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Hines K.-E.,University of Oslo | Bolle E.,University of Oslo | Rissi M.,University of Oslo | Volgyes D.,University of Oslo | And 5 more authors.
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

COMPET is a pre-clinical MRI compatible PET scanner which decouples sensitivity and resolution by the use of a novel detector design. The detector has been built using 8×8cm2 square layers consisting of 30 LYSO crystals (2×3×80mm2) interleaved with 24 Wavelength Shifting Fibers (WLS) (3×1×80mm3). By stacking several layers into a module, the point-of-interaction (POI) can be measured in 3D. Four layers form a PET ring where the sensitivity can be increased by stacking several layers. The layers can be stacked so that no inter-crystal or inter-module gap is formed. COMPET has used four assembled layers for module and scanner characterization. The modules are connected to the COMPET data-acquisition chain and the reconstructed images are produced with the novel geometry-independent COMPET image reconstruction algorithm. Time and energy resolution have been resolved and found to be around 4 ns and 14% respectively. Tests for MRI interference and count rate performance have been carried out. The reconstruction algorithm has been verified with data acquired by means of a COMPET full ring PET scanner. © 2013 Elsevier B.V.

Yamazaki T.,University of Geneva | Yamazaki T.,Tokyo Institute of Technology | Walchli S.,Rikshospitalet Radiumhospitalet Medical Center | Fujita T.,University of Geneva | And 6 more authors.
Cardiovascular Research | Year: 2010

AimsProteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress-strain sensors. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing.Methods and resultsWe studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes. Conclusion Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertrophy. © 2010 The Author.

Hustad S.,University of Bergen | Eussen S.,University of Bergen | Midttun O.,University of Bergen | Ulvik A.,University of Bergen | And 5 more authors.
Clinical Chemistry | Year: 2012

BACKGROUND: Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary. METHODS: Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (-25 °C), stability was studied crosssectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models. RESULTS: For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at -25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non - first order. CONCLUSIONS: Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies. © 2011 American Association for Clinical Chemistry.

Dale E.,Rikshospitalet Radiumhospitalet Medical Center
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al] | Year: 2010

To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide. Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction. Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V(40Gy)) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01). There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V(40Gy)) seemed to protect against fibrosis development.

Shaw A.C.,University College London | Van Balkom I.D.,Lentis Psychiatric Institute | Van Balkom I.D.,University of Groningen | Bauer M.,Miami Childrens Hospital | And 11 more authors.
American Journal of Medical Genetics, Part A | Year: 2010

Marshall-Smith syndrome (MSS) is a distinctive entity of unknown etiology with fewer than 50 patients described in the medical literature to date. Through an International collaboration and use of an online wiki to facilitate data collection and sharing, we further delineate the phenotype and natural history of this syndrome. We present 15 new patients, the oldest being 30 years, provide an update on four previously published cases, and compare all patients with other patients reported in literature. Main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behavior, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features are characteristic with high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum are common. Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. Array-CGH was performed on 12 of the cohort and no copy number variants of clear clinical relevance were identified. The present study is the first reported use of an online wiki to aid delineation of a genetic syndrome, and illustrates its value in collecting detailed data in rare conditions. © 2010 Wiley-Liss, Inc.

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