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- Stenman, U H, et al.
(författare)
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Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen
- 1999
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 20:Suppl. 1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.
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| 3. |
- Adami, Hans-Olov, et al.
(författare)
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The aetiology and pathogenesis of human breast cancer
- 1995
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Ingår i: Mutation research. - 0027-5107 .- 1873-135X. ; 333:1-2, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn--and by inference in utero--and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.
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| 4. |
- Albin, Maria, et al.
(författare)
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Retention patterns of asbestos fibres in lung tissue among asbestos cement workers
- 1994
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Ingår i: Occupational and Environmental Medicine. - 1470-7926. ; 51:3, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- Retention patterns in lung tissue (determined by transmission electron microscopy and energy dispersive spectrometry) of chrysotile, tremolite, and crocidolite fibres were analysed in 69 dead asbestos cement workers and 96 referents. There was an accumulation of tremolite with time of employment. Among workers who died within three years of the end of exposure, the 13 with high tremolite concentrations had a significantly longer duration of exposure than seven in a low to intermediate category (medians 32 v 20 years; p = 0.018, one sided). Crocidolite showed similar patterns of accumulation. In workers who died more than three years after the end of exposure, there were no correlations between concentrations of amphibole fibres and time between the end of exposure and death. Chrysotile concentrations among workers who died shortly after the end of exposure were higher than among the referents (median difference in concentrations 13 million fibres (f)/g dry weight; p = 0.033, one sided). No quantitative differences in exposure (duration or intensity) could be shown between workers with high and low to intermediate concentrations. Interestingly, all seven workers who had had a high intensity at the end of exposure (> 2.5 f/ml), had low to intermediate chrysotile concentrations at death, whereas those with low exposure were evenly distributed (31 subjects in both concentration categories); hence, there was a dependence between last intensity of exposure and chrysotile concentration (p = 0.014). Among 14 workers with a high average intensity of exposure, both those (n = 5) with high tissue concentrations of chrysotile and those (n = 10) with high tissue concentrations of tremolite fibres had more pronounced fibrosis than those with low to intermediate concentrations (median fibrosis grades for chrysotile: 2 v 1, p = 0.021; for tremolite: 2 v 0.5, p = 0.012). Additionally, workers who died shortly after the end of exposure with high concentrations of chrysotile and crocidolite had smoked more than those with low intermediate concentrations (medians for chrysotile 35 v 15 pack-years, p = 0.030; for crocidolite 37 v 15 pack-years, p = 0.012). The present data indicate that chrysotile has a relatively rapid turnover in human lungs, whereas the amphiboles, tremolite and crocidolite, have a slower turnover. Further, chrysotile retention may be dependent on dose rate. Chrysotile and crocidolite deposition and retention may be increased by tobacco smoking; chrysotile and tremolite by fibrosis.
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| 8. |
- Chalot, Michel, et al.
(författare)
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Metabolism of [N-15]alanine in the ectomycorrhizal fungus Paxillus involutus
- 1995
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Ingår i: Experimental Mycology. - : Elsevier BV. - 0147-5975. ; 19:4, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- Alanine metabolism in the ectomycorrhizal fungus Paxillus involutus was investigated using [N-15]alanine. Short-term exposure of mycelial discs to [N-15]alanine showed that the greatest flow of N-15 was to glutamate and to aspartate. Levels of enrichment were as high as 15-20% for glutamate and 13-18% for aspartate, whereas that of alanine reached 30%. Label was also detected in the amino-N of glutamine and in serine and glycine, although at lower levels. Preincubation of mycelia with aminooxyacetate, an inhibitor of transamination reactions, resulted in complete inhibition of the flow of the label to glutamate, aspartate, and amino-N of glutamine, whereas [N-15]alanine rapidly accumulated. This evidence indicates the direct involvement of alanine aminotransferase for translocation of N-15 from alanine to glutamate. Alanine may be a convenient reservoir of both nitrogen and carbon. (C) 1995 Academic Press, Inc.
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| 10. |
- Federzoni, L., et al.
(författare)
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Comparison of computer models representing powder compaction process: State of the art review
- 1999
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Ingår i: Powder Metallurgy. - : Informa UK Limited. - 0032-5899 .- 1743-2901. ; 42:4, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a benchmark study on the use of simulation models to represent the powder compaction process. A two level part that represents a synchroniser hub is used as detailed experimental information for this part is documented in the literature. The models used incorporate different representations of friction and material yielding behaviour together with different fill densities. The study shows that computer modelling is capable of predicting density distributions and tool set force levels for the powder compaction process. It has highlighted the sensitivity of the output with respect to friction, fill density, and material yield models. It has also shown that models that incorporate material behaviour using different material models yield surprisingly reasonable results. Based on best performance, it is now possible to predict density to within 0·05 g cm-3 and tool set force within 10%for an iron powder. The computational requirements indicate a simulation time of typically 1 h for a two level component. This makes simulation a practical tool for this industry sector.
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