M. Gentile | Università degli Studi "La Sapienza" di Roma (original) (raw)
Papers by M. Gentile
PLoS ONE, 2012
To understand how cytotoxic agent-induced cancer cell death affects the immune system is of funda... more To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients.
AIDS Research and Human Retroviruses, 1999
The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial ... more The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.
Virology, 1999
A peculiar characteristic of cells infected with human herpesvirus 6 (HHV6) is the absence of vir... more A peculiar characteristic of cells infected with human herpesvirus 6 (HHV6) is the absence of viral glycoproteins on the plasma membrane, which may reflect an atypical intracellular transport of the virions and/or the viral glycoproteins, different from that of the other members of the herpesvirus family. To investigate the maturation pathway of HHV-6 in the human T lymphoid cell line HSB-2, we used lectin cytochemistry and immunogold labeling combined with several electron microscopical techniques, such as ultrathin frozen sections, postembedding, and fracture-label. Immunolabeling with anti-gp116 and anti-gp82-gp105 monoclonal antibodies revealed that the viral glycoproteins are undetectable on nuclear membranes and that at the inner nuclear membrane nucleocapsids acquire a primary envelope lacking viral glycoproteins. After de-envelopment, cytoplasmic nucleocapsids acquire a thick tegument and a secondary envelope with viral glycoproteins at the level of neo-formed annulate lamellae or at the cis-side of the Golgi complex. Cytochemical labeling using helix pomatia lectin revealed that the newly acquired secondary viral envelopes contain intermediate forms of glycocomponents, suggesting a sequential glycosylation of the virions during their transit through the Golgi area before their final release into the extracellular space. Immunogold labeling also showed that the viral glycoproteins, which are not involved in the budding process, reach and accumulate in the endosomal/lysosomal compartment. Pulse-chase analysis indicated degradation of the gp116, consistent with its endosomal localization and with the absence of viral glycoproteins on the cell surface of the infected cells.
Clinical Microbiology and Infection, 2010
To investigate the burden of influenza-like illness (ILI), patients attending an emergency depart... more To investigate the burden of influenza-like illness (ILI), patients attending an emergency department during the influenza season were tested for several common respiratory viruses, using PCRbased methods. Influenza A viruses were detected in 25 of 103 recruited patients (24%), rhinoviruses in 15%, and respiratory syncytial virus in only one. The data suggest that triage criteria based on ILI case definitions would not contain the spread of the influenza virus during pandemic alerts and could lead to unnecessary isolation of patients with other infections. Application of broader triage criteria followed by timely molecular diagnosis could be effective in preventing new respiratory agent transmission.
Ultrasound in Obstetrics and Gynecology, 2006
Results: Eleven cases of suspected venous anomalies of the cardinal and umbilical veins were eval... more Results: Eleven cases of suspected venous anomalies of the cardinal and umbilical veins were evaluated. B-flow provided complete 3D rendition of anomalous anatomy in interrupted IVC with azygos continuation, three cases of agenesis of ductus venosus, one draining into the right atrium, one to the IVC, and one to the right iliac vein; one case of persistent left SVC with drainage to the coronary sinus, one case of PRUV, and one intra-abdominal umbilical vein varix. B-flow was found to have added value as compared to both power Doppler and inversion mode in the evaluation of these lesions, by demonstrating the three dimensional structure of the affected vessels in these complex lesions. The modality was found to improve diagnostic capability as well as communication with professionals and parents. Conclusions: In cases of venous anomalies, B-flow modality can become an important adjunct to complete fetal assessment, and may aid in diagnosis, counseling, and professional consultation.
Ultrasound in Obstetrics & Gynecology, 2004
Cat-eye syndrome (CES) is a rare disorder of chromosome 22 characterized by tetrasomy of the regi... more Cat-eye syndrome (CES) is a rare disorder of chromosome 22 characterized by tetrasomy of the region that spans the chromosome 22p arm, and part of 22q11 (CES chromosome) 1 . We report a case of CES diagnosed prenatally through cytogenetic and fluorescence in-situ hybridization (FISH) analysis following chorionic villus sampling performed for increased nuchal translucency thickness (NT) at 12 weeks' gestation. Two-dimensional (2D) and three-dimensional (3D) ultrasound and echocardiography were performed, and disclosed some peculiar CES findings such as preauricular skin tags, and, for the first time prenatally, an anomalous connection of the left pulmonary veins to a dilated coronary sinus.
Clinical Microbiology and Infection, 2010
To investigate the burden of influenza-like illness (ILI), patients attending an emergency depart... more To investigate the burden of influenza-like illness (ILI), patients attending an emergency department during the influenza season were tested for several common respiratory viruses, using PCRbased methods. Influenza A viruses were detected in 25 of 103 recruited patients (24%), rhinoviruses in 15%, and respiratory syncytial virus in only one. The data suggest that triage criteria based on ILI case definitions would not contain the spread of the influenza virus during pandemic alerts and could lead to unnecessary isolation of patients with other infections. Application of broader triage criteria followed by timely molecular diagnosis could be effective in preventing new respiratory agent transmission.
PLoS ONE, 2012
To understand how cytotoxic agent-induced cancer cell death affects the immune system is of funda... more To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients.
AIDS Research and Human Retroviruses, 1999
The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial ... more The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.
Virology, 1999
A peculiar characteristic of cells infected with human herpesvirus 6 (HHV6) is the absence of vir... more A peculiar characteristic of cells infected with human herpesvirus 6 (HHV6) is the absence of viral glycoproteins on the plasma membrane, which may reflect an atypical intracellular transport of the virions and/or the viral glycoproteins, different from that of the other members of the herpesvirus family. To investigate the maturation pathway of HHV-6 in the human T lymphoid cell line HSB-2, we used lectin cytochemistry and immunogold labeling combined with several electron microscopical techniques, such as ultrathin frozen sections, postembedding, and fracture-label. Immunolabeling with anti-gp116 and anti-gp82-gp105 monoclonal antibodies revealed that the viral glycoproteins are undetectable on nuclear membranes and that at the inner nuclear membrane nucleocapsids acquire a primary envelope lacking viral glycoproteins. After de-envelopment, cytoplasmic nucleocapsids acquire a thick tegument and a secondary envelope with viral glycoproteins at the level of neo-formed annulate lamellae or at the cis-side of the Golgi complex. Cytochemical labeling using helix pomatia lectin revealed that the newly acquired secondary viral envelopes contain intermediate forms of glycocomponents, suggesting a sequential glycosylation of the virions during their transit through the Golgi area before their final release into the extracellular space. Immunogold labeling also showed that the viral glycoproteins, which are not involved in the budding process, reach and accumulate in the endosomal/lysosomal compartment. Pulse-chase analysis indicated degradation of the gp116, consistent with its endosomal localization and with the absence of viral glycoproteins on the cell surface of the infected cells.
Clinical Microbiology and Infection, 2010
To investigate the burden of influenza-like illness (ILI), patients attending an emergency depart... more To investigate the burden of influenza-like illness (ILI), patients attending an emergency department during the influenza season were tested for several common respiratory viruses, using PCRbased methods. Influenza A viruses were detected in 25 of 103 recruited patients (24%), rhinoviruses in 15%, and respiratory syncytial virus in only one. The data suggest that triage criteria based on ILI case definitions would not contain the spread of the influenza virus during pandemic alerts and could lead to unnecessary isolation of patients with other infections. Application of broader triage criteria followed by timely molecular diagnosis could be effective in preventing new respiratory agent transmission.
Ultrasound in Obstetrics and Gynecology, 2006
Results: Eleven cases of suspected venous anomalies of the cardinal and umbilical veins were eval... more Results: Eleven cases of suspected venous anomalies of the cardinal and umbilical veins were evaluated. B-flow provided complete 3D rendition of anomalous anatomy in interrupted IVC with azygos continuation, three cases of agenesis of ductus venosus, one draining into the right atrium, one to the IVC, and one to the right iliac vein; one case of persistent left SVC with drainage to the coronary sinus, one case of PRUV, and one intra-abdominal umbilical vein varix. B-flow was found to have added value as compared to both power Doppler and inversion mode in the evaluation of these lesions, by demonstrating the three dimensional structure of the affected vessels in these complex lesions. The modality was found to improve diagnostic capability as well as communication with professionals and parents. Conclusions: In cases of venous anomalies, B-flow modality can become an important adjunct to complete fetal assessment, and may aid in diagnosis, counseling, and professional consultation.
Ultrasound in Obstetrics & Gynecology, 2004
Cat-eye syndrome (CES) is a rare disorder of chromosome 22 characterized by tetrasomy of the regi... more Cat-eye syndrome (CES) is a rare disorder of chromosome 22 characterized by tetrasomy of the region that spans the chromosome 22p arm, and part of 22q11 (CES chromosome) 1 . We report a case of CES diagnosed prenatally through cytogenetic and fluorescence in-situ hybridization (FISH) analysis following chorionic villus sampling performed for increased nuchal translucency thickness (NT) at 12 weeks' gestation. Two-dimensional (2D) and three-dimensional (3D) ultrasound and echocardiography were performed, and disclosed some peculiar CES findings such as preauricular skin tags, and, for the first time prenatally, an anomalous connection of the left pulmonary veins to a dilated coronary sinus.
Clinical Microbiology and Infection, 2010
To investigate the burden of influenza-like illness (ILI), patients attending an emergency depart... more To investigate the burden of influenza-like illness (ILI), patients attending an emergency department during the influenza season were tested for several common respiratory viruses, using PCRbased methods. Influenza A viruses were detected in 25 of 103 recruited patients (24%), rhinoviruses in 15%, and respiratory syncytial virus in only one. The data suggest that triage criteria based on ILI case definitions would not contain the spread of the influenza virus during pandemic alerts and could lead to unnecessary isolation of patients with other infections. Application of broader triage criteria followed by timely molecular diagnosis could be effective in preventing new respiratory agent transmission.