| 1. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Evidence for colocalization of glucocorticoid receptor with cytoplasmic microtubules in human gingival fibroblasts, using two different monoclonal anti-GR antibodies, confocal laser scanning microscopy and image analysis
- 1991
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 39:4A, s. 419-432
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Tidskriftsartikel (refereegranskat)abstract
- The cellular distribution of the glucocorticoid receptor (GR) in relation to the microtubule protein tubulin was studied in human gingival fibroblasts, using two different anti-GR antibodies of different Ig-classes, by indirect immunofluorescence immunocytology. Further studies were performed by confocal laser scanning microscopy and digital image analysis. The study focused on fluorochrome separation, optical sectioning, digital subtraction techniques and reconstruction of projections obtained using stacks of recorded transversal sections. The data presented further strengthens the notion of a structural colocalization between GR and cytoplasmic microtubules in human fibroblasts.
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| 2. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Evidence for reversible, non-microtubule and non-microfilament-dependent nuclear translocation of hsp90 after heat shock in human fibroblasts
- 1992
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Ingår i: European Journal of Cell Biology. - 0171-9335 .- 1618-1298. ; 58:2, s. 356-364
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Tidskriftsartikel (refereegranskat)abstract
- A monoclonal antibody (29A) directed against rat liver heat shock protein M(r) 90,000 (hsp90) was produced. By Western immunoblotting of cytosols prepared from several different tissues and species, 29A was shown to specifically recognize only one band with M(r) approximately 90,000. Localization of hsp90 in human gingival fibroblasts was studied using the 29A antibody by indirect mono- and double-staining immunofluorescence and confocal laser scanning microscopy. The distribution was compared to that of the glucocorticoid receptor (GR) and various cytoskeletal structures. Cells were analyzed in interphase and mitosis under basal culture conditions, after heat shock and after microtubule and microfilament depolymerization, sometimes combined with heat shock. A major part of hsp90 immunoreactivity was diffusely distributed throughout the interphase cytoplasm, but a weak nuclear staining with non-stained nucleoli was also present, however, only detectable after methanol and not after formaldehyde/Triton X-100 fixation. Heat shock induced a time-dependent translocation of hsp90 from the cytoplasm to the cell nucleus reaching a plateau after 15 h. This compartment shift was reversible and also occurred in the absence of intact microtubules or intact microfilaments.
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| 3. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Glucocorticoid receptor inhibits microtubule assembly in vitro.
- 1995
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Ingår i: Molecular and cellular endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 110:1-2, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- The effect of glucocorticoid hormones, purified glucocorticoid receptor (GR) and purified heat shock protein M(r) 90,000 (hsp90) on microtubule (MT) assembly in vitro was tested by a spectrophotometric MT assembly assay and electron microscopy. GR significantly prolonged the nucleation phase, slowed down the assembly rate and reduced the maximal amplitude of MT assembly compared with control. The effects were partially reversed by the addition of glucocorticoid hormone. GR associated with MTs. These results indicate that GR affects MT assembly in vitro, which may be a functional correlate to the structural association of GR with MTs. This implies that factors affecting GR may affect MT assembly in vivo.
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| 4. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Immunocytochemical localization of glucocorticoid receptor in human gingival fibroblasts and evidence for a colocalization of glucocorticoid receptor with cytoplasmic microtubules
- 1990
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Ingår i: European Journal of Cell Biology. - 0171-9335 .- 1618-1298. ; 53:2, s. 390-401
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Tidskriftsartikel (refereegranskat)abstract
- The cellular distribution of the glucocorticoid receptor (GR) in relation to various intracellular and plasma membrane structures in human fibroblasts was studied using indirect immunofluorescence techniques with monoclonal and polyclonal antibodies. During interphase, GR was located predominantly in the cytoplasm, showing a similar pattern as tubulin. In mitotic cells, GR and tubulin were localized in mitotic spindles and in telophase midbodies. Colchicine and vinblastine induced a similar redistribution of GR and tubulin to the cell periphery. This redistribution was reversible for colchicine but not for vinblastine. Vinblastine also induced paracrystals containing GR and tubulin. These results support the hypothesis that GR interacts in vivo with cytoplasmic microtubules.
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| 5. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Morphometric studies of the localization of the glucocorticoid receptor in mammalian cells and of glucocorticoid hormone-induced effects
- 1994
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Ingår i: Journal of Histochemistry and Cytochemistry. - : SAGE Publications. - 0022-1554 .- 1551-5044. ; 42:5, s. 645-657
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Tidskriftsartikel (refereegranskat)abstract
- We studied the subcellular distribution of the glucocorticoid receptor (GR) by light microscopy (LM) and confocal laser scanning microscopy (CLSM) in different mammalian cell types. The effect of added glucocorticoid hormones on GR distribution was investigated by photometric quantitation on optical sections obtained by CLSM followed by statistical analysis. In the control interphase cytoplasm, the distribution of GR was fibrillar in some and diffuse in other cell types. Fibrillar GR was distributed along cytoplasmic microtubules (MTs) with predilection for a subset of MTs. GR was also observed in the centrosomes. Nuclear GR was both diffuse and granular in distribution. During cell division, GR appeared in the mitotic apparatus at all stages of mitosis. These findings were not fixation-dependent. Glucocorticoid treatment increased both the nuclear and cytoplasmic GR signal. However, this was detectable only after precipitating but not cross-linking fixation. There was both intra- and intercellular GR heterogeneity in the absence and presence of hormone but no indication of a hormone-induced nuclear translocation of GR. We present a hypothetical model of two independent GR populations in the nucleus and cytoplasm, respectively, without any discernible ligand-induced nuclear translocation of GR. The extranuclear GR population may exert effect(s) on site in the cytoplasm without involving nuclear genomic transcription.
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| 6. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Subcellular distribution of the glucocorticoid receptor and evidence for its association with microtubules
- 1995
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 52:1, s. 1-16
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Forskningsöversikt (refereegranskat)abstract
- The cellular distribution of the glucocorticoid receptor (GR) has not yet been firmly established. The extensive literature indicates that GR is present both in the cytoplasm and the cell nucleus, however, some studies have failed to detect cytoplasmic GR. It is still controversial as to whether GR is randomly diffusing in the cytoplasm and nucleus, or if the GR-distribution is organized or controlled in some way, which may be of importance for the transduction of glucocorticoid effects to cells. There is evidence that both non-activated and activated GR is associated with the plasma membrane, a number of cytoplasmic organelles and the nucleus. Both morphological and biochemical evidence show that GR is associated with microtubules during different stages of the cell cycle, i.e. GR co-localizes, co-purifies and co-polymerizes with tubulin. This indicates that GR is structurally linked to the intracellular MT-network which may be of importance in the mechanism of action of glucocorticoid hormones. The literature in this field is reviewed including the reported data on subcellular GR-localization.
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| 7. |
- Antoni, Gunnar, et al.
(författare)
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In Vivo Visualization of Amyloid Deposits in the Heart with C-11-PIB and PET
- 2013
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 54:2, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-C-11]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole (C-11-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of C-11-PIB PET in systemic amyloidosis affecting the heart. Methods: Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type- and healthy volunteers (n = 5) were investigated with PET/CT using C-11-PIB to study cardiac amyloid deposits and with C-11-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. Results: Myocardial C-11-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in C-11-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with C-11-PIB. No correlation between C-11-PIB retention index and myocardial blood flow as measured with C-11-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient. Conclusion: C-11-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.
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| 8. |
- Beshara, Soheir, et al.
(författare)
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Assessment of erythropoiesis following renal transplantation
- 1997
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Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 58:3, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22) ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.
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| 9. |
- Dubol, Manon, et al.
(författare)
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Acute nicotine exposure blocks aromatase in the limbic brain of healthy women : A [11C]cetrozole PET study
- 2023
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Ingår i: Comprehensive Psychiatry. - : Elsevier. - 0010-440X .- 1532-8384. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.
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| 10. |
- Eklöf, Mats, 1953, et al.
(författare)
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Dialogträning på vårdarbetsplatser
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund, syfte och design Begreppet dialog har använts för att definiera välfungerande och utvecklingsinriktad kommunikation och inbegriper att uttrycka genuina uppfattningar, erfarenheter och känslor, att vänta in, lyssna på och respektera andra perspektiv än det egna samt att vara beredd att låta sig påverkas. Studien var en klusterrandomiserad kontrollerad studie av en dialogträningsmetods effekter på dialogklimat och psykosocial arbetsmiljö bland personal vid enheter inom svensk sjukvård. Träningseffekter och träningsprocessen studerades även i en kvalitativ intervjustudie bland tränade. Träningen genomfördes på fem enheter inom svensk sjukvård och fem enheter utgjorde kontrollgrupp. Kontrollbetingelsen bestod av en konventionell föreläsning om dialog på arbetsplatsen. Metod Inklusionskriterier för enheter var chefens motivation och intresse, frånvaro av allvarliga samarbetssvårigheter samt att organisationsförändringar inte planerades under studieperioden. Träningen genomfördes i mindre grupper och följde en fast struktur men där utrymme fanns för situationsanpassade processinterventioner och kunskapsförmedling av tränarna. Tre legitimerade psykoterapeuter med erfarenhet av att leda gruppsamtal var tränare. Data insamlades med enkäter före träning samt 3 och 6 månader efter träning. 277 personer deltog, varav 158 tränades. Intervjuer med 21 deltagare genomfördes efter träningsperioden. Resultat Den kvantitativa effektstudien indikerade positiv träningseffekt på dialogklimat och psykosocial arbetsmiljö, dock med varierande grad av säkerhet. Resultaten pekade på att effekter kunde öka mellan tre- och sexmånadersuppföljningarna, vilket var oväntat. Den kvalitativa studien fann att deltagare kunde berätta om a) omedelbara träningseffekter i termer av Dialogöppningar (öppet klimat under träningen, utrymme för lyssnande och tal, tid för reflektion och perspektivbyte, vägledning i att formulera egna ståndpunkter, medvetenhet om styrkan i normer och värderingar) samt b) Förändrade kommunikationsmönster i arbetet (undvikande av förolämpningar och ironi, att våga säga sin mening och begära, att vara hänsynsfull och balanserad samt att konstruktivt konfrontera). De kvalitativa resultaten visade också förhållanden som möjliggör respektive försvårar dialog på vårdarbetsplatser, samt att motstånd mot träningen förekommit. Slutsatser Vi drog slutsatsen att dialogträning enligt den beskrivna metodiken var effektiv som medel att påverka kommunikationen bland deltagarna i dialogisk riktning och att öka deras inflytande i arbetet. Keywords Dialog, Feedback, Inflytande, Intervention, Kommunikation, Mixed method, Mixed models, Psykosocial, Teamklimat, Vård.
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