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Larsson, J. Peter
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Publikasjoner (8 av 8) Visa alla publikasjoner
Engström, L., Ruud, J., Eskilsson, A., Larsson, A., Mackerlova, L., Kugelberg, U., . . . Blomqvist, A. (2012). Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells. Endocrinology, 153(10), 4849-4861
Åpne denne publikasjonen i ny fane eller vindu >>Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells
Vise andre…
2012 (engelsk)Inngår i: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 153, nr 10, s. 4849-4861Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.

sted, utgiver, år, opplag, sider
Endocrine Society, 2012
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-84885 (URN)10.1210/en.2012-1375 (DOI)000309210200027 ()
Merknad

Funding Agencies|Swedish Research Council|7879|Swedish Cancer Foundation|100533|Swedish Brain Foundation||Gustav V:s 80-ars Fond||

Tilgjengelig fra: 2012-11-01 Laget: 2012-10-26 Sist oppdatert: 2017-12-07
Eliasson, P., Rehn, M., Hammar, P., Larsson, P., Sirenko, O., A Flippin, L., . . . Jönsson, J.-I. (2010). Hypoxia mediates low cell-cycle activity and increases the proportion of long-term reconstituting hematopoietic stem cells during in vitro culture. Experimental Hematology, 38(4), 301-310
Åpne denne publikasjonen i ny fane eller vindu >>Hypoxia mediates low cell-cycle activity and increases the proportion of long-term reconstituting hematopoietic stem cells during in vitro culture
Vise andre…
2010 (engelsk)Inngår i: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 38, nr 4, s. 301-310Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective. Recent evidence suggests that hematopoietic stem cells (HSCs) in the bone marrow (BM) are located in areas where the environment is hypoxic. Although previous studies have demonstrated positive effects by hypoxia, its role in HSC maintenance has not been fully elucidated, neither has the molecular mechanisms been delineated. Here, we have investigated the consequence of in vitro incubation of HSCs in hypoxia prior to transplantation and analyzed the role of hypoxia-inducible factor (HIF)-1 alpha. Materials and Methods. HSC and progenitor populations isolated from mouse BM were cultured in 20% or 1% O-2, and analyzed for effects on cell cycle, expression of cyclin-dependent kinase inhibitors genes, and reconstituting ability to lethally irradiated mice. The involvement of HIF-1 alpha was studied using methods of protein stabilization and gene silencing. Results. When long-term FLT3(-)CD34(-)Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were cultured in hypoxia, cell numbers were significantly reduced in comparison to normoxia. This was due to a decrease in proliferation and more cells accumulating in G(0). Moreover, the proportion of HSCs with long-term engraftment potential was increased. Whereas expression of the cyclin-dependent kinase inhibitor genes p21(cip1), p27(Kip1), and p57(Kip2) increased in LSK cells by hypoxia, only p21(cip1) was upregulated in FLT3(-)CD34(-)LSK cells. We could demonstrate that expression of p27(KiP1) and p57(Kip2) was dependent of HIF-1 alpha. Surprisingly, overexpression of constitutively active HIF-1 alpha or treatment with the HIF stabilizer agent FG-4497 led to a reduction in HSC reconstituting ability. Conclusions. Our results imply that hypoxia, in part via HIF-1 alpha, maintains HSCs by decreasing proliferation and favoring quiescence.

sted, utgiver, år, opplag, sider
Elsevier, 2010
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-54780 (URN)10.1016/j.exphem.2010.01.005 (DOI)000276054300005 ()
Merknad

Original Publication: Pernilla Eliasson, Matilda Rehn, Petter Hammar, Peter Larsson, Oksana Sirenko, Lee A Flippin, Jorg Cammenga and Jan-Ingvar Jönsson, Hypoxia mediates low cell-cycle activity and increases the proportion of long-term reconstituting hematopoietic stem cells during in vitro culture, 2010, EXPERIMENTAL HEMATOLOGY, (38), 4, 301-310. http://dx.doi.org/10.1016/j.exphem.2010.01.005 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/

On the day of the defence date the title of this article was "Hypoxia, via hypoxia-inducible factor (HIF)-1, mediates low cell cycle activity and preserves the engraftment potential of mouse hematopoietic stem cells" and one of the authors is no longer included in the article.

When finally published online the title of this article changed name to Hypoxia mediates low cell-cycle activity and increases the proportion of long-term-reconstituting hematopoietic stem cells during in vitro culture.

Tilgjengelig fra: 2010-04-09 Laget: 2010-04-09 Sist oppdatert: 2017-12-12bibliografisk kontrollert
Malusek, A., Larsson, J. P. & Alm Carlsson, G. (2007). Monte Carlo study of the dependence of the KAP-meter calibration coefficient on beam aperture, X-ray tube voltage, and reference plane. Physics in medicine and biology, 52(4), 1157-1170
Åpne denne publikasjonen i ny fane eller vindu >>Monte Carlo study of the dependence of the KAP-meter calibration coefficient on beam aperture, X-ray tube voltage, and reference plane
2007 (engelsk)Inngår i: Physics in medicine and biology, ISSN 0031-9155, Vol. 52, nr 4, s. 1157-1170Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The Monte Carlo method was used to study the dependence of the calibration coefficient on the tube voltage, beam aperture and reference plane in simplified over-couch geometries modelling VacuTec's type 70157 KAP-meter both with and without an additional filter. The MCNP5 code was used to calculate (i) energy imparted to air cavities of the KAP-meter and (ii) spatial distribution of air collision kerma at entrance and exit planes of the KAP-meter and at a plane close to the patient. From these data, the air kerma area product and calibration coefficient were calculated and their dependence on the tube voltage and beam aperture was analysed. It was found that the variation of the calibration coefficient as a function of tube voltage was up to 40% when the additional filter was used. The additional filter placed closely in front of the KAP-meter decreased the calibration coefficient for the patient plane by about 10% compared to the ideal additional filter. The effect of the beam aperture was small at the patient plane and negligible for the exit plane.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-13034 (URN)10.1088/0031-9155/52/4/020 (DOI)
Tilgjengelig fra: 2008-03-13 Laget: 2008-03-13 Sist oppdatert: 2015-03-20
Larsson, P. (2006). Calibration of Ionization Chambers for Measuring Air Kerma Integrated over Beam Area in Diagnostic Radiology. (Doctoral dissertation). Institutionen för medicin och vård
Åpne denne publikasjonen i ny fane eller vindu >>Calibration of Ionization Chambers for Measuring Air Kerma Integrated over Beam Area in Diagnostic Radiology
2006 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The air kerma area product PKA is an important quantity used by hospital physicists in quality assurance and optimization processes in diagnostic radiology and is recommended by national authorities for setting of diagnostic reference levels. PKA can be measured using a transmission ionization chamber (kerma area product (KAP) meter) mounted on the collimator housing. Its signal QKAP must be calibrated to give values of PKA. The objective of this thesis is to analyze the factors influencing the accuracy of the calibration coefficients k= PKA/QKAP and of reported PKA-values.

Due to attenuation and scatter in the KAP-meter and presence of extra-focal radiation, values of PKA depend on the choice of integration area A and the distance of the reference plane from the focal spot yielding values of PKA that may differ by as much as 23% depending on this choice. The two extremes correspond to (1) PKA=PKA,o integrated over the exit surface of the KAP-meter resulting in geometry independent calibration coefficients and (2) PKA=PKA,Anom integrated over the nominal beam area in the patient entrance plane resulting in geometry dependent calibration coefficients.

Three calibration methods are analysed. Method 1 aims at determine PKA,Anom, for clinical use at the patient entrance plane. At standard laboratories, the method is used to calibrate with respect to radiation incident on the KAP-meter. Problems with extra-focal and scattered radiation are then avoided resulting in calibration coefficients with low standard uncertainty (±1.5 %, coverage factor 2). Method 2 was designed in this work to approach determination of PKA,o using thermoluminescent detectors to monitor contributions from extra-focal radiation and account for the heel effect. The uncertainty in derived calibration coefficients was ± 3% (coverage factor 2). Method 3 uses a Master KAP-meter calibrated at a standard laboratory for incident radiation to calibrate clinical KAP-meters. It has potential to become the standard method in the future replacing the tedious method 2 for calibrations aiming at determination of PKA,o.

Commercially available KAP-meters use conducting layers of indium oxide causing a strong energy dependence of their calibration coefficients. This dependence is investigated using Monte Carlo simulations and measurements. It may introduce substantial uncertainties in reported PKA– values since calibration coefficients as obtained from standard laboratories are often available only at one filtration (2.5 mm Al) as function of tube voltage or HVL. This is not sufficient since higher filtrations are commonly used in practice, including filters of Cu. In extreme cases, calibration coefficients for the same value of HVL but using different tube voltages and filtrations can deviate by as much as 30%. If standardised calibration methods are not used and choice of calibration coefficients not carefully chosen with respect to beam quality, the total uncertainty in reported PKA–values may be as large as 40-45%. Conversion of PKA-values to risk related quantities is briefly discussed. The large energy dependence of the conversion coefficients, ε/PKA, for determination of energy imparted,ε, to the patient reduces to a lower energy dependence of calibration coefficients CQ,ε = ε/QKAP for determination of ε from the KAP-meter signal.

sted, utgiver, år, opplag, sider
Institutionen för medicin och vård, 2006
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 970
Emneord
KAP-meter, DAP-meter, PKA, kerma area product, energy dependence, calibration
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-7848 (URN)91-85643-32-7 (ISBN)
Disputas
2006-12-08, Elsa Brändströmsalen, Södra Entrén, Campus US, Linköpings Universitet, Linköping, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2015-03-20
Larsson, P., Malusek, A., Persliden, J. & Alm Carlsson, G. (2006). Energy dependence in KAP-meter calibration coefficients: Dependence on calibration method, type of KAP-meter, and added filter close to the KAP-meter. Physics in Medicine and Biology
Åpne denne publikasjonen i ny fane eller vindu >>Energy dependence in KAP-meter calibration coefficients: Dependence on calibration method, type of KAP-meter, and added filter close to the KAP-meter
2006 (engelsk)Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560Artikkel i tidsskrift (Fagfellevurdert) Submitted
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-14178 (URN)
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2017-12-13
Larsson, P., Persliden, J. & Alm Carlsson, G. (1998). Ionization chambers for measuring air kerma integrated over beam area: Deviations in calibration values using simplified calibration methods. Physics in Medicine and Biology, 43(3), 599-607
Åpne denne publikasjonen i ny fane eller vindu >>Ionization chambers for measuring air kerma integrated over beam area: Deviations in calibration values using simplified calibration methods
1998 (engelsk)Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, Vol. 43, nr 3, s. 599-607Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Calibrations of kerma-area product meters (KAP meters) are often performed using simplified methods. The accuracy thus obtained can be insufficient, especially when the KAP meters are used for optimizing radiological procedures. The deviations between the best available calibration factor (k) and the simplified calibration factor were measured at different clinical x-ray installations. Depending on the type of x-ray installation and calibration method, the quotient ranged from 0.83 to 1.19, reflecting the error made in practice using these methods. A simple alternative calibration method based on comparison with a KAP meter calibrated by the best available method is described. Depending on tube potential and the stability of the electrometers, the uncertainty in the calibration factor derived with this method was between 3.8% and 5.6% (at 95% confidence level).

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-14176 (URN)10.1088/0031-9155/43/3/011 (DOI)
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2015-03-20
Larsson, P. & Alm Carlsson, G. (1996). Evaluation of the uncertainties in KAP-meter calibrations. Linköping: Linköping University Electronic Press
Åpne denne publikasjonen i ny fane eller vindu >>Evaluation of the uncertainties in KAP-meter calibrations
1996 (engelsk)Rapport (Annet vitenskapelig)
Abstract [en]

This report was prepared in order to give more details to the uncertainty evaluation of the Kerma area product meter calibration procedure described in the paper:

Larsson J P Persliden J Sandborg S and Alm Carlsson G 1996 Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration. Phys. Med. Biol. 41 2381-2398.

Figures and equations referred to in this report will be found in the paperabove.

For convenience, however, the equations in the paper that are used in the uncertainty analysis are retyped on the next two sides, see text in section 2.7. in the paper for further details. The numbering of the equations are kept as in the paper.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 1996. s. 14
Serie
Report / Institutionen för radiofysik, Universitetet i Linköping, 1990-1997, ISSN 1102-1799 ; 82
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-14175 (URN)LIU-RAD-R-082 (ISRN)91-7871-814-7 (ISBN)
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2015-03-20bibliografisk kontrollert
Larsson, P., Persliden, J., Sandborg, M. & Alm Carlsson, G. (1996). Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration. Physics in Medicine and Biology, 41(11), 2381-2398
Åpne denne publikasjonen i ny fane eller vindu >>Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration
1996 (engelsk)Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, Vol. 41, nr 11, s. 2381-2398Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Kerma - area product meters (KAP meters) are frequently used in diagnostic radiology to measure the integral of air-collision kerma over an area perpendicular to the x-ray beam. In this work, a precise method for calibrating a KAP meter to measure is described and calibration factors determined for a broad range of tube potentials (40 - 200 kV). The integral is determined using a large number of TL dosimeters spread over and outside the nominal field area defined as the area within 50% of maximum . The method is compared to a simplified calibration method which approximates the integral by multiplying the kerma in the centre of the field by the nominal field area . While the calibration factor using the precise method is independent of field area and distance from the source, that using the simplified method depends on both. This can be accounted for by field inhomogeneities caused by the heel effect, extrafocal radiation and scattered radiation from the KAP meter. The deviations between the calibration factors were as large as for collimator apertures of and distances from the source of 50 - 160 cm. The uncertainty in the calibration factor using the precise method was carefully evaluated and the expanded relative uncertainty estimated to be with a confidence level of 95%.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-14174 (URN)10.1088/0031-9155/41/11/010 (DOI)
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2015-03-20
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