| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Alopaeus, Tea, et al.
(författare)
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Med de nya svenska klimatmålen i sikte : Gapanalys samt strategier och förutsättningar för att nå etappmålen 2030 med utblick mot 2045
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under våren 2017 presenterade Naturvårdsverket scenarier för hur växthusgasutsläppen i Sverige skulle kunna utvecklas till 2035. Sedan Naturvårdsverket presenterade scenarierna har ett nytt klimatpolitiskt ramverk för Sverige beslutats av riksdagen med nya klimatmål till 2030, 2040 och 2045. Regeringen har även presenterat ett antal nya styrmedel i budgetpropositionen.Naturvårdsverket ska inom miljömålssystemet löpande och strategiskt analysera och utvärdera styrmedel och åtgärder. Naturvårdsverket har mellan maj och november 2017 gjort en första uppföljning mot de nya klimatmålen. I denna rapport presenteras hur beslutade och planerade styrmedel kan komma att falla ut givet olika antagande. En översiktlig analys av styrmedel görs också.Arbetsgruppens sammansättning har varierat över tid. Sammantaget har följande personer på Naturvårdsverket deltagit i arbetsgruppen: Tea Alopaeus (projektledare), Björn Boström, Mats Björsell, Martin Boije, Joanna Dickinson, Dag Henning, Daniel Engström Stenson, Eva Jernbäcker (projektledare till september), Julien Morel, Miriam Münnich Vass, Karl-Anders Stigzelius, Ulrika Svensson, Per Wollin.Stockholm 29 november 2017Björn RisingerGeneraldirektör
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| 3. |
- Bram Ednersson, Susanne, et al.
(författare)
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Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 181:6, s. 770-781
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1year from diagnosis (REF/REL), and 53 who were progression-free more than 5years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P=76x10(-10)). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P=14x10(-9)). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.
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| 4. |
- Choi, Young Hun, et al.
(författare)
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Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice
- 2006
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 116:12, s. 3240-3251
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Tidskriftsartikel (refereegranskat)abstract
- Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated hpogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance.
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| 5. |
- Gjertsson, Inger, 1962, et al.
(författare)
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Are B lymphocytes of importance in severe Staphylococcus aureus infections?
- 2000
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Ingår i: Infection and immunity. - 0019-9567. ; 68:5, s. 2431-4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the role of B cells in experimental, superantigen-mediated Staphylococcus aureus arthritis and sepsis, we used gene-targeted B-cell-deficient mice. The mice were inoculated intravenously with a toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus strain. The B-cell-deficient and thus agamma-globulinemic mice showed striking similarities to the wild-type control animals with respect to the development of arthritis, the mortality rate, and the rate of bacterial clearance. Surprisingly, we found that the levels of gamma interferon in serum were significantly lower (P < 0. 0001) in B-cell-deficient mice than in the controls, possibly due to impaired superantigen presentation and a diminished expression of costimulatory molecules. In contrast, the levels of interleukin-4 (IL-4), IL-6, and IL-10 in serum were equal in both groups. Our findings demonstrate that neither mature B cells nor their products significantly contribute to the course of S. aureus-induced septic arthritis.
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| 6. |
- Höper, Linnea, et al.
(författare)
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Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
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| 7. |
- Rüetschi, Ulla, 1962, et al.
(författare)
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SILAC-Based Quantitative Proteomic Analysis of Diffuse Large B-Cell Lymphoma Patients.
- 2015
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Ingår i: International journal of proteomics. - : Hindawi Limited. - 2090-2166 .- 2090-2174. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma, is a heterogeneous disease where the outcome for patients with early relapse or refractory disease is very poor, even in the era of immunochemotherapy. In order to describe possible differences in global protein expression and network patterns, we performed a SILAC-based shotgun (LC-MS/MS) quantitative proteomic analysis in fresh-frozen tumor tissue from two groups of DLBCL patients with totally different clinical outcome: (i) early relapsed or refractory and (ii) long-term progression-free patients. We could identify over 3,500 proteins; more than 1,300 were quantified in all patients and 87 were significantly differentially expressed. By functional annotation analysis on the 66 proteins overexpressed in the progression-free patient group, we found an enrichment of proteins involved in the regulation and organization of the actin cytoskeleton. Also, five proteins from actin cytoskeleton regulation, applied in a supervised regression analysis, could discriminate the two patient groups. In conclusion, SILAC-based shotgun quantitative proteomic analysis appears to be a powerful tool to explore the proteome in DLBCL tumor tissue. Also, as progression-free patients had a higher expression of proteins involved in the actin cytoskeleton protein network, such a pattern indicates a functional role in the sustained response to immunochemotherapy.
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| 8. |
- Stenson, Martin
(författare)
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Diffuse large B-cell lymphoma - proteomic and metabolomic studies on prognosis and treatment failure
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Background and aim: Every year almost 600 patients in Sweden are diagnosed with diffuse large B-cell lymphoma (DLBCL), the most common lymphoma, and with immunochemotherapy, approximately 60 % are cured. Yet, for patients with primary refractory disease or early relapse, the prognosis is very poor. Despite advances in molecular subclassification of DLBCL, the major tool used to risk stratify patients is the clinically based International Prognostic Index (IPI). However, there is still no available system that with precision can identify the individual patients at highest risk of treatment failure. The aim of this thesis was to search for novel prognostic and predictive biomarkers, and also investigate the mechanisms behind chemoresistance in DLBCL. Patients and methods: In paper I and III, tumor tissue from two groups of DLBCL patients; (i) patients with primary refractory disease or early relapse (REF/REL; paper I: n=5, paper III: n=44); and (ii) long-term progression-free patients, clinically considered cured (CURED; paper I: n=5, paper III: n=53), was examined with mass spectrometry proteomic approaches to explore possible differences in global protein expression, but also with the aim to reveal new mechanisms involved in immunochemotherapy resistance. In paper II, metabolomic examination with nuclear magnetic resonance spectroscopy was performed on serum from REF/REL (n=27) and CURED (n=60) DLBCL patients, to determine if differences in clinical outcome could be correlated to diverse metabolomic profiles. Results and Conclusions: In paper I, a large number of proteins could be identified and quantified. Overexpression of actin-related proteins was found among the CURED patients, a finding that appeared to be confirmed in paper III, where in addition a novel discovery regarding overexpression of multiple ribosomal proteins in the REF/REL group was made. The findings suggest previously undescribed mechanisms for immunochemotherapy resistance in DLBCL patients. In paper II, differences in the serum metabolome was found between the two groups, that could be separated with multivariate statistical analyses. Even though the results are encouraging they need to be confirmed in larger unselected studies, with aims of further exploring actin-related and ribosomal proteins, not only as possible prognostic/predictive biomarkers, but also regarding their functional role in treatment resistance in DLBCL.
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| 9. |
- Stenson, Martin, et al.
(författare)
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Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study
- 2016
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 57:8, s. 1814-1822
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Tidskriftsartikel (refereegranskat)abstract
- The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used H-1 nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n=60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease.
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