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  • 201. Jenab, Mazda
    et al.
    Bueno-de-Mesquita, H Bas
    Ferrari, Pietro
    van Duijnhoven, Franzel J B
    Norat, Teresa
    Pischon, Tobias
    Jansen, Eugène H J M
    Slimani, Nadia
    Byrnes, Graham
    Rinaldi, Sabina
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Kaaks, Rudolf
    Linseisen, Jakob
    Boeing, Heiner
    Bergmann, Manuela M
    Trichopoulou, Antonia
    Misirli, Gesthimani
    Trichopoulos, Dimitrios
    Berrino, Franco
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Ros, Martine M
    van Gils, Carla H
    Peeters, Petra H
    Brustad, Magritt
    Lund, Eiliv
    Tormo, María-José
    Ardanaz, Eva
    Rodríguez, Laudina
    Sánchez, Maria-José
    Dorronsoro, Miren
    Gonzalez, Carlos A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roddam, Andrew
    Key, Timothy J
    Khaw, Kay-Tee
    Autier, Philippe
    Hainaut, Pierre
    Riboli, Elio
    Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study2010In: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 340, p. b5500-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. CONCLUSIONS: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

  • 202.
    Jiang, Wei
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Regeneration in the adult brain after focal cerebral ischemia: exploration of neurogenesis and angiogenesis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Ischemic stroke ranks as the third major cause of clinical mortality and the leading cause of handicap in adults. Each year, stroke occurs in about 30,000 Swedes. The severity of an acute ischemic stroke depends mainly on the degree and duration of local cerebral blood flow (lCBF) reduction. Prompt reperfusion improves neurological deficits, spontaneous electrical activity, energy metabolism, cerebral protein synthesis (CPS), and tissue repair, among which cell proliferation (neurogenesis, gliosis) and revascularization (angiogenesis) may have important functional and therapeutic implications.

    Aims of the thesis: (1) To establish the photothrombotic ring stroke(PRS) model with late spontaneous reperfusion in adult mice; (2) To explore angiogenesis and neurogenesis in adult brain after focal cerebral ischemia.

    Materials and Methods: The PRS model in C57 BL adult mice and the middle cerebral artery suture occlusion (MCAO) model in adult Wistar rats were used. The 5-bromodeoxyuridine (BrdU) was delivered into animal after stroke induction to label DNA duplication. CBF, CPS and adenosine triphosphate (ATP) were measured by laser-Doppler flowmetry (LDF), [14C]–Iodoantipyrine and [3H]-Leucine double tracer autoradiography, and bioluminescence, respectively. Immunocytochemistry / immunofluoresence were performed to detect different proteins. The cell marker colocalization was analyzed by three-dimension (3-D) confocal. The cell counting was performed with a stereological counting system.

    Results: The PRS model was established in adult mice by irradiating the exposed skull with a 514.5 nm argon laser ring beam (3 mm diameter, 0.21 mm thick) at an intensity of 0.65 W/cm2 for 60s, with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15s. The central cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit, where lCBF LDF declined promptly to 43% of the baseline value at 30 min post irradiation. The lCBF-IAP amounted to 46-17-58 ml/100g/min, where CPS varied from 57-38-112% at 4h-48h-7days post ischemia. ATP declined at 4h, achieved its maximum level at 48h and was markedly reduced at 7 days postischemia. Morphologically, at 4h some neurons in the region at-risk appeared swollen, at 48h the majority were severely swollen, eosinophilic and pyknotic. Tissue morphology became partly restored at 7 days post stroke, when numerous cortical cells were immunolabeled by BrdU or the mitosis-specific marker phosphorylated histone H3 (Phos-H3). Some of these cells were even doubly immunopositive to the neuron-specific marker Neu N and the astrocyte marker GFAP, as analyzed by 3-D confocal. In adult rats exposed to MCAO, widespread BrdU-immunolabeled cells appeared in the cortex, ipsilateral striatum and dentate gyrus of the hippocampus. Some of which were doubleimmunolabeled by the neuron specific markers Map-2, β-tubulin III and Neu N as analyzed by 3-D confocal. As early as 24h postischemia, BrdU-immunopositive endothelial cells were aligned as microvessels, some of which exhibited distinguishable lumens in the ischemic boundary zone, where VEGF-A, B, C proteins and their receptors flt-1, fik-1, flt-4 were overexpressed at 72h after MCAO.

    Conclusion: PRS model in adult mice elicits a dynamic deterioration and then restoration of local CBF, CPS, ATP and tissue morphology in the spontaneously reperfused cerebral cortex at 7d after stroke, where cortical neurogenesis and gliosis occurred. In adult rats with MCAO, neurogenesis occurred at 30 and 60d in the penumbral cortex and striatum. Angiogenesis occurred as early as 24h, which contributed to the spontaneous reperfusion frequently observed in this setting of acute ischemic stroke.

  • 203. Jitpean, Supranee
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Höglund, Odd V
    Ström, Bodil Holst
    Hagman, Ragnvi
    Decreased plasma Chromogranin A361-372 (Catestatin) but not Chromogranin A17-38 (Vasostatin) in female dogs with bacterial uterine infection (pyometra).2015In: BMC veterinary research, ISSN 1746-6148, Vol. 11, no 1, p. 14-Article in journal (Refereed)
    Abstract [en]

    BackgroundPyometra often induces systemic inflammatory response syndrome (SIRS) and early diagnosis is crucial for survival. Chromogranin A (CgA) is a neuroendocrine secretory protein that is co-released with catecholamines from the adrenal medulla and sympathetic nerve endings. A prognostic value of CgA has been found in humans that are critically ill or that have SIRS associated with infection. CgA has not yet been studied in dogs with bacterial infection. The aim of the study was to investigate CgA, measured by Chromogranin A361-372 (Catestatin; Cst) and Chromogranin A17-38 (Vasostatin; VS) in healthy dogs and in dogs with pyometra.ResultsFifty dogs with pyometra, sampled prior to surgery and 64 healthy female dogs were included. In 19 pyometra cases, blood samples were also collected postoperatively. Concentrations of Cst and VS were measured in heparinised plasma and Cst also measured in EDTA plasma, by in-house radioimmunoassays. Student¿s t-test and Wilcoxon two-sample test was used to test for differences between dog groups. Pre- and postoperative samples in dogs with pyometra were analysed by paired t-test. Pearson correlation was used to investigate associations of laboratory variables and hospitalization. P < 0.05 was considered significant.Concentrations of Cst were decreased in pyometra dogs (mean ± SE, 1.01 ± 0.05 nmol/L) compared to healthy dogs (mean ± SE, 1.70 ± 0.03 nmol/L) (p ¿ 0.0001). VS concentrations did not differ significantly between dogs with pyometra (0.40 ± 0.04 nmol/L) and healthy dogs (0.42 ± 0.03 nmol/L). Mean ± SE pre- and postoperative concentration of Cst (1.0 ± 0.04 nmol/L and 0.9 ± 0.2 nmol/L) and VS (0.36 ± 0.04 nmol/L and 0.36 ± 0.04 nmol/L) in dogs with pyometra did not differ significantly. Neither Cst nor VS concentrations were associated with duration of hospitalization and were not significantly different in the four dogs with pyometra that had prolonged (¿3 d) postoperative hospitalization.ConclusionConcentrations of Cst, but not VS, were decreased in pyometra. Cst and VS concentrations before and after ovariohysterectomy did not differ significantly and were not associated with duration of hospitalization. Further studies are warranted to evaluate a possible diagnostic or prognostic value for Cst and VS.

  • 204.
    Johansson, Anders
    et al.
    Linköping Univ, Dept Behav Sci, S-58183 Linköping, Sweden.
    Odén, Anders
    Chalmers, Dept Math Sci, S-41296 Gothenburg, Sweden.
    Dahlgren, Lars-Owe
    Linkoping Univ, Dept Behav Sci, S-58183 Linkoping, Sweden.
    Sjöström, Björn
    University of Skövde, School of Life Sciences.
    A comparison of experiences of training emergency care in military exercises and competences among conscript nurses with different levels of education2007In: Military medicine, ISSN 0026-4075, E-ISSN 1930-613X, Vol. 172, no 10, p. 1046-1052Article in journal (Refereed)
    Abstract [en]

    The military emergency care education of nurses is primarily concerned with the treatment of soldiers with combat-related injuries. Even though great progress has been made in military medicine, there is still the pedagogical question of what emergency care education for military nurses should contain and how it should be taught. The aim of this study was to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education. A descriptive study was performed to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education in nursing. There were statistical differences between nurses with general nursing education and nurses with a general nursing education and supplementary education. A reasonable implication of the differences is that the curriculum must be designed differently depending on the educational background of the students. Hence, there is an interaction between background characteristics, e.g., the level of previous education and differences pertaining to clinical experience of the participants, and the impact of the exercise itself.

  • 205.
    Johansson, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rudolfsson, Stina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pietras, Kristian
    Jones, Jonathan
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Granfors, Torvald
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy2010In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 177, no 2, p. 1031-1041Article in journal (Refereed)
    Abstract [en]

    Mast cells affect growth in various human tumors, but their role in prostate cancer (PC) is unclear. Here, we identify mast cells as independent prognostic markers in PC using a large cohort of untreated PC patients with a long follow-up. By analyzing mast cells in different tissue compartments, our data indicate that intratumoral and peritumoral mast cells have anti- opposed to protumor properties. Intratumoral mast cells negatively regulate angiogenesis and tumor growth, whereas peritumoral mast cells stimulate the expansion of human prostate tumors. We also observed mast cell recruitment particularly to the peritumoral compartment in men during the formation of castrate-resistant prostate tumors. In our ortothopic rat model, mast cells accumulated in the peritumoral tissue where they enhanced angiogenesis and tumor growth. In line with this, prostate mast cells expressed high levels of the angiogenic factor FGF-2. Similar to the situation in men, mast cells infiltrated rat prostate tumors that relapsed after initially effective castration treatment, concurrent with a second wave of angiogenesis and an up-regulation of FGF-2. We conclude that mast cells are novel independent prognostic markers in PC and affect tumor progression in animals and patients. In addition, peritumoral mast cells provide FGF-2 to the tumor micro environment, which may contribute to their stimulating effect on angiogenesis.

  • 206.
    Johansson, Jessica
    Örebro University, Department of Clinical Medicine.
    Effect of interleukin-1beta on tyrosine uptake in fibroblasts of schizophrenic patients and healthy controls2007Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A repeated finding in schizophrenic patients is an aberrant tyrosine transport, shown in fibroblast cell model. Altered levels of the pro-inflammatory cytokine interleukin-1beta (IL-1β) are indicated in schizophrenic patients and IL-1β has shown to have inhibitory effect on amino acid transport systems. Based on these findings, the aim of this study was to examine the effect of IL-1β on tyrosine uptake in fibroblasts of schizophrenic patients and healthy controls. Fibroblast cell lines from schizophrenic patients (n=10) and healthy controls (n=10) were treated with IL-1β and uptake of 14C (U)-L-tyrosine was measured using the cluster tray method. Fibroblasts untreated with IL-1β were used as controls. Treatment with IL-1β significantly inhibited the tyrosine uptake in fibroblasts of schizophrenic patients and controls. No difference in uptake levels between fibroblasts of schizophrenic patients and controls was found. This study provides one potential explanation for the aberrant tyrosine transport seen in patients with schizophrenia and thus combines the immunological and neuropharmacological factors implicated in the pathophysiology/etiology of schizophrenia.

  • 207. Johansson Wensman, Jonas
    et al.
    Leuchowius, Karl-Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Walter and Eliza Hall Institute of Medical Research, Australia .
    Yan, Jiting
    Berg, Anna-Lena
    Bode, Liv
    Ludwig, Hanns
    Belák, Sándor
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Berg, Mikael
    Visualization of Borna Disease Virus Protein Interactions with Host Proteins using in situ Proximity Ligation Assay2016In: British journal of virology, ISSN 2055-6128, Vol. 3, no 1, p. 11-23Article in journal (Refereed)
    Abstract [en]

    Borna disease virus type 1 (BDV) comprises highly conserved neurotropic non-segmented negative strand RNA-virus variants causing neurological and behavioral disorders in a wide range of mammalian animals, possibly including humans. Viral persistence in the brain has been frequently observed, however, the exact mechanisms behind BDV’s ability to establish persistence despite a prominent immune response are not known. Here we have used in situ proximity ligation assay (in situ PLA), a selective tool for studying virus-host protein-protein interactions. BDV P (phosphoprotein) and N (nucleoprotein) have previously been reported to interact with several host proteins, thereby interfering with various signaling pathways. In this study, we focused on some of these interactions (BDV P-HMGB1, BDV N/P-Cdc2). First, we used rat glioma cell cultures persistently infected with a laboratory strain of BDV (C6BV) to establish the assay. Next, in situ PLA was applied to detect BDV P in brain tissues of infected animals. Finally, protein-protein interactions were visualized in both C6BV and brain tissues of experimentally as well as naturally infected animals (rat and horse, respectively). BDV proteins and their interactions with host proteins could be shown in cell cultures (HMGB1, Cdc2) and in brain tissues of rat (HMGB1, Cdc2) and horse (Cdc2 only) infected with BDV. In this study, we have for the first time directly visualized protein-protein interactions between BDV and its host, and thereby confirmed previous data to demonstrate findings in cell cultures to be applicable also in experimentally and naturally infected animals.

  • 208.
    Johnzon, Carl-Fredrik
    et al.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Ronnberg, Elin
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    The Role of Mast Cells in Bacterial Infection2016In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 186, no 1, p. 4-14Article, review/survey (Refereed)
    Abstract [en]

    Mast cells (MCs) are particularly abundant at host-environment interfaces, such as skin and intestinal mucosa. Because of their Location, it has been hypothesized that MCs can act as sentinel cells that sense microbial attacks and initiate a protective immune response. Several studies have suggested that animals deficient in MCs exhibit a worsened pathology in various experimental models of bacterial infection. However, other studies have indicated that MCs under certain circumstances may have a detrimental impact on bacterial disease, and there are also recent studies indicating that MCs are dispensable for the clearance of bacterial pathogens. Herein, we review the current knowledge of the role of MCs in bacterial infection.

  • 209.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Davidson, Alice E.
    UCL Institute of Ophthalmology, London, UK.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellgren, Therese
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Tuft, Stephen J.
    UCL Institute of Ophthalmology, London, UK; Moorfields Eye Hospital, London, UK.
    Koskela, Timo
    Koskelas Eye Clinic, Umeå, Sweden.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Hardcastle, Alison J.
    UCL Institute of Ophthalmology, London, UK.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)2015In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 4, p. 463-473Article in journal (Refereed)
    Abstract [en]

    Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.

  • 210.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    One Health: a doctor's perspective2015In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 176, no 14, p. 351-353Article in journal (Refereed)
  • 211. Kagera, Irene
    et al.
    Kahenya, Peter
    Mutua, Florence
    Anyango, Gladys
    Kyallo, Florence
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Status of aflatoxin contamination in cow milk produced in smallholder dairy farms in urban and peri-urban areas of Nairobi County: a case study of Kasarani sub county, Kenya.2019In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 9, no 1, article id 1547095Article in journal (Refereed)
    Abstract [en]

    Introduction: Milk consumption in Kenya supersedes other countries in East Africa. However, milk contamination with aflatoxin M1 (AFM1) is common, but the magnitude of this exposure and the health risks are poorly understood and need to be monitored routinely. This study aimed at assessing the awareness, knowledge and practices of urban and peri-urban farmers about aflatoxins and determining the levels of aflatoxin contamination in on-farm milk in a selected area within Nairobi County. Materials and methods: A cross-sectional study was undertaken to assess aflatoxin contamination levels of milk in Kasarani sub-county. A total of 84 milk samples were collected from small-holder dairy farms and analyzed for AFM1 using Enzyme-Linked Immunosorbent Assay (ELISA). Results and Discussion: Ninety nine percent of the samples (83/84) analysed were contaminated with AFM1. The mean aflatoxin level was 84 ng/kg with 64% of the samples exceeding the EU legal limit of 50 ng/kg. Whereas 80% of the farmers were aware of aflatoxin, there was no correlation between farmers' knowledge and gender with AFM1 prevalence. Conclusion: This study concludes that AFM1 is a frequent contaminant in milk and there is need to enhance farmers awareness on mitigation.

  • 212. Kampa, Naruepon
    et al.
    Lord, Peter
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Avdelningen för sjukhusfysik.
    Hoppe, Astrid
    Effects of measurement of plasma activity input on normalization of glomerular filtration rate to plasma volume in dogs2007In: Veterinary Radiology & Ultrasound, ISSN 1058-8183, E-ISSN 1740-8261, Vol. 48, no 6, p. 585-593Article in journal (Refereed)
    Abstract [en]

    Glomerular filtration rate (GFR) normalized to body fluid volumes to adjust for differing body size and conformation is more physiologically correct than a relationship with body weight (BW). GFR can be normalized to plasma volume by a renographic method that uses the Rutland-Patlak plot with plasma activity and kidney activity inputs. A plasma time-activity curve is obtained from a region of interest (ROI) of the left ventricle (LV), the size of which is in theory not critical. The aims of the study were to evaluate the effect of different LV ROI sizes, the effect of extravascular activity in the thorax over the LV ROI, and different time intervals for the semilogarithmic LV plot. Seventy-two scintigrams were used, with three different-sized automatic and a manual LV ROI, all with and without subtracting extravascular activity, and with LV curve time intervals of 30-120 s and 60-240 s. GFR/plasma volume was not affected by LV ROI sizes but significantly affected by extravascular activity subtraction and different time intervals. Subtracting extravascular activity from the LV ROI did not improve precision, but increased variability caused by different LV ROI sizes and time intervals chosen for the LV plot. The ROI for measuring extravascular activity apparently contained a considerable and variable intravascular component, which when subtracted, created noisy and unreliable LV curves. Manual LV ROI, without extravascular subtraction, and a time interval for LV input between 1 and 4 min are recommended as they gave the least variability determined by statistical analysis. With these methods, normal individual GFR/plasma volume in normal beagle dogs was 29.2 +/- 6.5 ml/min/l.

  • 213.
    Karlsson, Cecilia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Betydelsen av den preanalytiska tiden vid analys av koncentration ammoniak hos hund och katt2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Ammoniak (NH3) är en kvävehaltig gas som genereras vid nedbrytning av proteiner, nukleinsyror och urea. NH3 elimineras till största del i levern genom ureacykeln och avlägsnas sedan via urinen. Normal fastekoncentration av NH3 i plasma hos hund och katt är < 98 μmol/L resp. < 95 μmol/L. Vid vissa sjukdomar som exempelvis leversjukdom kan det leda till hyperammonemi och livshotande tillstånd, därför är analysen av NH3-koncentrationen i plasma av klinisk relevans. Analys av koncentrationen NH3 i plasma är dock komplicerad då koncentrationen av analyten succesivt ökar in vitro. En vanlig avsatt tid för centrifugering och analys av NH3 är 15 minuter eftersom det har visat sig att koncentrationen av NH3 annars kan komma att bli starkt tidsberoende. Syftet med studien var att utvärdera hur koncentrationen av NH3 i plasma påverkas med tiden, från provtagning till centrifugering och analys av NH3.

    Koncentrationen av NH3 analyserades på lithium-heparin plasmaprover från 20 hundar och 7 katter i olika åldrar och kön. Tidsintervall för centrifugering och analys efter provtagning var 10 minuter, 1 timme och 6 timmar. Analyserna utfördes på instrumentet Catalyst Dx (Idexx laboratories, inc. Westbrook, Maine, USA) och genom en torrkemisk metod och analysbricka innehållandes ett reagens (bromfenolblått), som genom en reaktion med analyten gav ett blått färgomslag, intensiteten av detta avlästes spektrofotometriskt vid 587 nm. Resultaten visade att koncentrationen av NH3 i plasma ökade vid provförvaring över 1 timme hos både hund och katt. Prover som förvarades ocentrifugerade visade en högre koncentration av NH3 än de prover som centrifugerats direkt och förvarats som plasma. Därav vikten att hålla den avsatta analystiden.

  • 214.
    Kask, Kristiina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Hormones, Mood and Cognition2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition.

    In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated.

    Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects.

    The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal.

    Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning.

    The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI.

    We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase.

    Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women.

    In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.

  • 215.
    Kernell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Cardiac disease in pregnancy and consequences for reproductive outcomes, comorbidity and survival2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Advances in medical treatment during the last 50 years have resulted in more individuals with congenital heart disease (CHD) and Marfan syndrome reaching childbearing age. The substantial physiological changes during pregnancy result in a high-risk situation, and pregnancy is a major concern in women with these conditions.

    Aims

    • To describe the socio-demographic characteristics, birth characteristics and reproductive patterns of individuals with CHD and women with Marfan syndrome.
    • To investigate obstetric and neonatal outcomes in the firstborn children of individuals with CHD and women with Marfan syndrome.
    • To study long-term cardiovascular outcomes after childbirth in women with Marfan´syndrome.

    Methods

    The studies are population-based register studies. The study population in the first paper included all women born between 1973 and 1983 who were alive and resident in Sweden at the age of 13 (494 692 women, of whom 2 216 were women with CHD). In the second paper, the same definition of the study population was chosen, except that it involved all men born between 1973 and 1983 (522 216 men, of whom 2 689 men with CHD). The third and fourth papers involved a study population of all Swedish women born between 1973 and 1993 who were still living in Sweden at age 13. This population consisted of 1 017 538 women, 273 of whom had been diagnosed with Marfan syndrome.

    Results and conclusions

    The individuals studied were more often born preterm, and were small-for-gestational age babies. They were more likely to have been born by cesarean section. In women with CHD, these characteristics were repeated in their firstborn children. No increased risks were found in children of men with CHD or in children of women with Marfan syndrome. There was no increased risk of aortic dissection in women with Marfan syndrome during pregnancy compared to women with Marfan syndrome who did not give birth. Higher frequencies of cardiac arrhythmia and valvular heart disease were found after childbirth in women with Marfan syndrome. Pregnancy in women with CHD is a high-risk situation associated with increased risk of adverse neonatal outcomes for the expected child. Pregnancy in women without CHD, but where the father has CHD is not so associated with increased risk of adverse obstetric or neonatal outcomes. Pregnancy in women with Marfan syndrome is not associated with adverse outcomes for the expected child.

  • 216.
    Khalaf, Hazem
    et al.
    Örebro University, School of Medical Sciences.
    Palm, Eleonor
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Cellular Response Mechanisms in Porphyromonas gingivalis Infection2017In: Periodontitis: A Useful Reference / [ed] Pachiappan Arjunan, InTech, 2017, p. 45-68Chapter in book (Refereed)
    Abstract [en]

    The pathogenicity of the periodontal biofilm is highly dependent on a few key species, of which Porphyromonas gingivalis is considered to be one of the most important pathogens. P. gingivalis expresses a broad range of virulence factors, of these cysteine proteases (gingipains) are of special importance both for the bacterial survival/proliferation and for the pathological outcome. Several cell types, for example, epithelial cells, endothelial cells, dendritic cells, osteoblasts, and fibroblasts, reside in the periodontium and are part of the innate host response, as well as platelets, neutrophils, lymphocytes, and monocytes/macrophages. These cells recognize and respond to P. gingivalis and its components through pattern recognition receptors (PRRs), for example, Toll-like receptors and protease-activated receptors. Ligation of PRRs induces downstream-signaling pathways modifying the activity of transcription factors that regulates the expression of genes linked to inflammation. This is followed by the release of inflammatory mediators, for example, cytokines and reactive oxygen species. Periodontal disease is today considered to play a significant role in various systemic conditions such as cardiovascular disease (CVD). The mechanisms by which P. gingivalis and its virulence factors interact with host immune cells and contribute to the pathogenesis of periodontitis and CVD are far from completely understood.

  • 217.
    Klasson, Anna
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences.
    MRI Contrast Enhancement using Gd2O3 Nanoparticles2008Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.

    Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.

    This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.

  • 218. Klütsch, C F C
    et al.
    Seppälä, E H
    Fall, Tove
    Department of Clinical Sciences, Swedish University of Agricultural Sciences.
    Uhlén, M
    Hedhammar, Å
    Lohi, H
    Savolainen, P
    Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia2011In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 42, no 1, p. 100-103Article in journal (Refereed)
    Abstract [en]

    The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.

  • 219.
    Klütsch, Cornelya
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Seppälä, E. H.
    Fall, T.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Gene Technology.
    Hedhammar, Å.
    Lohi, H.
    Savolainen, Peter
    KTH, School of Biotechnology (BIO), Gene Technology.
    Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia2011In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 42, no 1, p. 100-103Article in journal (Refereed)
    Abstract [en]

    P>The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.

  • 220. Kyro, Cecilie
    et al.
    Olsen, Anja
    Bueno-de-Mesquita, H. B(as).
    Skeie, Guri
    Loft, Steffen
    Aman, Per
    Leenders, Max
    Dik, Vincent K.
    Siersema, Peter D.
    Pischon, Tobias
    Christensen, Jane
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Cottet, Vanessa
    Kuehn, Tilman
    Chang-Claude, Jenny
    Boeing, Heiner
    Trichopoulou, Antonia
    Naska, Androniki
    Oikonomidou, Despoina
    Masala, Giovanna
    Pala, Valeria
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Peeters, Petra H.
    Bakken, Toril
    Weiderpass, Elisabete
    Asli, Lene Angell
    Sanchez, Soledad
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Amiano, Pilar
    Maria Huerta, Jose
    Barricarte, Aurelio
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Slimani, Nadia
    Freisling, Heinz
    Ferrari, Pietro
    Gunter, Marc J.
    Murphy, Neil
    Riboli, Elio
    Tjonneland, Anne
    Landberg, Rikard
    Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2014In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, no 10, p. 1881-1890Article in journal (Refereed)
    Abstract [en]

    Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

  • 221. Källberg, Eva
    et al.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ivars, Fredrik
    Leanderson, Tomas
    Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model2010In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 70, no 13, p. 1461-1470Article in journal (Refereed)
    Abstract [en]

    Our results argue for a role for IDO mediated immune suppression in the early stages of prostate cancer progression. However, since the intra-tumor IDO expression in J(-/-) mice was indistinguishable from that of C57BL/6 animals the IDO expression in the tumor tissue appears to be irrelevant for TRAMP tumor incidence.

  • 222.
    Källebring, Tina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    THE EXPRESSION OF THROMBOMODULIN, TISSUE FACTOR, TISSUE FACTOR PATHWAY INHIBITOR AND ENDOTHELIAL PROTEIN C RECEPTOR IN NORMAL AND IUGR PLACENTA2005Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study was to examine the expression of Thrombomodulin, Tissue Factor, Tissue Factor Pathway Inhibitor and Endothelial Protein C Receptor in placenta throughout the three phases of the third trimester in the normal placenta and in IUGR placenta from full term.

    Twenty-five normal placenta samples and twenty-five IUGR placenta samples were obtained and each sample was stained by immunohistochemistry using monoclonal antibodies. Each antibody was optimised for antigen retrieval method and for optimal dilution, before been applied to the test tissue.

    The results showed that each of the antibodies mentioned was expressed in normal placenta and in IUGR placenta.

    No significant difference could be established concerning the expression of each antibody mentioned between normal and IUGR placenta.

  • 223.
    La Hera, Pedro
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. SLU, Dept Forestry Technol, Umeå, Sweden and Swedish Cluster Forest Technol, Vindeln, Sweden.
    Shiriaev, Anton S.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Norwegian Univ Sci & Technol, Dept Engn Cybernet, Trondheim, Norway.
    Freidovich, Leonid B
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Mettin, Uwe
    Gusev, Sergey V.
    Stable walking gaits for a three-link planar biped robot with one actuator2013In: IEEE Transactions on robotics, ISSN 1552-3098, E-ISSN 1941-0468, IEEE transactions on robotics, Vol. 29, no 3, p. 589-601Article in journal (Refereed)
    Abstract [en]

    We consider a benchmark example of a three-link planar biped walker with torso, which is actuated in between the legs. The torso is thought to be kept upright by two identical torsional springs. The mathematical model reflects a three-degree-of-freedom mechanical system with impulse effects, which describe the impacts of the swing leg with the ground, and the aim is to induce stable limit-cycle walking on level ground. The main contribution is a novel systematic trajectory planning procedure for solving the problem of gait synthesis. The key idea is to find a system of ordinary differential equations for the functions describing a synchronization pattern for the time evolution of the generalized coordinates along a periodic motion. These functions, which are known as virtual holonomic constraints, are also used to compute an impulsive linear system that approximates the time evolution of the subset of coordinates that are transverse to the orbit of the continuous part of the periodic solution. This auxiliary system, which is known as transverse linearization, is used to design a nonlinear exponentially orbitally stabilizing feedback controller. The performance of the closed-loop system and its robustness with respect to various perturbations and uncertainties are illustrated via numerical simulations.

  • 224.
    Lampman, Richard
    University of Illinois at Urbana-Champaign.
    23. Emerging Vector-borne Diseases of Public Health in Europe and North America2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic Universit Press , 2012, 2, p. 191-198Chapter in book (Other (popular science, discussion, etc.))
  • 225.
    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.

  • 226.
    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.

  • 227. 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.

  • 228.
    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.

  • 229.
    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)
  • 230. 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.

  • 231.
    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)
  • 232. 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.

  • 233. 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.

  • 234.
    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.

  • 235.
    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.

  • 236. 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.

  • 237.
    Lindahl, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gill, Jatinder Paul Singh
    Hazarika, Razibuddin Ahmed
    Fairoze, Nadeem Mohamed
    Bedi, Jasbir S
    Dohoo, Ian
    Chauhan, Abhimanyu Singh
    Grace, Delia
    Kakkar, Manish
    Risk Factors for Brucella Seroprevalence in Peri-Urban Dairy Farms in Five Indian Cities.2019In: Tropical medicine and infectious disease, ISSN 2414-6366, Vol. 4, no 2, article id E70Article in journal (Refereed)
    Abstract [en]

    Brucellosis is endemic among dairy animals in India, contributing to production losses and posing a health risk to people, especially farmers and others in close contact with dairy animals or their products. Growing urban populations demand increased milk supplies, resulting in intensifying dairy production at the peri-urban fringe. Peri-urban dairying is under-studied but has implications for disease transmission, both positive and negative. In this cross-sectional study, five Indian cities were selected to represent different geographies and urbanization extent. Around each, we randomly selected 34 peri-urban villages, and in each village three smallholder dairy farms (defined as having a maximum of 10 dairy animals) were randomly selected. The farmers were interviewed, and milk samples were taken from up to three animals. These were tested using a commercial ELISA for antibodies against Brucella abortus, and factors associated with herd seroprevalence were identified. In all, 164 out of 1163 cows (14.1%, 95% CI 12.2-16.2%) were seropositive for Brucella. In total, 91 out of 510 farms (17.8%, 95% CI 14.6-21.4%) had at least one positive animal, and out of these, just seven farmers stated that they had vaccinated against brucellosis. In four cities, the farm-level seroprevalence ranged between 1.4-5.2%, while the fifth city had a seroprevalence of 72.5%. This city had larger, zero-grazing herds, used artificial insemination to a much higher degree, replaced their animals by purchasing from their neighbors, were less likely to contact a veterinarian in case of sick animals, and were also judged to be less clean. Within the high-prevalence city, farms were at higher risk of being infected if they had a young owner and if they were judged less clean. In the low-prevalence cities, no risk factors could be identified. In conclusion, this study has identified that a city can have a high burden of infected animals in the peri-urban areas, but that seroprevalence is strongly influenced by the husbandry system. Increased intensification can be associated with increased risk, and thus the practices associated with this, such as artificial insemination, are also associated with increased risk. These results may be important to identify high-risk areas for prioritizing interventions and for policy decisions influencing the structure and development of the dairy industry.

  • 238.
    Lindahl, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. International Livestock Research Institute, Nairobi, Kenya;Swedish University of Agricultural Research, Uppsala, Sweden.
    Ragan, Izabela K
    Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA;Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
    Rowland, R R
    Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
    Wainaina, Martin
    International Livestock Research Institute, Nairobi, Kenya.
    Mbotha, Deborah
    International Livestock Research Institute, Nairobi, Kenya;Institute for Parasitology and Tropical Veterinary Medicine, Freie Universitaet Berlin, Berlin, Germany.
    Wilson, William
    Arthropod-Borne Animal Diseases Research Unit, USDA, ARS, Manhattan, KS, USA.
    A multiplex fluorescence microsphere immunoassay for increased understanding of Rift Valley fever immune responses in ruminants in Kenya2019In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 269, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever virus (RVFV) is an important mosquito-borne pathogen with devastating impacts on agriculture and public health. With outbreaks being reported beyond the continent of Africa to the Middle East, there is great concern that RVFV will continue to spread to non-endemic areas such as the Americas and Europe. There is a need for safe and high throughput serological assays for rapid detection of RVFV during outbreaks and for surveillance. We evaluated a multiplexing fluorescence microsphere immunoassay (FMIA) for the detection of IgG and IgM antibodies in ruminant sera against the RVFV nucleocapsid Np, glycoprotein Gn, and non-structural protein NSs. Sheep and cattle sera from a region in Kenya with previous outbreaks were tested by FMIA and two commercially available competitive ELISAs (BDSL and IDvet). Our results revealed strong detection of RVFV antibodies against the Np, Gn and NSs antigen targets. Additionally, testing of samples with FMIA Np and Gn had 100% agreement with the IDvet ELISA. The targets developed in the FMIA assay provided a basis for a larger ruminant disease panel that can simultaneously screen several abortive and zoonotic pathogens.

  • 239.
    Lindahl, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. International Livestock Research Institute, PO Box 30709,Nairobi 00100, Kenya; Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Young, Jarrah
    Wyatt, Amanda
    Young, Mary
    Alders, Robyn
    Bagnol, Brigitte
    Kibaya, Augustino
    Grace, Delia
    Do vaccination interventions have effects?: A study on how poultry vaccination interventions change smallholder farmer knowledge, attitudes, and practice in villages in Kenya and Tanzania2019In: Tropical Animal Health and Production, ISSN 0049-4747, E-ISSN 1573-7438, Vol. 51, no 1, p. 213-220Article in journal (Refereed)
    Abstract [en]

    Poultry are important for many poor households in developing countries, but there are many constraints to poultry production, including disease. One of the most important diseases of chickens is Newcastle disease (ND). Even though there are effective vaccines against this disease available in most countries, uptake by small-scale poultry keepers is often low. In this study, two areas in Kenya and Tanzania were studied, where some villages had received additional support to get vaccination and other villages had not. In Kenya, 320 households from 10 villages were interviewed, of which half of the villages had active promotion of vaccination through village-based advisors. In Tanzania, 457 households were interviewed, of which 241 came from villages that have had active support through either a project or government extension services. Knowledge about vaccines and the attitudes towards vaccinating against ND was evaluated using mixed multivariable logistic models. Results indicate that in Kenya, the most important determinants for understanding the function of a vaccine were having had support in the village and to have knowledge about ND signs, while in Tanzania gender and previous vaccine use were important in addition to having had support. Attitudes towards vaccination were mainly determined by knowledge, where more knowledge about how vaccines work in general or about ND contributed to more positive attitudes. Among Kenyan farmers that had never used the vaccine before, the amount of birds they lost to disease and predators also influenced attitudes. In conclusion, this study supports the notion that knowledge is a very important component of extension support and that simply making vaccines available may not be sufficient for high levels of uptake.

  • 240.
    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.

  • 241. 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.

  • 242.
    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.

  • 243.
    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.

  • 244. 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.

  • 245.
    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.

  • 246.
    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.

  • 247.
    Loncarevic, Semir
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    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 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.

  • 248.
    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.

  • 249.
    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.

  • 250.
    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.

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