| 1. |
- Ohlsson-Nevo, Emma, et al.
(författare)
-
Patients' perspective in the context of proton beam therapy : summary of a Nordic workshop
- 2020
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 59:10, s. 1139-1144
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: On 15-16 November 2019, the Skandion Clinic in Sweden hosted the first Nordic workshop on 'Patients' perspective in proton beam therapy'. The workshop was conducted to describe and compare the patient care in PBT clinics in the Nordic countries and to initiate a collaboration, with the target to ensure patient participation and reduce the risk of inequity of access by lowering the barriers for accepting PBT in a distant clinic. The overarching aim of this workshop was to describe and compare the use of patients' perspectives in the Nordic PBT clinics.MATERIAL AND METHODS: Twelve participants attended the workshop, representing Denmark, Norway and Sweden. The participants were registered nurses working in patient care, researchers, physicist and leaders of the Skandion Clinic.RESULTS: The consensus of the workshop was that systematic use of patient experiences on individual and group level is essential for developing clinical practice and understanding the overall effects of PBT. A difference in how the Nordic countries use patient experiences in clinical practise was found. The importance of lowering the barriers for participation in national proton trials and proton treatment were emphasized, however, there is a lack of knowledge about individual and organizational barriers to accepting PBT, and further research is therefore needed.CONCLUSION: Collaboration between the Nordic countries regarding patients' perspectives in the context of PBT is of importance to compare national differences as well as to find similarities, but most importantly to learn from each other and to improve patient care. Nordic collaboration with focus on systematic collection of patient-reported outcomes in the context of PBT is unique. Collaboration in research offers the possibility to increase the inclusion of patients' perspectives in study protocols.
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| 2. |
- Ohlsson, Sophie, et al.
(författare)
-
Novel distribution of the secretory leucocyte proteinase inhibitor in kidney
- 2001
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 10:6, s. 347-350
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Tidskriftsartikel (refereegranskat)abstract
- The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight, tissue-specific inhibitor of, for example, elastase and cathepsin G, which also have antimicrobial capacity. SLPI has been localised to the respiratory, gastrointestinal and genital tracts, but so far not to the kidney. The presence of SLPI in renal tubuli cells was demonstrated using immunohistochemistry and, by means of in situ hybridisation on human renal biopsies, we were able to demonstrate SLPI production. In various inflammatory conditions in the kidneys, the protease-antiprotease balance is disturbed. For this reason, as well as the possible role in the defence against ascending urinary tract infections, it is interesting to establish a source of SLPI in renal tubuli cells.
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| 3. |
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| 4. |
- Bergh, Anders, et al.
(författare)
-
Didecyl squarate — A practical amino-reactive cross-linking reagent for neoglycoconjugate synthesis
- 2001
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Ingår i: Glycoconjugate Journal. - 1573-4986. ; 18:8, s. 615-621
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Tidskriftsartikel (refereegranskat)abstract
- The present paper describes the synthesis and use of the hydrophobic squaric decyl ester glycosides in neoglycoconjugate chemistry. The 2-aminoethyl glycosides of agr-D-mannopyranose, lactose, globotriose, globotetraose, GM3, and sialyl Lewisx, as well as the 2-(2-aminoethylthio)ethyl glycoside of agr-D-mannopyranose, beta-D-glucopyranose, and galabiose were reacted with squaric acid didecyl ester to afford the hydrophobic squaric decyl ester glycosides. These glycosides were efficient reagents for the conjugation to amino-functional microtiter plates, BSA and aminated Sepharose EAH 4B. The decyl ester moiety of the squaric decyl ester glycosides constitutes a traceless hydrophobic tag, which has the major advantage, as compared to the corresponding ethyl esters, that it enables easy purification of the glycosides with silica chromatography and that unreacted excesses glycosides from conjugation reaction mixtures can easily be recovered by means of C18 solid phase extraction.
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| 5. |
- Björnham, Oscar, 1976-, et al.
(författare)
-
Measurements of the binding force between the Helicobacter pylori adhesin BabA and the Lewis b blood group antigen using optical tweezers
- 2005
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Ingår i: Journal of Biomedical Optics. - Bellingham, WA : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 10:4, s. 044024-044032
-
Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is a world-wide spread bacterium that causes persistent infections and chronic inflammations that can develop into gastritis and peptic ulcer disease. It expresses several adhesin proteins on its surface that bind to specific receptors in the gastric epithelium. The most well-known adhesin is BabA, which has previously been shown to bind specifically to the fucosylated blood group antigen Lewis b (Leb). The adhesion forces between BabA and the Leb antigen are investigated in this work and assessed by means of optical tweezers. A model system for in situ measurements of the interaction forces between individual bacteria and beads coated with Leb is developed. It is found that the de-adhesion force in this model system, measured with a loading rate of ~100 pN/s, ranges from 20 to 200 pN. The de-adhesion force appears predominantly as multiples of an elementary force, which is determined to 25±1.5 pN and identified as the unbinding force of an individual BabA-Leb binding. It is concluded that adhesion in general is mediated by a small number of bindings (most often 1 to 4) despite that the contact surface between the bacterium and the bead encompassed significantly more binding sites.
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| 6. |
- Ellervik, Ulf, et al.
(författare)
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2-Bromoethyl glycosides for synthesis of glycoconjugates on solid support
- 2005
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 61:9, s. 2421-2429
-
Tidskriftsartikel (refereegranskat)abstract
- 2-Bromoethyl glycosides can easily and in high yields be transformed into sulfones by treatment with a suitable thiol followed by oxidation with mCPBA. The observation that the so formed sulfones were cleaved by treatment with NaOMe/MeOH was used to design a new safety catch linker for synthesis of glycoconjugates on solid support. (C) 2005 Elsevier Ltd. All rights reserved.
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| 7. |
- Flygare, Lennart, et al.
(författare)
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Chronic recurrent multifocal osteomyelitis involving both jaws : report of a case including magnetic resonance correlation
- 1997
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Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier. - 1079-2104 .- 1528-395X. ; 83:2, s. 300-305
-
Tidskriftsartikel (refereegranskat)abstract
- A case of chronic recurrent multifocal osteomyelitis in a 14-year-old girl is presented. The disease had an initial aggressive osteolytic appearance involving both the maxilla and the mandible. Conservative treatment with minimal surgical intervention has been successful in this case during a 2-year follow-up period. The value of magnetic resonance imaging and bone scintigraphy in this case and the cause of chronic recurrent multifocal osteomyelitis is discussed.
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| 8. |
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| 9. |
- Hanson, Jörgen, et al.
(författare)
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P2PIE : a New Enterprise Application Integration Solution 60-70
- 2015
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Ingår i: Proceedings of the CAiSE-2015 Industry Track co-located with 27th Conference on Advanced Information Systems Engineering (CAiSE 2015). ; , s. 60-70
-
Konferensbidrag (refereegranskat)abstract
- In order to provide unified and consistent data and functionality, enterprises need to make all their applications work in an integrated manner. However, integration has become more difficult to handle when enterprises extend their business globally, more applications are implemented for supporting business activities, and more computing paradigms are adopted, e.g., cloud, social, and mobile, just to name a few. The state-of-the-art integration solutions have limitations to address the difficulty. In this paper, point to point integration engine-P2PIE, a new integration solution is presented and discussed. The solution combines distributed execution of integration with centralized management console, which innovate the fundamental integration infrastructures of point to point paradigm, and message systems. P2PIE is developed and tested by Sandvik over the decade. The solution has addressed Sandvik’s challenges in enterprise application integration. Agility, cost reduction and reliability of this solution are proved.
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| 10. |
- Hellman, Karin, et al.
(författare)
-
Discovery of Procognitive Antipsychotics by Combining Muscarinic M-1 Receptor Structure-Activity Relationship with Systems Response Profiles in Zebrafish Larvae
- 2020
-
Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 11:2, s. 173-183
-
Tidskriftsartikel (refereegranskat)abstract
- Current antipsychotic drugs are notably ineffective at addressing the cognitive deficits associated with schizophrenia. N-Desmethylclozapine (NDMC), the major metabolite of clozapine, displays muscarinic M-1 receptor (M-1) agonism, an activity associated with improvement in cognitive functioning. Preclinical and clinical data support that M-1 agonism may be a desired activity in antipsychotic drugs. However, NDMC failed clinical phase II studies in acute psychotic patients. NDMC analogues were synthesized to establish a structure-activity relationship (SAR) at the M-1 receptor as an indication of potential procognitive properties. In vitro evaluation revealed a narrow SAR in which M-1 agonist activity was established by functionalization in the 4- and 8-positions in the tricyclic core. In vivo behavioral response profiles were used to evaluate antipsychotic efficacy and exposure in zebrafish larvae and peripheral side effect related M-1 activity in adult zebrafish. The NDMC analogue 13f demonstrated antipsychotic activity similar to clozapine including M-1 agonist activity. Cotreatment with trospium chloride, an M1 peripheral acting antagonist, counteracted peripheral side effects. Thus, the NDMC analogue 13f, in combination with a peripherally acting anticholinergic compound, could be suitable for further development as an antipsychotic compound with potential procognitive activity.
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| 11. |
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| 12. |
- Isaksson, Olle, 1943, et al.
(författare)
-
Regulation of cartilage growth by growth hormone and insulin-like growth factor I.
- 1991
-
Ingår i: Pediatric nephrology (Berlin, Germany). - 0931-041X. ; 5:4, s. 451-3
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Tidskriftsartikel (refereegranskat)abstract
- A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate.
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| 13. |
- Jass, Jana, et al.
(författare)
-
Physical properties of Escherichia coli P pili measured by optical tweezers
- 2004
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 87:6, s. 4271-4283
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanical behavior of individual P pili of uropathogenic Escherichia coli has been investigated using optical tweezers. P pili, whose main part constitutes the PapA rod, composed of approximately 10(3) PapA subunits in a helical arrangement, are distributed over the bacterial surface and mediate adhesion to host cells. They are particularly important in the pathogenesis of E. coli colonizing the upper urinary tract and kidneys. A biological model system has been established for in situ measurements of the forces that occur during mechanical stretching of pili. A mathematical model of the force-versus-elongation behavior of an individual pilus has been developed. Three elongation regions of pili were identified. In region I, P pili stretch elastically, up to a relative elongation of 16 +/- 3%. The product of elasticity modulus and area of a P pilus, EA, was assessed to 154 +/- 20 pN (n=6). In region II, the quaternary structure of the PapA rod unfolds under a constant force of 27 +/- 2 pN (n approximately 100) by a sequential breaking of the interactions between adjacent layers of PapA subunits. This unfolding can elongate the pilus up to 7 +/- 2 times. In region III, pili elongate in a nonlinear manner as a result of stretching until the bond ruptures.
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| 14. |
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| 15. |
- Larsson, Andreas, et al.
(författare)
-
Quantitative studies of the binding of the class II PapG adhesin from uropathogenic Escherichia coli to oligosaccharides.
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 11:10, s. 2255-2261
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Tidskriftsartikel (refereegranskat)abstract
- Binding of the class II PapG adhesin, found at the tip of filamentous pili on Escherichia coli, to the carbohydrate moiety of globoseries glycolipids in the human kidney is a key step in development of pyelonephritis, a severe form of urinary tract infection. An assay based on surface plasmon resonance for quantification of the binding of the class II PapG adhesin to oligosaccharides has been developed. Using this assay dissociation constants ranging from 80 to 540 M were determined for binding of the PapG adhesin to di-pentasaccharide fragments from the globoseries of glycolipids. A series of galabiose derivatives, modified at the anomeric position, O-2′ or O-3′, was also investigated. The anomeric position appeared to be the most promising for development of improved inhibitors of PapG-mediated adhesion of E. coli. p-Methoxyphenyl galabioside was found to be most potent (Kd=140 M), and binds to PapG almost as well as the Forssman pentasaccharide.
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| 16. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 17. |
- Nilsson, Anders, 1958, et al.
(författare)
-
Hormonal regulation of longitudinal bone growth.
- 1994
-
Ingår i: European journal of clinical nutrition. - 0954-3007. ; 48 Suppl 1
-
Tidskriftsartikel (refereegranskat)abstract
- The regulation of postnatal somatic growth is complex. Genetic, nutritional factors and hormones exert regulatory functions. Hormones that have an established role in the regulation include growth hormone (GH), thyroid hormone and sex steroids. GH promotes mainly the growth of the long bones in terms of final height, while the action of the sex steroids and thyroid hormone is less well known. Longitudinal bone growth is the result of chondrocyte proliferation and subsequent endochondral ossification in the epiphyseal growth-plates. The growth-plate is a cartilaginous template that is located between the epiphysis and the metaphysis of the long bones. GH and insulin-like growth factor-I (IGF-I) have different target cells in the epiphyseal growth-plate. GH stimulates the slowly dividing prechondrocytes in the germinative cell layer while IGF-I promotes the clonal expansion in the proliferative cell layer of a GH primed cell. Thyroid hormone blocks the clonal expansion and stimulates chondrocyte maturation. IGF-I mRNA is primarily regulated by GH, and IGF-I is produced in several tissues such as the liver, muscle, fat and epiphyseal growth plates. However, IGF-I mRNA is also increased during compensatory growth of heart and kidneys and by estrogen in the Fallopian tube in the rat. Nutrition, i.e. energy from fat and carbohydrates and proteins, also influences the final height, but the cellular mechanism of action is not known. The aim of this article is to review hormonal action on longitudinal bone growth.
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| 18. |
- Ohlsson, Bodil, et al.
(författare)
-
A prospective evaluation of the diagnostic value of video capsule endoscopy in patients initially classified as irritable bowel syndrome
- 2009
-
Ingår i: European journal of internal medicine. - : Science direct. - 0953-6205 .- 1879-0828. ; 20:1, s. 48-52
-
Tidskriftsartikel (refereegranskat)abstract
- Background Irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction in the absence of detectable organic disease. The recently developed technique, video capsule endoscopy (CE), has been shown to be much more sensitive than traditional enterography in detecting mucosal changes in the small intestine. This study was performed to see if any earlier, not detectable by other standard methods, mucosal changes could be found in the small intestine in patients diagnosed as having IBS. Methods All consecutive women who, over the past five years, had received a well-founded diagnosis of IBS at the Department of Medicine were identified. Twenty-eight women, mean age 36 ± 12 years were willing to participate in the study. They underwent a CE after a pre-test with a dummy capsule. The actual IBS activity was estimated by the validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) Index questionnaires. Results The duration of the IBS symptoms was a mean of 10 years (range 3–25). Symptoms were present, according to the scores of the GSRS and the PGWB index, at the time the patients underwent the CE. In the majority, 24 of 27 IBS patients examined, no specific small intestinal lesions were seen on CE. In two patients, CE revealed multiple small intestinal lesions such as ulcerations and/or erosions, and in one patient a duodenal ulceration. Conclusion In the vast majority of patients who fulfil the symptom criteria of IBS, no pathological mucosal lesions can be found by CE explaining the symptomatology. However, a subgroup of these patients may benefit from investigation by CE to reconsider the diagnosis.
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| 19. |
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| 20. |
- Ohlsson, Claes, 1965, et al.
(författare)
-
The role of liver-derived insulin-like growth factor-I.
- 2009
-
Ingår i: Endocrine reviews. - : The Endocrine Society. - 1945-7189 .- 0163-769X. ; 30:5, s. 494-535
-
Forskningsöversikt (refereegranskat)abstract
- IGF-I is expressed in virtually every tissue of the body, but with much higher expression in the liver than in any other tissue. Studies using mice with liver-specific IGF-I knockout have demonstrated that liver-derived IGF-I, constituting a major part of circulating IGF-I, is an important endocrine factor involved in a variety of physiological and pathological processes. Detailed studies comparing the impact of liver-derived IGF-I and local bone-derived IGF-I demonstrate that both sources of IGF-I can stimulate longitudinal bone growth. We propose here that liver-derived circulating IGF-I and local bone-derived IGF-I to some extent have overlapping growth-promoting effects and might have the capacity to replace each other (= redundancy) in the maintenance of normal longitudinal bone growth. Importantly, and in contrast to the regulation of longitudinal bone growth, locally derived IGF-I cannot replace (= lack of redundancy) liver-derived IGF-I for the regulation of a large number of other parameters including GH secretion, cortical bone mass, kidney size, prostate size, peripheral vascular resistance, spatial memory, sodium retention, insulin sensitivity, liver size, sexually dimorphic liver functions, and progression of some tumors. It is clear that a major role of liver-derived IGF-I is to regulate GH secretion and that some, but not all, of the phenotypes in the liver-specific IGF-I knockout mice are indirect, mediated via the elevated GH levels. All of the described multiple endocrine effects of liver-derived IGF-I should be considered in the development of possible novel treatment strategies aimed at increasing or reducing endocrine IGF-I activity.
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| 21. |
- Ohlsson, Jörgen, et al.
(författare)
-
A galabiose-based two-dimensional scaffold for the synthesis of inhibitors targeting Pk- and P-antigen binding proteins.
- 2003
-
Ingår i: Tetrahedron Letters. - 0040-4039. ; 44:14, s. 2785-2787
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Tidskriftsartikel (refereegranskat)abstract
- A disaccharide scaffold based on galabiose (Gal1–4Gal) was synthesized. Four different acceptors were evaluated in the -galactosylation and a relationship between the nucleophilicity, yield, and /-selectivity was found. The scaffold contains two orthogonal derivatisation sites, i.e. at O-2′ and the anomeric position, and as proof of concept, one derivatised galabioside was synthesized. Compounds based on this galabiose-scaffold are potential inhibitors of P- and Pk-antigen binding proteins.
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| 22. |
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| 23. |
- Ohlsson, Jörgen, et al.
(författare)
-
Discovery of potent inhibitors of PapG adhesins from uropathogenic Escherichia coli through synthesis and evaluation of galabiose derivatives
- 2002
-
Ingår i: ChemBioChem. - 1439-4227. ; 3:8, s. 772-779
-
Tidskriftsartikel (refereegranskat)abstract
- The synthesis of two galabioside (Golalpha1-4Gal) collections based on diversification at the O-1 and O-3' atoms is reported. The galabiosides were evaluated as inhibitors of hemagglutination of human erythrocytes by two strains of Escherichia coli that expressed the class I and class II PapG adhesins, respectively. The class I adhesin. was found to prefer aromatic substituents both at the O-1 and the O-3' position of the galabiose disaccharide. One galabioside, p-methoxyphenyl [3-O-(m-nitrobenzyl)-alpha-D-galacto-pyranosyl]-(1-4)-beta-D-galactopyro noside], had an IC50 value of 4.1 mum, which is the best inhibition of the class I adhesin to date.
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| 24. |
- Ohlsson, Jörgen
(författare)
-
Potent inhibitors of uropathogenic E. coli papG adhesins; Synthesis, conformational studies and biological evaluation of galabiose derivatives and synthesis of glycosphingolipid analogues
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The importance of carbohydrates in biological systems has become evident during the last fifty years. It is well known that pathogenic bacteria and viruses attach to glycoconjugates present at mammalian cell surfaces, and that this attachment is a prerequisite for the later stages of infection. Obviously, this interaction is interesting as a target for the development of novel ways to treat bacterial infections. In this thesis, the affinities of galabiose derivatives for PapG class I and II adhesins from uropathogenic E. coli have been investigated. The objective of this project was to further explore the binding event between galabiose and the adhesins, aiming at finding a high-affinity inhibitor. A high-affinity galabioside might have a future as an anti-adhesive therapeutic agent targeting urinary tract infections. A large-scale synthesis of galabiose was developed and seven collections of galabiosides, totally 66 different galabiosides were synthesised and evaluated. For the class I adhesin the best known inhibitor so far was identified, being 20-30 times more potent than the natural ligand globotetraose. For the class II adhesin, associated with pyelonephritis, galabiosides with about the same affinity as the natural tetrasaccharide ligand were found. For the class II adhesin the Kd-values of the best galabiosides are still about 0.1 mM. However, this Kd-value is in the same range as the more synthetically demanding tetrasaccharide. These inhibitors represent the best inhibitors known against the class I and II PapG adhesin and the results constitute an advancement towards anti-adhesion therapeutic agents targeting urinary tract infections. In the examination of glycolipid-lectin interactions, the lipid part has often been neglected. However, during the last years, evidence has accumulated that the mode of presentation influences the recognition event. In order to mimic the binding characteristics in Nature as close as possible, the lipid part should resemble its natural counterpart. In this thesis, synthetic routes to w-mercapto and w-carboxy analogues of glycosphingolipids are described. The lipids were designed to be suitable for functionalization of gold and aminofunctionalized surfaces and to be as similar the natural glycosphingolipids as possible.
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| 25. |
- Ohlsson, Jörgen, et al.
(författare)
-
Structure–activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins
- 2005
-
Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 3:5, s. 886-900
-
Tidskriftsartikel (refereegranskat)abstract
- Four collections of Gal1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the PN and PO adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3 and methoxymethylation at O2 of galabiose provided inhibitors of the S. suis strains type PN adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure–activity relationship models for E. coli PapG adhesin and S. suis adhesin type PO were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.
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| 26. |
- Ohlsson Nevo, Emma, 1960-, et al.
(författare)
-
Patients' perspective in the context of proton beam therapy : summary of a Nordic workshop
- 2020
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 59:10, s. 1139-1144
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionOn 15–16 November 2019, the Skandion Clinic in Sweden hosted the first Nordic workshop on ‘Patients’ perspective in proton beam therapy’. The workshop was conducted to describe and compare the patient care in PBT clinics in the Nordic countries and to initiate a collaboration, with the target to ensure patient participation and reduce the risk of inequity of access by lowering the barriers for accepting PBT in a distant clinic. The overarching aim of this workshop was to describe and compare the use of patients’ perspectives in the Nordic PBT clinics.Material and MethodsTwelve participants attended the workshop, representing Denmark, Norway and Sweden. The participants were registered nurses working in patient care, researchers, physicist and leaders of the Skandion Clinic.ResultsThe consensus of the workshop was that systematic use of patient experiences on individual and group level is essential for developing clinical practice and understanding the overall effects of PBT. A difference in how the Nordic countries use patient experiences in clinical practise was found. The importance of lowering the barriers for participation in national proton trials and proton treatment were emphasized, however, there is a lack of knowledge about individual and organizational barriers to accepting PBT, and further research is therefore needed.ConclusionCollaboration between the Nordic countries regarding patients’ perspectives in the context of PBT is of importance to compare national differences as well as to find similarities, but most importantly to learn from each other and to improve patient care. Nordic collaboration with focus on systematic collection of patient-reported outcomes in the context of PBT is unique. Collaboration in research offers the possibility to increase the inclusion of patients’ perspectives in study protocols.
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| 27. |
- Ohlsson, Sophie, et al.
(författare)
-
Circulating cytokine profile in anti-neutrophilic cytoplasmatic autoantibody-associated vasculitis: prediction of outcome?
- 2004
-
Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 13:4, s. 275-283
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The anti-neutrophilic cytoplasmatic autoantibody-associated vasculitides (AASV) are diseases of relapsing-remitting inflammation. Here we explore the cytokine profile in different phases of disease, looking for pathogenic clues of possible prognostic value. Results: Interleukin (IL)-6, IL-8 and IL-10 were significantly elevated in plasma. Patients in the stable phase who subsequently developed adverse events had higher IL-8 values. Patients in the stable phase who relapsed within 3 months had lower IL-10 values and higher IL-6 levels. Conclusions: Patients with AASV have raised circulating cytokine levels compared with healthy controls, even during remission. Raised IL-8 seems associated with poor prognosis. Lower levels of IL-10 and higher levels of IL-6 herald a greater risk of relapse. Patients with systemic vasculitis in clinical remission have persistent disease activity, kept under control by inhibitory cytokines.
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| 28. |
- Pettersson, Inger, 1962, et al.
(författare)
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Natural (ghrelin) and synthetic (hexarelin) GH secretagogues stimulate H9c2 cardiomyocyte cell proliferation.
- 2002
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 175:1, s. 201-9
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Tidskriftsartikel (refereegranskat)abstract
- Recent experimental data demonstrate cardiovascular effects of the GH secretagogues (GHSs) hexarelin and ghrelin, the proposed natural ligand for the GHS receptor. Moreover, specific cardiac binding sites for GHSs have been suggested. The aim of the present study was to investigate if the natural ligand ghrelin and synthetic GHS peptide hexarelin and analogues have direct effects on the cardiomyocyte cell line, H9c2. Hexarelin stimulated thymidine incorporation in a dose-dependent manner with significant responses at 3 micro M (147+/-3% of control, P<0.01) and elicited maximal effects at concentrations around 30 micro M. This activity was seen already after 12 h of incubation with a maximal effect after 18 h (176+/-9% of control, P<0.01). Ghrelin also had a significant stimulatory effect on thymidine incorporation (129+/-2% of control at 3 micro M and 18 h, P<0.05). The stimulatory effect on thymidine incorporation of hexarelin, Tyr-Ala-hexarelin, EP80317 and ghrelin was specific and no stimulatory effect was observed with the truncated GH-releasing peptide EP51389 or the non-peptidyl GHS MK-0677. In competitive binding studies, (125)I-labeled Tyr-Ala-hexarelin was used as radioligand and competition curves showed displacement with hexarelin, Tyr-Ala-hexarelin, EP80317 and ghrelin, whereas MK-0677 and EP51389 produced very little displacement at 1 micro M concentration, adding further support for an alternative subtype binding site in the heart compared with the pituitary. In conclusion, we have demonstrated a dose-dependent and specific stimulation of cardiomyocyte thymidine incorporation by natural and synthetic GHS analogues, suggesting increased cell proliferation and binding of GHS to H9c2 cardiomyocyte cell membranes. These findings support potential peripheral effects of GHS on the cardiovascular system independent of an increased GH secretion.
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| 29. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 30. |
- Svensson, Johan, 1964, et al.
(författare)
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Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice.
- 2006
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 189:3, s. 617-27
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Tidskriftsartikel (refereegranskat)abstract
- IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer's disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I(-/-)), resulting in an approximately 80-85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I(-/-) and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I(-/-) mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF(-/-) mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I(-/-) mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I(-/-) mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.
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| 31. |
- Svensson, Johan, 1964, et al.
(författare)
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Liver-derived IGF-I regulates exploratory activity in old mice.
- 2005
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 289:3
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) replacement in hypopituitary patients improves well-being and initiative. Experimental studies indicate that these psychic effects may be reflected in enhanced locomotor activity in mice. It is unknown whether these phenomena are mediated directly by GH or by circulating IGF-I. IGF-I production in the liver was inactivated at 6-10 wk of age (LI-IGF-I-/- mice), resulting in an 80-85% reduction of circulating IGF-I, and, secondary to this, increased GH secretion. Using activity boxes on three different occasions during 1 wk, 6-mo-old LI-IGF-I-/- mice had similar activity levels, and 14-mo-old mice had a moderate but significant decrease in activity level, compared with control mice. At 20 mo of age, the LI-IGF-I-/- mice displayed a more prominent decrease in activity level with decreased horizontal activity throughout the test period, and at day 1, there were several signs of an altered habituation process with different time patterns of locomotor activity and horizontal activity compared with the control mice. At days 3 and 5, rearing activity was lower in the 20-mo-old LI-IGF-I-/- mice. Anxiety level was unaffected in all age groups, as measured using the Montgomery's elevated plus-maze. In conclusion, old LI-IGF-I-/- mice displayed a decrease in both horizontal and rearing (exploratory) activity level and an altered habituation process. These results indicate that liver-derived IGF-I mediates at least part of the effects of GH on exploratory activity in mice.
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| 32. |
- Svensson, Johan, 1964, et al.
(författare)
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Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II expression.
- 2007
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 193:3, s. 359-66
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Tidskriftsartikel (refereegranskat)abstract
- The GH/-IGF-I axis is important for kidney size and function and may also be involved in the development of renal failure. In this study, the role of liver-derived endocrine IGF-I for kidney size and function was investigated in mice with adult liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice). These mice have an 80-85% reduction of serum IGF-I level and compensatory increased GH secretion. Seven-month-old as well as 24-month-old LI-IGF-I(-/-) mice had decreased kidney weight. Glomerular filtration rate, assessed using creatinine clearance as well as creatinine clearance corrected for body weight, was unchanged. The 24-h urine excretion of sodium and potassium was increased in the LI-IGF-I(-/-) mice. In the 24-month-old mice, there was no between-group difference in kidney morphology. Microarray and real-time PCR (RT-PCR) analyses showed a high renal expression of IGF-II in the control mice, whereas in the LI-IGF-I(-/-) mice, there was a tissue-specific decrease in the renal IGF-II mRNA levels (-79%, P < 0.001 vs controls using RT-PCR). In conclusion, deficiency of circulating liver-derived IGF-I in mice results, despite an increase in GH secretion, in a global symmetrical decrease in kidney size, increased urinary sodium and potassium excretion, and a clear down regulation of renal IGF-II expression. However, the LI-IGF-I(-/-) mice did not develop kidney failure or nephrosclerosis. One may speculate that liver-derived endocrine IGF-I induces renal IGF-II expression, resulting in symmetrical renal growth.
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| 33. |
- Tivesten, Åsa, 1969, et al.
(författare)
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Growth hormone-induced blood pressure decrease is associated with increased mRNA levels of the vascular smooth muscle KATP channel.
- 2004
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 183:1, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) deficiency is associated with abnormal vascular reactivity and development of atherosclerosis. GH treatment in GH deficient states restores systemic vascular resistance, arterial compliance, endothelium-dependent and endothelium-independent vasodilation, and may reverse markers of early atherosclerosis. However, very little is known about the molecular mechanisms underlying these effects. In the present study, male Sprague Dawley rats were hypophysectomized and treated for two weeks with GH (recombinant human GH, 2 mg/kg/day) or saline as s.c. injections twice daily. GH decreased aortic systolic blood pressure compared with saline-treated animals, while the diastolic blood pressure was not significantly changed. GH treatment increased cardiac output as determined by Doppler-echocardiography and the calculated systemic vascular resistance was markedly reduced. In order to identify GH-regulated genes of importance for vascular function, aortic mRNA levels were analyzed by the microarray technique and correlated to the systolic blood pressure levels. Using this approach, we identified 18 GH-regulated genes with possible impact on vascular tone and atherogenesis. In particular, mRNA levels of the inwardly rectifying potassium channel Kir6.1 and the sulfonylurea receptor 2B, which together form the vascular smooth muscle ATP-sensitive potassium channel, were both up-regulated by GH treatment and highly correlated to systolic blood pressure. Our findings establish a major role for GH in the regulation of vascular physiology and gene expression. Increased expression of the ATP-sensitive potassium channel, recently shown to be crucial in the regulation of vascular tone, constitutes a possible mechanism by which GH governs vascular tone.
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| 34. |
- Tivesten, Åsa, 1969, et al.
(författare)
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Liver-derived insulin-like growth factor-I is involved in the regulation of blood pressure in mice.
- 2002
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Ingår i: Endocrinology. - 0013-7227. ; 143:11, s. 4235-42
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Tidskriftsartikel (refereegranskat)abstract
- IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice. Echocardiography showed increased posterior wall thickness in combination with decreased stroke volume and cardiac output, whereas other systolic variables were unchanged, suggesting that these cardiac effects were secondary to increased peripheral resistance. Acute nitric oxide-synthase inhibition increased systolic BP more in LI-IGF-I-/- mice than in control mice. LI-IGF-I-/- mice showed impaired acetylcholine-induced vasorelaxation in mesenteric resistance vessels and increased levels of endothelin-1 mRNA in aorta. Thus, the increased peripheral resistance in LI-IGF-I-/- mice might be attributable to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice.
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| 35. |
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| 36. |
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| 37. |
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