Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global <it>HDAC </it>expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.</p> <p>Methods</p> <p>Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV <it>HDACs </it>was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene <it>β-glucuronidase</it>. Protein levels were evaluated by western blotting.</p> <p>Results</p> <p>We found that mRNA levels of class II and IV <it>HDACs </it>were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, <it>p </it>< 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue.</p> <p>Conclusion</p> <p>Our study establishes a negative correlation between <it>HDAC </it>gene expression and the glioma grade suggesting that class II and IV <it>HDACs </it>might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of <it>HDAC </it>mRNA in glioblastomas.</p

Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina

Fil: Libster, Romina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Coviello, Silvina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Hijano, Diego R. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Dunaiewsky, Mariana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Reynoso, Natalia. Hospital Municipal Materno Infantil de San Isidro; Argentina.Fil: Cavalieri, Maria L. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Guglielmo, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Areso, M. Soledad. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Gilligan, Tomas. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santucho, Fernanda. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Gregorio, Gabriela L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Moreno, Rina. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Lutz, Maria I. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Panigasi, Alicia L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Saligari, Liliana. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Caballero, Mauricio T. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Egües Almeida, Rodrigo M. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Gutierrez Meyer, Maria E. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Neder, Maria D. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Davenport, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Del Valle, Maria P. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santidrian, Valeria S. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Mosca, Guillermina. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alvarez, Liliana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Landa, Patricia. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Pota, Ana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Boloñati, Norma. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Dalamon, Ricardo. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Sanchez Mercol, Victoria I. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Espinoza, Marco. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Peuchot, Juan Carlos. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Karolinski, Ariel. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bruno, Miriam. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Borsa, Ana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Ferrero, Fernando. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bonina, Angel. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Ramonet, Margarita. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Albano, Lidia C. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Luedicke, Nora. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alterman, Elias. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Savy, Vilma L. ANLIS Dr.C.G.Malbrán. Instituto de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Virosis Respiratoria; Argentina.Fil: Chappell, James D. Vanderbilt University. Pathology, Nashville, Tennessee; Estados Unidos.Fil: Edwards, Kathryn M. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Melendi, Guillermina A. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Polack, Fernando P. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. Results: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). Conclusions: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years

The Promigratory Activity of the Matricellular Protein Galectin-3 Depends on the Activation of PI-3 Kinase

Expression of galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and galectin-3−/− mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, galectin-3−/− sarcoma cells were more adherent and less migratory than galectin-3+/+ sarcoma cells on laminin-111. When galectin-3 was transiently expressed in galectin-3−/− sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular galectin-3 led to the recruitment of SHP-2 phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700