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1.	Zar, Gustav, et al. (författare) Whole-genome sequencing based on formalin-fixed paraffin-embedded endomyocardial biopsies for genetic studies on outcomes after heart transplantation 2019 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6 Tidskriftsartikel (refereegranskat)abstract Background Whole-genome sequencing (WGS) of heart transplant recipient- and donor-derived cardiac biopsies may facilitate organ matching, graft failure prediction, and immunotolerance research. The objective of this study was to determine the feasibility of WGS based on formalin-fixed paraffin-embedded endomyocardial biopsies. Methods and results The study included serial donor- and recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. DNA extraction and WGS were conducted. Additional WGS sequencing quality metrics and coverage were obtained with the Genome Analysis Toolkit (GATK). 455 endomyocardial samples from 37 heart transplant recipients were acquired from routine rejection monitoring and stored as formalin-fixed paraffin-embedded samples. They were analyzed after 3–26 years of storage. DNA was extracted from 114 samples and WGS was run on 85 samples. DNA extraction yielded 313 ng (IQR 96–601) for all samples. A coverage of 11.3x (IQR 9.0–15.9) was recorded for all WGS samples. Three samples stored for > 25 years yielded a coverage of > 25x. Data were generated for 1.7 billion reads per sample (IQR 1.4–2.7). A Transition/Transversion (TiTv) ratio of 2.09 ± 0.05 was calculated for all WGS samples. No associations were found among storage time, DNA yield, or sequencing quality metrics. Conclusions The present study demonstrated the feasibility of whole-genome sequencing based on endomyocardial biopsies. This process could enable large-scale retrospective genomic studies using stored histopathological samples.
2.	Alim, Abdul, 1983- (författare) Mechanisms in Tendon Healing : Pain, Biomarkers and the Role of Mast Cells 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Tendon injuries and tendinopathy are common disorders, but the underlying mechanisms are not well understood. The overall aim of this thesis was to better understand the mechanisms underlying tendon healing, pain, and inflammation.The aim of the first study was to assess biomarkers of tendon healing, including procollagen type I (PINP) and type III (PIIINP) in relation to patient outcome in 65 patients with Achilles tendon rupture (ATR). At two weeks post-ATR, PINP and PIIINP-levels were quantified using microdialysis followed by ELISA. At one-year post-ATR patient outcome was assessed using the validated Achilles tendon Total Rupture Score. We found that higher ratio of PINP and PIIINP to total protein were significantly associated with less pain but more fatigue in the affected limb.In the second study, we applied Intermittent Pneumatic Compression (IPC) therapy for two weeks to stimulate tendon healing. The patients received either adjuvant IPC treatment or treatment-as-usual in a plaster cast without IPC. We observed that IPC therapy significantly increased PINP levels in the injured tendon, suggesting enhanced healing response.In our third study, we investigated healing response and the role of mast cells (MCs) in-vivo using an ATR rat model. Three weeks postoperatively, we demonstrated an increased number of MCs and a higher proportion of degranulated MCs in the injured tendon compared to the control. We further established that MCs in the injured tendon were positive for the glutamate receptor NMDAR1.In our final study, we assessed the effect of glutamate stimulation on in-vitro-derived mouse bone marrow MCs. Mast cell degranulation was quantified through β-hexosaminidase release, immunofluorescence was used to quantify NMDARs at the protein level, and RT-qPCR/microarray was used to study the expression of NMDARs and associated genes. Glutamate induced a robust upregulation of glutamate receptors of both ionotropic and metabotropic type, both at the mRNA and at protein level. NMDAR1 co-localized with glutamate in the membrane of MCs, thereby confirming an interaction between glutamate and its receptor. Glutamate also induced expression of pro-inflammatory compounds such as IL-6 and CCL2 and transcription factors such as Egr2, Egr3 and FosB. Moreover, the NMDA-channel blocker MK-801 completely abrogated the response of MCs to glutamate, supporting a functional glutamate–glutamate receptor axis in MCs.Together, findings presented in this dissertation reveal possible mechanisms of tendon healing in relation to pain and function, and establish a novel principle for how immune cells can communicate with nerve cells after ATR.
3.	Almqvist, Gustav, et al. (författare) Presentationsformatets betydelse vid kommunikation av risk 2016 Ingår i: Risker och riskhantering i näringsliv och samhälle. - Stockholm : SSE Institute for Research. - 9789186797225 ; , s. 67-94 Bokkapitel (övrigt vetenskapligt/konstnärligt)
4.	Andell, Pontus, et al. (författare) Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study 2017 Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:21, s. 1696-1703 Tidskriftsartikel (refereegranskat)abstract Objective: Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.Methods: We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed.Results: In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%).Conclusions: Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.
5.	Andersson, Anton, et al. (författare) Design of a Foiling Optimist 2018 Ingår i: Journal of Sailboat Technology. ; 2018, s. 1-24 Tidskriftsartikel (refereegranskat)abstract Because of the successful application of hydrofoils on the America's Cup catamarans in the past two campaigns the interest in foiling sailing craft has boosted. Foils have been fitted to a large number of yachts with great success, ranging from dinghies to ocean racers. An interesting question is whether one of the slowest racing boats in the world, the Optimist dinghy, can foil, and if so, at what minimum wind speed. The present paper presents a comprehensive design campaign to answer the two questions. The campaign includes a newly developed Velocity Prediction Program (VPP) for foiling/non-foiling conditions, a wind tunnel test of sail aerodynamics, a towing tank test of hull hydrodynamics and a large number of numerical predictions of foil characteristics. An optimum foil configuration is developed and towing tank tested with satisfactory results. The final proof of the concept is a successful on the water test with stable foiling at a speed of 12 knots.
6.	Andersson, Charlotte, et al. (författare) A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery 2014 Ingår i: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 16:12, s. 1310-1316 Tidskriftsartikel (refereegranskat)abstract BackgroundHeart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. Methods and resultsAll individuals with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n=16827). In total, 1787 (10.6%) died within 30days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute surgery, and body mass index category the following variables predicted mortality (points): male gender (1), age 56-65years (2), age 66-75years (4), age 76-85years (5), or age >85years (7), being underweight (4), normal weight (3), or overweight (1), undergoing acute surgery (5), undergoing high-risk procedures (intra-thoracic, intra-abdominal, or suprainguinal aortic) (3), having renal disease (1), cerebrovascular disease (1), and use of insulin (1). The c-statistic was 0.79 and calibration was good. Mortality risk ranged from <2% for a score <5 to >50% for a score 20. Internal validation by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P<0.05 performed only slightly better, c-statistic=0.81, but was limited in use by its complexity. ConclusionsFor patients with heart failure, this simple index can accurately identify those at low risk for perioperative mortality.
7.	Andersson, Charlotte, et al. (författare) Enhanced Ribosome and tRNA Contents in Escherichia coli Expressing a Truncated Vitreoscilla Hemoglobin Mutant Analyzed by Flow Field-Flow Fractionation 2003 Ingår i: Biotechnology Letters. - 1573-6776. ; 25:18, s. 1499-1504 Tidskriftsartikel (refereegranskat)abstract The ribosome and tRNA levels of Escherichia coli cells, transformed with a native or mutated Vitreoscilla hemoglobin genes (vhb), were investigated using asymmetrical flow field-flow fractionation (AFFFF). Mutagenesis of vhb by error-prone PCR was carried out to alter the growth behavior of microaerobically cultivated native VHb-expressing E. coli. A VHb mutant, pVMT1, was identified, which was able to reach a remarkably high final A600 of 15, the value of which being 160% higher than that of a VHb control carrying pVHb8 (A600 5.8). AFFFF revealed that cells expressing mutant vhbs showed up to a doubling in the number of active 70S ribosomes cell-1, an almost 3-fold increase in the number of tRNAs cell-1, and up to a 26% increase in the mass fraction of active 70S ribosomes.
8.	Andersson, Claes-Henrik, et al. (författare) Synthesis and IR Spectroelectrochemical Studies of a [60]Fulleropyrrolidine-(tricarbonyl)chromium Complex : Probing C-60 Redox States by IR Spectroscopy 2011 Ingår i: European Journal of Inorganic Chemistry. - : John Wiley & Sons. - 1434-1948 .- 1099-1948 .- 1099-0682. ; :11, s. 1744-1749 Tidskriftsartikel (refereegranskat)abstract The synthesis of a new fulleropyrrolidine-(tricarbonyl)chromium complex: 1-methyl-2-(4-methoxyphenyl)-3,4-[60]fulleropyrrolidine-(tricarbonyl)chromium is described together with its characterization by IR, NMR and cyclic voltammetry. IR spectro-electrochemistry has been used to probe the redox level of the fullerene derivative via the relative position of the vibrational bands of the CO ligands, which are sensitive to the electronic state of the complex. Other strategies to incorporate a tricarbonylchromium moiety to fullerene C60 are also briefly discussed and evaluated.
9.	Andersson, Charlotte, et al. (författare) Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System 2014 Ingår i: Clinical Cardiology. - : Wiley. - 1932-8737 .- 0160-9289. ; 37:11, s. 680-686 Tidskriftsartikel (refereegranskat)abstract BackgroundPast research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HypothesisAS is not an independent risk factor for adverse outcomes in noncardiac surgery. MethodsAll patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n=2823; mean age, 75.5years, 53% female) were matched with patients without AS (n=2823) on propensity score for AS and surgery type. ResultsIn elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P=0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P=0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P=0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P=0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P<0.0001). ConclusionsAS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.
10.	Andersson, Christoffer, et al. (författare) Skördekartering av salix 2004 Rapport (refereegranskat)
11.	Andersson, David (författare) Deciding Fast and Slow : How Intuitive and Reflective Thinking Influence Decision Making 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Paper I “Intuition and cooperation reconsidered”: Does intuition make people more cooperative? Rand et al. (Rand, Greene, & Nowak, 2012) reported increased cooperation in social dilemmas after forcing individuals to decide quickly. We test the robustness of this finding in a series of five experiments involving about 2,500 subjects in three countries. None of the experiments confirms the Rand et al. (2012) finding, indicating that their result was an artefact of excluding about 50% of the subjects who failed to respond on time.Paper II “Intuition and moral decision-making – the effect of time pressure and cognitive load on moral judgment and altruistic behavior”: Do individuals intuitively favor certain moral actions over others? This study explores the role of intuitive thinking — induced by time pressure and cognitive load — in moral judgment and behavior. Overall we find converging evidence that intuitive states do not influence moral decisions. Across all samples and decision tasks men were more likely to make utilitarian moral judgments and act selfishly compared to women, providing further evidence that there are robust gender differences in moral decision-making.Paper III “Public views on policies involving nudges”: When should nudging be deemed as permissible and when should it be deemed as intrusive to individuals’ freedom of choice? The main objective of this study is to elicit public views on the use of nudges in policy. In particular we investigate attitudes toward two broad categories of nudges that we label pro-self (i.e. focusing on private welfare) and pro-social (i.e. focusing on social welfare) nudges. Results show that the level of acceptance toward nudge-policies was generally high. Nudge polices classified as pro-social had a significantly lower acceptance rate compared to pro-self nudges.Paper IV “The effect of fast and slow decisions on financial risk-taking”: Are individuals financial risk taking influenced by time available? We experimentally compare fast and slow decisions in a series of experiments on financial risk taking in three countries involving over 1,700 subjects. We find that time pressure increases risk aversion for gains and risk taking for losses compared to time delay; implying that time pressure increase the reflection effect of Prospect Theory.Paper V “Incidental effect and financial risk-taking – a neural investigation: This study builds on the results from Paper IV. Here I explore the influence of incidental negative emotions on financial risk-taking in an fMRI environment in order to assess underlying neural mechanisms. I experimentally compare neutral and unpleasant valence framing on gambles involving pure monetary gain and pure monetary loss. I find a significantly increased BOLD response in left amygdala and bilateral visual cortex when contrasting when showing unpleasant pictures, a neural effect which is in line with previous neuroimaging studies on negative emotions. However the neural effect of showing unpleasant pictures did not affect choices in the risk tasks. Consequently, I did not find any support for the hypothesis that the reflection effect of Prospect theory should be more pronounced when making risky choices influenced by incidental negative emotions.
12.	Andersson, David, et al. (författare) DESCRIBING AND COMPARING HEALTH-RELATED QUALITY OF LIFE DERIVED FROM EQ-5D AND SF-6D IN A SWEDISH GENERAL POPULATION in VALUE IN HEALTH, vol 13, issue 7, pp A240-A240 2010 Ingår i: VALUE IN HEALTH. - : Blackwell Publishing Ltd. ; , s. A240-A240 Konferensbidrag (refereegranskat)abstract n/a
13.	Andersson, Gustav, et al. (författare) Arteries in the area targeted with successful sclerosing injections for Achilles tendinosis are under distinct neural control 2006 Konferensbidrag (refereegranskat)abstract It has been scientifically demonstrated that there are blood vessels with pathologically high blood flow inside and outside the ventral part of the Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. Injections of local anaesthesia on the outside of the ventral part of the tendon have been found to temporarily abolish the tendon pain, and this has been an inspiration in the development of a new approach in the treatment of tendinosis: Based on ultrasound- (US) and colour Doppler- (CD) guidance, the sclerosing substance polidocanol, for many years used in treatment of varicose veins, was injected targeting the area of high-flow blood vessels just outside the ventral part of the Achilles tendon. The treatment has in pilot studies and a randomized controlled clinical study been shown to cure the pain in about 70-80 % of the patients. Also, follow up examinations, using US and CD, have shown a possible remodeling potential of the tendon. There is some previous information available on the innervation patterns of the human Achilles tendon itself. However, the innervation patterns of the area just outside the ventral part of the tendon, i.e. the area that is targeted by the sclerosing injections (target area), are unknown. This includes a lack of information concerning the nerve-related characteristics of the blood vessels in the area. In this study, therefore, tissue specimens from this target area, obtained during surgical treatment of patients with chronic painful mid-portion Achilles tendinosis, were examined. Histological and immunohistochemical examinations were performed. In the tissue of the target area, in which loose connective tissue and fat cells were frequent constituents, there was a presence of arteries and nerve fascicles. The arteries were of varying dimensions, some being very large. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5 (PGP 9.5). Some of the arteries were supplied by an extensive perivascular innervation, as seen via PGP 9.5 staining. As seen via processing for the rate limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), sympathetic innervation was found to be a constituent of this innervation. There was furthermore a marked occurrence of immunoreactions for the α1-adrenoreceptor in arterial walls. Also, there was a presence of immunoreactions for the substance P (SP)-preferred receptor, the neurokinin-1 (NK-1) receptor in arterial walls. This receptor was particularly detected in the endothelial parts. The study shows that the arteries in the target area are accompanied by nerve fascicles and that there is a presence of a perivascular innervation, as well as a presence of adrenergic and NK-1 receptors in arterial walls, in this region. Thus, arteries in this area are under distinct neural control. The nerve-related characteristics of the area targeted in the successful polidicanol injection treatment for Achilles tendinosis are here for the first time shown.
14.	Andersson, Gustav, et al. (författare) Clinical significance of stromal ER and PR expression in periampullary adenocarcinoma 2019 Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 7:1 Tidskriftsartikel (refereegranskat)abstract Background: Tamoxifen treatment has previously been reported to confer life-prolonging effects in patients with advanced pancreatic cancer, and most evidently so in women. None of these trials did however include biomarkers, and the relevance of female hormone signaling in pancreatic or other periampullary adenocarcinoma remains largely unexplored. The aim of this study was to examine the extent and potential clinical significance of estrogen receptor-α (ER) and progesterone receptor (PR) expression in pancreatic and other periampullary cancers. Methods: ER and PR expression was examined using immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, with long-term clinical follow-up. Non-parametric and Chi square tests were applied to examine the associations of stromal ER and PR expression with patient and tumor characteristics. Kaplan-Meier analysis and log rank test were applied to illustrate survival differences in relation to ER and PR expression. Cox regression proportional hazards models were applied to examine the associations between investigative factors and risk of death and recurrence, and to test for interactions between KRAS mutation status and hormone receptor expression in relation to survival. Results: Expression of both ER and PR was more frequent in the tumor-associated stroma than in the epithelium. A significant prognostic interaction, independent of tumor morphology, was found between stromal PR expression and KRAS mutation status in relation to both overall and recurrence-free survival (pinteraction = 0.026 and pinteraction = 0.005), in particular in women (pinteraction = 0.002 and pinteraction = 0.005). Specifically, stromal PR expression was associated with a prolonged survival in patients with KRAS-mutated tumors, whereas the opposite was seen for KRAS wild-type tumors. The prognostic value of ER positivity was limited to the subgroup of women with tumors of pancreatic origin. Conclusions: These results demonstrate that stromal PR rather than ER expression, together with KRAS mutation status, provides long-term prognostic information in patients with periampullary adenocarcinoma. Further study into the mechanistic basis for these observations may unveil important clues to the pathogenesis of these cancers and open up for the discovery of novel treatment options.
15.	Andersson, Gustav, et al. (författare) Hormonal factors and pancreatic cancer risk in women : The Malmö Diet and Cancer Study 2018 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:1, s. 52-62 Tidskriftsartikel (refereegranskat)abstract The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population-based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age-adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age-adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen-only regimen (age-adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.
16.	Andersson, Gustav, et al. (författare) In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T 2018 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8 Tidskriftsartikel (refereegranskat)abstract Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.
17.	Andersson, Gustav, 1983- (författare) Influences of paratendinous innervation and non-neuronal substance P in tendinopathy : studies on human tendon tissue and an experimental model of Achilles tendinopathy 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Pain of the musculoskeletal system is one of the most common reasons for people seeking medical attention, and is also one of the major factors that prevent patients from working. Chronic tendon pain, tendinopathy, affects millions of workers world-wide, and the Achilles tendon is an important structure often afflicted by this condition. The pathogenesis of tendinopathy is poorly understood, but it is thought to be of multifactoral aetiology. It is known that tendon pain is often accompanied not only by impaired function but also by structural tissue changes, like vascular proliferation, irregular collagen organisation, and hypercellularity, whereby the condition is called tendinosis. In light of the poor knowledge of tendinosis pathophysiology and recent findings of a non-neuronal signalling system in tendon tissue, the contributory role of neuropeptides such as substance P (SP) has gained increased interest. SP, known for afferent pain signalling in the nervous system, also has multiple efferent functions and has been described to be expressed by non-neuronal cells. As pain is the most prominent symptom of tendinopathy, the focus of the studies in this thesis was the innervation patterns of the tissue ventral to the Achilles tendon (i.e. the tissue targeted in many contemporary treatment methods) as well as the distribution of SP and its preferred receptor, the neurokinin-1 receptor (NK-1R), in the tendon tissue itself. It was hereby hypothesised that the source of SP affecting the Achilles tendon might be the main cells of the tendon tissue (the tenocytes) as well as paratendinous nerves, and that SP might be involved in tendinosis- development. The studies were conducted, via morphological staining methods including immunohistochemistry and in situ hybridisation, on tendon biopsies from patients suffering from Achilles tendinosis and on those from healthy volunteers. The hypothesis of the thesis was furthermore tested using an experimental animal model (rabbit) of Achilles tendinopathy, which was first validated. The model was based on a previously established overuse protocol of repetitive exercise. In the human biopsies of the tissue ventral to the Achilles tendon, there was a marked occurrence of sympathetic innervation, but also sensory, SP-containing, nerve fibres. NK-1R was expressed on blood vessels and nerve fascicles of the paratendinous tissue, but also on the tenocytes of the tendon tissue proper itself, and notably more so in patients suffering from tendinosis. Furthermore, the human tenocytes displayed not only NK-1R mRNA but also mRNA for SP. The animal model was shown to produce objectively verified tendinosis-like changes, such as hypercellularity and increased vascularity, in the rabbit Achilles tendons, after a minimum of three weeks of the exercise protocol. The contralateral leg of the animals in the model was found to be an unreliable control, as bilateral changes occured. The model furthermore demonstrated that exogenously administered SP triggers an inflammatory response in the paratendinous tissue and accelerates the intratendinous tendinosis-like changes such that they now occur after only one week of the protocol. Injections of saline as a control showed similar results as SP concerning hypercellularity, but did not lead to vascular changes or pronounced paratendinous inflammation. In summary, this thesis concludes that interactions between the peripheral sympathetic and sensory nervous systems may occur in Achilles tendinosis at the level of the ventral paratendinous tissue, a region thought to be of great importance in chronic tendon pain since many successful treatments are directed toward it. Furthermore, the distribution of NK-1R:s in the Achilles tendon described in these studies gives a basis for SP, whether produced by nerves mainly outside the tendon or by tenocytes within the tendon, to affect blood vessels, nerve structures, and/or tendon cells, especially in tendinosis patients. In light of this and of previously known SP-effects, such as stimulation of angiogenesis, pain signalling, and cell proliferation, the proposed involvement of SP in tendinosis development seems likely. Indeed, the animal model of Achilles tendon overuse confirms that SP does induce vascular proliferation and hypercellularity in tendon tissue, thus strengthening theories of SP playing a role in tendinosis pathology.
18.	Andersson, Gustav, et al. (författare) Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon 2017 Ingår i: Histology and Histopathology. - 0213-3911 .- 1699-5848. ; 32:3, s. 263-270 Tidskriftsartikel (refereegranskat)abstract Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.
19.	Andersson, Gustav, 1983-, et al. (författare) Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis 2007 Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 15:10, s. 1272-1279 Tidskriftsartikel (refereegranskat)abstract Ultrasound and Doppler examination has shown high blood flow-neovascularisation inside and outside the ventral Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. In patients with Achilles tendinosis, injections with the sclerosing substance polidocanol, targeting the areas with increased blood flow, have been demonstrated to give pain relief. A drawback when interpreting these findings is the fact that the pattern of nerve supply in the target area, i.e. the ventral area of the tendon, is so far unknown. In this study, therefore, tissue specimens from this area, obtained during surgical treatment of patients with chronic painful midportion Achilles tendinosis, were examined. In the examined area, containing loose connective tissue, the general finding was a presence of large and small arteries and nerve fascicles. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5. The nerve fascicles contain sensory nerve fibers, as shown via staining for the sensory markers substance P (SP) and calcitonin gene-related peptide, and sympathetic nerve fibers as seen via processing for tyrosine hydroxylase. In addition, there were immunoreactions for the SP-preferred receptor, the neurokinin-1 receptor, in blood vessel walls and nerve fascicles. Some of the blood vessels were supplied by an extensive peri-vascular innervation, sympathetic nerve fibers being a distinct component of this innervation. There was also a marked occurrence of immunoreactions for the alpha1-adrenoreceptor in arterial walls as well as in the nerve fascicles. Altogether, these findings suggest that the area investigated is under marked influence by the nervous system, including sympathetic and sensory components. Thus, sympathetic/sensory influences may be involved in the pain mechanisms from this area. In conclusion, the nerve-related characteristics of the area targeted by the polidicanol injection treatment for Achilles tendinosis, are shown here for the first time.
20.	Andersson, Gustav, 1990, et al. (författare) Non-exponential decay of a giant artificial atom 2019 Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2481 .- 1745-2473. ; 15:11, s. 1123-1127 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract In quantum optics, light–matter interaction has conventionally been studied using small atoms interacting with electromagnetic fields with wavelength several orders of magnitude larger than the atomic dimensions1,2. In contrast, here we experimentally demonstrate the vastly different ‘giant atom’ regime, where an artificial atom interacts with acoustic fields with wavelength several orders of magnitude smaller than the atomic dimensions. This is achieved by coupling a superconducting qubit3 to surface acoustic waves at two points with separation on the order of 100 wavelengths. This approach is comparable to controlling the radiation of an atom by attaching it to an antenna. The slow velocity of sound leads to a significant internal time-delay for the field to propagate across the giant atom, giving rise to non-Markovian dynamics4. We demonstrate the non-Markovian character of the giant atom in the frequency spectrum as well as non-exponential relaxation in the time domain.
21.	Andersson, Gustav, et al. (författare) Pancreatic cancer risk in relation to sex, lifestyle factors, and pre-diagnostic anthropometry in the Malmö Diet and Cancer Study 2016 Ingår i: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 7:1 Tidskriftsartikel (refereegranskat)abstract Background: Lifestyle factors may influence the risk of developing pancreatic cancer. Whereas cigarette smoking is an established risk factor, the effects of high alcohol intake and obesity are more uncertain. The aim of the present study was to examine the associations of pre-diagnostic anthropometry, alcohol consumption, and smoking habits with pancreatic cancer risk in a Swedish prospective, population-based cohort, with particular reference to potential sex differences. Methods: The studied cohort consists of 28,098 participants, including all incident cases of pancreatic cancer, in the Malmö Diet and Cancer Study up until December 31, 2013 (n = 163). Non-parametric and chi-squared tests were applied to compare the distribution of risk factors between cases and non-cases. Cox regression proportional hazards models were used to estimate the relationship between investigative factors and pancreatic cancer risk. Anthropometric factors included height, weight, body mass index (BMI), waist and hip circumference, waist-hip ratio (WHR), and body fat percentage. Results: BMI was not a significant risk factor for pancreatic cancer, but a higher WHR was significantly associated with an increased risk in the entire cohort (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.28-4.35, p for trend = 0.009). Regular smoking was a significant risk factor among both women (HR 2.62, 95% CI 1.61-4.27) and men (HR 3.57, 95% CI 1.70-7.47), whereas occasional smoking was a significant risk factor only in women (HR 3.29, 95% CI 1.50-7.19). Passive smoking at work for >20 years was significantly associated with an increased risk in the entire cohort (HR 1.73, 95% CI 1.15-2.58) and in women selectively (HR 2.01, 95% CI 1.21-3.31). Alcohol consumption was not a significant risk factor. A significant interaction was found between female sex and age (p = 0.045), but no other factor, in relation to pancreatic cancer risk. Conclusions: WHR was the only pre-diagnostic anthropometric factor associated with pancreatic cancer risk, with no sex-related differences. Regular smoking was confirmed as a significant risk factor in both sexes, whereas occasional and passive smoking were significant risk factors only in women. Despite the lack of a significant interaction between smoking and sex in relation with pancreatic cancer risk, potential sex differences should be considered in future epidemiological studies.
22.	Andersson, Gustav, 1983-, et al. (författare) Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon 2008 Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 150:1-3, s. 81-87 Tidskriftsartikel (refereegranskat)abstract Nerve signal substances, such as the tachykinin substance P (SP), may be involved in the changes that occur in response to tendinopathy (tendinosis). It is previously known that the level of SP innervation within tendon tissue is limited, but results of experimental studies have suggested that SP may have stimulatory, angiogenetic and healing effects in injured tendons. Therefore, it would be of interest to know if there is a local SP-supply in tendon tissue. In the present study, the patterns of expression of SP and its preferred receptor, the neurokinin-1 receptor (NK-1 R), in normal and tendinosis human Achilles tendons were analyzed by use of both immunohistochemistry and in situ hybridization. We found that there was expression of SP mRNA in tenocytes, and that tenocytes showed expression of NK-1 R at protein as well as mRNA levels. The observations concerning both SP and NK-1 R were most evident for tenocytes in tendinosis tendons. Our findings suggest that SP is produced in tendinosis tendons, and furthermore that SP has marked effects on the tenocytes via the NK-1 R. It cannot be excluded that the SP effects are of importance concerning the processes of reorganization and healing that occur for tendon tissue in tendinosis. In conclusion, it appears as if SPergic autocrine/paracrine effects occur in tendon tissue during the processes of tendinosis, hitherto unknown effects for human tendons.
23.	Andersson, Gustav, et al. (författare) Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival : validatory study of two independent patient cohorts 2014 Ingår i: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 14:1, s. 36- Tidskriftsartikel (refereegranskat)abstract Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
24.	Andersson, Gustav (författare) Sex, hormonal factors and pancreatic cancer 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Pancreatic cancer represents three percent of all incident cancer cases in developed countries, but stands the 7th most common cause of cancer related death. Worldwide, pancreatic cancer is more common among men, however in Sweden, the incidence ratio between sexes is levelling. Despite extensive research to map underlying risk factors, results are still largely inconclusive. Furthermore, there is a lack of knowledge regarding the influence of hormonal factors on risk and clinical outcome. A few studies have investigated the expression of female hormone receptors in pancreatic cancer, and others have reported beneficial effects of tamoxifen treatment in advanced pancreatic cancer, particularly in elderly women. The primary aim of this thesis was to investigate potential risk factors for pancreatic cancer, with particular reference to sex differences, and furthermore, to evaluate the presence and prognostic significance of hormone receptors in pancreatic and other periampullary cancers. Finally, based on the third paper, we composed a protocol for a clinical trial investigating the impact of tamoxifen treatment in women with advanced pancreatic cancer.The thesis is based on the Malmö Diet and Cancer Study (MDCS), a prospective population-based cohort with 28 098 participants, as well as a retrospective cohort with 175 consecutive cases of resected pancreatic and other periampullary adenocarcinoma. Cox proportional hazards regression models were applied to study the potential associations between investigative baseline factors and risk of pancreatic cancer in the MDCS. Immunohistochemical expression of estrogen and progesterone receptors (ER, PR) was analysed on tumour tissue microarrays from the retrospective cohort.Paper I confirms smoking as one of the most significant risk factors for pancreatic cancer, also proposing a greater risk increase among women.Paper II demonstrates an increased risk of pancreatic cancer among women with high age at menarche and a lower risk among postmenopausal women with a history of ever using hormonal replacement therapy.Paper III provides evidence of a prognostic interaction between stromal PR expression and KRAS mutation status in periampullary cancer, being particularly evident in women. More specifically, stromal PR positivity signified a prolonged survival in patients with KRAS-mutated tumours, and shorter survival in patients with KRAS wild-type tumours.Paper IV is a protocol for a single-centre, randomized, double-blind, placebo-controlled, two-arm, phase II clinical trial, investigating the effects of tamoxifen treatment on survival and quality of life in women with advanced pancreatic cancer.In summary, the thesis provides further evidence of tobacco smoking as one of the strongest risk factors for pancreatic cancer, with women being potentially more susceptible to these hazardous effects. Moreover, exogenous female hormones appear to have a protective effect, which is also in line with findings from some previous studies. The presence of ER and PR in the tumour-associated stroma in pancreatic and other periampullary adenocarcinoma, and the prognostic interaction between PR expression and KRAS status further supports that hormonal factors drive the pathogenesis and progression of these cancers. Based on the observations in Paper III, we will launch a randomized trial with tamoxifen treatment and control in women with advanced pancreatic cancer, that will also include relevant biomarker analyses.
25.	Andersson, Gustav, et al. (författare) Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model 2011 Ingår i: British Journal of Sports Medicine. - Loughborough : British Assoc. of Sport and Medicine. - 0306-3674 .- 1473-0480. ; 45:13, s. 1017-1022 Tidskriftsartikel (refereegranskat)abstract Background Tenocytes produce substance P (SP) and its receptor (neurokinin-1 receptor (NK-1R) is expressed throughout the tendon tissue, expecially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these canges.Objectives To test whether development of tendinosislike changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of ecercise with local administration of SP in an establish Achilles tendinopathy model.Methods Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in sity hybridisation to detect NK-1R were conducted.Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes.Conclusions SP accelerated the development of tendinosis-like changes in the rabbit. Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to parateninitis.
26.	Andersson, Gustav, 1983-, et al. (författare) Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy : contralateral effects suggest the involvement of central neuronal mechanisms 2011 Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 45:5, s. 399-406 Tidskriftsartikel (refereegranskat)abstract Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion-extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.
27.	Andersson, Johan, et al. (författare) Processintern metananrikning vid gödselrötning : försök i pilotskala 2014 Rapport (refereegranskat)
28.	Andersson, Karl, et al. (författare) Förslag till handlingsplan för utveckling av LTU Skellefteå : Att synas med stolthet 2008 Rapport (övrigt vetenskapligt/konstnärligt)
29.	Andersson, Karl Gustav (författare) Finite Fields and Error-Correcting Codes - Lecture Notes in Mathematics 2015 Annan publikation (övrigt vetenskapligt/konstnärligt)
30.	Andersson, M, et al. (författare) Accuracy in multiangle light scattering measurements for molar mass and radius estimations. Model calculations and experiments. 2003 Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 75:16, s. 4279-4291 Tidskriftsartikel (refereegranskat)abstract Multiangle light scattering (MALS) is a well-established technique used to determine the size of macromolecules and particles. In this study, different extrapolation procedures used in MALS were investigated with regard to accuracy and robustness in the obtained molar mass and rms radius. Three different mathematical transformations of the light scattering function referred to as the Debye, Zimm, and Berry methods for constructing the Debye plot were investigated for two idealized polymer shapes, homogeneous spheres and random coils, with radii from 25 to 250 nm. The effect of the angular interval used for the extrapolation was investigated, as was the robustness of the different transformations toward errors in the measured light scattering intensity at low angles. For an rms radius less than 50 nm, the relative error in molar mass due to extrapolation was less than 1% independent of the method used. For larger radii, the error increased and the extrapolation procedure became more critical. For random coil polymers, the Berry method was superior in terms of accuracy and robustness. For spheres, the Debye method was superior. The Zimm method was inferior to the others. The different extrapolation methods were evaluated and compared on experimental data from a size exclusion chromatography-MALS analysis of an ultrahigh molar mass poly(ethylene oxide) (PEO). The PEO data qualitatively verified the calculations and stressed the importance of optimizing the extrapolation procedure after careful evaluation of the experimental data. A discussion of how to detect erroneous data in an experimental Debye plot is given.
31.	Andersson, Martin, et al. (författare) Analysis of film coating thickness and surface area of pharmaceutical pellets using fluorescence microscopy and image analysis 2000 Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - 0731-7085. ; 22:2, s. 325-339 Tidskriftsartikel (refereegranskat)
32.	Andersson, M, et al. (författare) NIR spectroscopy on moving solids using a scanning grating spectrometer - impact on multivariate process analysis 2005 Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439. ; 75:1, s. 1-11 Tidskriftsartikel (refereegranskat)abstract The effect of sample movement on spectral response during fiber probe diffuse reflectance near-infrared spectrometry (NIR) sampling was characterized. This is of central importance in Process Analytical Chemistry (PAC) and Process Analytical Technology (PAT). The incitement to this study was the observation of spectral artifacts during measurements of powder samples in process streams when using a mechanically scanning spectrometer. Artifacts appeared as momentary changes in the spectral response during acquisition of a scan. These transitions emanate from continuous replacement of the sample subfraction seen by the probe and are typical for turbid media where sample properties may vary locally with respect to scattering and/or absorption. The impact on qualitative and quantitative analysis using chemometric methods such as principal component analysis (PCA) and partial least squares (PLS) regression was evaluated through experimental and theoretical simulations. It was generally found that spectra with the smallest residuals after projection onto the models came from non-moving samples or samples moving only slowly. It is shown that the magnitude of the spectral residuals is directly connected to the effective sample size, which relates both to sample speed as well as to the sample area presented to the probe. Implications for in-line/on-line process analysis of solids are discussed. (C) 2004 Elsevier B.V. All rights reserved.
33.	Andersson, M, et al. (författare) Size and Structure Characterization of Ethylhydroxyethyl Cellulose by the Combination of Field-Flow Fractionation with Other Techniques. Investigation of Ultralarge Components 2004 Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 5:1, s. 97-105 Tidskriftsartikel (refereegranskat)abstract Ethylhydroxyethyl cellulose (EHEC) of three different viscosity classes (EHEC I, II, and III) was analyzed by programmed cross-flow asymmetrical flow field-flow fractionation coupled to multiangle light scattering and refractive index detectors to determine their size and molar mass distribution. Two size populations were detected in the two lower viscosity classes, EHEC I and II, one high molar mass and one ultrahigh molar mass (UHM). The two covered molar masses from 104 up to 109 g·mol-1. The highest viscosity class EHEC III was less size-dispersed covering molar masses from 5 × 105 to 5 × 107 g·mol-1. Filtering of the EHEC II solution removed small amounts of compact UHM material. Enzyme treatments were performed on EHEC II to further characterize it. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and anion ion-exchange chromatography coupled to pulsed amperometric detection showed that the UHM component contained EHEC.
34.	Andersson, Mikael, et al. (författare) The multivariate use of vibrational spectroscopy for chemical characterisation of chromatography media 2002 Ingår i: Vibrational Spectroscopy. - 0924-2031 .- 1873-3697. ; 29, s. 133-138 Tidskriftsartikel (refereegranskat)
35.	Andersson, Roland, et al. (författare) Gut barrier failure in critical illness: lessons learned from acute pancreatitis 2006 Ingår i: Journal of Organ Dysfuntion. - : Informa UK Limited. - 1747-1060 .- 1747-1079. ; 2:2, s. 93-100 Tidskriftsartikel (refereegranskat)abstract Gut barrier function is essential in critical illness and contributes to the systemic inflammatory response. Failure of the gut barrier includes both changes in microbial ecology, permeability and potential translocation, as well as local gut inflammatory response. The present review summarizes experiences made from acute pancreatitis, including pathophysiological mechanisms and ways of intervention.
36.	Andersson, Sarah, et al. (författare) Malmbanan Diaries 2010 Rapport (övrigt vetenskapligt/konstnärligt)abstract This booklet is a report for a case study visit during four day field trip, a group of nine PhD students and their supervisors – all part of the National Research School for Architecture and Planning in the Urban Landscape, APULA – set out to explore what may be considered the outback of Western Europe’s conurbations, the transnational region of Kiruna -Narvik.Both “remote” and “resourceful”, “threatened” and “thriving” (equally relative notions), this region seemed to offer possibilities to reflect upon many of the current tendencies influencing contemporary planning practice and research.
37.	Andersson, Ulf, 1973, et al. (författare) Strategies for Cost- and Time-effective Use of Abrasive Waterjet Cutting 2005 Ingår i: Proc of the 2005 WJTA American Waterjet Conference. ; 2005, s. 7B-2 Konferensbidrag (refereegranskat)
38.	Axelsson, Jakob B, et al. (författare) Initiation of acute pancreatitis by heparan sulphate in the rat. 2008 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 43:4, s. 480-489 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The initiating events in the onset of pancreatitis are poorly understood. Possible candidates may be endogenous ligands, acting on receptors within ductal, acinar or stellate cells, which have previously been shown to cause a systemic inflammatory response syndrome. The aim of this study was to investigate whether acute pancreatitis could be induced by heparan sulphate (HS)infused into the pancreatic ducts in the rat. MATERIAL AND METHODS: Retrograde biliary-pancreatic infusion of heparan sulphate of different structures, taurodeoxycholate (TDC) or phosphate buffered saline (PBS) was performed. Local pancreatic inflammation was evaluated after 6 h by means of morphological evaluation, neutrophil and macrophage infiltration and levels of plasma amylase. Systemic inflammation was evaluated by measuring plasma IL-6, MCP-1 and CINC-1 concentrations. RESULTS: Heparan sulphate induced a local inflammatory response visualized as a rapid infiltration of neutrophils and macrophages into the pancreas. Heparan sulphate induced inflammation and oedema without causing damage to acinar cells, as measured by morphological changes and plasma amylase concentrations. Furthermore, an increase in serum concentrations of CINC-1 and IL-6 was seen. The positive control (TDC) had increased levels of all variables analysed and the negative control (heparan sulphate administered intraperitoneally) was without effects. CONCLUSIONS: Our findings suggest a receptor-mediated innate immune response of the pancreatic cells induced by heparan sulphate. This finding may be helpful in elucidating some of the mechanisms involved during the initiation of pancreatitis, as well as in the search for a potential future therapeutic application.
39.	Axelsson, Jakob B, et al. (författare) Intestinal bacteria and permeability during experimental acute pancreatitis in rats 2006 Ingår i: Annals of Gastroenterology. - 1108-7471. ; 19:3, s. 276-284 Tidskriftsartikel (refereegranskat)abstract Background: An increase in intestinal permeability and subsequent bacterial translocation has been demonstrated in critical illness. Cellulose derivatives have in the past been shown to reduce gut leakage following liver resection. Aims: The aim of the present study was to evaluate changes in microbial counts in experimental acute pancreatitis and the effect of pre-treatment with cellulose derivatives and N-acetyl cysteine. Subjects: 92 male Sprague Dawley rats. Methods: Acute pancreatitis was induced by intraductal taurodeoxycholic acid infusion. Animals received oral pretreatment and were randomized to either sham operation or the pancreatitis groups, with or without pre-treatment with cellulose derivatives, the antioxidant or their combinations. Intestinal bacterial populations and permeability were evaluated using bacterial counts and Ussing chamber, respectively. Results: The number of E. coli increased in the luminal content and ileal and colonic mucosa, but levels were restored to almost those seen in controls in all pre-treatment groups except for N-acetyl cysteine. When intestinal permeability was measured, none of the treatment groups showed significant differences compared to challenge, except for Nacetyl cysteine, which significantly increased permeability. Conclusion: Pre-treatment with cellulose derivatives was more efficient against disturbances in intestinal permeability and microbial populations than the antioxidant Nacetyl cysteine.
40.	Backman, Ludvig, et al. (författare) Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy : peptidergic elevation preceding tendinosis-like tissue changes 2011 Ingår i: Journal of Musculoskeletal and Neuronal Interactions - JMNI. - : International Society of Musculoskeletal and Neuronal Interactions. - 1108-7161. ; 11:2, s. 133-140 Tidskriftsartikel (refereegranskat)abstract Objectives: To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established modelfor Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in thetendon. Methods: Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercisedcontrols. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed.Results: EIA revealedincreased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in thecontrols (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statisticallysignificant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptorwas also found on tenocytes.Conclusions: Achilles tendon SP-levels are elevated already after 1 week of loading. This showsthat increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise,as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends wereobserved in the contralateral Achilles tendon.
41.	Backman, Ludvig J, et al. (författare) Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity : comparison between two model systems 2013 Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 23:6, s. 687-696 Tidskriftsartikel (refereegranskat)abstract The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α(2A) AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α(2A) AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α(2A) AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.
42.	Backman, Ludvig, et al. (författare) Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation 2011 Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 6:11, s. e27209- Tidskriftsartikel (refereegranskat)abstract It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell (R) technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10(-7) M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.
43.	Bockgård, Gustav, 1975- (författare) Syntax som social resurs : En studie av samkonstruktionssekvensers form och funktion i svenska samtal 2004 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract One prerequisite in order for conversation to take place is cooperation between the participants. In other words, each person must adjust his or her behavior according to the actions of the other participants. One method that the speakers use in interaction is the co-construction of syntactic units. A speaker can complete or add on to a unit begun by another person. The subject of this dissertation is conversational sequences containing co-constructed units. The methods employed are drawn from the field known as interactional linguistics, which can be viewed as a subdiscipline of conversation analysis (CA) with influences from linguistics. The focus of interactional linguistics is the investigation of how linguistic forms interact with various social norms and structures and with the actions carried out during interaction. As a starting point for the analysis, a distinction between different categories of co-constructions is made. The various categories have quite different prototypical functions when they occur in an interactive situation. However, there are also certain functional qualities that cross the boundaries between categories. A very prominent pattern in the material is that speakers do not continue another person’s utterance in order to interrupt them or manipulate their words. Instead, the producer of the syntactic continuation strengthens solidarity between herself and the other speaker by helping, showing sympathy, indicating understanding, or agreeing with that person. “Sponging off” another speaker’s syntactic unit constitutes an excellent resource for initiating and maintaining various cooperative projects.
44.	Boman, Karolina, et al. (författare) Podocalyxin-like and rna-binding motif protein 3 are prognostic biomarkers in urothelial bladder cancer : A validatory study 2017 Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 5:1, s. 1-10 Tidskriftsartikel (refereegranskat)abstract Background: Urothelial bladder cancer (UBC) is a disease that often is discovered when the tumour is non-muscle invasive, i.e. in Ta or T1 stage. Some patients will progress into muscle-invasive disease, a potentially deadly condition. Although there are some prognostic models, the need for prognostic and predictive biomarkers is considerate and urgent. Membranous expression of podocalyxin-like protein 1 (PODXL) and low expression of the RNA-binding motif 3 (RBM3) has previously been shown to be associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer, including UBC. In this study, we sought to validate the prognostic impact of PODXL and RBM3 in an independent cohort of UBC. Methods: Using tissue microarrays and immunohistochemistry, PODXL and RBM3 expression was evaluated in 272 incident UBC cases from the prospective, population-based cohort study Malmö Diet and Cancer. Kaplan-Meier analysis and Cox proportional hazards modelling were used to evaluate the prognostic impact of these markers on 5-year overall survival (OS). Results: In line with previous studies, both membranous PODXL expression and low RBM3 expression was significantly associated with disadvantageous clinicopathological features. Membranous PODXL expression was significantly associated with a reduced 5-year overall survival in the entire cohort (univariable HR 3.28; 95% CI 1.89-5.69), but this association did not remain significant in multivariable analysis. In T1 tumours, PODXL was significantly associated with reduced survival in univariable analysis (HR = 2.83; 95% CI 1.04-7.72) and borderline significant in multivariable analysis (HR = 2.60; 95% CI 0.91-7.39). Low RBM3 expression was an independent predictor of a reduced survival in the entire cohort (univariable HR 3.19; 95% CI 2.02-5.04, and multivariable HR 1.85; 95% CI 1.11-3.09), and in T1 tumours (univariable HR 2.64; 95% CI 1.11-6.27, and multivariable HR 2.63; 95% CI 1.01-6.84). Conclusions: A link between membranous PODXL expression and clinically more aggressive tumours was further confirmed, but PODXL expression was not an independent prognostic biomarker in this study. Low RBM3 expression was validated as an independent factor of poor prognosis in UBC, including T1 disease. These findings suggest that these biomarkers could be useful in stratifying patients with non-muscle invasive disease for more aggressive first line treatment.
45.	Brolen, Gabriella, et al. (författare) Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage 2010 Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 145:3, s. 284-294 Tidskriftsartikel (refereegranskat)abstract Human embryonic stem cells offer a potential unlimited supply for functional hepatocytes, since they can differentiate into hepatocyte-like cells displaying a characteristic hepatic morphology and expressing various hepatic markers. These cells could be used in various applications such as studies of drug metabolism and hepatotoxicity, which however, would require a significant expression of drug metabolizing enzymes. To derive these cells we use a stepwise differentiation protocol where growth- and maturation factors are added. The first phase involves the formation of definitive endoderm. Next, these cells are treated with factors known to promote the induction and proliferation towards hepatic progenitor cell types. In the last phase the cells are terminally differentiated and maturated into functional hepatocyte-like cells. The cultures were characterized by analysis of endodermal or hepatic markers and compared to cultures derived without induction via definitive endoderm. Hepatic functions such as urea secretion, glycogen storage, indocyanine green uptake and secretion, and cytochrome P450-expression and activity were evaluated. The DE-Hep showed a hepatocyte morphology with sub-organized cells and exhibited many liver-functions including transporter activity and capacity to metabolize drugs specific for important cytochrome P450 sub-families. This represents an importantstep in differentiation of hESC into functional hepatocytes. (C) 2009 Elsevier B.V. All rights reserved.
46.	Christensen, Jens, et al. (författare) Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy 2015 Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 11 Tidskriftsartikel (refereegranskat)abstract Background/Aim: Tendinopathies are pathological conditions of tissue remodelling occurring in the major tendons of the body, accompanied by excessive nociceptive signalling. Tendinopathies have been shown to exhibit an increase in the number of mast cells, which are capable of releasing histamine, tryptase and other substances upon activation, which may play a role in the development of tendinopathies. This study set out to describe the distribution patterns of a family of receptors called protease-activated receptors (PARs) within the Achilles tendon. These four receptors (PAR1, PAR2, PAR3, PAR4) are activated by proteases, including tryptase released from mast cells, and are involved in fibrosis, hyperalgesia and neovascularisation, which are changes seen in tendinopathies. Method: In order to study which structures involved in tendinopathy that these proteases can affect, biopsies from patients suffering of mid-portion Achilles tendinosis and healthy controls were collected and examined using immunohistochemistry. Tendon cells were cultured to study in vitro expression patterns. Results: The findings showed a distribution of PARs inside the tendon tissue proper, and in the paratendinous tissue, with all four being expressed on nerves and vascular structures. Double staining showed co-localisation of PARs with nociceptive fibres expressing substance P. Concerning tenocytes, PAR2, PAR3, and PAR4, were found in both biopsies of tendon tissue and cultured tendon cells. Conclusions: This study describes the expression patterns of PARs in the mid-portion of the Achilles tendon, which can help explain the tissue changes and increased pain signalling seen in tendinopathies. These findings also show that in-vitro studies of the effects of these receptors are plausible and that PARs are a possible therapeutic target in the future treatment strategies of tendinopathy.
47.	Christiansen, Mia N., et al. (författare) Age-specific Trends in Incidence, Mortality and Comorbidities of Heart Failure in Denmark 1995-2012 2017 Ingår i: Circulation. - 0009-7322. ; 135:13, s. 1214-1223 Tidskriftsartikel (refereegranskat)abstract BACKGROUND—: The cumulative burden and importance of cardiovascular risk factors have changed over the last decades. Specifically, obesity rates have increased among younger people, whereas cardiovascular health has improved in the elderly. Little is known regarding how these changes have impacted the incidence and the mortality rates of heart failure. Therefore, we aimed to investigate the age-specific trends in the incidence and 1-year mortality rates following a first time diagnosis of heart failure in Denmark between 1995 and 2012. METHODS—: We included all Danish individuals over the age of 18 years with a first-time in-hospital diagnosis of heart failure. Data was collected from 3 nationwide Danish registries. Annual incidence rates of heart failure and 1-year standardized mortality rates were calculated under the assumption of a Poisson distribution. RESULTS—: We identified 210,430 individuals with a first-time diagnosis of heart failure between 1995 and 2012; the annual incidence rates per 10,000 person-years declined among older individuals (rates in 1995 vs. 2012: 164 vs. 115 in >74 years, 63 vs. 35 in 65-74 years, and 20 vs. 17 in 55-64 years, p<0.0001 for all) but increased among the younger (0.4 vs. 0.7 in 18-34 years, 1.3 vs. 2.0 in 35-44 years, and 5.0 vs. 6.4 in 45-54 years, p<0.0001 for all). The proportion of patients with incident heart failure below 51 years doubled from 3% in 1995 to 6% in 2012 (p<0.0001). Sex- and age-adjusted incidence rate ratios for 2012 vs. 1996 were 0.69 (95%CI 0.67-0.71; p <0.0001) among people >50 years, and 1.52 (95%CI 1.33-1.73; p<0.0001) among individuals ≤50 years; it remained essentially unchanged upon additional adjustment for diabetes, ischemic heart disease, and hypertension. Standardized 1-year mortality rates declined for middle-aged patients with heart failure but remained constant for younger (<45 years) and elderly (≥65 years). The prevalence of comorbidities (including diabetes, hypertension, and atrial fibrillation) increased, especially in younger patients with heart failure. CONCLUSIONS—: Over the last two decades, the incidence of heart failure in Denmark declined among older (>50 years), but increased among younger (≤50 years) individuals. These observations may portend a rising burden of heart failure in the community.
48.	Christiansen, Mia Nielsen, et al. (författare) Prevalence of heart failure and other risk factors among first-degree relatives of women with peripartum cardiomyopathy 2019 Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:14, s. 1057-1062 Tidskriftsartikel (refereegranskat)abstract Objectives: Peripartum cardiomyopathy (PPCM) is a rare disease carrying a risk of death and chronic heart failure.It is unknown if women with PPCM have a family history of heart failure. We investigated the prevalence of heart failure and hypertension in first-degree relatives to women with PPCM. Methods: A cohort of 61 women with PPCM was identified through the nationwide Danish registers from 2005 to 2014, and each individual diagnosis of PPCM was validated through review of patient records. We excluded 13 women due to lack of data on relatives. In a case-control design, the 48 remaining women were matched (on age, year of childbirth, parity and number of siblings) to 477 birth-giving Danish women without heart failure. We obtained information on first-degree relatives (parents and siblings) through the National Danish Registers. Results: The cohort of 48 women with PPCM had a mean age of 31 years (SD 6). The prevalence of heart failure in any first-degree relative was higher in women with PPCM, compared with controls (23% vs 10%, p=0.011). A first-degree relative with any cardiovascular diagnosis was not more frequent in women with PPCM versus controls (77% vs 70%, p=0.280), but for siblings only, any cardiovascular diagnosis was more frequent in siblings to women with PPCM (29% vs 16%, p=0.026). Conclusion: Having a first-degree relative with heart failure was significantly more frequent in a cohort of validated PPCM cases than in controls, supporting the notion of shared aetiology between PPCM and other forms of heart failure.
49.	Czembrowski, Piotr, et al. (författare) Valuing individual characteristics and the multifunctionality of urban green spaces : The integration of sociotope mapping and hedonic pricing 2019 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3 Tidskriftsartikel (refereegranskat)abstract We categorize Stockholm's urban green spaces according to the use values and social meanings they support, based on a sociotope mapping, and estimate their impact on property prices with a hedonic pricing model. The approach allows us to identify the most and least desired green space characteristics (attributes) and to assess the willingness to pay for the multifunctionality of green spaces. To do this, we test the following hypotheses, each with a separate hedonic pricing model: .The proximity of all green space characteristics increases the property prices, but the specific monetary value of these characteristics differs; . the multifunctionality of green spaces is well recognized and highly valued by real estate buyers. We find partial support for the first hypothesis: the green space attributes of aesthetics, social activity and nature seem to be desired by real estate buyers, whereas physical activity and play seem not to be desired. We also find support for the second hypothesis: the higher the number of characteristics an urban green space has, the stronger its impact on property prices. This study furthers the discussion on the economic value of urban green spaces by assigning monetary value to their perceived character and use values. In doing so, it highlights the need to understand green spaces both as ecological features and social constructs.
50.	Danielson, Patrik, et al. (författare) Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study. 2007 Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 80:24-25, s. 2235-2238 Tidskriftsartikel (refereegranskat)abstract We have recently obtained evidence favoring the occurrence of an up-regulation of a non-neuronal cholinergic system in chronic painful patellar tendon tendinosis. It seems possible that this up-regulation to a certain degree may be involved in the manifestations of the disease. Today, there is a new, very successful, line of treatment of patellar tendinosis in the form of Doppler guided sclerosing injections. However, a few patients seem resistant to this therapy. Therefore, we have in this pilot study investigated biopsies from the patellar tendon of three such therapy-resistant patients, using immunohistochemistry. In situ hybridization was also applied. Comparisons were made with a material of specimens from both normal (n=16) and tendinosis (n=7) tendons, also previously examined. The study showed that there were extensive immunoreactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter, as well as for the M(2) muscarinic acetylcholine receptor, in the overwhelming majority of the tenocytes. The immunoreactions were more pronounced than those generally obtained in the tendinosis tissue of the previously studied patients and clearly more pronounced than those of patellar tendon tissue of controls. Also, for the first time, we here present findings of mRNA for ChAT within tenocytes. In conclusion, it appears as if there is an excessive local acetylcholine (ACh) production and an occurrence of marked ACh effects in cases of severe tendinosis. An excessive production of local ACh might be related to pain sensation and the processes that occur in tendinosis development, such as cell proliferation. Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis.

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