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Sökning: WFRF:(Lennartsson Johan)

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1.
  • Dahlberg, Lena, 1970-, et al. (författare)
  • Ensamhet bland äldre personer i Norden
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Rapporten presenterar översikter av tidigare forskning och analyser av känslan av ensamhet bland äldre personer. Överlag finns det kunskap om ensamhetens konsekvenser för ohälsa, men det behövs ytterligare forskning där starkare slutsatser kan dras om sambandens riktning, och ett tydligare fokus på ensamhet i gruppen äldre personer. En systematisk översikt visar att det finns god kunskap om en del faktorer som ökar risken för ensamhet, men mer forskning behövs om andra potentiella riskfaktorer. Analyserna visar en relativt låg och stabil förekomst av ensamhet bland äldre personer i Norden, samt att ohälsa och olika indikatorer för social exkludering (t.ex. bristande sociala relationer, otillräcklig inkomst, samt otrygghet i närområdet) har samband med ensamhet. Slutligen konstateras att forskningen om nordiska interventioner för att minska ensamhet bland äldre personer är begränsad.
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2.
  • Heldin, Johan, et al. (författare)
  • Dynamin inhibitors impair platelet-derived growth factor beta-receptor dimerization and signaling
  • 2019
  • Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 380:1, s. 69-79
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of plasma membrane composition and dynamics in the activation process of receptor tyrosine kinases (RTKs) is still poorly understood. In this study we have investigated how signaling via the RTK, platelet-derived growth factor beta-receptor (PDGFR-beta) is affected by Dynasore or Dyngo-4a, which are commonly used dynamin inhibitors. PDGFR-beta preferentially internalizes via clathrin-coated pits and in this pathway, Dynamin II has a major role in the formation and release of vesicles from the plasma membrane by performing the membrane scission. We have found that dynamin inhibitors impedes the activation of PDGFR-beta by impairing ligand-induced dimerization of the receptor monomers, which leads to a subsequent lack of phosphorylation and activation both of receptors and downstream effectors, such as ERK1/2 and AKT. In contrast, dynamin inhibitors did not affect epidermal growth factor receptor (EGFR) dimerization and phosphorylation. Our findings suggest that there is a link between plasma membrane dynamics and PDGFR-beta activation, and that this link is not shared with the epidermal growth factor receptor.
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4.
  • Skogar, Örjan, et al. (författare)
  • Parkinson’s disease patients’ subjective descriptions of characteristics of chronic pain, sleeping patterns and health-related quality of life
  • 2012
  • Ingår i: Neuropsychiatric Disease and Treatment. - 1176-6328 .- 1178-2021. ; 8, s. 435-442
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Nonmotor symptoms are common in Parkinson’s disease (PD). Health-related quality of life (HRQoL) is negatively affected by different factors, of which pain and sleep disturbances are important contributors. This study was performed to evaluate and describe subjective experiences of pain, sleeping patterns, and HRQoL in a cohort of PD patients with chronic pain.Methods: A total of 45 participants with established PD for more than 2 years, and PD-related pain for the preceding three months, were recruited from three sites in Sweden. Data regarding time point for onset, duration and degree of pain parameters, body localization of pain, external influences, and treatments were obtained. HRQoL was evaluated with the Short Form-36® Health Survey, and sleeping patterns were registered with the Parkinson’s disease Sleep Scale, both completed along with a questionnaire.Results: In one-third of participants, pain preceded the PD diagnosis. Median pain score measured with a visual analog scale was 6.6 and 5.9 (for females and males, respectively) the week before the study. In almost half of the participants, pain was present during all their waking hours. Significantly more females described their pain as troublesome, while more males described their pain as irritating. Feelings of numbness and creeping sensations at night were strongly associated with the maximal visual analog scale scores. Polypharmacy was common; 89% used medication for anxiety/insomnia, and 18% used antidepressants. Only one-third of patients who reported pain relief with analgesics had these prescribed on their drug lists. Sleep was characterized by frequent awakenings. Urinary urgency and restless legs were frequently reported as troublesome. Patients rated HRQoL as significantly worse in all items compared with a healthy reference population matched for age and sex.Conclusions: Experiences of chronic PD-related pain are complex; there is substantial sleep fragmentation and negative impact on HRQoL.
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5.
  • Stenseke, Marie, et al. (författare)
  • Kris i naturen – vår existens har blivit sårbar
  • 2019
  • Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
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6.
  • Törnhage, Carl-Johan, et al. (författare)
  • Short- and long-term effects of tactile massage on salivary cortisol concentrations in Parkinsons disease : a randomised controlled pilot study
  • 2013
  • Ingår i: BMC Complementary and Alternative Medicine. - : BioMed Central (BMC). - 1472-6882. ; 13:357
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Parkinson's disease (PD) is a chronic neurodegenerative disorder with limited knowledge about the normal function and effects of non-pharmacological therapies on the hypothalamic-pituitary-adrenal (HPA) axis. The aim of the study was to analyse the basal diurnal and total secretion of salivary cortisol in short- and long-term aspects of tactile massage (TM).METHODS:Design: Prospective, Controlled and Randomised Multicentre Trial.Setting and interventions: Forty-five women and men, aged 50-79 years, were recruited. Twenty-nine of them were blindly randomised to tactile massage (TM) and 16 of them to the control group, rest to music (RTM). Ten interventions were given during 8 weeks followed by a 26 weeks of follow up. Salivary cortisol was collected at 8 am, 1 pm, 8 pm, and 8 am the next day, on five occasions. With the first and eighth interventions, it was collected immediately before and after intervention.Main outcome measures: The primary aim was to assess and compare cortisol concentrations before and immediately after intervention and also during the follow-up period. The secondary aim was to assess the impact of age, gender, body mass index (BMI), duration and severity of PD, effects of interventional time-point of the day, and levodopa doses on cortisol concentration.RESULTS:The median cortisol concentrations for all participants were 16.0, 5.8, 2.8, and 14.0 nmol/L at baseline, later reproduced four times without significant differences. Cortisol concentrations decreased significantly after TM intervention but no change in diurnal salivary cortisol pattern was found. The findings of reduced salivary cortisol concentrations immediately after the interventions are in agreement with previous studies. However, there was no significant difference between the TM and control groups. There were no significant correlations between cortisol concentrations and age, gender, BMI, time-point for intervention, time interval between anti-parkinson pharmacy intake and sampling, levodopa doses, duration, or severity of PD.CONCLUSIONS:Diurnal salivary cortisol rhythm was normal. Salivary cortisol concentrations were significantly reduced after the TM intervention and after RTM, but there were no significant differences between the groups and no sustained long-term effect. No associations were seen between salivary cortisol concentration and clinical and/or pharmacological characteristics.
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7.
  • Wåhlén, Erik, et al. (författare)
  • Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
  • 2023
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 665, s. 195-201
  • Tidskriftsartikel (refereegranskat)abstract
    • The interplay between membrane subregions and receptor tyrosine kinases (RTK) will influence signaling in both normal and pathological RTK conditions. In this study, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFR-β) internalizations were investigated by immunofluorescent microscopy following simultaneous treatment with EGF and PDGF-BB. We found that the two receptors utilize separate routes of internalization, which merges in a common perinuclear endosomal compartment after 45 min of stimulation. This is further strengthened when contrasting the recruitment of either EGFR or PDGFR-β to either clathrin or caveolin-1: PDGFR-β dissociates from caveolin-1 upon stimulation, and engages clathrin, whilst an increased recruitment of EGFR, to both clathrin and caveolin-1, was observed upon EGF stimulation. The association between EGFR and caveolin-1 is supported by the observation that EGFR was localized in lipid raft associated fractions, whereas PDGFR-β was not. We also found that disruption of lipid rafts using MβCD led to an increased EGFR dimerization and phosphorylation in response to ligand, as well as a dramatic decrease in AKT- and a smaller but robust decrease in ERK1/2 phosphorylation. This suggest that lipid rafts may be important to effectively connect the EGFR with downstream proteins to facilitate signaling. Our data implies that cholesterol depletion of the plasma membrane affect the signaling of EGFR and PDGFRβ differently.
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8.
  • Wåhlén, Erik, et al. (författare)
  • Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
  • 2022
  • Ingår i: Cellular Signalling. - : Elsevier. - 0898-6568 .- 1873-3913. ; 96
  • Tidskriftsartikel (refereegranskat)abstract
    • It has become clear that lipid rafts functions as signaling hotspots connecting cell surface receptors to intracellular signaling pathways. However, the exact involvement of lipid rafts in receptor tyrosine kinase signaling is still poorly understood. In this study, we have analyzed platelet-derived growth factor (PDGF) receptor β (PDGFR-β) signaling in two different cell lines depleted of cholesterol, and as a consequence, disruption of lipid rafts. Cholesterol depletion of BJ-hTERT fibroblasts using methyl-β-cyclodextrin (MβCD) did not affect PDGFR-β activation as measured by its tyrosine phosphorylation. However, we did observe a small reduction in AKT phosphorylation and a more robust decrease of ERK1/2 activation. In contrast, in the osteosarcoma cell line U2OS, we noticed a deficient receptor activation. Interestingly, in U2OS cells, the ERK1/2 pathway was unaffected, but instead AKT and SRC signaling was reduced. These results suggest that cell type specific wiring of signaling pathways can lead to differential sensitivity to cholesterol depletion. Furthermore, MβCD treatment had a much more pronounced morphological effect on U2OS compared to BJ-hTERT cells. This is consistent with a previous report claiming that cancer cells are more sensitive to cholesterol depletion than normal cells. Our data supports the possibility that cholesterol lowering drugs may impede tumor growth.
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9.
  • Wåhlén, Erik, et al. (författare)
  • Silencing of Rho GTPases Cdc42, Rac1 or RhoA reduces PDGFRα and -β phosphorylation and downstream signaling of STAT1 and STAT3
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Platelet-derived growth factor receptors (PDGFR) have been implicated in both pathological and physiological signaling and play a major role in the homeostasis of the tumor microenvironment. It has previously been shown that Cdc42, which belongs to the family of Rho GTPases, impairs the degradation of EGFR and VEGFR2. In the current work, we have investigated how Cdc42 as well as Rac1 and RhoA affect PDGFRα and -β signaling and downstream activation of AKT, ERK1/2, STAT1 and STAT3. In response to individual depletion of all Rho GTPases both PDGFRα and -β show a significant reduction in their phosphorylation. We could see a delayed internalization in response to Cdc42 or Rac1 depletion and an increased steady-state amount in response to RhoA depletion for both PDGFRα and -β. Downstream of both receptors, we saw a dramatic effect on STAT signaling, however, AKT and ERK1/2 signaling was unaffected. PDGF-BB-induced STAT1 and STAT3 phosphorylation was severely impaired in response to the depletion of either Cdc42, Rac1 or RhoA. Furthermore, STAT1 protein levels were also decreased in response to depletion of the Rho GTPases. In conclusion, we show that both PDGFRα and PDGFRβ rely on Cdc42, Rac1 and RhoA for proper signaling. Furthermore, we also show that STAT1 and STAT3 depend on Cdc42, Rac1 and RhoA for their signaling downstream of PDGFRs, and STAT1 for its protein stability.
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