Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo

Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa−/−). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

High-powEr Phosphorous-based DFB Lasers for Cold Atom Systems (HELCATS)

No abstract available

Deep underground rotation measurements: GINGERino ring laser gyroscope in Gran Sasso

GINGERino is a large frame laser gyroscope investigating the ground motion in the most inner part of the underground international laboratory of the Gran Sasso, in central Italy. It consists of a square ring laser with a $3.6$ m side. Several days of continuous measurements have been collected, with the apparatus running unattended. The power spectral density in the seismic bandwidth is at the level of $10^{-10} \rm{(rad/s)/\sqrt{Hz}}$. A maximum resolution of $30\,\rm{prad/s}$ is obtained with an integration time of few hundred seconds. The ring laser routinely detects seismic rotations induced by both regional earthquakes and teleseisms. A broadband seismic station is installed on the same structure of the gyroscope. First analysis of the correlation between the rotational and the translational signal are presented.Published0345027TM. Sviluppo e Trasferimento TecnologicoJCR Journa

Infected pancreatic necrosis : outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

Peer reviewe

Introducing the “analogs for Venus’ geologically recent surfaces” initiative: an opportunity for identifying and analyzing recently active volcano-tectonic areas of Venus trough a comparative study with terrestrial analogs

Several missions to Venus have been recently selected for launch [1–6], opening a new era for the exploration of the planet. One of the key questions that the future missions need to address is whether Venus is presently volcanically active [7–15]. Studying areas of active volcanism and tectonism on Venus is crucial to reveal clues about the geologic past of the planet, as well as provide information about the volatile content of its interior and the formation of its dense atmosphere. The “Analogsfor VENus’ GEologically Recent Surfaces” (AVENGERS) initiative aims to build a comprehensive database of terrestrial analog sites for the comparative study of recent and possibly on- going volcanic activity on Venus. Besides its scientific relevance, the AVENG- ERS initiative also acts as a bridge for international scientific collaboration, including the leadership and/or team members from the currently selected missions to Venus