelli, C., Amicone, L., Ippolito, G., van Noort, V., Conigliaro, A., Alonzi, T., Tripodi, M., Mancone, C., Department of Cellular Biotechnologies and Haematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), L. Spallanzani, National Institute for Infectious Diseases (IRCCS), European Molecular Biology Laboratory [Heidelberg] (EMBL), and This work was supported by grants from MIUR Ministero dell’Universit `a e Ricerca Scientifica (FIRB 2012, codice progetto RBFR12NSCF), Associazione Italiana per la Ricerca sul Cancro (AIRC) andMinistero della Salute (Ricerca Finalizzata 40H27, Ricerca Corrente).

Subjects
Liver Cirrhosis, Proteomics, hepatitis C virus, Male, MESH: Isotope Labeling, HSC, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Fibrosis, MESH: Up-Regulation, Membrane Protein, hepatic stellate cell, liver fibrosis, hepatic iron overload, 0303 health sciences, biology, MESH: Proteomics, Medicine (all), hepatocellular carcinoma, Biomedicine, hepatitis c infection, vitronectin, Hepatitis C, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Up-Regulation, 3. Good health, cell culture-derived HCV, Isotope Labeling, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Hepatic iron overload, Hepatitis C infection, Liver fibrosis, Vitronectin, Biomarkers, Cell Line, Humans, Iron Overload, Membrane Proteins, Molecular Biology, HCV, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Biomarker (medicine), MESH: Membrane Proteins, MESH: Liver Cirrhosis, Human, Liver Cirrhosi, Hepatitis C virus, MESH: Iron Overload, 03 medical and health sciences, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Hepatitis C, MESH: Humans, MESH: Biological Markers, Liver fibrosi, Proteomic, Biomarker, medicine.disease, MESH: Vitronectin, MESH: Male, digestive system diseases, MESH: Cell Line, Biomedicine / Abbreviations: HCC, HCVcc, Immunology, Cancer research, Hepatic stellate cell, biology.protein, Steatosis
Abstract

Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Published
2014
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18. RESEARCH NOTE Evaluation of the BDProbeTec strand displacement amplification assay in comparison with the AMTD II direct test for rapid diagnosis of tuberculosis.

Author

Visca, P., De Mori, P., Festa, A., Montrone, M. L., Amicosante, M., and Pucillo, L. P.

Subjects
*MYCOBACTERIUM tuberculosis, *TUBERCULOSIS, *ZIEHL-Neelsen stain, *MYCOBACTERIA identification, *MICROBIOLOGY, *BIOLOGICAL assay
Abstract

The BDProbeTec MTB assay for direct detection of Mycobacterium tuberculosis was evaluated in comparison with the AMTD-II assay on 94 samples from different patients with clinical suspicion of tuberculosis. Using a combination of culture on Lowenstein–Jensen medium (with or without preculture in BACTEC 9000) and clinical diagnosis as the standard, BDProbeTec MTB showed high sensitivity and specificity (96.1% and 100%, respectively), similar to AMTD-II (96.1% and 97.1%, respectively), with significantly higher sensitivity than the Ziehl–Neelsen stain for acid-fast bacilli (73%, p < 0.05). [ABSTRACT FROM AUTHOR]

Published
2004
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19. Dendritic cells derived from BCG-infected precursors induce Th2-like immune response

Author

Nunzia Sanarico, Leopoldo Paolo Pucillo, Vittorio Colizzi, Antonio Ciaramella, Carlo Ramoni, Angelo Martino, Silvia Vendetti, Alessandra Sacchi, Francesca Spadaro, Martino, A., Sacchi, A., Sanarico, N., Spadaro, F., Ramoni, C., Ciaramella, A., Pucillo, L. P., Colizzi, V., and Vendetti, S.

Subjects
Lipopolysaccharides, Immunology, CD1a, Biology, complex mixtures, Peripheral blood mononuclear cell, Monocytes, Proinflammatory cytokine, Th2 Cells, Immune system, Polarization, medicine, Humans, Immunology and Allergy, Cytokine, Monocyte, Mycobacteria, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin, hemic and immune systems, Cell Differentiation, Dendritic Cells, Cell Biology, Fetal Blood, Mycobacterium bovis, Coculture Techniques, medicine.anatomical_structure, Differentiation, BCG Vaccine, Cytokines, Tumor necrosis factor alpha, Tuberculosis vaccines, BCG vaccine
Abstract

Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a– DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor α, IL-1β, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.

Published
2004
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20. Non-pathogenic Mycobacterium smegmatis induces the differentiation of human monocytes directly into fully mature dendritic cells

Author

Alessandra Sacchi, Elisabetta Volpe, Leopoldo Paolo Pucillo, Angelo Martino, Silvia Vendetti, Chiara Agrati, Vittorio Colizzi, Rafaella De Santis, Martino, A., Sacchi, A., Volpe, E., Agrati, C., De Santis, R., Pucillo, L. P., Colizzi, V., and Vendetti, S.

Subjects
Adult, Adolescent, T-Lymphocytes, Mycobacterium smegmatis, Immunology, Antigen presentation, Cell Communication, CD1a, Monocytes, Microbiology, Th2 Cells, Immune system, Humans, Immunology and Allergy, Monocyte differentiation, Cells, Cultured, biology, Follicular dendritic cells, Tumor Necrosis Factor-alpha, CLEC7A, Cell Differentiation, Dendritic Cells, Th1 Cells, Hematopoietic Stem Cells, Acquired immune system, biology.organism_classification, Interleukin-12, Interleukin-10, Interleukin 12, M. smegmati, Dendritic cell
Abstract

Mycobacterium smegmatis infects human monocytes that can be precursors of dendritic cells. We tested whether the interaction of M. smegmatis with monocytes modulated their differentiation into dendritic cells. We found that M. smegmatis-infected monocytes differentiated into CD1a-CCR7 + dendritic cells in the presence of GM-CSF and IL-4 and acquired a mature phenotype since they expressed CD83 molecules in the absence of maturation stimuli. Dendritic cells derived from M. smegmatis-infected monocytes stimulated with bacterial products, produced IL-10 and still retained the capacity to produce IL-12. Consequently, they polarized naïve T lymphocytes towards a mixed Th1/Th2 immune response inducing both IFN-γ and IL-4 production. These findings suggest that the exposure to environmental mycobacteria could modulate the differentiation of dendritic cells making them able to migrate into secondary lymphoid organs and modulate the adaptive immune response. This could explain one of the mechanisms by which environmental mycobacteria can influence the immune response to pathogenic species. © 2005 Springer Science+Business Media, Inc.

Published
2005

21. 25-Hydroxyvitamin D Plasma Levels in Natural Populations of Pigmented and Partially Pigmented Land Iguanas from Galápagos ( Conolophus spp.).

Author

Di Giacomo C, Pucillo L, Sevilla C, Fucci G, Massoud R, Bernardini S, Fraziano M, and Gentile G

Subjects
Animals, Ecuador, Vitamin D analogs & derivatives, Iguanas, Lizards
Abstract

We report the first data on 25-hydroxyvitamin D plasma levels in natural populations of three species of land iguana endemic to the Galápagos Islands ( Conolophus marthae , C. subcristatus , and C. pallidus ). The pigment is present throughout the whole body in the skin of C. subcristatus and C. pallidus . On the contrary, pigment is not present in the skin of an extended part of the body in C. marthae . The only existing population of C. marthae is syntopic with a population of C. subcristatus , and the two species are closely related. These circumstances would suggest that, under the assumption that the species show a similar basking behavior and in the absence of compensatory mechanisms, lighter pigmentation should favor higher vitamin D levels. Thus, C. marthae , compared with C. subcristatus in Wolf Volcano, could show higher levels of 25(OH)D plasma levels, or equal, if compensatory mechanisms exist. The three species showed levels in the range of average values for healthy iguanas. However, contrary to the expectation, C. marthae consistently exhibited the lowest 25(OH)D plasma levels. We discuss possible factors affecting vitamin concentration and hypothesize that C. marthae may use the habitat to limit exposure to the high UVB irradiation at Wolf Volcano., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Cristina Di Giacomo et al.)

Published
2022
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22. Cystic echinococcosis in a single tertiary care center in Rome, Italy.

Author

Petrone L, Cuzzi G, Colace L, Ettorre GM, Busi-Rizzi E, Schininà V, Pucillo L, Angeletti C, Pane S, Di Caro A, Bordi E, Girardi E, Pozio E, Corpolongo A, Teggi A, Brunetti E, and Goletti D

Subjects
Adult, Animals, Cysts pathology, Echinococcosis epidemiology, Echinococcus pathogenicity, Humans, Italy, Liver parasitology, Male, Middle Aged, Echinococcosis therapy, Liver pathology, Tertiary Care Centers
Abstract

Background: Cystic echinococcosis (CE) is a chronic, clinically complex, and neglected disease. Its prevalence in Italy, a country of medium to high endemicity, remains poorly defined, as notification has long ceased to be mandatory., Methods: We set up a retrospective cohort study involving all CE patients followed at our institute between January 2005 and December 2012. Demographical and clinical features were recorded and analyzed., Results: CE was found in 28 patients (64.3%), mostly Italians from the central regions (50%), followed by subjects from the islands (33.3%) and Southern Italy (16.7%). Their median age was 45 years (IQR: 38.5-66.5), with Eastern Europeans being significantly younger (28 years, IQR: 19-39) than other patients (P ≤ 0.0001). A total of 149 cysts, mostly with hepatic localization (96%), were described. Based on the WHO classification, the cysts were mainly small (80.5%) and active (CE1 (73.8%); CE2 (7.4%)). Active cysts were more common in Eastern Europeans (85.7%) than Italians (66.7%)., Conclusion: Our data confirm CE occurrence in Italy. We emphasize the importance to have a national CE registry, opportunely recently introduced. This is essential to assess CE prevalence in this country, implement appropriate control measures, and improve patient management.

Published
2013
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23. Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones.

Author

Pasca MR, Degiacomi G, Ribeiro AL, Zara F, De Mori P, Heym B, Mirrione M, Brerra R, Pagani L, Pucillo L, Troupioti P, Makarov V, Cole ST, and Riccardi G

Subjects
Base Sequence, DNA Primers genetics, DNA, Bacterial genetics, Drug Resistance, Multiple, Bacterial genetics, Europe, Genes, Bacterial, Humans, In Vitro Techniques, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis genetics, Racemases and Epimerases genetics, Antitubercular Agents pharmacology, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Spiro Compounds pharmacology, Thiazines pharmacology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology
Abstract

The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant Mycobacterium tuberculosis clinical isolates from four European hospitals were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.

Published
2010
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24. Simple and reliable method for detection and genotyping of hepatitis C virus RNA in dried blood spots stored at room temperature.

Author

Solmone M, Girardi E, Costa F, Pucillo L, Ippolito G, and Capobianchi MR

Subjects
Genotype, Hepacivirus genetics, Hepatitis C virology, Humans, Reproducibility of Results, Temperature, Blood Specimen Collection methods, Hepacivirus classification, Hepacivirus isolation & purification, RNA, Viral blood
Abstract

We describe a simple, sensitive, and reproducible method for using whole blood collected onto filter paper (dried blood spots) for detection and genotyping of hepatitis C virus RNA that can be useful in large field studies, particularly in settings where collection, preparation, storage, and shipment of samples at controlled temperature can be difficult.

Published
2002
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25. Mixed cryoglobulinemia secondary to visceral Leishmaniasis.

Author

Casato M, de Rosa FG, Pucillo LP, Ilardi I, di Vico B, Zorzin LR, Sorgi ML, Fiaschetti P, Coviello R, Laganà B, and Fiorilli M

Subjects
Adult, Animals, Antigens, Protozoan blood, Cryoglobulinemia blood, Cryoglobulinemia immunology, Humans, Leishmania immunology, Male, Vasculitis diagnosis, Cryoglobulinemia complications, Leishmaniasis, Visceral etiology
Abstract

We describe a case of type II mixed cryoglobulinemia, with monoclonal IgMkappa rheumatoid factor, associated with visceral leishmaniasis caused by Leishmania infantum. Involvement of Leishmania antigen(s) in the formation of cryoprecipitable immune complexes was suggested by the fact that cryoglobulinemic vasculitis subsided after antiparasite therapy and that anti-Leishmania antibodies, as well as rheumatoid factor, were enriched in the cryoprecipitate. We observed 2 additional patients with visceral leishmaniasis and cryoglobulinemic vasculitis. All 3 patients had seemingly contracted leishmaniasis in Italy, were hepatitis C virus negative, and were initially diagnosed as having autoimmune disorders. These findings indicate that Leishmania can be an etiologic agent of type II mixed cryoglobulinemia. This parasitosis should be taken into consideration in the differential diagnosis of vasculitides in endemic areas.

Published
1999
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26. Predictors of long-term response to high-dose interferon therapy in type II cryoglobulinemia associated with hepatitis C virus infection.

Author

Casato M, Agnello V, Pucillo LP, Knight GB, Leoni M, Del Vecchio S, Mazzilli C, Antonelli G, and Bonomo L

Subjects
Adult, Aged, Cryoglobulinemia complications, Cryoglobulinemia physiopathology, Female, Humans, Interferon alpha-2, Male, Middle Aged, Recombinant Proteins, Time Factors, Treatment Outcome, Cryoglobulinemia drug therapy, Hepatitis C complications, Interferon-alpha administration & dosage
Abstract

We have prospectively studied patients with type II cryoglobulinemia since 1985 to assess the efficacy of treatment with interferon-alpha at cumulative doses ranging from 234 to 849 MU. In the present study we retrospectively evaluated in this cohort parameters associated with complete response to therapy in 31 consecutive patients with type II cryoglobulinemia associated with hepatitis C virus (HCV) infection. Prevalence of complete response of cryoglobulinemia (disappearance of symptoms and signs of vasculitis and decrease of cryocrit below 10% of the initial value) was 62%, with a median response duration of 33 months and a range of 3 to 100 months. Three patients were putatively cured, as they remained in complete remission for more than 5 years off therapy. Eighteen patients (58%) had liver disease evidenced by histopathology and/or raised transaminase levels. Prevalence of normalization of transaminase levels was 100%, with a median response duration of 36 months. Relapse of hypertransaminasemia occurred in 100% and 8% of patients receiving less than or greater than 621 MU, respectively. By logistic regression analysis, the only pretherapy parameter that associated significantly (P = .0393) with complete response of cryoglobulinemia was the solitary anti-C22 (HCV core) antibody pattern, which was observed in 29% of patients. Association with older age and low cryocrit approached statistical significance (P = . 06), while no significant correlations were found with serum IgM levels, duration of disease, HCV genotype, NS5a gene mutations, liver histology, HLA-DR phenotype, or WA cross-idiotype. Complete responses were also associated, on univariate statistical analysis, with low pretherapy HCV viremia. Responses were accompanied by decrease of viremia, of anti-HCV antibody levels and cryocrit. The usefulness of a high dose regimen is underscored by the higher rates of sustained responses of cryoglobulinemia and transaminase levels compared with previous studies.

Published
1997

27. Formalin-treated bacteria as selective B cell mitogens: results in primary and acquired immunodeficiencies.

Author

Sirianni MC, Pucillo LP, Fiorilli M, Aiuti F, Banck G, and Forsgren A

Subjects
Adolescent, Adult, Bacteria drug effects, Cell Division, Child, Child, Preschool, Female, Formaldehyde pharmacology, Humans, Immunologic Deficiency Syndromes immunology, Infant, Leukemia, Lymphoid immunology, Male, B-Lymphocytes immunology, Bacteria immunology, Lymphocyte Activation, Mitogens pharmacology
Abstract

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

Published
1981

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