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- Sandblom, Gabriel, et al.
(författare)
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Prostate Cancer Registration in Four Swedish Regions 1996 : Differences in Incidence, Age Structure and Management
- 1999
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 33:5, s. 306-311
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In 1996 registration of prostate cancer in four of the six Swedish regions was started to facilitate evaluation of geographical variations in incidence and treatment.Material and methods: For all cases of prostate cancer, personal identification number, tumour stage, tumour grade and primary treatment were registered.Results: In the four regions covered by the register, 3541 cases of prostate cancer were registered. Altogether there were 5795 cases of prostate cancer diagnosed in Sweden the same year. The age-standardized incidence varied from 89/100 000 to 169/100 000 among counties. The proportion of localized tumours correlated positively to the incidence (p < 0.05) and negatively to mean age at diagnosis (p < 0.01). There was also a significant positive correlation between the proportion of localized tumours and the percentage of patients given curative treatment. All registered variables showed large geographical variations, especially concerning percentage of T1c tumours, treatment of localized tumours and choice of palliative treatment.Conclusion: Diagnostic activity varied considerably among counties, resulting in large variation in age-standardized incidence. High incidence is associated with a larger proportion of localized tumours, which, in turn, is associated with early age at diagnosis. In counties where a policy of detecting tumours early is practised, curative treatment is also given more often. Treatment of localized tumours and preference for palliative treatment seem to depend on local traditions. The lack of cytological and histopathological standards makes geographical comparisons based on tumour grade impossible.
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- Goldsteins, Gundars, et al.
(författare)
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Characterisation of two highly amyloidogenic mutants of transthyretin
- 1997
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 36:18, s. 5346-5352
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Tidskriftsartikel (refereegranskat)abstract
- The plasma protein transthyretin (TTR) has the potential to form amyloid under certain conditions. More than 50 different point mutations have been associated with amyloid formation that occurs only in adults. It is not known what structural changes are introduced into the structure of this otherwise stable molecule that results in its aggregation into insoluble amyloid fibrils. On the basis of calculations of the frequency of known mutations over the polypeptide, we have constructed two mutants in the D-strand of the polypeptide. These molecules, containing either a deletion or a substitution at amino acid positions 53−55, were unstable and spontaneously formed aggregates upon storage in TBS (pH 7.6). The precipitates were shown to be amyloid by staining with thioflavin T and Congo Red. Their ultrastructure was very similar to that of amyloid fibrils deposited in the vitreous body of patients with familial amyloidotic polyneuropathy type 1 with an amino acid replacement in position 30 (TTRmet30). Like amyloid isolated from the vitreous body of the eye, the amyloid precipitates generated from the TTR mutants exposed a trypsin cleavage site between amino acid residues 48 and 49, while plasma TTRmet30 isolated from amyloidosis patients as well as wild-type TTR only showed minor trypsin sensitivity. Our data indicate that the mutants we have constructed are similar to amyloid precursors or may share structural properties with intermediates on a pathway leading to amyloid deposits of plasma TTR.
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- Goldsteins, Gundars, et al.
(författare)
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Exposure of cryptic epitopes on transthyretin only in amyloid and in amyloidogenic mutants
- 1999
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 96:6, s. 3108-3113
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Tidskriftsartikel (refereegranskat)abstract
- The structural requirements for generation of amyloid from the plasma protein transthyretin (TTR) are not known, although it is assumed that TTR is partly misfolded in amyloid. In a search for structural determinants important for amyloid formation, we generated a TTR mutant with high potential to form amyloid. We demonstrated that the mutant represents an intermediate in a series of conformational changes leading to amyloid. Two monoclonal antibodies were generated against this mutant; each displayed affinity to ex vivo TTR and TTR mutants with amyloidogenic folding but not to wild-type TTR or mutants exhibiting the wild-type fold. Two cryptic epitopes were mapped to a domain of TTR, where most mutations associated with amyloidosis occur and which we propose is displaced at the initial phase of amyloid formation, opening up new surfaces necessary for autoaggregation of TTR monomers. The results provide direct biochemical evidence for structural changes in an amyloidogenic intermediate of TTR.
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- Gustafsson, Åke, 1953-
(författare)
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Functional and molecular aspects of interferon action in human natural killer cells and other leucocytes
- 1985
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Interferons comprise a class of structurally related proteins which exert several regulatory effects in responsive cells. These effects include the establishment of an antiviral state, the inhibition of cellular proliferation and the alteration of different immune reactions. In particular, the IFN:s rapidly augment the lytic activity of the natural killer (NK) cells. In the present thesis, some of the functional and molecular mechanisms by which IFN:s act on NK cells and other leucocytes are studied. A good correlation is found between the ability of different tumor cell lines to induce IFN production among peripheral blood lymphocytes and their sensitivity to NK cell cytotoxicity, indicating that IFN might regulate the activity of NK cells through a positive feed-back mechanism. When studying the interaction between the NK cells and two target cell lines it is demonstrated that the two cell lines are not recognized by the same receptors. The augmentation of NK cell cytotoxicity by IFN is shown to involve both alteration of receptor structures on the NK cell and enhancement of steps in their lytic machinery. The effects of IFN on the synthesis of individual proteins is then studied by two-dimensional electrophoresis. It is demonstrated that IFN-a and IFN-ß within 1.5 hours induce the synthesis of nine proteins (Mf80, 75, 62, 58, 53, 38, 36, 33 and 30 kD) in human lymphocytes. Tne induction is dependent on a rapid de novo RNA synthesis, which is initiated less than 30 minutes after the addition of IFN. The expression of the nine proteins is well correlated to the development of augmented NK cell cytotoxicity. Four of the proteins (Mr 80, 62, 38 and 33 kD) are found to be expressed in a panel of ten hematopoetic and two anchorage-dependent cell lines, whereas the remaining proteins seem to be expressed in leucocytes only. IFN induce the synthesis of the same proteins in both purified large granular lymphocytes (responsible for the main NK cell activity in man), T cells and monocytes, demonstrating that the augmentation of NK cell activity does not involve the formation of unique 1NK-cel11 specific proteins. Rather, the augmentation of the lytic activity of both NK cells, cytotoxic T cells and monocytes seem to involve common stages in their lytic mechanisms. In contrast to IFN-a and IFN-ß, IFN-y, does not induce any detectable proteins in either NK cells or T cells. This lack of effect of IFN-y on the protein synthesis is not a general phenomenon, since the effects of IFN-a and IFN-y are similar 1n a glioma cell line. These results demonstrate that there exists at least one pathway to augment the NK cell cytotoxicity which does not involve the increased synthesis of the nine IFN-a/IFN-ß inducible proteins and indicates that either these proteins are mainly involved in other effects of IFN, or that the augmentation by IFN-a/IFN-ß and IFN-y involve different pathways. When the effects of IFN-a on the synthesis of membrane-associated proteins is studied, it is demonstrated that only the 80 kD IFN-a inducible protein is associated with the cell membrane. In addition, IFN-a seems to induce three additional, me mb rane-as so ci a ted proteins (Mr 94, 76 and 66 kD) which are not detected in whole cell lysates.
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- Ling, Erik, et al.
(författare)
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Bioenergins nuvarande och framtida konkurrenskraft - föreställningar om konkurrenskraft
- 1998
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study is to develop a framwork that will enable an increased understanding of the competitiveness of bioenergy today and in the future. The conceptions that the actors of the energy system uphold are studied and analysed. The conceptions of the actors are seen as key factors for the understanding of the function of the energy system and accordingly also for the understanding of the competitiveness of bioenergy.
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