The PML/RARalpha fusion protein inhibits tumor necrosis factor-alpha-induced apoptosis in U937 cells and acute promyelocytic leukemia blasts

We investigated the effect of the acute promyelocytic leukemia (APL) specific PML/RARalpha fusion protein on the sensitivity to TNF-alpha-mediated apoptosis. The U937 leukemia cell line was transduced with PML/RARalpha cDNA. PML/RARalpha expression caused a markedly reduced sensitivity to TNF-alpha, even if apoptosis was triggered by agonistic antibodies to TNF-alpha receptors I and II (TNF-alphaRI, II). PML/RARalpha induced a 10-20-fold decrease of the TNF-alpha-binding capacity via downmodulation of both TNF-alphaRI and TNF-alphaRII: this may mediate at least in part the reduced sensitivity to TNF-alpha. Furthermore, the fusion protein did not modify Fas expression (CD95) or sensitivity to Fas-mediated apoptosis. The pathophysiological significance of these findings is supported by two series of observations. (a) Fresh APL blasts exhibit no TNF-alpha binding and are resistant to TNF-alpha-mediated apoptosis. Conversely, normal myeloblasts-promyelocytes show marked TNF-alphaR expression and are moderately sensitive to TNF-alpha-mediated cytotoxicity. Similarly, blasts from other types of acute myeloid leukemia (AML M1, M2, and M4 FAB types) show an elevated TNF-alpha binding. (b) The NB4 APL cell line, which is PML/RARalpha+, shows low TNF-alphaR expression capacity and is resistant to TNF-alpha-triggered apoptosis; conversely a PML/RARalpha- NB4 subclone (NB4.306) exhibits detectable TNF-alpha-binding capacity and is sensitive to TNF-alpha-mediated cytotoxicity. These studies indicate that the PML/RARalpha fusion protein protects against TNF-alpha-induced apoptosis, at least in part via downmodulation of TNF-alphaRI/II: this phenomenon may play a significant role in APL, which is characterized by prolonged survival of leukemic blasts.     

Determination of cadmium and lead in vegetables by stripping chronopotentiometry.

A method for the determination of cadmium and lead in vegetables by stripping chronopotentiometric analysis, after digestion of the sample with concentrated sulphuric acid and dry-ashing, is described. Metal ions were concentrated as their amalgams on a glassy carbon-working electrode previously coated with a thin mercury film and then stripped by a suitable oxidant. Potential and time data were digitally derived and E was plotted versus dt/dE(-1), thus increasing both the sensitivity of the method and the resolution of the analysis. Quantitative analysis was carried out by the method of standard addition; good linearity was obtained in the range of examined concentrations, as was shown by the determination coefficients, which were 0.998 (n = 4) for cadmium and 0.993 (n = 4) for lead. Recoveries of 85-100% for cadmium and of 84-97% for lead were obtained from a sample spiked at different levels. Accuracy was demonstrated by analysis of a matching reference sample of cabbage. The detection limits were 1.8 ng g(-1) of wet mass for cadmium and 5.1 ng g(-1) of wet mass for lead. The relative standard deviations (mean of nine determinations), evaluated on a real sample, were 6.7 and 6.2%, respectively. Results obtained on 10 different commercial samples of pepper (Capsicum annuum), and egg plant (Solanum melongena) were not significantly different from those obtained by graphite furnace atomic absorption spectrophotometry technique. The average content was in the range 3.1-18.6 ng g(-1) for cadmium and 38.2-64.3 ng g(-1) for lead.     

Working With Patients Involved in the Mafia: Considerations From Italian Psychotherapy Experiences.

The authors report their main findings on the psychological characteristics of Mafia members studied in the past 10 years. Clinical data were collected, such as psychotherapy reports of therapists who treated patients belonging to the Mafia and clinical interviews of important Italian Mafia informers. The psychological profile of a Mafia member and his relatives is described. The importance of the process of identity construction that a mafioso must learn in order to join the Cosa Nostra organization is outlined. The psychological distress mafiosi suffer and the type of psychotherapy they require are reported, including brief excerpts from clinical sessions. Therapists and analysts always feel troubled working with these patients, and supervision is often required. Italian clinical work differs greatly from that represented in American movies, and specific theoretical and clinical training is necessary to treat the particular characteristics of these patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

SiP Tuner With Integrated LC Tracking Filter for Both Cable and Terrestrial TV Reception

A silicon tuner has been designed for the reception of analog or digital TV signals from a cable or a terrestrial network. It exhibits 5 dB NF over the 42-870 MHz frequency range and integrates a self-calibrated LC tracking filter. This allows 55 dB video SNR under fully loaded spectrum conditions. The (N + 1) image channel is rejected by more than 62 dB thanks to a fully integrated full complex mixer with auto calibration. The 5.7 mm² active die is fabricated in 40-GHz f_T BiCMOS 0.25 mum technology and dissipates 780 mW running from a 3.3 V supply.     

Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects

Palmitoylethanolamide (PEA) is an endogenous lipid produced on demand by neurons and glial cells that displays neuroprotective properties. It is well known that inflammation and neuronal damage are strictly related processes and that microglia play a pivotal role in their regulation. The aim of the present work was to assess whether PEA could exert its neuroprotective and anti-inflammatory effects through the modulation of microglia reactive phenotypes. In N9 microglial cells, the pre-incubation with PEA blunted the increase of M1 pro-inflammatory markers induced by lipopolysaccharide (LPS), concomitantly increasing those M2 anti-inflammatory markers. Images of microglial cells were processed to obtain a set of morphological parameters that highlighted the ability of PEA to inhibit the LPS-induced M1 polarization and suggested that PEA might induce the anti-inflammatory M2a phenotype. Functionally, PEA prevented Ca²⁺ transients in both N9 cells and primary microglia and antagonized the neuronal hyperexcitability induced by LPS, as revealed by multi-electrode array (MEA) measurements on primary cortical cultures of neurons, microglia, and astrocyte. Finally, the investigation of the molecular pathway indicated that PEA effects are not mediated by toll-like receptor 4 (TLR4); on the contrary, a partial involvement of cannabinoid type 2 receptor (CB2R) was shown by using a selective receptor inverse agonist.     

A family systems approach for preventing adolescent runaway behavior

A family therapy approach, combining the conceptual frameworks of the Bowen model and Olson's Circumplex model, was used to restructure family relationships in order to prevent further runaway behavior of a 15-year-old Mexican-American female. A structured family interview was conducted to identify problems, a genogram was used to obtain the family's history, and therapy (family, individual, and mother-daughter) was provided to change the family system. The Family Satisfaction Scale was administered to evaluate the effectiveness of this therapeutic approach.     

MLH1 and MSH2 constitutional mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer

Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) may have a significant impact on the clinical management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for the selection of candidates for genetic testing. However, reports of mismatch repair (MMR) gene mutations in families not fulfilling the minimal diagnostic criteria point out the necessity to identify additional clinical parameters suggestive of genetic predisposition to colorectal cancer (CRC) related to MMR defects. We thus investigated a series of 32 Italian putative HNPCC individuals selected on the basis of one of the following criteria: 1) family history of CRC and/or other extracolonic tumors; 2) early-onset CRC; and 3) presence of multiple primary malignancies in the same individual. These patients were investigated for the presence of MLH1 and MSH2 mutations by single-strand conformation polymorphism analysis. Pathogenetic truncating mutations were identified in 4 (12.5%) cases, 3 of them involving MSH2 and 1 MLH1. In addition, 2 missense MLH1 variants of uncertain significance were observed. All pathogenetic mutations were associated with early age (<40 years) at onset and proximal CRC location. Our results support the contention that constitutional MMR mutations can also occur in individuals without the classical HNPCC pattern. Moreover, evaluation of the clinical parameters associated with MMR mutations indicates that early onset combined with CRC location in the proximal colon can be definitely considered suggestive of MMR-related hereditary CRC and should be included among the guidelines for referring patients for genetic testing.     

An empirical approach for ranking environmental and energy saving measures in the hotel sector

The energy demand of the hotel sector of an Italian region is here utilized for hierarchizing, by means of an empirical method, efficient measures devoted to energy saving and reduction of CO₂ emissions.Due to the large number of consumers present in the selected territorial area and the lack in detailed data, the energy demand assessment is here carried out by the analysis of a sample of representative consumers.A short set of indexes, referring to energy and environmental performances, are defined and calculated for different clusters of hotels, grouped on the basis of site characteristics, opening periods, number of beds, and building age. Such indexes are utilized to establish lists of actions with assigned priorities stemming from energy, environmental and economics issues.Energy planners and decision makers can easily use this approach for defining, implementing and monitoring energy efficiency as well as sustainability policies in the tourist sector of a given geographical area, starting from a limited set of data. The method has been proposed by authors within the assessment of the Sicilian Energy Masterplan.