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Search Results: 1 - 10 of 26165 matches for " Bruno Di Stefano "
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Low affinity PEGylated hemoglobin from Trematomus bernacchii, a model for hemoglobin-based blood substitutes
Daniela Coppola, Stefano Bruno, Luca Ronda, Cristiano Viappiani, Stefania Abbruzzetti, Guido di Prisco, Cinzia Verde, Andrea Mozzarelli
BMC Biochemistry , 2011, DOI: 10.1186/1471-2091-12-66
Abstract: To investigate the effects of PEGylation on protein structure and function, we compared the PEGylation products of human hemoglobin and Trematomus bernacchii hemoglobin, a natural variant endowed with a remarkably low oxygen affinity and high tetramer stability. We show that extension arm facilitated PEGylation chemistry based on the reaction of T. bernacchii hemoglobin with 2-iminothiolane and maleimido-functionalyzed polyethylene glycol (MW 5000 Da) leads to a tetraPEGylated product, more homogeneous than the corresponding derivative of human hemoglobin. PEGylated T. bernacchii hemoglobin largely retains the low affinity of the unmodified tetramer, with a p50 50 times higher than PEGylated human hemoglobin. Moreover, it is still sensitive to protons and the allosteric effector ATP, indicating the retention of allosteric regulation. It is also 10-fold less reactive towards nitrogen monoxide than PEGylated human hemoglobin.These results indicate that PEGylated hemoglobins, provided that a suitable starting hemoglobin variant is chosen, can cover a wide range of oxygen-binding properties, potentially meeting the functional requirements of blood substitutes in terms of oxygen affinity, tetramer stability and NO dioxygenase reactivity.Hemoglobin-based oxygen carriers (HBOCs) are a novel therapeutic class consisting of hemoglobin (Hb) derivatives administered intravenously as substitutes for blood transfusions. Modifications of the natural tetramer are required to reduce toxicity, as unmodified, cell-free Hb, once dissociated into dimers, is easily filtered by the kidneys and causes severe nephrotoxicity. Moreover, Hb extravasates through the endothelium, where it scavenges the vasoactive mediator nitrogen monoxide (NO), causing a range of toxic effects that include vasoconstriction and blood pressure increase. The strategies so far explored to avoid such effects mainly aim at increasing the molecular size of the natural Hb tetramers, thus limiting the size-dependent ve
An ES-Like Pluripotent State in FGF-Dependent Murine iPS cells
Bruno Di Stefano,Christa Buecker,Federica Ungaro,Alessandro Prigione,Hsu-Hsin Chen,Maaike Welling,Maureen Eijpe,Gustavo Mostoslavsky,Paul Tesar,James Adjaye,Niels Geijsen,Vania Broccoli
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016092
Abstract: Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a na?ve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display na?ve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.
Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis
Elena Fiorio, Anna Mercanti, Marianna Terrasi, Rocco Micciolo, Andrea Remo, Alessandra Auriemma, Annamaria Molino, Veronica Parolin, Bruno Di Stefano, Franco Bonetti, Antonio Giordano, Gian Cetto, Eva Surmacz
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-305
Abstract: Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data.HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors.Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.Recent epidemiological and clinical data confirmed that obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive breast tumors and resistance to certain anti-breast cancer treatments [1-4]. The molecular mechanisms of this link are not clear, but several studies in animal and cellular models suggested that excess body weight could promote breast cancer through increased production of an adipocyte-derived hormone leptin [5-7]. The primary function of leptin is to regulate energy balance and food intake by acting in the brain, but the hormone also plays an important role in peripheral organs, modulating fertility, lactation, and immune response [8,9]. Leptin levels in humans correlate with adiposity and are usually higher in females than in males [8].Leptin action is mediated through the transmembrane leptin receptor ObR [10]. The human ObR can be expressed as at least four isoforms with different COOH-terminal cytoplasmic domains [11]. The full (long)
Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation: An ex-vivo pilot experimental study in animal models
Vincenzo Lamonaca, Antonino Virga, Marta Ida Minervini, Roberta Di Stefano, Alessio Provenzani, Pietro Tagliareni, Giovanna Fleres, Angelo Luca, Giovanni Vizzini, Ugo Palazzo, Bruno Gridelli
World Journal of Gastroenterology , 2009,
Abstract: AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs).METHODS: Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80°C, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic.RESULTS: The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts.CONCLUSION: RTA appears to be very effective in killing hydatid cysts of explanted liver and lung. Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration, injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.
Two sides of the Myc-induced DNA damage response: from tumor suppression to tumor maintenance
Stefano Campaner, Bruno Amati
Cell Division , 2012, DOI: 10.1186/1747-1028-7-6
Abstract: c-MYC (henceforth MYC) is an immediate-early serum response gene essential for embryonic development, cellular proliferation and survival, and a cellular proto-oncogene that is frequently up-regulated in cancer. The Myc protein is a basic Helix-Loop-Helix Leucine Zipper (bHLHZip) transcription factor, which forms transcriptionally active dimers with another bHLHZip protein called Max [1,2]. Dimerization with Max endows Myc with sequence specific DNA binding ability, preferentially to sites containing the E-box sequence CACGTG. The transactivation properties of this complex are carried out by the N-terminal portion of Myc [3]. Myc is a multifunctional transcription factor able to regulate cell cycle, growth, metabolism, differentiation, apoptosis, transformation, genomic instability, and angiogenesis. Recently, transcription independent functions of Myc have been proposed particularly concerning the role of Myc in regulating pre-replication complexes assembly onto DNA replication origins [4]. While low Myc levels are necessary and sufficient for cellular viability and proliferation, pathological activation of this proto-oncogene has been linked to over-expression and gain of function mutations [5-7]. Pathological over-expression is frequently achieved by transcriptional up-regulation due to chromosomal translocation leading to promoter rearrangement [8-12], gene amplification [13,14] or by virus mediated insertional mutagenesis [15,16]. In prostate and breast cancers, a significant fraction of tumors demonstrate amplification of an otherwise unrearranged c-MYC locus (Pietilainen et al., 1995; Bubendorf et al., 1999; Sato et al., 1999; Naidu et al., 2002). In contrast, the Myc mRNA and protein over-expression that is observed in 70-80% of colon carcinomas (Smith and Goh, 1996) results from aberrant transcriptional control of the MYC locus involving mutations in APC-b-catenin-TCF-4 pathway members (Barker et al., 2000). Similarly, in Human acute T-cell lymphoblastic le
The 'off-hour' effect in trauma care: a possible quality indicator with appealing characteristics
Stefano Di Bartolomeo
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2011, DOI: 10.1186/1757-7241-19-33
Abstract: Although the importance of quality indicators (QI) is undisputed, the debate concerning their validity is incessant. A recent systematic review [1] concluded that 'there is not a common set of clearly defined, evidence-based and broadly accepted QIs for evaluating the quality of trauma care.'A recent study [2] compared the mortality of trauma patients admitted inside and outside normal working hours in a North-American trauma system. Evenings, nights, and weekends were intended as non-working hours - also referred as 'after' or 'off' hours, as opposed to 'office' or 'business' hours. The study found no difference, however previous studies that investigated the so-called 'weekend' or 'off-hour' effect in various diseases yielded inconsistent results; sometimes such a difference was found [3-8,15] and sometimes not [9-15].This commentary discusses why the evaluation of the 'off-hour' effect can also be considered a QI. Furthermore, it examines the theoretical characteristics of such a QI, with a special emphasis on its potential to overcome the usual obstacles for QIs in trauma care.QIs aim at measuring quality. The common definition of quality by the United States Institute of Medicine is 'the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge [16].' Thus, any QI should be related to a certain level of the desired health outcomes. Any person is allowed to consider an outcome as 'desired' and devise the consequent QIs. Nevertheless, there is little doubt that health-care quality ultimately aims at influencing mortality and/or morbidity. Indeed, the above mentioned two outcomes are most used QIs themselves, under the category of 'outcome indicators'' of the classic classification by Donabedian [17]. However, it has been identified that the effects of quality on mortality may be difficult to measure because of a low signal-to-noise ratio [18]. It has be
El Láser Er: Yag como alternativa en la práctica odontológica operatoria
Di Stefano,Rosanna;
Acta Odontológica Venezolana , 2004,
Abstract: this work is based on the clinical experience with er: yag laser, which is the most recent type of all the forms of application laser in the different specialties within the field of dentistry. furthermore, the er:yag laser is the most employed and suitable type of laser which is being used on the hard tissue section of the tooth.(1) experience would be presented obtained in the private clinic on patients treated with the er: yag laser along one year. only cavities class i, ii, iii, iv and v, according the classification of black (2) , were carried out. all these cavities were done on the level of: enamel, enamel and dentin and dentin near the pulp cameral. the sample embraced patients of both sex, clasified according to the type of treated cavities and according to the verbal valuation of pain. all of the treatments were done neither without anesthesia nor phosphoric acid to 35% for the engroving of the surface of the enamel and the dentin. the patients have did not neither operative symptoms. all the patients were surprise by the speedness, the painless and the silence of the procedure by using the er:yag laser.
Por una historia de la secularización y de la laicidad en la Argentina
Di Stefano,Roberto;
Quinto sol , 2011,
Abstract: discussing with the frame on the same phenomena recently proposed by fortunato mallimaci, this paper suggests a periodization and some hypotheses for the interpretation of secularism and secularization process in argentina from the bourbon reforms to the present. from an explanation of the sense that the author gives to the concepts of secularism and secularization, it offers a periodization scheme that appeals to the concepts of "umbral de secularización" and "pacto laico" coined by jean baubérot for france and for latin europe. as an interpretive scheme, the article does not constitute a summary of the history of catholicism or the relations between church and state. for this reason, the stages that the author considers are worth reinterpreting-essentially the turn of the century- have deserved more attention than others and therefore have greater development.
El Láser Er: Yag como alternativa en la práctica odontológica operatoria
Rosanna Di Stefano
Acta Odontológica Venezolana , 2004,
Abstract: Este trabajo, se basa sobre la experiencia clínica con el láser de Erbio, por ser éste, el más reciente de todos los tipos de láser de aplicación en las diferentes especialidades de la Odontología. Además, de ser el utilizado e indicado específicamente para el tratamiento sobre los tejidos dentarios duros.(1) Se presentarán experiencias obtenidas en la clínica privada sobre pacientes tratados con el láser Er: YAG a lo largo de un a o. Se realizaron sólo cavidades clase: I, II, III, IV y V según clasificación de Black (2), a nivel de esmalte, esmalte y dentina, y dentina cercana a la pulpa cameral. La muestra, abarca pacientes de ambos sexos, clasificados según el tipo de cavidades tratadas y según valoración verbal del dolor. Todos los tratamientos se realizaron sin anestesia y sin utilizar ácido fosfórico al 35%, para el grabado de la superficie del esmalte y la dentina. Los pacientes no tuvieron sintomatología operatoria ni post-operatoria y se mostraron sorprendidos por la rapidez, lo indoloro y lo silencioso del procedimiento. This work is based on the clinical experience with Er: YAG laser, which is the most recent type of all the forms of application laser in the different specialties within the field of dentistry. Furthermore, the Er:YAG laser is the most employed and suitable type of laser which is being used on the hard tissue section of the tooth.(1) Experience would be presented obtained in the private clinic on patients treated with the Er: YAG laser along one year. Only cavities class I, II, III, IV and V, according the classification of Black (2) , were carried out. All these cavities were done on the level of: enamel, enamel and dentin and dentin near the pulp cameral. The sample embraced patients of both sex, clasified according to the type of treated cavities and according to the verbal valuation of pain. All of the treatments were done neither without anesthesia nor phosphoric acid to 35% for the engroving of the surface of the enamel and the dentin. The patients have did not neither operative symptoms. All the patients were surprise by the speedness, the painless and the silence of the procedure by using the Er:YAG laser.
Enhancement of high-energy distribution tail in Monte Carlo semiconductor simulations using a Variance Reduction Scheme
Vincenza Di Stefano
Le Matematiche , 2009,
Abstract: The Multicomb variance reduction technique has been introduced in the Direct Monte Carlo Simulation for submicrometric semiconductor devices. The method has been implemented in bulk silicon. The simulations show that the statistical variance of hot electrons is reduced with some computational cost. The method is efficient and easy to implement in existing device simulators.
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