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201.
R Nassini P Pedretti N Moretto C Fusi C Carnini F Facchinetti AR Viscomi AR Pisano S Stokesberry C Brunmark N Svitacheva L McGarvey R Patacchini AB Damholt P Geppetti S Materazzi 《PloS one》2012,7(8):e42454
Background
The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.Methodology/Principal Findings
By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves.Conclusions
Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases. 相似文献202.
Vito Cantisani Salvatore Ulisse Eleonora Guaitoli Corrado De Vito Riccardo Caruso Renzo Mocini Vito D’Andrea Valeria Ascoli Alfredo Antonaci Carlo Catalano Francesco Nardi Adriano Redler Paolo Ricci Enrico De Antoni Salvatore Sorrenti 《PloS one》2012,7(11)
Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection. 相似文献
203.
C Corrado AM Flugy S Taverna S Raimondo G Guggino R Karmali G De Leo R Alessandro 《PloS one》2012,7(8):e42310
The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous leukaemia (CML) by imatinib mesylate. While imatinib has been extremely effective for chronic phase CML, blast crisis CML are often resistant. New therapeutic options are therefore needed for this fatal disease. Although more common in solid tumors, increased microvessel density was also reported in chronic myelogenous leukaemia and was associated with a significant increase of angiogenic factors, suggesting that vascularity in hematologic malignancies is a controlled process and may play a role in the leukaemogenic process thus representing an alternative therapeutic target. Carboxyamidotriazole-orotate (CTO) is the orotate salt form of carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor that in vitro has been shown to possess antileukaemic activities. CTO, which has a reduced toxicity, increased oral bioavailability and stronger efficacy when compared to the parental compound, was tested in this study for its ability to affect imatinib-resistant CML tumor growth in a xenograft model. The active cross talk between endothelial cells and leukemic cells in the bone marrow involving exosomes plays an important role in modulating the process of neovascularization in CML. We have thus investigated the effects of CTO on exosome-stimulated angiogenesis. Our results indicate that CTO may be effective in targeting both cancer cell growth and the tumor microenvironment, thus suggesting a potential therapeutic utility for CTO in leukaemia patients. 相似文献
204.
Luisa Diomede Cristina Soria Margherita Romeo Sofia Giorgetti Loredana Marchese Patrizia Palma Mangione Riccardo Porcari Irene Zorzoli Mario Salmona Vittorio Bellotti Monica Stoppini 《PloS one》2012,7(12)
Availability of living organisms to mimic key step of amyloidogenesis of human protein has become an indispensable tool for our translation approach aiming at filling the deep gap existing between the biophysical and biochemical data obtained in vitro and the pathological features observed in patients. Human β2-microglobulin (β2-m) causes systemic amyloidosis in haemodialysed patients. The structure, misfolding propensity, kinetics of fibrillogenesis and cytotoxicity of this protein, in vitro, have been studied more extensively than for any other globular protein. However, no suitable animal model for β2-m amyloidosis has been so far reported. We have now established and characterized three new transgenic C. elegans strains expressing wild type human β2-m and two highly amyloidogenic isoforms: P32G variant and the truncated form ΔN6 lacking of the 6 N-terminal residues. The expression of human β2-m affects the larval growth of C. elegans and the severity of the damage correlates with the intrinsic propensity to self-aggregate that has been reported in previous in vitro studies. We have no evidence of the formation of amyloid deposits in the body-wall muscles of worms. However, we discovered a strict correlation between the pathological phenotype and the presence of oligomeric species recognized by the A11 antibody. The strains expressing human β2-m exhibit a locomotory defect quantified with the body bends assay. Here we show that tetracyclines can correct this abnormality confirming that these compounds are able to protect a living organism from the proteotoxicity of human β2-m. 相似文献
205.
206.
Antonio Pisani Massimo Imbriaco Carmela Zizzo Giuseppe Albeggiani Paolo Colomba Riccardo Alessandro Francesco Iemolo Giovanni Duro 《BMC cardiovascular disorders》2012,12(1):1-4
Background
Infective Endocarditis (IE) is considered as a multifaceted problem in every aspect from etiology and presentation to diagnosis and management. Early recognition of this disease and especially its complications, remain a critical task for the cardiologist. Atrial endocarditis is a rare and sometimes unrecognized complication of mitral valve endocarditis.Case presentation
We present a 48 year-old male patient who was admitted to our clinic because of recent onset of malaise, fever, jaundice and peripheral edema. Important physical findings were peripheral stigmata of IE in addition to holosystolic murmur over the left sternal border. Transthoracic and transesophageal echocardiophy revealed a severe eccentric MR due to a flailed posterior mitral valve caused by IE. The presence of atrial septal endocarditis caused by jet streaming was also observed. Blood culture was positive for streptococcus oralis and antibiotic therapy was immediately initiated. Considering the large burden of infective tissue, the patient was planned for an early surgical intervention. A minimally invasive resection of the atrial mass, direct closure of the defect, resection of the diseased portions of mitral leaflets and implantation of a biological mitral valve prosthesis was performed. Intra-operative and histological findings confirmed provisional diagnosis by echocardiography.Conclusions
Together with comprehensive echocardiographic evaluation, attention should be placed on mural vegetations and excluded among all cases of mitral valve endocarditis, particularly those with severe eccentric regurgitant jets. 相似文献207.
Simone Fattorini Riccardo Santoro Emanuela Maurizi Alicia T.R. Acosta Andrea Di Giulio 《Comptes rendus biologies》2012,335(10-11):708-711
Few studies have investigated insect ensembles, i.e. phylogenetically bounded groups of species that use a similar set of resources within a community. The zonation of dune vegetation makes these ecosystems ideal for the study of insect ensembles in a short space. In this study, we investigated if the tenebrionid beetles forming an ensemble on a dune zonation showed variations in community organization (relative abundances and species diversity) in different but spatially associated biotopes defined by different plant communities. Three biotopes (corresponding to European Commission habitat 2110, 2120 and 2230) of a well-preserved Mediterranean dune were sampled using square plots of 2 × 2 m at three places. To investigate if there was some association between species and habitat we applied a χ2 test. Variations in community structure parameters were investigated using Shannon index. The three biotopes host tenebrionid communities with similar species composition and overall abundances, confirming that they form a single ensemble. However, tenebrionid species are differently associated with different biotopes along the zonation, with some species occurring with different proportions among the biotopes. A local selection process can be postulated as a mechanism responsible for these differences. 相似文献
208.
209.
Neri M Ugolini D Dianzani I Gemignani F Landi S Cesario A Magnani C Mutti L Puntoni R Bonassi S 《Mutation research》2008,659(1-2):126-136
Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes. 相似文献
210.
Salmaso M Malacarne G Troggio M Faes G Stefanini M Grando MS Velasco R 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2008,116(8):1129-1143
Grapevine molecular maps based on microsatellites, AFLP and RAPD markers are now available. SSRs are essential to allow cross-talks
between maps, thus upgrading any growing grapevine maps. In this work, single nucleotide polymorphisms (SNPs) were developed
from coding sequences and from unique BAC-end sequences, and nested in a SSR framework map of grapevine. Genes participating
to flavonoids metabolism and defence, and signal transduction pathways related genes were also considered. Primer pairs for
351 loci were developed from ESTs present on public databases and screened for polymorphism in the “Merzling” (a complex genotype
Freiburg 993–60 derived from multiple crosses also involving wild Vitis species) × Vitis vinifera (cv. Teroldego) cross population. In total 138 SNPs, 108 SSR markers and a phenotypic trait (berry colour) were mapped in
19 major linkage groups of the consensus map. In specific cases, ESTs with putatively related functions mapped near QTLs previously
identified for resistance and berry ripening. Genes related to anthocyanin metabolism mapped in different linkage groups.
A myb gene, which has been correlated with anthocyanin biosynthesis, cosegregated with berry colour on linkage group 2. The possibility
of associating candidate genes to known position of QTL is discussed for this plant.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Marzia Salmaso and Giulia Malacarne contributed equally to the present work. 相似文献