| 51. |
- Li, Sandra, et al.
(författare)
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Interference with Glycosaminoglycan-Chemokine Interactions with a Probe to Alter Leukocyte Recruitment and Inflammation In Vivo
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e104107-
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Tidskriftsartikel (refereegranskat)abstract
- In vivo leukocyte recruitment is not fully understood and may result from interactions of chemokines with glycosaminoglycans/GAGs. We previously showed that chlorite-oxidized oxyamylose/COAM binds the neutrophil chemokine GCP-2/CXCL6. Here, mouse chemokine binding by COAM was studied systematically and binding affinities of chemokines to COAM versus GAGs were compared. COAM and heparan sulphate bound the mouse CXC chemokines KC/CXCL1, MIP-2/CXCL2, IP-10/CXCL10 and I-TAC/CXCL11 and the CC chemokine RANTES/CCL5 with affinities in the nanomolar range, whereas no binding interactions were observed for mouse MCP-1/CCL2, MIP-1 alpha/CCL3 and MIP-1 beta/CCL4. The affinities of COAM-interacting chemokines were similar to or higher than those observed for heparan sulphate. Although COAM did not display chemotactic activity by itself, its co-administration with mouse GCP-2/CXCL6 and MIP-2/CXCL2 or its binding of endogenous chemokines resulted in fast and cooperative peritoneal neutrophil recruitment and in extravasation into the cremaster muscle in vivo. These local GAG mimetic features by COAM within tissues superseded systemic effects and were sufficient and applicable to reduce LPS-induced liver-specific neutrophil recruitment and activation. COAM mimics glycosaminoglycans and is a nontoxic probe for the study of leukocyte recruitment and inflammation in vivo.
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| 52. |
- Lindén, Mårten, et al.
(författare)
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Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer
- 2012
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 12:1, s. 135-144
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Tidskriftsartikel (refereegranskat)abstract
- Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.
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| 53. |
- Lindén, Mårten, et al.
(författare)
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Tumour expression of bladder cancer-associated urinary proteins
- 2013
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 112:3, s. 407-415
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Tidskriftsartikel (refereegranskat)abstract
- WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?:The current basis for diagnosis and prognosis in urinary bladder cancer is based on the pathologists' assessment of a biopsy of the tumour. Urinary biomarkers are preferable as they can be non-invasively sampled. Urinary cytology is the only test with widespread use but is hampered by poor reproducibility and low sensitivity.By studying the protein expression in bladder tumour tissue samples of proteins previously found in elevated levels in the urine of patients with bladder cancer, we have been able to show that these proteins originate from the tumour. The immunoreactivity of three of the investigated proteins increased with higher stage. Also a serine peptidase inhibitor was found to be predictive of progression from non-muscle-invasive to muscle-invasive tumours.OBJECTIVES:To analyse the expression of five bladder cancer-associated urinary proteins and investigate if expression is related to the malignant phenotype of the tumour.To explore the possible prognostic value of these proteins.PATIENTS AND METHODS:Urine samples, 16 from patients with bladder cancer and 26 from controls, were used in Western Blotting experiments.Tissue microarrays with bladder tissue from 344 patients diagnosed with bladder cancer between 1984 and 2005 was used in immunohistochemistry experiments.The proteins apolipoprotein E (APOE), fibrinogen β chain precursor (FGB), leucine-rich α2-glycoprotein (LRG1), polymerase (RNA) I polypeptide E (POLR1E), α1-antitrypsin (SERPINA1) and topoisomerase 2A (TOP2A) were probed with antibodies validated by the Human Protein Atlas.RESULTS:Increased expressions of APOE, FGB and POLR1E were correlated with increased tumour stage (P < 0.001).Expression of SERPINA1 in Ta and T1 tumours was found to increase the risk of tumour progression (hazard ratio 2.57, 95% confidence interval 1.13-5.87; P = 0.025)CONCLUSIONS: All proteins previously detected in urine from patients with bladder cancer were also expressed in bladder cancer tissue.The expression of APOE, FGB and POLR1E increased with stage and they are potential diagnostic markers.SERPINA1 was identified as a prognostic marker candidate.
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| 54. |
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| 55. |
- Lorentzon, Ronny, et al.
(författare)
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The Achilles heel of exercise.
- 2000
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355:9218, s. 1909-10; author reply 1911
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Tidskriftsartikel (refereegranskat)
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| 56. |
- Müezzinler, Aysel, et al.
(författare)
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Smoking and All-cause Mortality in Older Adults : Results From the CHANCES Consortium
- 2015
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Ingår i: American Journal of Preventive Medicine. - : Elsevier BV. - 0749-3797 .- 1873-2607. ; 49:5, s. e53-e63
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.
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| 57. |
- Muhrman, Karolina, 1976-, et al.
(författare)
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Lärarstudenters övergång från lärarutbildning till arbete som lärare i skolan
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport handlar om övergången från lärarutbildning till arbete som lärare i skolan. Rapporten bygger på intervjuer med tjugo relativt nyutexaminerade lärare och en enkät som besvarats av 87 skolledare. Resultaten visar att förväntningarna på de nya lärarnas kunskaper och förmåga att klara alla delar av yrket efter utbildningen är hög hos skolledarna. Samtidigt beskriver de nya lärarna att de upplever många utmaningar med läraryrket och att det finns ett behov av en mentor som kan ge stöd under det första året. De flesta nya lärare får en mentor, men i många fall får varken mentorn eller den nya läraren någon tid avsatt för att träffas. Detta kan leda till att de nya lärarna trots att de har en mentor inte får det stöd de har behov av. I svaren från informanterna framkommer både tankar om hur mottagandet av nya lärare skulle kunna bli bättre och hur lärarutbildningen skulle kunna utvecklas för att det ska bli en bättre övergång. Resultaten från dessa svar är grunden till de förslag på implikationer som avslutar rapporten.
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| 58. |
- Mustamäki, Noora, et al.
(författare)
-
Fjällbacka, Västerhavet, 1989–2019; Torhamn, södra Egentliga Östersjön, 2002–2019; Kvädöfjärden, Egentliga Östersjön, 1981–2019; Holmöarna, Bottniska viken, 1989–2019
- 2020
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Ingår i: Faktablad från integrerad kustfiskövervakning.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Inom den nationella miljöövervakningen av kust och hav bedrivs årligen sedan slutet av 1980-talet ett program för integrerad kustfiskövervakning i fyra nationella referensområden, ett vardera i Bottniska viken, Egentliga Östersjön, södra Egentliga Östersjön och Västerhavet. Syftet med programmet är att kartlägga fiskbeståndens status samt fiskens hälsotillstånd och miljögiftsbelastning för att upptäcka förändringar som indikerar storskalig påverkan av miljöhot som eutrofiering, miljögifter, klimatförändringar och andra miljöfaktorer. Detta faktablad sammanfattar resultaten från den integrerade kustfiskövervakningen i alla fyra områden under tidsperioden 1980–2019.
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| 59. |
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| 60. |
- Nethander, Maria, 1980, et al.
(författare)
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An atlas of genetic determinants of forearm fracture.
- 2023
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Ingår i: Nature genetics. - : Springer Nature. - 1546-1718 .- 1061-4036. ; 55:11, s. 1820-1830
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4-/- mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.
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