879 research outputs found
Importance of Aggregated Islet Amyloid Polypeptide for the Progressive Beta-Cell Failure in Type 2 Diabetes and in Transplanted Human Islets
No full textOriginal Publication: Gunilla Westermark and Per Westermark, Importance of Aggregated Islet Amyloid Polypeptide for the Progressive Beta-Cell Failure in Type 2 Diabetes and in Transplanted Human Islets, 2008, EXPERIMENTAL DIABETES RESEARCH, (2008), 528354. http://dx.doi.org/10.1155/2008/528354 Copyright: Authors</p
The systemic amyloidoses: clearer understanding of the molecular mechanisms offers hope for more effective therapies.
No full textFibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model
No full textBackground: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. Principal Findings: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. Conclusions: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns. © 2009 Westermark et al.Original Publication:P. Westermark, Katarzyna Lundmark and Gunilla Westermark, Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model, 2009, PLoS ONE, (4), 6, e6041.http://dx.doi.org/10.1371/journal.pone.000604
Transthyretin and Amyloid in the Islets of Langerhans in Type-2 Diabetes
No full textTransthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretincontaining cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.Original Publication: Gunilla Westermark and Per Westermark, Transthyretin and Amyloid in the Islets of Langerhans in Type-2 Diabetes, 2008, EXPERIMENTAL DIABETES RESEARCH, (2008), 429274. http://dx.doi.org/10.1155/2008/429274 Copyright: Authors</p
Restaureringen av Bosgårdens lerstall - Tema: Tillämpning [Elektronisk resurs]
No full textStallbyggnaden på Bosgården iBorgå, Finland, kanske inte äger något högt kulturhistoriskt värde i sig, men dess byggnadsteknik har fascinerat arkitekterna Leticia Achcar, Stockholm, och Mikael Westermark, Helsingfors. Restaureringen av stallbyggnaden blev för dem ett intressant experiment i lerhusbyggande. </p
Otto Mørkholm, Early Hellenistic Coinage. From the Accession of Alexander to the Peace ofApamea (336-188 B.C.). Éd. par P. Grierson et U. Westermark
No full textde Callataÿ François. Otto Mørkholm, Early Hellenistic Coinage. From the Accession of Alexander to the Peace ofApamea (336-188 B.C.). Éd. par P. Grierson et U. Westermark. In: L'antiquité classique, Tome 64, 1995. pp. 439-441
15. Mørkholm (Otto), Early Hellenistic Coinage from the Accession of Alexander to the Peace of Apamea (336-188 BC), edited by Philip Grierson and Ulla Westermark
No full textLe Rider Georges. 15. Mørkholm (Otto), Early Hellenistic Coinage from the Accession of Alexander to the Peace of Apamea (336-188 BC), edited by Philip Grierson and Ulla Westermark. In: Revue des Études Grecques, tome 105, fascicule 500-501, Janvier-juin 1992. p. 274
Amyloid Deposition in Transplanted Human Pancreatic Islets : A Conceivable Cause of Their Long-Term Failure
No full textFollowing the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the beta-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.Original Publication:Arne Andersson, Sara Bohman, L A Hakan Borg, Johan Paulsson, Sebastian Schultz, Gunilla Westermark and Per Westermark, Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure, 2008, EXPERIMENTAL DIABETES RESEARCH, (2008), 562985.http://dx.doi.org/10.1155/2008/562985Copyright: Author
Further evidence for amyloid deposition in clinical pancreatic islet grafts
No full textBackground. The reasons for the long-term complete or partial loss of islet graft function are unknown, but there are obviously other reasons than just pure allogeneic graft rejection. Earlier studies have shown that deposition of islet amyloid polypeptide amyloid in transplanted islets may indicate a mechanism for loss of β cells. Materials and Methods. Sections from liver material from four deceased islet-bearing recipients have been scrutinized for the presence of amyloid. Clinical data and certain aspects of the islet graft pathology of these patients have been published previously. RESULT.: With this extended histological analysis, we demonstrate the occurrence of amyloid deposits in islets transplanted into the liver in three of four patients with type 1 diabetes. Conclusion. The finding adds evidence to the assumption that aggregation of islet amyloid polypeptide might be an important cause of progressing β-cell dysfunction in clinically transplanted islets
DNA repair by HDR in experimental tumorigenesis
No full textThe aim of this thesis was to further understand how defects in the homology-directed repair (HDR) pathway affect tumor formation and development. To study proteins involved in HDR is challenging since most of its members are required for cell viability. For our studies we have therefore taken a dominant-negative approach to address the importance of the BRCA1 interacting protein BARD1 in HDR (paper I) and investigate the role of HDR in PDGFB-induced gliomagenesis by interfering with a key protein, RAD51 (paper II). In addition we have also investigated how Platelet-derived growth factor A receptor (PDGFRA) is transcriptionally regulated by interleukin-1b (IL-1b) (paper III).The breast cancer susceptibility gene BRCA1 is frequently mutated in hereditary breast and ovarian cancers. BRCA1 has been implicated in many different cellular processes, among them DNA repair by HDR. In Paper I we investigated if BARD1 was involved in HDR through its interaction with BRCA1. We could show that expression of a truncated BARD1 decreased HDR of an induced double-strand break and that this decrease was even more pronounced in Brca1-deficient cells expressing a splice variant of Brca1 that still are able to bind BARD1. We could also show that the role of BARD1 in HDR was dependent on binding to BRCA1 and that the HDR defect resulting from the truncated BARD1 was caused by lack of regulatory elements in the C-terminal end of BARD1 and not caused by improper cellular localization of either the BARD1 construct or the endogenous Brca1 protein. We conclude that BARD1 is important for HDR and that the repair function of BARD1 is dependent on its interaction with BRCA1.The expression of PDGFRa is strictly regulated during embryogenesis and aberrant PDGFRa expression can lead to malignant transformation, in brain tumors for example. Highly malignant gliomas are the most frequent primary tumor of the central nervous system in adults. To study the effect of different genetic changes in gliomagenesis, glioma-like tumors can be induced by intracerebral injections of oncogene carrying retroviruses. The RCAS/tv-a model system provides the possibility to study combinations of different genetic alterations in a specific cell type. In paper II we have used wild type and Arf-/- nestin tv-a (Ntv-a) transgenic mice, where expression of the RCAS constructs were directed to neural progenitor cells. It has previously been shown that expression of PDGFB can induce glioma-like tumors in these mice.To investigate the role of HDR in tumorigenesis we co-expressed RAD51 or a DNA repair deficient RAD51 (RAD51KR) contruct with PDGFB in either wild type or Arf-/- Ntv-a mice. We could show that co-expression of RAD51 or RAD51KR can suppress PDGFB-induced tumorigenesis in wild type mice. However, only RAD51 was able to suppress tumor formation in the Arf-null background. We could also show that all the PDGFB-induced tumors were aneuploid, independent of genotype, tumor grade or tumor size. Interestingly, expression of RAD51 or RAD51KR reduced aneuploidy in the PDGFB-induced tumors.List of scientific papersI. Westermark UK, Reyngold M, Olshen AB, Baer R, Jasin M, Moynahan ME (2003). BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks. Mol Cell Biol. 23(21): 7926-36. https://pubmed.ncbi.nlm.nih.gov/14560035II. Westermark UK, Forsberg N, Bråsäter D, Helgadottir HR, Eriksson A, Zetterberg A, Jasin M, Nistér M, Uhrbom L (2008). RAD51 suppresses PDGFB-induced gliomagenesis and genetic instability in wild type and Arf-/- mice. [Submitted]III. Afink G, Westermark UK, Lammerts E, Nistér M (2004). C/EBP is an essential component of PDGFRA transcription in MG-63 cells. Biochem Biophys Res Commun. 315(2): 313-8. https://pubmed.ncbi.nlm.nih.gov/14766209</p
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