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  • 201.
    Landgren, Emilia
    et al.
    Halmstad University, School of Business and Engineering (SET).
    Wallman, Sabina
    Halmstad University, School of Business and Engineering (SET).
    Hästavmaskningsmedels påverkan på miljö och välfärd2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Healthy, natural pastures is very valuable for biodiversity in the form of both plants and animals. An efficient use of pastures helps to preserve biodiversity, but grazing animals needs to be de-wormed to keep them healthy and to prevent harmful parasites spread on the pasture. The awareness about the environmental impact of the frequent use of deworming agents is low among the public. Some people are unaware that the absorption in horses of anthelmintics is incomplete, which make the circumstances about enviromental effect important to investigate further. The scientific evidence in this area is limited and more studies and trials are needed to deepen the knowledge about the effects of anthelmintics in the environment. Our report includes a compilation of studies conducted on anthelmintics and equine parasites, as well as an experiment which was conducted at the University of Halmstad biogaslaboratory April 2014. Anthelmintics have been shown to have negative impact on the manure ecosystem and especially against manure living fauna. Deworming routines has changed over the years as the equine industry has developed. Nevertheless, there’s still a lack of concrete approach to deworming.

  • 202.
    Larson, Greger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Liu, Ranran
    Zhao, Xingbo
    Yuan, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fuller, Dorian
    Barton, Loukas
    Dobney, Keith
    Fan, Qipeng
    Gu, Zhiliang
    Liu, Xiao-Hui
    Luo, Yunbing
    Lv, Peng
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Li, Ning
    Patterns of East Asian pig domestication, migration, and turnover revealed by modern and ancient DNA.2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 17, p. 7686-7691Article in journal (Refereed)
    Abstract [en]

    The establishment of agricultural economies based upon domestic animals began independently in many parts of the world and led to both increases in human population size and the migration of people carrying domestic plants and animals. The precise circumstances of the earliest phases of these events remain mysterious given their antiquity and the fact that subsequent waves of migrants have often replaced the first. Through the use of more than 1,500 modern (including 151 previously uncharacterized specimens) and 18 ancient (representing six East Asian archeological sites) pig (Sus scrofa) DNA sequences sampled across East Asia, we provide evidence for the long-term genetic continuity between modern and ancient Chinese domestic pigs. Although the Chinese case for independent pig domestication is supported by both genetic and archaeological evidence, we discuss five additional (and possibly) independent domestications of indigenous wild boar populations: one in India, three in peninsular Southeast Asia, and one off the coast of Taiwan. Collectively, we refer to these instances as "cryptic domestication," given the current lack of corroborating archaeological evidence. In addition, we demonstrate the existence of numerous populations of genetically distinct and widespread wild boar populations that have not contributed maternal genetic material to modern domestic stocks. The overall findings provide the most complete picture yet of pig evolution and domestication in East Asia, and generate testable hypotheses regarding the development and spread of early farmers in the Far East.

  • 203. Lebbad, Marianne
    et al.
    Mattsson, Jens G
    Christensson, Bodil
    Ljungström, Bitte
    Backhans, Annette
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Molecular Evolution.
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    From mouse to moose: multilocus genotyping of Giardia isolates from various animal species.2010In: Veterinary parasitology, ISSN 0304-4017, E-ISSN 1873-2550, Vol. 168, no 3-4, p. 231-239Article in journal (Refereed)
    Abstract [en]

    Giardia intestinalis is a protozoan parasite that consists of seven genetically distinct assemblages (A to G). Assemblage A and B parasites have been detected in a wide range of animals including humans, while the other assemblages (C to G) appear to have a narrower host range. However, the knowledge about zoonotic transmission of G. intestinalis is limited. To address this question, 114 Giardia isolates from various animals in Sweden including pets, livestock, wildlife and captive non-human primates were investigated by a sequence-based analysis of three genes (beta-giardin, glutamate dehydrogenase and triose phosphate isomerase). Assemblage A infections were detected in nine ruminants, five cats and one dog, while three sheep were infected with both assemblages A and E. Multilocus genotypes (MLGs) were defined for assemblage A, and three of these MLGs have previously been detected in Giardia isolates from humans. The newly described sub-assemblage AIII, until now reported mainly in wild hoofed animals, was found in one cat isolate. Assemblage B occurred in three monkeys, one guinea pig and one rabbit. The rabbit isolate exhibited sequences at all three loci previously detected in human isolates. The non-zoonotic assemblages C, D, E, F or G were found in the remaining 83 G. intestinalis isolates, which were successfully amplified and genotyped, generating a wide variety of both novel and known sub-genotypes. Double peaks in chromatograms were seen in assemblage B, C, D and E isolates but were never observed in assemblage A, F and G isolates, which can reflect differences in allelic sequence divergence. No evidence of genetic exchange between assemblages was detected. The study shows that multilocus genotyping of G. intestinalis is a highly discriminatory and useful tool in the determination of zoonotic sub-groups within assemblage A, but less valuable for subtyping assemblages B, C, D and E due to the high frequency of double peaks in the chromatograms. The obtained data also suggest that zoonotic transmission of assemblages A and B might occur to a limited extent in Sweden.

  • 204.
    LeBlanc, Neil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Leijon, Mikael
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Belak, Sandor
    A novel combination of TaqMan RT-PCR and a suspension microarray assay for the detection and species identification of pestiviruses2010In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 142, no 1-2, p. 81-86Article in journal (Refereed)
    Abstract [en]

    The genus pestivirus contains four recognized species: classical swine fever virus, border disease virus, bovine viral diarrhoea virus types 1 and 2. All are economically important and globally distributed but classical swine fever is the most serious, concerning losses and control measures. It affects both domestic pigs and wild boars. Outbreaks of this disease in domestic pigs call for the most serious measures of disease control, including a stamping out policy in Europe. Since all the members of the pestivirus genus can infect swine, differential diagnosis using traditional methods poses some problems. Antibody tests may lack specificity due to cross-reactions, antigen capture ELISAs may have low sensitivity, and virus isolation may take several days or even longer time to complete. PCR-based tests overcome these problems for the most part, but in general lack the multiplexing capability to detect and differentiate all the pestiviruses simultaneously. The assay platform described here addresses all of these issues by combining the advantages of real-time PCR with the multiplexing capability of microarray technology. The platform includes a TaqMan real-time PCR designed for the universal detection of pestiviruses and a microarray assay that can use the amplicons produced in the real-time PCR to identify the specific pestivirus.

  • 205.
    Lee, Francis
    Linköping University, The Tema Institute, Technology and Social Change. Linköping University, Faculty of Arts and Sciences.
    Purity and interest: on relational work and epistemic value in the biomedical sciences2015In: Value practice in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, oxford: Oxford University Press, 2015, p. 207-223Chapter in book (Refereed)
  • 206. Lequarre, Anne-Sophie
    et al.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andre, Catherine
    Fredholm, Merete
    Hitte, Christophe
    Leeb, Tosso
    Lohi, Hannes
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Georges, Michel
    LUPA: A European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs2011In: The Veterinary Journal, ISSN 0007-1935, E-ISSN 1879-3606, Vol. 189, no 2, p. 155-159Article, review/survey (Refereed)
    Abstract [en]

    The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend.

  • 207.
    Lerner, Henrik
    Linköping University, Department of Culture and Communication, Centre for Applied Ethics. Linköping University, Faculty of Arts and Sciences.
    Transeminarium om eutanasi för människa och av djur2010In: Svensk Veterinärtidning, ISSN 0346-2250, Vol. 62, no 10, p. 23-25Article, review/survey (Other academic)
  • 208. Leufkens, Anke M
    et al.
    Van Duijnhoven, Fränzel J B
    Siersema, Peter D
    Boshuizen, Hendriek C
    Vrieling, Alina
    Agudo, Antonio
    Gram, Inger T
    Weiderpass, Elisabete
    Dahm, Christina
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Charlotta
    Mattiello, Amalia
    Herman, Silke
    Kaaks, Rudolf
    Steffen, Annika
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Peeters, Petra H
    van Gils, Carla H
    van Kranen, Henk
    Lund, Eliv
    Dumeaux, Vanessa
    Engeset, Dagrun
    Rodríguez, Laudina
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Manjer, Jonas
    Almquist, Martin
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Tsilidis, Konstantinos K
    Straif, Kurt
    Leon-Roux, Maria
    Vineis, Paul
    Norat, Teresa
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Cigarette smoking and colorectal cancer risk in the European prospective investigation into cancer and nutrition study2011In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 9, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.

  • 209. Ley, Cecilia
    et al.
    Ekman, S.
    Elmén, A.
    Nilsson, G.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Interleukin-6 and tumour necrosis factor in synovial fluid from horses with carpal joint pathology2007In: Journal of Veterinary Medicine A, ISSN 0931-184X, E-ISSN 1439-0442, Vol. 54, no 7, p. 346-351Article in journal (Refereed)
    Abstract [en]

    The carpal joints are common sites of traumatic arthritis and osteoarthritis (OA) in athletic horses. The pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF) may be of great importance in the development of intra-articular lesions. The aim of the present study was to investigate possible associations between synovial fluid levels of bioactive IL-6 and TNF and different types of joint lesions seen in traumatic arthritis and OA. Synovial fluid was collected from horses with carpal lameness immediately before arthroscopic surgery. Articular cartilage, synovial membranes and intra-articular ligaments were assessed macroscopically at arthroscopy. Synovial fluid levels of IL-6 and TNF were determined by bioassays, and the cytokine levels between different grades of morphologic changes in each type of assessed tissue were compared. The highest levels of IL-6 were detected in joints with chip fractures. All joints with chip fractures also showed some degree of synovitis. Tumour necrosis factor bioactivity was low and not associated with any joint lesion. Hence, TNF is not useful as a biomarker indicating a specific joint lesion in equine traumatic arthritis or OA. We conclude that a dramatic increase of IL-6 in synovial fluid indicates the presence of osteochondral fragmentation, although low or undetectable levels of IL-6 do not exclude chip fractures. The role of IL-6 in the disease process of osteochondral fragmentation needs further investigation.

  • 210.
    Liedberg, Gunilla
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Women with fibromyalgia: Employment and daily life2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: The major symptoms of fibromyalgia have been shown to severely impact everyday activities. As a consequence, many women have problems remaining in a work role. Not being able to fulfil valued roles influences quality of life. Moreover, consequences in terms of high costs in compensation for reduced work ability are also of importance for society. Today, the number of young women diagnosed with fibromyalgia is increasing.

    Objectives: The general aim of this thesis was to increase and deepen knowledge of the life situation of women with fibromyalgia; to examine how to manage a work role when in constant pain, and especially the situation for newly-diagnosed women.

    Subjects and Methods: 278 women with longstanding pain were included. The thesis includes five different studies, two of them with a focus on the work situation, two with focus on young, newly-diagnosed women’s life situation, and one investigating time-use and activity patterns in working and non-working women with fibromyalgia. Methods used are a postal questionnaire, instruments commonly used in fibromyalgia, a diary, and interviews.

    Results: Despite limitations in physical capacity, 48% of the women are working, full-time or part-time. However, most job loss is associated with the fibromyalgia symptoms, and the women report that the symptoms influence their daily activities during most of their waking time. There is a rapid increase in sickness absence in the newly-diagnosed women, and the young women in particular do not return to the labour market during the first year after receiving their diagnosis. The non-working women have a more demanding family situation, and are also less satisfied with their present situation than working women.

    Conclusion: When individual adjustments of the work situation are made and the women participate to a level that matches their ability, they are able to continue in a work role. In evaluating the women’s work capacity, the total life situation of the women should be considered.

  • 211.
    Liljebrink, Y.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Bergh, A.
    Goniometry: is it a reliable tool to monitor passive joint range of motion in horses?2010In: Equine Veterinary Journal, ISSN 0425-1644, E-ISSN 2042-3306, Vol. 42, p. 676-682Article in journal (Refereed)
    Abstract [en]

    P>Reasons for performing study: Simple objective assessment tools are essential to monitor the clinical efficacy of therapeutic interventions used in equine orthopaedics and rehabilitation. In human medicine, goniometry is a validated tool to quantify restrictions in joint range of motion (ROM); however, the technique is not validated in horses. Objectives: To validate 2 different goniometry techniques for the measurement of passive flexion of the fetlock, carpus and hock by examining; 1) the intra- and inter-tester reliability; 2) the differences between 2 goniometry techniques and 3) differences between standing and anaesthetised horses. Methods: The study is composed of three parts: 1) the intra- and inter-tester reliability was examined on 10 horses, where each horse was assessed by 5 pairs of testers measuring ROM with a universal goniometer; 2) the differences between 2 goniometry techniques were examined on 14 horses, each assessed by 2 investigators (either working in pairs with one investigator holding the limb and the other measuring the joint angle, or working individually at the same time holding and measuring); 3) on 6 horses, the differences between standing and anaesthetised horses were assessed by 2 investigators with the same techniques as described above. Nonparametric tests (Mann-Whitney, Wilcoxon sign-rank) and Intraclass Correlation Coefficient (ICC) were used for statistical analysis (P < 0.05). Results: 1) The intra-tester reliability was high to excellent (ICC 0.8-1) and the inter-tester reliability low to average (ICC 0.1-0.5); 2) significant differences in joint ROM were registered in carpus and hock when measuring in pairs compared to singly and 3) significant differences in joint ROM were registered measuring anaesthetised compared to standing horses. Conclusions: As shown in human studies, goniometry is a promising tool in documenting passive flexion of fetlock, carpus and hock, if used by the same investigator. However, additional studies are needed for further validation.

  • 212. Lind, Eva Osterman
    et al.
    Rautalinko, Erik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Uggla, Arvid
    Waller, Peter J.
    Morrison, David A.
    Höglund, Johan
    Parasite control practices on Swedish horse farms2007In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 49, no 1, p. 25-Article in journal (Refereed)
    Abstract [en]

    Background: Virtually all horses are infected with helminth parasites. For some decades, the control of parasites of Swedish horses has been based on routine treatments with anthelmintics, often several times per year. Since anthelmintic resistance is becoming an increasing problem it is essential to develop more sustainable control strategies, which are adapted to different types of horse management. The aim of this study was to obtain information on practices used by Swedish horse owners for the control of endoparasites. Methods: A questionnaire with 26 questions about management practices and parasite control routines was posted to 627 randomly selected horse establishments covering most types of horse management in Sweden. Results: The response rate was good in all categories of respondents (66-78%). A total of 444 questionnaires were used in the analyses. It was found that virtually all horses had access to grazing areas, usually permanent. Generally, pasture hygiene was infrequently practiced. Thirty-six percent of the respondents clipped or chain harrowed their pastures, whereas weekly removal of faeces from the grazing areas was performed by 6% of the respondents, and mixed or rotational grazing with other livestock by 10%. The number of anthelmintic treatments per year varied from 1-8 with an average of 3.2. Thirty-eight percent considered late autumn (Oct-Dec) to be the most important time for deworming. This finding, and an increased use of macrocyclic lactones in the autumn, suggests a concern about bot flies, Gasterophilus intestinalis. Only 1% of the respondents stated that faecal egg counts (FEC) were performed on a regular basis. The relatively high cost of FEC analyses compared to purchase of anthelmintics was thought to contribute to the preference of deworming without a previous FEC. From the study it was evident that all categories of horse owners took advice mainly from veterinarians. Conclusion: The results show that routines for endoparasite control can be improved in many horse establishments. To increase the knowledge of equine endoparasite control and follow the recommendations for how to reduce the spread of anthelmintic resistance, a closer collaboration between parasitologists and veterinary practitioners is desirable.

  • 213.
    Lindehammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurophysiology UHL.
    Muscle function in Juvenile Idiopathic Arthritis: A two-year follow-up2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This is a study of muscle function in Juvenile Idiopathic Arthritis (JIA). Rheumatoid arthritis (RA) is a disease that primarily affects the synovial membrane of joints. Muscle weakness, atrophy and pain occur in adult RA. This may be a consequence of joint pain, stiffness and immobility. Muscle inflammation and neuropathy occur as complications in adults. Muscle function in JIA has been much less studied.

    The aim of the study was to examine whether muscle weakness and atrophy also occur in children with JIA.

    This was a longitudinal study over a two-year period, where muscle strength and thickness were measured repeatedly in a group of 20 children and teenagers with JIA. Muscle strength was measured using different methods and in several muscle groups. Muscle biopsies were obtained and nerve conduction velocity studies performed.

    The study concludes that, compared to healthy people, children and teenagers with JIA have as a group reduced muscle strength and muscle thickness. For most of these children and teenagers, muscle strength is only slightly lower than expected, but a few have marked muscle weakness. This is most apparent in patients with severe polyarthritis where the weakness seems to be widespread. Patients with isolated arthritis may also have greatly reduced strength and thickness of muscles near the inflamed joint.

    There is a risk of decreasing strength in patients with polyarthritis and in muscles near an active arthritis.

    Minor changes are common in muscle biopsies, and findings may indicate immunological activity in the muscles.

    Atrophy of type II fibres, as in adult RA, was not found in JIA.

    No patient had signs of neuropathy.

  • 214. Lindqvist, Breezy M.
    et al.
    Wingren, Sten
    Motlagh, Parviz Behnam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Whole genome DNA methylation signature of HER2-positive breast cancer2014In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 9, no 8, p. 1149-1162Article in journal (Refereed)
    Abstract [en]

    In order to obtain a comprehensive DNA methylation signature of HER2-positive breast cancer (HER2+ breast cancer), we performed a genome-wide methylation analysis on 17 HER2+ breast cancer and compared with ten normal breast tissue samples using the Illumina Infinium HumanMethylation450 BeadChip (450K). In HER2+ breast cancer, we found altered DNA methylation in genes involved in multicellular development, differentiation and transcription. Within these genes, we observed an overrepresentation of homeobox family genes, including several genes that have not been previously reported in relation to cancer (DBX1, NKX2-6, SIX6). Other affected genes included several belonging to the PI3K and Wnt signaling pathways. Notably, HER2, AKT3, HK1, and PFKP, genes for which altered methylation has not been previously reported, were also identified in this analysis. In total, we report 69 candidate biomarker genes with maximum differential methylation in HER2+ breast cancer. External validation of gene expression in a selected group of these genes (n = 13) revealed lowered mean gene expression in HER2+ breast cancer. We analyzed DNA methylation in six top candidate genes (AKR1B1, INA, FOXC2, NEUROD1, CDKL2, IRF4) using EpiTect Methyl II Custom PCR Array and confirmed the 450K array findings. Future clinical studies focusing on these genes, as well as on homeobox-containing genes and HER2, AKT3, HK1, and PFKP, are warranted which could provide further insights into the biology of HER2+ breast cancer.

  • 215.
    Lindström, Meta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Gynekologer och barnmorskor inom svensk abortvård: åsikter, erfarenheter och upplevelser2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To investigate gynecologists’ and midwives’ views and experiences regarding work in abortion care in Sweden.

    Methods: Questionnaire to gynecologists (n=269) and midwives (n=258 comprising 48 questions, response 85%. The quantitative studies (articles I-III) were supplemented by a qualitative study (article IV), consisting of focus-group interviews with gynecologists and midwives/nurses.

    Results: From the questionnaire studies it was apparent that all the gynecologists had worked in abortion care, whilst not all midwives had done so. The male gynecologists were older than both their female colleagues and the midwives; they had most years of experience but were now working least with abortion patients. Both groups considered it absolutely right, that Sweden have legal abortion and that the law was being followed. Most thought that women should be allowed to have an abortion even after they had felt fetal movements. The midwives were generally somewhat more restrictive than the gynecologists. Half of all thought that the work with abortion patients brought something positive with it. Those having worked longest and most extensively, especially during the previous year were most liberal. Both groups felt that there was a difference between working with surgical and late abortions compared with medical abortions. One in four had had misgivings when involved in surgical and medical abortions, and one in two with abortions after the 18th week. All were positive about the transition to medical abortions, and roughly two thirds of the midwives thought that the primary care sector should be able to take care of these, whereas less than half of the gynecologists thought this. The majority considered it important to receive further and continuing professional development and ongoing guidance. From the focus-group interviews it was clear that the experiences of the gynecologists were largely connected with the technical development of abortion methods and those of the midwives/nurses with improved pain relief. The work was sometimes described in paradoxical terms and was occasionally experienced as frustrating, especially in connection with repeat abortions. Neither of the two groups, however, had had any doubts about participating in abortion. The gynecologists described how women now expected to get an abortion, whereas previously they had asked for one. The midwife/nurse group maintained that the meetings with the women had become considerably more frequent. The interaction between the two professional groups was marked by great trust in each other’s professional competence.

    Conclusions: Gynecologists and midwives working in abortion care support Swedish abortion legislation and have no doubts about participating in abortions, despite the fact that they have frequently experienced complex and difficult work situations. The character of the work is experienced as contradictory and frustrating, but also as challenging and rewarding. The awareness that the two professional groups have of the importance of continuing professional development and ongoing guidance should be acted on. Furthermore, their collective views and experiences should be made use of, so that abortion care can be developed, not only in order to promote women’s health, but also to improve the work environment for the abortion staff.

  • 216.
    Ling, Agnes
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Immune cell infiltration and prognosis in colorectal cancer2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Colorectal cancer (CRC) is globally the second most common form of cancer among women, and third in men. It is also one of the most common causes of cancer-related death in high-income countries. Surgical resection is the basis for curative therapy but still almost half of the patients die from metastatic disease. It is therefore imperative to strive on in the search for more efficient strategies to improve patient survival. The success scores for accurate prediction of patient prognosis remain discouraging and novel markers to identify high-risk patients are called for.

    The tumour immune response has proven critical to prognosis in CRC. A high amount of tumour infiltrating lymphocytes have in studies been found to significantly improve patient outcome. The opposite has been seen in patients with sparsely infiltrated tumours. Findings in this area have driven forth the design of the Immunoscore® system, which may be implemented in clinic as a complement to the TNM staging system. Ongoing research is also focusing on which immune evading mechanisms CRC might deploy in order to progress and metastasize.

    Aim: To study immune cell infiltration in relation to prognosis in CRC. More specifically the aim has been to investigate the prognostic importance of different subsets of immune cells infiltrating the tumour, not only according to quantity but also to intratumoural subsite (tumour invasive front, tumour centre and within the tumour epithelium). The tumour immune response was also evaluated in different molecular subgroups of CRC. Another part of this thesis concerns possible molecular mechanisms involved in tumour immune escape in CRC.

    Methods: CRC cases in the Colorectal Cancer in Umeå Study (CRUMS) were evaluated using immunohistochemistry, gene expression analyses as well as methylation analyses. Cytokine and chemokine expression was evaluated in CRC tumour tissues and one CRC cell line (Caco2) and derivatives using semi-quantitative real-time PCR. Methylation was analysed using methylation-specific pyrosequencing.

    Results: We found high quantities of both cytotoxic T cells (CTLs) as well as of regulatory T cells (Tregs) to associate with a better patient outcome. The infiltration of CTLs within the tumour epithelium provided the strongest prognostic information, whilst Tregs withheld the strongest association to prognosis at the tumour invasive front and tumour centre. We could further show that a high Th1 lymphocyte infiltration was strongly associated with a better prognosis in patients with CRC, independently of intratumoural subsite. Another finding was that the extent of Th1 infiltration and patient outcome differed in different molecular subgroups of CRC. We also found down-regulation of TAP1, a protein involved in antigen presentation by MHC class I, to be significantly associated with low infiltration of various subtypes of immune cells. Down-regulation of TAP1 was also correlated to poor prognosis in patients with early stages of CRC. Furthermore, we found TAP1 expression to be inversely correlated with methylation at sites close to the TAP1 promoter region.

    Conclusion: Tumour infiltrating T lymphocytes have a significant positive impact on prognosis in CRC patients. Different subsets of T lymphocytes vary in their dependency on intratumoural subsite, in to what extent they exert their prognostic influence. We moreover found varying Th1 lymphocyte infiltration rates as well as prognostic impact thereof, in different molecular subgroups of CRC. Our results also show down-regulation of TAP1 to be a mechanism of tumour immune escape in CRC. Further findings suggest methylation of the TAP1 gene to be a putative mechanism for TAP1 down-regulation.

  • 217. Ljungvall, I.
    et al.
    Höglund, K.
    Tidholm, A.
    Olsen, L. H.
    Borgarelli, M.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Haggström, J.
    Cardiac Troponin I Is Associated with Severity of Myxomatous Mitral Valve Disease, Age, and C-Reactive Protein in Dogs2010In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 24, no 1, p. 153-159Article in journal (Refereed)
    Abstract [en]

    Background Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. Objective To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations. Animals Eighty-one client-owned dogs with MMVD of varying severity. Methods Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. Results Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008-0.029] ng/mL, P = .0011) and severe (0.043 [0.031-0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001-0.004] ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001-0.024] ng/mL, P < .0001) and moderate (P = .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. Conclusions and Clinical Importance Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.

  • 218.
    Ljuslinder, Ingrid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Increased epidermal growth factor receptor expression at the invasive margin is a negative prognostic factor in colorectal cancer2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 9, p. 2031-2037Article in journal (Refereed)
    Abstract [en]

    The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is often expressed in solid malignant tumours, and the expression has been correlated to disease progression. Multiple new agents targeted against the EGFR have been developed during the last decade, but treatment selecting criteria are still not clear. This immunohistochemical study includes 386 colorectal cancer patients and focuses on EGFR expression variations within the tumour, comparing central parts to the invasive margin. Positive immunostaining for EGFR was evident in the central part in 176/386 (46%) of analyzed primary tumours. The invasive margin was positive in 222/386 (58%). A similar expression in both the central part and the invasive front was evident in 286/386 (74%). An increased score at the invasive margin compared to central parts (EGFR(i)) was evident in 97/386 (25%) of the tumours. Moreover, the results show a significant survival disadvantage for the EGFR(i) group, both in potentially curatively resected colon cancer patients (n = 170, p = 0.01) and in potentially curatively resected colon and rectal cancer patients combined (n = 273, p = 0.013). Multivariate survival analysis adjusted for age, gender, bowel localisation, grade, stage and tumour type showed an increased risk of cancer death for EGFR(i) tumours (HR, 1.53; 95% CI, 1.04-2.23; p = 0.029). A significant correlation between EGFR expression at the invasive margin and the presence of budding was seen (p = 0.0001). This investigation of a large patient material implies that EGFR immunohistochemical analysis still has a role in risk evaluation of colorectal cancer patients.

  • 219.
    Loncarevic, Semir
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Milanovic, A
    Department of Food Hygiene, Veterinary Faculty, Sarajevo, Bosnia.
    Caklovica, F
    Department of Food Hygiene, Veterinary Faculty, Sarajevo, Bosnia.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Occurrence of Listeria species in an abattoir for cattle and pigs in Bosnia and Hercegovina1994In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 35, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    Altogether 496 samples of meat, lymph nodes, process water and swabs from different places in the abattoir were examined for the presence of Listeria spp. L. monocytogenes was isolated from 31 (6%) and other Listeria spp. from 65 (13%) samples L. monocytogenes was isolated from 2 of 10 beef meat samples, 4 of 50 pig meat samples and 1 of 21 lymph nodes of pigs. No Listeria bacteria were isolated from lymph nodes of cattle. The highest percentage of Listeria was recovered from the unclean sections (cattle 22% and pigs 27%) and the highest frequency was observed during the winter months.

  • 220.
    Loncarevic, Semir
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Tham, Wilhelm
    Örebro University, School of Hospitality, Culinary Arts & Meal Science. Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science. Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Occurrence of Listeria species in broilers pre- and post-chilling in chlorinated water at the two slaughterhouses1994In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 35, no 2, p. 149-154Article in journal (Refereed)
    Abstract [en]

    Altogether 323 pooled samples of neck skins from 1615 broilers from 2 processing plants (A and B) were examined for the presence of Listeria species. The broilers were sampled pre-chilling - after leaving the final rinser but before entering the chiller with chlorinated water - and post-chilling - immediately upon leaving the chiller. Free available chlorine in the chilling water varied from 2 to 15 ppm in plant A and was about 10 ppm in plant B. Listeria monocytogenes was only isolated from broilers in plant A sampled post-chilling (58% of 62 samples). L. innocua was isolated from 19% and 39% of broilers sampled pre-chilling in plants A and B, respectively. Post-chilling, L. innocua was isolated from 3% and 6% of samples from plants A and B, respectively.

  • 221.
    Lundgren, Magdalena
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Interplay between hormones, nutrients and adipose depots in the regulation of insulin sensitivity: an experimental study in rat and human adipocytes2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity and specifically central obesity is related to insulin resistance, type 2 diabetes and other components of the so-called metabolic syndrome. The aim of this study was to elucidate the interplay between hormones, nutrients and adipose depots in normal and insulin-resistant fat cell metabolism.

    High levels of free fatty acids (FFAs) induce insulin resistance in muscle and liver in vivo. In the present study, rat adipocytes were treated with high physiological levels of oleic or palmitic acid in vitro for 4-24 h. This treatment had no effect on basal or insulin-stimulated glucose uptake capacity in these cells, neither did it affect the levels of the insulin signalling proteins; insulin receptor substrate (IRS)-1 or –2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B (PKB) or glucose transporter (GLUT) 4, or the regulation of lipolysis rate.

    Visceral adiposity is considered to be more harmful than peripheral adiposity with respect to metabolic and cardiovascular complications. In adipose biopsies from subjects undergoing abdominal surgery, we found that glucose uptake capacity was elevated in omental as compared to subcutaneous adipocytes. The sensitivity (EC50) or maximum relative response to insulin, measured as % of basal, did however not differ between the depots. In women, subcutaneous adipocytes displayed a higher lipolysis rate following cAMP-stimulation than omental adipocytes, whereas there was a tendency towards the opposite in adipocytes from men. No differences were found between depots or sexes in the ability of insulin to inhibit lipolysis or in the levels of the lipolysis regulating proteins, i.e. protein kinase A (PKA), hormone sensitive lipase (HSL) and perilipin.

    Glucocorticoids, e.g. cortisol, exert pronounced insulin-antagonistic effects and are associated with redistribution of fat from peripheral to central fat depots in humans. Treatment of human subcutaneous and omental adipocytes in vitro, with the cortisol analogue dexamethasone, resulted in a dose dependent down-regulation of basal and insulin-stimulated glucose uptake capacity in omental, but not in subcutaneous cells. Concomitantly, the levels of IRS-1 and PKB were decreased only in omental adipocytes after dexamethasone treatment. The relative effect of insulin to stimulate glucose uptake was however not altered by dexamethasone treatment. The cAMP-stimulated lipolysis rate was elevated by dexamethasone treatment in cells from the subcutaneous depot in women and tended to be elevated in omental cells from men. No alterations however, were seen in the levels of the assessed lipolysis regulating proteins.

    Subcutaneous as well as omental fat cell size correlated negatively to insulin action in subcutaneous fat cells in vitro after adjusting for age, sex and body fat parameters in non-diabetic, but not in type 2 diabetic, subjects. Large subcutaneous fat cell size was strongly related to plasma leptin levels in non-diabetic and in type 2 diabetic subjects.

    We conclude that 1) adipocytes seem to be less vulnerable to elevated levels of fatty acids than muscle and liver cells, 2) the interactions between glucocorticoids and insulin in the regulation of glucose uptake differ between adipose depots, 3) depot specific hormonal lipolysis regulation differs between sexes and 4) fat cell size is related to insulin action in subcutaneous fat cells and to circulating levels of leptin.

  • 222.
    Lundholm, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikberg, Maria L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. anders.bergh@umu.se.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15651Article in journal (Refereed)
    Abstract [en]

    Macrophage infiltration has been associated with an improved prognosis in patients with colorectal cancer (CRC), but a poor prognosis in prostate cancer (PC) patients. In this study, the distribution and prognostic value of proinflammatory M1 macrophages (NOS2(+)) and immunosuppressive M2 macrophages (CD163(+)) was evaluated in a cohort of 234 PC patients. We found that macrophages infiltrating PC were mainly of an M2 type and correlated with a more aggressive tumor and poor patient prognosis. Furthermore, the M1/M2 ratio was significantly decreased in PC compared to CRC. Using in vitro cell culture experiments, we could show that factors secreted from CRC and PC cells induced macrophages of a proinflammatory or immunosuppressive phenotype, respectively. These macrophages differentially affected autologous T lymphocyte proliferation and activation. Consistent with this, CRC specimens were found to have higher degrees of infiltrating T-helper 1 cells and active cytotoxic T lymphocytes, while PC specimens displayed functionally inactive T cells. In conclusion, our results imply that tumour-secreted factors from cancers of different origin can drive macrophage differentiation in opposite directions and thereby regulate the organization of the anti-tumour immune response. Our findings suggest that reprogramming of macrophages could be an important tool in the development of new immunotherapeutic strategies.

  • 223.
    Lundin, Desiré
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Do the new signal transduction modulators have activity in vitro in tumor cells from ovarian carcinoma and lymphoma?2005Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    During the last decades, chemotherapy with cytotoxic drugs has played a significant role in cancer therapy. It’s important to develop new anticancer drugs, and drug sensitivity testing in vitro can be used to find the right diagnosis for the newly developed substances.

    The aim of this study was to investigate the cytotoxic activity of the new signal transduction modulators bortezomib, gefitinib and PKC412. The well-established substances cisplatin, cytarabine, doxorubicin and vincristin were investigated for comparison.

    The activity of the cytotoxic drugs was analysed in human tumor samples from patients with ovarian carcinoma (n=16) and lymphoma (n=15) by using the Fluorometric Microculture Cytotoxicity Assay (FMCA). The testing of cellular drug resistance by FMCA was accomplished successfully in 33 out of the 34 samples (97%).

    The results of this study indicated that the activity of cytotoxic drugs in tumor cells obtained from patients with ovarian carcinoma and lymphoma may be detected by the FMCA. It also suggested that bortezomib and gefitinib could represent promising agents for treatment of ovarian carcinoma and that PKC412 might be of less use for patients with this diagnose.

  • 224.
    Läikkö, Tina
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, SLU, Uppsala; Meat and Fish Hygiene Unit, Helsinki, Finland.
    Båverud, Viveca
    Department of Bacteriology, National Veterinary Institute, Uppsala.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, SLU, Uppsala.
    Fridén, S.
    Vännäs District Veterinary Station, Mariahällan, Vännäs.
    Grip Hansson, A.
    ännäs District Veterinary Station, Mariahällan, Vännäs.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, SLU, Uppsala.
    Canine tinsillitis associated with Listeria monocytogenes2004In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 154, no 23, p. 732-732Article in journal (Refereed)
  • 225.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors.

    Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids.

    Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA).

    Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior.

    Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.

  • 226.
    Löfgren, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Strömberg, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Meyerson, Bengt
    Department of Neuroscience, Division of Pharmacology, Box 593, BMC, SE-751 24 Uppsala, Sweden..
    Bäcktröm, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Chronic subordination stress augments combined progesterone and estradiol withdrawal behaviorManuscript (Other academic)
    Abstract [en]

    Exposure to stress is a risk factor for developing pre-menstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD), and stress enhances the anxiogenic effect of female sex steroids in animals. This study examines the interaction between chronic subordination stress and withdrawal from progesterone (P4) and estradiol (E2) (PEWD) in producing behaviors analogous to anxiety and irritability in rats. At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (~35 days) and two older rats (~50 days). The housing condition was aimed at producing chronic subordination stress in the younger animals. Chronic subordination stress was assessed by the elevated plus maze (EPM) and by corticosterone (CORT) analysis. A triad of three 35-day-old rats was used as age control. Social rank within the triads was determined using a food competition test (FCT) and the tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5 mg/kg progesterone combined with 10 µg/kg 17β estradiol. Twenty-four hours after the last injection, the subordinate and dominant animals were tested in the open-field test (OFT) and in the intruder test (IT). The IT consists of a 10-minute exposure to 3 unfamiliar rats. Chronic subordination stress reduced EPM open-arm time and altered the CORT response. It also made the subordinate animals more vulnerable to PEWD. The effects were increased locomotion in the OFT, increased defensive burying, and increased social anxiety in the intruder test (IT). Dominant animals did not react to PEWD. Thus, chronic subordination stress augments PEWD.

  • 227.
    Lönn, Johanna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. PEAS Institute, Linköping, Sweden.
    Shahzad, Faisal
    PEAS Institute, Linköping, Sweden.
    Uhlin, Fredrik
    Department of Nephrology UHL, County Council of Östergötland, Linköping, Sweden; Department of Medicine and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Almroth, Gabriel
    Department of Nephrology UHL, County Council of Östergötland, Department of Medicine and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden.
    Nayeri, Fariba
    PEAS Institute, Linköping, Sweden; Department of Molecular and Clinical Medicine, Division of Infectious Diseases, University Hospital, Linköping, Sweden.
    High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure2012In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 3, no 4, p. 516-523Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased affinity to HSPG (P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

  • 228.
    Lönnqvist, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Applications of human skin in vitro2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic wounds are a substantial problem in today’s health care and place significant strains on the patient. Successful modelling of the wound healing process is pivotal for the advancement of wound treatment research. Wound healing is a dynamic and multifactorial process involving all constituents of the skin. The progression from haemostasis and inflammation to proliferation of epidermal  keratinocytes and dermal fibroblasts, and final scar maturation can be halted and result in a chronic wound that fails to re-epithelialise. The wound healing process constitutes an example of dynamic reciprocity in tissue where cellular changes take place on cues from the extracellular matrix and vice versa when tissue homeostasis is disturbed. The extracellular matrix provides a structural context for the resident cells and the epidermal keratinocytes, and a functioning interplay between the two tissue compartments is crucial for successful wound healing to take place. Work included in this thesis has applied viable human full thickness skin in vitro to investigate the re-epithelialisation process and barrier function of intact skin.The use of full thickness skin in vitro can take into account the contextual aspect of the process where the epidermal keratinocytes are activated and obtain a migratory phenotype, and are continuously dependent on the cues from the extracellular matrix and support of the dermis. When utilising skin for studies on re-epithelialisation, circular standardised full thickness wounds were created and cultured  for up to four weeks in tissue culture. In paper I, the organisation of a thick neoepidermis was investigated in the in vitro wound healing model when resident cells were provided with a porous suspended three dimensional gelatin scaffold. In paper II we investigated the use of a fluorescent staining conventionally used for proliferation studies to facilitate the tracing of transplanted epidermal cells in in vitro  wounds, in order to improve and expand the use of the model. In paper III the model was utilised to investigate the treatment approach of acidification of wounds to evaluate the suitability of such intervention in regards to keratinocyte function and re-epithelialisation. Studies on re-epithelialisation with the aid of the in vitro wound healing model provided insight in neoepidermal structure with porous gelatin scaffolding in the wound, a novel methodological approach to tracing cells and response to constrained wound healing environment. In paper IV, intact human skin was evaluated for modelling the cytotoxic response after exposure to a known irritant compound. To study barrier function, intact skin was exposed to irritants by restricting exposure topically, and full thickness skin in vitro was found suitable for modelling cytotoxicity responses. Employing human full thickness skin in vitro makes use of the actual target tissue of interest with epidermal and dermal cells, and full barrier function.

  • 229.
    Magnusson, Ulf
    Swedish University of Agricultural Sciences.
    21. Overview of Infectious Diseases and the Wildlife-Livestock Interface2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 183-185Chapter in book (Other (popular science, discussion, etc.))
  • 230. Mansa, S.
    et al.
    Palmér, E.
    Grondahl, C.
    Lonaas, L.
    Nyman, Görel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Long-term treatment with carprofen of 805 dogs with osteoarthritis2007In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 160, no 13, p. 427-430Article in journal (Refereed)
    Abstract [en]

    The pain-relieving effect of carprofen and tolerance to the drug were investigated in 805 dogs that were lame as a result of osteoarthritis. The dogs were of different breeds, ages and bodyweights and of both sexes, and were selected from 51 veterinary clinics. Each dog was treated orally by its owner with 4 mg/kg carprofen for 84 consecutive days. Twenty-four dogs were removed from the study because of side effects, and 55 left the study for reasons unrelated to the treatment. The condition of the dogs and the benefit of the treatment were evaluated by the veterinary surgeons and the owners after 14 days, and at the end of the period of treatment, when 194 of the dogs (26-7 per cent) were no longer lame, and 357 (49-2 per cent) had improved. The period for which the dogs had been lame before entering the study significantly (P < 0.01) affected the results and the rate of improvement. Too much exercise during the 84 days of treatment caused some dogs to relapse.

  • 231. Mared, Malin
    et al.
    Catchpole, Brian
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fall, Tove
    Evaluation of circulating concentrations of glucose homeostasis biomarkers, progesterone, and growth hormone in healthy Elkhounds during anestrus and diestrus2012In: American Journal of Veterinary Research, ISSN 0002-9645, E-ISSN 1943-5681, Vol. 73, no 2, p. 242-247Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether circulating concentrations of biomarkers of glucose homeostasis, progesterone, and growth hormone in healthy female Elkhounds differ during diestrus and anestrus and to compare those findings with data from dogs of other breeds.

    Animals: 22 healthy female dogs of Elkhound breeds (known to have a high incidence of diestrus-associated diabetes mellitus) and 18 healthy female non-Elkhound dogs.

    Procedures: For each dog, a blood sample (12 mL) was collected once during anestrus and once 2 to 8 weeks after cessation of estrual bleeding. Serum or whole blood samples were analyzed for glucose, growth hormone, insulin-like growth factor-1, C-peptide, fructosamine, and glycated hemoglobin A1c concentrations. Homeostasis model assessments (HOMAs) of pancreatic beta-cell function and insulin secretion were calculated.

    Results: In Elkhounds, C-peptide concentration and the HOMA for beta-cell function (markers of insulin secretion) were higher in samples obtained during diestrus, compared with findings in samples obtained during anestrus. The HOMA for insulin sensitivity was lower (albeit not significantly) during diestrus than it was during anestrus in Elkhounds. Markers of insulin secretion and sensitivity were similar during anestrus and diestrus in the dogs of other breeds. Serum progesterone concentrations were greater during diestrus than during anestrus in Elkhounds and non-Elkhound dogs. All other variables did not differ between diestrus and anestrus within or between the 2 breed groupings.

    Conclusions and Clinical Relevance: Results provided evidence that circulating insulin concentrations during diestrus are higher than those during anestrus in Elkhounds, which could contribute to development of diestrus-associated diabetes mellitus.

  • 232. Marincevic-Zuniga, Yanara
    et al.
    Zachariadis, Vasilios
    Cavelier, Lucia
    Castor, Anders
    Barbany, Gisela
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Fogelstrand, Linda
    Heyman, Mats
    Abrahamsson, Jonas
    Lonnerholm, Gudmar
    Nordgren, Ann
    Syvanen, Ann-Christine
    Nordlund, Jessica
    PAX5-ESRRB is a recurrent fusion gene in B-cell precursor pediatric acute lymphoblastic leukemia2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 1, p. E20-E23Article in journal (Refereed)
  • 233.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Tannerstedt, Jörgen
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Nya aspekter på aminosyrors roll i den muskulära anpassningen till träning2006In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 15, no 3, p. 56-60Article in journal (Other academic)
    Abstract [sv]

    Sammanfattningsvis kan sägas att tillgängligheten av protein/aminosyror är nödvändig för den muskulära anpassningen till träning vid både styrke- och uthållighetsträning. Betydligt fler studier har undersökt effekterna på styrketräning, men vid båda typer av träning är dock kunskaperna om de bakomliggande mekanismerna ännu så länge små. Genom den omfattande forskning som pågår inom området kommer med all säkerhet de molekylära och cellulära förändringar som sker i samband med träning att kartläggas inom en relativt snar framtid. Därmed öppnas nya möjligheter att förbättra och optimera träningen, t.ex. genom kombination av olika typer av aktiviteter (uthållighet och styrketräning). Denna kunskap är också avgörande för att förstå och eventuellt kunna påverka träningseffekten genom förändringar i nutritionens sammansättning.

  • 234. McGreevy, Paul Damien
    et al.
    Sundin, Maria
    Karlsteen, Magnus
    Berglin, Lena
    University of Borås, Swedish School of Textiles.
    Ternström, Johanna
    Hawson, Lesley
    Richardsson, Helena
    McLean, Andrew N
    Problems at the human: horse interface and prospects for smart textile solutions2014In: Journal of Veterinary Behavior: Clinical Applications and Research, ISSN 1558-7878, E-ISSN 1878-7517, Vol. 9, no 1, p. 34-42Article in journal (Refereed)
    Abstract [en]

    The significant potential for so-called “smart textiles” in the design of the next generation of devices that measure pressure, tension, moisture, and heat at the humanehorse interface is discussed in this article. Research techniques from theoretical and experimental physics laboratories, combined with wireless technology, can be readily adapted to measure and store metrics for numerous variables in equine structure and function. Activities, such as breathing, the extension and flexion of joints, limb kinematics, and cardiac function, can be logged as indicators of physiological and behavioral conditioning (training). Such metrics may also, one day, support veterinary diagnostics but also play a role in safeguarding sporthorse welfare, especially in elite contexts where the horse may be pushed to its functional limits. As such, they are likely to emerge as an area of great interest to equitation and welfare scientists. It is important to note that smart textiles sense and react to exogenous stimuli via integrated sensors. So, beyond the equitation science laboratory, the emergence of polymers and smart materials may enhance the effectiveness of, or challenge us to completely rethink, traditional items of saddlery, thus improving equitation. The integration of smart textiles in all sorts of extant and emergent equipment for everyday equestrians could, in the future, lead to equipment that responds appropriately to the demands of equitation in its various forms. Rethinking equitation through physics and the use of smart textiles seems to have merit in that it is a novel means of both investigating and addressing problems that compromise the welfare and performance of horses. The purpose of this article is to envision the use of smart textiles in research, clinical, equestrian, and horse care contexts.

  • 235.
    Mellroth, Peter
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Peptidoglycan Recognition Proteins: Major Regulators of Drosophila Immunity2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    All eukaryotic organisms have an innate immune system characterized by germ-line encoded receptors and effector molecules, which mediate detection and clearance of microbes such as bacteria, fungi, and parasites. VertebrateDrosophila as a genetically tractable organism with a

    This thesis concerns the peptidoglycan recognition protein (PGRP) gene family in the fruit fly. The family consists of thirteen genes, of which a few have been reported to be part of the signaling pathways that regulates immune

    Data presented show that the putative receptors have affinity for peptidoglycan, but not for lipopolysaccharide, or the fungal cell wall polymer beta-glucan. PGRP-SA, receptor of the Toll pathway, has a preference for

    In a search for novel PGRP receptors I found two PGRP proteins that instead displayed enzymatic activity towards peptidoglycan. They are of the N-actylmuramoyl L-alanine amidase type, which degrades peptidoglycan by splittingStaphylococcus aureus peptidoglycan looses its immune elicitor capacity. This is in contrast to lysozyme-degraded peptidoglycan, which isDrosophila PGRPs to be potential enzymes. PGRP-SB1 is the other enzymatic PGRP described within this thesis. It has a moreBacillus megaterium.

    In conclusion, receptor PGRP proteins binds bacterial peptidoglycan and triggers immune gene pathways and enzymatic PGRPs have the capacity to reduce the elicitor property of peptidoglycan.

  • 236.
    Midhagen, Gunnar
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology.
    Adult Coeliac Disease in Clinical Practice2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Coeliac disease (CD) is considered to be the result of a complex interplay of intrinsic (genetic) factors and variable extrinsic (environmental) factors. The complex background of CD explains its wide spectrum of clinical manifestations. For a very long time CD was considered more or less a disease of childhood, which was extremely rare in adults. Nowadays we know that CD is one of the most common food intolerance disorders.

    An epidemiological study of CD in a geographically defined area of Sweden (Paper1) showed a prevalence of 95.5/ 100 000 inhabitants. Among the associated diseases an especially high incidence of associated thyroid disease, 10.8% was observed.

    In a fifteen-year cohort follow up study of all CD-patients residing in the counties of Örebro and Linköping (Paper 2) the total mortality was increased with 38% (SMR 1.38 95% C.I. 0.31-0.83). This was mainly explained by a 48% increased death rate in ischemic heart disease, significant in patients over 65 years (SMR 1.58 95% C.I. 1.00-2.06). However, there was a 47 % lower risk of all malignancies (SIR 0.53 95% C.I. 0.31-0.83).

    A cohort of 22 consecutively biopsy-proven adult CD patients (Paper 3), were followed in respect of antibody titres from diagnosis and after 1, 3, 6, and 12 months on a gluten free diet (GFD). All antibody titres fell sharply within one month. Thus excluding a CD diagnosis serologically on a patient who has initiated a GFD by herself is not to recommend.

    In another cohort with CD patients (Paper IV) who were diagnosed 8-12 years earlier recommended and who were recommended, the reliability of diet history, serological and biochemical markers to predict the appearance of the small intestinal mucosa were analysed (Paper IV). The history of a strict GFD gave a predictive value of 88% of a mucosa in remission. The values of serological tests (AGA, EmA and tTG) to predict a mucosa in remission were 93% for all.

    In CD patients in remission gastro-intestinal symptoms were evaluated with the GSRS questionnaire. Subjects with CD reported significantly more GI-symptoms than a general population sample (p<0.01). This was particularly true for women with CD who scored worse than female controls .By contrast men with CD reported no more symptoms than male controls.

  • 237.
    Miller, Philip S.
    et al.
    International Union for Conservation of Nature, Apple Valley, MN, USA.
    Citino, Scott
    White Oak Conservation Center, Yulee, FL, US.
    2. Facilitating Recovery of Threatened and Endangered Species2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 29-38Chapter in book (Other (popular science, discussion, etc.))
  • 238.
    Mogren, Lars
    et al.
    SLU Sveriges lantbruksuniversitet, Sweden.
    Löfström, Charlotta
    RISE - Research Institutes of Sweden, Bioscience and Materials, Agrifood and Bioscience.
    Alsanius, Beatrix
    SLU Sveriges lantbruksuniversitet, Sweden.
    Håll bevattningsrören rena2017Other (Other (popular science, discussion, etc.))
  • 239. Mollbrink, Johanna
    et al.
    Danielsson-Tham (Intervjuobjekt), Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Livet efter Stutis –: livmedelshygien2015In: Bladmagen, ISSN 0282-3926, Vol. 49, no 2, p. 16-16Article in journal (Other (popular science, discussion, etc.))
  • 240.
    Moore, Jason W.
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Environmental crises and the metabolic rift in world-historical perspective2000In: Organization & environment, ISSN 1086-0266, E-ISSN 1552-7417, Vol. 13, no 2, p. 123-157Article in journal (Refereed)
    Abstract [en]

    This article proposes a new theoretical framework to study the dialectic of capital and nature over the longue durée of world capitalism. The author proposes that today’s global ecological crisis has its roots in the transition to capitalism during the long sixteenth century. The emergence of capitalism marked not only a decisive shift in the arenas of politics, economy, and society, but a fundamental reorganization of world ecology, characterized by a “metabolic rift,” a progressively deepening rupture in the nutrient cycling between the country and the city. Building upon the historical political economy of Marx, Foster, Arrighi, and Wallerstein, the author proposes a new research agenda organized around the concept of systemic cycles of agro-ecological transformation. This agenda aims at discerning the ways in which capitalism’s relationship to nature developed discontinuously over time as recurrent ecological crises have formed a decisive moment of world capitalist crisis, forcing successive waves of restructuring over long historical time.

  • 241.
    Morrell, J. M.
    et al.
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden .
    Johannisson, A.
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden .
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology. Linköping University, Faculty of Health Sciences.
    Effect of Osmolarity and Density of Colloid Formulations on the Outcome of SLC-Selection of Stallion Spermatozoa2011In: ISRN Veterinary Science, ISSN 2090-4452, E-ISSN 2090-4460, Vol. 2011, article id 128984Article in journal (Refereed)
    Abstract [en]

    The osmolarity and density of colloids used to prepare spermatozoa for assisted reproduction may affect sperm quality in the resultant preparation. In this study, two osmolarities of Androcoll-E for single-layer or density gradient centrifugation of stallion spermatozoa were compared: “normal” (320 mOsm) or “high” (345 mOsm). Mean yields for the two centrifugation techniques did not differ between treatments or osmolarities (single layer centrifugation:30.19±16.9×106 and 25.8±18.5×106 spermatozoa; density gradient centrifugation: 31.84±19.7×106 and 26.46±20.0×106 spermatozoa respectively for the two osmolarities). However, use of the high osmolarity colloid for single layer centrifugation increased the proportion of morphologically normal spermatozoa (𝑃<.05). Therefore, increasing the osmolarity of the colloid formulation may be beneficial for processing ejaculates containing a high proportion of abnormal spermatozoa by SLC. Reducing the density of the colloid used for the SLC substantially increased the yield of motile spermatozoa compared to the normal density colloid (mean ± SD: 72.6±28.9×106 versus 28.9±24.7×106), while also prolonging sperm survival by 24 hours compared to the uncentrifuged ejaculate. This increased yield may render Single Layer Centrifugation practical for use in the field.

  • 242.
    Morrell, J. M.
    et al.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Nongbua, T.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Valeanu, S.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lundstedt-Enkel, Katrin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Edman, A.
    Viking Genet, Ornsro, Skara, Sweden..
    Johannisson, A.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Bull breed affects which parameters of sperm quality are indicative of fertility2016In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 169, p. 112-113Article in journal (Other academic)
  • 243.
    Munoz-Fuentes, Violeta
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Forsberg, Catharina Linde
    Vila, Carles
    Morrell, Jane M.
    Single-layer centrifugation separates spermatozoa from diploid cells in epididymal samples from gray wolves, Canis lupus (L.)2014In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 82, no 5, p. 773-776Article in journal (Refereed)
    Abstract [en]

    Sperm samples may be used for assisted reproductive technologies (e.g., farmed or endangered species) or as a source of haploid DNA or sperm-specific RNA. When ejaculated spermatozoa are not available or are very difficult to obtain, as is the case for most wild endangered species, the epididymides of dead animals (e.g., animals that have been found dead, shot by hunters or poachers, or that that require euthanasia in zoological collections) can be used as a source of sperm. Such epididymal sperm samples are usually contaminated with cellular debris, erythrocytes, leukocytes, and sometimes also bacteria. These contaminants may be sources of reactive oxygen species that damage spermatozoa during freezing or contribute undesired genetic material from diploid cells. We used single-layer centrifugation through a colloid formulation, Androcoll-C, to successfully separate wolf epididymal spermatozoa from contaminating cells and cellular debris in epididymal samples harvested from carcasses. Such a procedure may potentially be applied to epididymal sperm samples from other species.

  • 244.
    Mustafa, Mudassir Imran
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media.
    Design Principles for Data Export: Action Design Research in U-CARE2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this thesis, we report the findings of designing data export functionality in Uppsala University Psychosocial Care Program (U-CARE) at Uppsala University. The aim of this thesis was to explore the design space for generic data export functionality in data centric clinical research applications for data analysis. This was attained by the construction and evaluation of a prototype for a data-centric clinical research application. For this purpose Action Design Research (ADR) was conducted, situated in the domain of clinical research. The results consist of a set of design principles expressing key aspects needed to address when designing data export functionality. The artifacts derived from the development and evaluation process each one constitutes an example of how to design for data export functionality of this kind.

  • 245.
    Mörner, Torsten
    et al.
    National Veterinary Institute, Uppsala, Sweden.
    Beasley, Val
    University of Illinois at Urbana-Champaign.
    22. Monitoring for Diseases in Wildlife Populations2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 186-190Chapter in book (Other (popular science, discussion, etc.))
  • 246. Nilsson, A
    et al.
    Ahman, B
    Norberg, H
    Redbo, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Eloranta, E
    Olsson, K
    Activity and heart rate in semi-domesticated reindeer during adaptation to emergency feeding2006In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 88, no 1-2, p. 116-123Article in journal (Refereed)
    Abstract [en]

    Although reindeer are well adapted to limited food resources during winter, semi-domesticated reindeer are regularly fed when snow conditions are bad in order to prevent starvation. Feeding sometimes results in health problems and loss of animals. This study was made to assess if activity pattern in reindeer could be used as a tool for the reindeer herder in early detection of animals that are not adapting to feeding. The frequency of 10 behavioural categories was recorded in five groups of penned, eight-month-old, female semi-domesticated reindeer. Three reindeer per group were fitted with heart rate monitors. Lying was the most frequent behaviour, whilst there were few cases of agonistic behaviour. Heart rate varied during the day, with peaks during feeding and low heart rates in the early morning. Restricted feed intake resulted in more locomotion and seeking but less ruminating compared to feeding ad libitum. This was followed by a generally lower heart rate in reindeer in the restricted groups compared to controls. Subsequent feeding with different combinations of lichens, silage and pellets ad libitum resulted initially in significantly more of the animals lying curled up, compared to controls, combined with increased heart rates. As the experiment continued the general activity pattern, as well as the heart rate, gradually became more similar in all groups. Lying curled was the behavioural indicator most consistently affected by feed deprivation and adaptation to feeding and may thus be a useful indicator to distinguish individual reindeer that are not adjusting to feeding.

  • 247.
    Nilsson, Anders S.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Phage therapy-constraints and possibilities2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 192-198Article, review/survey (Refereed)
    Abstract [en]

    The rise of antibiotic-resistant bacterial strains, causing intractable infections, has resulted in an increased interest in phage therapy. Phage therapy preceded antibiotic treatment against bacterial infections and involves the use of bacteriophages, bacterial viruses, to fight bacteria. Virulent phages are abundant and have proven to be very effective in vitro, where they in most cases lyse any bacteria within the hour. Clinical trials on animals and humans show promising results but also that the treatments are not completely effective. This is partly due to the studies being carried out with few phages, and with limited experimental groups, but also the fact that phage therapy has limitations in vivo. Phages are large compared with small antibiotic molecules, and each phage can only infect one or a few bacterial strains. A very large number of different phages are needed to treat infections as these are caused by genetically different strains of bacteria. Phages are effective only if enough of them can reach the bacteria and increase in number in situ. Taken together, this entails high demands on resources for the construction of phage libraries and the testing of individual phages. The effectiveness and host range must be characterized, and immunological risks must be assessed for every single phage.

  • 248.
    Nilsson, Andreas
    Örebro University, School of Health and Medical Sciences.
    Physical activity assessed by accelerometry in children2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Physical activity (PA) is likely to constitute an important aspect of health-related behaviour in growing children. However, the knowledge on levels and patterns of PA in children is limited, due to the difficulty of precisely measuring this complex behaviour in normal daily living. Information on variables that significantly contributes to the variability in PA patterns is warranted as it may inform strategies for promoting physically active lifestyles in school-age youth. The overall purpose of the present studies was to increase the knowledge about the use of accelerometry when assessing PA in children, and examine sources of variability in objectively assessed PA behaviour in children. The study samples included 1954 nine- and 15-year-old children from four geographical locations in Europe (Norway, Denmark, Estonia and Portugal), and additionally 16 Swedish seven-year-old boys and girls. PA was assessed by the MTI accelerometer during free-living conditions, including both weekdays and weekend days. A part of the PA assessment was conducted using different time sampling intervals (epochs). Predictions of estimates of daily energy expenditure from accelerometer output were calculated using previously published equations. Potential correlates of PA behaviour were assessed by self-report. The main findings were; a) the epoch setting had a significant effect when interpreting time spent at higher intensities of PA in young children, b) predicted energy expenditure differed substantially between equations, c) between- and within-day differences in overall levels of PA, time spent at moderate-to-vigorous intensity physical activity and time spent sedentary differed between age, gender and geographical location, d) outdoor play and sports participation were differentially associated with objectively measured PA in 9- and 15-year-old children. It is concluded that the sporadic nature of children’s physical activity require very short epoch settings for detecting high intensity PA, and that different published equations for estimations of daily energy expenditure cannot be used interchangeably. The interpretations of average energy expenditure from available equations should be made with caution. Based on a large sample of children of different ages, weekend days and leisure time during weekdays seem appropriate targets when promoting PA in order to increase the proportion of children achieving current recommendations on health enhancing PA. Further, significant correlates of PA behaviour dependent on age group are presented, which should be considered when planning interventions for promoting PA in school-age youth.

  • 249.
    Nilsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adamo, Hanibal
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19608Article in journal (Refereed)
    Abstract [en]

    Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.

  • 250.
    Nilsson, Staffan
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Chest pain and ischemic heart disease: Diagnosis and management in primary health care2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims. In patients consulting for chest pain, it is of great importance to evaluate the possibility of ischemic heart disease (IHD). The aims in this thesis were to investigate the accuracy of the general practitioners’ clinical assessments and the applicability of exercise testing and myocardial perfusion scintigraphy (MPS) in patients consulting for chest pain in primary care.

    Statins are known to prevent IHD. A further aim was therefore to investigate if a relation could be detected on a population basis between the use of statins and the morbidity of acute myocardial infarction (AMI).

    Methods. All patients from 20 to 79 years, consulting for a new episode of chest pain in three primary health care centres, were included during almost two years from 1998 to 2000. The patients were managed according to the clinical evaluation. The presence of IHD was excluded either by clinical examination only, or if stable IHD was in question, by exercise testing and if the exercise test was inconclusive by an additional MPS. If unstable IHD or myocardial infarction was suspected, referral for emergency hospital examination was made.

    Correlations between statin sales and the morbidity of AMI in Sweden’s municipalities were analysed in an ecological, register based study. Adjustment was made for sales of antidiabetics, socio-economic deprivation indexes and geographic coordinates.

    Results. Consultations for chest pain represented 1.5% of all consultations in the ages 20 to 79 and were made by 554 patients. In 281 patients IHD was excluded by clinical examination only. In 208 patients stable IHD and in 65 unstable IHD was in question. Four patients (1.4%) evaluated as not having IHD, were diagnosed with angina pectoris or AMI within three months. Exercise testing was performed in 191 patients and revealed no IHD in 134 and IHD in 14 patients. In 43 patients the exercise test results were equivocal. Thirty-nine of these patients underwent MPS, which showed no IHD in 20 and IHD in 19 of the patients.

    In a follow up almost six years later, neither mortality rate nor prevalence of IHD differed significantly between the 384 study patients evaluated not to have IHD and the population controls.

    Statin sales and AMI-incidence or mortality showed no strong associations from 1998 to 2002.

    Conclusions.

    ·Primary care is an appropriate level of care for ruling out IHD as the cause of chest pain, with sufficient safety and for diagnostics of stable IHD.

    ·Exercise testing and myocardial perfusion scintigraphy are useful procedures when investigating chest pain patients in primary care.

    ·The results indicate that preventive measures other than increased statin treatment should be considered to further decrease AMI-morbidity.

2345678 201 - 250 of 397
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