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- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers
- 1999
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Ingår i: Br J Cancer. - 0007-0920. ; 80:9, s. 1400-4
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.
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- Bäck, Sven, et al.
(författare)
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Ferrous sulphate gel dosimetry and MRI for proton beam dose measurements
- 1999
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 44:8, s. 1983-1996
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Tidskriftsartikel (refereegranskat)abstract
- Ferrous sulphate gel dosimetry has the potential for measurement of absorbed dose distributions in proton therapy. The chemical properties of the gel are altered according to the radiation dose and these changes can be evaluated in three dimensions using MRI. The purpose of this work was to investigate the properties of a ferrous gel used with clinical proton beams. The gel was irradiated with both monoenergetic and range-modulated proton beams. It was then evaluated using MRI. The depth dose by means of the 1/T1 distribution was studied and compared with data from a plane-parallel plate ionization chamber. 1/T1 was shown to be proportional to the dose at a mean proton energy of approximately 90 MeV. The dose response was no different from that obtained using photon beams. However, on normalization at the entrance, the relative 1/T1 at the Bragg peak was 15-20% lower than the corresponding ionization chamber data for the monoenergetic proton beam. Better agreement was found for the modulated beam, but with significant differences close to the distal edge of the 1/T1 distribution. The change in sensitivity with depth was explained by means of a linear energy transfer dependence. This property was further studied using Monte Carlo methods.
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- Rydberg, Lennart, 1944, et al.
(författare)
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Extracorporeal ("ex vivo") connection of pig kidneys to humans. II. The anti-pig antibody response.
- 1996
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 3:4, s. 340-53
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Tidskriftsartikel (refereegranskat)abstract
- Pig kidneys were extracorporeally "ex vivo" connected to the circulation of two volunteer male dialysis patients (Breimer et al., this issue). The patients were pretreated by daily plasmapheresis for 3 consecutive days, which reduced the anti-pig lymphocytotoxic titer from 8 to 2 in the first patient and from 8 to 1 in the second patient. The anti-pig hemagglutinating titers were reduced from 32 to 4 in the first patient and from 2 to 1 in the second patient. No drugs, except heparin, were given. The perfusion lasted for 65 min in patient 1 and the experiment was terminated due to increased vascular resistance in the pig kidney. Ultrastructural investigation showed a picture similar to a hyperacute vascular rejection. Immunohistochemical studies showed a weak staining of IgM antibodies, but no IgG in the small arteries and glomeruli. The pig kidney of patient 2 was perfused for 15 min and the experiment terminated due to serious side effects of the patient. Light and electron microscopical investigation showed virtually no structural changes of the kidney tissue and immunostaining for human antibodies was negative. In both patients, serum samples collected 2-5 weeks postperfusion showed a strong anti-pig antibody titer rise (up to 512) which thereafter declined but stabilized on a higher level than before the experiment. The antibody response in the two patients was different. In patient 1, the major anti-pig antibodies directed to carbohydrate antigens were of IgG (IgG1 and IgG2 subclasses) type, while the IgM response was less prominent and virtually no IgA antibodies were produced. Despite the short duration of the perfusion in patient 2, a humoral immune response was seen that was mainly confined to the IgA immunoglobulin class (IgA1 subclass). Blood group glycospingolipid fractions, prepared from the contralateral kidney of the donor pigs, were used for immunostaining with patient serum samples. In both patients, the antibodies produced after the perfusion, mainly recognized the Galα1-3Gal epitope both as part of the "linear B" pentasaccharide but also on more complex carbohydrate structures. Patient 1 was HLA-immunized before the experiment due to a kidney allograft and had a panel reactivity of 85% before the perfusion. No change in the panel reactivity of HLA-antibodies was found after the perfusion experiments. Patient 2 had no HLA antibodies before and remained negative after the perfusion. Patient serum samples collected before and after the perfusion were tested for reactivity against human endothelial cell lines. No antibodies were generated.
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- Andersson, K, et al.
(författare)
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YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.
- 1996
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Ingår i: Molecular Microbiology. - 0950-382X .- 1365-2958. ; 20:5, s. 1057-69
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Tidskriftsartikel (refereegranskat)abstract
- The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.
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