830 research outputs found

    Guest editorial

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    Loss of heterozygosity is related to p53 mutations and smoking in lung cancer

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    Carcinogenesis results from an accumulation of several genetic alterations. Mutations in the p53 gene are frequent and occur at an early stage of lung carcinogenesis. Loss of multiple chromosomal regions is another genetic alteration frequently found in lung tumours. We have examined the association between p53 mutations, loss of heterozygosity (LOH) at frequently deleted loci in lung cancer, and tobacco exposure in 165 tumours from non-small cell lung cancer (NSCLC) patients. A highly significant association between p53 mutations and deletions on 3p, 5q, 9p, 11p and 17p was found. There was also a significant correlation between deletions at these loci. 86% of the tumours with concordant deletion in the 4 most involved loci (3p21, 5q11–13, 9p21 and 17p13) had p53 mutations as compared to only 8% of the tumours without deletions at the corresponding loci (P< 0.0001). Data were also examined in relation to smoking status of the patients and histology of the tumours. The frequency of deletions was significantly higher among smokers as compared to non-smokers. This difference was significant for the 3p21.3 (hMLH1 locus), 3p14.2 (FHIT locus), 5q11–13 (hMSH3 locus) and 9p21 (D9S157 locus). Tumours with deletions at the hMLH1 locus had higher levels of hydrophobic DNA adducts. Deletions were more common in squamous cell carcinomas than in adenocarcinomas. Covariate analysis revealed that histological type and p53 mutations were significant and independent parameters for predicting LOH status at several loci. In the pathogenesis of NSCLC exposure to tobacco carcinogens in addition to clonal selection may be the driving force in these alterations. © 2001 Cancer Research Campaign http://www.bjcancer.co

    Taxonomy and evolutionary relationships within species of section Rimosae (Inocybe) based on ITS, LSU and mtSSU sequence data

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    The present study aimed at elucidating the structure of Inocybe subg. Inosperma sect. Rimosae but included also representatives from subg. Mallocybe and the genus Auritella. Phylogenetic relationships were inferred using ITS, LSU and mtSSU sequence data. The analyses recovered the ingroup as a monophyletic, strongly supported clade. The results indicate that recognizing Auritella on the genus level renders Inocybe paraphyletic. The species traditionally placed in sect. Rimosae were found to be distributed over two strongly supported clades, Maculata and Rimosae s.s. The Maculata clade clusters with sect. Cervicolores and the two represent subg. Inosperma in a strict sense. Rimosae s.s. emerges as an independent, supported clade well separated from Inosperma s.s. Twenty-one terminal groups were correlated with morphologically distinct species. In addition several taxa on single branches and minor less supported clades were recovered. A key to the identified species of the Maculata and Rimosae s.s. clades which occur in Northwest Europe is provided

    Three-Body Halo States in Effective Field Theory: Renormalization and Three-Body Interactions in the Helium-6 System

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    In this paper we study the renormalization of Halo effective field theory applied to the Helium-6 halo nucleus seen as an alpha-neutron-neutron three-body state. We include the 0(+) dineutron channel together with both the 3/2(-) and 1/2(-) neutron-alpha channels into the field theory and study all of the six lowest-order three-body interactions that are present. Furthermore, we discuss three different prescriptions to handle the unphysical poles in the P-wave two-body sector. In the simpler field theory without the 1/2(-) channel present we find that the bound-state spectrum of the field theory is renormalized by the inclusion of a single three-body interaction. However, in the field theory with both the 3/2(-) and 1/2(-) included, the system can not be renormalized by only one three-body operator

    Allele diversity of the H-ras-1 variable number of tandem repeats in Norwegian lung cancer patients

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    We have examined restriction fragment length polymorphisms of the H-ras-1 gene in germ-line DNA from 214 lung cancer patients and 309 unaffected controls. When DNA samples were digested with MspI/HpaII, Southern blot analysis revealed at least 22 different alleles, grouped according to their frequencies as common, intermediate, and rare. The frequency of rare alleles in lung cancer patients (16/428) is significantly different (p = 0.002) from that in the control group (5/618). Individuals with rare alleles were found to be at 4.7-fold greater risk of lung cancer than those with no rare alleles.publishedVersio

    Pharmacological profiling of the hemodynamic effects of cannabinoid ligands: a combined in vitro and in vivo approach

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    The receptors mediating the hemodynamic responses to cannabinoids are not clearly defined due to the multifarious pharmacology of many commonly used cannabinoid ligands. While both CB1 and TRPV1 receptors are implicated, G protein-coupled receptor 55 (GPR55) may also mediate some of the hemodynamic effects of several atypical cannabinoid ligands. The present studies attempted to unravel the pharmacology underlying the in vivo hemodynamic responses to ACEA (CB1 agonist), O-1602 (GPR55 agonist), AM251 (CB1 antagonist), and cannabidiol (CBD; GPR55 antagonist). Agonist and antagonist profiles of each ligand were determined by ligand-induced GTPγS binding in membrane preparations expressing rat and mouse CB1 and GPR55 receptors. Blood pressure responses to ACEA and O-1602 were recorded in anesthetized and conscious mice (wild type, CB1−/− and GPR55−/−) and rats in the absence and presence of AM251 and CBD. ACEA demonstrated GTPγS activation at both receptors, while O-1602 only activated GPR55. AM251 exhibited antagonist activity at CB1 and agonist activity at GPR55, while CBD demonstrated selective antagonist activity at GPR55. The depressor response to ACEA was blocked by AM251 and attenuated by CBD, while O-1602 did not induce a depressor response. AM251 caused a depressor response that was absent in GPR55−/− mice but enhanced by CBD, while CBD caused a small vasodepressor response that persisted in GPR55−/− mice. Our findings show that assessment of the pharmacological profile of receptor activation by cannabinoid ligands in in vitro studies alongside in vivo functional studies is essential to understand the role of cannabinoids in hemodynamic control

    Detection of signal recognition particle (SRP) RNAs in the nuclear ribosomal internal transcribed spacer 1 (ITS1) of three lineages of ectomycorrhizal fungi (Agaricomycetes, Basidiomycota)

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    During a routine scan for Signal Recognition Particle (SRP) RNAs in eukaryotic sequences, we surprisingly found in silico evidence in GenBank for a 265-base long SRP RNA sequence in the ITS1 region of a total of 11 fully identified species in three ectomycorrhizal genera of the Basidiomycota (Fungi): Astraeus, Russula, and Lactarius. To rule out sequence artifacts, one specimen from a species indicated to have the SRP RNA-containing ITS region in each of these genera was ordered and re-sequenced. Sequences identical to the corresponding GenBank entries were recovered, or in the case of a non-original but conspecific specimen differed by three bases, showing that these species indeed have an SRP RNA sequence incorporated into their ITS1 region. Other than the ribosomal genes, this is the first known case of non-coding RNAs in the eukaryotic ITS region, and it may assist in the examination of other types of insertions in fungal genomes.RHN acknowledges financial support from FORMAS (215-2011- 498) and from Stiftelsen Olle Engkvist Byggmästare. MPM was partially supported by Plan Nacional I+D+i project CGL2012-35559. CW acknowledges a Marie Skłodowska-Curie post doc grant (660122, CRYPTRANS)Peer reviewe

    Topical and Systemic Cannabidiol Improves Trinitrobenzene Sulfonic Acid Colitis in Mice

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    Background/Aims: Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis. Methods: Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay. Results: Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis. Conclusion: The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation. Copyright (C) 2012 S. Karger AG, Base
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