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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 171) Sort By: Publication Date Relevance Took: 2.230 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 7 1 2 3 4 > Last >> (171 articles found) Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors. Apr 15, 2006 Rosaria Bassi,Viviana Anelli,Paola Giussani,Guido Tettamanti,Paola Viani,Laura Riboni The mitogenic role of sphingosine-1-phosphate (S1P) and its involvement in basic fibroblast growth factor (bFGF)-induced proliferation were examined in primary cultures of cerebellar astrocytes. Exposure to bFGF resulted in a rapid increase of extracellular S1P formation, bFGF inducing astrocytes t... ( view more )o release S1P, but not sphingosine kinase, in the extracellular milieu. The SK inhibitor N,N-dimethylsphingosine inhibited S1P release as well as bFGF-induced growth stimulation. S1P application in quiescent astrocytes caused a dose-dependent increase in DNA synthesis. This gliotrophic effect was induced by a brief exposure to low nanomolar S1P, mimicked by the S1P receptor agonist dihydro-S1P, and inhibited by pertussis toxin (PTX), an inactivator of G(i)/G(o)-proteins. S1P also induced activation of extracellular signal-regulated kinase that was inhibited again by PTX. Moreover, the S1P lyase inhibitor 4-deoxypyridoxine induced the cellular accumulation of S1P but did not affect DNA synthesis. These results support the view that S1P exerted a mitogenic effect on cerebellar astrocytes extracellularly, most likely through cell surface S1P receptors. In agreement, mRNAs for S1P1, S1P2, and S1P3 receptors are expressed in cerebellar astrocytes (Anelli et al., 2005. J Neurochem 92:1204-1215). Ceramide, a negative regulator of astrocyte proliferation and down-regulated by bFGF (Riboni et al., 2002. Cerebellum 1:129-135), efficiently inhibited S1P-induced proliferation. The S1P action appears to be part of an autocrine/paracrine cascade stimulated by bFGF and, together with ceramide down-regulation, essential for astrocytes to respond to bFGF. The results suggest that S1P and bFGF/S1P may play an important role in physiopathological glial proliferation, such as brain development, reactive gliosis and brain tumor formation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Mutations of the p53 gene in male breast cancer. May 1, 1995 A Anelli,T F Anelli,B Youngson,P P Rosen,P I Borgen BACKGROUND. Cancer of the male breast (MBC) is rare, accounting for less than 1% of cancer in males and representing less than 1% of all breast cancers. Reports of abnormalities in the expression of the tumor suppressor gene p53 in MBC have been few. METHODS. To assess the expression and mutations ... ( view more )of the p53 gene, 35 patients with 36 MBC (one patient with bilateral breast carcinoma) were examined using immunohistochemical methods, polymerase chain reaction (PCR)-single strand conformation polymorphism and DNA sequencing. RESULTS. Thirty-one of the 36 carcinomas were studied by immunohistochemistry and by the PCR-based approach. Five patients were studied by immunohistochemistry only. Twelve patients (41.4%) of the 29 studied by molecular analysis presented an altered pattern in the single strand conformation polymorphism gel and point mutations were confirmed in all by direct DNA sequencing. Thirty-six tumors were studied by immunohistochemistry and 2 (5.5%) patients showed overexpression of the p53 protein. There were no statistically significant differences in p53 status with respect to: age, stage, estrogen receptors, progesterone receptors, tumor type. Patients with normal p53 showed a predisposition, although not statistically significant, for a longer disease free survival (5.6 years versus 4.2 years) and overall survival (5.9 years versus 4.8 years) than did patients with genetically altered p53. CONCLUSIONS. The incidence of male patients detected with p53 mutations (41.4%) in this series is concordant with the incidence of p53 mutations in female breast cancer, supporting the idea that cancer of the male breast is similar to the female counterpart. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Jul 1, 1994 T F Anelli,A Anelli,K N Tran,D E Lebwohl,P I Borgen BACKGROUND. Although an uncommon disease, male breast cancer (MBC) will be responsible for 300 deaths in 1993 in the United States. Because of the high rate of estrogen receptor positivity in males, adjuvant hormonal therapy with tamoxifen in the adjuvant setting has been used widely. Little is kno... ( view more )wn about the side effects of this estrogen receptor blocker in males. METHODS. The authors evaluated the side effects of adjuvant tamoxifen treatment in 24 patients (19 of whom were estrogen receptor positive) treated at the authors' institution between 1990 and 1993. RESULTS. Fifteen (62.5%) patients reported at least one side effect. The most common side effect was a decrease in libido, which occurred in 7 (29.2%) patients; followed by weight gain, which occurred in 6 (25%) patients; hot flashes, which occurred in 5 (20.8%); mood alterations, which occurred in 5 (20.8%); depression, which occurred in 4 (16.6%); insomnia, which occurred in 3 (12.5%); and deep venous thrombosis, which occurred in 1 (4.2%). Five (20.8%) patients terminated treatment with tamoxifen in less than 1 year because of these side effects. Two of these patients had decreased libido, two had hot flashes, and one suffered deep venous thrombosis. CONCLUSIONS. In contrast to female breast cancer patients, who have a 4% attrition rate to adjuvant tamoxifen treatment, MBC patients have a 20.8% attrition rate related to side effects of tamoxifen treatment. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sporulation of Clostridium botulinum types A, B, and E, Clostridium perfringens, and putrefactive anaerobe 3679 in dialysis sacs. Jan 1963 M D SCHNEIDER,N GRECZ,A ANELLIS Schneider, Morris D. (Quartermaster Food and Container Institute for the Armed Forces, U.S. Army, Chicago, Ill.), Nicholas Grecz, and Abe Anellis. Sporulation of Clostridium botulinum types A, B, and E, Clostridium perfringens, and Putrefactive Anaerobe 3679 in dialysis sacs. J. Bacteriol. 85:126-1... ( view more )33. 1963.-Concentrated cultures of spores of Clostridium botulinum type A (33A, 37A), B (41B, 51B), and E (strain VH), C. perfringens (strain E), and Putrefactive Anaerobe 3679 were prepared in intussuscepted cellulose dialysis tubing. The apparatus consisted of a telescoped cellulose bag immersed into a suitable sporulation medium in a large Pyrex tube. The initial inoculum was a heavy suspension in physiological saline solution of either vegetative cells or heat-shocked spores. The seed material was introduced into the interior of the dialysis bag. Maximal spore populations were obtained within 10 to 12 days. Strains of C. botulinum type E and C. perfringens, known for their poor sporulation in conventional cultures, gave good spore crops in the dialysis bag. Some crops were of the order of 10(10) and 10(11) viable spores per liter of medium. The spores produced in the dialysis bag were conspicuously large, particularly after incubation for 20 to 30 days. Observations of the characteristics of spores formed in telescoped bags indicate that two highly resistant strains of C. botulinum, 33A and 41B, were apparently less resistant to gamma rays than spores of the same strains produced in identical media in conventional cultures. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Procedure for cleaning of Clostridium botulinum spores. Sep 1962 N GRECZ,A ANELLIS,M D SCHNEIDER Grecz, N. (Quartermaster Food and Container Institute, Chicago, Ill.), A. Anellis, and M. D. Schneider. Procedure for cleaning of Clostridium botulinum spores. J. Bacteriol. 84:552-558. 1962.-Liberation of clean spores from vegetative sporangia of Clostridium botulinum strains was accomplished by t... ( view more )he use of lytic enzymes and sonic oscillation. Suspensions of crude spores in phosphate buffer (pH 7) were digested with lysozyme (200 mug/ml) and trypsin (100 mug/ml). Rapid lysis of sporangia was induced by ultrasonic oscillation of the reacting mixture at 10 kc for 5 min at 0, 0.5, 1, 2, 4, and 6 hr of incubation at 45 C. Intermittent washing of the reacting spore suspension with a solution of lysozyme and trypsin hastened purification of the spore crop. The cleaning procedure was completed by repeated washing of the spores with distilled water. The spores produced by this procedure were clean, as judged by their microscopic appearance, refractility to staining, loss of heat-sensitive toxin, and partition behavior in a two-phase system composed of polyethylene glycol and 3 m potassium phosphate buffer (pH 7.1). The cleaning procedure appeared not to affect the viability, resistance to heat and gamma radiation, or the toxic nature of C. botulinum spores. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. May 2008 Eleftheria Zeggini,Laura J Scott,Richa Saxena,Benjamin F Voight,Jonathan L Marchini,Tianle Hu,Paul I W de Bakker,Gonçalo R Abecasis,Peter Almgren,Gitte Andersen,Kristin Ardlie,Kristina Bengtsson Boström,Richard N Bergman,Lori L Bonnycastle,Knut Borch-Johnsen,Noël P Burtt,Hong Chen,Peter S Chines,Mark J Daly,Parimal Deodhar,Chia-Jen Ding,Alex S F Doney,William L Duren,Katherine S Elliott,Michael R Erdos,Timothy M Frayling,Rachel M Freathy,Lauren Gianniny,Harald Grallert,Niels Grarup,Christopher J Groves,Candace Guiducci,Torben Hansen,Christian Herder,Graham A Hitman,Thomas E Hughes,Bo Isomaa,Anne U Jackson,Torben Jørgensen,Augustine Kong,Kari Kubalanza,Finny G Kuruvilla,Johanna Kuusisto,Claudia Langenberg,Hana Lango,Torsten Lauritzen,Yun Li,Cecilia M Lindgren,Valeriya Lyssenko,Amanda F Marvelle,Christa Meisinger,Kristian Midthjell,Karen L Mohlke,Mario A Morken,Andrew D Morris,Narisu Narisu,Peter Nilsson,Katharine R Owen,Colin N A Palmer,Felicity Payne,John R B Perry,Elin Pettersen,Carl Platou,Inga Prokopenko,Lu Qi,Li Qin,Nigel W Rayner,Matthew Rees,Jeffrey J Roix,Anelli Sandbaek,Beverley Shields,Marketa Sjögren,Valgerdur Steinthorsdottir,Heather M Stringham,Amy J Swift,Gudmar Thorleifsson,Unnur Thorsteinsdottir,Nicholas J Timpson,Tiinamaija Tuomi,Jaakko Tuomilehto,Mark Walker,Richard M Watanabe,Michael N Weedon,Cristen J Willer,Wellcome Trust Case Control Consortium ,Thomas Illig,Kristian Hveem,Frank B Hu,Markku Laakso,Kari Stefansson,Oluf Pedersen,Nicholas J Wareham,Inês Barroso,Andrew T Hattersley,Francis S Collins,Leif Groop,Mark I McCarthy,Michael Boehnke,David Altshuler Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published an... ( view more )alyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles HMGB1 as an autocrine stimulus in human T98G glioblastoma cells: role in cell growth and migration. Mar 2008 Rosaria Bassi,Paola Giussani,Viviana Anelli,Thomas Colleoni,Marco Pedrazzi,Mauro Patrone,Paola Viani,Bianca Sparatore,Edon Melloni,Laura Riboni HMGB1 (high mobility group box 1 protein) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, mainly through RAGE (the receptor for advanced glycation end products); HMGB1-RAGE interactions have been found to be important in a number of c... ( view more )ancers. We investigated whether HMGB1 is an autocrine factor in human glioma cells. Western blots showed HMGB1 and RAGE expression in human malignant glioma cell lines. HMGB1 induced a dose-dependent increase in cell proliferation, which was found to be RAGE-mediated and involved the MAPK/ERK pathway. Moreover, in a wounding model, it induced a significant increase in cell migration, and RAGE-dependent activation of Rac1 was crucial in giving the tumour cells a motile phenotype. The fact that blocking DNA replication with anti-mitotic agents did not reduce the distance migrated suggests the independence of the proliferative and migratory effects. We also found that glioma cells contain HMGB1 predominantly in the nucleus, and cannot secrete it constitutively or upon stimulation; however, necrotic glioma cells can release HMGB1 after it has translocated from the nucleus to cytosol. These findings provide the first evidence supporting the existence of HMGB1/RAGE signalling pathways in human glioblastoma cells, and suggest that HMGB1 may play an important role in the relationship between necrosis and malignancy in glioma tumours by acting as an autocrine factor that is capable of promoting the growth and migration of tumour cells. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages. Mar 2008 Samar M Hammad,Heather G Crellin,Bill X Wu,Jessica Melton,Viviana Anelli,Lina M Obeid Sphingosine kinase 1 (SK1) and its product sphingosine-1-phosphate (S1P) have been implicated in the regulation of many cellular processes including growth regulation, protection from apoptosis, stimulation of angiogenesis, and most recently as mediators of the TNF-alpha inflammatory response. In t... ( view more )his study we set out to examine the role of SK1/S1P in the RAW macrophage response to the potent inflammatory stimulus lipopolysaccharide (LPS). We show that LPS increases cellular levels of SK1 message and protein. This increase is at the transcriptional level and is accompanied by increased SK activity and generation of S1P. S1P is able to cause increases in COX-2 and PGE2 levels in RAW cells. Knockdown of SK1 using siRNA is able to inhibit the TNF but not the LPS inflammatory response. Moreover, knockdown of SK1 enhances both TNF- and LPS-induced apoptosis. These data indicate that there is a dual and distinct role for SK1 and S1P in the TNF and the LPS inflammatory pathways. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles In vitro neuronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Mar 2008 Emanuele Cacci,Maria Antonietta Ajmone-Cat,Tonino Anelli,Stefano Biagioni,Luisa Minghetti The contribution of microglia to the modulation of neurogenesis under pathological conditions is unclear. Both pro- and anti-neurogenic effects have been reported, likely reflecting the complexity of microglial activation process. We previously demonstrated that prolonged (72 hr) in vitro exposure ... ( view more )to lipopolysaccharide (LPS) endows microglia with a potentially neuroprotective phenotype, here referred as to "chronic". In the present study we further characterized the chronic phenotype and investigated whether it might differently regulate the properties of embryonic and adult neural precursor cells (NPC) with respect to the "acute" phenotype acquired following a single (24 hr) LPS stimulation. We show that the LPS-dependent induction of the proinflammatory cytokines interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha was strongly reduced after chronic stimulation of microglia, as compared with acute stimulation. Conversely, the synthesis of the anti-inflammatory cytokine IL-10 and the immunomodulatory prostaglandin E2 (PGE2) was still elevated or further increased, after chronic LPS exposure, as revealed by real time PCR and ELISA techniques. Acutely activated microglia, or their conditioned medium, reduced NPC survival, prevented neuronal differentiation and strongly increased glial differentiation, likely through the release of proinflammatory cytokines, whereas chronically activated microglia were permissive to neuronal differentiation and cell survival, and still supported glial differentiation. Our data suggest that, in a chronically altered environment, persistently activated microglia can display protective functions that favor rather than hinder brain repair processes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2. Feb 8, 2008 Viviana Anelli,Christopher R Gault,Amy B Cheng,Lina M Obeid Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important role in the regulation of cell survival, growth, migration, and angiogenesis, acts both inside the cells and as an extracellular mediator through binding to five G protein-coupled receptors (S1P(1-5)). Sphingosine kina... ( view more )se 1 (SK1), the enzyme responsible for S1P production, is overexpressed in many solid tumors, including gliomas. One common feature of these tumors is the presence of "hypoxic regions," characterized by cells expressing high levels of hypoxia-inducible factors HIF-1alpha and HIF-2alpha, two transcription regulators that modulate the levels of proteins with crucial roles in tumor progression. So far, nothing is known about the role and the regulation of SK1 during tumor-induced hypoxia or about SK1 regulation and HIFs. Here we investigated the role of HIF-1alpha and HIF-2alpha in the regulation of SK1 during hypoxic stress in glioma-derived U87MG cells. We report that hypoxia increases SK1 mRNA levels, protein expression, and enzyme activity, followed by intracellular S1P production and S1P release. Interestingly, knockdown of HIF-2alpha by small interfering RNA abolished the induction of SK1 and the production of extracellular S1P after CoCl(2) treatment, whereas HIF-1alpha small interfering RNA resulted in an increase of HIF-2alpha and of SK1 protein levels. Moreover, using chromatin immunoprecipitation analysis, we demonstrate that HIF-2alpha binds the SK1 promoter. Functionally, we demonstrate that conditioned medium from hypoxia-treated tumor cells results in neoangiogenesis in human umbilical vein endothelial cells in a S1P receptor-dependent manner. These studies provide evidence of a link between S1P production as a potent angiogenic agent and the hypoxic phenotype observed in many tumors. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Extramedullary molecular evidence of the 5'KIAA1509/3'PDGFRB fusion gene in chronic eosinophilic leukemia. Feb 2008 Francesco Albano,Luisa Anelli,Antonella Zagaria,Angelo Lonoce,Roberta La Starza,Vincenzo Liso,Mariano Rocchi,Giorgina Specchia We report a case of chronic eosinophilic leukemia (CEL), demonstrating for the first time: (i) the association of CEL with the 5'KIAA1509/3'PDGFRB fusion gene as a consequence of a t(5;14)(q33;q32); (ii) the molecular detection of this rearrangement in an extramedullary site; (iii) the cloning and ... ( view more )sequencing of the KIAA1509 and PDGFRB genomic breakpoints. The 5'KIAA1509/3'PDGFRB fusion gene is predicted to encode a protein of 2059 amino acids. The genomic breakpoints were localized inside KIAA1509 intron 11 and PDGFRB intron 10. Sequence analysis in correspondence with these breakpoints revealed the presence of repetitive DNA, such Alu elements, which could promote chromosomal rearrangements. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Protein quality control in the early secretory pathway. Jan 23, 2008 Tiziana Anelli,Roberto Sitia Eukaryotic cells are able to discriminate between native and non-native polypeptides, selectively transporting the former to their final destinations. Secretory proteins are scrutinized at the endoplasmic reticulum (ER)-Golgi interface. Recent findings reveal novel features of the underlying molecu... ( view more )lar mechanisms, with several chaperone networks cooperating in assisting the maturation of complex proteins and being selectively induced to match changing synthetic demands. 'Public' and 'private' chaperones, some of which enriched in specializes subregions, operate for most or selected substrates, respectively. Moreover, sequential checkpoints are distributed along the early secretory pathway, allowing efficiency and fidelity in protein secretion. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Acetylcholine induces neurite outgrowth and modulates matrix metalloproteinase 2 and 9. Oct 19, 2007 Tonino Anelli,Ferdinando Mannello,Monica Salani,Gaetana A Tonti,Giancarlo Poiana,Stefano Biagioni The matrix metalloproteinases (MMPs), responsible for the degradation of extracellular matrix (ECM) proteins, may regulate brain cellular functions. Choline acetyltransferase (ChAT) transfected murine neuroblastoma cell line N18TG2, that synthesize acetylcholine and show enhancement of several neur... ( view more )ospecific markers (i.e., sinapsin I, voltage gated Na(+) channels, high affinity choline uptake) and fiber outgrowth, were studied for the MMP regulation during neuronal differentiation. Zymography of N18TG2 culture medium revealed no gelatinolytic activity, whereas after carbachol treatment of cells both MMP-9 and activated MMP-2 forms were detected. ChAT-transfected clone culture medium contains three MMP forms at 230, 92, and 66kDa. Carbachol treatment increased MMP-2 and MMP-9 gene expression in N18TG2 cells and higher levels for both genes were also observed in ChAT transfected cells. The data are consistent with the hypothesis that acetylcholine brings about the activation of an autocrine loop modulating MMP expression. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis. Oct 3, 2007 Tiziana Anelli,Stefania Ceppi,Leda Bergamelli,Margherita Cortini,Silvia Masciarelli,Caterina Valetti,Roberto Sitia The biogenesis of secretory IgM occurs stepwise under stringent quality control, formation of mu(2)L(2) preceding polymerization. How is efficiency of IgM secretion coupled to fidelity? We show here that ERp44, a soluble protein involved in thiol-mediated retention, interacts with ERGIC-53. Binding... ( view more ) to this hexameric lectin contributes to ERp44 localization in the ER-golgi intermediate compartment. ERp44 and ERGIC-53 increase during B-lymphocyte differentiation, concomitantly with the onset of IgM polymerization. Both preferentially bind mu(2)L(2) and higher order intermediates. Their overexpression or silencing in non-lymphoid cells promotes or decreases secretion of IgM polymers, respectively. In IgM-secreting B-lymphoma cells, mu chains interact first with BiP and later with ERp44 and ERGIC-53. Our findings suggest that ERGIC-53 provides a platform that receives mu(2)L(2) subunits from the BiP-dependent checkpoint, assisting polymerization. In this process, ERp44 couples thiol-dependent assembly and quality control. ( view less ) View Full Abstract View Article Details   Related Articles The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy. Sep 2007 Antonio F Saad,William D Meacham,Aiping Bai,Viviane Anelli,Saeed Elojeimy,Ayman E M Mahdy,Lorianne S Turner,Joe Cheng,Alicja Bielawska,Jacek Bielawski,Thomas E Keane,Lina M Obeid,Yusuf A Hannun,James S Norris,Xiang Liu Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance... ( view more ) of AC elevation, stable clones of DU145 cells with AC overexpression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Metastatic non-small cell lung cancer in Brazil: treatment heterogeneity in routine clinical practice. Aug 2007 Fauzia F Naime,Riad Naim Younes,Bruno G Kersten,Agnaldo Anelli,Carlos Augusto M Beato,Rogério M Andrade,Marcella P Carrara,Jefferson Luiz Gross Lung cancer is one of the main causes of cancer related deaths. Approximately three quarters of these tumors are non-small cell carcinomas. When diagnosed the majority of patients show the disease locally advanced or metastatic. The chemotherapy is the chosen therapy for patients with advanced lung... ( view more ) cancer. The majority of published studies with chemotherapy are performed in academic centers under a strict control of research protocols. PURPOSE: The aim of this study is to evaluate the usual management of metastatic NSCLC patients outside of a clinical trial setting in three different oncologic centers in Brazil. METHODS: This is a retrospective study of patients with metastatic non-small cell lung cancer admitted for treatment in three different Cancer Centers in Brazil. 564 patients from Brazilian public heath system and private/health insurance system were considered for the present study. RESULTS: Among 564 patients in this study, 335 (59.4%) received chemotherapy. For all patients, 47 different regimens of chemotherapy were identified. The median follow-up time was eight months and the overall median survival of all patient population submitted to chemotherapy was 9.7 months. DISCUSSION: There was a great heterogeneity in the regimens of drugs to treat metastatic NSCLC patients. The overall survival was significantly better for patients treated with first line chemotherapy compared to patients that only received best supportive care. Results of prospective randomized clinical trials should be carefully analyzed before transferred to the daily clinical practice. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles "Home-brew" FISH assay shows higher efficiency than BCR-ABL dual color, dual fusion probe in detecting microdeletions and complex rearrangements associated with t(9;22) in chronic myeloid leukemia. Apr 15, 2007 Francesco Albano,Luisa Anelli,Antonella Zagaria,Nicoletta Archidiacono,Vincenzo Liso,Giorgina Specchia,Mariano Rocchi We carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+ chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the hybridization patterns obtained with this approach to those obtaine... ( view more )d with the "home brew" BAC/PAC system. Our results are the following: chromosome 22 microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22 microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9); and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew FISH system represents an accurate method for revealing a subset of CML patients with der(9) microdeletions. ( view less ) View Full Abstract View Article Details   Related Articles Expression of L-type calcium channel alpha(1)-1.2 and alpha(1)-1.3 subunits on rat sacral motoneurons following chronic spinal cord injury. Mar 16, 2007 R Anelli,L Sanelli,D J Bennett,C J Heckman In the presence of the monoamines serotonin and norepinephrine, motoneurons readily generate large persistent inward currents (PICs). The resulting plateau potentials amplify and sustain motor output. Monoaminergic input to the cord originates in the brainstem and the sharp reduction in monoamine l... ( view more )evels that occurs following acute spinal cord injury greatly decreases motoneuron excitability. However, recent studies in the adult sacral cord of the rat have shown that motoneurons reacquire the ability to generate PICs and plateau potentials within 1-2 months following spinal transection. Ca(v)1.3 L-type calcium channels are involved in generating PICs in both healthy and injured animals. Additionally, expression of Ca(v)1.2 and Ca(v)1.3 L-type calcium channels is altered in several pathological conditions. Therefore, in this paper we analyzed the expression of L-type calcium channel alpha(1) subunits within the motoneuron pool following a complete transection of the spinal cord at the level of the sacral vertebra (S)2 segment. The analysis was done both caudally (S4 segment) and rostrally [thoracic vertebra (T)6 segment] from the injury site. The S4 segment was significantly reduced in diameter when compared with control animals, and this reduction was more evident in the white matter. Ca(v)1.2 alpha(1) subunit expression significantly increased (26%) in the motoneuron pool located caudally but not rostrally from the injury site. In contrast, the expression of Ca(v)1.3 alpha(1) subunit remained unchanged in both S4 and T6 segments. The differential expression of the two alpha(1) subunits in spinal injury suggests that Ca(v)1.2 and Ca(v)1.3 channels have different functions in neuronal adaptation following spinal cord injury. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Combination of C(17) sphingoid base homologues and mass spectrometry analysis as a new approach to study sphingolipid metabolism. 2007 Stefka Spassieva,Jacek Bielawski,Viviana Anelli,Lina M Obeid In recent years, sphingolipid metabolites ceramide, sphingosine, and sphingosine-1-phosphate have emerged as important second messengers in addition to their role as precursors of biomembrane components. The investigation of these sphingolipid metabolites requires the development of new, more sensi... ( view more )tive methods for assaying the enzymes involved in their production. This chapter describes the utilization of mass spectrometry technology in combination with nonnaturally occurring C(17) sphingoid bases in the in vitro assays of two of the enzymes of the sphingolipid pathway, ceramide synthase and sphingosine kinase. These new in vitro methods provide high sensitivity and extreme accuracy even when crude extracts are used as enzyme sources. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Clinical predictors of health-related quality of life after pacemaker implantation. Dec 2006 Werner Benzer,Neil Oldridge,Michael Anelli Monti,Thomas Berger,Florian Hintringer,Stefan Höfer BACKGROUND: Health-related quality of life (HRQL) is increasingly accepted as an outcome measure when considering the effectiveness of therapeutic interventions. Little is known about the HRQL of patients with different clinical circumstances before and after pacemaker implantation (PMI). The purpo... ( view more )se of this study was to investigate the influence of clinical symptoms and ECG diagnoses as predictors of improved HRQL in patients referred for PMI. METHODS: Sixty eight patients with different indications for PMI completed the MacNew Heart Disease Health-related Quality of Life Questionnaire (MacNew) and the Short Form-36 Health Survey (SF-36) before and one, three and six months after PMI. Symptoms, ECG indications and pacing mode were collected using the European Pacemaker Patient Identification Card codes. RESULTS: Within the first month after PMI overall Mac-New but not SF-36 scores improved significantly and was maintained during the entire 6 month follow up period. Improvement in HRQL as measured with the MacNew was rather related to baseline symptoms and ECG diagnosis than to the pacing mode. CONCLUSION: The important finding of this study is that improved HRQL seen after PMI appears to be largely driven by baseline symptoms and the ECG diagnoses rather than the pacing mode of the device. ( view less ) View Full Abstract View Article Details   Related Articles Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver. Nov 2006 Antonin Libra,Cristina Fernetti,Vito Lorusso,Massimo Visigalli,Pier Lucio Anelli,Frantisek Staud,Claudio Tiribelli,Lorella Pascolo Contrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was t... ( view more )o investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned PCR products as standards, were performed on total RNA of both cell lines and normal liver to evaluate the transcription of 12 transport genes: SLCO1A2, SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1, SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in the tumoral and nontumoral cell lines. Compared with normal liver, the expression of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable, whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal liver. Transport studies and gene expression analyses indicated that B22956 ion is a good substrate to the liver-specific OATP1B3, reported to be poorly expressed or absent in human liver tumors. Therefore, B22956 may be helpful in detecting hepatic neoplastic lesions by CE-MRI. ( view less ) View Full Abstract View Article Details   Related Articles Measuring dendritic distribution of membrane proteins. Sep 30, 2006 Edmund W Ballou,W Bryan Smith,Roberta Anelli,C J Heckman Neurons perform much of their integrative work in the dendritic tree, and spinal motoneurons have the largest tree of any cell. Electrical excitability is strongly influenced by dendrite membrane properties, which are difficult to measure directly. We describe a method to measure the distribution o... ( view more )f ion channel membrane densities along dendritic trajectories. The method combines standard immunohistochemistry with reconstruction procedures for both large-scale and small-scale optical microscopy. Software written for Matlab then extracts the colocalization of the target ion channel with the target dye injected cell, and calculates the relative channel density per square micron of cell surface area, as a function of distance from the cell body. The technique can be used to quantify the localization and distribution of any immunoreactive moiety, and the software provides a flexible vehicle for sensitivity analysis, to validate heuristics for selecting thresholds. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Molecular cytogenetic characterization of deletions on der(9) in chronic myelocytic leukemia. Jun 2006 Antonella Zagaria,Luisa Anelli,Francesco Albano,Laura Vicari,Ettore Mariano Schiavone,Mario Annunziata,Fabrizio Pane,Vincenzo Liso,Mariano Rocchi,Giorgina Specchia The t(9;22)(q34;q11), generating the Philadelphia chromosome, is found in more than 90% of patients with chronic myelocytic leukemia (CML). Deletions adjacent to the translocation breakpoint on the derivative chromosome 9 have been described by several groups. These studies revealed two primary poi... ( view more )nts: (1) genomic microdeletions were concomitant with the t(9;22) rearrangement; and (2) the location of the deleted sequence was centromeric to ABL and telomeric to BCR genes. We report on a detailed molecular cytogenetic characterization of chromosomal rearrangements in two CML patients bearing a complex variant t(9;22) and insertions of chromosome 22 sequences in 9q34. Our study shows that the location of the deleted sequences was downstream of the ABL gene and that genomic microdeletions were concomitant with the ins(9;22)(q34;q11q11) rearrangement. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Analysis of factors predicting survival in patients with hepatocellular carcinoma treated with percutaneous laser ablation. May 2006 Claudio Maurizio Pacella,Giancarlo Bizzarri,Giampiero Francica,Giuseppe Forlini,Alessandra Petrolati,Dario Valle,Vincenzo Anelli,Antonio Bianchini,Stefano De Nuntis,Sara Pacella,Zaccaria Rossi,John Osborn,Roberto Stasi BACKGROUND/AIMS: The factors which predict the long-term outcome in patients with hepatocellular carcinoma who are treated with percutaneous laser ablation (PLA) are not well established. METHODS: We prospectively analyzed treatment and survival parameters of 148 cirrhotic patients with nonsurgical... ( view more ) hepatocellular carcinoma who had undergone PLA at a single institution during an 11-year period. RESULTS: Single tumors were seen in 129 of 148 (87%) patients, and 2-3 nodules were seen in 19 (13%) patients, for a total of 169 tumors. The median overall time survival was 39 months (95% confidence interval [CI], 30-47 months). The 1-, 2-, 3-, 4-, and 5-year cumulative survival rates were 89, 75, 52, 43, and 27%, respectively. From multiple regression analysis, the independent predictors of survival were found to be tumor grading (P=0.002; risk ratio [RR] 0.37, 95% CI 0.20-0.70), bilirubin levels < or =2.5mg/dl (P=0.014; RR 1.58, 95% CI 1.09-2.28), and the achievement of complete tumor ablation (P=0.020; RR 0.53, 95% CI 0.31-0.90). An initial complete tumor ablation was the only factor associated with longer survival in patients with Child-Turcotte-Pugh class A cirrhosis (P=0.012; hazard ratio [HR] 0.48, 95% CI 0.23-1.03). CONCLUSIONS: A complete tumor ablation results in improved survival in all patients with nonsurgical hepatocellular carcinoma. Ideal candidates for PLA are those with a well-differentiated histology, and normal bilirubin levels. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gadocoletic acid trisodium salt (b22956/1): a new blood pool magnetic resonance contrast agent with application in coronary angiography. Mar 2006 Christoph de Haën,Pier Lucio Anelli,Vito Lorusso,Alberto Morisetti,Fabio Maggioni,Jie Zheng,Fulvio Uggeri,Friedrich M Cavagna RATIONALE AND OBJECTIVES: Inversion recovery, three-dimensional, gradient-recalled echo magnetic resonance coronary angiography (IR-3D-GRE-MRCA), performed after administration of an intravascular T1-relaxing agent with prolonged permanence in the blood, is one of the most promising approaches to n... ( view more )oninvasive magnetic resonance imaging (MRI) of the coronaries. The aim of the present study was the evaluation of the physicochemical properties in solution, pharmacokinetics, elimination from the body, protein binding, and signal enhancement characteristics of gadocoletic acid trisodium salt (B22956/1), a candidate gadolinium-based MRI contrast agent for coronary angiography. METHODS: The pharmacokinetics and elimination from the body of gadocoletate ion, the contrastographically active component of gadocoletic acid trisodium salt, was evaluated after intravenous administration in rats and monkeys, using for assays high-performance liquid chromatography, x-ray fluorescence, and inductively coupled plasma atomic emission spectrometry. The binding of the gadocoletate ion to animal and human serum albumin was studied by means of ultrafiltration. The imaging properties of blood outside coronary arteries after contrast agent administration were evaluated in cynomolgus monkeys (Macaca fascicularis) by measuring aortic signal-to-noise and contrast-to-noise ratios in lower body angiograms. The suitability of gadocoletic acid trisodium salt for achieving contrast-enhanced magnetic resonance coronary angiography (ceMRCA) was tested in Yucatan micropigs with an IR-3D-GRE sequence. All in vivo relaxation rate measurement and images were obtained using a 1.5 T Siemens Symphony scanner. RESULTS: The fractional binding of gadocoletate ion at a concentration of 0.5 mM to serum albumin at the physiological concentration was 95%, 92%, 88%, and 86% for human, monkey, pig, and rat, respectively. In rats and monkeys, gadocoletate ion was excreted unmetabolized through the biliary and urinary routes. It was recovered with feces depending on the injected dose in percentages from 18% to 97%, providing evidence for a saturable biliary pathway. Plasma pharmacokinetics showed the complete elimination of gadocoletate ion within 24 hours after administration. In the monkey, the gadocoletate ion showed the pharmacokinetic behavior of a compound with partial vascular confinement and long plasma half-life, which may be ascribed to elevated binding to serum albumin. These properties manifested themselves in lower body angiograms with excellent image contrast between vessels and muscle. The slowly decaying aortic blood signal-to-noise and contrast-to-noise ratios over a 15-minute period is expected to allow 3-dimensional coronary angiography. The potential of gadocoletic acid trisodium salt for ceMRCA was also demonstrated in Yucatan micropigs. Elevated blood signal intensity and almost total myocardial signal suppression was maintained for almost 1 hour after administration, ie, for much longer than expected to be necessary for coronary angiography. During the whole period high resolution images of the right coronary artery could be obtained. CONCLUSIONS: On the basis of the pharmacokinetic profile and imaging characteristics, gadocoletic acid trisodium salt shows promise as a MR contrast agent for coronary angiography. 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