| 1. |
- Lau, Joey, et al.
(författare)
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Implantation site-dependent dysfunction of transplanted pancreatic islets
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1544-1550
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function. RESEARCH DESIGN AND METHODS—Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression. RESULTS—Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets. CONCLUSIONS—Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.
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| 2. |
- Margolin, Sara, et al.
(författare)
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A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.
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| 3. |
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| 4. |
- Henriksnäs, Johanna, et al.
(författare)
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Markedly Decreased Blood Perfusion of Pancreatic Islets Transplanted Intraportally Into the Liver : Disruption of Islet Integrity Necessary for Islet Revascularization
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:3, s. 665-673
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased hi islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels.
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| 5. |
- Lau, Joey, et al.
(författare)
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Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets
- 2009
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 18:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas Would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were Cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS-1). Capillary numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the intrapancreatic site reflected expansion of remnant donor endothelial cells or increased ingrowth of blood vessels from the host. also islets from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP-positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites.
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| 6. |
- Lyckesvärd, Madeleine Nordén, et al.
(författare)
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Linking loss of sodium-iodide symporter expression to DNA damage
- 2016
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 344:1, s. 120-131
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (< 1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. (C) 2016 Elsevier Inc. All rights reserved.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Palm, Fredrik, et al.
(författare)
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Effects of the contrast medium iopromide on renal hemodynamics and oxygen tension in the diabetic rat kidney
- 2003
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Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 530, s. 653-659
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the effects of the contrast medium (CM) iopromide on regional renal blood flow and oxygen tension (pO2) in the streptozotocin (STZ)-induced diabetic Wistar Furth rats. RESULTS: In normoglycemic rats, CM injection induced a transient decrease followed by an increase in renal cortical blood flow (CBF), whereas CBF increased directly in the diabetic animals. Renal outer medullary blood flow (OMBF) increased in controls, while it decreased in the diabetic animals following CM injection. In control rats a marked initial decrease in OM pO2 following injection of CM was observed. In animals diabetic for 4 weeks only a slight decrease was seen, whereas in 9-week diabetic animals a persistent increase was recorded. CONCLUSIONS: An altered oxygen tension and hemodynamic response to CM was found in diabetic rats. If these disturbances may contribute to the development of renal dysfunction by CM in the diabetic rat kidney remains to be elucidated.
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| 12. |
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| 13. |
- Tersmeden, Fredrik, et al.
(författare)
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350 näsor under 350 år
- 2018
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Bok (populärvet., debatt m.m.)abstract
- Lättsamt biografiskt översiktsverk med korta personbeskrivningar i ord och bild av dels de 190 personer som t o m 2017 införlivats i Akademiska Föreningens Nasotek, dels ytterligare 160 lundaanknutna historiska personer.
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| 14. |
- Thornell, Lars-Eric, et al.
(författare)
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Fibre typing of intrafusal fibres
- 2015
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Ingår i: Journal of Anatomy. - : John Wiley & Sons. - 0021-8782 .- 1469-7580. ; 227:2, s. 136-156
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Forskningsöversikt (refereegranskat)abstract
- The first descriptions of muscle spindles with intrafusal fibres containing striated myofibrils and nervous elements were given approximately 150years ago. It took, however, another 100years to establish the presence of two types of intrafusal muscle fibres: nuclear bag and nuclear chain fibres. The present paper highlights primarily the contribution of Robert Banks in fibre typing of intrafusal fibres: the confirmation of the principle of two types of nuclear bag fibres in mammalian spindles and the variation in occurrence of a dense M-band along the fibres. Furthermore, this paper summarizes how studies from the Umea University group (Laboratory of Muscle Biology in the Department of Integrative Medical Biology) on fibre typing and the structure and composition of M-bands have contributed to the current understanding of muscle spindle complexity in adult humans as well as to muscle spindle development and effects of ageing. The variable molecular composition of the intrafusal sarcomeres with respect to myosin heavy chains and M-band proteins gives new perspectives on the role of the intrafusal myofibrils as stretch-activated sensors influencing tension/stiffness and signalling to nuclei.
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| 15. |
- von Seth, Erik, et al.
(författare)
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Distribution of intraportally implanted microspheres and fluorescent islets in mice
- 2007
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 16:6, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the distribution of intraportally transplanted islets in mice. We initially administered 2000 polystyrene microspheres with a diameter of 50 microm intraportally into normoglycemic C57BL/6 mice. In separate experiments other mice were injected similarly with 300 microspheres each with a diameter of 100 or 200 microm. One week later the animals were killed, and the lungs and livers were removed and divided into lobes. The number of microspheres in each individual liver lobe and in the lungs was counted using a stereomicroscope. In other experiments, athymic C57BL/6 mice were similarly implanted with 250 islets isolated from transgenic mice expressing the enhanced yellow fluorescent protein in the islet cells. The distribution of microspheres and islets was independent of size, and fairly homogenous within the liver, with the exception of the caudate lobe, which contained fewer microspheres and islets, respectively. Approximately one third of all microspheres and islets were present as aggregates. Eighty-five to 90% of the implanted microspheres were identified in the liver sections, whereas 60-65% of the implanted islets were recovered. Aggregates or single fluorescent cells were observed in the liver of islet-implanted mice. We conclude that islets and microspheres implanted into the liver distribute fairly homogenously and quite a few of them exist as aggregates or, with respect to islets, as fragments.
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| 16. |
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| 17. |
- Andersson, Swen-Olof, et al.
(författare)
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Managing localized prostate cancer by radical prostatectomy or watchful waiting: Cost analysis of a randomized trial (SPCG-4)
- 2011
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Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 45:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The cost of radical prostatectomy (RP) compared to watchful waiting (WW) has never been estimated in a randomized trial. The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care. Material and methods. This investigation used the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, comparing RP to WW, and included data from 212 participants living in two counties in Sweden from 1989 to 1999 (105 randomized to WW and 107 to RP). All costs were included from randomization date until death or end of follow-up in July 2007. Resource use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient. Results. During a median follow-up of 12 years, the overall cost in the RP group was 34% higher (p andlt; 0.01) than in the WW group, corresponding to euroa,not sign6123 in Sweden. The difference was driven almost exclusively by the cost of the surgical procedure. The cost difference between RP and WW was two times higher among men with low (2--6) than among those with high (7--10) Gleason score. Conclusion. In this economic evaluation of RP versus WW of localized prostate cancer in a randomized study, RP was associated with 34% higher costs. This difference, attributed exclusively to the cost of the RP procedure, was not overcome during extended follow-up.
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| 18. |
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| 19. |
- Beausang, Angela, et al.
(författare)
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"Möjligheten att rädda några av dessa kvinnors liv har inte vägts in"
- 2014
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Ingår i: Dagens Medicin. - : Dagens Medicin.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
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| 20. |
- Bentzer, Peter, et al.
(författare)
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Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat.
- 2003
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 20:5, s. 447-461
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.
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| 21. |
- Blomberg, Sara, et al.
(författare)
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Combining synchrotron light with laser technology in catalysis research
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 1600-5775 .- 0909-0495. ; 25:5, s. 1389-1394
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Tidskriftsartikel (refereegranskat)abstract
- High-energy surface X-ray diffraction (HESXRD) provides surface structural information with high temporal resolution, facilitating the understanding of the surface dynamics and structure of the active phase of catalytic surfaces. The surface structure detected during the reaction is sensitive to the composition of the gas phase close to the catalyst surface, and the catalytic activity of the sample itself may affect the surface structure, which in turn may complicate the assignment of the active phase. For this reason, planar laser-induced fluorescence (PLIF) and HESXRD have been combined during the oxidation of CO over a Pd(100) crystal. PLIF complements the structural studies with an instantaneous two-dimensional image of the CO2 gas phase in the vicinity of the active model catalyst. Here the combined HESXRD and PLIF operandomeasurements of CO oxidation over Pd(100) are presented, allowing for an improved assignment of the correlation between sample structure and the CO2distribution above the sample surface with sub-second time resolution.
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| 22. |
- Boström, Pontus, 1982, et al.
(författare)
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Hypoxia converts human macrophages into triglyceride-loaded foam cells.
- 2006
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 26:8, s. 1871-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerotic lesions have regions that are hypoxic. Because the lesion contains macrophages that are loaded with lipid, we investigated whether hypoxia can influence the accumulation of lipids in these cells. METHODS AND RESULTS: Exposure of human macrophages to hypoxia for 24 hours resulted in an increased formation of cytosolic lipid droplets and an increased accumulation of triglycerides. Exposure of the macrophages to oxidized low-density lipoprotein (oxLDL) increased the accumulation of cytosolic lipid droplets because of an increase in cellular cholesterol esters. The accumulation of lipid droplets in oxLDL-treated cells was further increased after hypoxia, caused by an increased level of triglycerides. Expression analyses combined with immunoblot or RT-PCR demonstrated that hypoxia increased the expression of several genes that could promote the accumulation of lipid droplets. Hypoxia increased the mRNA and protein levels of adipocyte differentiation-related protein (ADRP). It is well known that an increased expression of ADRP increases the formation of lipid droplets. Hypoxia decreased the expression of enzymes involved in beta-oxidation (acyl-coenzyme A synthetase and acyl-coenzyme A dehydrogenase) and increased the expression of stearoyl-coenzyme A desaturase, an important enzyme in the fatty acid biosynthesis. Moreover, exposure to hypoxia decreased the rate of beta-oxidation, whereas the accumulation of triglycerides increased. CONCLUSIONS: The results demonstrate that exposure of human macrophages to hypoxia causes an accumulation of triglyceride-containing cytosolic lipid droplets. This indicates that the hypoxia present in atherosclerotic lesions can contribute to the formation of the lipid-loaded macrophages that characterize the lesion and to the accumulation of triglycerides in such lesions.
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| 23. |
- Carlbom, Lina, et al.
(författare)
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[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:5, s. 1286-1292
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Tidskriftsartikel (refereegranskat)abstract
- [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.
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| 24. |
- Carlbom, Lina, et al.
(författare)
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Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:9, s. 1968-1972
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals.METHODS: Eight individuals with longstanding type 1 diabetes and ten sex-, age- and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with (15)O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references.RESULTS: Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.
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| 25. |
- Carlsson, Anna, et al.
(författare)
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Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1
- 2002
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 59:11, s. 1804-1807
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Tidskriftsartikel (refereegranskat)abstract
- Migraine is the most common type of chronic episodic headache. To find novel susceptibility genes for familial migraine with and without aura, a genomewide screen was performed in a large family from northern Sweden. Evidence of linkage was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of 5.41 for marker D6S452. The patients with migraine shared a common haplotype of 10 Mb between markers D6S1650 and D6S1960.
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| 26. |
- Carlsson, Frida, et al.
(författare)
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Prevalence of annoyance attributed to electrical equipment and smells in a Swedish population, and relationship with subjective health and daily functioning
- 2005
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Ingår i: Public Health. - : Elsevier BV. - 1476-5616 .- 0033-3506. ; 119:7, s. 568-577
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Self-reported annoyance from electrical equipment has been in evidence since the mid-1980s, and the first reports of illness from everyday chemicals arose in the 1960s. However, the extent of the problem has not yet been fully established.AIMS: The aim of this study was to estimate the prevalence of annoyance related to electrical and chemical factors in a Swedish general population, and to assess possible relationships with subjective health and daily functioning.METHODS: In total, 13,604 subjects, representative of the population of Scania, Sweden, answered a survey containing five questions regarding annoyance from five environmental factors: fluorescent tube lighting, visual display units, other electrical equipment, air that smells of chemicals, and other smells. The survey also obtained data on self-reported health (SRH-7), mental well-being [General Health Questionnaire (GHQ)-12], work situation and daily functioning.RESULTS: Almost one-third of the respondents reported annoyance from at least one environmental factor. Annoyance was more frequent among women, subjects of working age and immigrants. Subjects who reported environmental annoyance scored higher on GHQ-12 and lower on SRH-7, indicating impaired subjective physical and mental well-being. They were also more likely to report deteriorated daily functioning.CONCLUSIONS: Annoyance related to electrical and/or chemical factors was common in a Swedish population. Subjects reporting environmental annoyance rated their overall health significantly poorer than the general population. The association with subjective health and functional capacity increased with severity of annoyance, which suggests that there is some connection between environmental annoyance, well-being and functional capacity.
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| 27. |
- Carlsson, Frida, et al.
(författare)
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Representativity of a postal public health questionnaire survey in Sweden, with special reference to ethnic differences in participation
- 2006
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 34:2, s. 132-139
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Non-participation in health surveys is a common phenomenon. When differences between participants and non-participants are considerable, the external validity of the sample survey may decrease and false conclusions might be drawn about the health status of the population. For this reason, the authors aimed to investigate the representativity of a postal questionnaire survey performed in the county of Scania, Sweden, in 1999-2000. The survey, which was based on an 18- to 80-year-old population sample, had a 58% response rate (n = 13 604).METHODS: For some variables, the information obtained using the questionnaire was compared with information obtained from a population register that covers all the population in the county (for the 18- to 80-year-old group, n = 850 476). The population register includes, among other data, information on age, gender, educational level, country of birth, and healthcare expenditure.RESULTS: Men, individuals with a low level of education, and immigrants were under-represented in the survey. However, except for immigrants, the under-representation was not large. Among immigrants, particularly those born in former Yugoslavia, the Arabic-speaking countries, and Poland were very significantly under-represented in the study. By contrast, immigrants born in other Nordic countries had responded to almost the same extent as respondents born in Sweden. The survey sample had about the same healthcare utilization costs as did the general population.CONCLUSIONS: In summary, the "Health Survey for Scania, 2000" seems largely representative of the total Scanian population. A major concern, however, is the under-representation of the immigrant population.
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| 28. |
- Carlsson, Gunilla
(författare)
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Det våldsamma mötets fenomenologi : - om hot och våld i psykiatrisk vård
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study focuses on the phenomenology of the violent encounter, and is to be understood as the study of the violent encounter as a phenomenon, i.e. as experienced. The overall aim is to elucidate, analyse and describe violent encounters within psychiatric care as experienced by carers and patients. Moreover, the study aims at promoting the development of a phenomenological research approach in caring science in general and elucidating tacit caring knowledge in particular.The thesis includes three empirical studies and one methodological study. The research is guided by a phenomenological and lifeworld theoretical approach. Research data consist of narratives and qualitative interviews, as well as reenactment interviews with carers and patients. Data are analysed for meaning. The analysis and synthesis of meaning are aimed at openness and meaning sensitivity through a reflective attitude characterised by the intent to bridle the process of understanding. The goal of the analysis is to describe the general structure of the phenomenon and its meaning constituents.The result shows that violence and threat do not evolve in “naked” caring, characterised by encounters where carers are able to touch their patients at the same time as being touched, speaking both literally and figuratively. It is through “naked” caring and caring touch that the carers are able to reach the patients and to give undisguised invitations to genuine presence. The possibilities of touch rely on the carers’ capacity to be authentic and to genuinely wish well. Violence is on the contrary nourished by touch without caring intention, or non-touch, i.e. caring where the reciprocity of touching and being touched is missing between patients and caregivers.In the discussion, the different meanings of the violent encounter are related to the philosophy of Merleau-Ponty and Lévinas. The philosophical dimensions of touch are investigated and it is discussed how the “naked” encounter can be understood from a phenomenological ethical standpoint. The discussion focuses on the caregivers’ vulnerability and the high demands they are subjected to. It is also argued that a foundation of caring science is needed in caring practice in order to make possible a development of a caring attitude that prevents violence.
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| 29. |
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| 30. |
- Carlsson, Per-Olof, et al.
(författare)
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Testfasen i miljöklassningsprojekten : Delrapport september 2007
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport är en redovisning av resultat och underlag i testfasen imiljöklassningsprojekten.I januari 2005 inleddes tre forskningsprojekt med målet att föreslå ettsystem för miljöklassning av byggnader. Forskningsprojekten har engemensam projektgrupp där 27 företag ingår. Syftet med projekten är attta fram förslag till indikatorer och kriterier för klassning inom områdenaenergi, innemiljö och farliga ämnen. Projekten avslutas hösten 2007.Under perioden december 2006 – mars 2007 genomfördes ett test avflera alternativa förslag till indikatorer. Testet utfördes i nära samverkanmed 16 företag från projektgruppen och ytterligare 10 bostadsrättföreningaroch 6 småhusägare. Sammanlagt ingick 46 byggnader av olika typ(flerbostadshus, kontor, sjukhus, småhus etc.).Testet utfördes genom att företag, föreningar och småhusägare samladein nödvändiga data för klassning av ett antal preliminära indikatorer. Defick också svara på frågor om prioritering av aspekter, indikatorer ochvilka resurser som krävdes.Insamlingen av mätdata kompletterades sedan med intervjuer för att fåin ytterligare information och synpunkter.Denna rapport innehåller resultat i form av:Indata från dem som testat.Försök till klassning av respektive byggnad.Synpunkter på genomförandet av testningen.Synpunkter på klassningssystemet.Dessutom ingick en studie av kopplingen mellan energideklarationer ochmiljöklassning. Några av byggnaderna energideklarerades och dessa datajämfördes med vad som behövs för miljöklassning.Rapporten innehåller samtliga dokument från testningen och kommeratt vara ett viktigt underlag i det fortsatta arbetet. Under hösten 2007kommer ett förslag till klassningssystem att presenteras.
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| 31. |
- Carlsson, Per-Ola, et al.
(författare)
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Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus
- 2018
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 18:7, s. 1735-1744
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Tidskriftsartikel (refereegranskat)abstract
- Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800-4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.
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| 32. |
- Carlsson, Staffan, et al.
(författare)
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Boxing for biodiversity: evaluation of an artificiallycreated decaying wood habitat
- 2016
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Ingår i: Biodiversity and Conservation. - : Springer Science+Business Media B.V.. - 0960-3115 .- 1572-9710. ; 25:2, s. 393-405
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Tidskriftsartikel (refereegranskat)abstract
- Many saproxylic species are threatened in Europe because of habitat decline.Hollow trees represent an important habitat for saproxylic species. Artificial habitats mayneed to be created to maintain or increase the amount of habitat due to natural habitat decline.This study investigated the extent to which saproxylic beetles use artificial habitats in woodenboxes. The boxes were placed at various distances (0–1800 m) from known biodiversityhotspots with hollow oaks and studied over 10 years. Boxes were mainly filled with oak sawdust, oak leaves, hay and lucerne flour. In total, 2170 specimens of 91 saproxylic beetlespecies were sampled in 43 boxes. The abundance of species associated with tree hollows,wood rot and animal nests increased from the fourth to the final year, but species richnessdeclined for all groups. This study shows that wooden boxes can function as saproxylicspecies habitats. The artificial habitats developed into a more hollow-like environment duringthe decade long experiment with fewer but more abundant tree hollow specialists.
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| 33. |
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| 34. |
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| 35. |
- Ericsson, Olle, et al.
(författare)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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Ingår i: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 36. |
- Eriksson, Olof, et al.
(författare)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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| 37. |
- Espes, Daniel, 1985-, et al.
(författare)
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Longitudinal Assessment of 11C-5-Hydroxytryptophan Uptake in Pancreas After Debut of Type 1 Diabetes
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:4, s. 966-975
-
Tidskriftsartikel (refereegranskat)abstract
- The longitudinal alterations of the pancreatic β-cell and islet mass in the progression of type 1 diabetes (T1D) are still poorly understood. The objective of this study was to repeatedly assess the endocrine volume and the morphology of the pancreas for up to 24 months after T1D diagnosis (n = 16), by 11C-5-hydroxytryptophan (11C-5-HTP) positron emission tomography (PET) and MRI. Study participants were examined four times by PET/MRI: at recruitment and then after 6, 12, and 24 months. Clinical examinations and assessment of β-cell function by a mixed-meal tolerance test and fasting blood samples were performed in connection with the imaging examination. Pancreas volume has a tendency to decrease from 50.2 ± 10.3 mL at T1D debut to 42.2 ± 14.6 mL after 24 months (P < 0.098). Pancreas uptake of 11C-5-HTP (e.g., the volume of the endocrine pancreas) did not decrease from T1D diagnosis (0.23 ± 0.10 % of injected dose) to 24-month follow-up, 0.21 ± 0.14% of injected dose, and exhibited low interindividual changes. Pancreas perfusion was unchanged from diagnosis to 24-month follow-up. The pancreas uptake of 11C-5-HTP correlated with the long-term metabolic control as estimated by HbA1c (P < 0.05). Our findings argue against a major destruction of β-cell or islet mass in the 2-year period after diagnosis of T1D.
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| 38. |
- Espes, Daniel, et al.
(författare)
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Quantification of Beta-Cell Mass in Intramuscular Islet Grafts using Radiolabeled Exendin-4
- 2016
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Ingår i: Transplantation Direct. - 2373-8731. ; 2:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor [beta]-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular [beta]-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys40-Exendin-4.Methods: One hundred to 400 islets were transplanted to the abdominal muscle of nondiabetic mice. After 3 to 4 weeks, 0.2 to 0.5 MBq [177Lu]DO3A-VS-Cys40-Exendin-4 was administered intravenously. Sixty minutes postinjection abdominal organs and graft bearing muscle were retrieved, and the radioactive uptake measured in a well counter within 10 minutes. The specific uptake in native and transplanted islets was assessed by autoradiography. The total insulin-positive area of the islet grafts was determined by immunohistochemistry.Results: Intramuscular islet grafts could easily be visualized by this tracer, and the background uptake was very low. There was a linear correlation between the radioactivity uptake and the number of transplanted islets, both for standardized uptake values and the total radiotracer uptake in each graft (percentage of injected dose). The quantified total insulin area of surviving [beta] cells showed an even stronger correlation to both standardized uptake values (R = 0.96, P = 0.0002) and percentage of injected dose (R = 0.88, P = 0.0095). There was no correlation to estimated [alpha] cell mass.Conclusions: [177Lu]DO3A-VS-Cys40-Exendin-4 could be used to quantify [beta]-cell mass after experimental intramuscular islet transplantation. This technique may well be transferred to the clinical setting by exchanging Lutetium-177 radionuclide to a positron emitting Gallium-68.
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| 39. |
- Espes, Daniel, et al.
(författare)
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Striated Muscle as Implantation Site for Transplanted Pancreatic Islets
- 2011
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Ingår i: Journal of Transplantation. - : Hindawi Limited. - 2090-0007 .- 2090-0015. ; 2011, s. 352043-
-
Forskningsöversikt (refereegranskat)abstract
- Islet transplantation is an attractive treatment for selected patients with brittle type 1 diabetes. In the clinical setting, intraportal transplantation predominates. However, due to extensive early islet cell death, the quantity of islets needed to restore glucose homeostasis requires in general a minimum of two donors. Moreover, the deterioration of islet function over time results in few insulin-independent patients after five-year followup. Specific obstacles to the success of islet transplantation include site-specific concerns for the liver such as the instant blood mediated inflammatory reaction, islet lipotoxicity, low oxygen tension, and poor revascularization, impediments that have led to the developing interest for alternative implantation sites over recent years. Within preclinical settings, several alternative sites have now been investigated and proven favorable in various aspects. Muscle is considered a very promising site and has physiologically properties and technical advantages that could make it optimal for islet transplantation.
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| 40. |
- Gustafson, Johan, et al.
(författare)
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High-energy surface X-ray diffraction for fast surface structure determination
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6172, s. 758-761
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the interaction between surfaces and their surroundings is crucial in many materials-science fields such as catalysis, corrosion, and thin-film electronics, but existing characterization methods have not been capable of fully determining the structure of surfaces during dynamic processes, such as catalytic reactions, in a reasonable time frame. We demonstrate an x-ray-diffraction–based characterization method that uses high-energy photons (85 kiloelectron volts) to provide unexpected gains in data acquisition speed by several orders of magnitude and enables structural determinations of surfaces on time scales suitable for in situ studies. We illustrate the potential of high-energy surface x-ray diffraction by determining the structure of a Pd surface in situ during catalytic CO oxidation and follow dynamic restructuring of the surface with subsecond time resolution.
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| 41. |
- Hadimeri, Henrik, et al.
(författare)
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A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure
- 2013
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Ingår i: Renal failure. - : Informa Healthcare. - 0886-022X .- 1525-6049. ; 35:6, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Background: The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome.Methods: The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 mu mol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement.Results: At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium x phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1.Conclusions: However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.
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| 42. |
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| 43. |
- Hovbrandt, Pia, et al.
(författare)
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Psychosocial working conditions and social participation. A 10-year follow-up of senior workers.
- 2021
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 18:17, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Social participation is important for health, and it is well known that high strain jobs impact negatively on mental and physical health. However, knowledge about the impact of psychosocial working conditions on social participation from a long-term perspective is lacking. The purpose of this study was to investigate the associations between different job types and social participation from a long-term perspective. A comprehensive public health questionnaire “The Scania Public Health Survey”, was used, and psychosocial working conditions were measured with a Swedish translation of the Job Content Questionnaire. Based on data from 1098 working respondents aged 55 at baseline and a 10-year follow-up when the respondents were not working, the analyses revealed that social participation varied by job type. Jobs with high decision latitude, as in active and relaxed jobs, seem to predict high social participation, even after cessation of employment. Besides that, the result suggests that high social participation during working life is a predictor of high social participation from a long-term perspective which promotes healthy aging. Incentives for working longer are strongly related to good working conditions. A supportive work environment with possibilities for employees to participate in decision making, i.e., high control, is vital for a sustainable working life. This may contribute to an extended working life and may also support social participation prior to retirement as well as after retirement and thus to healthy aging.
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| 44. |
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| 45. |
- Lindnér, Per, 1956, et al.
(författare)
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Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
- 1994
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Ingår i: Anticancer research. - 0250-7005. ; 14:3A, s. 847-52
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Tidskriftsartikel (refereegranskat)abstract
- In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.
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| 46. |
- Lundälv, Jörgen, 1966, et al.
(författare)
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Hur trygg är en spårvagnsresa? En studie om risker, otillgänglighet och barriärer för personer med funktionsnedsättningar.
- 2024
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Ingår i: Socialmedicinsk Tidskrift. - 0037-833X. ; 101:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- Studien har identifierat ett antal intressanta möjligheter och potentialer för att främja säkerhet och utökade åtgärder för att förebygga de risker och olyckor som kan inträffa vid färd med spårvagn. Studien visar hur personer med olika funktionsnedsättningar måste ha möjlighet att göra hela sin resa med kollektivtrafik. I artikeln diskuteras hur respondenterna avstår från att resa, dels för att de inte alltid kan avgöra vilken spårvagn som kommer och om den som kommer blir tillgänglig, men också för att undvika en osäker ramp. Osäkra tillstånd kan skapa stress och ökad transportfattigdom. Blotta vetskapen om att något kan hända leder till ”resestress” eller ”kollektivtrafikstress”, som visar sig på olika sätt, som irritation på medpassagerare eller frustration över oförmågan att ta sig till skolan eller jobbet i tid.
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| 47. |
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| 48. |
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| 49. |
- Lyth, Johan, et al.
(författare)
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A decision support model for cost-effectiveness of radical prostatectomy in localized prostate cancer
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - London, United Kingdom : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to develop a probabilistic decision support model to calculate the lifetime incremental cost-effectiveness ratio (ICER) between radical prostatectomy and watchful waiting for different patient groups.Material and methods: A randomized trial (SPCG-4) provided most data for this study. Data on survival, costs and quality of life were inputs in a decision analysis, and a decision support model was developed. The model can generate cost-effectiveness information on subgroups of patients with different characteristics.Results: Age was the most important independent factor explaining cost-effectiveness. The cost-effectiveness value varied from 21,026 Swedish kronor (SEK) to 858,703 SEK for those aged 65 to 75 years, depending on Gleason scores and prostate-specific antigen (PSA) values. Information from the decision support model can support decision makers in judging whether or not radical prostatectomy (RP) should be used to treat a specific patient group.Conclusions: The cost-effectiveness ratio for RP varies with age, Gleason scores, and PSA values. Assuming a threshold value of 200,000 SEK per quality-adjusted life-year (QALY) gained, for patients aged ≤70 years the treatment was always cost-effective, except at age 70, Gleason 0-4 and PSA ≤10. Using the same threshold value at age 75, Gleason 7-9 (regardless of PSA) and Gleason 5-6 (with PSA >20) were cost-effective. Hence, RP was not perceived to be cost-effective in men aged 75 years with low Gleason and low PSA. Higher threshold values for patients with clinically localized prostate cancer could be discussed
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| 50. |
- Mansouri, Mahmoud Reza, et al.
(författare)
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Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure
- 2008
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:23, s. 3776-83
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Tidskriftsartikel (refereegranskat)abstract
- Premature ovarian failure (POF) is characterized by hypergonadotropic hypogonadism and amenorrhea before the age of 40. The condition has a heterogeneous background but genetic factors are demonstrated by the occurrence of familial cases. We identified a mother and daughter with POF both of whom carry an X;autosome translocation [t(X;11)(q24;q13)]. RNA expression studies of genes flanking the X-chromosome breakpoint revealed that both patients have reduced expression levels of the gene Progesterone Receptor Membrane Component-1 (PGRMC1). Mutation screening of 67 females with idiopathic POF identified a third patient with a missense mutation (H165R) located in the cytochrome b5 domain of PGRMC1. PGRMC1 mediates the anti-apoptotic action of progesterone in ovarian cells and it acts as a positive regulator of several cytochrome P450 (CYP)-catalyzed reactions. The CYPs are critical for intracellular sterol metabolism, including biosynthesis of steroid hormones. We show that the H165R mutation associated with POF abolishes the binding of cytochrome P450 7A1 (CYP7A1) to PGRMC1. In addition, the missense mutation attenuates PGRMC1's ability to mediate the anti-apoptotic action of progesterone in ovarian cells. These findings suggest that mutant or reduced levels of PGMRC1 may cause POF through impaired activation of the microsomal cytochrome P450 and increased apoptosis of ovarian cells.
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