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1.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
2.	Huang, Ranyang, et al. (författare) Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U-937 and Mono Mac 6 1993 Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 38:4, s. 359-367 Tidskriftsartikel (refereegranskat)abstract Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
3.	Allard, Christina, et al. (författare) Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11 2015 Annan publikation (populärvet., debatt m.m.)abstract Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
4.	Brechensbauer Brandin, Madeleine, et al. (författare) Centralen : Studier i området kring Stockholms Centralstation 1989 Rapport (populärvet., debatt m.m.)abstract Denna skrift handlar om Centralen i Stockholm och dess närmaste omgivningar, Centralplan, T-centralen, Vasagatan och Klarabergsgatan. Den är resultatet av Arkitekturskolans arbete läsåret 1983- 84 och innehåller förutom en rad projekt också historiska utblickar och samtidskritiska resonemang. En stor del av innehållet redovisades redan våren 1984 - det skedde genom en utställning på Arkitekturmuseet och en preliminär publikation. Materialet har sedan svällt ut med innehållsrika uppsatser om Centralen, om äldre och nyare insatser för att förena konst och arkitektur och om den föga kända, ännu obebyggda Blekholmen.
5.	Gatchell, Michael, et al. (författare) Commissioning of the DESIREE storage rings - a new facility for cold ion-ion collisions 2014 Ingår i: XXVIII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2013). - : Institute of Physics (IOP). ; 488:1 Konferensbidrag (refereegranskat)abstract We report on the ongoing commissioning of the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. Beams of atomic carbon anions (C-) and smaller carbon anion molecules (C-2(-), C-3(-), C-4(-) etc.) have been produced in a sputter ion source, accelerated to 10 keV or 20 keV, and stored successfully in the two electrostatic rings. The rings are enclosed in a common vacuum chamber cooled to below 13 Kelvin. The DESIREE facility allows for studies of internally relaxed single isolated atomic, molecular and cluster ions and for collision experiments between cat-and anions down to very low center-of-mass collision energies (meV scale). The total thermal load of the vacuum chamber at this temperature is measured to be 32 W. The decay rates of stored ion beams have two components: a non-exponential component caused by the space charge of the beam itself which dominates at early times and an exponential term from the neutralization of the beam in collisions with residual gas at later times. The residual gas limited storage lifetime of carbon anions in the symmetric ring is over seven minutes while the 1/e lifetime in the asymmetric ring is measured to be about 30 seconds. Although we aim to improve the storage in the second ring, the number of stored ions are now sufficient for many merged beams experiments with positive and negative ions requiring milliseconds to seconds ion storage.
6.	Gustafsson, Lena, et al. (författare) Rapid ecological response and intensified knowledge accumulation following a north European mega-fire 2019 Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 34:4, s. 234-253 Forskningsöversikt (refereegranskat)abstract Deepened knowledge on response of biota and ecological processes following fire is essential for a future with warmer climate and more disturbances. In 2014 the first mega-fire (13,100 ha) for at least a century in Scandinavia hit south-central Sweden, in a production forest landscape shaped by clearcutting forestry. Ecological dynamics is followed in >20 projects from universities, authorities and citizen science initiatives, rapidly accumulating substantial amounts of data. We outline projects and summarize their results during the first four years, demonstrating a rapid succession of fungi, lichens, vascular plants, birds, mammals, ticks, butterflies, beetles, and drastically altered carbon dynamics. We characterize forest operations including regeneration measures and point to patterns in pest and pathogen infestations. 8,000 ha is set aside for natural succession, with the rest harvested and managed for forest production, offering excellent opportunities for studies on salvage logging effects, already evident for birds. We demonstrate a strong regrowth of deciduous trees, and the protected part will in some decades likely develop into the largest deciduous-dominated area in boreal north Europe outside Russia. Continued studies of biodiversity and ecological processes are urgent for this unique area.
7.	Hartman, Henrik, et al. (författare) First storage of ion beams in the Double Electrostatic Ion-Ring Experiment : DESIREE 2013 Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 84:5 Tidskriftsartikel (refereegranskat)abstract We report on the first storage of ion beams in the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. We have produced beams of atomic carbon anions and small carbon anion molecules (Cn-, n = 1, 2, 3, 4) in a sputter ion source. The ion beams were accelerated to 10 keV kinetic energy and stored in an electrostatic ion storage ring enclosed in a vacuum chamber at 13 K. For 10 keV C2- molecular anions we measure the residual-gas limited beam storage lifetime to be 448 s +/- 18 s with two independent detector systems. Using the measured storage lifetimes we estimate that the residual gas pressure is in the 10-14 mbar range. When high current ion beams are injected, the number of stored particles does not follow a single exponential decay law as would be expected for stored particles lost solely due to electron detachment in collision with the residual-gas. Instead, we observe a faster initial decay rate, which we ascribe to the effect of the space charge of the ion beam on the storage capacity.
8.	Jernelöv, Arne, et al. (författare) Tankar kring begreppet - Sustainable Development 1990 Rapport (övrigt vetenskapligt/konstnärligt)abstract Begreppet 'sustainable development' har fått omfattande politisk acceptans men är inte ett operationellt koncept eftersom det är odefinierat och opreciserat. I artikeln diskuteras frågan om tidshorisont, huruvida begreppet bör avse teknologier eller projekt och hur en analys av 'sustainability' kan gå till.
9.	Jordan, Stanley C, et al. (författare) IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. 2017 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
10.	Larsson, Lars E, et al. (författare) Harmonisation of the appearance of digital radiographs from different vendors by means of common external image processing 2010 Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 92-97 Tidskriftsartikel (refereegranskat)abstract The aim of the present study was to evaluate the use of common external image processing to compensate for differences in appearance between digital X-ray images from different vendors. Twenty posteroanterior chest radiographs were collected from each of three different modalities from different vendors (GE, Siemens and Canon) with vendor-specific image processing applied. The images were also extracted with neutral process parameters and processed with external image-processing software. Six experienced radiologists rated the quality and the similarity of the images with the original Siemens images. The externally processed GE images were rated of higher quality than the original GE images and more similar to the original Siemens images (p < 0.001). The opposite was obtained for the Canon images. The externally processed Siemens images were rated of similar quality as the original images. The present study indicates the possibility of using common external image processing to harmonise the appearance of images from different vendors, although the exposure parameters may need to be adjusted for individual vendors.
11.	Larsson, Lars, et al. (författare) Harmonization of the appearance of digital radiographs from different vendors by means of common external image processing 2009 Ingår i: Third Malmö Conference on Medical Imaging: Optimisation in X-Ray and Molecular Imaging, Malmö, Sweden, 25-27 June 2009. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
12.	Lindberg, Anne, 1957- (författare) Chronic obstructive pulmonary disease (COPD) : prevalence, incidence, decline in lung function and risk factors 2004 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The Obstructive Lung Disease in Northern Sweden (OLIN) Studies started in 1985 as an epidemiological project with the aim to detect preventable risk factors for obstructive lung diseases and allergy. In recent years there has been a focus also on obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) besides asthma and allergy. The aim of this thesis was to estimate the prevalence and incidence of COPD, risk factors for COPD, and decline in lung function in relation to COPD.The OLIN cohort I (cI) was recruited in 1985/86 and consisted of all 6610 subjects born 1919-20, 1934-35 and 1949-50 in eight geographical areas of Norrbotten. A postal questionnaire survey was performed in 1985/86, 1992 and in 1996. All subjects reporting respiratory symptoms at the questionnaire in 1985/86 were invited to examination in 1986, 1996 and 2002-03. A random sample of 1500 subjects from the participants at the 1996 postal questionnaire survey was invited to examination in 1996 and 2003. The participation rate has been high, ≥85%. The OLIN cohort III (cIII) was recruited in 1992, a postal questionnaire was sent to a random sample of 5681 subjects aged 20-69 years. In 1994/95 a random sample of 970 subjects were invited to examination of whom 666 participated.The prevalence of COPD in the general population sample (cIII) in ages <45 was 4.1%, 11.6%, 9.1%, and 5.1% according to the criteria of BTS1 , ERS2 , GOLD3 , and ATS4 respectively. The corresponding figures in ages ≥45 were 9.7%, 15.4%, 17.1%, and 16.5% respectively. In the age-stratified general population sample (>45 y, cI), the prevalence was 8.1% and 14.3% according to the BTS and GOLD criteria. The prevalence was strongly associated with higher age and smoking but not gender. The prevalence among smokers 76-77 years old was 45% and 50% (BTS and GOLD criteria). A majority of subjects with COPD had respiratory symptoms (in prevalent BTS 94%), most commonly cough and sputum production. Nearly a half of the subjects with COPD had contacted health care due to respiratory complaints other than common colds, but only a minority reported a physician diagnosis relevant for COPD (16% of prevalent COPD according to BTS in cIII, 31% in cI). The 10-year cumulative incidence of COPD (1986-1996) was estimated at 8.2% (BTS) and 13.5% (GOLD) in the symptomatics of cI, associated with higher age and smoking but not gender. Persistent smoking, male gender and reported chronic productive cough were associated with a faster decline in FEV1. Among incident cases of COPD a large proportion (23% of incident BTS) had a rapid decline in FEV1, >90 ml/year, corresponding to a decrease of 28 percent-units of normal value during ten years.The 7-year cumulative incidence of COPD in the random sample of cI (1996-2003) was estimated at 4.9% and 11.0% (NICE guidelines5 and GOLD) and associated with smoking but not gender. The incidence according to GOLD, but not NICE, was associated with increasing age. In multi-variate analysis most respiratory symptoms were markers of increased risk for developing COPD.In conclusion, the prevalence and the incidence of COPD were associated with age and smoking and affected by the use of different spirometric criteria. Respiratory symptoms marked an increased risk for developing COPD. A high proportion of subjects developing COPD had a rapid decline in lung function. Further, there was a substantial underdiagnosis of COPD.1 British Thoracic Society: FEV1/VC<0.70 & FEV1<80%predicted (pred), 2 European Respiratory Society: FEV1/VC<88%pred in men, <89%pred in women, 3 Global initiative for Chronic Obstructive Lung Disease:FEV1/FVC<0.70, 4 American Thoracic Society: FEV1/FVC<0.75 + symptoms or physician diagnosis, 5 The British National Institute for Clinical Excellence: FEV1/FVC<0.70 & FEV1<80%pred.
13.	Lindberg, Anne, et al. (författare) Decline in FEV1 in relation to incident chronic obstructive pulmonary disease in a cohort with respiratory symptoms. 2007 Ingår i: COPD. - : Informa UK Limited. - 1541-2555. ; 4:1, s. 5-13 Tidskriftsartikel (refereegranskat)abstract Data on the relationship between decline in lung function and development of COPD are sparse. We assessed the decline in FEV1 during 10 years among subjects with respiratory symptoms by two different methods and evaluated risk factors for decline and its relation to incident Chronic Obstructive Pulmonary Disease, COPD. A cross-sectional postal questionnaire was in 1986 sent to 6610 subjects of three age strata. All subjects reporting respiratory symptoms were invited to a structured interview and spirometry. A follow-up survey was performed 10 years later, and totally 1109 subjects performed spirometry in both 1986 and 1996. COPD was defined according to the ATS/ERS standards (FEV1/FVC < or =0.70). The decline in FEV1 was 39 ml/year in men vs. 28 ml/year in women, p = < 0.001 (-1.53 vs. -0.12 change in percent of predicted normal value over 10 years (pp), p = 0.023), among smokers 39 vs. non-smokers 28 ml/year, p < 0.001 (-3.30 vs. 0.69 pp, p < 0.001), in subjects with chronic productive cough 36 vs. not 32 ml/year, p = 0.044 (-2.00 vs. -0.02 pp, p = 0.002). Incident cases of moderate COPD (n = 83) had a decline of 62 ml/year (-12.6 pp) and 22.9% of them had a decline > 90 ml/year (-27.8 pp over 10 years). Gender-specific analysis revealed that smoking was a stronger risk factor in women than in men, while higher age was a significant risk factor in men only. In conclusion, decline in FEV1 was associated with age, smoking, and chronic productive cough, but the risk factor pattern was gender-dependent. Among incident cases of COPD the decline was steeper and close to a quarter had a rapid decline.
14.	Lindberg, Lars, et al. (författare) Nitric oxide gives maximal response after coronary artery bypass surgery 1994 Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 8:2, s. 182-187 Tidskriftsartikel (refereegranskat)abstract The dose-response to inhalation of nitric oxide (NO) after coronary artery bypass surgery was studied in seven patients with normal preoperative lung function and chest radiograms. During postoperative controlled ventilation with PEEP 5 and 10 cmH2O, the patients inhaled NO in concentrations of 2 to 25 ppm, in random order, for 6 to 10 minutes. Hemodynamic and oximetric data were analyzed before, 5 minutes after start of the NO inhalation, and 5 minutes after the cessation. The response was the same at all concentrations; mean pulmonary artery pressure decreased by 11 +/- 1% (P < 0.05) and pulmonary vascular resistance decreased by 22 +/- 2% (P < 0.05). Systemic hemodynamics did not change, but oximetric parameters tended to improve. Changes in PEEP did not affect the response. It is concluded that, in patients who have undergone coronary artery bypass grafting, inhalation of 2 to 25 ppm NO causes a dose-independent decrease in pulmonary artery pressure and pulmonary vascular resistance. In order to investigate the dose-response curve, concentrations lower than 2 ppm of NO must be used.
15.	Lloyd-Spets, Anita, et al. (författare) SiC based field effect gas sensors for industrial applications 2001 Ingår i: Physica status solidi. A, Applied research. - 0031-8965 .- 1521-396X. ; 185:1, s. 15-25 Tidskriftsartikel (refereegranskat)abstract The development and field-testing of high-temperature sensors based on silicon carbide devices have shown promising results in several application areas. Silicon carbide based field-effect sensors can be operated over a large temperature range, 100-600 degreesC, and since silicon carbide is a chemically very inert material these sensors can be used in environments like exhaust gases and flue gases from boilers. The sensors respond to reducing gases like hydrogen, hydrocarbons and carbon monoxide. The use of different temperatures, different catalytic metals and different structures of the gate metal gives selectivity to different gases and arrays of sensors can be used to identify and monitor several components in gas mixtures. MOSFET sensors based on SIC combine the advantage of simple circuitry with a thicker insulator, which increases the long term stability of the devices. In this paper we describe silicon carbide MOSFET sensors and their performance and give: examples of industrial applications such as monitoring of car exhausts and flue gases. Chemometric methods have been used for the evaluation of the data.
16.	Looman, Camilla, 1977- (författare) The ABC of KRAB zinc finger proteins 2003 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract All living organisms consist of cells and the identity of a cell is defined by the genes it expresses. To assure proper function, a cell receives continuous information on which genes to turn on and off. This information is, to a large extent, provided by transcription factors. Krüppel-related zinc finger proteins probably constitute the largest family of transcription factors in mammals and many of these proteins carry a potent repressor domain called Krüppel-associated box (KRAB). The human genome alone encodes more than 200 KRAB zinc finger proteins but still very little is known about their biological functions. The Krüppel-related zinc finger genes appear to have been involved in a massive expansion throughout evolution. To unravel some of the secrets underlying this evolutionary success, we studied the molecular evolution of KRAB zinc finger genes. We show that the frequently occurring duplications of these genes are accompanied by a low sequence constraint in their zinc finger region. In addition, we show that the number of zinc finger motifs carried within these proteins is far from fixed. New zinc finger motifs are frequently added while others are inactivated or even discarded from the coding region. The structurally independent Krüppel zinc finger motif has, through these mechanisms, served as a highly adaptive building block for the generation of new transcriptional regulators. The mouse, rat and human genomes carry four different variants of the KRAB domain – KRAB(AB), KRAB(Ab), KRAB(AC) and KRAB(A). This thesis presents the identification of a novel KRAB domain, KRAB C, as well as a functional analysis of the different KRAB domains. We conclude that all different KRAB domains share a common co-repressor, TIFβ, and effectively repress transcription. These functions are mainly mediated by the KRAB A box but are clearly influenced by the presence of a KRAB B, b or C box. Furthermore, we show that all KRAB zinc finger gene subfamilies originate from the KRAB(AB) zinc finger genes.In addition, this thesis includes a structural and functional analysis of four novel mouse and human KRAB zinc finger genes; MZF6D, HKr18, HKr19 and HZF12. Whereas HKr18 and HZF12 seem to be ubiquitously expressed, MZF6D and HKr19 show a more restricted expression pattern. Northern blot and in situ hybridisation analyses of MZF6D showed that the expression of this gene is restricted to meiotic germ cells. MZF6D might thus be involved in the formation of male gametes. The expression of HKr19, on the other hand, seems to be restricted to lymphoid cells, indicating a possible role for this KRAB zinc finger gene in the regulation of lineage commitment.
17.	Lorant, Tomas, 1975-, et al. (författare) Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients 2018 Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 18:11, s. 2752-2762 Tidskriftsartikel (refereegranskat)abstract Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19+ memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA-incompatible donor (HLA-B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.
18.	Lu, Ming, et al. (författare) Expression and association of TRPC subtypes with Orai1 and STIM1 in human parathyroid 2010 Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 44:5, s. 285-294 Tidskriftsartikel (refereegranskat)abstract The mechanism behind Ca2+ entry into the parathyroid cells has been widely debated, and the molecular identities of the responsible ion channels have not been established yet. In this study, we show that the parathyroid cells lack voltage-operated Ca2+ channels. Passive store depletion by thapsigargin, on the other hand, induces a large non-voltage-activated non-selective cation current. The increase in intracellular Ca2+ caused by thapsigargin is attenuated by 2-aminoethoxydiphenyl borate, a blocker of store-operated Ca2+ entry (SOCE). Candidate molecules for non-voltage-operated Ca2+ signaling were investigated. These included members of the transient receptor potential canonical (TRPC) ion channel family, as well as Ca2+ release-activated Ca2+ modulator 1 (Orai1) and stromal interaction molecule 1 (STIM1) that are key proteins in the SOCE pathway. Using RT-PCR screening, quantitative real-time PCR, and western blot, we showed expression of TRPC1, TRPC4, and TRPC6; Orai1; and STIM1 genes and proteins in normal and adenomatous human parathyroid tissues. Furthermore, co-immunoprecipitation experiments demonstrated a ternary complex of TRPC1-Orai1-STIM1, supporting a physical interaction between these molecules in human parathyroid.
19.	Lundbäck, Bo, et al. (författare) Not 15 But 50% of smokers develop COPD?—Report from the Obstructive Lung Disease in Northern Sweden Studies 2003 Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 97:2, s. 115-122 Tidskriftsartikel (refereegranskat)abstract Background: The prevalence of chronic obstructive pulmonary disease (COPD) according to guidelines of today seems considerably higher than has been reported also in recent literature.Aim: To estimate the prevalence of COPD as defined by British Thoracic Society (BTS) criteria and the recent global initiative for chronic obstructive lung disease (GOLD) criteria. Further aims were to assess the proportion of underdiagnosis and of symptoms in subjects with COPD, and to study risk factors for COPD.Methods: In 1996, 5892 of the Obstructive Lung Disease in Northern Sweden (OLIN) Study's first cohort could be traced to a third follow-up survey, and 5189 completed responses (88%) were received corresponding to 79% of the original cohort from December 1985. Of the responders, a random sample of 1500 subjects were invited to a structured interview and a lung function test, and 1237 of the invited completed a lung function test with acceptable quality.Results: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, while it was 14% according to the GOLD criteria. The absolutely dominating risk factors were increasing age and smoking, and approximately a half of elderly smokers fulfilled the criteria for COPD according to both the BTS and the GOLD criteria. Family history of obstructive airway disease was also a risk factor, while gender was not. Of those fulfilling the BTS criteria for COPD, 94% were symptomatics, 69% had chronic productive cough, but only 31% had prior to the study been diagnosed as having either chronic bronchitis, emphysema, or COPD. The corresponding figures for COPD according GOLD were 88, 51, and 18%.Conclusions: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.
20.	Nilsson, Kerstin, et al. (författare) 54 forskare: Inte alla klarar höjd pensions-ålder 2017 Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412. Tidskriftsartikel (populärvet., debatt m.m.)abstract Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet, så att fler klarar att arbeta i högre ålder. Att enbart genom ekonomiska åtgärder höja pensionsåldern är inte långsiktigt hållbart, skriver 54 forskare.DEBATT \| PENSIONForskning visar att cirka var fjärde har en diagnos eller skada orsakad av sitt arbete. Detta gör arbetsorsakad sjukdom och skada till ett betydelsefullt folkhälsoproblem. Att då enbart genom ekonomiska åtgärder höja pensionsåldern för samtliga (yrkes)grupper utifrån deras kronologiska ålder är inte långsiktigt hållbart när individers biologiska ålder är så olika bland annat till följd av arbetslivet. Detta är en demokratifråga. Forskning om äldre i arbetslivet och hållbart arbete visar att man då främst flyttar individer från pensionssystemet till sjukförsäkringssystemet och ökar klyftorna i samhället.Debatt Det här är en argumenterande text med syfte att påverka. Åsikterna som uttrycks är skribentens egna.Vi är 54 forskare som nu gemensamt har skrivit denna debattartikel. Anledningen är att vi är oroade över att cirka var fjärde blir sjuk av sitt arbete samtidigt som man i det förslag som ligger om att senarelägga ålderspensionen i princip utgår ifrån att arbetskraftsdeltagande enbart styrs av ekonomin. Vi vill trycka på betydelsen av åtgärder i arbetslivet för att komma tillrätta med ohälsan, det vill säga inte enbart ekonomiska restriktioner som tvingar folk som inte kan, vill och orkar att stanna kvar i arbetslivet till en högre kronologisk ålder.Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att förtjäna möjligheter till pension. Vi bör dock inte enbart utgå ifrån antalet år sedan en person föddes, då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Den svenska sjukförsäkringsreformen 2008 avsåg att få tillbaka människor i arbete. Men studien fann att den faktiskt bidrog till att fler gick i tidig ålderspension av dem som var i åldern 55–64 år. Ökningen var störst bland korttidsutbildade. Mer än 5 procent fler gick i tidig ålderspension då det blev svårare att få sjukpenning och sjukersättning. Vi kan notera att det är vanligare att manliga chefer tar ut tidig ålderspension, jämfört med kvinnliga maskinskötare inom tillverkningsindustrin. I vissa yrken är det dessutom vanligare att människor, trots pension, både orkar och faktiskt ges möjlighet att arbeta vidare om de har en specialkompetens som efterfrågas. Om vi endast kombinerar ekonomiska morötter med piskor finns en stor risk att vi ökar klyftan mellan grupper som både kan och vill fortsätta att yrkesarbeta och personer som av olika skäl inte längre kan eller orkar.Ta nytta av den forskning som vi har tagit fram. Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas och våra attityder som är kopplade till ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.”Morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi.Forskning visar att pedagogik som bygger på ”morötter” oftast är betydligt bättre än ”piskor” för att nå framgångsrika och långsiktiga mål. ”Morötter” i samhället, för organisationer, företag och individer är därför viktiga för god arbetshälsa och fortsatt produktivitet och kan bidra till ett längre arbetsliv även för grupper som tidigare inte ens klarat av att arbeta fram till pensionsåldern. Genom forskning inom området har bland annat swage-modellen utarbetats. Detta är ett verktyg som visar på komplexiteten i ett hållbart arbetsliv och tillsammans med systematiskt arbetsmiljöarbete, handlingsplaner och åtgärder syftar till ett mer hållbart arbetsliv. Morötter är enligt forskningen i detta sammanhang åtgärder för en god fysisk och mental arbetsmiljö, avpassad arbetsbelastning, stödjande teknik, att man kan anpassa arbetstakten, alternativa arbetstidsmodeller vid behov. Det är viktigt att man känner sig trygg och förväntas och tillåts vara delaktig, att man blir sedd av chefen och arbetskamraterna. Att de egna arbetsuppgifterna upplevs som meningsfulla och behövda av andra skapar självförverkligande och tillfredsställelse i arbetet. Att man känner att ens arbetsuppgifter och man själv är viktig för organisationen och företaget. Att man trots högre ålder inkluderas i olika nysatsningar och får tillgång till kompetensutveckling och inte blir åsidosatt eller åldersdiskriminerad. Utvärderingar visar att de äldre medarbetarna som fick några av dessa anpassningar och möjligheter var mer effektiva, utvilade, stimulerade när de var på arbetet samtidigt som sjukfrånvaron minskade. Vilket i sin tur bidrar till ett längre arbetsliv för grupper som tidigare inte klarat av att arbeta fram till pensionsåldern. I organisationer som bygger på en deltagar- och lärandekultur rustas de anställda för att klara omställningar, nya arbetsuppgifter och vid behov även yrkesbyten.Med en åldrande befolkning där allt fler lever allt längre behöver vi arbeta till en högre ålder i framtiden för att pensionssystemet ska hålla. Men ”morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi. Det kräver också att vi ändrar våra attityder och förhållningssätt till äldre på arbetsmarknaden, vilket vi bäst gör genom att organisationer och företag får incitament till och erbjuder mer individanpassade arbetsvillkor, särskilt för personer i högre ålder. Låt oss därför använda den framtagna kunskapen i praktiken för att göra arbetslivet friskt och hållbart för alla åldrar.
21.	Nilsson, Kerstin, et al. (författare) Vi är oroade över senare ålderspension 2017 Ingår i: Dagens Samhälle. - 1652-6511. Tidskriftsartikel (populärvet., debatt m.m.)abstract Var fjärde person blir i dag sjuk till följd av sitt arbete. Att höja pensionsåldern för alla yrkesgrupper, utan konkreta åtgärder för att minska ohälsan, är därför problematiskt och mycket oroande. Det är, enligt forskarna, inte långsiktigt samhällsekonomiskt lönsamt att utan andra åtgärder höja pensionsåldern för alla. Vi – 54 forskare – är mycket oroade över konsekvenserna av att, som föreslagits, senarelägga ålderspensionen.Förslaget utgår i princip från arbetskraftsdeltagande i princip enbart styrs av ekonomin, medan forskningen visar att det bara är en av flera faktorer som styr hur länge och hur mycket människor väljer att arbeta.Det här sättet att lösa problemet med en åldrande befolkning och ett sviktande pensionssystem är inte samhällsekonomiskt lönsamt på lång sikt, utan riskerar bara att flytta runt folk mellan olika ersättningssystem. Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att tjäna in vår pension. Vi bör dock inte enbart utgå ifrån ålder eller antalet år sedan en person föddes då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De med kortare utbildningstid har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har också oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Ta nytta av den forskning som vi har tagit fram. Ekonomin är självklart viktigt för att vi ska vilja arbeta, men den är som sagt enbart en av flera faktorer med betydelse vårt arbetsliv.Hälsotillståndet, både det fysiska och det mentala, har en avgörande betydelse för hur länge och hur mycket vi orkar arbeta. Ett fysiskt och mentalt belastande arbete är en stark riskfaktor för en nedsatt hälsa i slutet av arbetslivet. Arbetstid, arbetstakt och möjlighet till återhämtning spelar en allt större roll ju äldre vi blir. Andra aspekter är arbetsinnehåll, hur meningsfulla och stimulerande arbetsuppgifterna är, balansen mellan arbete och familjesituation och fritidsaktiviteter. Organisationskultur, ledarskapet, stöd i arbetet och kompetens har stor betydelse för om vi ska kunna och vilja arbeta till en högre ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.Ett hållbart och acceptabelt pensionssystem måste därför utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas samt de attityder som är kopplade till ålder.
22.	Rollborn, Niclas, et al. (författare) Good Agreement Between Hba1c Analyzed Using Capillary Electrophoresis, HPLC, Immunological and Enzymatic Methods 2019 Ingår i: Journal of Diabetes, Metabolism and its Complications. ; 1:1, s. 1-7 Tidskriftsartikel (refereegranskat)abstract Purpose: Hemoglobin A1c (HbA1c) is an essential marker for assessment of glycemic control in diabetes patients. The aim of this study was to evaluate the agreement between different HbA1c methods.Methodology: We used blood samples to compare HbA1c results analyzed with Capillarys 3 Tera, Roche Tina-Quant HbA1c Gen 3, BioRad Variant II Turbo (3 sites), Mono S® and Abbott Architect enzymatic method. The comparisons were made as paired instrument comparisons with Capillarys 3 Tera.Results: The linear correlations between the HbA1c methods were as follows:Cobas 6000 = 0.982 x Capillarys 3 Tera + 0.975, R² = 0.994;Architect c8000 = 0.982 x Capillarys 3 Tera + 1.064, R² = 0.994; Mono S® = 0.916 x Capillarys 3 Tera + 3.397, R² = 0.965;BioRad Variant II Turbo = 0.923 x Capillarys 3 Tera + 4.062, R² = 0.990; Tosoh G8 = 0.963 x Capillarys 3 Tera + 3.895, R² = 0.996.Conclusions: The different instrument platforms showed the best agreement in the 50-70 mmol/mol interval. Above and below this range the methods separated into 2 groups, one consisting of Capillarys 3 Tera, Roche Tina-Quant and Abbott enzymatic method and the other group consisting of BioRad Variant II Turbo, Tosoh G8 and Mono S®.
23.	Sundström, Johan, Professor, 1971-, et al. (författare) Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults 2019 Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
24.	Thomas, Richard D., et al. (författare) DESIREE : Physics with cold stored ion beams 2015 Ingår i: DR2013. - : EDP Sciences. ; 84, s. 01004-01004 Konferensbidrag (refereegranskat)abstract Here we will briefly describe the commissioning of the Double ElectroStatic Ion Ring ExpEriment (DESIREE) facility at Stockholm University, Sweden. This device uses purely electrostatic focussing and deflection elements and allows ion beams of opposite charge to be confined under extreme high vacuum and cryogenic conditions in separate rings and then merged over a common straight section. This apparatus allows for studies of interactions between cations and anions at very low and well-defined centre-of-mass energies (down to a few meV) and at very low internal temperatures (down to a few K).
25.	Thomas, Richard D., et al. (författare) The double electrostatic ion ring experiment : A unique cryogenic electrostatic storage ring for merged ion-beams studies 2011 Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 82:6, s. 065112- Tidskriftsartikel (refereegranskat)abstract We describe the design of a novel type of storage device currently under construction at Stockholm University, Sweden, using purely electrostatic focussing and deflection elements, in which ion beams of opposite charges are confined under extreme high vacuum cryogenic conditions in separate rings and merged over a common straight section. The construction of this double electrostatic ion ring experiment uniquely allows for studies of interactions between cations and anions at low and well-defined internal temperatures and centre-of-mass collision energies down to about 10 K and 10 meV, respectively. Position sensitive multi-hit detector systems have been extensively tested and proven to work in cryogenic environments and these will be used to measure correlations between reaction products in, for example, electron-transfer processes. The technical advantages of using purely electrostatic ion storage devices over magnetic ones are many, but the most relevant are: electrostatic elements which are more compact and easier to construct; remanent fields, hysteresis, and eddy-currents, which are of concern in magnetic devices, are no longer relevant; and electrical fields required to control the orbit of the ions are not only much easier to create and control than the corresponding magnetic fields, they also set no upper mass limit on the ions that can be stored. These technical differences are a boon to new areas of fundamental experimental research, not only in atomic and molecular physics but also in the boundaries of these fields with chemistry and biology. For examples, studies of interactions with internally cold molecular ions will be particular useful for applications in astrophysics, while studies of solvated ionic clusters will be of relevance to aeronomy and biology.
26.	Abe, O, et al. (författare) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials 2005 Ingår i: Lancet (London, England). - 1474-547X. ; 366:9503, s. 2087-2106 Tidskriftsartikel (refereegranskat)
27.	Agarwal, Prasoon, et al. (författare) MYCN Amplification Is Associated with Reduced Expression of Genes Encoding gamma-Secretase Complex and NOTCH Signaling Components in Neuroblastoma 2023 Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:9 Tidskriftsartikel (refereegranskat)abstract Amplification of the MYCN oncogene is found in similar to 20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN's contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the gamma-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding gamma-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of gamma-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of gamma-secretase genes and NOTCH-target genes. Chemical inhibition of gamma-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the gamma-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.
28.	Agarwal, Prasoon, et al. (författare) MYCN Amplification Is Associated with Reduced Expression of Genes Encoding γ-Secretase Complex and NOTCH Signaling Components in Neuroblastoma 2023 Ingår i: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:9 Tidskriftsartikel (refereegranskat)abstract Amplification of the MYCN oncogene is found in ~20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN’s contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the γ-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding γ-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of γ-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of γ-secretase genes and NOTCH-target genes. Chemical inhibition of γ-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the γ-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.
29.	Arabi, Azadeh, et al. (författare) c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. 2005 Ingår i: Nat Cell Biol. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 7:3, s. 303-10 Tidskriftsartikel (refereegranskat)
30.	Aripaka, Karthik, 1986- (författare) Studies on the biological functions of interaction between components in Wnt, TGF-β and HIF pathways for cancer progression 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Cancer is a disease that involves aggressive changes in the genome and aberrant signals between the living cells. Signalling pathways such as TGF-β (Transforming growth factor-β), Wnt, EGF (epidermal growth factor) and HIF (Hypoxia-inducible factor) evolved to regulate growth and development in mammals. These factors are also implicated for tumorigenesis due to failure or aberrant expression of components in these pathways. Cancer progression is a multistep process, and these steps reflect genetic alterations driving the progressive transformation of healthy human cells into highly malignant derivatives. Many types of cancers are diagnosed in the human population, such as head & neck, cervical, brain, liver, colon, prostate, uterine, breast, and renal cell cancer.Prostate cancer is the second most common cancer and one of the foremost leading cancer-related deaths in men in the world. Aberrant Wnt3a signals promote cancer progression through the accumulation of β-Catenin. In the first paper, we have elucidated intriguing functions for Tumour necrosis factor receptor-associated factor 6 (TRAF6) as a coregulatory factor for the expression of Wnt-target genes which was confirmed in vivo by using CRISPR/Cas9 genomic editing, in zebrafish. Our data suggest that Wnt3a promotes TRAF6 interaction with Wnt components, and TRAF6 is required for gene expression of β-Catenin as well as for the Wnt-ligand co-receptor LRP5. From the in vivo studies, we elucidated positive regulation of TRAF6, which is crucial for survival and development of zebrafish. This study identifies TRAF6 as an evolutionary conserved co-regulatory protein in the Wnt pathway that also promotes the progression of prostate and colorectal cancer due to its positive effects on Wnt3a signalling.Hypoxia is a condition due to O2 deprivation, and Hypoxia-inducible factors (HIF) transcription factors are responsible for the maintenance of oxygen homeostasis in living cells. Irregularities in these HIF transcription factors trigger pathological cellular responses for initiation and progression of malignant cancers. Renal cell carcinoma, malignant cancer arising in renal parenchyma and renal pelvis and, hypoxia plays a vital role in its progression. In the second paper, we have investigated the clinicopathological relevance of several hypoxic and TGF-β component proteins such as HIF-1α/2α/3α, TGF-β type 1 receptor (ALK5-FL) and the intracellular domain of ALK5 (ALK5-ICD), SNAI1 and PAI-1 with patient survival in clear cell renal cell carcinoma (ccRCC). We showed that HIF-2α associated with low cancer-specific survival. HIF-2α and SNAI1 positively correlated with ALK5-ICD, pSMAD2/3, PAI-1 and SNAI1 with HIF-2α; HIF-1α positively correlated with pSMAD2/3. Further, under normoxic conditions, our data suggest that ALK5 interacts with HIF-1α and HIF-2α, and promotes their expression and target genes such as GLUT1 and CA9, in a VHL dependent manner through its kinase activity. These findings shed light on the critical aspect of cross-talk between TGF-β signalling and hypoxia pathway, and also the novel finding of an interaction between ALK5 and HIF-α might provide a more in-depth understanding of mechanisms behind tumour progressionIn the third paper, an ongoing study, we investigated the role of HIF-3α in the progression of Renal cell carcinoma and its association with the components of TGF-β and HIF pathways. We have observed increased levels of HIF-3α in ccRCC and pRCC (papillary renal cell carcinoma) which are associated with advanced tumour stage, metastasis and larger tumours. Also, we found HIF-3α show a significant positive association with pro-invasive gene SNAI1, which is a crucial regulator of epithelial to mesenchymal transition. TRAF6 an E3 ligase known to be a prognostic marker in RCC and we observed HIF-3α associates with TRAF6.
31.	Arnemo, Ulf, et al. (författare) Rapid innovators in emerging economies : Challenges and opportunities for Swedish firms 2016 Rapport (övrigt vetenskapligt/konstnärligt)
32.	Arroyo, Carlos, 1977, et al. (författare) Large-scale low-speed facility for investigating intermediate turbine duct flows 2006 Ingår i: Paper AIAA-2006-1312, 44th AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, 9-12 January, 2006. Konferensbidrag (refereegranskat)
33.	Bahram, Fuad, et al. (författare) Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation. 2016 Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:3, s. 2837-2854 Tidskriftsartikel (refereegranskat)abstract The Myc oncoprotein is tightly regulated at multiple levels including ubiquitin-mediated protein turnover. We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-γ-induced expression of p27Kip1 (p27) repressed Myc's activity to suppress cellular senescence and differentiation. In this study we identified an additional activity of p27 to interfere with Myc independent of Ser-62 phosphorylation. p27 is required and sufficient for IFN-γ-induced turnover of Myc. p27 interacted with Myc in the nucleus involving the C-termini of the two proteins, including Myc box 4 of Myc. The C-terminus but not the Cdk2 binding fragment of p27 was sufficient for inducing Myc degradation. Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157 - a marker for active p27 localized in the nucleus. Further, these conditions correlated with favorable tumor stage and patient outcome. This novel regulation of Myc by IFN-γ/p27KIP1 potentially offers new possibilities for therapeutic intervention in tumors with deregulated Myc.
34.	Bahram, Fuad, et al. (författare) Posttranslational regulation of Myc function in response to phorbol ester/interferon-gamma-induced differentiation of v-Myc-transformed U-937 monoblasts 1999 Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 93:11, s. 3900-3912 Tidskriftsartikel (refereegranskat)abstract The transcription factors of the Myc/Max/Mad network are important regulators of cell growth, differentiation, and apoptosis and are frequently involved in tumor development. Constitutive expression of v-Myc blocks phorbol ester (TPA)-induced differentiation of human U-937 monoblasts. However, costimulation with interferon-gamma (IFN-gamma) and TPA restores terminal differentiation and G1 cell-cycle arrest despite continuous expression of v-Myc. The mechanism by which TPA + IFN-gamma counteract v-Myc activity has not been unravelled. Our results show that TPA + IFN-gamma treatment led to an inhibition of v-Myc- and c-Myc-dependent transcription, and a specific reduction of v-Myc:Max complexes and associated DNA-binding activity, whereas the steady state level of the v-Myc protein was only marginally affected. In contrast, TPA + IFN-gamma costimulation neither increased the expression of Mad1 or other mad/mnt family genes nor altered heterodimerization or DNA-binding activity of Mad1. The reduced amount of v-Myc:Max heterodimers in response to treatment was accompanied by partial dephosphorylation of v-Myc and c-Myc. Phosphatase treatment of Myc:Max complexes lead to their dissociation, thus mimicking the effect of TPA + IFN-gamma. In addition to modulation of the expression of Myc/Max/Mad network proteins, posttranslational negative regulation of Myc by external signals may, therefore, be an alternative biologically important level of control with potential therapeutic relevance for hematopoietic and other tumors with deregulated Myc expression.
35.	Bergström, Göran, 1964, et al. (författare) Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS. 2023 Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54 Tidskriftsartikel (refereegranskat)abstract Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
36.	Biglarnia, Ali-Reza, et al. (författare) Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation : Exemplification of the Surgical Technique and the Surveillance 2014 Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 260:2, s. e5-7 Tidskriftsartikel (refereegranskat)
37.	Björk, Jonas, et al. (författare) Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden 2015 Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 53:3, s. 403-414 Tidskriftsartikel (refereegranskat)abstract Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmo creatinine and CAPA cystatin C equations (MEAN(LM-REV+CAPA)), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEAN(CKD-EPI)), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine. Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m(2)). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates +/- 30% of mGFR; P-30) were compared. Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEAN(LM-REV+CAPA)/MEAN(CKD-EPI)/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m(2), and P-30 91.3%/91.0%/91.1%. The P-30 figures were about 7-14 -percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P-30 >= 90% and never <80%. Combined equations reached P-30 of 95% when the difference between eGFR(CREA) and eGFR(CYSC) was <10% but decreased to 82% at a difference of >= 40%. Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P-30 >= 90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.
38.	Borgenvik, Anna, et al. (författare) CDK2 as a therapeutic target in MYC-driven medulloblastoma Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Group 3 medulloblastoma (MB) is a malignant pediatric brain tumor that shows aberrant cell cycle activation, therapy resistance, and poor prognosis. Here, we identified that MYC expression and poor prognosis in Group 3 MB correlates with elevated levels of core cell cycle members CDK2 and cyclin A2, suggesting they would be promising targets for direct inhibition. Tumor cells in a novel transgenic MYC-driven MB mouse model further displayed increased p27 levels, decreased viability, and cell growth in vitro upon conditional CDK2 depletion using tamoxifen-induced recombination. Human Group 3 MB cells transduced with dominant-negative CDK2 mutants similarly exhibited decreased viability and increased p27 activation. As compared to controls, CDK2-depleted cells responded less to CDK2-specific inhibitors but were not more sensitive to BET inhibition or CDK4/6 inhibition as previously proposed. We finally used global transcriptional profiling and found that mTOR and B-Myb/ZMYM2 signaling pathways are compensating for CDK2 loss in Group 3MB cells. Our analysis suggests that specific inhibitors of these pathways could in combination with approved cell cycle inhibitors provide more efficient treatments for this severe childhood brain cancer.
39.	Borgenvik, Anna, 1987- (författare) MYC-driven Medulloblastoma : New Targeted Therapies and Mechanisms of Recurrence 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Medulloblastoma is the most common malignant brain tumor of childhood. It arises in the posterior fossa but presents with distinct histological and molecular features. Hence, medulloblastoma is divided into four molecular subgroups, WNT, SHH, Group 3, and Group 4. The overall 5-year survival is ~70% across subgroups but varies with high- and low-risk disease. Standard treatment of medulloblastoma consists of maximal safe tumor resection, radiotherapy, and adjuvant chemotherapy. Despite the rather high success rate of treatment for many patients it also comes with severe long-term debilitating side effects. MYC proteins are master regulators of gene expression often deregulated in cancer. MYC family members MYC and MYCN share similar roles and are found overexpressed or amplified in most medulloblastoma subgroups and correlate with a poor prognosis. Medulloblastoma dissemination and recurrence patterns differ between subgroups but are always associated with a poor prognosis. Recurrent medulloblastoma is not yet curable and will lead to death. In this thesis, we present the first transgenic mouse model of medulloblastoma recurrence and highlight the role of the transcription factor SOX9 in MYC-driven relapse mechanisms. By studying this recurrence model and matched primary-recurrent patient samples we propose a mechanism in which treatment-refractory and quiescent SOX9-positive cells in Group 3 medulloblastoma are necessary for tumor relapse, and how the recurrent tumors can be specifically treated with MGMT inhibitors and doxorubicin.In addition, we address efficient treatment options of primary MYC-driven medulloblastoma where BET bromodomain inhibition (JQ1) in combination with CDK2 inhibition (milciclib) of human Group 3 medulloblastoma will lead to apoptosis and prolonged survival of xenografted mice. This is explained by a dual hit on MYC transcriptional output and MYC protein stability exerted by JQ1 and milciclib respectively. Finally, in a different novel transgenic model of MYC-driven medulloblastoma, we show how temporal Cdk2 knock-out has no effect on MYC protein stability but slows down proliferation and prolongs survival of allografted mice. The need for better treatments and increased understanding of recurrent medulloblastoma is huge. To that end, this thesis focuses on and addresses novel treatments, the role of the cell cycle protein CDK2 as well as relapse mechanisms depending on dormant SOX9-positive cells in highly aggressive MYC-driven medulloblastoma.
40.	Brogren, Maria, et al. (författare) Optical coatings for temperature control of spacecraft 1998 Ingår i: Optik i Sverige, Stockholm, Sweden. Konferensbidrag (refereegranskat)
41.	Calmfors, Lars, et al. (författare) Dåliga jobbvillkor gör att Sverige tappar elitforskare 2014 Ingår i: Dagens nyheter. - : Bonnier. - 1101-2447. Tidskriftsartikel (populärvet., debatt m.m.)
42.	Campaner, S, et al. (författare) Cdk2 suppresses cellular senescence induced by the c-myc oncogene 2010 Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1476-4679 .- 1465-7392. ; 12:1, s. 54-U132 Tidskriftsartikel (refereegranskat)
43.	Castell, Alina, et al. (författare) MYCMI-7 : A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner 2022 Ingår i: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 2:3, s. 182-201 Tidskriftsartikel (refereegranskat)abstract Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered "undruggable," and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these molecules, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC, and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN-dependent manner and downregulates the MYC pathway on a global level as determined by RNA sequencing. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy toward a collection of patient-derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells be- come G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer, and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregu- lates MYC/MYCN, inhibits tumor growth, and prolongs survival through apoptosis with few side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for the treatment of MYC-driven cancer.Significance: Our findings demonstrate that the small-molecule MYCMI-7 binds MYC and inhibits interaction between MYC and MAX, thereby ham- pering MYC-driven tumor cell growth in culture and in vivo while sparing normal cells.
44.	Cetinkaya, Cihan, et al. (författare) Combined IFN-gamma and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells 2007 Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 6:10, s. 2634-2641 Tidskriftsartikel (refereegranskat)abstract The MYCN protooncogene is involved in the control of cell proliferation, differentiation, and survival of neuroblasts. Deregulation of MYCN by gene amplification contributes to neuroblastoma development and is strongly correlated to advanced disease and poor outcome, emphasizing the urge for new therapeutic strategies targeting MYCN function. The transcription factor N-Myc, encoded by MYCN, regulates numerous genes together with its partner Max, which also functions as a cofactor for the Mad/Mnt family of Myc antagonists/transcriptional repressors. We and others have previously reported that IFN-gamma synergistically potentiates retinoic acid (RA)induced sympathetic differentiation and growth inhibition in neuroblastoma cells. This study shows that combined treatment of MYCN-amplified neuroblastorna cells with RA+IFN-gamma down-regulates N-Myc protein expression through increased protein turnover, up-regulates Mad1 mRNA and protein, and reduces N-Myc/Max heteroclimerization. This results in a shift of occupancy at the ornithine decarboxylase N-Myc/Mad1 target promoter in vivo from N-Myc/Max to Madl/Max predominance, correlating with histone H4 deacetylation, indicative of a chromatin structure typical of a transcriptionally repressed state. This is further supported by data showing that RA + IFN-gamma treatment strongly represses expression of N-Myc/Mad1 target genes ornithine decarboxylase and hTERT. Our results suggest that combined IFN-gamma and RA signaling can form a basis for new therapeutic strategies targeting N-Myc function for patients with high-risk, MYCN-amplified neuroblastoma.
45.	Dahl, Östen, et al. (författare) Report on Esto-nian research within the language scien-ces 1994 Rapport (övrigt vetenskapligt/konstnärligt)
46.	Dimberg, Anna, et al. (författare) Retinoic acid-induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E and post-transcriptional upregulation of p27Kip1 2002 Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 99:6, s. 2199-2206 Tidskriftsartikel (refereegranskat)abstract All-trans retinoic acid (ATRA) is a potential therapeutic agent for the treatment of hematopoietic malignancies, because of its function as an inducer of terminal differentiation of leukemic blasts. Although the efficacy of ATRA as an anticancer drug has been demonstrated by the successful treatment of acute promyelocytic leukemia (APL), the molecular mechanisms of ATRA-induced cell cycle arrest of myeloid cells have not been fully investigated. In this study, we show that the onset of ATRA-induced G0/G1 arrest of human monoblastic U-937 cells is linked to a sharp down-regulation of c-Myc and cyclin E levels and an increase in p21WAF1/CIP1 expression. This is followed by an increase in p27Kip1 protein expression due to enhanced protein stability. The importance of an early decrease in Myc expression for these events was demonstrated by the failure of a U-937 subline with constitutive exogenous expression of v-Myc to cell cycle arrest and regulate cyclin E and p27Kip1 in response to ATRA. Preceding the initiation of G1 arrest, a transient rise in retinoblastoma protein (pRb), p107, and cyclin A levels was detected. Later, a rapid fall in the levels of cyclins A and B and a coordinate dephosphorylation of pRb at Ser780, Ser795, and Ser807/811 coincided with the accumulation of cells in G1. These results thus identify a decrease in c-Myc and cyclin E levels and a posttranscriptional up-regulation of p27Kip1 as important early changes, and position them in the complex chain of events regulating ATRA-induced cell cycle arrest of myeloid cells.
47.	Eich, Torsten, 1972-, et al. (författare) Rapid desensitisation of anti-HLA antibodies using the IgG degrading enzyme IdeS in sensitized patients with chronic kidney disease 2016 Ingår i: Tissue Antigens. - 0001-2815 .- 1399-0039. ; 87:4, s. 226-227 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
48.	Ejhed, Helene, et al. (författare) Miljömålsuppföljning Ingen övergödning 1995 och 2005 : Slutrapport 2007 Rapport (övrigt vetenskapligt/konstnärligt)abstract En uppföljning av två delmål för miljökvalitetsmålet Ingen övergödning mellan år 1995 och 2005 har genomförts av SMED på uppdrag av Naturvårdsverket. Det gäller specifikt delmålen om tillförseln av kväve och fosfor till havet respektive till vatten. Underlag och indata till beräkningarna har tagits fram inom det parallella PLC5- projektet som genomförs för rapportering till HELCOM och från TRK-projektet (Brandt och Ejhed 2002). Metodik för beräkningarna har utvecklats mycket sedan TRK-projektet och beskrivs utförligt i rapporten. En av de största förändringarna i metodik har genomförts för fosfor belastningsberäkningar från jordbruksmark där nya mer fysikaliska modeller använts. Ytterligare en stor förändring har varit användning av Tekniskt Beräkningssystem Vatten (TBV) som ska medföra en mer kvalitetssäkrad hantering av beräkningarnaResultaten i denna rapport presenteras och bedöms med avseende på kvalitet och jämförs med transporterade mängder i flodmynningarna, TRK-resultat och resultat i HBV-NP.Resultaten visar att den antropogena belastningen av kväve minskat med cirka 25 % från år 1995 till år 2005 för de svenska vattenburna utsläppen till haven söder om Ålands hav. Delmålet för kväve anger en minskning med 30 % till år 2010.Resultaten visar vidare att den antropogena bruttobelastningen av fosfor minskat med cirka 14 % från år 1995 till år 2005 för de svenska vattenburna utsläppen till sjöar, vattendrag och kustvatten. Delmålet för fosfor anger en minskning med minst 20 procent till år 2010
49.	Eloranta, Maija-Leena, et al. (författare) Type I interferon system activation and association with disease manifestations in systemic sclerosis 2010 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:7, s. 1396-1402 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFNalpha) and chemokines of importance in the disease process. METHODS: Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFNalpha produced and serum levels of IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc. RESULTS: Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjögren syndrome antigen autoantibodies. The pDCs were responsible for the IFNalpha production which required interaction with FcgammaRII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFNalpha (p=0.029). CONCLUSION: An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.
50.	Engström, Gunnar, et al. (författare) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Tidskriftsartikel (refereegranskat)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

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