120 research outputs found

    Thermodynamics of Ionization of Benzoic Acid in Urea + Water Mixtures

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    771-77

    mAb Das-1 recognizes 3\u27-Sulfated Lewis A/C, which is aberrantly expressed during metaplastic and oncogenic transformation of several gastrointestinal epithelia

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    INTRODUCTION: Multiple previous studies have shown the monoclonal antibody Das-1 (formerly called 7E12H12) is specifically reactive towards metaplastic and carcinomatous lesions in multiple organs of the gastrointestinal system (e.g. Barrett\u27s esophagus, intestinal-type metaplasia of the stomach, gastric adenocarcinoma, high-grade pancreatic intraepithelial neoplasm, and pancreatic ductal adenocarcinoma) as well as in other organs (bladder and lung carcinomas). Beyond being a useful biomarker in tissue, mAb Das-1 has recently proven to be more accurate than current paradigms for identifying cysts harboring advanced neoplasia. Though this antibody has been used extensively for clinical, basic science, and translational applications for decades, its epitope has remained elusive. METHODS: In this study, we chemically deglycosylated a standard source of antigen, which resulted in near complete loss of the signal as measured by western blot analysis. The epitope recognized by mAb Das-1 was determined by affinity to a comprehensive glycan array and validated by inhibition of a direct ELISA. RESULTS: The epitope recognized by mAb Das-1 is 3\u27-Sulfo-Lewis A/C (3\u27-Sulfo-LeA/C). 3\u27-Sulfo-LeA/C is broadly reexpressed across numerous GI epithelia and elsewhere during metaplastic and carcinomatous transformation. DISCUSSION: 3\u27-Sulfo-LeA/C is a clinically important antigen that can be detected both intracellularly in tissue using immunohistochemistry and extracellularly in cyst fluid and serum by ELISA. The results open new avenues for tumorigenic risk stratification of various gastrointestinal lesions

    Recurring Translocations in Barrett’s Esophageal Adenocarcinoma

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    Barrett’s esophagus (BE) is a premalignant metaplasia in patients with chronic gastroesophageal reflux disease (GERD). BE can progress to esophageal adenocarcinoma (EA) with less than 15% 5-year survival. Chromosomal aneuploidy, deletions, and duplication are early events in BE progression to EA, but reliable diagnostic assays to detect chromosomal markers in premalignant stages of EA arising from BE are lacking. Previously, we investigated chromosomal changes in an in vitro model of acid and bile exposure-induced Barrett’s epithelial carcinogenesis (BEC). In addition to detecting changes already known to occur in BE and EA, we also reported a novel recurring chromosomal translocation t(10:16) in the BE cells at an earlier time point before they undergo malignant transformation. In this study, we refine the chromosomal event with the help of fluorescence microscopy techniques as a three-way translocation between chromosomes 2, 10, and 16, t(2:10;16) (p22;q22;q22). We also designed an exclusive fluorescent in situ hybridization for esophageal adenocarcinoma (FISH-EA) assay that detects these chromosomal breakpoints and fusions. We validate the feasibility of the FISH-EA assay to objectively detect these chromosome events in primary tissues by confirming the presence of one of the fusions in paraffin-embedded formalin-fixed human EA tumors. Clinical validation in a larger cohort of BE progressors and non-progressors will confirm the specificity and sensitivity of the FISH-EA assay in identifying malignant potential in the early stages of EA

    Protection of construction pit for car-park building in Ljubljana

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    V diplomski nalogi je obravnavano varovanje gradbene jame za objekt parkirno garažne hiše v Ljubljani. Varovalna konstrukcija je bila izvedena s sidranimi slopi po tehnologiji injektiranja pod visokimi pritiski (jet grouting). Sidranje smo izvedli z začasnimi geotehničnimi sidri v enem ali dveh nivojih. V nalogi je podan pregled postopkov za izvedbo jet grouting slopov in začasnih geotehničnih sider po veljavnih standardih. Pozornost je posvečena načinom izvedbe, ki so uveljavljeni pri nas, in problemom, ki se pojavljajo zaradi odstopanja od zhatev tehnične regulative ali nezmožnosti upoštevanja le-te. To je delno posledica zastarele opreme in utečenih postopkov izvajanja del. Dodatno pa na to vplivajo tudi zahteve po čim cenejši izvedbi gradbenih del. V nalogi so predstavljene izkušnje pridobljene med izvedbo varovalne konstrukcije gradbene jame, rezultati kontrolnih preiskav in problemi, ki so se pojavili med izvedbo del, ter rešitve teh problemov. V fazi izvedbe varovalne konstrukcije iz jet grouting slopov smo največ pozornosti posvetili tehnologiji enofaznega postopka injektiranja in njeni učinkovitosti v danih razmerah. Pri izvedbi geotehničnih sider pa smo največ pozornosti posvetili vgradnji in napenjanju preskusnih sider. Na gradbišču nastali problemi so lahko tudi posledica nepopolne gradbene dokumentacije, vključno s starimi in pomanjkljivimi načrti sosednjih objektov. V nalogi je prav tako obravnavano reševanje problemov, povezanih z nepričakovano sestavo temeljnih tal. Ta je pomembno vplivala na težave in zamude pri izvedbi in nemoteno napredovanje del.The subject of this thesis is the execution construction pit for multi-storey car-park building in Ljubljana. The supporting structure was made with high pressure grouting (e.q jet grouting), and anchored with temporary ground anchors in one or two levels. An overview of jet grouting and temporary ground anchors procedures accoding to current standards is shown. A special attention is put on the currently valid execution of works in our country. We primarily examined the problems occurring due to the deviation from technical regulations or inability to stick to them, which may be the consequence of either old equipment or sticking to generally accepted procedures of the execution, as well as requirements for a cheaper execution. The thesis presents the description of experiences gained during the execution works, the results of control examinations, the problems that occurred during the execution and appropriate solutions. In the phase of the jet-grouting-piles execution, which were used as a supporting structure, the attention was on the technology of the single fluid system and its effectiveness in the ground, while with ground anchors the most attention was paid to ground anchor installation and. The problems occurring on the construction site are often result of an incomplete project documentation, often involving the old and incomplete documentation of neighbouring buildings. The solution of issues in relation to the unexpected ground conditions, which significantly delayed the execution of works, is examined

    The gut microbiota of marine fish

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    The body of work relating to the gut microbiota of fish is dwarfed by that on humans and mammals. However, it is a field that has had historical interest and has grown significantly along with the expansion of the aquaculture industry and developments in microbiome research. Research is now moving quickly in this field. Much recent focus has been on nutritional manipulation and modification of the gut microbiota to meet the needs of fish farming, while trying to maintain host health and welfare. However, the diversity amongst fish means that baseline data from wild fish and a clear understanding of the role that specific gut microbiota play is still lacking. We review here the factors shaping marine fish gut microbiota and highlight gaps in the research

    Salicylazosulphapyridine metabolism in clinical practice

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    This Thesis describes work on the metabolism of salicylazosulphapyridine in normal volunteers and in patients with ulcerative colitis or Crohn's disease. The effect of coincidental administration of iron and calcium in healthy volunteers on the absorption of sulphasalazine and its metabolites has been investi¬ gated. In patients with ulcerative colitis or Crohn's disease an attempt has been made to correlate the clinical state of the disease and the serum concentration of sulphasalazine or its metabolites. The relationship of the toxic effects due to sulphasalazine with the acetylator phenotype, dosage and serum concentration of the drug and its metabolites has also been explored. The feasibility of reintroducing the drug in patients with side effects has been studied. The metabolism of sulphasalazine in patients with ileostomy or colostomy was investigated

    Autoimmunity in Inflammatory Bowel Disease

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