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Sökning: WFRF:(Jakobsson Sven)

  • Resultat 1-10 av 76
  • [1]234567...8Nästa
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  • Lindskog, M., et al. (författare)
  • Overall survival in Swedish patients with renal cell carcinoma treated in the period 2002 to 2012: Update of the RENCOMP study with subgroup analysis of the synchronous metastatic and elderly populations
  • 2017
  • Ingår i: Urologic Oncology-Seminars and Original Investigations. - : ELSEVIER SCIENCE INC. - 1078-1439 .- 1873-2496. ; 35:9, s. 541.e15-541.e22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. Methods: Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (Ml) and the elderly (aged >= 75 y). Results: A total of 4,217 patients with mRCC were identified, including 1,533 patients with Ml and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (>= 75 vs. <75 y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, Ml, and elderly populations. Conclusion: This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in Ml and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age. (C) 2017 Elsevier Inc. All rights reserved.
  • Johansson, Ann-Sofie, 1967-, et al. (författare)
  • Lymphoblastic T-cell lymphoma in mice is unaffected by Celecoxib as single agent or in combination with cyclophosphamide
  • 2009
  • Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. ; 50:7, s. 1198-1203
  • Tidskriftsartikel (refereegranskat)abstract
    • Celecoxib, an inhibitor of cyclooxygenase-2, is a promising novel antitumor agent with pleitropic mechanisms of action. Whereas this drug induces growth arrest and apoptosis of B-lymphoma cells, its effect against aggressive T-cell neoplasms remains to be studied. We therefore evaluated Celecoxib therapy of immunocompetent mice transplanted with lymphoblastic T-cell lymphomas. Oral Celecoxib in clinically relevant and non-toxic doses did not affect the degree of hypersplenism or the number of viable lymphoma cells. The clinical deterioration of Celecoxib-treated mice was not different from untreated controls. The impact of adding Celecoxib (60 mg/kg) to cyclophosphamide (200 mg/kg x 1, i.p.) was assessed but showed no benefit compared to cyclophosphamide alone. Thus, Celecoxib lacks effect against lymphoblastic T-cell lymphoma in mice.
  • Jonsson, B. G., et al. (författare)
  • Skogspolitiken hotar biologiska mångfalden
  • 2008
  • Ingår i: Dagens Nyheter. ; 14 april
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Ledande svenska forskare varnar för att det nationella naturarvet äventyras: Vi skäms över våra beslutsfattares likgiltighet för miljön. Den svenska skogen har förvandlats till en jättelik odlingsyta. Där förr otaliga arter levde samman i harmoni dominerar numera helt gran, tall och inplanterade främmande trädslag. Denna skogsodling utgör ett hot mot den biologiska mångfalden vilket strider mot riksdagens miljökvalitetsmål. Den svenska skogspolitiken vilar officiellt på att produktion av skogsråvara och miljö är likvärdiga mål. Men i praktiken har produktionen satts i första rummet. Bortåt 2 000 skogslevande arters överlevnad hotas på grund av den förda politiken. Vi är djupt oroade och skäms över att det rika Sverige inte arbetar effektivt för att nå nationella och internationella miljömål. Det skriver 14 ledande forskare i bland annat växtekologi, ekologisk zoologi och botanik.
  • Larsson, Karin, et al. (författare)
  • Biological characterization of new inhibitors of microsomal PGE synthase-1 in preclinical models of inflammation and vascular tone
  • 2019
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 176:24, s. 4625-4638
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose Microsomal PGE synthase-1 (mPGES-1), the inducible synthase that catalyses the terminal step in PGE(2) biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES-1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti-constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES-1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models. Experimental Approach Potency was determined based on the reduction of PGE(2) formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti-inflammatory properties were assessed by acute paw swelling in a paw oedema rat model. Effect on vascular tone was determined with human ex vivo wire myography. Key Results We report five new mPGES-1 inhibitors (named 934, 117, 118, 322, and 323) that selectively inhibit recombinant human and rat mPGES-1 with IC50 values of 10-29 and 67-250 nM respectively. The compounds inhibited PGE(2) production in a cellular assay (IC50 values 0.15-0.82 mu M) and in a human whole blood assay (IC50 values 3.3-8.7 mu M). Moreover, the compounds blocked PGE(2) formation in an air pouch mouse model and reduced acute paw swelling in a paw oedema rat model. Human ex vivo wire myography analysis showed reduced adrenergic vasoconstriction after incubation with the compounds. Conclusion and Implications These mPGES-1 inhibitors can be used as refined tools in further investigations of the role of mPGES-1 in inflammation and microvascular disease.
  • Olofsson, M., et al. (författare)
  • Eyespot display in the peacock butterfly triggers antipredator behaviors in naïve adult fowl
  • 2013
  • Ingår i: Behavioral Ecology. - : Oxford University Press. - 1045-2249 .- 1465-7279. ; 24:1, s. 305-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Large conspicuous eyespots have evolved in multiple taxa and presumably function to thwart predator attacks. Traditionally, large eyespots were thought to discourage predator attacks because they mimicked eyes of the predators' own predators. However, this idea is controversial and the intimidating properties of eyespots have recently been suggested to simply be a consequence of their conspicuousness. Some lepidopteran species include large eyespots in their antipredation repertoire. In the peacock butterfly, Inachis io, eyespots are typically hidden during rest and suddenly exposed by the butterfly when disturbed. Previous experiments have shown that small wild passerines are intimidated by this display. Here, we test whether eyespots also intimidate a considerably larger bird, domestic fowl, Gallus gallus domesticus, by staging interactions between birds and peacock butterflies that were sham-painted or had their eyespots painted over. Our results show that birds typically fled when peacock butterflies performed their display regardless of whether eyespots were visible or painted over. However, birds confronting butterflies with visible eyespots delayed their return to the butterfly, were more vigilant, and more likely to utter alarm calls associated with detection of ground-based predators, compared with birds confronting butterflies with eyespots painted over. Because production of alarm calls and increased vigilance are antipredation behaviors in the fowl, their reaction suggests that eyespots may elicit fear rather than just an aversion to conspicuous patterns. Our results, therefore, suggest that predators perceive large lepidopteran eyespots as belonging to the eyes of a potential predator.
  • Pawelzik, Sven-Christian, et al. (författare)
  • Identification of Key Residues Determining Species Differences in Inhibitor Binding of Microsomal Prostaglandin E Synthase-1
  • 2010
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:38, s. 29254-29261
  • Tidskriftsartikel (refereegranskat)abstract
    • Microsomal prostaglandin E synthase-1 (MPGES1) is induced during an inflammatory reaction from low basal levels by pro-inflammatory cytokines and subsequently involved in the production of the important mediator of inflammation, prostaglandin E-2. Nonsteroidal anti-inflammatory drugs prevent prostaglandin E-2 production by inhibiting the upstream enzymes cyclooxygenases 1 and 2. In contrast to these conventional drugs, a new generation of NSAIDs targets the terminal enzyme MPGES1. Some of these compounds potently inhibit human MPGES1 but do not have an effect on the rat orthologue. We investigated this interspecies difference in a rat/human chimeric form of the enzyme as well as in several mutants and identified key residues Thr-131, Leu-135, and Ala-138 in human MPGES1, which play a crucial role as gate keepers for the active site of MPGES1. These residues are situated in transmembrane helix 4, lining the entrance to the cleft between two subunits in the protein trimer, and regulate access of the inhibitor in the rat enzyme. Exchange toward the human residues in rat MPGES1 was accompanied with a gain of inhibitor activity, whereas exchange in human MPGES1 toward the residues found in rat abrogated inhibitor activity. Our data give evidence for the location of the active site at the interface between subunits in the homotrimeric enzyme and suggest a model of how the natural substratePGH(2), or competitive inhibitors of MPGES1, enter the active site via the phospholipid bilayer of the membrane.
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