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  • 351.
    Ahmed, Ali
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Nationalekonomi. Linköpings universitet, Filosofiska fakulteten.
    Co-ethnic preferences in a cooking game: a study based on Come Dine With Me in Sweden2013Ingår i: Ethnic and Racial Studies, ISSN 0141-9870, E-ISSN 1466-4356, Vol. 36, nr 12, s. 2220-2236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study examines ethnic preferences using data from the television cooking show Come Dine With Me in Sweden. Amateur chefs compete by hosting dinner parties. Contestants rate each others performance and the host with the highest ratings wins a cash prize. The show gives an unorthodox opportunity to study ethnic preferences in a high-stakes game environment. The analysis of the collected data shows that native Swedish contestants rate co-ethnic hosts significantly more favourably than they rate other hosts, demonstrating the existence of co-ethnic preferences. This observation seems to be an outcome of own-group favouritism rather than dislike against other groups. Also, the observed co-ethnic preference is assumed to be subtle or non-conscious based on the nature of the analysed data.

  • 352.
    Ahmed, Tamer A. E.
    et al.
    University of Ottawa, Ontario, Canada.
    Giulivi, Antonio
    The Ottawa Hospital, Ontario, Canada.
    Griffith, May
    University of Ottawa, Ontario, Canada.
    Hincke, Max
    University of Ottawa, Ontario, Canada.
    Fibrin Glues in Combination with Mesenchymal Stem Cells to Develop a Tissue-Engineered Cartilage Substitute2011Ingår i: Tissue Engineering. Parts A, B and C, ISSN 2152-4947, E-ISSN 2152-4955, Vol. 17, nr 3-4, s. 323-335Artikel i tidskrift (Refereegranskat)
    Abstract [en]

     Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal (R) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous transforming growth factor-beta(2). Strongly, CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks; however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement of collagen II gene expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression and increased accumulation of Alcian blue-positive extracellular matrix; incorporation of HBDS into these glues did not improve aggrecan gene expression and extracellular matrix accumulation. The most significant effect on cartilage marker gene expression and accumulation was observed after encapsulation of hMSCs in FG. We conclude that FG is more promising than PR-FG as a scaffold for chondrogenic differentiation of hMSCs; however, immobilization of growth factors inside these fibrin scaffolds with the HBDS system has a negative impact on this process. In addition, BM-hMSCs are valid and potentially superior alternatives to chondrocytes for tissue engineering of articular cartilage.

  • 353.
    Ahn, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Baranowski, Jacek
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Dahlin, Lars-Göran
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nielsen, Niels-Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Nylander, Eva
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Wallby, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    TAVI without concomitant balloon dilatation2012Konferensbidrag (Övrigt vetenskapligt)
  • 354.
    Ahn, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Baranowski, Jacek
    Myasnikova, Irina
    Rahgozar, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Delshad, Baz
    First in man: wireless pressure sensors in left heart rooms'2014Konferensbidrag (Refereegranskat)
  • 355.
    Ahn, Henrik Casimir
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Mitral valve surgery - current results and future development to catheter based approaches2006Ingår i: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Konferensbidrag (Övrigt vetenskapligt)
  • 356.
    Ahn, Henrik Casimir
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    The Impella temporary assist device, the Swedish experience2006Ingår i: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Konferensbidrag (Övrigt vetenskapligt)
  • 357.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Baranowski, J
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Nielsen, Nils Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Nylander, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Tamas, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Wallby, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Transcatheter aortic valve implantation in high-risk surgical candidates with low risk-scores1984Konferensbidrag (Övrigt vetenskapligt)
  • 358.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Baranowski, Jacek
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Dahlin, Lars-Göran
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nielsen, Niels Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis2016Ingår i: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 101, nr 6, s. 2279-2284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis.

    METHODS: Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve.

    RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure.

    CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.

  • 359.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Holm, Jonas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Najar, Azad
    Scandinavian Real Heart AB, Vasteras, Sweden.
    Hellers, Goran
    Scandinavian Real Heart AB, Vasteras, Sweden.
    Szabó, Zoltán
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    A New Total Artificial Heart Concept Allowing Replacement or Support of the Native Heart2018Ingår i: Journal of Clinical & Experimental Cardiology, E-ISSN 2155-9880, Vol. 9, nr 2, artikel-id 1000569Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A total artificial heart (TAH) is typically used to bridge the time to heart transplantation. A device designed by Robert Jarvik has been improved through the years and under the name of Syncardia™ this has been the most successful commercially available TAH so far. Since 2008 the Carmat™ heart has been under development in Europe. The Scandinavian Real Heart™ is based on a unique physiological concept where the atrio-ventricular valve plane is of utmost importance in the pumping function of the heart. It consists of two identical parts driven separately by independent motors and in this first animal study we have used one part as a left ventricular assist device. This new concept makes the device flexible as it may be used not only as a TAH but also as a separate pump for left or right ventricular assist.

  • 360.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Jodal, M.
    Lindhagen, J
    Lundgren, O.
    Nilsson, Gert
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Bestämning av tunntarmsblodflödet med laser Doppler teknik1984Ingår i: Läkarsällskapets Riksstämma,1984, 1984Konferensbidrag (Övrigt vetenskapligt)
  • 361.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Johansson, K.
    Lindhagen, J.
    Nilsson, Gert
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Förändringar av blodflödet i ventrikeln i samband med mätt med laser Dopplerteknik1984Ingår i: Läkarsällskapets Riksstämma,1984, 1984Konferensbidrag (Övrigt vetenskapligt)
  • 362.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Johansson, K.
    Lindhagen, J.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Laser Doppler flowmetry in the assessment of gastric blood flow1984Ingår i: man. Scand J of Gastroenterology,1984, 1984, s. 98:33-98:33Konferensbidrag (Övrigt vetenskapligt)
  • 363.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Lindhagen, J.
    Nilsson, Gert
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Jodal, M.
    Lundgren, O.
    Evaluation of Laser Doppler Flowmetry in the assessment of blood flow in the small intestine1984Ingår i: Third World Congress of Microcirculation,1984, 1984Konferensbidrag (Övrigt vetenskapligt)
  • 364.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Lindhagen, J
    Nilsson, Gert
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Jodal, M
    Lundgren, O
    Evaluation of Laser Doppler Flowmetry in the assessment of intestinal blood flow1985Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 4, nr 88, s. 951-957Artikel i tidskrift (Refereegranskat)
    Abstract [en]

      

  • 365.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Lönn, Urban
    IMV/Thoraxkirurgi/Hjärtcentrum LiU/HU.
    Peterzén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Alternatives to circulatory support during coronary artery surgery1999Ingår i: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 16 suppl 2, s. 143-150Artikel i tidskrift (Refereegranskat)
  • 366.
    Ahn, Henrik Casimir
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nielsen, Niels Erik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Baranowski, Jacek
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study2016Ingår i: Journal of Cardiothoracic Surgery, ISSN 1749-8090, E-ISSN 1749-8090, Vol. 11, nr 124Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.

  • 367.
    Ahn, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Delshad, Baz
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Baranowski, Jacek
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    An implantable pressure sensor for long-term wireless monitoring of cardiac function- first study in man2016Ingår i: Journal of Cardiovascular Diseases & Diagnosis, ISSN 2329-9517, Vol. 4, nr 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Heart failure is a huge health problem. The possibility of long-term monitoring heart function more accurately in these patients has gained increasing interest. The primary aim of this study was to see if a wireless pressure sensor can be safely implanted to give accurate and reproducible long-term intracardiac pressure recordings. Another aim was to see if there are any adverse effects connected with the implant. A control group was included for comparison of clinical data.

    Methods: Forty patients with heart failure, 31 scheduled for open heart surgery and 9 for transcatheter aortic valve replacement (TAVR) were included to test the safety and feasibility of the Titan™ pressure sensor. The patients were randomized to the implant or control group.

    Findings: Initial sensor measurements showed very good correlation with reference pressure values from a fluid-filled catheter, and there was no need for calibration of the sensor. At the 6-month follow-up 11 patients had been wearing the implant for >1 year with a median time of 560 days. Ten of these had adequate sensor function. Compared to the control group there was no difference in adverse clinical events and the overall number of complications was low.

    Conclusions: This first study in man on a new implantable wireless hemodynamic monitor showed favorable results regarding our primary endpoints; accuracy of recordings over time and safety profile. The technology has great potential for monitoring at home since it is easy to use in the out-patient setting.

  • 368.
    Ahn, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Granfeldt, Hans
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Hübbert, Laila
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Peterzén, Bengt
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxanestesi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Long-term mechanical circulatory support in patients with a prosthetic aortic valve2012Konferensbidrag (Övrigt vetenskapligt)
  • 369.
    Ahnesjö, Anders
    et al.
    Uppsala University, Sweden.
    van Veelen, Bob
    Elekta Brachytherapy, Netherlands.
    Carlsson Tedgren, Åsa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Karolinska University Hospital, Sweden.
    Collapsed cone dose calculations for heterogeneous tissues in brachytherapy using primary and scatter separation source data2017Ingår i: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 139, s. 17-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objective: Brachytherapy is a form of radiation therapy using sealed radiation sources inserted within or in the vicinity of the tumor of, e.g., gynecological, prostate or head and neck cancers. Accurate dose calculation is a crucial part of the treatment planning. Several reviews have called for clinical software with model-based algorithms that better take into account the effects of patient individual distribution of tissues, source-channel and shielding attenuation than the commonly employed TG-43 formalism which simply map homogeneous water dose distributions onto the patient. In this paper we give a comprehensive and thorough derivation of such an algorithm based on collapsed cone point-kernel superposition, and describe details of its implementation into a commercial treatment planning system for clinical use. Methods: A brachytherapy version of the collapsed-cone algorithm using analytical raytraces of the primary photon radiation followed by successive scattering dose calculation for once and multiply scattered photons is described in detail, including derivation of the corresponding set of recursive equations for energy transport along cone axes/transport lines and the coupling to clinical source modeling. Specific implementation issues for setting up of the calculation grid, handling of intravoxel gradients and voxels partly containing non patient applicator material are given. Results: Sample runs for two clinical cases are shown, one being a gynecological application with a tungsten-shielded applicator and one a breast implant. These two cases demonstrate the impact of improved dose calculation versus TG-43 formalism. Conclusions: Use of model-based dose calculation algorithms for brachytherapy taking the three-dimensional treatment geometry into account increases the dosimetric accuracy in planning and follow up of treatments. The comprehensive description and derivations provided gives a rigid background for further clinical, educational and research applications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 370.
    Ahnström, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Askmalm Stenmark, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Fornander, Tommy
    Karolinska University Hospital.
    Skoog, Lambert
    Karolinska University Hospital.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer2009Ingår i: International Journal of Oncology, ISSN 1019-6439, Vol. 34, nr 2, s. 441-448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G(1) phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.93) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).

  • 371.
    Ahnström Waltersson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Cell cycle alterations and 11q13 amplification in breast cancer: prediction of adjuvant treatment response2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.

    Delarbeten
    1. Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.
    Öppna denna publikation i ny flik eller fönster >>Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.
    Visa övriga...
    2005 (Engelska)Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 91, nr 2, s. 145-151Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.

    Nyckelord
    Beta, fonder, prediction, OLS, LAD, WLS
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-17431 (URN)10.1007/s10549-004-6457-4 (DOI)15868442 (PubMedID)
    Tillgänglig från: 2009-03-25 Skapad: 2009-03-24 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer
    Öppna denna publikation i ny flik eller fönster >>Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer
    Visa övriga...
    2009 (Engelska)Ingår i: International Journal of Oncology, ISSN 1019-6439, Vol. 34, nr 2, s. 441-448Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G(1) phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.93) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).

    Nyckelord
    cell cycle, radiotherapy, chemotherapy, overexpression, Rb, p53
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-16619 (URN)10.3892/ijo_00000168 (DOI)
    Tillgänglig från: 2009-02-07 Skapad: 2009-02-06 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    3. Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.
    Öppna denna publikation i ny flik eller fönster >>Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.
    Visa övriga...
    2007 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 26, nr 49, s. 6997-7005Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (P<0.001). In ER-positive patients, amplification of at least one of the genes indicated a reduced recurrence-free survival (P=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47-5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32-0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.

    Nyckelord
    Cyclin D1, pak1, drug resistance, breast cancer, real-time PCR
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-17456 (URN)10.1038/sj.onc.1210506 (DOI)17486065 (PubMedID)
    Tillgänglig från: 2009-03-25 Skapad: 2009-03-25 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    4. miR-206 expression is downregulated in cyclin D1 amplified breast tumours
    Öppna denna publikation i ny flik eller fönster >>miR-206 expression is downregulated in cyclin D1 amplified breast tumours
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Amplification in the 11q13 region has been found in around 15% of all breast cancers and is strongly correlated with oestrogen receptor (ER) positive tumours. We have previously found that amplification of at least one of the genes PAK1 or CCND1 is associated with decreased recurrencefree survival among ER+ patients. Other genes in the amplicon might also contribute to this effect and situated close to CCND1 are the FGF-3, -4 and - 19 genes. The FGF-4 protein has been shown to inhibit the expression of the ERα regulator miR-206 in chicken embryo. In this study we analysed 23 tumours with and 27 tumours without previously detected 11q13 amplification to explore if 11q13 amplification is associated with decreased levels of miR-206 and if miR-206 is associated with ER expression. Using real-time PCR, we found that miR-206 expression was inversely correlated to CCND1 and 11q13 amplification (P=0.016 and P=0.022 respectively). Tumours with low miR-206 expression had higher levels of ERα than tumours with intermediate and high expression (P=0.043). We conclude that miR-206 might be an important regulator of the ERα. Our finding that low mir-206 is associated with CCND1 amplification and thereby also FGF-4 amplification points towards the possibility of a miR-206 regulator, FGF-4 or another FGF, present in the amplicon.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-17457 (URN)
    Tillgänglig från: 2009-03-25 Skapad: 2009-03-25 Senast uppdaterad: 2010-01-14Bibliografiskt granskad
  • 372.
    Ahnström Waltersson, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Fornander, Tommy
    Department of Cytology, Karolinska University Hospital, SE-104 01 Stockholm, Sweden.
    Skoog, Lambert
    Department of Cytology, Karolinska University Hospital, SE-104 01 Stockholm, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    miR-206 expression is downregulated in cyclin D1 amplified breast tumoursManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Amplification in the 11q13 region has been found in around 15% of all breast cancers and is strongly correlated with oestrogen receptor (ER) positive tumours. We have previously found that amplification of at least one of the genes PAK1 or CCND1 is associated with decreased recurrencefree survival among ER+ patients. Other genes in the amplicon might also contribute to this effect and situated close to CCND1 are the FGF-3, -4 and - 19 genes. The FGF-4 protein has been shown to inhibit the expression of the ERα regulator miR-206 in chicken embryo. In this study we analysed 23 tumours with and 27 tumours without previously detected 11q13 amplification to explore if 11q13 amplification is associated with decreased levels of miR-206 and if miR-206 is associated with ER expression. Using real-time PCR, we found that miR-206 expression was inversely correlated to CCND1 and 11q13 amplification (P=0.016 and P=0.022 respectively). Tumours with low miR-206 expression had higher levels of ERα than tumours with intermediate and high expression (P=0.043). We conclude that miR-206 might be an important regulator of the ERα. Our finding that low mir-206 is associated with CCND1 amplification and thereby also FGF-4 amplification points towards the possibility of a miR-206 regulator, FGF-4 or another FGF, present in the amplicon.

  • 373.
    Ahnström Waltersson, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Rutqvist, Lars Erik
    Department of Oncology, Huddinge University Hospital, Stockholm, Sweden.
    Skoog, Lambert
    Department of Cytology, Karolinska Hospital, Stockholm, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.2005Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 91, nr 2, s. 145-151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.

  • 374.
    Aho, Anna Carin
    et al.
    Linnaeus University, Sweden.
    Hultsjö, Sally
    Psychiat Clin, Sweden; Jönköping University, Sweden.
    Hjelm, Katarina
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Experiences of being parents of young adults living with recessive limb-girdle muscular dystrophy from a salutogenic perspective2017Ingår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, nr 6, s. 585-595Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recessive limb-girdle muscular dystrophies (LGMD2) involve progressive muscle weakness. Parental support is important for young adults living with LGMD2, but no study has been identified focusing on the parents experiences. The salutogenic perspective concentrates on how daily life is comprehended, managed and found meaningful, i.e. the persons sense of coherence. The aim of this study was to describe, from a salutogenic perspective, experiences of being parents of young adults living with LGMD2. Nineteen participants were included. Data were collected by semi-structured interviews and the self-administrated 13-item sense of coherence questionnaire. Interview data were analysed with content analysis and related to self-rated sense of coherence. The result shows experiences of being influenced, not only by thoughts and emotions connected to the disease but also by caregiving duties and the young adults well-being. Simultaneously, difficulty in fully grasping the disease was expressed and uncertainty about progression created worries about future management. Trying their best to support their young adults to experience well-being and to live fulfilled lives, the importance of having a social network, support from concerned professionals and eventually access to personal assistance was emphasized. The need to have meaningful pursuits of ones own was also described. The median sense of coherence score was 68 (range 53-86). Those who scored high (amp;gt;= 68) described satisfaction with social network, external support provided, work and leisure activities to a greater extent than those who scored low (amp;lt;68). The result shows that the young adults disease has a major impact on the parents lives. Assessment of how the parents comprehend, manage and find meaning in everyday life may highlight support needed to promote their health. (C) 2017 Elsevier B.V. All rights reserved.

  • 375.
    Aho, Anna Carin
    et al.
    Malmo Univ, Sweden.
    Hultsjö, Sally
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Cty Hosp Ryhov, Sweden.
    Hjelm, Katarina
    Uppsala Univ, Sweden.
    Perceptions of the transition from receiving the diagnosis recessive limb-girdle muscular dystrophy to becoming in need of human support and using a wheelchair: an interview study2019Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, nr 19, s. 2289-2298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To describe perceptions of the transition from receiving the diagnosis recessive limb-girdle muscular dystrophy to becoming in need of human support to manage daily life and using a wheelchair for ambulation, from the affected young adults and their parents perspectives. Method: A qualitative and descriptive study design was used. Semi-structured interviews were held with 14 young adults diagnosed with recessive limb-girdle muscular dystrophy and 19 parents. Phenomenography was used for data analysis. Results: The diagnosis was described as being a shock and difficult to comprehend but also as a relief and a tool for information. Beginning to use a wheelchair was perceived to be mentally difficult but it also provided freedom. New ways of living involved physical, emotional, practical, and social difficulties as well as experiences of learning to adapt to the disease. The transition was overshadowed by concern about disease progression and influenced by facilitating factors, which were young adult being seen as a person; supportive family and friends; mobilized internal resources; meaningful daily activities; adapted environment; and professional support. Conclusions: The different perceptions expressed in this study highlight the importance of identifying personal perceptions and needs in order to optimize support provided by healthcare professionals.

  • 376.
    Aho, Anna Carin
    et al.
    Linnaeus Univ, Dept Hlth & Caring Sci, Vaxjo, Sweden.
    Hultsjö, Sally
    Cty Hosp, Psychiat Clin, Jonkoping, Sweden.
    Hjelm, Katarina
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Hälsa, Aktivitet, Vård (HAV). Linköpings universitet, Hälsouniversitetet.
    Young adults' experiences of living with recessive limb-girdle muscular dystrophy from a salutogenic orientation: an interview study.2015Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 37, nr 22, s. 2083-2091Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To describe young adults' experiences of living with recessive limb-girdle muscular dystrophy (LGMD2) from a salutogenic orientation. Methods: A qualitative explorative interview study, including 14 participants aged 20-30 years, was performed focusing on comprehensibility, manageability and meaningfulness in daily life. Content analysis was used for data analysis. Result: Living with LGMD2 not only implies learning to live with the disease and the variations between good and bad periods but also means trying to make sense of a progressive disease that brings uncertainty about future health, by striving to make the best of the situation. Disease progression involves practical and mental struggle, trying to maintain control over one's life despite vanished physical functions that require continual adjustments to the body. Restrictions in a double sense were described, not only due to the disease but also due to poor comprehension of the disease in society. Lack of knowledge about LGMD2 among professionals often results in having to fight for the support needed. Conclusion: In order to manage daily life, it is important to be seen and understood as an individual in contacts with professionals and in society in general, to have informal social support and meaningful activities as well as access to personal assistance if necessary. Implications for Rehabilitation Recessive limb-girdle muscular dystrophy (LGMD2) is a group of progressive disorders, which manifest in physical and psychological consequences for the individual. According to the salutogenic orientation, people need to find life comprehensible, manageable and meaningful, i.e. to achieve a sense of coherence (SOC), but living with LGMD2 may recurrently challenge the individual's SOC. Through the holistic view of the individual's situation that the salutogenic orientation provides, professionals may support the individual to strengthen SOC and thereby facilitate the movement towards health.

  • 377.
    Aho, Anna-Carin
    et al.
    Linnéuniversitetet, Växjö, Sweden.
    Hultsjö, Sally
    Ryhovs sjukhus, Landstinget i Jönköping, Sweden.
    Hjelm, Katarina
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Health perceptions of young adults living with recessive limb-girdle muscular dystrophy2016Ingår i: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 72, nr 8, s. 1915-1925Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    The aim of this study was to describe health perceptions related to sense of coherence among young adults living with recessive limb-girdle muscular dystrophy.

    BACKGROUND:

    Limb-girdle muscular dystrophy refers to a group of progressive muscular disorders that may manifest in physical disability. The focus in health care is to optimize health, which requires knowledge about the content of health as described by the individual.

    DESIGN:

    A descriptive study design with qualitative and quantitative data were used.

    METHOD:

    Interviews were conducted between June 2012-November 2013 with 14 participants aged 20-30 years. The participants also answered the 13-item sense of coherence questionnaire. Qualitative data were analysed with content analysis and related to self-rated sense of coherence.

    FINDINGS:

    Health was viewed as intertwined physical and mental well-being. As the disease progressed, well-being was perceived to be influenced not only by physical impairment and mental strain caused by the disease but also by external factors, such as accessibility to support and attitudes in society. Factors perceived to promote health were having a balanced lifestyle, social relations and meaningful daily activities. Self-rated sense of coherence varied. The median score was 56 (range 37-77). Those who scored ≥56 described to a greater extent satisfaction regarding support received, daily pursuits and social life compared with those who scored <56.

    CONCLUSION:

    Care should be person-centred. Caregivers, with their knowledge, should strive to assess how the person comprehends, manages and finds meaning in daily life. Through dialogue, not only physical, psychological and social needs but also health-promoting solutions can be highlighted.

  • 378.
    Aho, Nikolas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Victimization, Prevalence, Health and Peritraumatic Reactions in Swedish Adolescents2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this thesis was to expand the knowledge of victimization in children and youth in Sweden. Victimization, prevalence, health and peritraumatic reactions were explored in a cross sectional, representative sample of 5,960 second grade high school students in Sweden. A computerized survey was developed and administered in class room setting.

    Lifetime victimization was found in 84.1% of the sample (m=83.0%, f=85.2%), and, in relation to the five domains, 66.4% had experienced conventional crime, 24% child maltreatment, 54.4% peer and sibling victimization, 21.8% sexual victimization, and 54% had experienced witness victimization. Females experienced significantly more child maltreatment, peer and sibling victimization, sexual victimization, and witnessed victimization, males more conventional crime (p<0.001). Using logistic regression risk factors for victimization were confirmed by a significant increase OR regarding gender, environment and lack of both parents.

    Symptoms (TSCC), were clearly associated with both victimizations per se and the number of victimizations. The results indicated a relatively linear increase in symptoms with an increase in number of events experienced. Mental health of the polyvictimized group was significantly worse than that of the non-polyvictimized group, with significantly elevated TSCC scores (t<0.001). Hierarchical regression analysis resulted in beta value reduction when polyvictimization was introduced supporting the independent effect on symptoms. Social anxiety was found in 10.2 % (n = 605) of the total group (n = 5,960). A significant gender difference emerged, with more females than males reporting social anxiety. Elevated PTSS was found in 14.8 % (n=883). Binary logistic regression revealed the highest OR for having had contact with child and adolescent psychiatry was found for the combined group with social anxiety and elevated PTSS (OR = 4.88, 95 % CI = 3.53–6.73, p<001). Significant associations were also found between use of child and adolescent psychiatry and female gender (OR = 2.05, 95 % CI = 1.70–2.45), Swedish birth origin (OR = 1.68, 95 % CI = 1.16–2.42) and living in a small municipality (OR = 1.33, 95 % CI = 1.02–1.73).

    Mediation models used peritraumatic reactions (PT): total, physiological arousal (PA), peritraumatic dissociation (PD), and intervention thoughts (IT) and JVQ and TSCC. Of the n=5,332 cases, a total of n=4,483 (84.1%) reported at least one victimizing event (m = 83.0%, f = 85.2%). Of these, 74.9% (n=3,360) also experienced a PT reaction of some kind. The effect mediated by PT tot was b= 0.479, BCa CI [0.342 – 0.640], representing a relatively small effect of 7.6%, κ2=0.076, 95% BCa CI [0.054- 0.101]. The mediating effect of JVQ on TSCC was mediated by PD more for males (b=0.394 BCa CI [0.170-0.636]) than for females (b=0.247, BCa CI [0.021-0.469]). The indirect effect of the JVQ on the TSCC tot mediated by the different PT reactions was significant for PD (b=0.355, BCa CI [0.199- 0.523]. In males a mediating effect of PD could be seen in the different models, while females had a more mixed result. IT did not show any indirect effect in males, but had a mixed effect for females.

    The empirical findings in this thesis lead to the conclusion that victimization is highly prevalent in children and youth and is related to health issues. The association of victimization on symptoms was mediated by peritraumatic reactions. Using a comprehensive instrument such as the JVQ provides the researcher or clinician the opportunity to acquire more complete measurement and also makes it possible to identify polyvictimization, a high-level category of events with severe impact on health.  

    Delarbeten
    1. The Prevalence of Potentially Victimizing Events, Poly-Victimization, and Its Association to Sociodemographic Factors: A Swedish Youth Survey
    Öppna denna publikation i ny flik eller fönster >>The Prevalence of Potentially Victimizing Events, Poly-Victimization, and Its Association to Sociodemographic Factors: A Swedish Youth Survey
    2016 (Engelska)Ingår i: Journal of Interpersonal Violence, ISSN 0886-2605, E-ISSN 1552-6518, Vol. 31, nr 4, s. 620-651Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Studying the extent to which children are exposed to victimizing events is important to fully understand the effect of such exposure in shaping them as adults. The aim of this study was to use self-report by adolescents to measure the prevalence of victimizing events and of poly-victimization. A representative sample of 5,960 students (aged 17) from high schools in Sweden was given the self-administrated version of the Juvenile Victimization Questionnaire (JVQ) along with questions concerning gender, birthplace, parents birthplace and employment, residence, educational program, and municipality size. The results show that 84.1% (83.0% young men and 85.2% young women) of the students had experienced victimization during their lifetime, and 10.3% were categorized as poly-victims (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] = [1.35, 1.94]). Adolescents living with both parents were at lower risk of any form of victimization for both genders, while females were at higher risk of maltreatment, peer victimization, and, most significantly, sexual victimization. In conclusion, the vast majority of young people have been victimized during their lifetime. A greater awareness of the impact of these victimizing events on children and adolescents is important as a basis for providing a safer milieu and establishing better interventions, especially for those that have been victimized on multiple occasions. The high-exposure group was determined by using 10 events as a cutoff. Findings on this group corresponded with findings in other international studies regarding distribution, elevated risk for females, and the possibility of limiting the effects of victimization by modifying living conditions.

    Ort, förlag, år, upplaga, sidor
    SAGE PUBLICATIONS INC, 2016
    Nyckelord
    JVQ; victim; youth; poly-victimization; sociodemographics
    Nationell ämneskategori
    Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:liu:diva-124456 (URN)10.1177/0886260514556105 (DOI)000367838200004 ()25392393 (PubMedID)
    Anmärkning

    Funding Agencies|Crime Victim Compensation and Support Authority in Sweden; Medical Research Council of Southeast Sweden

    Tillgänglig från: 2016-02-02 Skapad: 2016-02-01 Senast uppdaterad: 2018-02-21
    2. Victimization, polyvictimization , and health in Swedish adolescents
    Öppna denna publikation i ny flik eller fönster >>Victimization, polyvictimization , and health in Swedish adolescents
    2016 (Engelska)Ingår i: Adolescent Health, Medicine and Therapeutics, ISSN 1179-318X, Vol. 7, s. 89-99Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization.

    Ort, förlag, år, upplaga, sidor
    Dovepress, 2016
    Nyckelord
    victimization, childhood trauma, psychological symptoms, JVQ, TSCC
    Nationell ämneskategori
    Klinisk medicin Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi Psykiatri Neurovetenskaper
    Identifikatorer
    urn:nbn:se:liu:diva-132626 (URN)10.2147/AHMT.S109587 (DOI)27616895 (PubMedID)
    Tillgänglig från: 2016-11-17 Skapad: 2016-11-17 Senast uppdaterad: 2018-02-21Bibliografiskt granskad
    3. Posttraumatic stress symptoms and mental health services utilization in adolescents with social anxiety disorder and experiences of victimization
    Öppna denna publikation i ny flik eller fönster >>Posttraumatic stress symptoms and mental health services utilization in adolescents with social anxiety disorder and experiences of victimization
    Visa övriga...
    2013 (Engelska)Ingår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 22, nr 3, s. 177-184Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Recent findings from studies on adults show similarities between social anxiety disorder (SAD) and posttraumatic stress in the form of recurrent memories and intrusive and distressing images of earlier aversive events. Further, treatment models for SAD in adults have been successfully developed by using transdiagnostic knowledge on posttraumatic stress symptoms (PTSS). Studies on adolescents are though missing. The present study aimed at exploring the association between PTSS and SAD in Swedish adolescents. A second aim was to study mental health services utilization in relation to these conditions. A total of 5,960 high-school students participated and reported on SAD, life time victimization, PTSS and mental health service utilization. Socially anxious adolescents reported significantly higher levels of PTSS than adolescents not reporting SAD and this difference was seen in victimized as well as non-victimized subjects. Contact with a school counselor was the most common mental health service utilization in subjects with SAD and those with elevated PTSS. In the prediction of contact with a CAP-clinic, significant odds ratios were found for a condition of SAD and elevated PTSS (OR = 4.88, 95 % CI = 3.53–6.73) but not for SAD only. Screening of PTSS in adolescents with SAD is recommended. The service of school counselors is important in detecting and helping young people with SAD and elevated PTSS. Clinical studies on SAD and PTSS in adolescents could aid in modifying treatment models for SAD.

    Ort, förlag, år, upplaga, sidor
    Springer, 2013
    Nyckelord
    Social anxiety disorder, victimization, mental health service utilization, adolescents
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-89939 (URN)10.1007/s00787-012-0336-z (DOI)000315736200005 ()
    Tillgänglig från: 2013-03-11 Skapad: 2013-03-11 Senast uppdaterad: 2018-02-21
  • 379.
    Aho, Nikolas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gren Landell, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    The Prevalence of Potentially Victimizing Events, Poly-Victimization, and Its Association to Sociodemographic Factors: A Swedish Youth Survey2016Ingår i: Journal of Interpersonal Violence, ISSN 0886-2605, E-ISSN 1552-6518, Vol. 31, nr 4, s. 620-651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studying the extent to which children are exposed to victimizing events is important to fully understand the effect of such exposure in shaping them as adults. The aim of this study was to use self-report by adolescents to measure the prevalence of victimizing events and of poly-victimization. A representative sample of 5,960 students (aged 17) from high schools in Sweden was given the self-administrated version of the Juvenile Victimization Questionnaire (JVQ) along with questions concerning gender, birthplace, parents birthplace and employment, residence, educational program, and municipality size. The results show that 84.1% (83.0% young men and 85.2% young women) of the students had experienced victimization during their lifetime, and 10.3% were categorized as poly-victims (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] = [1.35, 1.94]). Adolescents living with both parents were at lower risk of any form of victimization for both genders, while females were at higher risk of maltreatment, peer victimization, and, most significantly, sexual victimization. In conclusion, the vast majority of young people have been victimized during their lifetime. A greater awareness of the impact of these victimizing events on children and adolescents is important as a basis for providing a safer milieu and establishing better interventions, especially for those that have been victimized on multiple occasions. The high-exposure group was determined by using 10 events as a cutoff. Findings on this group corresponded with findings in other international studies regarding distribution, elevated risk for females, and the possibility of limiting the effects of victimization by modifying living conditions.

  • 380.
    Aho, Nikolas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Proczkowska Björklund, Marie
    Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Peritraumatic reactions in relation to trauma exposure and symptoms of posttraumatic stress in high school students2017Ingår i: European Journal of Psychotraumatology, ISSN 2000-8066, E-ISSN 2000-8066, Vol. 8, nr 1, artikel-id 1380998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Exposure to traumatic events is clearly associated with a diversity of subsequent mental health problems, with posttraumatic stress disorder (PTSD) as the most prevalent disorder. Epidemiologically, trauma exposure rates are more prevalent than PTSD, indicating that most trauma victims do not develop PTSD. More knowledge is needed to understand the development of the different posttraumatic pathways including the significance of pretraumatic, peritraumatic and posttraumatic risk factors. Objective: To study peritraumatic reactions in relation to trauma exposure and symptoms of posttraumatic stress and to enhance our understanding of peritraumatic reactions as mediators between trauma and later symptomatology. Method: The study was composed of a representative community sample of 5332 second year high school students (mean age 17.3 years) who completed the Juvenile Victimization Questionnaire (SAQ/JVQ), Trauma Symptom Checklist for Children (TSCC) and answered questions about peritraumatic reactions. Mediation effects of peritraumatic reactions on the trauma exposure relationship to symptoms was tested using the PROCESS macro for SPSS. Results: Traumatic events are common (84.1%) and are accompanied in three-quarters of the students with at least one form of peritraumatic reaction. Peritraumatic reactions, especially peritraumatic dissociative reactions, mediate the relationship between trauma exposure and symptoms, and gender moderates the effect of peritraumatic dissociation. This moderating effect was found to be larger for boys than for girls, indicating gender differences in response to trauma. Conclusions: The results indicate the need to screen for peritraumatic reactions as early as possible after a traumatic event in order to identify those at risk for PTSD.

  • 381.
    Aho, Nikolas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Proczkowska-Björklund, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Victimization, polyvictimization , and health in Swedish adolescents2016Ingår i: Adolescent Health, Medicine and Therapeutics, ISSN 1179-318X, Vol. 7, s. 89-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization.

  • 382.
    Ahsani Ghahreman, Sarang
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier.
    En del av spelet: En studie av fotbollsdomarnas tillvaro i Gästrikland2008Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats
    Abstract [en]

    There is a clear difference between the way football players and leaders regard the role of the referee, compared to the way the refereeing body looks at it. The refereeing body regard themselves as fundamental for the existence of the sport, while the other mentioned parties merely see them as functional justice makers. This view places the referees outside the field of football. This establishes a football culture, which is conflicted when it comes to the role of the referees on the field. The conflict comes to its edge in youth football, where the referees are under severe pressure. The only way for the referees to handle this pressure is through experience and respect, which is essential for creation of a well working referring role. Thus, a change in the football culture is necessary in order to include the referees in the football family and change the general conception of the referees’ role and function.

  • 383.
    Aichhorn, Markus
    et al.
    Graz University of Technology.
    Pourovskii, Leonid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska högskolan.
    Georges, Antoine
    Ecole Polytech.
    Importance of electronic correlations for structural and magnetic properties of the iron pnictide superconductor LaFeAsO2011Ingår i: Physical Review B. Condensed Matter and Materials Physics, ISSN 1098-0121, E-ISSN 1550-235X, Vol. 84, nr 5, s. 054529-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present calculations of structural and magnetic properties of the iron-pnictide superconductor LaFeAsO including electron-electron correlations. For this purpose we apply a fully charge self-consistent combination of density-functional theory with the dynamical mean-field theory, allowing for the calculation of total energies. We find that the inclusion of correlation effects gives a good agreement of the arsenic z position with experimental data even in the paramagnetic (high-temperature) phase. Going to low temperatures, we study the formation of the ordered moment in the striped spin-density-wave phase, yielding an ordered moment of about 0.60 mu(B), again in good agreement with experiments. This shows that the inclusion of correlation effects improves both structural and magnetic properties of LaFeAsO at the same time.

  • 384.
    Aidemark, Jan
    et al.
    Linnaeus University, Sweden.
    Askenas, Linda
    Linnaeus University, Sweden.
    Martensson, Jan
    Jonköping University, Sweden.
    Strömberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Challenges for Heart Failure Patients Self-Care Systems Analysis of Patients Needs2014Ingår i: CENTERIS 2014 - CONFERENCE ON ENTERPRISE INFORMATION SYSTEMS / PROJMAN 2014 - INTERNATIONAL CONFERENCE ON PROJECT MANAGEMENT / HCIST 2014 - INTERNATIONAL CONFERENCE ON HEALTH AND SOCIAL CARE INFORMATION SYSTEMS AND TECHNOLOGIES, Elsevier, 2014, Vol. 16, s. 1256-1264Konferensbidrag (Refereegranskat)
    Abstract [en]

    Self-care is important for heart failure patients. However, what are the views of patients on their situation when it comes to realizing self-care? The aim of the paper is to investigate the self-care needs of HF patients, by understanding the issues they embrace in their self-care processes. In this paper we make a review of 17 interviews and make a classification of what the needs are for possible information technology support systems. Based on the analysis of these interviews, we identify the diversity of needs in support of activities related to different background conditions and the dynamics of change of learning and changes in the heart failure condition. The contribution of the paper is a framework for understanding the diversity of needs and the specific situations of this group of patients.

  • 385.
    Aidemark, Jan
    et al.
    Linnaeus University, Sweden.
    Askenas, Linda
    Linnaeus University, Sweden.
    Nygardh, Anette
    Jonköping University, Sweden.
    Strömberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    User involvement in the co-design of self-care support systems for heart failure patients2015Ingår i: CONFERENCE ON ENTERPRISE INFORMATION SYSTEMS/INTERNATIONAL CONFERENCE ON PROJECT MANAGEMENT/CONFERENCE ON HEALTH AND SOCIAL CARE INFORMATION SYSTEMS AND TECHNOLOGIES, CENTERIS/PROJMAN / HCIST 2015, ELSEVIER SCIENCE BV , 2015, Vol. 64, s. 118-124Konferensbidrag (Refereegranskat)
    Abstract [en]

    In this paper the nature of user involvement in a co-design process will be explored. The outlines of a research project aiming at developing support systems for self-care inpatients suffering from chronic heart failure will be presented. The project is planned to perform a co-design effort where users (patients and healthcare professionals) will be given the opportunity to influence the development of support systems. We will discuss a number of possibilities and challenges that lie in the design of this kind of project and also some findings from its early stages. This report presents the experiences of users input, which are discussed in the context of previous research on benefits of user contributions in systems development. (C) 2015 The Authors. Published by Elsevier B.V.

  • 386.
    Aifa, Sami
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Aydin, J
    Nordvall, G
    Lundström, Ingemar
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Svensson, Samuel
    Hermanson, O
    A basic peptide within the juxtamembrane region is required for EGF receptor dimerization2005Ingår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 302, nr 1, s. 108-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is fundamental for normal cell growth and organ development, but has also been implicated in various pathologies, notably tumors of epithelial origin. We have previously shown that the initial 13 amino acids (P13) within the intracellular juxtamembrane region (R645-R657) are involved in the interaction with calmodulin, thus indicating an important role for this region in EGFR function. Here we show that P13 is required for proper dimerization of the receptor. We expressed either the intracellular domain of EGFR (TKJM) or the intracellular domain lacking P13 (ΔTKJM) in COS-7 cells that express endogenous EGFR. Only TKJM was immunoprecipitated with an antibody directed against the extracellular part of EGFR, and only TKJM was tyrosine phosphorylated by endogenous EGFR. Using SK-N-MC cells, which do not express endogenous EGFR, that were stably transfected with either wild-type EGFR or recombinant full-length EGFR lacking P13 demonstrated that P13 is required for appropriate receptor dimerization. Furthermore, mutant EGFR lacking P13 failed to be autophosphorylated. P13 is rich in basic amino acids and in silico modeling of the EGFR in conjunction with our results suggests a novel role for the juxtamembrane domain (JM) of EGFR in mediating intracellular dimerization and thus receptor kinase activation and function. © 2004 Elsevier Inc. All rights reserved.

  • 387. Aifa, Sami
    et al.
    Johansen, Knut
    Nilsson, Ulrica K
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Lundström, Ingemar
    Svensson, Samuel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance2002Ingår i: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 14, nr 12, s. 1005-1013Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One early response to epidermal growth factor receptor (EGFR) activation is an increase in intracellular calcium. We have used surface plasmon resonance (SPR) to study real-time interactions between the intracellular juxtamembrane (JM) region of EGFR and calmodulin. The EGFR-JM (Met644-Phe688) was expressed as a GST fusion protein and immobilised on a sensor chip surface. Calmodulin specifically interacts with EGFR-JM in a calcium-dependent manner with a high on and high off rate. Chemical modification of EGFR-JM by using arginine-selective phenylglyoxal or deletion of the basic segment Arg645-Arg657 inhibits the interaction. Phosphorylation of EGFR-JM by protein kinase C (PKC) or glutamate substitution of Thr654 inhibits the interaction, suggesting that PKC phosphorylation electrostatically interferes with calmodulin binding to basic arginine residues. Calmodulin binding was also inhibited by suramin. Our results suggest that EGFR-JM is essential for epidermal growth factor (EGF)-mediated calcium-calmodulin signalling and for signal integration between other signalling pathways.

  • 388.
    Aifa, Sami
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Miled, N
    Frikha, F
    Aniba, MR
    Svensson, Samuel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Rebai, A
    Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation2006Ingår i: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 62, nr 4, s. 1036-1043Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mechanism by which ligand-activated EGFR induces autophosphorylation via dimerization is not fully understood. Structural studies have revealed an extracellular loop mediated receptor dimerization. We have previously presented experimental data showing the involvement of a positive 13 amino acid peptide (R645-R657, P13+) from the intracellular juxtamembrane domain (JM) of EGFR important for intracellular dimerization and autophosphorylation. A model was presented that suggest that P13+ interacts with a negative peptide (D979-E991, P13-) positioned distal to the tyrosine kinase domain in the opposite EGFR monomer. The present work shows additional data strengthening this model. In fact, by analyzing protein sequences of 21 annotated ErbB proteins from 9 vertebrate genomes, we reveal the high conservation of peptides P13+ and P13- with regard to their sequence as well as their position relative to the tyrosine kinase (TK) domain. Moreover in silico structure modeling of these ErbB intracellular domains supports a general electrostatic P13+/P13- interaction, implying that the C-terminal of one receptor monomer is facing the TK domain of the other monomer in the receptor dimer and vice versa. This model provides new insights into the molecular mechanism of ErbB receptor activation and suggests a new strategy to pharmacologically interfering with ErbB receptor activity. © 2005 Wiley-Liss, Inc.

  • 389.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Polypeptide-Based Nanoscale Materials2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Self-assembly has emerged as a promising technique for fabrication of novel hybrid materials and nanostructures. The work presented in this thesis has been focused on developing nanoscale materials based on synthetic de novo designed polypeptides. The polypeptides have been utilized for the assembly of gold nanoparticles, fibrous nanostructures, and for sensing applications.

    The 42-residue polypeptides are designed to fold into helix-loop-helix motifs and dimerize to form four-helix bundles. Folding is primarily driven by the formation of a hydrophobic core made up by the hydrophobic faces of the amphiphilic helices. The peptides have either a negative or positive net charge at neutral pH, depending on the relative abundance of Glu and Lys. Charge repulsion thus prevents homodimerization at pH 7 while promoting hetero-dimerization through the formation of stabilising salt bridges. A Cys incorporated in position 22, located in the loop region, allowed for directed, thiol-dependent, immobilization on planar gold surfaces and gold nanoparticles. The negatively charged (Glu-rich) peptide formed homodimers and folded in solution at pH < 6 or in the presence of certain metal ions, such as Zn2+. The folding properties of this peptide were retained when immobilized directly on gold, which enabled reversible assembly of gold nanoparticles resulting in aggregates with well-defined interparticle separations. Particle aggregation was found to induce folding of the immobilized peptides but folding could also be utilized to induce aggregation of the particles by exploiting the highly specific interactions involved in both homodimerization and hetero-association. The possibility to control the assembly of polypeptide-functionalized gold nanoparticles was utilized in a colorimetric protein assay. Analyte binding to immobilized ligands prevented the formation of dense particle aggregates when subjecting the particles to conditions normally causing extensive aggregation. Analyte binding could hence easily be distinguished by the naked eye. Moreover, the peptides were utilized to assemble gold nanoparticles on planar gold and silica substrates.

    Fibrous nanostructures were realized by linking monomers through a disulphide-bridge. The disulphide-linked peptides were found to spontaneously assemble into long and extremely thin peptide fibres as a result of a propagating association mediated by folding into four-helix bundles.

    Delarbeten
    1. Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Öppna denna publikation i ny flik eller fönster >>Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Visa övriga...
    2005 (Engelska)Ingår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, nr 6, s. 2480-2487Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Designed, synthetic polypeptides that assemble into four-helix bundles upon dimerization in solution were studied with respect to folding on planar gold surfaces. A model system with controllable dimerization properties was employed, consisting of negatively and positively charged peptides. Circular dichroism spectroscopy and surface plasmon resonance based measurements showed that at neutral pH, the peptides were able to form heterodimers in solution, but unfavorable electrostatic interactions prevented the formation of homodimers. The dimerization propensity was found to be both pH- and buffer-dependent. A series of infrared absorption−reflection spectroscopy experiments of the polypeptides attached to planar gold surfaces revealed that if the negatively charged peptide was immobilized from a loading solution where it was folded, its structure was retained on the surface provided it had a cysteine residue available for anchoring to gold. If it was immobilized as random coil, it remained unstructured on the surface but was able to fold through heterodimerization if subsequently exposed to a positively charged polypeptide. When the positively charged peptide was immobilized as random coil, heterodimerization could not be induced, probably because of high-affinity interactions between the charged primary amine groups and the gold surface. These observations are intended to pave the way for future engineering of functional surfaces based on polypeptide scaffolds where folding is known to be crucial for function.

    Ort, förlag, år, upplaga, sidor
    ACS Publications, 2005
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-15115 (URN)10.1021/la048029u (DOI)
    Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    2. Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
    Öppna denna publikation i ny flik eller fönster >>Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
    Visa övriga...
    2006 (Engelska)Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, nr 7, s. 2194 -2195Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

    Ort, förlag, år, upplaga, sidor
    ACS Publications, 2006
    Nyckelord
    Not aviable
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14041 (URN)10.1021/ja057056j (DOI)
    Tillgänglig från: 2006-09-28 Skapad: 2006-09-28 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    3. Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
    Öppna denna publikation i ny flik eller fönster >>Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
    Visa övriga...
    2008 (Engelska)Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, nr 17, s. 5780-5788Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

    Ort, förlag, år, upplaga, sidor
    ACS Publications, 2008
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-15116 (URN)10.1021/ja711330f (DOI)
    Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    4. Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
    Öppna denna publikation i ny flik eller fönster >>Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
    Visa övriga...
    2008 (Engelska)Ingår i: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, s. 688506-1-688506-8Konferensbidrag, Publicerat paper (Refereegranskat)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

    Nyckelord
    Heterodimerization, polypeptides, gold nanoparticles, four-helix bundle, helix-loop-helix, self-assembly
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-15118 (URN)10.1117/12.775806 (DOI)
    Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    5. Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
    Öppna denna publikation i ny flik eller fönster >>Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
    Visa övriga...
    2008 (Engelska)Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 47, nr 30, s. 5554-5556Artikel i tidskrift (Refereegranskat) Published
    Ort, förlag, år, upplaga, sidor
    Wiley InterScience, 2008
    Nyckelord
    fibers, helical structures, nanostructures, polypeptides, self-assembly
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-15120 (URN)10.1002/anie.200801155 (DOI)
    Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    6. Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    Öppna denna publikation i ny flik eller fönster >>Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    2008 (Engelska)Ingår i: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 8, nr 8, s. 2473-2478Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Gold nanoparticles were functionalized with a synthetic polypeptide, de novo-designed to associate with a charge complementary linker polypeptide in a folding-dependent manner. A heterotrimeric complex that folds into two disulphide-linked four-helix bundles is formed when the linker polypeptide associates with two of the immobilized peptides. The heterotrimer forms in between separate particles and induces a rapid and extensive aggregation with a well-defined interparticle spacing. The aggregated particles are redispersed when the disulphide bridge in the linker polypeptide is reduced.

    Ort, förlag, år, upplaga, sidor
    ACS Publications, 2008
    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:liu:diva-15121 (URN)10.1021/nl8014796 (DOI)
    Anmärkning
    The original title of this article was "Assembly of Decorated Gold Nanoparticles through a Hetero-Association and Folding-Dependent Bridging".Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2017-12-07
    7. Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
    Öppna denna publikation i ny flik eller fönster >>Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
    Visa övriga...
    2009 (Engelska)Ingår i: Small, ISSN 1613-6810, Vol. 5, nr 21, s. 2445-2452Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A strategy for colorimetric sensing of proteins, based on the induced assembly of polypeptide-functionalized gold nanoparticles, is described. Recognition was accomplished using a polypeptide sensor scaffold designed to specifically bind the model analyte, human carbonic anhydrase II (HCAII). The extent of particle aggregation, induced by the Zn2+-triggered dimerization and folding of a second polypeptide also present on the surface of the gold nanoparticle, gave a readily detectable colorimetric shift that was dependent on the concentration of the target protein. In the absence of HCAII, particle aggregation resulted in a major redshift of the plasmon peak whereas analyte binding prevented formation of dense aggregates, significantly reducing the magnitude of the redshift. The limit of detection of HCAII was estimated to be around 15 nM. The versatility of the technique was demonstrated using a second model system based on the recognition of a peptide sequence from the tobacco mosaic virus coat protein (TMVP by a recombinant antibody fragment. This strategy is proposed as a generic platform for robust and specific protein analysis that can be further developed for monitoring a wide range of target proteins.

    Nyckelord
    Not available.
    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:liu:diva-15122 (URN)10.1002/smll.200900530 (DOI)
    Tillgänglig från: 2008-10-16 Skapad: 2008-10-16 Senast uppdaterad: 2019-01-22Bibliografiskt granskad
  • 390.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Nesterenko, Irina
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Björefors, Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Division of Organic Chemistry, Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala University, SE-751 24 Uppsala, Sweden..
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds2008Ingår i: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, s. 688506-1-688506-8Konferensbidrag (Refereegranskat)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

  • 391.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Nesterenko, Irina
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Björefors, Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala UniVersity, SE-751 24 Uppsala, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles2008Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, nr 17, s. 5780-5788Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

  • 392.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Tai, Feng-I
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Department of Biochemistry andOrganic Chemistry Uppsala University, BMC, Box 576, 75123 Uppsala, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides2008Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 47, nr 30, s. 5554-5556Artikel i tidskrift (Refereegranskat)
  • 393.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Lundström, Ingemar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles2006Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, nr 7, s. 2194 -2195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

  • 394.
    Aili, Daniel
    et al.
    University of London Imperial College of Science Technology and Medicine.
    Gryko, Piotr
    University of London Imperial College of Science Technology and Medicine.
    Sepulveda, Borja
    Research Centre Nanosci and Nanotechnol CIN2 CSIC.
    Dick, John A. G.
    University of London Imperial College of Science Technology and Medicine.
    Kirby, Nigel
    Australian Synchrotron.
    Heenan, Richard
    Rutherford Appleton Lab.
    Baltzer, Lars
    Uppsala University.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Ryan, Mary P.
    University of London Imperial College of Science Technology and Medicine.
    Stevens, Molly M.
    University of London Imperial College of Science Technology and Medicine.
    Polypeptide Folding-Mediated Tuning of the Optical and Structural Properties of Gold Nanoparticle Assemblies2011Ingår i: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 11, nr 12, s. 5564-5573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, we present a detailed characterization using UV-vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix-loop-helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8 +/- 0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies.

  • 395.
    Aili Fagerholm, Siri
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Insulin signaling in primary adipocytes in insulin sensitive and insulin resistant states2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Increasing numbers of people world-wide develops the disease type 2 diabetes. Development of type 2 diabetes is characterized by a shift from an insulin sensitive state to an insulin resistant state in peripheral insulin responding organs, which originates from the development of insulin resistance in the adipose tissue. Insulin resistance in combination with reduced pancreatic insulin secretion lead to overt type 2 diabetes.

    In this thesis, the insulin signaling network in primary adipocytes was analyzed. Key proteins and mechanisms were studied to gain deeper knowledge of signaling both in the insulin sensitive state and in the insulin resistant state produced by rapid weight gain as well as in type 2 diabetes.

    The surface of the adipocyte is dotted with invaginations in the cell membrane called caveolae that act as important metabolic and signaling platforms in adipocytes, and also harbor the insulin receptor. In paper I we show that insulin stimulation of primary adipocytes results in a rapid phosphorylation of the insulin receptor and caveolin-1, and that internalization of the proteins is mediated by endocytosis of caveolae.

    Weight gain due to overfeeding and obesity has been associated with the development of insulin resistance in insulin sensitive tissues such as the adipose tissue. In paper II we show that short-term overfeeding for one month of lean subjects results in an insulin resistant state. At the end of the study, the subjects had developed a mild systemic insulin resistance. Moreover, in isolated subcutaneous adipocytes we found several alterations of the insulin signaling pathway that mimicked alterations found in isolated subcutaneous adipocytes from subjects with type 2 diabetes.

    In paper III we present a first dynamic mathematical model of the insulin signaling network in human adipocytes that are based on experimental data acquired in a consistent fashion. The model takes account of insulin signaling in both the healthy, insulin sensitive state and in the insulin resistant state of type 2 diabetes. We show that attenuated mTORC1-mediated positive feedback to control of phosphorylation of IRS1 at Ser307 is an essential component of the insulin resistant state of type 2 diabetes. A future application of the model is the identification and evaluation of drug targets for the treatment of insulin resistance and type 2 diabetes.

    In paper IV we examine the protein kinase that catalyzes the insulin stimulated mTORC1- mediated feedback to IRS1. We find that the phosphorylation of IRS1 at Ser307 is not likely to be catalyzed by the kinases S6K1, mTOR or PKB. However, a catalyzing protein kinase for the in vitro phosphorylation of IRS1 at Ser307 was found to be associated with the complex mTORC1.

    In conclusion, this thesis provide new insights and characterize mechanisms of the intrinsically complex insulin signaling network of primary adipocytes, both in insulin sensitive and insulin resistant states.

    Delarbeten
    1. Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
    Öppna denna publikation i ny flik eller fönster >>Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
    Visa övriga...
    2009 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 4, nr 6, s. e5985-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: The insulin receptor is localized in caveolae and is dependent on caveolae or cholesterol for signaling in adipocytes. When stimulated with insulin, the receptor is internalized. Methodology/Principal Findings: We examined primary rat adipocytes by subcellular fractionation to examine if the insulin receptor was internalized in a caveolae-mediated process. Insulin induced a rapid, t1/2 less than3 min, endocytosis of the insulin receptor in parallel with receptor tyrosine autophosphorylation. Concomitantly, caveolin-1 was phosphorylated at tyrosine(14) and endocytosed. Vanadate increased the phosphorylation of caveolin-1 without affecting insulin receptor phosphorylation or endocytosis. Immunocapture of endosomal vesicles with antibodies against the insulin receptor co-captured caveolin-1 and immunocapture with antibodies against tyrosine(14)-phosphorylated caveolin-1 co-captured the insulin receptor, demonstrating that the insulin receptor was endocytosed together with tyrosine(14)-phosphorylated caveolin-1. By immunogold electron microscopy the insulin receptor and caveolin-1 were colocalized in endosome vesicles that resembled caveosomes. Clathrin was not endocytosed with the insulin receptor and the inhibitor of clathrin-coated pit-mediated endocytosis, chlorpromazine, did not inhibit internalization of the insulin receptor, while transferrin receptor internalization was inhibited. Conclusion: It is concluded that in response to insulin stimulation the autophosphorylated insulin receptor in primary adipocytes is rapidly endocytosed in a caveolae-mediated process, involving tyrosine phosphorylation of caveolin-1.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-21319 (URN)10.1371/journal.pone.0005985 (DOI)
    Anmärkning
    Original Publication: Siri Fagerholm, Unn Örtegren Kugelberg, M. Karlsson, I. Ruishalme and Peter Strålfors, Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes, 2009, PLoS ONE, (4), 6, e5985. http://dx.doi.org/10.1371/journal.pone.0005985 Tillgänglig från: 2009-09-30 Skapad: 2009-09-30 Senast uppdaterad: 2013-07-08
    2. Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
    Öppna denna publikation i ny flik eller fönster >>Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
    Visa övriga...
    2009 (Engelska)Ingår i: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 15, nr 7-8, s. 228-234Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-20893 (URN)10.2119/molmed.2009.00037 (DOI)000276043800004 ()
    Tillgänglig från: 2009-09-24 Skapad: 2009-09-24 Senast uppdaterad: 2019-06-28
    3. Insulin Signaling in Type 2 Diabetes: Experimental and Modeling Analyses Reveal Mechanisms of Insulin Resistance in Human Adipocytes
    Öppna denna publikation i ny flik eller fönster >>Insulin Signaling in Type 2 Diabetes: Experimental and Modeling Analyses Reveal Mechanisms of Insulin Resistance in Human Adipocytes
    Visa övriga...
    2013 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, nr 14, s. 9867-9880Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems-level mechanistic understanding of insulin resistance in humans. We developed a dynamic mathematical model of insulin signaling – normally and in diabetes – based on quantitative steady-state and dynamic time-course data on signaling intermediaries in human mature adipocytes. At the core of insulin resistance is attenuation of a positive feedback from mammalian target of rapamycin in complex with raptor (mTORC1) to the insulin receptor substrate-1 (IRS1), which explains reduced sensitivity and signal strength throughout the signaling network. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84999 (URN)10.1074/jbc.M112.432062 (DOI)000317114000027 ()
    Tillgänglig från: 2012-10-30 Skapad: 2012-10-30 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    4. Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
    Öppna denna publikation i ny flik eller fönster >>Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
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    2013 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 4Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 phosphorylation on tyrosine residues by the insulin receptor. This in turn directly affects downstream signaling and is in human adipocytes implicated in the pathogenesis of insulin resistance and type 2 diabetes. The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). The mTORC1-downstream p70 ribosomal protein S6 kinase (S6K1), which is activated by insulin, can phosphorylate IRS1 at serine 307 in vitro and is considered the physiological protein kinase. Because the IRS1 serine 307-kinase catalyzes a critical step in the control of insulin signaling and constitutes a potential target for treatment of insulin resistance, it is important to know whether S6K1 is the physiological serine 307-kinase or not. We report that, by several criteria, S6K1 does not phosphorylate IRS1 at serine 307 in response to insulin in intact human primary adipocytes: (i) The time-courses for phosphorylation of S6K1 and its phosphorylation of S6 are not compatible with the phosphorylation of IRS1 at serine 307; (ii) A dominant-negative construct of S6K1 inhibits the phosphorylation of S6, without effect on the phosphorylation of IRS1 at serine 307; (iii) The specific inhibitor of S6K1 PF-4708671 inhibits the phosphorylation of S6, without effect on phosphorylation of IRS1 at serine 307. mTOR-immunoprecipitates from insulin-stimulated adipocytes contains an unidentified protein kinase specific for phosphorylation of IRS1 at serine 307, but it is not mTOR or S6K1.

    Ort, förlag, år, upplaga, sidor
    Public Library of Science, 2013
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-93257 (URN)10.1371/journal.pone.0059725 (DOI)000317717300032 ()
    Anmärkning

    Funding Agencies|Swedish Diabetes Fund||Novo Nordic Foundation||University of Linkoping||Swedish Research Council||

    Tillgänglig från: 2013-05-28 Skapad: 2013-05-28 Senast uppdaterad: 2019-06-28
  • 396.
    Ainsbury, Elizabeth A.
    et al.
    Publ Hlth England, England.
    Samaga, Daniel
    Bundesamt Strahlenschutz, Germany.
    Della Monaca, Sara
    Ist Super Sanita, Italy.
    Marrale, Maurizio
    Univ Palermo, Italy; Univ Palermo, Italy.
    Bassinet, Celine
    Inst Radioprotect and Surete Nucl, France.
    Burbidge, Christopher I.
    Environm Protect Agcy, Ireland.
    Correcher, Virgilio
    Ctr Moncloa, Spain.
    Discher, Michael
    Univ Salzburg, Austria.
    Eakins, Jon
    Publ Hlth England, England.
    Fattibene, Paola
    Ist Super Sanita, Italy.
    Guclu, Inci
    Turkish Atom Energy Commiss, Turkey.
    Higueras, Manuel
    Basque Ctr Appl Math, Spain.
    Lund, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Maltar-Strmecki, Nadica
    Rudjer Boskovic Inst, Croatia.
    McKeever, Stephen
    Oklahoma State Univ, OK 74078 USA.
    Raaf, Christopher L.
    Lund Univ, Sweden.
    Sholom, Sergey
    Oklahoma State Univ, OK 74078 USA.
    Veronese, Ivan
    Univ Milan, Italy; Natl Inst Nucl Phys, Italy.
    Wieser, Albrecht
    Helmholtz Zentrum Munchen, Germany.
    Woda, Clemens
    Helmholtz Zentrum Munchen, Germany.
    Trompier, Francois
    Inst Radioprotect and Surete Nucl, France.
    UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS2018Ingår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 178, nr 4, s. 382-404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the EURADOS Working Group 10-Retrospective dosimetry members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.

  • 397.
    Aira, Naomi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Andersson, Anna-Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Singh, Susmita K.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Mckay, Derek M.
    University of Calgary, Canada.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response2017Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 3, artikel-id e0005390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.

  • 398.
    Aittomaki, K.
    et al.
    Aittomäki, K., Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland, Department of Clinical Genetics, Helsinki University Central Hospital, POB 140, FI-00029 HUS Helsinki, Finland.
    Bergh, C.
    Department of Obstetrics, Institute of Women and Children's Health, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hazekamp, J.
    Department of Reproductive Medicine, Volvat Medical Center, Oslo, Norway.
    Nygren, K.-G.
    IVF Clinic, Sophiahemmet, Stockholm, Sweden.
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Soderstrom-Anttila, V.
    Söderström-Anttila, V., Infertility Clinic, Family Federation of Finland, Helsinki, Finland.
    Wennerholm, U.-B.
    Department of Obstetrics, Institute of Women and Children's Health, Sahlgrenska University Hospital, Göteborg, Sweden.
    Genetics and assisted reproduction technology2005Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, nr 5, s. 463-473Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In the past 20 years, a significant improvement has been shown in the treatment for infertility in both women and men through the development of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Only donated sperm could be previously used for treatment, now oocytes can also be donated. Furthermore, the combination of IVF and ICSI with advanced genetic methods has made preimplantation genetic diagnosis possible for many genetic conditions. These methods enable genetic testing of the early human embryo by using only a single cell, one blastomere biopsied from the embryo, as the sample from which the diagnosis of many chromosome rearrangements and other inherited diseases can be made. It has also been established that a considerable proportion of infertility is caused by genetic defects, which have several implications for infertility treatment. The purpose of this review is to give a concise introduction on how genetics is involved in assisted reproduction technology to specialists who may not be working in this particular field of gynecology, but who would need some knowledge of this for proper care of their patients. © Acta Obstet Gynecol Scand (2005).

  • 399. Aittomäki, K
    et al.
    Wennerholm, U-B
    Bergh, C
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Hazekamp, J
    Nygren, K-G
    Safety issues in assisted reproduction technology. Should ICSI patients have genetic testing before treatment? A practical proposition to help patient information2004Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 19, nr 3, s. 472-476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 × 106/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.

  • 400.
    Aittoniemi, J
    et al.
    Klin mikro Tampere, Finland.
    Turpeinen, H
    Virologen Turku, Finland.
    Tiitanen, M
    National Public Health Institute Helsinki, Finland.
    Knip, M
    Hospital for Children and Adolescents Helsinki, Finland.
    Simell, O
    Paediatrics Turku, Finland.
    Ilonen, J
    Virologen Turku, Finland.
    Vaarala, Outi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children2008Ingår i: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 69, nr 2, s. 108-111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of β-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for ≥3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28, p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency. © 2008 American Society for Histocompatibility and Immunogenetics.

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