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  • 251.
    Alkhori, Liza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
    Alenius, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    The corepressor Atrophin specifies odorant receptor expression in Drosophila2014In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, no 3, p. 1355-1364Article in journal (Refereed)
    Abstract [en]

    In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses one odorant receptor (OR) from a large genomic repertoire. How a receptor is specified is a tantalizing question addressing fundamental aspects of cell differentiation. Here, we demonstrate that the corepressor Atrophin (Atro) segregates OR gene expression between OSN classes in Drosophila. We show that the knockdown of Atro result in either loss or gain of a broad set of ORs. Each OR phenotypic group correlated with one of two opposing Notch fates, Notch responding, Nba (N(on)), and nonresponding, Nab (N(off)) OSNs. Our data show that Atro segregates ORs expressed in the Nba OSN classes and helps establish the Nab fate during OSN development. Consistent with a role in recruiting histone deacetylates, immunohistochemistry revealed that Atro regulates global histone 3 acetylation (H3ac) in OSNs and requires Hdac3 to segregate OR gene expression. We further found that Nba OSN classes exhibit variable but higher H3ac levels than the Nab OSNs. Together, these data suggest that Atro determines the level of H3ac, which ensures correct OR gene expression within the Nba OSNs. We propose a mechanism by which a single corepressor can specify a large number of neuron classes.-Alkhori, L., Öst, A., Alenius, M. The corepressor Atrophin specifies odorant receptor expression in Drosophila.

  • 252.
    Alkmin, Diego V.
    et al.
    University of Murcia, Spain.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Barranco, Isabel
    University of Murcia, Spain.
    Parrilla, Inmaculada
    University of Murcia, Spain.
    Vazquez, Juan M.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Roca, Jordi
    University of Murcia, Spain.
    Boar sperm cryosurvival is better after exposure to seminal plasma from selected fractions than to those from entire ejaculate2014In: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 69, no 2, p. 203-210Article in journal (Refereed)
    Abstract [en]

    Boar bulk ejaculates are now being collected instead of usual sperm-rich fractions (SRF) for artificial insemination purpose. The present study evaluated the influence of holding boar sperm samples before freezing surrounded in their own seminal plasma (SP), from either fractions/portions or the entire ejaculate, on post-thawing sperm quality and functionality. Ejaculates collected as bulk (BE) or as separate (first 10 mL of SRF [P1] and rest of SRF [P2]) from 10 boars were held 24 h at 15-17 degrees C and then frozen. Some bulk ejaculate samples were frozen immediately after collections as Control. In addition, epididymal sperm samples from the same 10 boars were collected post-mortem and extended in SP from P1 (EP1), P2 (EP2) and post SRF (EP3), and also held 24 h before freezing for a better understanding of the influence of SP on boar sperm cryopreservation. The sperm quality (motility, evaluated by CASA, and viability, evaluated by flow cytometry) and functionality (flow cytometry assessment of plasma membrane fluidity, mitochondrial membrane potential and intracellular generation of reactive oxygen species [ROS] in viable sperm) were evaluated at 30, 150 and 300 min post-thaw. Post-thawing sperm quality and functionality of P1 and P2 were similar but higher (p less than0.01) than BE samples. Control samples showed higher (p less than 0.01) post-thaw sperm quality and functionality than BE samples. Post-thawing sperm quality and functionality of EP1 and EP2 were similar but higher (p less than 0.05) than EP3. These results showed that boar sperm from BE are more cryosensitive than those from the SRF, particularly when held 24 h before freezing, which would be attributable to the cryonegative effects exerted by the SP from post SRF.

  • 253.
    Alkner, Björn A.
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Reg Jonkoping Cty, Linkoping, Sweden.
    Norrbrand, Lena
    KTH Royal Institute Technology, Sweden.
    Tesch, Per A.
    Karolinska Institute, Sweden.
    Neuromuscular Adaptations Following 90 Days Bed Rest With or Without Resistance Exercise2016In: AEROSPACE MEDICINE AND HUMAN PERFORMANCE, ISSN 2375-6314, Vol. 87, no 7, p. 610-617Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: This study examined the effects of long-term bed rest with or without a concurrent resistance exercise protocol on different muscle function indices of the knee extensors and their influence on previously shown atrophy, neural impairment, and slow-to-fast phenotype shift. METHODS: Nine men underwent 90 d of bed rest only (BR), while eight men in addition performed maximal supine squats every third day (BRE). Before and at day 1 and 5 following bed rest, surface quadriceps electromyographic (EMG) activity was measured during a sustained (60-s) submaximal isometric action and rate of force development (RFD) was assessed during a maximal isometric action, both in the supine squat position. Maximal torque was measured during isokinetic knee extensions at different angular velocities before and after (day 2 and 11) bed rest. RESULTS: EMG amplitude at a fixed submaximal load increased in BR, but not in BRE. The increase in amplitude during the sustained action was elevated in BR but not in BRE. RFD decreased in BR; this effect was attenuated day 1 and normalized day 5 in BRE. RFD expressed relative to maximal force was maintained in both groups. Angle-specific torque decreased equally for all velocities in BR. The decrease in isokinetic strength was attenuated day 2 in BRE. DISCUSSION: Phenotype changes were not reflected in muscle function measurements, probably because they were overridden by the effects of atrophy and neural adaptation. The protective effect of resistance exercise was more pronounced in tasks similar to the training action, inferring great impact of neural mechanisms.

  • 254.
    Alkner, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Orthopaedics, Eksjö, Region Jönköping County, Linköping, Sweden.
    Bring, Daniel K- I
    Division of Orthopedics and Biotechnology, Clintec, Karolinska Institutet, Stockholm, Sweden.
    Muscle Activation During Gravity-Independent Resistance Exercise Compared to Common Exercises2019In: Aerospace Medicine and Human Performance, ISSN 2375-6314, E-ISSN 2375-6322, Vol. 90, no 6, p. 506-512Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The aim was to study quadriceps muscle activation during resistance exercise using a flywheel device, developed as a gravity-independent resistance exercise device to be used during spaceflight, compared with traditional strength training exercises. METHODS: Eight healthy men experienced in resistance exercise performed the following exercises in random order: flywheel leg press (FW), knee extension isokinetic dynamometry (ID), barbell front squat (FS), weight stack leg press (LP), and weight stack knee extension (KE). They accomplished eight repetitions of coupled concentric and eccentric actions with simultaneous recordings of surface electromyography (EMG) from the three superficial quadriceps muscles and knee angles using electrogoniometry. Maximal voluntary contraction (MVC) in knee extension was performed before and after these measurements. RESULTS: EMG averaged across muscles and angles and normalized to MVC was 99/76% in FW, 48/41% FS, 65/47% LP, 81/52% KE, and 93/84% ID in concentric/eccentric phases, respectively. FW and ID showed higher mean EMG activity than LP and FS concentrically and higher than all other exercises eccentrically. No difference in activity between FW and ID was found. Pre- and post-MVC torque was comparable. DISCUSSION: Quadriceps muscle activation was superior in FW and ID exercises compared to the other exercises. The difference was most pronounced in the eccentric phase, but even concentric activation was lower in traditional closed chain exercises. This data supports that FW is an effective training tool and should be considered when designing strength training programs for spaceflights and on Earth.

  • 255.
    Alkner, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Orthopaedics, Eksjö, Region Jönköping County, Sweden.
    Halvardsson, Christina
    Falun Cent Hosp, Sweden.
    Brakenhielm, Gustaf
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Orthopaedics, Eksjö, Region Jönköping County, Sweden.
    Eskilsson, Therese
    Falun Cent Hosp, Sweden.
    Andersson, Erika
    Falun Cent Hosp, Sweden.
    Fritzell, Peter
    Falun and Futurum Acad Hlth and Care, Sweden.
    Effect of postoperative pneumatic compression after volar plate fixation of distal radial fractures: a randomized controlled trial2018In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 43, no 8, p. 825-831Article in journal (Refereed)
    Abstract [en]

    We investigated the difference between postoperative rehabilitation with or without adjunctive intermittent pneumatic compression therapy following distal radial fracture treated with volar plating. A total of 115 patients were randomized to a control or to an experimental group. After 4 weeks of immobilization the experimental group received intermittent pneumatic compression therapy in addition to conventional postoperative rehabilitation. Primary outcome up to 1 year postoperatively was assessed using the Canadian Occupational Performance Measure. No significant differences between groups were found. There were no clinically relevant differences regarding the secondary outcome measures swelling, strength, pain and flexibility. We conclude that postoperative intermittent pneumatic compression treatment had no major benefits. The results of the present study do not support general use of intermittent pneumatic compression initiated 4 weeks following volar plating surgery for distal radial fracture. Level of evidence: I

  • 256.
    Alkner, S.
    et al.
    Lund University Hospital.
    Bendahl, P.-O.
    Lund University Hospital.
    Ferno, M.
    Lund University Hospital.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Ryden, L.
    Lund University Hospital.
    Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: Results from a controlled randomised trial2009In: European Journal of Cancer, ISSN 0959-8049, Vol. 45, no 14, p. 2496-2502Article in journal (Refereed)
    Abstract [en]

    Background: Adjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial. Patients and methods: Premenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years. Results: In the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients less than40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40-49 years of age or ≥50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time. Conclusion: In this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women less than40 years of age. The effect of tamoxifen was not significantly dependent on time.

  • 257.
    Alkner, S
    et al.
    Lund University.
    Bendahl, P-O
    Lund University.
    Grabau, D
    Lund University.
    Lovgren, K
    Lund University.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Ryden, L
    Lund University.
    Ferno, M
    Lund University.
    AIB1 is a predictive factor for tamoxifen response in premenopausal women2010In: ANNALS OF ONCOLOGY, ISSN 0923-7534, Vol. 21, no 2, p. 238-244Article in journal (Refereed)
    Abstract [en]

    Background: Clinical trials implicate the estrogen receptor ( ER) coactivator amplified in breast cancer 1 (AIB1) to be a prognostic and a treatment-predictive factor, although results are not unanimous. We have further investigated this using a controlled randomised trial of tamoxifen versus control. Materials and methods: A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry. Results: AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence- free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8). Conclusions: In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.

  • 258.
    Allahverdiyeva, Yagut
    et al.
    University of Turku.
    Mamedov, Fikret
    Uppsala University.
    Holmstrom, Maija
    University of Turku.
    Nurmi, Markus
    University of Turku.
    Lundin, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Styring, Stenbjorn
    Uppsala University.
    Spetea Wiklund, Cornelia
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Aro, Eva-Mari
    University of Turku.
    Comparison of the electron transport properties of the psbo1 and psbo2 mutants of Arabidopsis thaliana2009In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, ISSN 0005-2728, Vol. 1787, no 10, p. 1230-1237Article in journal (Refereed)
    Abstract [en]

    Genome sequence of Arabidopsis thaliana (Arabidopsis) revealed two psbO genes (At5g66570 and At3g50820) which encode two distinct PsbO isoforms: PsbO1 and PsbO2, respectively. To get insights into the function of the PsbO1 and PsbO2 isoforms in Arabidopsis we have performed systematic and comprehensive investigations of the whole photosynthetic electron transfer chain in the T-DNA insertion mutant lines, psbO1 and psbo2. The absence of the PsbO1 isoform and presence of only the PsbO2 isoform in the psbo1 mutant results in (i) malfunction of both the donor and acceptor sides of Photosystem (PS) 11 and (ii) high sensitivity of PSII centers to photodamage, thus implying the importance of the PsbO1 isoform for proper structure and function of PSII. The presence of only the PsbO2 isoform in the PSII centers has consequences not only to the function of PSII but also to the PSI/PSII ratio in thylakoids. These results in modification of the whole electron transfer chain with higher rate of cyclic electron transfer around PSI, faster induction of NPQ and a larger size of the PQ-pool compared to WT, being in line with apparently increased chlororespiration in the psbo1 mutant plants. The presence of only the PsbO1 isoform in the psbo2 mutant did not induce any significant differences in the performance of PSII under standard growth conditions as compared to WT. Nevertheless, under high light illumination, it seems that the presence of also the PsbO2 isoform becomes favourable for efficient repair of the PSII complex.

  • 259.
    Allan, Douglas W.
    et al.
    University of British Columbia, Canada.
    Thor, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Transcriptional selectors, masters, and combinatorial codes: regulatory principles of neural subtype specification2015In: WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY, ISSN 1759-7684, Vol. 4, no 5, p. 505-528Article, review/survey (Refereed)
    Abstract [en]

    The broad range of tissue and cellular diversity of animals is generated to a large extent by the hierarchical deployment of sequence-specific transcription factors and co-factors (collectively referred to as TFs herein) during development. Our understanding of these developmental processes has been facilitated by the recognition that the activities of many TFs can be meaningfully described by a few functional categories that usefully convey a sense for how the TFs function, and also provides a sense for the regulatory organization of the developmental processes in which they participate. Here, we draw on examples from studies in Caenorhabditis elegans, Drosophila melanogaster, and vertebrates to discuss how the terms spatial selector, temporal selector, tissue/cell type selector, terminal selector and combinatorial code may be usefully applied to categorize the activities of TFs at critical steps of nervous system construction. While we believe that these functional categories are useful for understanding the organizational principles by which TFs direct nervous system construction, we however caution against the assumption that a TFs function can be solely or fully defined by any single functional category. Indeed, most TFs play diverse roles within different functional categories, and their roles can blur the lines we draw between these categories. Regardless, it is our belief that the concepts discussed here are helpful in clarifying the regulatory complexities of nervous system development, and hope they prove useful when interpreting mutant phenotypes, designing future experiments, and programming specific neuronal cell types for use in therapies.

  • 260.
    Allansson, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Per E
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Nelson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Overweight and obese children have lower cortisol levels than normal weight children2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 3, p. 295-299Article in journal (Refereed)
    Abstract [en]

    AimThe stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex. MethodsSalivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6-12years using Salivette((R)) tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the childrens height and weight, and these measurements were used to calculate their BMI. ResultsThe children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex. ConclusionOur findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children.

  • 261.
    Alleva, R.
    et al.
    Rizzoli Orthopaedic Institute, Bologna, Italy.
    Tomasetti, M.
    Institute of Experimental Pathology, University of Ancona, Ancona, Italy.
    Andera, L.
    Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
    Gellert, N.
    Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
    Borghi, B.
    Rizzoli Orthopaedic Institute, Bologna, Italy.
    Weber, C.
    Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany.
    Murphy, M.P.
    Mitochondrial Dysfunction Group, MRC Dunn Human Nutrition Unit, Cambridge, United Kingdom.
    Neuzil, Jiri
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology .
    Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection2001In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 503, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    Generation of free radicals is often associated with the induction and progression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and can help to elucidate specific apoptotic pathways. Here we studied whether coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiquinone) forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells to a-tocopheryl succinate (a-TOS), hydrogen peroxide, anti-Fas IgM or TRAIL led to induction of apoptosis. Cell death due to the chemical agents was suppressed in cells enriched with the reduced form of coenzyme Q. However, coenzyme Q did not block cell death induced by the immunological agents. Ubiquinol-10 inhibited reactive oxygen species (ROS) generation in cells exposed to a-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked apoptosis triggered by a-TOS or hydrogen peroxide. Therefore, it is plausible that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as an antioxidant in mitochondria. Our results also indicate that generation of free radicals may not be a critical step in induction of apoptosis by immunological agents. © 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

  • 262.
    Almby, Kristina
    et al.
    Uppsala Univ, Sweden.
    Edholm, David
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Anastomotic Strictures After Roux-en-Y Gastric Bypass: a Cohort Study from the Scandinavian Obesity Surgery Registry2019In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, no 1, p. 172-177Article in journal (Refereed)
    Abstract [en]

    BackgroundRoux-en-Y gastric bypass (RYGB) is the most common bariatric procedure worldwide. Anastomotic stricture is a known complication of RYGB. The aim was to explore the incidence and outcomes of strictures within the Scandinavian Obesity Surgery Registry (SOReg).MethodSOReg included prospective data from 36,362 patients undergoing bariatric surgery in the years 2007-2013. Outcomes were recorded at 30-day and at 1-year follow-up according to the standard SOReg routine. The medical charts of patients suffering from stricture after RYGB were requested and assessed.SettingNational bariatric surgery registryResultsAnastomotic stricture within 1year of surgery was confirmed in 101 patients representing an incidence of 0.3%. Risk factors for stricture were patient age above 60years (odds ratio (OR), 6.2 95% confidence interval (CI) 2.7-14.3), circular stapled gastrojejunostomy (OR 2.7, 95% CI 1.4-5.5), postoperative anastomotic leak (OR 8.9 95%, CI 4.7-17.0), and marginal ulcer (OR 30.0, 95% CI 19.2-47.0). Seventy-five percent of the strictures were diagnosed within 70days of surgery. Two dilatations or less was sufficient to successfully treat 50% of patients. Ten pecent of patients developed perforation during dilatation, and the risk of perforating at each dilatation was 3.8%. Perforation required surgery in six cases but there was no mortality. Strictures in SOReg may be underreported, which could explain the low incidence in the study.ConclusionMost strictures present within 2months and are successfully treated with two dilatations or less. Dilating a strictured gastrojejunostomy entails a risk of perforation (3.8%).

  • 263.
    Almeida, A. M.
    et al.
    CVZ Centre Vet and Zootecnia, Portugal; CIISA Centre Interdisciplinar Invest Sanidade Anim, Portugal; UNL, Portugal; IBET Institute Biol Expt and Tecnol, Portugal.
    Bassols, A.
    University of Autonoma Barcelona, Spain.
    Bendixen, E.
    Aarhus University, Denmark.
    Bhide, M.
    University of Vet Medical and Pharm, Slovakia.
    Ceciliani, F.
    University of Milan, Italy.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. University of Basque Country, Spain.
    Eckersall, P. D.
    University of Glasgow, Scotland.
    Hollung, K.
    Nofima AS, Norway.
    Lisacek, F.
    Swiss Institute Bioinformat, Switzerland.
    Mazzucchelli, G.
    University of Liege, Belgium.
    McLaughlin, M.
    University of Glasgow, Scotland.
    Miller, I.
    University of Vet Med, Austria.
    Nally, J. E.
    ARS, IA 50010 USA.
    Plowman, J.
    AgResearch, New Zealand.
    Renaut, J.
    Centre Rech Public Gabriel Lippmann, Luxembourg.
    Rodrigues, P.
    University of Algarve, Portugal.
    Roncada, P.
    University of Milan, Italy.
    Staric, J.
    University of Ljubljana, Slovenia.
    Turk, R.
    University of Zagreb, Croatia.
    Animal board invited review: advances in proteomics for animal and food sciences2015In: Animal, ISSN 1751-7311, E-ISSN 1751-732X, Vol. 9, no 1Article, review/survey (Refereed)
    Abstract [en]

    Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.

  • 264.
    Almen-Christensson, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Lindh-Åstrand, Lotta
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Prevention of menstrual migraine with perimenstrual transdermal 17-beta-estradiol: a randomized, placebo-controlled, double-blind crossover study2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, no 2, p. 498-500Article in journal (Refereed)
    Abstract [en]

    he effect of treatment with percutaneous E(2) (100 mu g/24 h) during 2 weeks perimenstrually on the number and severity of menstrual migraine attacks was studied in 27 women in a randomized, placebo-controlled, double-blind, crossover trial. We were not able to demonstrate any difference between E(2) supplementation and placebo on the number or severity of migraine attacks, but both regimens showed significant effects compared with before treatment.

  • 265.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Novel Strategies in the Thiopurine Treatment of Inflammatory Bowel Disease2010In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 29, no 04-Jun, p. 267-277Article in journal (Refereed)
    Abstract [en]

    Thiopurine drugs are widely used as immunomodulatory and corticosteroid-sparing agents in inflammatory bowel disease. Despite being old drugs, a renewed research and clinical interest in their application has emerged during the last decade. The application of pharmacogenetic insights and metabolic monitoring, together with treatment strategies in combination with anti-TNF-antibodies and possibilities to modulate their metabolism, has paved the way to a omoderno use of the thiopurines. These aspects are briefly overviewed herein.

  • 266.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Befrits, R.
    Gastrocentrum medicin, Karolinska universitetssjukhuset, Solna, Sweden.
    Eriksson, A.S.
    Medicinkliniken, Sahlgrenska universitetssjukhuset/Östra, Göteborg, Sweden.
    Halfvarson, J.
    Sektionen för gastroenterologi, Medicinska kliniken, Universitetssjukhuset, Örebro, Sweden.
    Hindorf, U.
    VO gastroenterologi, Universitetssjukhuset i Lund, Sweden.
    Lofberg, R.
    IBD-enheten, Sophiahemmet, Stockholm, Sweden.
    Modern läkemedelsterapi vid crohn - Nationella riktlinjer2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 2988-2993Article in journal (Refereed)
    Abstract [sv]

    Lättanvända begrepp och definitioner på sjukdomsaktivitet och behandlingseffekt bör få ökad spridning inom sjukvården.

    Majoriteten av patienter med Crohns sjukdom behöver långvarig läkemedelsbehandling, och ungefär hälften genomgår en eller flera operationer någon gång under sjukdomstiden.

    Det är viktigt att tidigt i sjukdomsförloppet identifiera riskfaktorer för utveckling av komplicerad och aggressiv sjukdom och behandla intensivt i dessa fall.

    En aktiv strategi med regelbundet övervägande av tillgängliga behandlingsalternativ medför att de flesta patienter med Crohns sjukdom behåller en god livskvalitet.

  • 267.
    Almer, Sven
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hindorf, U
    Inflammatorisk tarmsjukdom (IBD) och biologiska läkemedel2008Report (Other academic)
  • 268.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hindorf , U
    Lund University.
    6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients2009In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 41, no 3, p. 194-200Article in journal (Refereed)
    Abstract [en]

    Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety.

    Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times.

    Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80.

    Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.

  • 269.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Sektionen för gastroenterologi, medicinska kliniken, Universitetssjukhuset, Örebro .
    Andersson, Magnus V.
    Kirurgiska kliniken, Universitetssjukhuset, Örebro.
    Befrits, Ragnar
    Gastrocentrum medicin, Karolinska universitetssjukhuset, Solna.
    Hertervig, Erik
    VO gastroenterologi och nutrition, Universitetssjukhuset , Lund.
    Kilander, Anders
    Sektionen för gastroenterologi, Sahlgrenska universitetsjukhuset, Göteborg.
    Lindgren, Stefan
    Sektionen för gastroenterologi, Universitetssjukhuset MAS, Malmö.
    Suhr, Ole
    Sektionen för gastroenterologi, Norrlands universitetssjukhus, Umeå.
    Handläggning av svårt skov av ulcerös kolit. In: Löfberg R (ed): Inflammatorisk tarmsjukdom.2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 62-75Article in journal (Refereed)
    Abstract [sv]

    Patienter med svårt skov av ulcerös kolit bör vårdas på sjukhus och handläggas av gastroenterolog och kolorektal kirurg i nära samarbete.

    Skovets svårighetsgrad kan underskattas, varför noggrann bedömning av inflammationens utbredning och svårighetsgrad enligt validerade kriterier är viktigt.

    Intravenös behandling med kortikosteroider är en av hörn­stenarna i den akuta behandlingen.

    Patienter som inte förbättras på denna behandling, bör erbjudas medicinsk »rescue-behandling« eller kolektomi.

    Infliximab har visats vara en effektiv rescue-behandling och kan minska behovet av kol­ektomi inom de första 3 månaderna och upp till 3 år.

  • 270.
    Almqvist, Bengt
    et al.
    Lunds universitet.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Handbok i hörselmätning1990Book (Other academic)
    Abstract [sv]

    Denna bok ger en grundläggande kunskap om hörseln samt förmedlar förutsättningar för olika hörselmätmetoder. Viktiga inslag är felkällor vid hörselmätning, tolkning av mätresultat och lämplig teststrategi i olika tillämpningar. Inläst ur LIC, 1990

  • 271.
    Almqvist, Bengt
    et al.
    Lunds universitet.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Metodbok i praktisk hörselmätning1983Book (Other academic)
    Abstract [sv]

    Denna bok är avsedd att användas vid utbildning av audionomer. Den kan dessutom vara en viktig referenskälla för alla övriga yrkesgrupper inom hörselvården. De metodbeskrivningar som presenteras i boken har goda förutsättningar att bidra till förbättrad hörselmätning

  • 272.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences.
    Berlin, Gösta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Andersson, Bengt
    Sahlgrens University Hospital.
    Hahn-Zoric, Mirjana
    Sahlgrens University Hospital.
    Long-term treatment results and the immunoglobulin G subclass distribution patterns of proteinase-3-antineutrophil cytoplasm antibody (ANCA) and myeloperoxidase-ANCA in ANCA-associated vasculitis2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 2, p. 160-170Article in journal (Refereed)
    Abstract [en]

    Objective: Small vessel vasculitis associated with antibodies to neutrophil cytoplasm antigens has been denominated antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).

    Material and methods: Ninety-eight patients with various forms of AAV with renal involvement were studied retrospectively with regard to treatment, side-effects and outcome. The immunoglobulin G (IgG) subclass distribution patterns in serum were determined in 51 patients with nephelometry and those of anti-proteinase-3 (PR3) and anti-myeloperoxidase (MPO) in 44 patients by enzyme-linked immunosorbent assay.

    Results: Fifty-nine patients with a mean age of 63 years were given treatment with intermittent intravenous regimens of cyclophosphamide and continuous corticosteroids, whereas 39 patients with a mean age of 58 years were given continuous oral treatment. Malignancy, mainly due to skin tumours, was more common in AAV than in the general population. The total IgG subclass distribution pattern was asymmetric. The response to PR3 was of IgG1, IgG3 and IgG4 isotypes, while IgG1 and IgG3 predominated in the response to MPO.

    Conclusion: The aberrant IgG subclass distribution pattern detected in the autoantibodies may be of importance in the pathogenesis of AAV.

  • 273.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Ekermo, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Transfusion Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Månsson, Ann-Sofie
    Malmö University Hospital.
    Widell, Anders
    Malmö University Hospital.
    Monitoring hepatitis C infection in a major Swedish nephrology unit and molecular resolution of a new case of nosocomial transmission.2010In: Journal of medical virology, ISSN 1096-9071, Vol. 82, no 2, p. 249-256Article in journal (Refereed)
    Abstract [en]

    Hepatitis C virus (HCV) infection is a frequent problem in hemodialysis units. The prevalence and incidence of HCV infection over a decade were studied in a nephrology unit affected by previous nosocomial HCV transmission. The HCV non-structural 5B protein gene was sequenced to achieve phylogenetic analysis of a new (incident) case of infection. Proportions of patients who were and were not infected with HCV remained similar over the period, as did the inflow and outflow of patients infected previously. In 1997, 12/157 (8%) of patients at the unit (treatment: hemodialysis, peritoneal dialysis, and renal transplant recipients) were positive in HCV RNA, whereas in 2007 the overall number was 9/239 (4%). One patient acquired an HCV infection, and the NS5B sequence in that case clustered with genotype 2b sequences found in patients from an earlier outbreak. Comparing the HCV from the incident patient with several stored longitudinal samples and cloned PCR products from the most likely source patient revealed close phylogenetic relationship with an HCV quasispecies member from the possible source. The source patient and the incident newly infected patient were not scheduled on the same dialysis shift, although the records showed that simultaneous treatment occurred on two occasions during the months preceding transmission. In conclusion, over the 10-year period, the proportion of HCV-infected patients at the unit was unchanged. Only one new infection occurred, which originated from a fellow patient's quasispecies. This establishes phylogenetic analysis as a valuable tool for tracing patient sources of HCV transmission.

  • 274.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lonn, J
    University of Örebro, Sweden .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Sahlgrens University Hospital, Sweden .
    Hahn-Zoric, M
    Sahlgrens University Hospital, Sweden .
    Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin-6, High-Sensitivity C-Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 275.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lönn, J
    School of Health and Medical Sciences, Örebro, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Hahn-Zoric, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tillväxtfaktorer och inflammationsmarkörer vid kronisk njursvikt2013In: Njurmedicinskt vårmöte Jönköping 12-14 maj 2013, 2013Conference paper (Refereed)
  • 276.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Recidivating thrombocytopenia, renal failure and thymitis2017In: Recidivating thrombocytopenia, renal failure and thymitis, 2017Conference paper (Other academic)
  • 277.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Recurrent thrombocytopenia, renal failure and thymitis of unknown cause. A case report2017In: Vaskulär medicin, Vol. 33, no 3, p. 24-25Article in journal (Refereed)
    Abstract [en]

    A 45-year old man was admitted to an intensive care unit with flank pain and thrombocytopenia. He was treated for a suspected septicaemia but turned out to have signs of an unknown collagenosis which responded to plasma exchange, thymectomi and corticosteroids. Kidney biopsy revealed an intense tubulointerstitial reaction with suspected microthrombotic lesions in the vessels. The condition reoccurred with thrombocytopenia a couple of months later but responded to plasma exchange, corticosteroids and mycophenolate mofetil. An unknown collagenosis with findings of autoimmune thymitis and tubulointerstitial nephritis is the most probable cause of the condition.

  • 278.
    Almstrand, R
    et al.
    University of Gothenburg, Sweden .
    Lydmark, P
    University of Gothenburg, Sweden .
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sorensson, F
    University of Gothenburg, Sweden .
    Hermansson, M
    University of Gothenburg, Sweden .
    Dynamics of specific ammonia-oxidizing bacterial populations and nitrification in response to controlled shifts of ammonium concentrations in wastewater2013In: Applied Microbiology and Biotechnology, ISSN 0175-7598, E-ISSN 1432-0614, Vol. 97, no 5, p. 2183-2191Article in journal (Refereed)
    Abstract [en]

    Ammonia-oxidizing bacteria (AOB) are essential for the nitrification process in wastewater treatment. To retain these slow-growing bacteria in wastewater treatment plants (WWTPs), they are often grown as biofilms, e.g., on nitrifying trickling filters (NTFs) or on carriers in moving bed biofilm reactors (MBBRs). On NTFs, a decreasing ammonium gradient is formed because of the AOB activity, resulting in low ammonium concentrations at the bottom and reduced biomass with depth. To optimize the NTF process, different ammonium feed strategies may be designed. This, however, requires knowledge about AOB population dynamics. Using fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy, we followed biomass changes during 6 months, of three AOB populations on biofilm carriers. These were immersed in aerated MBBR tanks in a pilot plant receiving full-scale wastewater. Tanks were arranged in series, forming a wastewater ammonium gradient mimicking an NTF ammonium gradient. The biomass of one of the dominating Nitrosomonas oligotropha-like populations increased after an ammonium upshift, reaching levels comparable to the high ammonium control in 28 days, whereas a Nitrosomonas europaea-like population increased relatively slowly. The MBBR results, together with competition studies in NTF systems fed with wastewater under controlled ammonium regimes, suggest a differentiation between the two N. oligotropha populations, which may be important for WWTP nitrification.

  • 279.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Göransson, Nathanael
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study2016In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 6, no 3, p. 1-16Article in journal (Refereed)
    Abstract [en]

    New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

  • 280.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering.
    Zsigmond, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering.
    Brain Stimulation Steering of the Electric Field: A Patient-Specific Simulation Study2016Conference paper (Refereed)
  • 281.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Influence of Virchow-Robin spaces in the Electric Field Distribution in Subthalamic Nucleus Deep Brain Stimulation2019Conference paper (Refereed)
    Abstract [en]

    Objectives: Previous investigations have shown the appearance of cysts i.e. Virchow-Robin spaces (VR) in the basal ganglia and their relationship with parkinsonian symptoms [1-3]. Simulations [4]using the finite element method (FEM) suggests that VR affects the electric field around deep brain stimulation (DBS) electrodes. The aim of the study was to evaluate how the electric field is modified by the presence of cysts in the STN. Methods: The effect of cysts on the electric field around the DBS lead placed in the STN was evaluated using FEM. 3D patient-specific brain models were built with COMSOL 5.2 (COMSOL AB, Sweden) and an in-house developed software [5] to convert a T2 weighted MRI of Parkinsonian patients (ethics approval no: 2012/434-3) into electrical conductivity matrix readable by FEM software. VR was classified as CSF [6]assigning a high electrical conductivity (2.0 S/m). The stimulation amplitudes were set to the clinically programmed values. Depending on the lead used, the stimulation was set to voltage control (3389) or current control (6180, ring mode). The coordinates corresponding to the lowest (first) electrode and the third higher up in the lead, taken from the postoperative CT electrode artefact, were used to localize the leads in the brain model [7]. The electric field was visualized with a 0.2V/mm isosurface. Results: Simulations showed that the electric field distribution is affected by the cysts. The higher conductivity at these regions in the vicinity of the electrode redistributes the electric field pushing it away from the cyst. The same effect occurs regardless of the operating mode or the lead design as long as the directional lead is configured in ring mode. Conclusions: The use of patient-specific models has shown the importance of considering nuances of the patients’ anatomy in the STN. This information can be used to determine the stimulation parameter and to support the analysis of side effects induced by the stimulation. The potential advantage of directional leads can also be assessed by including in the model patient-specific data.

  • 282.
    Alping, Peter
    et al.
    Karolinska Inst, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden; Karolinska Univ Hosp, Sweden.
    Langer-Gould, Annette
    Kaiser Permanente, CA USA; Kaiser Permanente, CA USA.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Burman, Joachim
    Uppsala Univ, Sweden.
    Fink, Katharina
    Karolinska Inst, Sweden.
    Fogdell-Hahn, Anna
    Karolinska Inst, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Sweden.
    Hillert, Jan
    Karolinska Inst, Sweden.
    Kockum, Ingrid
    Stockholm Hlth Serv, Sweden.
    Lycke, Jan
    Univ Gothenburg, Sweden.
    Nilsson, Petra
    Lund Univ, Sweden.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Salzer, Jonatan
    Umea Univ, Sweden.
    Svenningsson, Anders
    Danderyd Hosp, Sweden.
    Virtanen, Suvi
    Karolinska Inst, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations2019In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, no 2, p. 230-233Article in journal (Refereed)
    Abstract [en]

    The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of amp;gt;3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

  • 283.
    Alstad, V.
    et al.
    Department of Oral and Maxillofacial Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Surgical removal of keratocystic odontogenic tumours via a Le Fort I osteotomy approach: a retrospective study of the recurrence rate2017In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 46, no 4, p. 6p. 434-439Article in journal (Refereed)
    Abstract [en]

    The keratocystic odontogenic tumour (KCOT) is one of the most aggressive odontogenic cysts and has a high recurrence rate. The treatment of these tumours is the subject of debate. A KCOT in the posterior maxilla with sinus involvement is rare. Few reports have been published in the literature. The purpose of this study was to evaluate the recurrence rate after surgical removal of maxillary KCOTs via a Le Fort I osteotomy. A search was performed to identify patients with a follow-up time of at least 5 years. Nine patients were included in the study. The following clinical variables were analyzed: age at surgery, sex, symptoms, site and size of the tumour, surgical approach, and recurrence rate. The surgical approaches were curettage (n=6) and enucleation (n=3). Recurrence was seen in three patients (33%); all had multilocular tumours. No recurrence was seen in patients with unilocular tumours. The Le Fort I osteotomy approach allows direct visualization and ensures wide excision, minimizing the risk of recurrence. In this series, cases with a multilocular KCOT showed a higher risk of recurrence due to the difficulty of removing the tumour in total. All recurrences took place within 2 years of the intervention; a 5-year follow-up is recommended.

  • 284.
    Alstrand, N
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hyllienmark, L
    Karolinska Institute.
    Wahlberg, J
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Symptomatic neuropathy in type 1 diabetes is preceded by subclinical electrophysiological abnormalities - a prospective study in DIABETOLOGIA, vol 53, issue , pp2010In: DIABETOLOGIA, Springer Science Business Media , 2010, Vol. 53Conference paper (Refereed)
    Abstract [en]

    n/a

  • 285.
    Altgärde, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hilding, Niclas
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Horse-related trauma in children and adults during a two year period2014In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 22, no 40Article in journal (Refereed)
    Abstract [en]

    Introduction: Horse riding, with almost 200,000 participants, is the eighth most popular sport in Sweden. Severe injuries can occur with horse riding accidents which is well documented. This study was undertaken to investigate if injuries associated with horse riding are common, which type of injuries occur, what mechanisms are involved and to estimate the costs to the society. Material and methods: All patients attending the emergency department at Link ping University Hospital, during the years 2003-2004, due to horse related trauma were prospectively recorded. The patients were divided into two groups according to age, 147 children and 141 adults. The medical records were retrospectively scrutinized. Results: The most common mechanism of injury was falling from the horse. Most commonly, minor sprains and soft tissue injuries were seen, but also minor head injuries and fractures, mainly located in the upper limb. In total 26 adults and 37 children were admitted. Of these 63 patients 19 were considered having a serious injury. In total, four patients needed treatment in intensive care units. The total cost in each group was 200,000 Euro/year. Conclusion: Horse riding is a sport with well known risks. Our results corresponds to the literature, however we have not observed the same incidence of serious injuries. In contrast we find these to be fairly uncommon. The injuries are mainly minor, with a small risk of long term morbidity. Over time regulations and safety equipment seem to have decreased the number of serious accidents.

  • 286.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Univ Autonoma Barcelona, Spain.
    Alvarez, M.
    Univ Leon, Spain.
    Anel-Lopez, L.
    Univ Leon, Spain.
    Guerra, C.
    Univ Leon, Spain.
    Chamorro, C. A.
    Univ Leon, Spain.
    Anel, L.
    Univ Leon, Spain.
    de Paz, P.
    Univ Leon, Spain.
    Martinez-Pastor, F.
    Univ Leon, Spain.
    Effect of length of time post-mortem on quality and freezing capacity of Cantabric chamois (Rupicapra pyrenaica parva) epididymal spermatozoa2018In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 198, p. 184-192Article in journal (Refereed)
    Abstract [en]

    Genome Resource Banks are keystones in the ex-situ conservation of wild species. Post-mortem (PM) collection of epididymal spermatozoa is an opportunistic and valuable source of germplasm, the time from the death of the animal limits its use. Seeking to improve germplasm preservation strategies for the chamois (Rupicapra sp.), the effect of PM time on epididymal sperm quality and freezability was studied using the Cantabrian chamois. Samples were classified according to PM collection time, up to 216 h (refrigerated), and cryopreserved (Tris-citric acid-fructose, 430 mOsm/kg, 15% egg yolk, 8% glycerol; freezing at - 20 degrees C/min). Sperm quality was assessed after recovery and post-thawing (motility by CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability and acrosomal damage by flow cytometry). The sperm mass pH and osmolality showed a positive correlation with time. Total sperm motility dropped after 2 days PM, with progressivity and sperm velocities remained similar up to 3 days PM. Sperm freezability was acceptable, with the post-thawing HOST, motility, progressivity, VAP, VCL, VSL and BCF negatively correlating with PM time. Overall, chamois epidydimal samples were not adequate for preservation after 6 days PM. Freezability capacity could make these spermatozoa suitable for specific ART even if kept refrigerated for several days PM.

  • 287.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez, M.
    University of Leon, Spain.
    Anel-Lopez, L.
    SaBio IREC CSIC UCLM JCCM, Spain.
    Lopez-Uruena, E.
    University of Leon, Spain.
    Manrique, P.
    University of Leon, Spain.
    Borragan, S.
    Cabarceno Pk, Spain.
    Morrell, J. M.
    Swedish University of Agriculture Science SLU, Sweden.
    de Paz, P.
    University of Leon, Spain.
    Anel, L.
    University of Leon, Spain.
    Effect of colloid (Androcoll-Bear, Percoll, and PureSperm) selection on the freezability of brown bear (Ursus arctos) sperm2016In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 85, no 6, p. 1097-1105Article in journal (Refereed)
    Abstract [en]

    The development of a species-specific conservation protocol that involves artificial insemination with frozen semen needs to validate an effective methodology for freezing semen. Colloid centrifugation has been suggested and widely applied as an effective tool for selecting animal spermatozoa for artificial breeding. The objective of the present study was to compare different methods of centrifugation, single layer using Androcoll-Bear and Percoll and double layer using PureSperm 100 (in two different discontinuous gradients 40%-80% and 45%-90%), for the selection of fresh brown bear sperm samples. In the before freezing group, all selected samples showed a higher progressive motility and viability (except Percoll for motility 43.0 +/- 5.3 [P < 0.051); all colloids except PureSperm 45/90% rendered samples with fewer damaged acrosomes. In the after thawing group, all tested centrifugation colloids showed a good capacity to decrease the number of damaged acrosomes. Furthermore, PureSperm treatment (45/90%) resulted in an increase in apoptotic-like changes not only immediately after thawing but also after the incubation test, leading us to suggest that this gradient could induce some kind of deleterious effects on the sperm samples. On the other hand, PureSperm treatment (40/80%) yielded a quality preservation capacity similar to Androcoll-Bear in number of damaged acrosomes, different relative to the control (control, 5.3 +/- 0.6; PureSperm 80, 2.0 +/- 0.3; Androcoll, 2.1 +/- 0.9 [P < 0.051) but a decrease in the number of viable spermatozoa recovered after thawing relative to the control (control, 21.2 +/- 3.1; PureSperm 80, 13.7 +/- 2.7 [P < 0.051). In conclusion, Androcoll-Bear constitutes a useful tool for handling of brown bear ejaculates owing to its simple handling and procedure with a reliable sperm selection and freezability. This colloid yielded an improvement in several sperm parameters in brown bear frozen-thawed semen; the selected spermatozoa of fresh samples with this colloid showed a better resistance to freezing compared with the control sample not only for motility but also for viability. (C) 2016 Elsevier Inc. All rights reserved.

  • 288.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery and Theriogenology, Faculty of Veterinary Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, Bangladesh.
    Venhoranta, Heli
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. University of Helsinki, Department of Production Animal Medicine, Faculty of Veterinary Medicine, Saari, Finland.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 3, article id 513Article in journal (Refereed)
    Abstract [en]

    Mating or cervical deposition of spermatozoa or seminal plasma (SP) modifies the expression of genes affecting local immune defense processes at the oviductal sperm reservoir in animals with internal fertilization, frequently by down-regulation. Such responses may occur alongside sperm transport to or even beyond the reservoir. Here, immune-related gene expression was explored with cDNA microarrays on porcine cervix-to-infundibulum tissues, pre-/peri-ovulation. Samples were collected 24 h post-mating or cervical deposition of sperm-peak spermatozoa or SP (from the sperm-peak fraction or the whole ejaculate). All treatments of this interventional study affected gene expression. The concerted action of spermatozoa and SP down-regulated chemokine and cytokine (P00031), interferon-gamma signaling (P00035), and JAK/STAT (P00038) pathways in segments up to the sperm reservoir (utero-tubal junction (UTJ)/isthmus). Spermatozoa in the vanguard sperm-peak fraction (P1-AI), uniquely displayed an up-regulatory effect on these pathways in the ampulla and infundibulum. Sperm-free SP, on the other hand, did not lead to major effects on gene expression, despite the clinical notion that SP mitigates reactivity by the female immune system after mating or artificial insemination.

  • 289.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Exosomes in specific fractions of the boar ejaculate contain CD44: A marker for epididymosomes?2019In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 140, p. 143-152Article in journal (Refereed)
    Abstract [en]

    Seminal plasma (SP) is a complex fluid containing proteins, peptides, enzymes, hormones as well as extracellular vesicles (EVs). The SP interacts with spermatozoa and the inner cell lining of the female genital tract, adsorbing proteins and exosomes that modulate sperm functions and female immune responsiveness. In the present study, boar sperm-free SP was studied using flow cytometry (FC) after membrane tetraspanins (CD9, CD63 and CD81) and membrane receptor CD44 marking of non-enriched (whole SP) or gradient fractions enriched through two-step discontinuous KBr-density-gradient ultracentrifugation, in whole ejaculate or in selected ejaculate fractions. The results, evaluated by transmission electron microscopy, confirmed the presence of exosomes in all fractions of the pig SP. Noteworthy, these pig SP-exosomes were CD44-bearing when analysed by FC, with bands detected by western blotting (WB) at the expected 85 kD size. The two-step discontinuous KBr-density-gradient ultracentrifugation enriched the population of exosomes in two specific gradient fractions, indicating exosomes (either prostasomes or epididymosomes) could be separated from low-density lipoprotein (LDL) but they co-sediment with the high-density lipoprotein (HDL)-bearing fraction. The findings pave for the selective isolation of exosomes in functional studies of their function when interacting with spermatozoa, the oocyte and/or the female genitalia, including hyaluronan-CD44 interplay. (C) 2019 Elsevier Inc. All rights reserved.

  • 290.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Univ Autonoma Barcelona, Spain.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    The risk of using monoclonal or polyclonal commercial antibodies: controversial results on porcine sperm CD44 receptor identification2019In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 54, no 4, p. 733-737Article in journal (Refereed)
    Abstract [en]

    Presence of the hyaluronan (hyaluronic acid, HA) receptor CD44 on spermatozoa has been difficult to pursue, mostly obeying to the use of different commercial mono- and/or polyclonal antibodies, often lacking proper controls. Here, we describe how the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor differs in ejaculated pig spermatozoa depending on the type of antibody and protocol used. While we were able to detect binding to spermatozoa and mark its presence in the sperm membrane, the use of blocking peptides clearly indicated that only the monoclonal antibody could confirm the specific presence and location of the CD44 receptor, whereas the polyclonal antibody was detecting multiple presumed CD44 isoforms or degraded proteins thus proving unspecific. These results call for strict protocols when attempting immunological determination of sperm membrane receptors.

    The full text will be freely available from 2020-02-11 15:44
  • 291.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Evidensia Valla Djursjukhus Linkoping, Linkoping, Sweden.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Hyaluronan improves neither the long-term storage nor the cryosurvival of liquid-stored CD44-bearing Al boar spermatozoa2018In: Journal of reproduction and development, ISSN 0916-8818, E-ISSN 1348-4400, Vol. 64, no 4, p. 351-360Article in journal (Refereed)
    Abstract [en]

    Hyaluronan (hyaluronic acid, HA) apparently improves sperm survival in vitro and in vivo (oviduct), maintaining sperm motility and inducing capacitation, but not acrosome exocytosis, either by direct action as a macromolecule or via CD44 membrane receptors. This study explored ejaculated, liquid-extended pig spermatozoa to ascertain (i) the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor, using a specific monoclonal commercial antibody; (ii) whether the CD44 receptor changed location when exposed to bicarbonate, a capacitating trigger, in vitro; and (iii) whether the addition of HA, of molecular size comparable to that produced in the oviduct sperm reservoir (0.0625 to 2.0 mg/ml; 0 HA: control), to semen extenders would improve sperm liquid storage in vitro or cryosurvival post freezing. Variables tested were sperm velocity and progressive motility (Qualisperm (TM)), sperm viability and acrosome status, membrane integrity and early destabilization, mitochondrial activation, and superoxide production (flow cytometry). The CD44 receptor presence in ejaculated, liquid-stored AI boar spermatozoa, as confirmed by a porcine-specific monoclonal antibody, maintained its membrane location under in vitro capacitation-inducing conditions. HA exposure to 24-, 48-, or 72-h liquid-stored (17-20 degrees C) spermatozoa lowered sperm velocity in membrane-intact spermatozoa, but increased mitochondrial superoxide production. Finally, HA addition during cooling did not improve cryosurvival but did increase mitochondrial activation and membrane destabilization in surviving cells. These results confirm the existence of a CD44 receptor in pig spermatozoa, but the usefulness of adding HA for long-term storage or cryopreservation of liquid-stored, extended boar semen remains in question, thereby warranting further non-empirical analyses of HA-sperm membrane interactions.

  • 292.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente-Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Exogenous Individual Lecithin-Phospholipids (Phosphatidylcholine and Phosphatidylglycerol) Cannot Prevent the Oxidative Stress Imposed by Cryopreservation of Boar Sperm.2017In: Journal of veterinary medicine and surgery, ISSN 2574-2868, Vol. 1, no 1Article in journal (Refereed)
    Abstract [en]

    Objective: Despite the use of high proportions of the chemically undefined lipoprotein/phospholipid-rich egg-yolk in extenders, boar sperm are highly sensitive to cooling, which induces ROS generation and disrupts the plasma membrane.

    Here, we studied whether replacement of hen egg-yolk by commercially defined lecithin phospholipids, derived from egg (LPGE: phosphatidyl glycerol, LPCE: phosphatidyl choline) or soybean (LPCS: phosphatidyl choline), could individually ameliorate such oxidative effects during cryopreservation of ejaculated (sperm rich fraction, SRF) or of cauda-epididymal sperm, retrieved post-mortem from the same males.

    Methods: A conventional extender (lactose buffer, with 20% egg-yolk, 0.5% OEP and 3% glycerol) was used as control. Cryodamage was assessed as loss of sperm motility, membrane and acrosome intactness, early membrane destabilization changes, mitochondrial potential, superoxide and ROS production, to finally determine lipid peroxidation (LPO) using specific probes.

    Results and conclusion: In general, the exogenous phospholipids assayed were unable of maintaining neither sperm motility nor viability post-thaw compared to controls, owing to increased ROS production and lipid peroxidation. In our study, mitochondrial superoxide production resulted in very high levels for all groups, whereas both ROS production and lipid peroxidation were reduced in the control group, containing emulsified hen egg yolk. Further studies using various dosage and combination of LPCS should be followed for their eventual protective effect.

    Keywords: Cryodamage; Sperm; Boar; Mitochondrial activation; Mitochondrial superoxide; ROS production; Lipid peroxidation

  • 293. Alvarsson, M
    et al.
    Sundkvist, G
    Lager, I
    Henricsson, M
    Berntorp, K
    Forbes, E
    Steen, L
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Orn, T
    Grill, V
    Different effects of withdrawal of insulin or glibenclamide treatment on beta cell function in recently diagnosed Type 2 diabetic patients.2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, p. 798-Conference paper (Other academic)
  • 294.
    Amandusson, Asa
    et al.
    Uppsala University, Sweden .
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Estrogenic influences in pain processing2013In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 34, no 4, p. 329-349Article, review/survey (Refereed)
    Abstract [en]

    Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

  • 295.
    Amandusson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Estrogen Receptor Expression in Relation to Pain Modulation and Transmission: Experimental Studies in Rats2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Estrogens have a remarkably wide range of actions in the mammalian brain. They not only play a pivotal role in reproductive behavior and sexual differentiation, but also contribute to e.g. thermoregulation, feeding, memory, neuronal survival and the perception of somatosensory stimuli. A multitude of studies on both animals and human subjects has demonstrated potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and therefore need to be evaluated specifically in relation to the localization and intrinsic characteristics of the neurons engaged. The overall aim of this thesis is to gain specific knowledge of the possible cellular mechanisms by which estrogens may influence the transmission of nociceptive stimuli at the level of the spinal cord.

    The estrogen receptors, by which estrogens regulate non-genomic as well as genomic mechanisms, are crucial to estrogen signaling in general and essential to the estrogen-induced effects in the brain. In Paper I, we use immunohistochemistry to label neurons containing estrogen receptor-! (ERα) in the medullary and spinal dorsal horn of female rats. Large numbers of ER!-expressing neurons were found in lamina I and lamina II, i.e. in the areas involved in the processing of primary afferent nociceptive information. This distribution in part overlaps that of enkephalin, a potent pain-inhibiting endogenous opioid. The effects of gonadal hormones on pain modulation may, to a great extent, be blocked by the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the prosecution of hormonal pain regulation. By combining immunohistochemical labeling of ERα with in situ hybridization of preproenkephalin mRNA (Paper II), we demonstrate that the majority of enkephalinergic neurons in the superficial laminae of the spinal and medullary dorsal horn express ER!. This co-localization and the fact that the preproenkephalin gene contains a sequence that binds ERs, suggest that estrogens may potentially regulate enkephalin expression in these cells. This is further supported by the findings in Paper III in which we show that a single subcutaneous injection of estradiol induces a significant increase (on average 68%) in preproenkephalin mRNA content in the spinal cord after 4 hours. The expression of the enkephalin gene in the spinal cord is thus sensitive to fluctuating estradiol levels. In Paper IV, a noxious injection of formalin is used to induce activation of a neuronal population involved in nociceptive transmission from the face. By using a dual-labeling immunohistochemistry protocol, we were able to identify ER!-expressing cells within this neuronal population suggesting that nociceptive-responsive neurons in the medullary dorsal horn express ER!. In all, our findings provide morphological as well as biochemical evidence in support for an estrogen-dependent modulation of nociceptive processing at the level of the dorsal horn.

    List of papers
    1. Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn of the female rat
    Open this publication in new window or tab >>Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn of the female rat
    1995 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 196, no 1-2, p. 25-28Article in journal (Refereed) Published
    Abstract [en]

    Using an immunohistochemical technique, we demonstrate that large numbers of neurons in the laminar spinal trigeminal nucleus and spinal gray matter of the female rat express estrogen receptors (ER). Densely packed ER-immunoreactive neurons were present in lamina II, but labeled neurons were also present in lamina I, the neck of the dorsal horn, and in lamina X. Labeling was present throughout the length of the spinal cord, with the exception of segments caudal to S1, which were unlabeled. The distribution of ER-containing neurons to areas that are involved in processing of primary afferent nociceptive information suggests that the pain modulatory effects of estrogen may be exerted at the spinal level.

    Keywords
    Gonadal hormones, Spinal trigeminal nucleus, Spinal cord, Substantia gelatinosa, Pain, Immunohistochemistry
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17972 (URN)10.1016/0304-3940(95)11828-K (DOI)7501248 (PubMedID)
    Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2017-12-13Bibliographically approved
    2. Colocalization of oestrogen receptor immunoreactivity and preproenkephalin mRNA expression to neurons in the superficial laminae of the spinal and medullary dorsal horn of rats
    Open this publication in new window or tab >>Colocalization of oestrogen receptor immunoreactivity and preproenkephalin mRNA expression to neurons in the superficial laminae of the spinal and medullary dorsal horn of rats
    1996 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 8, no 11, p. 2440-2445Article in journal (Refereed) Published
    Abstract [en]

    A double-labelling procedure combining immunohistochemical staining with in situ hybridization using a radiolabelled cRNA probe was employed to demonstrate oestrogen receptor-like immunoreactivity and preproenkephalin-A mRNA in the medullary and spinal dorsal horn of female rats. Both markers labelled large numbers of neurons in the substantia gelatinosa and its trigeminal homologue. Many of these neurons were double-labelled, displaying both oestrogen receptor-like-immunoreactivity and preproenkephalin-A mRNA; cell counts showed that 40-60% of the of the oestrogen receptor-like-immunoreactive cells in the superficial laminae also were labelled for preproenkephalin-A mRNA, and that 60-70% of the preproenkephalin-A mRNA-labelled neurons in the same laminae displayed oestrogen receptor-like immunoreactivity. Previous studies have shown that oestrogen receptors can bind to the promoter region of the preproenkephalin-A gene, and studies on the hypothalamus have demonstrated that oestrogen regulates enkephalin expression in select neuronal populations. The present results demonstrate that enkephalinergic neurons in the superficial dorsal horn contain oestrogen receptors and suggest that oestrogen may play an important role in the modulation of sensory and nociceptive processing in the lower medulla and spinal cord.

    Place, publisher, year, edition, pages
    Wiley InterScience, 1996
    Keywords
    Gonadal hormone enkephalin spinal cord, pain in situ hybridization
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17973 (URN)10.1111/j.1460-9568.1996.tb01207.x (DOI)8950107 (PubMedID)
    Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2017-12-13Bibliographically approved
    3. Estrogen-induced alterations of spinal cord enkephalin gene expression
    Open this publication in new window or tab >>Estrogen-induced alterations of spinal cord enkephalin gene expression
    1999 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 83, no 2, p. 243-248Article in journal (Refereed) Published
    Abstract [en]

    Enkephalin-synthesizing neurons in the super®cial laminae of the spinal and trigeminal dorsal horn are critical components of the endogenous pain-modulatory system. We have previously demonstrated that these neurons display intracellular estrogen receptors, suggesting that estrogen can potentially influence their enkephalin expression. By using Northern blot, we now show that a bolus injection of estrogen results in a rapid increase in spinal cord enkephalin mRNA levels in ovariectomized female rats. Thus, 4 h after estrogen administration the enkephalin mRNA-expression in the lumbar spinal cord was on average 68% higher (P , 0:05) than in control animals injected with vehicle only. A small increase in the amount of enkephalin mRNA was also seen after 8 h (P , 0:05), whereas no difference between estrogen-injected and control animals was found after 24 h or at time periods shorter than 4 h. Taken together with the previous anatomical data, the present findings imply that estrogen has an acute effect on spinal opioid levels in areas involved in the transmission of nociceptive information.

    Place, publisher, year, edition, pages
    Elsevier, 1999
    Keywords
    Preproenkephalin mRNA, Gonadal hormone, Pain, Spinal cord
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17974 (URN)
    Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2019-10-14Bibliographically approved
    4. Estrogen receptor-α expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat
    Open this publication in new window or tab >>Estrogen receptor-α expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat
    2010 (English)In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 14, no 3, p. 245-248Article in journal (Refereed) Published
    Abstract [en]

    Estrogens exert a substantial influence on the transmission of nociceptive stimuli and the susceptibility to pain disorders as made evident by studies in both animals and human subjects. The estrogen receptor (ER) seems to be of crucial importance to the cellular mechanisms underlying such an influence. However, it has not been clarified whether nociceptive neurons activated by pain express ERs. In this study, a noxious injection of formalin was given into the lower lip of female rats, thereby activating nociceptive neurons in the trigeminal subnucleus caudalis as demonstrated by immunohistochemical labeling of Fos. Using a dual-label immunohistochemistry protocol ERα-containing cells were visualized in the same sections. In the superficial layers of the medullary dorsal horn, 12 % of ERα-labeled cells, mainly located in lamina II, also expressed noxious-induced Fos. These findings show that nociceptive-responsive neurons in the medullary dorsal horn express ERα, thus providing a possible morphological basis for the hypothesis that estrogens directly regulate pain transmission at this level.

    Keywords
    Estrogen receptor, spinal trigeminal nucleus, gonadal hormone, pain, Fos
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17975 (URN)10.1016/j.ejpain.2009.05.008 (DOI)000275117700003 ()
    Note
    On the day of the defence date the status of this article was Submitted.Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2017-12-13Bibliographically approved
  • 296.
    Amandusson, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Estrogen receptor-α expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat2010In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 14, no 3, p. 245-248Article in journal (Refereed)
    Abstract [en]

    Estrogens exert a substantial influence on the transmission of nociceptive stimuli and the susceptibility to pain disorders as made evident by studies in both animals and human subjects. The estrogen receptor (ER) seems to be of crucial importance to the cellular mechanisms underlying such an influence. However, it has not been clarified whether nociceptive neurons activated by pain express ERs. In this study, a noxious injection of formalin was given into the lower lip of female rats, thereby activating nociceptive neurons in the trigeminal subnucleus caudalis as demonstrated by immunohistochemical labeling of Fos. Using a dual-label immunohistochemistry protocol ERα-containing cells were visualized in the same sections. In the superficial layers of the medullary dorsal horn, 12 % of ERα-labeled cells, mainly located in lamina II, also expressed noxious-induced Fos. These findings show that nociceptive-responsive neurons in the medullary dorsal horn express ERα, thus providing a possible morphological basis for the hypothesis that estrogens directly regulate pain transmission at this level.

  • 297.
    Amandusson, Åsa
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Hermanson, Ola
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Estrogen-induced alterations of spinal cord enkephalin gene expression1999In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 83, no 2, p. 243-248Article in journal (Refereed)
    Abstract [en]

    Enkephalin-synthesizing neurons in the super®cial laminae of the spinal and trigeminal dorsal horn are critical components of the endogenous pain-modulatory system. We have previously demonstrated that these neurons display intracellular estrogen receptors, suggesting that estrogen can potentially influence their enkephalin expression. By using Northern blot, we now show that a bolus injection of estrogen results in a rapid increase in spinal cord enkephalin mRNA levels in ovariectomized female rats. Thus, 4 h after estrogen administration the enkephalin mRNA-expression in the lumbar spinal cord was on average 68% higher (P , 0:05) than in control animals injected with vehicle only. A small increase in the amount of enkephalin mRNA was also seen after 8 h (P , 0:05), whereas no difference between estrogen-injected and control animals was found after 24 h or at time periods shorter than 4 h. Taken together with the previous anatomical data, the present findings imply that estrogen has an acute effect on spinal opioid levels in areas involved in the transmission of nociceptive information.

  • 298.
    Amasheh, Maren
    et al.
    Charite.
    Grotjohann, Ingo
    Charite.
    Amasheh, Salah
    Charite.
    Fromm, Anja
    Charite.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Zeitz, Martin
    Charite.
    Fromm, Michael
    Charite.
    Schulzke, Joerg-Dieter
    Charite.
    Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro: A novel model for studying the pathomechanisms of inflammatory bowel disease cytokines2009In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 44, no 10, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    Objective. In Inflammatory bowel disease (IBD), elevated cytokines are responsible for disturbed intestinal transport and barrier function. The mechanisms of cytokine action have usually been studied in cell culture models only; therefore the aim of this study was to establish an in vitro model based on native intestine to analyze distinct cytokine effects on barrier function, mucosal structure, and inherent regulatory mechanisms. Material and methods. Rat colon was exposed to tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in Ussing chambers. Transepithelial resistance (R-t) and H-3-mannitol fluxes were measured for characterization of the paracellular pathway. Transcellular transport was analyzed by horseradish peroxidase (HRP) flux measurements. Expression and distribution of tight junction proteins were characterized in immunoblots and by means of confocal laser-scanning microscopy (LSM). Results. Colonic viability could be preserved for 20 h in a specialized in vitro set-up. This was sufficient to alter mucosal architecture with crypt surface reduction. R-t was decreased (101 +/- 10 versus 189 +/- 10 Omega . cm(2)) with a parallel increase in mannitol permeability after cytokine exposure. Tight junction proteins claudin-1, -5, -7, and occludin decreased (45 +/- 10%, 16 +/- 7%, 42 +/- 8%, and 42 +/- 13% of controls, respectively), while claudin- 2 increased to 208 +/- 32%. Occludin and claudin- 1 translocated from the plasma membrane to the cytoplasm. HRP flux increased from 0.73 +/- 0.09 to 8.55 +/- 2.92 pmol . h(-1) . cm(-2). Conclusions. A new experimental IBD model with native colon in vitro is presented. One-day exposure to TNFa and IFNg alters mucosal morphology and impairs epithelial barrier function by up-regulation of the paracellular pore-former claudin-2 and down-regulation of the barrier-builders claudin-1, -5, and -7. These alterations resemble changes seen in IBD and thus underline their prominent role in IBD pathogenicity.

  • 299.
    Amatya, B
    et al.
    Karolinska University Hospital.
    El-Nour, H
    Karolinska University Hospital.
    Holst, M
    Astrid Lindgren Childrens Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Nordlind, K
    Karolinska University Hospital.
    Expression of tachykinins and their receptors in plaque psoriasis with pruritus2011In: BRITISH JOURNAL OF DERMATOLOGY, ISSN 0007-0963, Vol. 164, no 5, p. 1023-1029Article in journal (Refereed)
    Abstract [en]

    Pandgt;Background Cutaneous melanoma is rapidly increasing in incidence worldwide and approximately 5% of melanomas are hereditary. Deletions in chromosome 1p36 have been detected in melanoma but no candidate melanoma tumour suppressor gene has yet been found in this area. Recently, strong evidence has been reported that CHD5 is a tumour suppressor gene in this region. Objectives To investigate CHD5 involvement in familial melanoma. Methods Peripheral blood DNA from 47 melanoma families who do not carry mutations in any of the three currently recognized melanoma genes, 398 patients with sporadic melanoma and 398 geographically matched nonmelanoma-bearing controls were studied. Linkage investigation, single nucleotide polymorphism (SNP) genotyping and mutation screening studies were carried out on the CHD5 locus. Results The CHD5 gene was not excluded by linkage analysis in any of the families. On SNP genotyping, the CHD5 rs7513548 SNP was found to be significantly associated with sporadic melanoma (odds ratio 1 center dot 53, 95% confidence interval 1 center dot 13-2 center dot 06). The AG genotype was found in 208 cases and 169 controls (cf. 141 and 175 cases and controls, respectively, for the AA genotype). On CHD5 mutation screening, a total of 50 single-base substitutions were detected. Of these, 39 were intronic and 11 were exonic. While 32 were previously recognized variants, 18 were newly identified. Three, in exons 4, 31 and 32, led to nonsynonymous substitutions. A p.Met1576Ile substitution was identified in a mother and daughter, both with invasive cutaneous melanoma. Conclusions This study appears to be the first report of CHD5 variants in familial cutaneous melanoma. Such CHD5 variants could block or alter the ability of CHD5 to regulate the cell cycle pathway and to effect cellular control. As only one of the 47 families studied has this variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis.

  • 300.
    Ambrosi, Aurelie
    et al.
    Karolinska Institute.
    Salomonsson, Stina
    Karolinska Institute.
    Eliasson, Hakan
    Karolinska Institute.
    Zeffer, Elisabeth
    Karolinska Institute.
    Dzikaite, Vijole
    Karolinska Institute.
    Bergman, Gunnar
    Karolinska Institute.
    Fernlund, Eva
    Skane University Hospital.
    Theander, Elke
    Malmo University Hospital.
    Ryberg, Annika
    Umea University Hospital.
    Ohman, Annika
    Uppsala University.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Rantapaa, Solbritt
    Umea University Hospital.
    Fored, Michael
    Karolinska Institute.
    Blomqvist, Paul
    Karolinska Institute.
    Ekbom, Anders
    Karolinska Institute.
    Lindsrtom, Ulla
    Queen Silvia Childrens Hospital.
    Melander, Mats
    Queen Silvia Childrens Hospital.
    Winqvist, Ola
    Karolinska Institute.
    Gadler, Fredrik
    Karolinska Institute.
    Jonzon, Anders
    Uppsala University.
    Sonesson, Sven-Erik
    Karolinska Institute.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    Influence of Season of Birth and Maternal Age in the Development of Congenital Heart Block in Anti-Ro-SSA/La-SSB Positive Pregnancies in SCANDINAVIAN JOURNAL OF IMMUNOLOGY, vol 72, issue 3, pp 265-2652010In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, Blackwell Publishing Ltd , 2010, Vol. 72, no 3, p. 265-265Conference paper (Refereed)
    Abstract [en]

    n/a

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