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Molecular Pathogenesis of MALT lymphoma
No full textMucosa associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and
t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-κB pathway. Gastric MALT lymphomas harbouring such translocation do not respond to Helicobacter pylori eradication, while those without translocation can be cured by antibiotics.
To understand the molecular mechanism of MALT lymphoma with and without chromosome translocation, 24 cases (15 translocation-positive and 9 translocation-negative) of MALT lymphomas together with 7 follicular lymphomas and 7 mantle cell lymphomas were analysed by Affymetrix gene expression microarray platform. Unsupervised clustering showed that cases of MALT lymphoma were clustered as a single branch. However, within the MALT lymphoma group, translocation-positive cases were intermingled with translocation-negative cases. Gene set enrichment analysis (GSEA) of the NF-κB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas were characterized by an enhanced expression of NF-κB target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. The differential expression of these NF-κB target genes between MALT lymphoma with and without translocation was confirmed by quantitative RT-PCR and immunohistochemistry or Western blot.
Expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-κB activation in vitro. In addition, there was cooperation between expression of BCL10, MALT1 or API2-MALT1, and stimulation of the antigen receptor or CD40 or TLR in NF-κB activation as shown by both reporter assay and IκBα degradation. Interestingly, expression of BCL10 but not API2-MALT1 and MALT1, in the presence of LPS stimulation, also triggered IκBβ degradation, suggesting activation of different NF-κB dimers between these oncogenic products.
Study by co-immunoprecipitation showed that BCL10 directly interacts with MALT1. Sub-cellular localisation experiments in BJAB B-cells, showed that BCL10 localisation was affected by MALT1. When BCL10 was over-expressed, the protein was predominantly expressed in the nuclei, but when MALT1 was over-expressed, BCL10 was mainly localised in the cytoplasm. When both BCL10 and MALT1 were over-expressed, BCL10 was expressed in the cytoplasm in the early hours when the protein level was low, but in both the cytoplasm and nuclei after 9 hours when the protein level was high. Over-expression of API2-MALT1 did not shown any apparent effect on BCL10 sub-cellular localisation in vitro.
Finally, comparison of MALT lymphoma expression microarray with other lymphomas showed lactoferrin to be highly expressed in MALT lymphoma. This was confirmed by qRT-PCR, showing lactoferrin to be significantly over-expressed in MALT lymphoma compared to FL and MCL. Thus lactoferrin may be a potential marker for MALT lymphoma
Impact of Fusarium graminearum Contamination Levels of Barley on Deoxynivalenol and Zearalenone in Malt
No full textCilj istraživanja bio je ustanoviti utjecaj početnog stupnja kontaminacije ječma s plijesni Fusarium
graminearum na udjel deoksinivalenola (DON-a) i zearalenona (ZEA) u gotovom sladu. Također je
razmatran utjecaj pojedinih tehnoloških operacija tijekom procesa proizvodnje slada na razvoj
ispitivane plijesni i njezine sposobnosti sinteze DON-a i ZEA. Provedeno je mikroslađenje uzoraka
ječma s različitim početnim stupnjem kontaminacije s plijesni F. graminearum (0, 10 i 20%).
Mikrobiološke i toksikološke analize provedene su u uzorcima neslađenog ječma, zelenog slada te
suhog slada, pri čemu je određivan udjel zrna kontaminiranog s navedenom plijesni i koncentracija
mikotoksina. Rezultati istraživanja pokazali su da se najveća proliferacija plijesni dogodila tijekom
faze močenja i klijanja zrna, dok se tijekom faze sušenja stupanj kontaminacije značajno smanjio.
Nadalje, rezultati ukazuju na zaključak da ječam većeg početnog stupnja kontaminacije s plijesni F.
graminearum rezultira sladom koji je više kontaminiran mikotoksinima. Najveće koncentracije DON-a
određene su u uzorcima klice/korjenčića, dok su najveće koncentracije ZEA određene u suhom sladu.The aim of this study was to establish the impact of initial Fusarium graminearum contamination level of barley on deoxynivalenol (DON) and zearalenone (ZEA) content in kilned malt. The influence of applied unit operations during the malt production on development of the above-mentioned fungus and its ability to synthesize DON and ZEA was also considered. Barley samples contaminated with different initial F. graminearum contamination levels (0, 10 and 20%) were subjected to micromalting procedure. Barley samples, green malt and kilned malt underwent microbiological and toxicological analyses at which the share of F. graminearum contaminated grain and concentrations of mycotoxins were
determined. The results show that the strongest proliferation of fungus occurred during steeping and germination, while the drying phase significantly reduced the contamination level. Furthermore, the results indicate that barley with higher initial F. graminearum contamination level ensured higher concentrations of mycotoxins in kilned malt. The highest DON concentrations were determined in germ/rootlets samples, while the highest ZEA concentrations were determined in kilned malt
Impact of Fusarium graminearum infection levels of wheat malt on deoxynivalenol content during beer production
No full textCilj istraživanja bio je ustanoviti utjecaj početnog stupnja kontaminacije pšenice s plijesni F. graminearum na udjel deoksinivalenola (DON) u pivu i nusproizvodima vrenja, te utjecaj pojedine tehnološke operacije u procesu proizvodnje pšeničnog piva na koncentraciju DON-a. Provedeno je ukomljavanje uzoraka pšeničnog slada s različitim stupnjem kontaminacije s plijesni F. graminearum (0,5% - 12%), te fermentacija dobivenih uzoraka sladovine. Provedena je mikrobiološka i toksikološka analiza uzoraka slada (osušeni i stabilizirani slad), te toksikološka analiza sladovine, tropa, piva i otpadnog kvasca. Pri mikrobiološkoj analizi slada određivan je udjel zrna kontaminiranog s plijesni F. graminearum, dok je toksikološka analiza uključivala određivanje koncentracija DON-a u svim navedenim uzorcima. Rezultati toksikološke analize upuduju na zaključak da je DON stabilan tijekom proizvodnje piva, te prelazi iz slada u konačni proizvod tj. pivo, te u nusproizvode, trop i otpadni kvasac. Nadalje, stupanj kontaminacije značajno utječe na udjel DON-a u svim uzorcima, pri čemu najveću koncentraciju DON-a imaju uzorci s najvećim početnim stupnjem kontaminacije.Objectives of this study were to establish the impact of initial F. graminearum contamination level of wheat on deoxynivalenol (DON) content in beer and its byproducts and the influence of applied unit operations during wheat beer production process on DON concentration. Malt samples contaminated with different initial F. graminearum contamination levels (0.5 – 12%) were subjected to mashing procedure followed by fermentation procedure of wort samples. Wheat samples, dry malt (stabilized), wort, beer and byproducts (spent grain and yeast) underwent microbiological and toxicological analyses which determined the share of F. graminearum contaminated grain and DON concentrationResults of toxicological analyses show that DON was stable during beer production and that the toxin was transferred from malt to wort as well as the byproducts such as spent grain and yeast. Results also indicate that wheat with higher initial F. graminearum contamination level gives malt with higher DON concentration
The ECLW Collaborative Study .2. Patient Registration Form (PRF) instrument, training and reliability
No full textThis paper describes the development and testing of the Patient Registration Form (PRF), a standardized instrument for the description of patients seen by consultation-liaison (C-L) psychiatrists and psychosomatists in general hospitals, the referral patterns, the C-L interventions and their outcomes. The PRF study is part of a large multi-centre, European investigation on the effectiveness of mental health service delivery, conducted by the European C-L Workgroup for General Hospital Psychiatry and Psychosomatics (ECLW) and performed in the framework of the of the E.C. 4th Medical and Health Research Program. The final version of the PRF consists of 68 items. It was developed by the Program Management Group (PMG) and National Coordinators (NC) after long preparatory studies to assure both face and content validity and pilot testing. Two hundred and twenty consultants, who required 40 hours of training and came from 14 different European countries and 90 different sites, participated in the final reliability study. The PRF was tested in 13 written case histories. A 'gold standard' For the correct answers in each item was decided by 'consensus ratings' of the PMG and a subsequent 80% agreement by the NCs. A high standard (average kappa (kappa) greater than or equal to 0.70; at least 2/3 of the PRF items, kappa greater than or equal to 0.70) was required for the rater to be considered as 'reliable' (RR). The consultants considered the PRF both 'feasible' and 'acceptable' and 93.2% of them fulfilled the RR criteria. The calculated rater-'gold standard' reliability was satisfactory: only four PRF items were identified with low agreement coefficients and no biases were observed cross-nationally in the ratings. Given the implications of misclassification for evaluating C-L effectiveness and services, these results are important and the achievement unprecedented
Quality Assurance (QA) in Consultation Liaison Psychiatry and psychosomatics. Development and implementation of an European QA System.
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Impact of Fusarium graminearum infection levels of wheat on malt deoxynivalenol content
No full textCilj istraživanja bio je ustanoviti utjecaj početnog stupnja zagađenosti pšenice s plijesni F. graminearum na udjel DON-a u gotovom sladu i utjecaj pojedinih tehnoloških operacija tijekom procesa proizvodnje slada na razvoj ispitivane plijesni i njezine sposobnosti sinteze DON-a.
Provedeno je mikroslađenje uzoraka pšenice s različitim početnim stupnjem zagađenosti s plijesni F. graminearum (0 % - 50 %). Provedene su mikrobiološke i toksikološke analize istraživanja uzoraka neslađene pšenice, zelenog slada (zrno nakon močenja i klijanja, zračno suho), te suhog slada (stabilizirani slad), pri čemu je određivan udjel zrna zagađenog s F. graminearumom i koncentracija DON-a. Rezultati istraživanja pokazali su da se najveća proliferacija plijesni dogodila tijekom faze močenja i klijanja zrna, dok se tijekom faze sušenja stupanj zagađenosti s plijesni F. graminearum značajno smanjio. Najveće koncentracije DON-a određene su u uzorcima slada, što znači da je do najsnažnije sinteze došlo tijekom faze sušenja. Rezultati ukazuju na zaključak da pšenica većeg
početnog stupnja zagađenosti s plijesni F. graminearum rezultira sladom veće zagađenosti s DONom.Objectives of this study were to establish the impact of initial F. graminearum contamination level of wheat on DON content in dry malt and the influence of applied unit operations during malt production process on development of above-mentioned fungus and its ability to synthesize DON. Wheat samples contaminated with different initial F. graminearum contamination levels (0 – 50 %) were subjected to micromalting procedure. Wheat samples, green malt (grain after steeping and germination) and dry malt (stabilized) underwent microbiological and toxicological analyses at which the share of F. graminearum contaminated grain and DON concentration were determined. Results show that the strongest proliferation of fungus occurred during steeping and germination phase, while drying phase significantly reduced contamination level. Highest DON concentrations were determined in dry malt samples meaning that the strongest DON synthesis occurred during drying phase. Results
also indicate that wheat with higher initial F. graminearum contamination level ensures malt with higher DON concentration
Dreaming of drams: Authenticity in Scottish whisky tourism as an expression of unresolved Habermasian rationalities
No full textIn this paper, the production of whisky tourism at both independently owned and corporately owned distilleries in Scotland is explored by focusing on four examples (Arran, Glengoyne, Glenturret and Bruichladdich). In particular, claims of authenticity and Scottishness of Scottish whiskies through commercial materials, case studies, website-forum discussions and 'independent' writing about such whisky are analysed. It is argued that the globalisation and commodification of whisky and whisky tourism, and the communicative backlash to these trends typified by the search for authenticity, is representative of a Habermasian struggle between two irreconcilable rationalities. This paper will demonstrate that the meaning and purpose of leisure can be understood through such explorations of the tension between the instrumentality of commodification and the freedom of individuals to locate their own leisure lives in the lifeworld that remains. © 2011 Taylor & Francis
DETECTION OF BCL-6 REARRANGEMENTS AND p53 MUTATIONS IN MALT-LYMPHOMAS
No full textTwenty-seven lymphomas of mucosa-associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B-cell lymphomagenesis, including activation of proto-oncogenes (BCL-1, BCL-2, BCL-6, and c-MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein-Barr virus (EBV), and Kaposi's sarcoma-herpesvirus/human herpesvirus-8 (KSHV/HHV-8)]. Sixteen low-grade and 11 high-grade MALT-lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR-single strand conformation polymorphism followed by DNA direct sequencing. Alterations of BCL-1, BCL-2, or c-MYC, as well as infection by KSHV/HHV-8, scored negative in all MALT-lymphomas analysed. Conversely, rearrangements of BCL-6 and mutations of p53 clustered with a fraction of high-grade MALT-lymphomas. Deletions of 6q occurred in selected cases of both low- and high-grade MALT-lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT-lymphomas differs substantially from that of nodal B-cell lymphomas. Occasionally, however, a proportion of high-grade MALT-lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B-cell lymphomagenesis
The ECLW collaborative study III: training and reliability if ICD-10 diagnoses in the general hospital setting – an investigation of 220 consultants from 14 european countries.
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