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Sökning: LAR1:gu > Chalmers tekniska högskola > (2000-2004)

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  • Abel, Frida, 1974, et al. (författare)
  • Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.
  • 2002
  • Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 86:4, s. 596-604
  • Tidskriftsartikel (refereegranskat)abstract
    • The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.
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  • Abel, Frida, 1974 (författare)
  • Genetic studies of neuroblastoma with emphasis on the apoptotic pathway
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: The objective of this thesis was to find genes and chromosomal regions involved in neuroblastoma (NB) tumor progression. NB is a childhood tumor of the sympathetic nervous system that generally occurs spontaneously. Biologically, NB has a complex heterogeneity from tumor progression to tumor regression, dependent on clinical stage and age at diagnosis. The main genetic markers, which are also of prognostic value in NB, are amplification of the oncogene MYCN, deletion of chromosome arm 1p and gain of chromosome arm 17q. Results: We have been shown using fluorescence in situ hybridization (FISH) on a Scandinavian tumor material, that 17q gain is present in approximately 65% of all NB stages, is significantly associated with poor prognosis and predicts survival. The gene encoding somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, was not found to be mutated in any NB, when analyzed with PCR-based single stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing. In a tentative effort of defining of the location of a general embryonal tumor suppressor gene (TSG) on 1p, we combined the smallest region of overlap (SRO) of 1p deletions in NB tumors and germ cell tumors (GCTs). We thus delimited the NB/GCT SRO to approximately 5 cM between markers D1S508 and D1S244, and fine-mapped this region by radiation hybrid mapping and construction of a bacterial artificial chromosome (BAC) contig. A homozygously deleted region in an NB cell line was found to partially overlap the proximal part of the 5 cM-SRO defined by us, which further focused our search for a TSG to a 500 kb candidate region in 1p36.22. Two attractive candidate NB TSGs, DFFA and CASP9, are both located in 1p36.2 and encode key apoptotic mediators. In fact, DFFA resides in the 500 kb TSG candidate region. Via sequence analysis of the entire tumor material, we found three different coding alterations in DFFA which all affect the highly conserved N-terminal regulatory domain of DFF45. Using RT-PCR and real-time RT-PCR (TaqMan) studies, we were able to show that both DFFA and CASP9 are preferably expressed in NB tumors with favorable outcome. It has been proposed that lack of apoptosis plays an important role in tumor progression. We therefore screened an array with cDNAs involved in the apoptotic process, to find genes differentially expressed in NB tumors with unfavorable versus favorable biology. Using real-time RT-PCR analysis, we verified the differential expression of several transcripts encoding mitochondrial apoptotic mediators. Conclusions: We have shown that 17q gain is the most frequently detected alteration in NB and that it is associated with established prognostic factors. We narrowed down the TSG candidate region on 1p and found mutations in a gene localized in the region possessing fundamental functions in apoptosis. Our results also suggest that the mitochondrial apoptotic pathway is suppressed at multiple steps in advanced stages of NB tumors, due to imbalance between anti-apoptotic and pro-apoptotic mediators.
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4.
  • Abel, Frida, 1974, et al. (författare)
  • Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors.
  • 2004
  • Ingår i: International journal of oncology. - 1019-6439 .- 1791-2423. ; 25:5, s. 1297-302
  • Tidskriftsartikel (refereegranskat)abstract
    • DFF45 has essential functions in the final stage of apoptosis by acting both as a folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA) maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is therefore an attractive candidate NB tumor suppressor. In a previous study we found a rare allele variant, causing a non-polar to a polar amino acid exchange (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to be preferentially expressed in favorable NB tumors. We have extended the previous study and performed mutation analyses in another 56 NB tumors (100 in total) as well as a set of other tumors for coding mutations in DFFA. We have also performed studies of the DFFA expression in tumors using real-time PCR. We found a missense mutation (Ile15Met) in the remaining allele of a teratoma with heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown stage causing a deletion of amino acid 37 in DFF45. The one-base substitution detected in the teratoma was not present in the patients constitutional DNA, i.e. it is a true mutation present in the tumor DNA only. In conclusion, three different coding alterations have been found in the region encoding the N-terminal regulatory domain of DFF45, responsible for binding and achieving its chaperone and inhibitor functions on other proteins. Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.
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5.
  • Abrahamsson, Katarina, 1957, et al. (författare)
  • Air-sea exchange of halocarbons: the influence of diurnal and regional variations and distribution of pigments
  • 2004
  • Ingår i: Deep-Sea Research Part Ii-Topical Studies in Oceanography. - : Elsevier BV. - 0967-0645. ; 51:22-24, s. 2789-2805
  • Tidskriftsartikel (refereegranskat)abstract
    • Diurnal cycles of halocarbons, except methyl bromide and methyl chloride, were observed at six 24-h stations occupied in three different regions, the Summer Ice Edge, the Winter Ice Edge, and the Antarctic Polar Front, in the Atlantic sector of the Southern Ocean during a Swedish-South African expedition in 1997/1998. The diurnal cycles contained three phases; a productive phase, a phase of losses and a phase with steady state. The duration of the different phases varied for the different stations as well as for individual compounds. The measured production and losses of organo-halogens in the Antarctic Ocean based on values from each station, were in the order of a few to hundreds of Tg yr(-1). Bromochloromethane, tribromomethane, trichloroethene and diiodomethane were the four compounds found in highest concentrations throughout the investigation, and they were found to be the major contributors of organohalogens. Only the presence of the photosynthetic pigment 19'-hexanoyloxyfucoxanthin, biomarker pigment of haptophytes, could explain some of the variations in the distribution and production of halocarbons, and then only for iodinated compounds. The flux of organo-halogens from the oceans to the atmosphere was estimated in two ways, either based on calculations according to models or based on the measured concentrations. Large discrepancies were found, which could not be explained by chemical or biological degradation or adsorption to particles. This investigation, therefore, shows the need for assessing the rates of degradation and the air-sea exchange more accurately. (C) 2004 Elsevier Ltd. All rights reserved.
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6.
  • Abrahamsson, Katarina, 1957, et al. (författare)
  • Variations of biochemical parameters along a transect in the Southern Ocean, with special emphasis on volatile halogenated organic compounds
  • 2004
  • Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645. ; 51:22-24, s. 2745-2756
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of parameters of biogeochemical interest were monitored along a north-southerly transect (S 43-S 63degrees) in the Atlantic Sector of the Southern Ocean from the 8th to the 20th of December 1997. Changes in total dissolved inorganic carbon (C-T) and total alkalinity (A(T)) were mostly dependent on temperature and salinity until the ice edge was reached. After this point only a weak correlation was seen between these. Highest mean values of C-T and A(T) were observed in the Winter Ice Edge (WIE) (2195 and 2319 mumol kg(-1), respectively). Lowest mean AT (2277 mumol kg(-1)) was observed in the Sub-Antarctic Front (SAF), whereas lowest mean CT concentration (2068 mumol kg(-1)) was associated with the Sub-Tropical Front (STF). The pH in situ varied between 8.060 and 8.156 where the highest values were observed in the southern part of the Antarctic Polar Front (APF) and in the Summer Ice Edge (SIE) Region. These peaks were associated with areas of high chlorophyll a (chl a) and tribromomethane values. In the other areas the pH in situ was mainly dependent on hydrography. Bacterial abundance decreased more than one order of magnitude when going from north to south. The decrease appeared to be strongly related to water temperature and there were no elevated abundances at frontal zones. Microphytoplankton dominated in the SAF and APF, whereas the nano- and picoplankton dominated outside these regions. Volatile halogenated compounds were found to vary both with regions, and with daylight. For the iodinated compounds, the highest concentrations were found north of the STF. Brominated hydrocarbons had high concentrations in the STF, but elevated concentrations were also found in the APF and SIE regions. No obvious correlation could be found between the occurrence of individual halocarbons and chl a. On some occasions trichloroethene and tribromomethane related to the presence of nano- and microplankton, respectively.
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7.
  • Adermark, Louise, 1974, et al. (författare)
  • Ethanol acutely decreases astroglial gap junction permeability in primary cultures from defined brain regions
  • 2004
  • Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186. ; 45:7, s. 971-978
  • Tidskriftsartikel (refereegranskat)abstract
    • The acute effect of hyperosmotic ethanol on gap junction permeability was examined in astroglial cells in primary culture from five different brain regions. Gap junction permeability was analyzed by measuring dye spreading from cell to cell with the low molecular weight dye Lucifer Yellow. Ethanol concentrations 25-300 mM significantly decreased dye spreading in cultures from the cerebral cortex in a dose-dependent but time-independent manner for up to 60 min. Besides cerebral cortex, exposure to 150 mM ethanol decreased dye spreading in astroglial cultures from the hippocampus and from the brain stem, while cultures from the olfactory bulb and from the hypothalamus were not significantly affected. The ethanol-induced decrease in dye spreading in cultures from the cerebral cortex was not mediated through changes in cell volume, osmolarity, protein kinase C (PKC) phosphorylation, intracellular pH, or intracellular calcium concentration ([Ca 2+ ] i ). The decrease in dye spreading was abolished upon incubation in sodium-reduced buffer, and after blockage of the Na + /K + /2Cl - cotransporter with furosemide. The results presented here indicate that ethanol-mediated decrease in dye spreading is directly or indirectly dependent on sodium. © 2004 Elsevier Ltd. All rights reserved.
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