| 1. |
- Nilsen, Tom Ole, et al.
(författare)
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EFFECTS OF ANDROGENS AND CORTISOL ON GILL ION TRANSPORTERS AND OMSMOREGULATORY CAPACITY IN ATLANTIC SALMON (SALMO SALAR)
- 2014
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Ingår i: ICBF 2014, Edinburgh.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Sex steroids have been reported to compromise ion homeostasis in teleosts, yet there is limited and somewhat contradicting knowledge about the mechanisms through which androgens impact osmoregulatory capacity in salmonids. Immature Atlantic salmon post-smolts in seawater (SW) were injected with 11-ketoandrostenedione (OA; 25 µg/g BW), cortisol (F; 25 µg/g BW), F+OA (25 µg/g BW) and sham control (CON). After 8 days treatment, androgen treated fishdemonstrated a striking transcriptional increase in freshwater (FW)-type of ion transporters (NKA α1a ) , concurrent with no apparent ion perturbations, or down regulation of SW gill ion-transporters (NKA α1b). F treated post-smolts displayed increased gill NKA α1a transcription, with an additive effect of F+OA.. Moreover, F also resulted in decreased transcription of NKA α1b whilst fish treated with combinations of F and OA experienced severe ion perturbations and mortalities in SW, while no mortality occurred when only F was administered. Our findings suggests that androgens have, either directly or indirectly, a role in remodelling the gill epithelia for FW entry, rather than leading to osmoregulatory dysfunction in SW acclimated post-smolts. Moreover, maturing post-smolts may be sensitive to stress since combinations of elevated androgens and cortisol levels may have detrimental effects on homeostasis and fish welfare.
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| 2. |
- Aronsson, L., et al.
(författare)
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Intraductal Papillary Mucinous Neoplasms of the Pancreas : A Nationwide Registry-Based Study
- 2018
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 107:4, s. 302-307
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: To investigate the paraclinical and pathological features of surgically resected intraductal papillary mucinous neoplasms in Sweden. Materials and Methods: A review of prospectively collected data on patients undergoing pancreatic resection for a histopathologically verified intraductal papillary mucinous neoplasm between 2010 and 2016 was performed using the Swedish National Registry for Pancreatic and Periampullary Cancer. Results: A total of 3038 pancreatic resections were performed during the study period, of which 251 (8.3%) were due to intraductal papillary mucinous neoplasms. The intraductal papillary mucinous neoplasm cases comprised 227 noninvasive and 24 invasive lesions. There was an annual increase in the number of resected intraductal papillary mucinous neoplasms, from 13 in 2010 to 56 in 2016, and an increase in the proportion of intraductal papillary mucinous neoplasm to the total number of pancreatic resections (4.7%–11%). Biliary obstruction was the only independent predictor of invasive disease, with odds ratio 3.106 (p = 0.030). There was no difference in survival between low-, intermediate-, and high-grade dysplastic lesions (p = 0.417). However, once invasive, the prognosis was severely impacted (p < 0.001). Three-year survival was 90% for noninvasive intraductal papillary mucinous neoplasm and 39% for invasive intraductal papillary mucinous neoplasm. Survival was better in lymph node negative invasive intraductal papillary mucinous neoplasm (p = 0.021), but still dismal compared to noninvasive lesions (p < 0.001). Conclusion: The number of surgically resected intraductal papillary mucinous neoplasms is increasing in Sweden. Biliary obstruction is associated with invasive disease. Low-to-high-grade dysplastic intraductal papillary mucinous neoplasm has an excellent prognosis, while invasive intraductal papillary mucinous neoplasm has a poor survival rate.
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| 3. |
- Abreu, P., et al.
(författare)
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Measurement of the gluon fragmentation function and a comparison of the scaling violation in gluon and quark jets
- 2000
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 13:4, s. 573-589
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Tidskriftsartikel (refereegranskat)abstract
- The fragmentation functions of quarks and gluons are measured in various three-jet topologies in Z decays from the full data set collected with the DELPHI detector at the Z resonance between 1992 and 995. The results at different values of transverse momentum-like scales are compared. A parameterization of the quark and gluon fragmentation functions at a fixed reference scale is given. The quark and gluon fragmentation functions show the predicted pattern of scaling violations. The scaling violation for quark jets as a function of a transverse momentum-like scale is in a good agreement with that observed in lower energy e+e- annihilation experiments. For gluon jets it appears to be significantly stronger. The scale dependences of the gluon and quark fragmentation functions agree with the prediction of the DGLAP evolution equations from which the colour factor ratio CA/CF is measured to be: CA/CF = 2.26 ± 0.09stat. ± 0.06sys. ± 0.12clus.,scale..
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| 4. |
- Abreu, P., et al.
(författare)
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Search for sleptons in e+e- collisions at √s = 183 to 189 GeV
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 29-42
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Tidskriftsartikel (refereegranskat)abstract
- Data taken by the DELPHI experiment at centre-of-mass energies of 183 GeV and 189 GeV with a total integrated luminosity of 212 pb-1 have been used to search for the supersymmetric partners of the electrons, muons, and taus in the context of the Minimal Supersymmetric Standard Model (MSSM). The decay topologies searched for were the direct decay (ℓ̃ → ℓx̃), producing acoplanar lepton pairs plus missing energy, and the cascade decay (ℓ → ℓx̃0 2 → ℓγx̃0 1), producing acoplanar lepton and photon pairs plus missing energy. The observed number of events is in agreement with Standard Model predictions. The 95% CL excluded mass limits for selectrons, smuons and staus are mẽ ≤ 87 GeV/c2, mμ̃ ≤ 80 GeV/c2 and mτ̃ 75 GeV/c2, respectively, for values of μ=-200 GeV/c2 and tanβ=1.5.
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| 5. |
- Abreu, P., et al.
(författare)
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Study of dimuon production in photon-photon collisions and measurement of QED photon structure functions at LEP
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 15-28
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Tidskriftsartikel (refereegranskat)abstract
- Muon pair production in the process e+e- → e+e- μ+μ- is studied using the data taken at LEP1 (√s ≃ mz) with the DELPHI detector during the years 1992-1995. The corresponding integrated luminosity is 138.5 pb-1. The QED predictions have been tested over the whole Q2 range accessible at LEP1 (from several GeV2/c4 to several hundred GeV2/c4) by comparing experimental distributions with distributions resulting from Monte Carlo simulations using various generators. Selected events are used to extract the leptonic photon structure function Fγ 2. Azimuthal correlations are used to obtain information on additional structure functions, Fγ A and Fγ B, which originate from interference terms of the scattering amplitudes. The measured ratios Fγ A/Fγ 2 and FγB/Fγ 2 are significantly different from zero and consistent with QED predictions.
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| 6. |
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| 7. |
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| 8. |
- Andersson, S-O, et al.
(författare)
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Consultation skills of last semester medical students in Sweden: : video-recorded real-patient consultations in primary health care assessed by Calgary-Cambridge Global Consultation Rating Scale, a pilot study
- 2019
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Ingår i: MedEdPublish. - : F1000 Research Ltd. - 2312-7996. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- This article was migrated. The article was marked as recommended. Introduction: Doctor-patient consultation is an essential element of high quality health care. Education and training of medical students in consultation skills is important. The aim of this study was to investigate the medical students' consultation skills before graduation by assessment of the students' video recordings of consultations with real patients at primary health care centres. Methods: All students had to make a video recording of a meeting with a real patient for formative examination. 26 students participated in the study and delivered a video recording and a self-assessment. Four general practitioners assessed the video recordings by Calgary-Cambridge Global Consultation Rating Scale (CC-GCRS). Statistical testing included comparisons between groups of students and assessors using non-parametric methods. Results: The average CC-GCRS-rating was higher for female students. The students' strengths were related to relation and problem exploration. Their limitations were related to patient's perspective, providing structure and providing information. The students assessed their consultation skills higher than the assessors did, while the relative levels were similar. The distribution of rating scores across the assessors was small. Conclusion:Consultation skills were acceptable for most medical students, although there was room for improvement regarding patient centeredness skills. CC-GCRS was feasible and might be a valuable instrument to assess consultation skills for medical students at the end of their medical education.
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| 9. |
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| 10. |
- Andersson, S O, et al.
(författare)
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Prevalence of lower urinary tract symptoms in men aged 45-79 years : a population-based study of 40,000 Swedish men
- 2004
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Ingår i: BJU International. - Karolinska Inst, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Univ Hosp Orebro, Dept Urol, Orebro, Sweden. Univ Hosp Orebro, Ctr Assessment Med Technol, Orebro, Sweden. Vasteras Hosp, Dept Urol, Vasteras, Sweden. : WILEY. - 1464-4096 .- 1464-410X. ; 94:3, s. 327-331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To estimate the age-specific prevalence and severity of lower urinary tract symptoms (LUTS) among Swedish men, the intercorrelations between different symptoms, and to assess quality of life and health-seeking behaviour among men with LUTS. SUBJECTS AND METHODS In 1997, an International Prostate Symptom Score (IPSS) questionnaire, together with other questions about lifestyle, was mailed to all men aged 45-79 years living in two counties in Sweden; the analyses included 39 928 men. RESULTS Overall, 18.5% and 4.8% of the men were moderately and severely symptomatic; the prevalence of at least one symptom was 83%. LUTS were strongly age-dependent, with 1.8% of severe symptoms among men aged 45-49 years and increasing to 9.7% among those 75-79 years old. Frequent urination was the most common symptom among men aged <70 years and nocturia among those aged >70 years. Symptoms like hesitancy, poor flow and intermittency were highly correlated with each other (Spearman coefficients 0.56-0.60). There was a high correlation between the IPSS and a poor score for quality of life resulting from the bothersomeness of LUTS (r = 0.70). Among symptomatic subjects, 36% reported a poor quality of life (fairly bad, very bad or terrible). Only 29% of symptomatic subjects (IPSS >7) reported that they had been diagnosed previously for their urinary problems, and only 11% received medication for that. CONCLUSION Although the prevalence of LUTS in Sweden is high, the percentage of men whose quality of life is substantially affected is much lower.
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| 11. |
- Andersson, S.-O., et al.
(författare)
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The criteria nurses use in assessing acute trauma in military emergency care
- 2007
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Ingår i: Accident and Emergency Nursing. - : Elsevier BV. - 0965-2302 .- 1532-9267. ; 15:3, s. 148-156
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Tidskriftsartikel (refereegranskat)abstract
- Emergency medical care for seriously injured patients in war or warlike situations is highly important when it comes to soldiers' survival and morale. The Swedish Armed Forces sends nurses, who have limited experience of caring for injured personnel in the field, on a variety of international missions. The aim of this investigation was to identify the kind of criteria nurses rely on when assessing acute trauma and what factors are affecting the emergency care of injured soldiers. A phenomenographic research approach based on interviews was used. The database for the study consists of twelve nurses who served in Bosnia in 1994-1996. The criteria nurses rely on, when assessing acute trauma in emergency care, could be described in terms of domain-specific criteria such as a physiological, an anatomical, a causal and a holistic approach as well as contextual criteria such as being able to communicate, having a sense of belonging, the military environment, the conscript medical orderly and familiarity with health-caring activity. The present study shows that the specific contextual factors affecting emergency care in the field must also be practised before the nurse faces military emergency care situations. This calls for realistic exercises and training programs, where experience from civilian emergency care is interwoven with the knowledge specific to military medical care. © 2007 Elsevier Ltd. All rights reserved.
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| 12. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
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Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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| 13. |
- Bodlund, Owe, et al.
(författare)
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Effects of consulting psychiatrist in primary care. 1-year follow-up of diagnosing and treating anxiety and depression.
- 1999
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Ingår i: Scandinavian Journal of Primary Health Care. - 0281-3432 .- 1502-7724. ; 17:3, s. 153-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Epidemiological screening of anxiety and depressive disorders in primary care and evaluation of how these patients are identified and treated. Follow-up after 1 year of psychiatric consultation/liaison (C/L) and educational activities. SUBJECTS AND DESIGN: In the baseline study 374 unselected and consecutive patients, and in the follow-up study 254 patients (response rate 94.5% and 90.3%, respectively) answered the screening instrument HAD scale (Hospital Anxiety and Depression scale). The HAD results were compared to clinical diagnosis and treatment according to the medical records. Differences after 1 year were analysed. RESULTS: At follow-up the prevalence of anxiety had increased from 11.8% to 16.5% (p < 0.05), and of depression from 3.7% to 4.7% (NS) according to HAD. Also, at the follow-up more cases of anxiety disorders were clinically diagnosed--13% vs 8%--as well as an increased number of cases of depressive disorders--7.9% vs 4.0%. The agreement between HAD diagnosis and clinical judgement had increased significantly (p < 0.001) for anxiety disorders from 37% to 70%, and for depression from 20% to 45%. Treatment prevalence had also improved (p < 0.001) at the follow-up for anxiety disorders from 33% to 55% and for depression from 47% to 80%. In total, 4.0% of the baseline and 11.4% of the follow-up population were treated for anxiety and/or depression. CONCLUSIONS: Anxiety and depressive disorders are prevalent in primary care. However, only a minority of these patients are identified and treated. Psychiatric consultant support seems to be effective in improving GP's diagnostic and therapeutic skills thus enabling these widespread disorders to be identified at an early stage and properly treated.
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| 14. |
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| 15. |
- Demichelis, F., et al.
(författare)
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TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort
- 2007
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Ingår i: Oncogene. - Basingstoke : Nature Publ. Group. - 0950-9232 .- 1476-5594. ; 26:31, s. 4596-4599
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.
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| 16. |
- Hakansson, M C, et al.
(författare)
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The electronic structure of In- and As-terminated InAs(001) surfaces
- 1997
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Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 374:1-3, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- The InAs(001) 2 x 4 and 4 x 2 surfaces have been investigated by angle-resolved photoemission. The X(3) and X(5) points were found to be located 6.0 and 2.7 eV below the valence band maximum, respectively, and the dispersion of bulk bands along the Gamma-X direction in the bulk Brillouin zone were well described by a theoretical calculation. From angle-resolved valence band spectra measured along the high symmetry directions [110] and [1(1) over bar0$], three surface induced stares were identified on both the InAs(001)4 x 2 and the InAs(001)2 x 4 surface. (C) 1997 Elsevier Science B.V.
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| 17. |
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| 18. |
- Kravets, A. F., et al.
(författare)
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Exchange-induced phase separation in Ni-Cu films
- 2012
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Ingår i: Journal of Magnetism and Magnetic Materials. - : Elsevier BV. - 0304-8853 .- 1873-4766. ; 324:13, s. 2131-2135
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Tidskriftsartikel (refereegranskat)abstract
- Magneto-structural properties of films of diluted ferromagnetic alloys NixCu1-x in the concentration range 0.7 < x < 1.0 are studied experimentally. Films deposited by magnetron sputtering show partial phase separation, as evidenced by structural analysis and ferromagnetic resonance measurements. The phase diagram of the NixCu1-x bulk system is obtained using numerical theoretical analysis of the electronic structure, taking into account the interatomic exchange interactions. The results confirm the experimentally found partial phase separation, explain it as magnetic in origin, and indicate an additional metastable region connected with the ferromagnetic transition in the system.
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| 19. |
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| 20. |
- Roepstorff, P., et al.
(författare)
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Application of Plasma Desorption Mass Spectrometry to Molecular Weight Determination of Structural Protein from Insect Cuticle
- 1986
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Ingår i: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 13:12, s. 689-691
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Tidskriftsartikel (refereegranskat)abstract
- During sequence determination of a structural protein from the cuticle of the migratory locust, Locusta migratoria, a discrepancy was found between the molecular weight calculated from the sequence data (15 323) and that estimated by SDS-gel electrophoresis (21 600). The protein contains several repeated sequences, and the discrepancy might indicate that part of the sequence was missing or that the protein contained a large prosthetic group. The molecular weight of the protein was determined by 127I-plasma desorption mass spectrometry to be 15 329±50 which confirms the sequence data and shows the molecular weight determination based on SDS-electrophoresis to be too high.
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| 21. |
- Wadelius, Mia, et al.
(författare)
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Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer
- 1999
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Ingår i: Pharmacogenetics. - 0960-314X .- 1473-561X. ; 9:3, s. 333-40
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Tidskriftsartikel (refereegranskat)abstract
- The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.
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| 22. |
- Wadelius, Mia, et al.
(författare)
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Prostate cancer associated with CYP17 genotype
- 1999
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Ingår i: Pharmacogenetics. - 0960-314X .- 1473-561X. ; 9:5, s. 635-9
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Tidskriftsartikel (refereegranskat)abstract
- Androgens play an important role in the development of prostate cancer. Androgen regulating genes that show allelic variation may be susceptibility factors for the disease. One of these genes, CYP17, encodes the cytochrome P450c17alpha enzyme. It catalyses steroid 17alpha-hydroxylase/17,20 lyase activities at key points in testosterone biosynthesis. We investigated the association between a polymorphism in the CYP17 gene and prostate cancer in a population-based case-control study. All individuals studied were Caucasians born in Sweden, 178 were consecutive clinical prostate cancer patients, and 160 were age-matched control individuals randomly selected from the same catchment area. DNA was extracted from blood samples. A CYP17 gene fragment was amplified by polymerase chain reaction. The MspA1I restriction enzyme, which recognizes the base pair substitution, was used to identify the allelic variants CYP17A1 and CYP17A2. Significantly more men homozygous for the CYP17A1 allele were found among prostate cancer patients compared with control individuals; odds ratio 1.61 (95% confidence interval 1.02; 2.53), P = 0.04. According to a preliminary report, the CYP17A1/A1 genotype leads to higher circulating androgen levels, possibly by encoding for a more active androgen synthesizing CYP17 enzyme. Consequently, the CYP17A1/A1 genotype, which was found in a higher frequency among prostate cancer patients, may prove to be one of the important susceptibility factors for prostate cancer. If verified, this genotype is likely to convey a larger risk on a population basis, than the rare hereditary prostate cancer genes do.
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| 23. |
- Wallin, Maria, 1985, et al.
(författare)
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Peptide-induced formation of a tethered lipid bilayer membrane on mesoporous silica
- 2015
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Ingår i: European Biophysics Journal. - : Springer Science and Business Media LLC. - 1432-1017 .- 0175-7571. ; 44:1-2, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- Tethered bilayer lipid membranes (tBLMs) on solid supports have substantial advantages as models of artificial cell membranes for such biomedical applications as drug delivery and biosensing. Compared with untethered lipid membranes, tBLMs have more space between substrate and the bilayer and greater stability. The purpose of this work was to use these properties to fabricate and characterize a zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid tBLM containing 2 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide(poly(ethylen e glycol))-2000 (DSPE-PEG(2000)-NHS) lipid tethers on a 3-aminopropyltrimethoxysilane-modified mesoporous silica substrate. A quartz crystal microbalance with dissipation monitoring was used to monitor the process of vesicle adsorption and tBLM self-assembly, and atomic force microscopy was performed to characterize the structural properties of the tBLM obtained. Whereas tether-containing lipid vesicles ruptured neither spontaneously nor as a result of osmotic shock, introduction of an amphipathic alpha-helical (AH) peptide induced vesicle rupture and subsequent tBLM formation. Taken together, our findings suggest that the AH peptide is an efficient means of rupturing vesicles of both simple and complex composition, and is, therefore, useful for formation of tBLMs on solid and mesoporous materials for applications in biotechnology.
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| 24. |
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| 25. |
- Zegeye, Mulugeta M, 1986-, et al.
(författare)
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IL-6 as a Mediator of the Association Between Traditional Risk Factors and Future Myocardial Infarction : A Nested Case-Control Study
- 2021
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 41:4, s. 1570-1579
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Studies elucidating the importance of IL (interleukin)-6 trans-signaling associated with risk of future myocardial infarction (MI) are scarce. Additionally, whether elevation in IL-6 explains part of the association between traditional risk factors and future MI has not been explored.Approach and Results: We conducted a nested case-control study including a total of 584 participants (292 cases and 292 controls) from Västerbotten Intervention Programme and MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) cohorts. At baseline, plasma cholesterol levels were measured, and clinical characteristics of participants were collected. In this study, we measured the plasma concentration of IL-6, sIL-6R (soluble IL-6 receptor), and sgp130 (soluble-gp130). To estimate extent of IL-6 trans-signaling, we estimated plasma concentration of a novel biomarker, the IL-6 binary complex. IL-6 binary complex concentration was significantly elevated in participants who experienced MI compared with those who did not. Univariate analyses showed that a 2-fold increase in IL-6 binary complex was associated with 2.45× higher risk of future MI (95% CI relative risk, 1.65-3.66, P<0.001). Receiver operating characteristics analyses revealed that the predictive performance of IL-6 binary complex (area under the curve, 0.614) was equivalent to that of IL-6 (area under the curve, 0.603). Furthermore, using Process mediation analyses tool, we found statistically significant indirect effect of smoking and hypertension on future MI that is mediated through increased IL-6 binary complex or plasma IL-6.CONCLUSIONS: IL-6 and IL-6 binary complex concentration in plasma were significantly associated with future MI. Our data additionally imply that both the elevated plasma IL-6, and the IL-6 binary complex concentration could partly explain, and, thus, might hypothetically be functionally associated with the increased risk of MI in smokers and hypertensive participants.
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| 26. |
- Zegeye, Mulugeta M, 1986-, et al.
(författare)
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Soluble LDL-receptor is induced by TNF-α and inhibits hepatocytic clearance of LDL-cholesterol
- 2023
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Ingår i: Journal of Molecular Medicine. - : Springer. - 0946-2716 .- 1432-1440. ; 101:12, s. 1615-1626
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Tidskriftsartikel (refereegranskat)abstract
- Defective LDL-C clearance and hence its elevation in the circulation is an established risk factor for cardiovascular diseases (CVDs) such as myocardial infarction (MI). A soluble LDL-receptor (sLDL-R) has been detected in human plasma which correlates strongly with circulating LDL-C and classical conditions that promote chronic inflammation. However, the mechanistic interplay between sLDL-R, inflammation, and CVDs remains to be investigated. Here, we report that stimulation of HepG2 cells with TNF-α induces the release of sLDL-R into culture supernatants. In addition, TNF-α induces gene expression of peptidases ADAM-17 and MMP-14 in HepG2 cells, and inhibiting these peptidases using TMI 1 significantly reduces the TNF-α induced sLDL-R release. We found that a soluble form of recombinant LDL-R (100 nM) can strongly bind to LDL-C and form a stable complex (KD = E-12). Moreover, incubation of HepG2 cells with this recombinant LDL-R resulted in reduced LDL-C uptake in a dose-dependent manner. In a nested case-control study, we found that baseline sLDL-R in plasma is positively correlated with plasma total cholesterol level. Furthermore, a twofold increase in plasma sLDL-R was associated with a 55% increase in the risk of future MI [AOR = 1.55 (95% CI = 1.10-2.18)]. Nevertheless, mediation analyses revealed that a significant proportion of the association is mediated by elevation in plasma cholesterol level (indirect effect β = 0.21 (95% CI = 0.07-0.38). Collectively, our study shows that sLDL-R is induced by a pro-inflammatory cytokine TNF-α via membrane shedding. Furthermore, an increase in sLDL-R could inhibit hepatic clearance of LDL-C increasing its half-life in the circulation and contributing to the pathogenesis of MI. KEY MESSAGES: TNF-α causes shedding of hepatocytic LDL-R through induction of ADAM-17 and MMP-14. sLDL-R binds strongly to LDL-C and inhibits its uptake by hepatocytic cells. Plasma sLDL-R is positively correlated with TNF-α and cholesterol. Plasma sLDL-R is an independent predictor of myocardial infarction (MI). Plasma cholesterol mediates the association between sLDL-R and MI.
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