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  • 247001.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Endocrine surgery.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Endocrine surgery.
    Carcinoid tumors2006In: General Surgery: Principles and International Practice, Springer 2006 , 2006Chapter in book (Other scientific)
  • 247002.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Genetic syndromes associated with adrenal tumors2003Chapter in book (Other (popular scientific, debate etc.))
  • 247003.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Primary hyperparathyroidism2004In: Curr Opin Oncol, Vol. 16, no 1, p. 1-7Article in journal (Refereed)
  • 247004.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Small bowel neuroendocrine tumors.2001Chapter in book (Other scientific)
  • 247005.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgery on neuroendocrine tumours2007In: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism, ISSN 1521-690X, E-ISSN 1532-1908, Vol. 21, no 1, p. 87-109Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours of the gastrointestinal tract and pancreas present a major challenge to physicians in their recognition and treatment requirements, and surgical treatment of these tumours has become increasingly important for symptom palliation and survival. For some carcinoid tumours the extent of surgery may depend on tumour size. Midgut carcinoid is the most common cause of the carcinoid syndrome, requiring surgery for primary and mesenteric tumours to minimize the risk for abdominal complications but also for removal of liver metastases to palliate hormonal symptoms. Among endocrine pancreatic tumours, insulinoma and gastrinoma often cause severe symptoms of hormone excess despite their inconspicuous size, but they can be successfully removed with improved pre- and intraoperative localization. Other tumours--glucagonoma, VIPoma, and non-functioning endocrine pancreatic tumours--are often large or metastasizing, but generally require surgical debulking to alleviate hormonal symptoms and have favourable survival.

  • 247006.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical aspects of neuroendocrine tumours2009In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 45, no Suppl 1, p. 237-50Article in journal (Refereed)
  • 247007.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Parathyroid carcinoma2009In: Clinical endocrine oncology / [ed] Ian D. Hay & John A.H. Wass, Malden: Blackwell Publishing , 2009, 2, p. 180-184Chapter in book (Other (popular science, discussion, etc.))
  • 247008.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Gastrointestinal carcinoids2009In: Endocrine surgery: A companion to specialist surgical practice / [ed] Tom W.J. Lennard, London: Saunders , 2009, p. 163-169Chapter in book (Other (popular science, discussion, etc.))
  • 247009.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gastrointestinal carcinoids2005In: Endocrine Surgery, Elsevier Ltd Edinburgh , 2005, p. 163-197Chapter in book (Other scientific)
  • 247010.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Midgut carcinoid tumours: surgical treatment and prognosis2005In: Best Pract Res Clin Gastroenterol, Vol. 19, p. 717-728Article in journal (Refereed)
  • 247011.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Osmak, Liliana
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Management of midgut carcinoids2005In: J Surg Oncol, Vol. 89, no 3, p. 161-169Article in journal (Other (popular scientific, debate etc.))
  • 247012.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Osmak, Liliana
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Surgical treatment of endocrine pancreatic tumours2004In: Neuroendocrinology, Vol. 80, no suppl 1, p. 62-66Article, review/survey (Other (popular scientific, debate etc.))
  • 247013.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Segersten, Ulrika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Westin, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Parathyroid glands in calcium regulation and human disease2005In: Trends in Comparative Endocrinology and Neurobiology, ISSN 0077-8923, Vol. 1040, p. 53-58Article, review/survey (Other (popular scientific, debate etc.))
  • 247014.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Carcinoid: Presentation and diagnosis surgical managment2009In: Endocrine surgery: Principles and practice / [ed] Johnathan G.H. Hubbard, William B. Inabnet & Chung-Yau Lo, London: Springer , 2009, p. 585-598Chapter in book (Other academic)
  • 247015.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Carcinoid tumors2004In: A Companion to Specialist Surgical Practice: Endocrine Surgery, Elsevier Ltd Edinburgh , 2004Chapter in book (Other scientific)
  • 247016.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences. endokrin tumörbiologi.
    Pancreatic tumours as part of the MEN-1 syndrome.2005In: Best Practice & Research Clinical Endocrinology & Metabolism, Elsevier , 2005Chapter in book (Other scientific)
  • 247017.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences.
    Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN12002In: Langenbeck's Archives of Surgery, Vol. 386, p. 558-569Article in journal (Refereed)
  • 247018.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Juhlin, Claes
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Papillary thyroid carcinoma1995In: Curr Surg, Vol. 52, p. 69-Article in journal (Refereed)
  • 247019.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Juhlin, Claes
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Surgical treatment of secondary hyperparathyroidism1996In: Acta Chir Austriaca, Vol. 124, p. 26-Article in journal (Refereed)
  • 247020.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Juhlin, Claes
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    The surgical treatment of multiglandular parathyroid disease2002In: Thyroid and Parathyroid Surgery, Elsevier , 2002Chapter in book (Other scientific)
  • 247021.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ljunghall, Sverker
    Department of Medical Sciences.
    Lundgren, Ewa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Natural history of untreated primary hyperparathyroidism1997In: Textbook of Endocrine surgery, W B Saunders company , 1997, p. 303-Chapter in book (Other scientific)
  • 247022.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Lundgren, Ewa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Natural history of untreated primary hyperparathyroidism2005In: Textbook of Endocrine Surgery, 2005Chapter in book (Other (popular scientific, debate etc.))
  • 247023.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Lundgren, Ewa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Primary hyperparathyroidism.2001Chapter in book (Other scientific)
  • 247024.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences. Endokrin tumörbiologi.
    Rastad, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Familial hyperparthyroidism1994In: Current controversy in parathyroid operation adn reoperation, 1994, p. 115-130Chapter in book (Refereed)
  • 247025.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical Management of MEN-1 and -2: State of the Art2009In: Surgical Clinics of North America, ISSN 0039-6109, E-ISSN 1558-3171, Vol. 89, no 5, p. 1047-1068Article, review/survey (Refereed)
    Abstract [en]

    Multiple endocrine neoplasia syndrome type 1 (MEN-1) consists of endocrine tumors of the parathyroid, the endocrine pancreas-duodenum, and the pituitary. Surveillance and screening for the endocrinopathies is recommended in gene carriers. Surgery for MEN-1-related hyperparathyroidism is generally performed as radical subtotal parathyroidectomy, because less surgery is likely to result in persistent or recurrent disease. Multiple endocrine neoplasia syndrome type 2 (MEN-2) consists of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Prophylactic thyroidectomy based on DNA testing in the MEN-2 syndrome is considered one of the greater achievements in cancer treatment, because it may be performed before thyroid carcinoma development and provides cure for the patient.

  • 247026.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical Management of Multiglandular Parathyroid Disease2013In: Surgery of the Thyroid and Parathyroid Glands / [ed] Gregory W. Randolph, Philadelphia: Saunders Elsevier, 2013, 2, p. 620-638Chapter in book (Other academic)
    Abstract [en]

    In 1934, Albright et al.[1] discovered the unusual entity of parathyroid water-clear–cell hyperplasia and thought this resulted from some form of extrinsic glandular stimulation. The more common parathyroid chief-cell hyperplasia was described in 1958 by Cope et al.[2] and was believed to have a similar genesis. However, stimulating agents causing the disease have still not been identified in sporadic parathyroid hyperplasia, in contrast to hyperparathyroidism (HPT) secondary to uremia or long-term lithium therapy (see  Chapter 66, Surgical Management of Secondary and Tertiary Hyperparathyroidism). Despite the fact that they represent a minority among HPT patients, ever since the early days of parathyroid surgery cases of parathyroid hyperplasia have continued to intrigue pathologists and parathyroid surgeons (see  Chapter 70, Surgical Pathology of the Parathyroid Glands). Hyperplasia is easily …

  • 247027.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical managment of MEN 1 and MEN 2: State of the art2009In: Endocrine surgery / [ed] Martha A. Zeiger & Ronald F. Martin, Philadelphia: Saunders , 2009, p. 1047-1068Chapter in book (Other (popular science, discussion, etc.))
  • 247028.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Natural History of untreated primary hyperparathyroidism2016In: Textbook of Endocrine Surgery: / [ed] Dr. Orlo H Clark MD, Dr. Quan-Yang Duh MD, Dr. Electron Kebebew MD, Dr. Jessica E Gosnell MD and Dr. Wen T Shen MA MD, Jaypee Brothers Medical Publishers , 2016, 3Chapter in book (Refereed)
  • 247029.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Resection of Small intestinal neuroendocrine tumors2016In: Atlas of endocrine surgical techniques / [ed] Sally E Carty, Jaypee Brothers Medical Publishers , 2016Chapter in book (Refereed)
  • 247030.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 12012In: Clinics, ISSN 1807-5932, E-ISSN 1980-5322, Vol. 67, no S 1, p. 173-178Article, review/survey (Refereed)
    Abstract [en]

    Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple endocrine neoplasia syndrome type 1, and have a pronounced effect on life expectancy as the principal cause of disease-related death. Previous discussions about surgical management have focused mainly on syndromes of hormone excess and, in particular, the management of multiple endocrine neoplasia syndrome type 1-related Zollinger-Ellison syndrome. Since hormonal syndromes tend to occur late and indicate the presence of metastases, screening with biochemical markers and endoscopic ultrasound is recommended for early detection of pancreatico-duodenal tumors, and with early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in the absence of disseminated liver metastases. The suggested operation includes distal 80% subtotal pancreatic resection together with enucleation of tumors in the head of the pancreas, and in cases with Zollinger-Ellison syndrome, excision of duodenal gastrinomas together with clearance of regional lymph node metastases. This strategy, with early and aggressive surgery before metastases have developed, is believed to reduce the risks for tumor recurrence and malignant progression.

  • 247031.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Remedial Parathyroid Surgery2012In: Surgery of the Thyroid and Parathyroid Glands / [ed] D. Oertli, R. Udelsman, Springer Berlin/Heidelberg, 2012, 2, p. 555-577Chapter in book (Refereed)
  • 247032.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Multiple Endocrine Neoplasia type 22018In: Textbook of Complex General Surgical Oncology / [ed] Shane Y Morita, Charles M Balch, V. Suzanne Klimberg, Timothy M. Pawlik, Mitchell C. Posner, Kenneth K. Tanabe, McGraw-Hill, 2018Chapter in book (Refereed)
  • 247033.
    Åkerström, Hanna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of Scandinavian Languages.
    Interpunktion i runstensinskrifter från tidig vikingatid2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Uppsatsens syfte är att undersöka interpunktionens form och funktion i tidigvikingatida runinskrifter samt att därigenom också föra den teoretiska och metodiska diskussionen kring fenomenet runinterpunktion framåt. Undersökningens material består av runstensinskrifter från danskt område och från Götaland. Till viss del beskrivs interpunktionens form med hjälp av termer och metod lånade från grafonomin. Studiet av interpunktionens funktion begränsar sig främst till en syntaktisk analys med syfte att identifiera i vilken mån de syntaktiska gränsernas nivåer bestämmer hur interpunktionen används. Till viss del berörs även andra funktioner, till exempel textavgränsning, med utgångspunkt i innehållet. Undersökningens resultat visar framförallt på en mycket varierad användning av interpunktion. Till stor del kan bruket förstås som betingat av nivån på de syntaktiska gränserna. Avvikelser finns, dels som resultat av att interpunktionen haft andra funktioner, dels på grund av att en viss interpunktionstyp inte tycks ha använts med någon särskild funktion alls. Samband mellan interpunktionens form och funktion kan i vissa fall fastställas inom den enskilda inskriften. Dessa funktioner kan bestå i att en bestämd form av interpunktion endast markerar en viss typ av syntaktisk gräns, eller att interpunktionen förutom en syntaktisk gräns också markerar en tematisk. I Götaland visar det tidigaste materialet upp en relativt enhetlig princip utifrån vilken inskrifterna interpunkteras; i första hand markeras satsgränser med interpunktion. Det tidiga danska materialet uppvisar däremot en större variation. Utvecklingen i både det danska materialet och det från Götaland går mot att så gott som varje syntaktisk gräns interpunkteras.    

  • 247034.
    Åkerström, Hanna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of Scandinavian Languages.
    Sm 144 Gursten: En småländsk runsten från tidig vikingatid2012Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    I denna uppsats undersöks Gurstenstenen, en småländsk runsten från tidig vikingatid. Syftet är att granska tidigare läsningar och tolkningar och revidera dessa där det behövs, samt att utifrån en sannolik tolkning av inskriften säga något om dess sakliga bakgrund och syfte. Eftersom studien syftar till att läsa och förstå text utgår metoden från en beskrivning av läsandet som psykologisk process. I varje del av detta arbete har den mest sannolika lösningen valts utifrån en jämförelse med annat runmaterial. Resultatet innebär en nyläsning och -tolkning av en av inskriftens rader. Läsningen är kuþaskaki faþi sunuR naut smiþa kata uif siþaR un…, vilket tolkas Goða-Skeggi fáði. Sonr naut smíða Káta. Víf síðarr unn[i] och översätts ’Gode-Skägge (det vill säga godens eller godarnas Skägge) ristade. Sonen fick (eller fick nytta av) Kåtes smiden. Hustrun förunnade (eller gav lov) senare’. Sonen bör vara Kåtes son och hustrun Kåtes hustru. Möjligen är Skägge identisk med Kåtes son. Förleden Gode- är troligen samma ord som fvn. goði ’hednisk präst’. Inskriften är förmodligen en minnesinskrift över den döde Kåte, samt en manifestation av en betydelsefull händelse kopplad till att de föremål som nämns byter ägare.

  • 247035.
    Åkerström, Jenny
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Business Studies.
    Gröndahl, Lena
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Business Studies.
    Repatriering: Vart tar kunskapen vägen?2007Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Globaliseringen innebär möjligheter för företag att verka på en större marknad, men detta innebär också att organisationen blir mer utspridd och svårkontrollerad. Ett ökat fokus på kunskap som resurs för att skapa konkurrensfördelar samt att använda expatriering som ett verktyg för hantering av den utspridda organisationen har lett fram till valet av syfte med denna uppsats. Vi vill utifrån vår modell över hur repatrioters kunskap kan överföras och bidra till organisationens utveckling, beskriva och analysera hur företag idag tar tillvara på repatrioters kunskap. Vi har valt att göra vår undersökning på företag noterade på Stockholmsbörsen som använder sig av expatriering utanför Norden.

    Som grund för vår modell ligger teori om den kunskap repatrioter införskaffar under utlandstjänstgöring, hur kunskap kan överföras samt hur den kan utveckla organisationen och stärka dess konkurrenskraft. Utifrån vår modell har vi sedan skapat ett frågeformulär som ligger till grund för vår empiri. Frågeformuläret besvarades av 18 företag och resultatet visar att respondenterna överlag anser att repatrioters kunskaper gynnar organisationen samt att den bidrar till en stärkt konkurrenskraft. Trots detta är det enbart 3 av de 18 företagen som har en formell strategi för kunskapsöverföring vid repatriering. Ett flertal av företagen använder sig däremot av informella metoder, då främst genom personifierad kunskapsöverföring. Detta kommer dock troligtvis att ändras då många av företagen uppgett att de inom de närmsta fem åren med stor sannolikhet kommer att utveckla en strategi för kunskapsöverföring vid repatriering. Behovet av en bättre genomarbetad strategi tycks komma av en framtida utökad användning av expatriering inom organisationen.

  • 247036.
    Åkerström, Maria
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Education.
    Fungerande målarbete, ledarskapets vision!?2009Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
  • 247037.
    Åkerström, Maria
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Förändring och utveckling för framtiden en möjlighet redan i dag: En studie om entreprenörskap i Svenska kyrkan2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The research question on which this thesis is based is in what way entrepreneurship occurs in the Church of Sweden. This question is answered by analyzing such conditions and occurrences as a phenomenon in the governance and leadership function in the operation of the Church of Sweden. The purpose of the thesis is to investigate conditions and occurrences of entrepreneurship in the Church of Sweden through existing processes, systems and ceremonial forms in the organisation. The abduction method is used interactively with the hypothetical deductive method and the inductive method.

     

    Various theories of entrepreneurship are presented, as well as various types of organisations. The theoretical section concludes with analysis models that are used in the analysis in the thesis. The empirical material is presented based on various categories, which include entrepreneurship and organisation in the control function and leadership function in the Church of Sweden as well as in operations and governing documents.

     

    The results are analyzed by viewing entrepreneurship based on a collective and an individual perspective. In the analysis it is possible to interpret a number of different occurrences and conditions for entrepreneurship based on human, process-oriented and organisational phenomena. The conclusions and concluding discussion proceed from the conditions that exist for entrepreneurship and how its occurrence may demonstrate entrepreneurship as a phenomenon in the Church of Sweden. Entrepreneurship occurs at several different levels in the organisation, and prerequisites exist for developing entrepreneurship further while there may also be phenomena that work against entrepreneurship. Finally there is a brief reflection on methodology, with proposals for continued research.

     

  • 247038.
    Åkerström, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Samband mellan arbetsgrad och kinesiofobi hos vuxna individer med långvarig smärta och förändring av dessa variabler efter fyra veckors smärtrehabilitering2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    ABSTRACT

    Purpose: The purpose of the study was threefold. Firstly, to investigate if a four week program in pain rehabilitation had any effect on how much individuals with persistent pain worked and their degree of kinesiophobia. Secondly, to study if there was a correlation between how much these individuals worked and their degree of kinesiophobia. Thirdly, to study if there was a correlation between the change in these variables.

    Method: 112 patients who had participated in a four week rehabilitation program took part in the study. The study had a retrospective design, which was based on a review on medical records and consisted of three minor parts. The first part had a quasi-experimental comparative design and the other two parts had non-experimental cross-sectional correlative designs. Kinesiophobia was analyzed with the Swedish version of the Tampa Scale of Kinesiophobia (TSK-SV). How much a patient was working was measured in percent.

    Results: Both work status and kinesiophobia had improved significant in every measurement. The highest improvement in the variable of kinesiophobia was discovered by the end of the program in pain rehabilitation and by the twelve month follow-up in the variable about how much patients was working. Analysis with Spearman’s rang correlation coefficient showed a weak statistical significant correlation between how much individuals work and their degree of kinesiophobia in the twelve months follow-up. There was however no statistical significant correlation between the change of how much individuals worked and the change of their degree of kinesiophobia, neither in the two nor in the twelve months follow-up.

    Conclusions: This is one of the first studies that have been done who investigate the correlation between kinesiophobia and how much individuals with persistent pain are working and it shows that there is a need to continue to investigate the correlation between them, both for the individual as well as for the society in general and if possible also study what importance self-efficacy has in this context.

  • 247039.
    Åkerström, Mona-Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Grimby-Ekman, Anna
    Univ Gothenburg, Sahlgrenska Acad, Occupat & Environm Med, Gothenburg, Sweden..
    Lundberg, Mari
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Sociol, Huddinge, Sweden..
    Work ability is influenced by kinesiophobia among patients with persistent pain2017In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 33, no 8, p. 634-643Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate how kinesiophobia fluctuates in patients over a four weeks multimodal rehabilitation program and to study the relationship between work ability and kinesiophobia. The study included 112 patients (94 women, 18 men). Measurements were made before, directly after, 2months after, and 12months after the program. The level of work ability was rated by the patients on a scale from 0% to 100%, and kinesiophobia was measured by the Swedish version of the Tampa Scale for Kinesiophobia (TSK-SV). Kinesiophobia decreased between the start of the multimodal rehabilitation program and the follow-up periods. Work ability increased over time, but not between baseline and the 2-month follow-up. Decreases in the TSK-SV score between baseline and the 2-month follow-up were related to the increased probability of improved work ability at the 12-month follow-up. In conclusion, a decrease in kinesiophobia seems to be related to increased work ability of patients participating in a 4-week multimodal rehabilitation program.

  • 247040.
    Åkerström, Stig
    Uppsala University, Disciplinary Domain of Science and Technology.
    Studies on organic sulphur containing complexesof group I elements and thallium and some of their reactions with tetraalkylthiuram disulphides1965Doctoral thesis, comprehensive summary (Other academic)
  • 247041.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University.
    Genetic Alterations and Molecular Signatures in Aldosterone Producing Adenomas2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Primary Aldosteronism (PA) is caused by autonomous overproduction of aldosterone. Aldosterone is necessary for fluid and ion homeostasis. Aberrant overproduction leads to hypertension and cardiovascular damage. With a prevalence of over 5% in the worlds’ hypertensive community, and with over a billion people worldwide having high blood pressure, PA represents a major contributor to health care costs and morbidity. Importantly, 30% of PA patients have a unilateral dominant secretion, an aldosterone producing adenoma (APA), making it possible to cure a substantial portion of patients with surgery. Unfortunately, there is a large underdiagnosis of PA, leading to delayed diagnosis in many patients, worsening their outcome after surgery. A need for better screening techniques, raised awareness and treatment options for PA is warranted.

    Since 2011, the genetic understanding of APAs has revolutionized. Somatic mutations turning on an autonomous aldosterone production has been observed in up to 80% of tumors. In this thesis we have investigated the genetic landscape and phenotypes of APAs. By international collaborations we have collected one of the largest cohorts of APAs ever sequenced. We have confirmed and extended the understanding of KCNJ5 mutations, its associated phenotype and the specificity for APAs. We have confirmed a high rate of mutations in ATP1A1, ATP2B3 and CACNA1D, and noted distinct clinical and molecular phenotypes in these tumors. We describe a marker of Zona Glomerulosa cells, perhaps important for the normal regulation and function of these cells. We observe somatic mutations in CTNNB1, occurring in a mutually exclusive manner to the other mutations. Using in situ sequencing, we note genetic heterogeneity in APAs with KCNJ5 mutations. Finally, we evaluate intratumoral aldosterone measurement on a large cohort of tumors, validating a high specificity for APAs. Noting also a difference in the level of intratumoral aldosterone between APAs and a possible association with genotype. Remarkably, we also note a robust correlation between the intracellular concentrations and plasma-aldosterone. We hope that with gained knowledge of the genetic background, the understanding of both pathologic and normal states of the adrenals will increase, and hopefully benefit patients in the future.

    List of papers
    1. Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter
    Open this publication in new window or tab >>Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter
    Show others...
    2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e41926-Article in journal (Refereed) Published
    Abstract [en]

    Background: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.

    Materials and Methods: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.

    Results: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p < 0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p < 0.005).

    Discussion: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-183242 (URN)10.1371/journal.pone.0041926 (DOI)000306950200128 ()
    Available from: 2012-10-25 Created: 2012-10-23 Last updated: 2017-12-07Bibliographically approved
    2. Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.
    Open this publication in new window or tab >>Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.
    Show others...
    2015 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, no 5, p. 735-744Article in journal (Refereed) Published
    Abstract [en]

    Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.

    Keywords
    ATP1A1; CACNA1D; KCNJ5; primary aldosteronism; aldosterone-producing adenoma
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-266639 (URN)10.1530/ERC-15-0321 (DOI)000364022400010 ()26285814 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Research Council
    Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2017-12-01
    3. Activating mutations in CTNNB1 in aldosterone producing adenomas
    Open this publication in new window or tab >>Activating mutations in CTNNB1 in aldosterone producing adenomas
    Show others...
    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19546Article in journal (Refereed) Published
    Abstract [en]

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalenceof 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitutea large proportion of PA cases and represent a surgically correctable form of the disease. The WNTsignaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling ismutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutationsin a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of thetumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Allof the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3.The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggestingactivation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and directmeasurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. Thisreport provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occurin APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway maybe important in APA formation.

    National Category
    Endocrinology and Diabetes Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-277306 (URN)10.1038/srep19546 (DOI)000368736400001 ()26815163 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Research Council
    Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2017-11-30Bibliographically approved
    4. Intratumoural Aldosterone and Heterogeneity in Genetic Subtypes of Aldosterone Producing Adenomas
    Open this publication in new window or tab >>Intratumoural Aldosterone and Heterogeneity in Genetic Subtypes of Aldosterone Producing Adenomas
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Context

    Primary Aldosteronism is the most common endocrine cause of hypertension. Unilateral disease in the form of Aldosterone producing adenomas (APAs) is found in 1.5-3% of hypertensive. Determining the source of aldosteronism is necessary for correct diagnosis and further molecular analysis.

    Objective

    To evaluate tissue aldosterone as a marker of aldosterone production and correlate it to patient phenotype and tumour mutation status, and to explore molecular heterogeneity in APAs.

    Design

    Forty-six frozen tumour samples from patients diagnosed with APAs were included. Tumours were derived from a single endocrine referral center, and had been stored from 1985 to 2015. Tissue aldosterone concentration was related to clinical characteristics, genotype and molecular phenotype. Genetic heterogeneity was investigated by biopsies and in situ sequencing. Immunohistochemical analysis of Nephronectin, CYP11B1 and CYP11B2 were performed. qRT-PCR and in situ mRNA expression were used to analyze CYP11B2 mRNA expression.

    Results

    Tissue aldosterone content was specific for aldosterone producing tumours and proved stable after long-term storage at -70C. CYP11B2 expression and aldosterone concentrations were higher in tumours with ATP1A1, ATP2B3 and CACNA1D mutations compared to those with KCNJ5 mutations (p<0.0001 and p=0.0018 respectively). The tissue aldosterone content correlated with CYP11B2 protein expression (r2=0.48, p<0.0001), and both CYP11B2 expression and tissue aldosterone content were associated with the plasma level of aldosterone (r2=0.33, p=0.0002 and r2=0.75, p<0.0001 respectively). In four tumours with suspicion of genetic heterogeneity, sampling of DNA revealed a heterogeneous KCNJ5 mutation in one tumour. Using in situ sequencing we confirmed heterogeneous expression of mutated KCNJ5 cDNA in the others. In three tumours classified as APAs, no mutation nor any aldosterone or CYP11B2 were detected, suggesting non-functional tumours.

    Conclusion

    Tissue aldosterone content is specific for aldosterone producing lesions, correlates with plasma levels, and displays variable levels depending on tumour genotype. Genetic heterogeneity is evident in a subgroup of KCNJ5 mutated tumours. The present results show that CYP11B2 expression and tissue aldosterone measurement may be used to clarify the source of aldosterone secretion. 

    National Category
    Clinical Medicine Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-281039 (URN)
    Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2016-04-21
  • 247042.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Genetic Alterations in Aldosterone Producing Adenomas2014Licentiate thesis, comprehensive summary (Other academic)
    List of papers
    1. Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter
    Open this publication in new window or tab >>Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter
    Show others...
    2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e41926-Article in journal (Refereed) Published
    Abstract [en]

    Background: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.

    Materials and Methods: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.

    Results: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p < 0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p < 0.005).

    Discussion: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-183242 (URN)10.1371/journal.pone.0041926 (DOI)000306950200128 ()
    Available from: 2012-10-25 Created: 2012-10-23 Last updated: 2017-12-07Bibliographically approved
    2. Activating Mutations in CTNNB1 in Aldosterone Producing Adenomas
    Open this publication in new window or tab >>Activating Mutations in CTNNB1 in Aldosterone Producing Adenomas
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-218662 (URN)
    Available from: 2014-02-13 Created: 2014-02-13 Last updated: 2015-06-26Bibliographically approved
    3. Somatic Mutations in ATP1A1 and ATP2B3 in Aldosterone Producing Adenomas
    Open this publication in new window or tab >>Somatic Mutations in ATP1A1 and ATP2B3 in Aldosterone Producing Adenomas
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    ATP1A1, ATP2B3, Aldosterone producing adenomas, Mutation, KCNJ5
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-218659 (URN)
    Available from: 2014-02-13 Created: 2014-02-13 Last updated: 2014-03-11
  • 247043.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Azizan, Elena A B
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Moser, Ana
    Robinson, Bruce
    Iwen, Alexander K
    Dralle, Henning
    Walz, Martin K.
    Lehnert, Hendrik
    Sidhu, Stan
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Brown, Morris J
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Activating Mutations in CTNNB1 in Aldosterone Producing AdenomasManuscript (preprint) (Other academic)
  • 247044.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Carling, T.
    Endocrine Research Unit, Yale University, New Haven, CT, USA..
    Beuschlein, F.
    Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany..
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Genetics of adrenocortical tumours2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 6, p. 540-550Article in journal (Refereed)
    Abstract [en]

    The recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease-causing mutations have been described for aldosterone-producing adenomas, cortisol-producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation. Moreover, compounds that bind specifically to altered proteins may be used as screening targets or therapeutic agents. Regulation of cortisol release by interaction with an altered subunit in adenylate cyclase may be more complex, but may provide a new option for regulating steroid release. Information about derangements in adrenocortical carcinoma is already helpful for determining patient prognosis. With further knowledge, we may be able to identify novel biomarkers that effectively and noninvasively help in differentiating between benign and malignant disease. It is clear that the next few years will provide much novel information that hopefully will aid in the treatment of patients with adrenocortical tumours.

  • 247045.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Verdugo, Alberto Delgado
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Starker, Lee F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Cupisti, Kenko
    Willenberg, Holger S.
    Knoefel, Wolfram T.
    Saeger, Wolfgang
    Feller, Alfred
    Ip, Julian
    Soon, Patsy
    Anlauf, Martin
    Alesina, Pier F.
    Schmid, Kurt W.
    Decaussin, Myriam
    Levillain, Pierre
    Wangberg, Bo
    Peix, Jean-Louis
    Robinson, Bruce
    Zedenius, Jan
    Backdahl, Martin
    Caramuta, Stefano
    Iwen, K. Alexander
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kraimps, Jean-Louis
    Dralle, Henning
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sidhu, Stan
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lehnert, Hendrik
    Walz, Martin K.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Carling, Tobias
    Choi, Murim
    Lifton, Richard P.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e41926-Article in journal (Refereed)
    Abstract [en]

    Background: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.

    Materials and Methods: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.

    Results: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p < 0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p < 0.005).

    Discussion: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

  • 247046.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Moser, Ana
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Robinson, Bruce
    Iwen, Alexander K
    Dralle, Henning
    Walz, Martin K.
    Lehnert, Hendrik
    Sidhu, Stan
    Gomez-Sanchez, Celso
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Activating mutations in CTNNB1 in aldosterone producing adenomas2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19546Article in journal (Refereed)
    Abstract [en]

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalenceof 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitutea large proportion of PA cases and represent a surgically correctable form of the disease. The WNTsignaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling ismutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutationsin a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of thetumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Allof the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3.The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggestingactivation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and directmeasurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. Thisreport provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occurin APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway maybe important in APA formation.

  • 247047.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Svedlund, Jessica
    Gomez-Sanchez, Celso
    Nilsson, Mats
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Peyman, Björklund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Intratumoural Aldosterone and Heterogeneity in Genetic Subtypes of Aldosterone Producing AdenomasManuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Context

    Primary Aldosteronism is the most common endocrine cause of hypertension. Unilateral disease in the form of Aldosterone producing adenomas (APAs) is found in 1.5-3% of hypertensive. Determining the source of aldosteronism is necessary for correct diagnosis and further molecular analysis.

    Objective

    To evaluate tissue aldosterone as a marker of aldosterone production and correlate it to patient phenotype and tumour mutation status, and to explore molecular heterogeneity in APAs.

    Design

    Forty-six frozen tumour samples from patients diagnosed with APAs were included. Tumours were derived from a single endocrine referral center, and had been stored from 1985 to 2015. Tissue aldosterone concentration was related to clinical characteristics, genotype and molecular phenotype. Genetic heterogeneity was investigated by biopsies and in situ sequencing. Immunohistochemical analysis of Nephronectin, CYP11B1 and CYP11B2 were performed. qRT-PCR and in situ mRNA expression were used to analyze CYP11B2 mRNA expression.

    Results

    Tissue aldosterone content was specific for aldosterone producing tumours and proved stable after long-term storage at -70C. CYP11B2 expression and aldosterone concentrations were higher in tumours with ATP1A1, ATP2B3 and CACNA1D mutations compared to those with KCNJ5 mutations (p<0.0001 and p=0.0018 respectively). The tissue aldosterone content correlated with CYP11B2 protein expression (r2=0.48, p<0.0001), and both CYP11B2 expression and tissue aldosterone content were associated with the plasma level of aldosterone (r2=0.33, p=0.0002 and r2=0.75, p<0.0001 respectively). In four tumours with suspicion of genetic heterogeneity, sampling of DNA revealed a heterogeneous KCNJ5 mutation in one tumour. Using in situ sequencing we confirmed heterogeneous expression of mutated KCNJ5 cDNA in the others. In three tumours classified as APAs, no mutation nor any aldosterone or CYP11B2 were detected, suggesting non-functional tumours.

    Conclusion

    Tissue aldosterone content is specific for aldosterone producing lesions, correlates with plasma levels, and displays variable levels depending on tumour genotype. Genetic heterogeneity is evident in a subgroup of KCNJ5 mutated tumours. The present results show that CYP11B2 expression and tissue aldosterone measurement may be used to clarify the source of aldosterone secretion. 

  • 247048.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Backman, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Moser, Ana
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Robinson, Bruce
    Iwen, K Alexander
    Dralle, Henning
    D Volpe, Cristina
    Bäckdahl, Martin
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Walz, Martin K
    Lehnert, Hendrik
    Sidhu, Stan
    Zedenius, Jan
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.2015In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, no 5, p. 735-744Article in journal (Refereed)
    Abstract [en]

    Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.

  • 247049.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Moser, Ana
    Robinson, Bruce
    Iwen, Alexander K
    Dralle, Henning
    Volpe, Cristina D
    Bäckdahl, Martin
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Walz, Martin K.
    Lehnert, Hendrik
    Sidhu, Stan
    Zedenius, Jan
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Peyman, Björklund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Somatic Mutations in ATP1A1 and ATP2B3 in Aldosterone Producing AdenomasManuscript (preprint) (Other academic)
  • 247050.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Moser, Ana
    Robinson, Bruce
    Iwen, Alexander K
    Dralle, Henning
    Volpe, Cristina D
    Bäckdahl, Martin
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Walz, Martin K.
    Lehnert, Hendrik
    Sidhu, Stan
    Zedenius, Jan
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Peyman, Björklund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Somatic Mutations in ATP1A1 and ATP2B3 in Aldosterone Producing AdenomasManuscript (preprint) (Other academic)
4938493949404941494249434944 247001 - 247050 of 249765
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