Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Biopsia percutánea de páncreas trasplantado bajo guía ecográfica: un procedimiento seguro

Objetivo. Describir la tasa de complicaciones de la biopsia percutánea de páncreas trasplantado bajo guía ecográfica usando una aguja N16 Gauge. Material y métodos. En este estudio retrospectivo se analizaron los resultados de las biopsias de páncreas trasplantado en el Hospital Italiano de Buenos Aires entre 1997 y 2012. En todos los pacientes la indicación del procedimiento fue la sospecha de rechazo. Lue - go de verificar que no existían contraindicaciones, se realizó la biopsia percutánea del páncreas trasplantado guiada por ecografía usando una aguja N16 Gauge. Las muestras fueron valoradas inmediatamente por un patólogo para establecer que el material obtenido era suficiente. Se documentaron las complicaciones. Resultados. En el servicio de Intervencionis - mo del Hospital Italiano de Buenos Aires se realizaron un total de 92 biopsias percutáneas de páncreas en 47 pacientes. En el 86% de las biopsias se realizaron 2 tomas y en el 14% sólo una. El 100% de las biopsias fue diagnóstico. Solo en dos pacientes se registraron complicaciones que fueron una fístula pancreática post-punción, que curó con tratamiento conservador, y un intenso dolor post-punción con reacción va - sovagal, que revirtió con maniobras para aumentar el retor - no venoso. Conclusión. Nuestros resultados con aguja 16G son similares a los reportados por otros autores con agujas de menor calibre (18G o 20G), por lo que podemos interpretar que la biopsia percutánea de páncreas trasplantado bajo guía ecográfica con aguja 16G es una técnica segura (2,2% de complicaciones) y eficaz para el diagnóstico histopatológico de rechazo (100%)

TGF-beta specifically enhances the metastatic attributes of murine lung adenocarcinoma: implications for human non-small cell lung cancer

Lung cancer is the most frequent and one of the most deadly cancer types and is classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Transforming growth factor beta (TGFb) regulates a wide array of cell functions and plays a major role in lung diseases, including NSCLC. TGFb signals through the complex of TGFb type I and type II receptors, triggering Smad and non-Smad signaling pathways such as PI3K/Akt and MEK1/ERK. We investigated the role of TGFb1 on the progression of the murine lung adenocarcinoma cell line LP07. Furthermore, we undertook a retrospective study with tissue samples from stage I and II NSCLC patients to assess the clinical pathologic role and prognostic significance of TbRI expression. We demonstrated that although lung cancer cell monolayers responded to TGFb1 anti-mitogenic effects and TGFb1 pulse (24 h treatment) delayed tumor growth at primary site; a switch towards malignant progression upon TGFb1 treatment was observed at the metastatic site. In our model, TGFb1 modulated in vitro clonogenicity, protected against stress-induced apoptosis and increased adhesion, spreading, lung retention and metastatic outgrowth. PI3K and MEK1 signaling pathways were involved in TGFb1-mediated metastasis stimulation. Several of these TGFb responses were also observed in human NSCLC cell lines. In addition, we found that a higher expression of TbRI in human lung tumors is associated with poor patient’s overall survival by univariate analysis, while multivariate analysis did not reach statistical significance. Although additional detailed analysis of the endogenous signaling in vivo and in vitro is needed, these studies may provide novel molecular targets for the treatment of lung cancer.Fil: Vazquez, Paula Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Daroqui, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas, Argentina; Montefiore Medical Center. Department of Oncology; Estados Unidos de América;Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Dalurzo, Mercedes Liliana. Hospital Italiano de Buenos Aires; Argentina;Fil: Smith, David Eduardo. Hospital Italiano de Buenos Aires; Argentina;Fil: Grasselli, Julieta. Hospital Italiano de Buenos Aires; Argentina;Fil: Pallota, Maria Guadalupe. Hospital Italiano de Buenos Aires; Argentina;Fil: Ehrlich, Marcelo. Tel Aviv University. George S. Wise Faculty of Life Sciences. Department of Neurobiochemistry; Israel;Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Typical and atypical carcinoid tumors of the lung: A Clinicopathological correlation OF OF 783 cases with Emphasis on histological features.

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcome. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2mm, necrosis, lymphatic invasion and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlate with clinical outcome. Based on our analysis, we consider that the separation of low and intermediate grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of over grading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcome