| 21. |
- Högberg, Carl, et al.
(författare)
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Succinate independently stimulates full platelet activation via cAMP and PI3β kinase signaling.
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:2, s. 361-372
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Tidskriftsartikel (refereegranskat)abstract
- Background: The citric cycle intermediate succinate has recently been identified as ligand for the G-protein coupled receptor (GPCR) SUCNR1. We have previously found that this receptor is one of the most expressed GPCRs in human platelets. Objective: The aim of this study was to investigate the role of SUCNR1 in platelet aggregation and to explore the signalling pathways of this receptor in platelets. Methods and Results: Using RT-PCR, we could demonstrate that SUCNR1 is expressed in human platelets at a level corresponding to that of the P2Y(1) receptor. Light transmission aggregation experiments showed a dose-dependent aggregation induced by succinate reaching a maximum response at 0.5mM. The effect of succinate on platelet aggregation was confirmed with flow cytometry showing increased surface expression of activated GPIIb/IIIa, and P-selectin. Intracellular SUCNR1 signalling was found to result in decreased cAMP levels, Akt phosphorylation mediated by PI3Kβ activation and receptor desensitisation. Further, succinate-induced platelet aggregation was demonstrated to depend on Src, generation of thromboxane A(2) and ATP release. The platelet SUCNR1 is subject to desensitization through both homologous and heterologous mechanisms. In addition, the P2Y(12) receptor inhibitor ticagrelor completely prevented platelet aggregation induced by succinate. Conclusions: Our experiments show that succinate induces full aggregation of human platelets via SUCNR1. Succinate-induced platelet aggregation depends on thromboxane A(2) generation, ATP release and P2Y(12) activation.
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| 22. |
- Högberg, Jonas, 1976, et al.
(författare)
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Bremsstrahlung imaging of 90Y microspheres shows poor resemblance with distributions of 99mTc-MAA in liver
- 2010
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Ingår i: Journal of the European Society of Therapeutic Radiology and Oncology. - 0167-8140. ; 94:1, s. 25-26
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE To study the resemblance between the distributions of pre- therapeutic 99mTc-MAA and therapeutic 90Y-microspheres, used for ra- dioembolization of liver tumours, making use of gamma- and bremsstrahlung imaging. Furthermore, to establish the accuracy of this method by compar- isons of spatial resolution and radioactivity, performed on line source in water phantom and on resected tumour and normal liver from patients previously treated with 90Y-microspheres. MATERIALS 3 patients diagnosed with liver tumours and planned for surgery; 1 with hepatocellular carcinoma and 2 with cholangiocarcinoma, were treated with SIRTEX R © 90Y-microspheres after standard diagnostic SPECT/CT imag- ing with 99mTc-MAA. The images acquired with gamma camera were com- pared regarding distributions of radioactivity; gamma radiation from the 99mTc-MAA distributions and bremsstrahlung from the distributions of 90Y- microspheres (the latter with a wide bremsstrahlung energy window). Resec- tions of tumour- and some normal liver tissues were performed on all three patients; the resected tissues were sliced, smaller samples were punched out and the radioactivity was measured with a NaI-detector. Furthermore, autoradiography was performed on some slices. A line source with the in- ner diameter 1 mm was positioned in a cylindrical water phantom with the diameter 20 cm; first the line source was filled with 99mTc, then emptied and filled with 90Y. SPECT/CT imaging was performed on both line source se- tups. The spatial resolutions for both radionuclides were then compared. The results from the imaging comparisons performed on the patients were then evaluated with the complementary radiological methods described above. RESULTS The comparison of images from 99mTc-MAA and 90Y showed a considerable deviance in activity distribution for two of the patients. One ex- ample is shown in the figure, the upper image showing 99mTc-MAA and the lower showing 90Y-microspheres. The moderate difference in spatial resolu- tions for 99mTc and 90Y, (15 vs 18 mm FWHM) confirmed the accuracy of these findings. The other radiological methods did also confirm the macro- scopic activity distribution as shown with bremsstrahlung imaging. CONCLUSIONS Bremsstrahlung imaging is a satisfying and reliable method in showing the actual macroscopic distribution of therapeutic 90Y-microspheres used for radioembolization of liver tumours. The results further demonstrate the need for a better diagnostic method than the one currently used, with 99mTc-MAA, thereby providing a better pre-dosimetry; hopefully with a better selection of patients, regarding tumour regression and a lower risk of liver failure.
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| 23. |
- Högberg, Jonas, 1976, et al.
(författare)
-
On the dose heterogeneity in normal liver tissue due to treatment of liver tumors with yttrium-90 microspheres
- 2012
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Ingår i: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012. European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:suppl 2, s. S281-S281
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: When treating patients with primary or metastatic liver cancer, applying external radiotherapy, an absorbed dose of 30 - 35 Gy to the whole normal liver tissue volume is associated with a 5 % risk of radiation-induced hepatitis. If less than half of the normal liver volume is being exposed, the threshold for a 5 % risk of hepatitis is increased to above 60 Gy for both primary and metastatic liver cancer. Experience with patients treated with SIR-Spheres® (Sirtex Medical Ltd.), resin microspheres aggregated with yttrium-90, has shown that most patients tolerate an average absorbed dose to normal liver tissue higher than 60 Gy. The high tolerance for this treatment procedure can probably be explained by the resulting heterogenic distribution of radioactivity. It is of interest to study the degree of heterogeneity in the distribution of radioactivity in normal liver tissue, in order to explain or even predict the tolerance to radiation. The aim of this study was to describe the degree of heterogeneity by comparing the relative standard deviations of the radioactivity concentration for different sample mass categories. Materials and Methods: Two patients with cholangiocarcinoma were planned for a combined treatment with yttrium-90-aggregated SIR-Spheres followed by surgery 9 days after radiotherapy. According to standard protocol for treatments with SIR-Spheres, the therapies were preceded by Tc-99m-labled Macro aggregated albumin (Tc-99m-MAA) distribution studies for pre-therapeutic dosimetry and lung shunting evaluations. After surgery the resected tissue, containing both tumour and normal tissue, was studied regarding the distribution of radioactivity. Several small circular samples of normal liver tissue were punched out from 2 mm thick slices of resected tissue, deliberately varying the sizes, and thus the masses of the tissue samples (from 6 to 102 mg). The samples were weighed and categorized in two (first patient) and three (second patient) groups, depending on sample mass. After this the radioactivity was measured with a NaI(Tl) detector. The relative standard deviations (SD/Median) for the radioactivity concentration for each sample mass group were determined and compared. Results: The relative standard deviation for the radioactivity concentration was decreasing rapidly with increasing sample mass. Conclusion: The results indicate a considerable degree of heterogeneity in the distribution of microspheres. One probable explanation for this heterogeneity is clustering of microspheres in the blood vessels.
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| 24. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements.
- 2012
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Ingår i: Journal of radiological protection : official journal of the Society for Radiological Protection. - : IOP Publishing. - 1361-6498. ; 32:4, s. 439-46
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of β(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. Methods and Materials. The dose rates from β(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®) Mod 2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. Results. The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. Conclusion. The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.
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| 25. |
- Johansson, Lars-Olof, 1961-, et al.
(författare)
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Boundary dialogues in co-creation of ICT-innovations
- 2012
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Ingår i: IRIS 35, Proceedings of the 35th Information Systems Research Seminar in Scandinavia: Designing the Interactive Society, 2012.
-
Konferensbidrag (refereegranskat)abstract
- This paper is based on a user-centric innovation project, Free2Ride, which is seen as an example of community interaction that overcomes boundaries. The Free2Ride projects goal was to develop a piece of ICT safety equipment consisting of a sender (on the horse) and a receiver (application in a smartphone) to be used by equestrian club members during their everyday riding activities. We will answer the research question of what the characteristics of a boundary dialogue in user-centric innovation activities are. The aim of the paper is to propose a model describing the characteristics of boundary dialogue in user-centric innovation that involve different communities of practices such as ICT developers, users and researchers. An important element of that model is the mental wandering, inwards and outwards, by core members in a community. We discuss the temporal as well as the symbolic nature of the mental wandering during the boundary dialogue in user-centric innovation activities. We applied a combination of research approaches consisting of action research and engaged scholarship approach. The theoretical framework for analyzing our findings is communities of practices with a specific interest in boundary spanning and learning dialogues.
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| 26. |
- Johansson, Lars-Olof, et al.
(författare)
-
Dynamics in an innovation boundary context : exploring a living labprocess from a community of practice perspective
- 2011
-
Ingår i: Proceedings of IRIS 2011. - Turku : Turku Centre for Computer Science. - 9789521226489 ; , s. 1-
-
Konferensbidrag (refereegranskat)abstract
- This paper is based on studies of a living lab process, which is an open, user-centric, innovation approach, where several actors from industry, user groups and academia are involved. We aim to describe and analyze the dynamics in an innovation boundary context based on a living lab process. An action-oriented research approach was applied and the empirical results are from The Find Project (TFP), with the aim of customizing an ICT product based on the needs of a user group. The findings are analyzed from a community of practice perspective where the three different communities i) researchers from Halmstad Living Lab (HLL), ii) ICT developers (ICTD), and iii) next of kin's to demented elderly persons (NOKD) represented the units of analysis. The analysis identified several boundary situations that played a vital role for the innovation process. The contribution of our research to innovation theory is a process model describing the dynamics in an innovation boundary context with regard to boundary objects-in-use as well as to brokering. The research highlights two different levels of brokering: i) product/service brokering; and ii) process brokering.
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| 27. |
- Johansson, Lars-Olof, 1961-, et al.
(författare)
-
Exploring brokering situations in an innovation boundary context
- 2011
-
Ingår i: Selected Papers of the Information Systems Research Seminar in Scandinavia. - Trondheim : Tapir Akademisk Forlag. ; , s. 15-
-
Bokkapitel (refereegranskat)abstract
- This paper is based on studies of a living lab process, which is an open, user-centric, innovation approach, where several actors from industry, user groups and academia are involved. We aim to describe and analyze the dynamics in an innovation boundary context based on a living lab process. An action-oriented research approach was applied and the empirical results are from The Find Project (TFP), with the aim of customizing an ICT product based on the needs of a user group. The findings are analyzed from a community of practice perspective where the three different communities i) researchers from Halmstad Living Lab (HLL), ii) ICT developers (ICTD), and iii) next of kin’s to demented elderly persons (NOKD) represented the units of analysis. The analysis identified several boundary situations that played a vital role for the innovation process. The contribution of our research to innovation theory is a process model describing the dynamics in an innovation boundary context with regard to boundary objects-in-use as well as to brokering. The research highlights two different levels of brokering: i) product/service brokering; and ii) process brokering.
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| 28. |
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| 29. |
- Lambeck, Kurt, et al.
(författare)
-
The Scandinavian Ice Sheet: from MIS 4 to the end of the Last Glacial Maximum
- 2010
-
Ingår i: Boreas. - : Wiley. - 1502-3885 .- 0300-9483. ; 39:2, s. 410-435
-
Forskningsöversikt (refereegranskat)abstract
- Glacial rebound modelling, to establish constraints on past ice sheets from the observational evidence of palaeo-shoreline elevations, is well established for the post- Last Glacial Maximum (post-LGM) period, for which the observational evidence is relatively abundant and well distributed spatially and in time. This is particularly the case for Scandinavia. For the earlier part of the glacial cycle this evidence becomes increasingly sparse and uncertain such that, with the exception of the Eemian period, there are very few, if any, direct sea-level indicators that constrain any part of the Scandinavian Ice Sheet evolution before the LGM. Instead, we assume that ice-sheet basal conditions during Marine Isotope Stage 3 (MIS 3) are the same as those for the LGM, focus on establishing these conditions from the rebound analysis for the LGM and Lateglacial period, and then extrapolate to the earlier period using observationally constrained locations of the ice margins. The glacial rebound modelling and inversion follow previously established formulations, with the exception that the effects of water loading from proglacial lakes that form within the Baltic Basin and elsewhere have been included. The data set for the inversion of the sea- and lake-level data has been extended to include marine-limit data in order to extend the observational record further back in time. The result is a sequence of time slices for the Scandinavian Ice Sheet from the time of MIS 4 to the Lateglacial that are characterized by frozen basal conditions until late in the LGM interval when rapid thinning occurred in the eastern and southern sectors of the ice sheet. The primary function of these models is as an interpolator between the fragmentary observational constraints and to produce quantitative models for the glaciation history with predictive capabilities, for example regarding the evolution of the Baltic Basin.
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| 30. |
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