| 11. |
- Bernsen, MR, et al.
(författare)
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On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m-2 Cisplatin and 250 mg m-2 decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 107 IU IFN-a2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of II tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells, however, its exact immunological pathomechanism(s) remain to be established. ⌐ 2003 Cancer Research UK.
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| 12. |
- Bernsen, Monique R, et al.
(författare)
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Heparan sulphate epitope-expression is associated with the inflammatory response in metastatic malignant melanoma
- 2003
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 52:12, s. 780-783
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulphate (HS) represents a heterogeneous class of molecules on cell membranes and extracellular matrices. These molecules are involved in a variety of biological processes, including immune responses, through their binding and functional modulation of proteins. Recently a panel of HS-epitope-specific, human single chain antibodies have been generated by phage display, facilitating analysis of the structural heterogeneity of HS in relation to pathological conditions. In a pilot study a heterogeneous staining pattern in melanoma metastases was observed with one of the clones (EW4G1). Using a double-staining technique, the expression of this epitope was studied in 12 metastatic melanoma lesions in relation to the presence of a CD3 + cell infiltrate. Different staining patterns with EW4G1 were observed in the different lesions. The different staining patterns were associated with the presence and pattern of inflammation with CD3+ cells. A pronounced staining pattern of blood vessels with EW4G1 was associated with a more or less brisk presence of CD3+ cells, while a pronounced staining of tumour cells or tumour cell matrix or absence of staining with EW4G1 was associated with absence of CD3+ cells. These results suggest a dualistic role for HS in the recruitment and intratumoural migration of CD3+ cells, depending on the location of expression of its epitope recognized by EW4G1. Further characterization of the structural diversity of HS and its function in T-cell recruitment and migration is therefore warranted, since detailed understanding of this relation may provide new targets for therapeutic intervention, such that better homing and migration of T cells (in)to tumours might be achieved in immunologically based treatment strategies.
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| 13. |
- Bruger, A, et al.
(författare)
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High order accurate solution of the incompressible Navier-Stokes equations
- 2005
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Ingår i: Journal of Computational Physics. - : Elsevier BV. - 0021-9991 .- 1090-2716. ; 203:1, s. 49-71
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Tidskriftsartikel (refereegranskat)abstract
- High order methods are of great interest in the study of turbulent flows in complex geometries by means of direct simulation. With this goal in mind, the incompressible Navier-Stokes equations are discretized in space by a compact fourth order finite difference method on a staggered grid. The equations are integrated in time by a second order semi-implicit method. Stable boundary conditions are implemented and the grid is allowed to be curvilinear in two space dimensions. The method is extended to three dimensions by a Fourier expansion. In every time step, a system of linear equations is solved for the velocity and the pressure by an outer and an inner iteration with preconditioning. The convergence properties of the iterative method are analyzed. The order of accuracy of the method is demonstrated in numerical experiments. The method is used to compute the flow in a channel, the driven cavity and a constricted channel.
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| 14. |
- Brüger, Arnim, et al.
(författare)
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High order accurate solution of the incompressible Navier-Stokes equations
- 2003
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- High order methods are of great interest in the study of turbulent flows in complex geometries by means of direct simulation. With this goal in mind, the incompressible Navier-Stokes equations are discretized in space by a compact fourth order finite difference method on a staggered grid. The equations are integrated in time by a second order semi-implicit method. Stable boundary conditions are implemented and the grid is allowed to be curvilinear in two space dimensions. In every time step, a system of linear equations is solved for the velocity and the pressure by an outer and an inner iteration with preconditioning. The convergence properties of the iterative method are analyzed. The order of accuracy of the method is demonstrated in numerical experiments. The method is used to compute the flow in a channel, the driven cavity and a constricted channel.
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| 15. |
- Brüger, Armin, et al.
(författare)
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Splitting methods for high order solution of the incompressible Navier-Stokes equations in 3D
- 2005
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Ingår i: International Journal for Numerical Methods in Fluids. - : Wiley. - 0271-2091 .- 1097-0363. ; 47:10-11, s. 1157-1163
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Tidskriftsartikel (refereegranskat)abstract
- The incompressible Navier-Stokes equations are discretized in space by a hybrid method and integrated in time by the method of lines. The solution is determined on a staggered curvilinear grid in two space dimensions and by a Fourier expansion in the third dimension. The space derivatives are approximated by a compact finite difference scheme of fourth-order on the grid. The solution is advanced in time by a semi-implicit method. In each time step, systems of linear equations have to be solved for the velocity and the pressure. The iterations are split into one outer iteration and three inner iterations. The accuracy and efficiency of the method are demonstrated in a numerical experiment with rotated Poiseuille flow perturbed by Off-Sommerfeld modes in a channel.
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| 16. |
- Clinchy, Birgitta, 1957-, et al.
(författare)
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Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma
- 2007
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 109:9, s. 1742-1749
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS. Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL-6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS. A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N-stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS. IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. © 2007 American Cancer Society.
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| 17. |
- Dahlfors, Gunilla, et al.
(författare)
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Inhibitory effect of diabetes on proliferation of vascular smooth muscle after balloon injury in rat aorta
- 2000
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Ingår i: Experimental Diabetes Research. - 1687-5214 .- 1687-5303. ; 1:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- The effect of streptozotocin-induced diabetes on cell proliferation in rat aortic intima-media, as well as on local gene expression of transforming growth factor-β1 (TGF-β1) was studied. TGF-β1 mRNA was measured by solution hybridization and TGF-β1 protein by ELISA. Proliferation was measured by bromodeoxyuridine incorporation into DNA two days after balloon injury. All BrdU-labelled cells observed were smooth muscle cells. After a diabetes duration of 2 and 4 weeks, labelled cells were significantly fewer compared with controls. Circulating levels of total TGF-β1 were lowered in rats with 2 weeks diabetes. Although the balloon injury procedure by itself stimulated the gene expression of TGF-β1, no significant difference in TGF-β1 mRNA content between diabetic and control rats after injury was found. In conclusion: vascular smooth muscle proliferation in vivo is inhibited by the diabetic state in this model of insulin deficient diabetes and this inhibition is not related to an impaired local expression of TGF-β1.
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| 18. |
- Eliasson, Bengt
(författare)
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Numerical simulation of kinetic effects in ionospheric plasma
- 2001
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, we study numerically the one-dimensional Vlasov equation for a plasma consisting of electrons and infinitely heavy ions. This partial differential equation describes the evolution of the distribution function of particles in the two-dimensional phase space (x,v). The Vlasov equation describes, in statistical mechanics terms, the collective dynamics of particles interacting with long-range forces, but neglects the short-range "collisional" forces. A space plasma consists of electrically charged particles, and therefore the most important long-range forces acting on a plasma are the Lorentz forces created by electromagnetic fields.What makes the numerical solution of the Vlasov equation to a challenging task is firstly that the fully three-dimensional problem leads to a partial differential equation in the six-dimensional phase space, plus time, making it even hard to store a discretized solution in the computer's memory. Secondly, the Vlasov equation has a tendency of structuring in velocity space (due to free streaming terms), in which steep gradients are created and problems of calculating the v (velocity) derivative of the function accurately increase with time.The method used in this thesis is based on the technique of Fourier transforming the Vlasov equation in velocity space and then solving the resulting equation. We have developed a method where the small-scale information in velocity space is removed through an outgoing wave boundary condition in the Fourier transformed velocity space. The position of the boundary in the Fourier transformed variable determines the amount of small-scale information saved in velocity space.The numerical method is used to investigate a phenomenon of tunnelling of information through an ionospheric layer, discovered in experiments, and to assess the accuracy of approximate analytic formulæ describing plasma wave dispersion. The numerical results are compared with theoretical predictions, and further physical experiments are proposed.
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| 19. |
- Eliasson, Bengt, 1965-
(författare)
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Numerical Vlasov–Maxwell Modelling of Space Plasma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Vlasov equation describes the evolution of the distribution function of particles in phase space (x,v), where the particles interact with long-range forces, but where shortrange "collisional" forces are neglected. A space plasma consists of low-mass electrically charged particles, and therefore the most important long-range forces acting in the plasma are the Lorentz forces created by electromagnetic fields. What makes the numerical solution of the Vlasov equation a challenging task is that the fully three-dimensional problem leads to a partial differential equation in the six-dimensional phase space, plus time, making it hard even to store a discretised solution in a computer’s memory. Solutions to the Vlasov equation have also a tendency of becoming oscillatory in velocity space, due to free streaming terms (ballistic particles), in which steep gradients are created and problems of calculating the v (velocity) derivative of the function accurately increase with time. In the present thesis, the numerical treatment is limited to one- and two-dimensional systems, leading to solutions in two- and four-dimensional phase space, respectively, plus time. The numerical method developed is based on the technique of Fourier transforming the Vlasov equation in velocity space and then solving the resulting equation, in which the small-scale information in velocity space is removed through outgoing wave boundary conditions in the Fourier transformed velocity space. The Maxwell equations are rewritten in a form which conserves the divergences of the electric and magnetic fields, by means of the Lorentz potentials. The resulting equations are solved numerically by high order methods, reducing the need for numerical over-sampling of the problem. The algorithm has been implemented in Fortran 90, and the code for solving the one-dimensional Vlasov equation has been parallelised by the method of domain decomposition, and has been implemented using the Message Passing Interface (MPI) method. The code has been used to investigate linear and non-linear interaction between electromagnetic fields, plasma waves, and particles.
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| 20. |
- Forestier, Erik, et al.
(författare)
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Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias : A nordic series of 24 cases and review of the literature
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:2, s. 149-158
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Forskningsöversikt (refereegranskat)abstract
- Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.
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