Change search
Refine search result
1234567 151 - 200 of 444
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 151. Grubb, Tamara
    et al.
    Frendin, Jan H. M.
    Edner, Anna
    Funkquist, Pia
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nyman, Gorel
    The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses2013In: Veterinary Anaesthesia and Analgesia, ISSN 1467-2987, E-ISSN 1467-2995, Vol. 40, no 6, p. E19-E30Article in journal (Refereed)
    Abstract [en]

    Objectives Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion ((V) over dot(A)/(Q) over dot) mismatch and increased pulmonary shunt fraction ((Q) over dots/(Q) over dott). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO(2)), calculated ((Q) over dots/(Q) over dott) and ET-1 concentration; and Study 2) assess ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). Study design Prospective research trial. Animals Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. Methods Study 1) Cardiopulmonary data including PaO2, SaO(2), ((Q) over dots/(Q) over dott) and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures ANOVA with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) ((V) over dot(A)/(Q) over dot) matching and ((Q) over dots/(Q) over dott) were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. Results Study 1) PaO2 and SaO2 were higher and calculated ((Q) over dots/(Q) over dott) was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. Conclusions and Clinical Relevance PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving ((V) over dot(A)/(Q) over dot) matching and decreasing ((Q) over dots/(Q) over dott) without affecting ET-1.

  • 152.
    Guez, Michel
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Chronic neck pain: An epidemiological, psychological and SPECT study with emphasis on whiplash-associated disorders2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic neck pain, a common cause of disability, seems to be the result of several interacting mechanisms. In addition to degenerative and inflammatory changes and trauma, psychological and psychosocial factors are also involved. One common type of trauma associated with chronic neck pain is whiplash injury; this sometimes results in whiplash-associated disorder (WAD), a controversial condition with largely unknown pathogenetic mechanisms. We studied the prevalence of chronic neck pain of traumatic and non-traumatic origin and compared the prevalence of, sociodemographic data, self-perceived health, workload and chronic lowback pain in these groups. In a ready-made questionnaire (MONICA study), we added questions about cervical spine and low-back complaints. 6,000 (72%) completed a self-administered questionnaire. 43% reported neck pain: 48% of women and 38% of men. Women of working age had more neck pain than retired women, a phenomenon not seen in men. 19% of the studied population suffered from chronic neck pain and it was more frequent in women. A history of neck trauma was common in those with chronic neck pain. Those with a history of neck trauma perceived their health worse and were more often on sick-leave. About 50% of those with traumatic and non-traumatic chronic neck pain also had chronic low-back pain.

    We assessed the subjective and objective neuropsychological functioning in 42 patients with chronic neck pain, 21 with a whiplash trauma, and 21 without previous neck trauma. Despite cognitive complaints, the WAD patients had normal neuropsychological functioning, but the WAD group especially had deviant MMPI results—indicating impaired coping ability and somatization.WAD patients had no alterations in cerebral blood-flow pattern, as measured by rCBF-SPECT and SPM analysis, compared to healthy controls. This contrasts with the non-traumatic group with chronic neck pain, which showed marked blood-flow changes. The blood-flow changes in the non-traumatic group were similar to those described earlier in pain patients but— remarkably enough—were different from those in the WAD group. Chronic neck pain of whiplash and non-traumatic origin appears to be unique in some respects. A better understanding of the underlying pathological mechanisms is a prerequisite for prevention of the development of such chronic pain syndromes and for improvement of the treatment of patients with severe symptoms.

  • 153.
    Gunnarsson, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bed'hom, Bertrand
    Sahlqvist, Anna-Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekwall, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tixier-Boichard, Michele
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The Dark brown plumage color in chickens is caused by an 8.3-kb deletion upstream of SOX102011In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 24, no 2, p. 268-274Article in journal (Other academic)
    Abstract [en]

    The Dark brown (DB) mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin, but only in certain parts of the plumage. Here, we present genetic evidence that an 8.3-kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the DB phenotype. The SOX10 transcription factor has a well-established role in melanocyte biology and is essential for melanocyte migration and survival. Previous studies have demonstrated that the mouse homolog of a highly conserved element within the deleted region is a SOX10 enhancer. The mechanism of action of this mutation remains to be established, but one possible scenario is that the deletion leads to reduced SOX10 expression which in turn down-regulates expression of key enzymes in pigment synthesis such as tyrosinase. Lower tyrosinase activity leads to a shift toward a more pheomelanistic (reddish) plumage color, which is the characteristic feature of the DB phenotype.

  • 154.
    Guo, Yongzhi
    Umeå University, Faculty of Medicine, Medical Biochemistry and Biophsyics.
    Plasmin: a potent pro-inflammatory factor2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Plasmin, the central molecule of the plasminogen activator system, is a broad-spectrum serine protease. Plasmin is important for the degradation of fibrin and other components of the extracellular matrix (ECM) during a number of physiological and pathological processes. The aim of this thesis was to elucidate the functional roles of plasmin during pathological inflammation and infection in autoimmune and non-autoimmune diseases. For this purpose, mouse models of rheumatoid arthritis (RA), bacterial arthritis, infection, and sepsis have been used.

    Previous studies from our laboratory have shown that plasminogen-deficient mice are resistant to the development of collagen type II-induced arthritis (CIA). In contrast, others have shown that plasmin plays a protective role in antigen-induced arthritis (AIA). To investigate the contrasting roles of plasminogen deficiency in models of CIA and AIA, a new animal model of arthritis called local injection-induced arthritis (LIA) was developed. In this model, we replaced methylated bovine serum albumin, which is normally used as an immunogen in the AIA model, with collagen type II (CII) to induce arthritis. When wild-type and plasminogen-deficient mice were injected intra-articularly with CII or 0.9% NaCl following CIA induction, plasminogen-deficient mice developed typical CIA, but the disease was less severe than in wild-type mice and was restricted to the injected joints. When the AIA model was used, plasminogen-deficient mice developed a much more severe arthritis than the wild-type mice. These results indicate that both the antigen and joint trauma caused by the local injection are critical to explaining the contrasting roles of plasminogen deficiency in CIA and AIA. This indicates that CIA and AIA have distinct pathogenic mechanisms and plasmin plays contrasting roles in different types of arthritis models.

    To study the functional roles of plasmin in the host inflammatory response during infectious arthritis, a Staphylococcus aureus-induced bacterial arthritis model was established. When wild-type mice were injected intra-articularly with 1 × 106 colony-forming units (CFU) of S. aureus per joint, all the bacteria were completely eliminated from the injected joints in 28 days. However, in the plasminogen-deficient mice, the S. aureus counts were 27-fold higher at day 28 than at day 0. When human plasminogen was given to the plasminogen-deficient mice daily for 7 days, the bacterial clearance was greatly improved and the necrotic tissue in the joint cavity was also completely eliminated. Supplementation of plasminogen-deficient mice with plasminogen also restored the expression level of interleukin-6 (IL-6) in the arthritic joints. In summary, plasmin has protective roles during S. aureus-induced arthritis by enhancing cytokine expression, removing necrotic tissue, and mediating bacterial killing and inflammatory cell activation.

    The functional roles of plasmin during infection and sepsis were also studied in mice. Infection was induced by injecting 1 × 107 CFU of S. aureus intravenously and the sepsis model was induced by injecting 1.6 × 108 CFU of S. aureus. In the infection model, the wild-type mice had a 25-day survival rate of 86.7%, as compared to 50% in the plasminogen-deficient group. However, when sepsis was induced, the average survival for plasminogen-deficient mice was 3 days longer than for wild-type mice. Twenty-four hours after the induction of sepsis, the serum levels of IL-6 and IL-10 as well as the bacterial counts in all organs investigated were significantly higher in wild-type mice than in plasminogen-deficient mice. In wild-type mice, blockade of IL-6 by intravenous injection of anti-IL-6 antibodies significantly prolonged the onset of mortality and improved the survival rate during sepsis. These data indicate that plasmin plays different roles during infection and sepsis. Furthermore, plasmin appears to be involved in the regulation of inflammatory cytokine expression during sepsis.

    Taken together, our data indicate that plasmin plays multifunctional pro-inflammatory roles in different autoimmune and non-autoimmune diseases. The pro-inflammatory roles of plasmin include activation of inflammatory cells, regulation of cytokine expression, and enhancement of the bacterial killing ability of the host.

  • 155.
    Gustafsson, Mattias
    Örebro University, Department of Clinical Medicine.
    Vilken betydelse har skelettscintigrafi vid diagnos av scaphoideumfraktur?2007Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    En scaphoideumfraktur är den vanligaste frakturen bland karpalbenen i handen. Frakturen orsakas vanligen av ett kraftigt extensionsvåld mot handleden.

    Scaphoideums stora rörlighet i handen och dess begränsade blodförsörjning bidrar till att scaphoideumfrakturer kan vara svårläkta.

    Scaphoideumfrakturer kan vara svåra att påvisa på konventionell röntgen, även vid upprepade undersökningar. Visar konventionell röntgen ett negativt resultat, men klinisk misstanke om fraktur kvarstår, finns olika undersökningsmetoder att tillgå för att en säker diagnos ska kunna ställas.

    Syftet med den här litteraturstudien var att undersöka betydelsen av skelettscintigrafi som undersökningsmetod vid diagnos av scaphoideumfraktur.

    Resultatet visar att skelettscintigrafi har stor betydelse vid diagnos av en scaphoideumfraktur.

    Kan inte en säker diagnos ställas på konventionell röntgen är skelettscintigrafi en metod som båda kan påvisa och exkludera en scaphoideumfraktur.

  • 156.
    Haftor, Darek
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Computer Science, Physics and Mathematics.
    Mirijamdotter, AnitaLinnaeus University, Faculty of Science and Engineering, School of Computer Science, Physics and Mathematics.
    Information and Communication Technologies, Society and Human Beings: Theory and Framework (Festschrift in honor of Gunilla Bradley)2011Collection (editor) (Other academic)
    Abstract [en]

    Information and Communication Technologies, Society and Human Beings: Theory and Framework addresses the extensive area of effects of ICT on human beings and the interaction between ICT, individuals, organizations, and society. This premier reference source features contributions from over 45 distinguished researchers from around the world, each presenting high quality research on social informatics, human computer interaction, organizational behavior, and macro-ergonomics. This unique publication is perfect for students, teachers, researchers, engineers, practitioners, managers, policy-makers, and media alike.

  • 157.
    Hagelin, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Hau, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Attitude of Swedish veterinary and medical students to animal experimentation2000In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 146, no 26, p. 757-760Article in journal (Refereed)
    Abstract [en]

    Nearly all veterinary and medical students (94 per cent) found it morally acceptable to use animals in research and believed it to be a necessity in order to treat human diseases. In contrast with the medical students a substantial proportion ofveterinary students (40 per cent) considered themselves animal rights activists. Unlike themedical curriculum, the veterinary curriculum contains a two-week course in laboratoryanimal medicine, and a higher proportion of the students who had not been through this course was opposed to the use of animals in research than of the students who had completed the course. The course modified the views of half the students; more than 26 per cent of them became more positive towards animal use in research after the courser whereas 3 per cent became more negative.

  • 158. Hagglund, Sara
    et al.
    Hu, Kefei
    Blodorn, Krister
    Makabi-Panzu, Boby
    Gaillard, Anne-Laure
    Ellencrona, Karin
    Chevret, Didier
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Bengtsson, Karin Lovgren
    Riffault, Sabine
    Taylor, Geraldine
    Valarcher, Jean Francois
    Eleouet, Jean-Francois
    Characterization of an Experimental Vaccine for Bovine Respiratory Syncytial Virus2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 7, p. 997-1004Article in journal (Refereed)
    Abstract [en]

    Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are major causes of respiratory disease in calves and children, respectively, and are priorities for vaccine development. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complex (ISCOM), is effective in calves with maternal antibodies. The present study focuses on the antigenic characterization of this vaccine for the design of new-generation subunit vaccines. The results of our study confirmed the presence of membrane glycoprotein (G), fusion glycoprotein (F), and nucleoprotein (N) proteins in the ISCOMs, and this knowledge was extended by the identification of matrix (M), M2-1, phosphoprotein (P), small hydrophobic protein (SH) and of cellular membrane proteins, such as the integrins alpha(V)beta(1), alpha(V)beta(3), and alpha(3)beta(1). The quantity of the major protein F was 4- to 5-fold greater than that of N (similar to 77 mu g versus similar to 17 mu g/calf dose), whereas G, M, M2-1, P, and SH were likely present in smaller amounts. The polymerase (L), M2-2, nonstructural 1 (NS1), and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from the BRSV-ISCOM-immunized calves contained high titers of IgG antibody specific for F, G, N, and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T-cell responses. The absence of immunopathological effects of the cellular proteins, such as integrins, needs to be further confirmed, and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiating infected from vaccinated animals.

  • 159.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences.
    Cell adhesion proteins in different invasive patterns of colon carcinomas: a morphometric and molecular genetic study2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis.

    This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations.

    We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found.

    In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.

     

  • 160.
    Halin Bergström, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rudolfsson, Stina H.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype2016In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 18, no 3, p. 152-161Article in journal (Refereed)
    Abstract [en]

    Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen-sensitive, androgen receptor-positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone.

  • 161.
    Hammarberg, Karl-Erik
    et al.
    Hushållningssällskapet Dalarna Gävleborg, Storvik, Sverige.
    Danielsson-Tham, Marie-LouiseÖrebro University, School of Hospitality, Culinary Arts & Meal Science.
    Bakteriologi, hygien och egenkontroll vid ystning i småskalig produktion: Kompendium Juni 20042004Collection (editor) (Other (popular science, discussion, etc.))
  • 162.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Androgen controlled regulatory systems in prostate cancer: potential new therapeutic targets and prognostic markers2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    BACKGROUND: Prostate cancer is by far the most common cancer among Swedish men. Some patients have an aggressive lethal disease, but the majority of affected men have long expected survival. Unfortunately, the diagnostic tools available are insufficient in predicting disease aggressiveness. Novel prognostic markers are therefore urgently needed. Furthermore, metastatic prostate cancer is generally treated with castration, but the long-term effects are insufficient. Additional studies are therefore needed to explore how the effects of this therapy can be enhanced. Prostate growth and regression is beside testosterone controlled by locally produced regulators. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are two of the major regulators in the normal prostate and in prostate tumours.

    MATERIALS AND METHODS: VEGF and EGFR were explored in the prostate, by treating rats with either anti-VEGF or anti-EGFR treatment during castration and testosterone-stimulated prostate growth. Rats with implanted androgen-independent prostate tumours were treated with an inhibitor of both VEGF receptor-2 (VEGFR-2) and EGFR. Stereological techniques, immunohistochemistry, western blotting and quantitative real-time PCR were used to evaluate these experiments. Furthermore, prostate tissue from untreated prostate cancer patients was used to retrospectively explore the expression of phosphorylated-EGFR (pEGFR) in relation to outcome.

    RESULTS: Anti-VEGF treatment during testosterone-stimulated prostate growth, inhibited vascular and prostate growth. Anti-EGFR treatment during castration and testosterone-stimulated prostate growth resulted in enhanced castration effects and inhibited prostate growth. Anti-vascular treatment of androgen-independent prostate cancer with an inhibitor of VEGFR-2 and EGFR, that targets the normal and tumour vasculature, enhanced the effects of castration. Low immunoreactivity for pEGFR in prostate epithelial cells, both in the tumour and also in the surrounding non-malignant tissue, was associated with good prognosis.

    CONCLUSIONS: Anti-vascular treatment, with an inhibitor of VEGFR-2 and EGFR, in combination with castration could be an effective way to treat androgen-insensitive prostate tumours. VEGF and EGFR signalling are necessary components in testosterone-stimulated prostate growth. Phosphorylation of EGFR could be a useful prognostic marker for prostate cancer patients. Tumours may affect the surrounding non-malignant tissue and pEGFR immunoreactivity in the morphologically normal prostate tissue can be used to retrieve prognostic information.

  • 163.
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Association between Hospital Waste and the House Crow (Corvus splendens) in the Dissemination of Antibiotic Resistance and the Epidemic Escherichia coli Clone O25b-ST131 in BangladeshManuscript (preprint) (Other academic)
    Abstract [en]

    Multiresistant bacteria constitute a serious health risk. In order to investigate the environmental contamination of antibiotic resistance in areas with poor waste management in Bangladesh, fecal samples from 238 house crows living in the surroundings of two major hospitals were screened for members of the Enterobacteriaceae family with extended spectrum beta-lactamase (ESBL)-production. These were compared with 31 ESBL-producing patient isolates, and the susceptibility of E. coli isolates was tested. Without selective pressure, 65.8% of the E. coli isolates from crows were resistant to one or more of 13 antibiotics, and 39.1% were multiresistant. The highest resistance rates were against tetracycline (52.2%), trimethoprim-sulphamethoxazole (43.5%), nalidixic acid (39.8%) and ampicillin (33.5% ). Fifty-nine percent of the crows were ESBL-carriers, and the isolates harbored CTX-M-1, CTX-M-15, CTX-M-55, CTX-M-79 or CTX-M-14-like genes. Two thirds of these ESBL-producers were multi-drug resistant. The ESBL-producing isolates from patients showed a higher rate of resistance compared with the ESBL-producers from crows. One hundred percent were multi-drug resistant, and most common was resistance to ciprofloxacin (93.3%) and trimethoprim-sulphamethoxazole (60%). The corresponding figures for ESBL-producing crow isolates were 41.3% and 57.3%. The crows and patients shared the epidemic E. coli clone O25b-ST131, which carried CTX-M-15 and CTX-M-14-like enzymes. Dissemination of ESBL-producing Klebsiella pneumoniae was also observed among the crows. In conclusion, the Bangladeshi house crow is the bird with the highest carriage rate of ESBL-producing bacteria observed so far. Their scavenging behavior at poorly managed hospital waste dumps, makes them into both reservoirs and active spreaders of antibiotic resistance into the environment. Nationwide programs are necessary to both improve the management of hospital waste and sewage and the control of the antibiotic usage to prevent further environmental contamination. 

  • 164.
    Hasan, Badrul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Alam, Munirul
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    The Gull (Chroicocephalus brunnicephalus) as an Environmental Bioindicator and Reservoir for Antibiotic Resistance on the Coastlines of the Bay of Bengal2014In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 20, no 5, p. 466-471Article in journal (Refereed)
    Abstract [en]

    The presence and frequency of multiresistant bacteria in wild birds act as indicators of the environmental contamination of antibiotic resistance. To explore the rate of contamination mediated by Escherichia coli, 150 fecal samples from the brown-headed gull (Chroicocephalus brunnicephalus) and 8 water samples from the Bay of Bengal area were collected, cultured, and tested for antibiotic susceptibility. Special attention was paid to extended-spectrum beta-lactamase (ESBL)-producing isolates, which were further characterized genetically. Antibiotic resistance was found in 42.3% (36/85) of the E. coli isolates and multidrug resistance in 11.8%. Isolates from the area with a higher human activity were more resistant than those from an area with a lower level of activity. Most frequent was resistance to ampicillin (29.4%), followed by trimethoprim-sulfamethoxazole (24.7%) and quinolones (22.4%). Carriage of ESBL-producing E. coli was relatively high (17.3%) in the gulls, whereas no ESBL producers were found in the water. All ESBL-producing E. coli isolates, but one, carried blaCTX-M-15 or blaCTX-M-15-like genes. A blaCTX-M-14-like enzyme was found as an exception. Gulls from two different colonies shared E. coli clones and harbored the clinically relevant sequence types ST10, ST48, and ST131. The high frequency of antibiotic resistance and ESBL production among E. coli isolates from gulls indicates that the environmental contamination of antibiotic resistance has already gone far on the coastlines of the Bay of Bengal. Considering the limited control over the antibiotic consumption and waste from human activities in Bangladesh, there is no easy solution in sight.

  • 165. Hauffe, Heidi C
    et al.
    Niklasson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Olsson, Therese
    Bianchi, Alessandro
    Rizzoli, Annapaola
    Klitz, William
    Ljungan Virus Detected in Bank Voles (Myodes glareolus) and Yellow-Necked Mice (Apodemus flavicollis) from Northern Italy2010In: Journal of Wildlife Diseases, ISSN 0090-3558, E-ISSN 1943-3700, Vol. 46, no 1, p. 262-266Article in journal (Refereed)
    Abstract [en]

    Identified in 1998, Ljungan virus (LV; Picornaviridae) causes type 1 diabetes-like symptoms and myocarditis in bank voles (Myodes glareolus) from Sweden and Denmark, and may be a zoonotic agent of several important diseases (e.g., intrauterine fetal death, I diabetes, Guillain-Barre syndrome, and myocarditis). Using a real-time reverse transcriptase-polymerase chain reaction assay and sequence anlalysis, we detected LV in bank voles, and for the first time, in yellow-necked mice collected during 2006 from a site in northern Italy. The global distribution of LV and its role as a mammalian pathogen deserve further attention.

  • 166.
    Havarinasab, Said
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Effect of thimerosal on the murine immune system: especially induction of systemic autoimmunity2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The organic mercury compound ethylmercurithiosalicylate (thimerosal), an antiseptic and a preservative, has recently raised public health concern due to its presence in vaccines globally. Thimerosal dissociates in the body to thiosalicylate and ethyl mercury (EtHg), which is partly converted to inorganic mercuric mercury (Hg2+). The immunosuppressive, immunostimulatory, and de novo autoimmunogen effect of thimerosal in mice, as well as the accelerating/aggravating effect on spontaneous systemic autoimmunity including dose-response aspects were the subject of this thesis.

    Thimerosal perorally (590 μg Hg/kg body weight (bw)/day) to genetically susceptible (H-2s) mice caused immunosuppression during the first week with reduction of the total number of splenocytes, T- and B-cells. The suppression lasted 2 weeks for CD4+ cells, but was superseded by a strong immunostimulation/proliferation including T- as well as B-cells, and polyclonal B-cell activation (PBA). Antinuclear antibodies targeting the 34-kDa nucleolar protein fibrillarin (AFA) appeared after 10 days, followed by renal mesangial and systemic vessel wall immune-complex (IC) deposits. The Lowest Observed Adverse Effect Level (LOAEL) was in the order AFA = glomerular and splenic vessel wall deposits < hyperimmunoglobulinemia < PBA. The LOAEL for AFA was 118 μg Hg/kg bw/day. The LOAEL for the different parameters of this thimerosal-induced systemic autoimmune condition (HgIA) was 3-11-fold higher compared with HgIA induced by HgCl2. The thimerosal-induced HgIA shared with HgCl2 a significant dose-response relationship, and requirement for: T-cells, the costimulatory factor CD28, the IFN-γ/IFN-γ-receptor pathway,but not IL-4. The mRNA expression in lymph nodes of IL-2, IFN-γ, IL-4, and IL-15 was significantly increased but not delayed compared with HgCl2.

    Treatment with the ubiquitous organic Hg compound methyl Hg using equimolar doses of Hg (533 μg Hg/kg bw/day) caused a transient immunosuppression, followed by a weak immunostimulation and AFA. The IgG AFA isotypes induced by the organic Hg compounds MeHg and EtHg were stable and dominated by a Th1-like pattern over a broad time- and dose range. Treatment with inorganic HgCl2 caused a dose- and time-dependent pattern of IgG AFA isotypes. Low doses favored a Th1-like pattern, a high dose a balanced or Th2-like pattern. Middle-range doses showed initially a Th1-like pattern which gradually evolved into a balanced or Th2-like pattern. The qualitative difference in IgG AFA isotypes between organic and inorganic Hg may be due to differences in activation and/or suppression of T-helper cell subsets or factors influencing the Th1/Th2-function. Speciation of the renal Hg2+ concentration and comparison with the threshold dose for induction of AFA by HgCl2 showed that even with the lowest doses of thimerosal and MeHg used in this thesis, the AFA response might from a dose threshold point of view have been caused by conversion of the organic Hg species to Hg2+.

    Primary treatment with inorganic Hg (HgCl2) accelerates/aggravates murine systemic autoimmunity, both spontaneous (genetic) and induced by other means. This capacity was assessed for thimerosal over a broad dose range using the (NZB X NZW)F1 hybrid mouse model. Significantly increased antinuclear antibodies (ANA) was seen after 4-7 weeks treatment (LOAEL 147 μg Hg/kg bw/day), and the response was dose-dependent up to 13 weeks. Renal mesangial and systemic vessel walls deposits similar to those in de novo HgIA were present after 7 weeks treatment. Twenty-two to 25 weeks treatment with thimerosal caused, in a dose-dependent fashion (LOAEL 295 μg Hg/kg bw/day), relocalization of the spontaneously developing glomerular IC deposits from the capillary vessel walls to the mesangium, which attenuated histological kidney damage and proteinuria, and increased survival. Thimerosal caused systemic vessel wall IC-deposits over a broad dose range: the Low Observed Adverse Effect Level (LOAEL) for renal and splenic vessel wall IC deposits was 18 and 9 μg Hg/kg bw/day, respectively. The No Observed Adverse Effect Level (NOAEL) could not be determined for the latter, since deposits were present even with the lowest dose used.

    Thimerosal causes in genetically susceptible mice an initial, transient immunosuppression which is superseded by a strong immunostimulation and systemic autoimmunity, sharing many characteristics with the HgIA induced by inorganic HgCl2. The IgG AFA isotype pattern is however qualitatively different, and the threshold dose substantially higher. In contrast, long-term treatment with thimerosal induces systemic vessel wall IC-deposits also using doses below those needed to induce HgIA de novo in H-2s mice.

  • 167. Hecker, Yanina P.
    et al.
    Coceres, Veronica
    Wilkowsky, Silvina E.
    Jaramillo Ortiz, Jose M.
    Morrell, Eleonora L.
    Verna, Andrea E.
    Ganuza, Agustina
    Cano, Dora B.
    Lischinsky, Lilian
    Angel, Sergio O.
    Zamorano, Patricia
    Odeon, Anselmo C.
    Leunda, Maria R.
    Campero, Carlos M.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moore, Dadin P.
    A Neospora caninum vaccine using recombinant proteins fails to prevent foetal infection in pregnant cattle after experimental intravenous challenge2014In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 162, no 3-4, p. 142-153Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the immunogenicity and protective efficacy of rNcSAG1, rNcHSP20 and rNcGRA7 recombinant proteins formulated with immune stimulating complexes (ISCOMs) in pregnant heifers against vertical transmission of Neospora caninum. Twelve pregnant heifers were divided into 3 groups of 4 heifers each, receiving different formulations before mating. Immunogens were administered twice subcutaneously: group A animals were inoculated with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) formulated with ISCOMs; group B animals received ISCOM-MATRIX (without antigen) and group C received sterile phosphate-buffered saline (PBS) only. The recombinant proteins were expressed in Escherichia coil and purified nickel resin. All groups were intravenously challenged with the NC-1 strain of N. caninum at Day 70 of gestation and dams slaughtered at week 17 of the experiment. Heifers from group A developed specific antibodies against rNcSAG1, rNcHSP20 and rNcGRA7 prior to the challenge. Following immunization, an statistically significant increase of antibodies against rNcSAG1 and rNcHSP20 in all animals of group A was detected compared to animals in groups B and C at weeks 5, 13 and 16 (P< 0.001). Levels of antibodies against rNcGRA7 were statistical higher in group A animals when compared with groups B and Cat weeks 5 and 16 (P> 0.001). There were no differences in IFN-gamma production among the experimental groups at any time point (P> 0.05). Transplacental transmission was determined in all foetuses of groups A, B and C by Western blot, immunohistochemistry and nested PCR. This work showed that rNcSAG1, rNcHSP20 and rNcGRA7 proteins while immunogenic in cattle failed to prevent the foetal infection in pregnant cattle challenged at Day 70 of gestation. 

  • 168.
    Hedberg, Carina
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Kyhlstedt, Madeleine
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Samvarierar frukostfrekvens och betyg?: En kvantitativ studie om sambandet mellan frukostfrekvens och betyg hos gymnasieelever på samhälls- och naturvetenskapliga programmen2008Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet med denna studie var att undersöka om det hos gymnasieelever på samhälls- och naturvetenskapliga programmen finns ett samband mellan frukostfrekvens och prestation mätt i betyg. För att kunna uppnå syftet användes följande frågeställningar:

    • Finns det en korrelation mellan frukostfrekvens och betyg (betyg mäts i medelpoäng för svenska, engelska, matematik och samhällskunskap)?

    • Kan potentiella confounders förklara detta eventuella samband?

    Metod

    Den undersökta populationen bestod av 238 gymnasieelever i åldrarna 15-19 år. 122 av dessa var flickor och 116 var pojkar. På tre valda gymnasieskolor i Stockholms län gjordes ett riktat slumpmässigt urval bland eleverna. Studien byggde på självrapporterad data som inhämtades genom en enkät. Vi ställde frågor om exempelvis kroppsstorlek, frukostfrekvens, betyg, föräldrarnas postgymnasiala studienivå, studietid utanför lektionstid och boendeform.

    Resultat

    Könsfördelningen var jämn – 51,3 % var flickor och 48,7 % var pojkar. För båda könen gällde att drygt två tredjedelar åt frukost samtliga veckans skoldagar. Anmärkningsvärt är att en av tio flickor aldrig åt frukost under en skolvecka. En stor andel elever hade betyget MVG och särskilt utmärkande var flickornas betyg i engelska där hela tre fjärdedelar hade det högsta betyget. Gällande programmen var både antalet elever och kön relativt jämnt fördelade. Medianmedelpoängen utifrån de fyra betygen i matematik, svenska, engelska och samhällskunskap var för flickor 17,5 (sd 2,5) och för pojkar 16,8 (sd 2,7). Det fanns en positiv korrelation (Spearman’s) mellan frukostfrekvens och medianmedelpoäng. För att ta hänsyn till möjliga confounders gjordes en logistisk regression. Av de oberoende variablerna visade sig endast frukostfrekvens och vilket program eleven gick vara signifikanta prediktorer för medelpoängen. Således hade de som åt frukost bättre betyg än de som inte gjorde det och de som gick naturvetenskapliga programmet hade bättre betyg än de som gick samhälls-vetenskapliga programmet. 20 % av variationen i medelpoäng förklaras alltså av de två variablerna frukostfrekvens och gymnasieprogram.

    Slutsats

    Slutsatsen är att det finns ett positivt samband mellan frukostfrekvens och prestation mätt i betyg. Även efter kontroll för confounders var denna korrelation signifikant. Även vilket gymnasieprogram eleven studerade korrelerade med medelpoäng.

  • 169.
    Hedenqvist, Patricia
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, VHC POB 7054, SE-75007 Uppsala, Sweden..
    Trbakovic, Amela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Ley, Cecilia
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pathol, POB 7028, SE-75007 Uppsala, Sweden..
    Ekman, Stina
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pathol, POB 7028, SE-75007 Uppsala, Sweden..
    Jensen-Waern, Marianne
    Swedish Univ Agr Sci, Dept Clin Sci, VHC POB 7054, SE-75007 Uppsala, Sweden..
    Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting2016In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 107, p. 123-131Article in journal (Refereed)
    Abstract [en]

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 x 10 mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 43 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5 mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.

  • 170.
    Heiene, Reidun
    et al.
    University of Utrecht.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Neusüß, Christian
    Aalen University.
    Hedeland, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Carbamylated hemoglobin project AKI vs CKD- or the magnitude of the chronic component2016Conference paper (Refereed)
  • 171.
    Hellander-Edman, Anna
    et al.
    Department of Animal Environment & Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Makdoumi, Karim
    Örebro University Hospital. Department of Ophthalmology.
    Mortensen, Jes
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Ekesten, Bjorn
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Corneal cross-linking in 9 horses with ulcerative keratitis2013In: BMC Veterinary Research, ISSN 1746-6148, E-ISSN 1746-6148, Vol. 9, p. 128-Article in journal (Refereed)
    Abstract [en]

    Background: Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting.

    Results: Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4-26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis.

    Conclusions: CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species.

  • 172.
    Hellström, Anders
    et al.
    National Veterinary Institute, Uppsala, Sweden.
    Chukalova, Natalia
    AtlantNiro, Kaliningrad, Russia.
    Rodjuk, Galina
    AtlantNiro, Kaliningrad, Russia.
    Ekman, Elisabet
    Swedish University of Agricultural Sciences.
    Norrgren, Leif
    Swedish University of Agricultural Sciences.
    8. Aquaculture and Fish Health2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 63-72Chapter in book (Other (popular science, discussion, etc.))
  • 173.
    Henriksson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity in healthy Swedish children: A longitudinal study until 4.5 years of age including evaluation of methods to assess physical activity and energy intake2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Childhood obesity according to the World Health Organization is one of the most serious public health challenges of the 21st century. The proportion of childhood obesity is high both globally and in Sweden. This is of great concern since obese children tend to stay obese in adulthood. In order to develop strategies to prevent early childhood obesity more knowledge is needed regarding factors explaining why children become overweight and obese. Preventive strategies require accurate and easy-to-use methods to assess physical activity in response to energy expenditure as well as energy intake in young children, but such methods are largely lacking or have shown limited accuracy. The aims of this thesis were: 1) to describe the longitudinal development of body composition from 1 week to 4.5 years of age; 2) to study relationships between measures of body composition and the physical activity level (PAL) at 1.5 and 3 years of age; 3) to evaluate if heart rate recording and movement registration using Actiheart can capture variations in total energy expenditure (TEE) and activity energy expenditure (AEE) at 1.5 and 3 years; 4) to evaluate the potential of a 7-day activity diary to assess PAL at 1.5 and 3 years of age; 5) to evaluate a new tool (TECH) using mobile phones for assessing energy intake at 3 years of age.

    Healthy children were investigated at 1 and 12 weeks (n=44), at 1.5 (n=44), 3 (n=33) and 4.5 (n=26) years of age. Body composition was measured using air-displacement plethysmography at 1 and 12 weeks and at 4.5 years of age. At 1.5 and 3 years, body composition, TEE, PAL and AEE were assessed using the doubly labelled water method and indirect calorimetry. Heart rate and movements were recorded using Actiheart (four days) and physical activities were registered using the 7-day diary. Energy intake was assessed using TECH during one complete 24-hour period.

    Average percentage of total body fat (TBF) and average fat mass index (FMI) were higher (+3 to +81 %), while fat-free mass index (FFMI) was slightly lower (-2 to -9 %), in children in the study from 12 weeks until 4.5 years of age when compared to corresponding reference values. A relationship between TBF% and PAL was found both at 1.5 and 3 years of age. At 3 years, but not at 1.5 years, this could be explained by a relationship between PAL and FFMI. Actiheart recordings explained a significant but small fraction (8%) of the variation in free-living TEE at 1.5 and 3 years, and in AEE (6 %) at 3 years, above that explained by body composition variables. At 1.5 and 3 years of age, PAL estimated by means of the activity diary using metabolic equivalent (MET) values by Ainsworth et al. was not significantly different from reference PAL, but the accuracy for individuals was low. Average energy intake assessed by TECH was not significantly different from TEE. However, the accuracy for individuals was poor.

    The results of this thesis suggest that 1) The higher body fatness of the children in the study compared to the corresponding reference values may indicate the presence of a secular trend in body composition development characterized by a high body fatness. 2) Body fatness might counteract physical activity at 1.5 years of age when the capacity to perform physical activity is limited, but not at 3 years of age when such a capacity has been developed. 3) Actiheart recordings explained a significant but small fraction of the variation in TEE at 1.5 and 3 years, and in AEE at 3 years of age, above that explained by body composition variables. 4) The activity diary and TECH produced mean values in agreement with reference PAL and TEE, respectively, but the accuracy for individual children was low.

    In conclusion, the results of this thesis suggest the presence of a secular trend in body composition development in healthy Swedish children, from infancy up to 4.5 years of age, which is characterized by a high body fatness. Methods to assess physical activity and energy intake at 1.5 and 3 years of age provided some promising results on a group level, although further research is needed to increase the accuracy of these methods in individual children.

  • 174.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bonn, E. Stephanie
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bergström, Anna
    Karolinska Institutet, Institute of Enviromental Medicine, Stockholm, Sweden.
    Bälter, Katarina
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bälter, Olle
    Royal Institute of Technology, School of Computer Science and Communication, Stockholm, Sweden.
    Delisle, Christine
    Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    A New Mobile Phone-Based Tool for Assessing Energy and Certain Food Intakes in Young Children: A Validation Study2015In: JMIR mhealth and uhealth, E-ISSN 2291-5222, Vol. 3, no 2, article id e38Article in journal (Refereed)
    Abstract [en]

    Background: Childhood obesity is an increasing health problem globally. Obesity may be established already at pre-school age. Further research in this area requires accurate and easy-to-use methods for assessing the intake of energy and foods. Traditional methods have limited accuracy, and place large demands on the study participants and researchers. Mobile phones offer possibilities for methodological advancements in this area since they are readily available, enable instant digitalization of collected data, and also contain a camera to photograph pre- and post-meal food items. We have recently developed a new tool for assessing energy and food intake in children using mobile phones called the Tool for Energy Balance in Children (TECH). Objective: The main aims of our study are to (1) compare energy intake by means of TECH with total energy expenditure (TEE) measured using a criterion method, the doubly labeled water (DLW) method, and (2) to compare intakes of fruits and berries, vegetables, juice, and sweetened beverages assessed by means of TECH with intakes obtained using a Web-based food frequency questionnaire (KidMeal-Q) in 3 year olds. Methods: In this study, 30 Swedish 3 year olds were included. Energy intake using TECH was compared to TEE measured using the DLW method. Intakes of vegetables, fruits and berries, juice, as well as sweetened beverages were assessed using TECH and compared to the corresponding intakes assessed using KidMeal-Q. Wilcoxon matched pairs test, Spearman rank order correlations, and the Bland-Altman procedure were applied. Results: The mean energy intake, assessed by TECH, was 5400 kJ/24h (SD 1500). This value was not significantly different (P=.23) from TEE (5070 kJ/24h, SD 600). However, the limits of agreement (2 standard deviations) in the Bland-Altman plot for energy intake estimated using TECH compared to TEE were wide (2990 kJ/24h), and TECH overestimated high and underestimated low energy intakes. The Bland-Altman plots for foods showed similar patterns. The mean intakes of vegetables, fruits and berries, juice, and sweetened beverages estimated using TECH were not significantly different from the corresponding intakes estimated using KidMeal-Q. Moderate but statistically significant correlations (ρ=.42-.46, P=.01-.02) between TECH and KidMeal-Q were observed for intakes of vegetables, fruits and berries, and juice, but not for sweetened beverages. Conclusion: We found that one day of recordings using TECH was not able to accurately estimate intakes of energy or certain foods in 3 year old children.

  • 175.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Britt
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Flinke Carlsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age2015Manuscript (preprint) (Other academic)
    Abstract [en]

    In order to develop strategies to prevent early childhood obesity more knowledge about longitudinal body composition development is needed. Previous studies have shown that there is a negative relationship between the physical activity level (PAL) and total body fat (TBF) in children. The aims of this study were: 1) To describe the longitudinal development of body composition from 1 week to 4·5 years of age. 2) To study the relationships between measures of body composition and PAL at 3 years of age. 3) To compare the relationships between body composition measures and PAL at 3 years of age to the corresponding relationships at 1·5 years of age. Body composition was measured using air-displacement plethysmography at 1 week, 12 weeks and at 4·5 years of age. At 1·5 and 3 years body composition and PAL were assessed using the doubly labelled water method and indirect calorimetry. The results showed that TBF% and fat mass index (FMI) were higher than corresponding reference values, during infancy and childhood. We found a relationship between TBF% and PAL at 3 years of age but this was explained by a relationship between PAL and fat-free mass index (FFMI). The corresponding relationship at 1·5 years of age could not be explained by a relationship between PAL and FFMI. In conclusion, the children in this study had higher body fatness compared to the corresponding reference values. This may indicate an identification of a secular trend in body composition development which is characterized by a high body fatness. Our findings also suggest that body fatness might counteract physical activity at 1·5 years of age when the capacity to perform physical activity is limited, however this result was not observed at 3 years of age when such a capacity has been developed.

  • 176.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Glucose, insulin, and the insulin-like growth factor binding protein 1 in the circulation of pregnant women in relation to their own body composition and to that of their infants2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Aim: Intrauterine factors influence infant size and body composition but the mechanisms involved are incompletely known. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e. glucose, insulin, HOMA-IR (homeostasis model assessment-insulin resistance), haemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein 1), in their circulation and related these variables to the body composition of their infants.

    Methods: Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32.

    Results: Insulin/HOMA-IR were positively related to body mass index, fat mass index and fat mass (r2=0.32-0.36, P<0.001) of the women. Their glucose, insulin and HOMA-IR values were positively (P≤0.009) associated, while IGFBP-1was negatively (P=0.001) associated, with infant fat mass. Insulin and HOMA-IR were positively associated with fat mass of daughters (P<0.001), but not of sons (P≥0.65) (Sex-interaction: P≤ 0.042).

    Conclusion: Glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggested that a previously identified relationship between fat mass of mothers and daughters is mediated by insulin resistance.

  • 177.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Parental fat-free mass is related to the fat-free mass of infants and maternal fat mass is related to the fat mass of infant girls2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 5, p. 491-497Article in journal (Refereed)
    Abstract [en]

    Aim: Existing studies suggest that weight and body composition of parents influence the size and body composition of their offspring, but are often inconclusive and conducted by means of inappropriate body composition methodology. Our aim was to study infant size and body composition variables in relation to body composition variables of their mothers and fathers in a well-nourished population using an accurate methodology.

    Methods: Between 2008 and 2011, we used air displacement plethysmography to measure the body composition of 209 parent–infant units. Parents were measured when women were in gestational week 32. Their healthy, singleton, full-term infants were measured at 1 week.

    Results: Infant fat-free mass in grams was positively related (p ≤ 0.007) to the fat-free mass in kilograms of the mothers (15.6 g/kg) and the fathers (9.1 g/kg). Furthermore, the fat mass of the daughters, but not of the sons, was positively related to the fat mass of the mothers (5.8 g/kg, p = 0.007).

    Conclusion: This study found associations between the fat-free mass of parents and infants and an association between the fat mass of mothers and their infant girls. These findings may help to understand early life factors behind overweight and obesity.

  • 178.
    Henriksson, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Backman, Cristina M
    Harvey, Brandon K
    Kadyrova, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bazov, Igor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Shippenberg, Toni S
    Bakalkin, Georgy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain2014In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1839, no 11, p. 1226-1232Article in journal (Refereed)
    Abstract [en]

    The dynorphin kappa-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.

  • 179. Hernández-Castellano, Lorenzo E
    et al.
    Nally, Jarlath E
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wanapat, Metha
    Alhidary, Ibrahim A
    Fangueiro, David
    Grace, Delia
    Ratto, Marcelo
    Bambou, Jean Christophe
    de Almeida, André M
    Dairy science and health in the tropics: challenges and opportunities for the next decades.2019In: Tropical Animal Health and Production, ISSN 0049-4747, E-ISSN 1573-7438, Vol. 51, no 5, p. 1009-1017Article in journal (Refereed)
    Abstract [en]

    In the next two decades, the world population will increase significantly; the majority in the developing countries located in the tropics of Africa, Asia, Latin America, and the Caribbean. To feed such a population, it is necessary to increase the availability of food, particularly high-value animal protein foods produced locally, namely meat and dairy products. Dairy production in tropical regions has a lot of growth potential, but also poses a series of problems, particularly as dairy production systems were developed in temperate countries and in most cases are difficult to implement in the tropics. Drawbacks include hot weather and heat stress, the lack of availability of adequate feeds, poor infrastructure, and cold chain and the competition with cheap imports from temperate countries. This position paper reviews the major drawbacks in dairy production for the five major dairy species: cattle, water buffalo, sheep, goat, and camel, as well as the future trends in research and development. It also concerns the major trends in reproduction and production systems and health issues as well as environmental concerns, particularly those related to greenhouse gas emissions. Tropical Animal Health and Production now launches a topical collection on Tropical Dairy Science. We aim to publish interesting and significant papers in tropical dairy science. On behalf of the editorial board of the Tropical Animal Health and Production, we would like to invite all authors working in this field to submit their works on this topic to this topical collection in our journal.

  • 180.
    Herrmann, John A.
    University of Illinois at Urbana-Champaign.
    36. Agricultural Terrorism: The US Perspective2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 296-305Chapter in book (Other (popular science, discussion, etc.))
  • 181.
    Hilborn, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer: Impact on tamoxifen treatment2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast  cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.

    Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different  aspects of their role in breast cancer.

    Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.

  • 182.
    Hillström, Anna
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Bylin, Jonas
    Evidensia Sodra Djursjukhuset, Stockholm, Sweden..
    Hagman, Ragnvi
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Björhall, Karin
    AstraZeneca R&D, RIA IMed, Dept Translat Sci, Molndal, Sweden..
    Tvedten, Harold
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Königsson, Kristian
    AstraZeneca R&D Sodertalje, Safety Assessment, Sodertalje, Sweden..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kjelgaard-Hansen, Mads
    Novo Nordisk, Translat Haemophilia Pharmacol, Malov, Denmark..
    Measurement of serum C-reactive protein concentration for discriminating between suppurative arthritis and osteoarthritis in dogs2016In: BMC Veterinary Research, ISSN 1746-6148, E-ISSN 1746-6148, Vol. 12, article id 240Article in journal (Refereed)
    Abstract [en]

    Background: In a dog with joint pain, it is important to determine whether it has suppurative joint disease, characterized by exudation of neutrophils in the synovial fluid, or not, as this affects choice of diagnostic tests and treatments. The aim of this study was to evaluate whether measurement of serum C-reactive protein (CRP) concentration could be used to discriminate between dogs with suppurative arthritis and osteoarthritis (OA). Furthermore, the concentrations of serum and synovial fluid interleukin (IL) 6 concentrations were measured in dogs with joint disease and in healthy dogs, and were correlated to serum CRP concentrations. Methods: Dogs with joint pain were enrolled prospectively and were classified to have suppurative arthritis or OA based on synovial fluid analysis and radiographic/arthroscopic findings. Healthy Beagles were enrolled as a comparative group. CRP and IL-6 concentrations were measured with canine-specific immunoassays. The performance of CRP concentration in discriminating between dogs with suppurative arthritis and OA was evaluated using a previously established clinical decision limit for CRP (20 mg/l), and by receiver operator characteristic (ROC) curve and logistic regression analysis. Comparisons of CRP and IL-6 concentrations between groups were performed using t-tests, and correlations by Spearman rank correlation coefficients. Results: Samples were obtained from 31 dogs with suppurative arthritis, 34 dogs with OA, and 17 healthy dogs. Sixty-two out of 65 dogs with joint disease were correctly classified using the clinical decision limit for CRP. Evaluation of ROC curve and regression analysis indicated that serum CRP concentrations could discriminate between suppurative arthritis and OA. Dogs with suppurative arthritis had higher serum CRP and serum and synovial fluid IL-6 concentrations compared to dogs with OA (p < 0.001). Dogs with OA had higher synovial fluid IL-6 concentrations (p < 0.001), but not higher serum CRP (p = 0.29) or serum IL-6 (p = 0.07) concentrations, compared to healthy dogs. There was a positive correlation between synovial fluid IL-6 and serum CRP concentrations (r(s) = 0.733, p < 0.001), and between serum IL-6 and serum CRP concentrations (r(s) = 0.729, p < 0.001). Conclusion: CRP concentration was found to discriminate well between dogs with suppurative arthritis and OA.

  • 183.
    Hirche, Elin
    University of Skövde, School of Bioscience.
    AM I FUNNY NOW?: The Neurological Basis of Humor Styles2019Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    The present thesis will provide an overview of how the four humor styles, affiliative, self-enhancing, aggressive, and self-defeating humor, are connected to different brain areas. The thesis will also include an overview of how humor in general, and especially three factors of humor including, processing, appreciation, and comprehension is connected to different brain areas. The present study found a connection between these three factors of humor and activation in the prefrontal cortex (PFC) and inferior frontal gyrus (IFG). The four humor styles were all connected to activity in the midbrain and nucleus accumbens (NAc), though they were found to differ in other parts of the brain. Affiliative humor and self-enhancing humor are humor styles found to share activation of similar brain areas, whereas self-enhancing and aggressive humor was found to the least extent share activation of the same brain areas. No neural differences in relation to the four humor styles have been found between men and woman, or between cultures.

  • 184.
    Hjelmblink, Finn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Understanding Life After Stroke2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke is an acute, neurological dysfunction of vascular origin with sudden occurrence and it influences physical, cognitive and psychological functions. Initial treatment aims at eliminating or reducing the brain damage. Soon, however, the influence of the stroke on the entire life of stroke survivors has to be considered.

    This thesis explores the meaning of life after stroke to 19 elderly stroke survivors during the first year post stroke. Survivors were interviewed twice and the interviews were analysed through qualitative methods.

    Study I was about four survivors who delayed hospital arrival far beyond time limits for trombolytic treatment. The survivors had a strong need for control of body, autonomy and integrity and they demanded to be encountered in consultations as a person by a person. To make them search for emergency evaluation in time might demand an emergency care treating them according to these needs.

    In Study II the voice of an aphasic survivor was heard. Because of the damaged language his rehabilitation unilaterally focussed on language training and his need for comprehensive support and planning for the future was not observed. Implementation of a qualitative research method for text analysis adapted to practical use in dialogues with aphasic persons might ensure these survivors an adequate rehabilitation.

    Study III showed how time models in narratives helped stroke survivors to overcome uncertainty and recreate narrative coherence in their lives. Professionals can support survivors through revealing and reinforcing the meaning of these models.

    Study IV found that the meaning of rehabilitation to stroke survivors was social reintegration. Many probably did not socially reintegrate because their own strategies and subjectively experienced disabilities were unacknowledged in their rehabilitation. Through integrating illness-as-lived perspectives with biomedical perspectives, subjective dysfunctions and rehabilitation strategies of survivors could be acknowledged in stroke rehabilitation.

  • 185.
    Holdstock, Camilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Gastric Bypass in Morbid Obesity: Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.

    We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.

    We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.

    We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.

    We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.

    In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.

  • 186.
    Hultling, C
    et al.
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Rosenlund, B
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Fridström, M
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Sjöblom, P
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Hillensjö, T
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Assisted ejaculation and in-vitro fertilization in the treatment of infertile spinal cord-injured men: the role of intracytoplasmic sperm injection.1997In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, no 3, p. 499-502Article in journal (Refereed)
    Abstract [en]

    The objective of the present longitudinal descriptive study was to extend previous observations on the benefit of in-vitro fertilization (IVF) in cases of anejaculatory infertility due to spinal cord injuries (SCI) and to report results achieved by intracytoplasmic sperm injection (ICSI). The study was performed in a national referral unit for SCI, Spinalis SCI Research Unit, the Karolinska Institute. The patient material consisted of couples with SCI men seeking treatment for their infertility. The inclusion criteria were: stable relationship, motile spermatozoa in a diagnostic sample and no female contraindications. Spermatozoa were retrieved through electroejaculation or vibratory stimulation. If the sperm quality was judged to be sufficient, standard IVF was performed. ICSI was employed if the semen quality was extremely poor. We have treated 25 couples in 52 cycles, leading to 81 ovum retrievals and 47 embryo transfers. Total sperm counts were very variable (0.01-978 x 10(6)). Before the introduction of ICSI the fertilization rate was 30%. ICSI increased the fertilization rate to 88%. There was no association between the pregnancy rate and the sperm count, level of injury or fertilization technique. A total of 16 clinical pregnancies was established, leading to 11 deliveries. This gives a cumulative pregnancy rate per couple of 56%.

  • 187.
    Hysing, Tommy
    Örebro University, Department of Clinical Medicine.
    Uppföljning av TSH`s beslutsgränser för analys av TPO-antikroppar2006Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Mätning av autoantikroppar mot tyreoperoxidas (TPO) är en

    viktig del för att diagnostisera autoimmun tyreoideafunktions rubbning. Hos det stora flertalet som har en autoimmun tyreoidea sjukdom hittar man TPO-antikroppar. Vid hypotyreos är det av betydelse att se om det finns TPO-antikroppar för att påvisa eller utesluta autoimmunitet som orsak till hypotyreosen.

    Ett problem är att det inte finns något allmänt accepterat referensintervall för TPO-antikroppar. I Sverige varierar det mellan 2 och 60 kIU/l beroende på vilken mätmetod som används.

    Syftet med denna undersökning är att se hur vanligt det är med förhöjda värden för tyreoidea stimulerande hormon (TSH) och hur fördelningen av antikroppar för tyreoidea peroxidas (TPO-antikroppar) ser ut vid normala och subnormala TSH-värden.

    De serumprover som ingick i undersökningen analyserades med en fluoroimmunoassay teknik på instrumentet AutoDELFIAÔ , Perkin-Elmer. Proverna valdes slumpmässigt från de rutinprover som kommer till laboratoriet.

    Mellan 8 – 13 % av de undersökta patientproverna har en lätt förhöjning (4,3 – 6,0 mIU/l) av TSH-värdena. Totalt för alla värden mer än 4,3 mIU/l är 15 %.

    Kvinnor har en högre andel av TPO-antikroppar jämfört med män vilket andra undersökningar också visat.

    Referensintervallet, < 35 kIU/l, för TPO-antikroppar är relevant gentemot frågeställningen. I den undersökta populationen är det ett prov som hamnar utanför detta intervall.

    44 % hade förhöjda värden på TPO-antikroppar vid måttligt förhöjda TSH värden, detta indikerar att analys av TPO-antikroppar bör göras när TSH visar värden > 4,3 mIU/l.

    Den metodjämförelse som gjordes mellan fluoroimmunoassay och kemiluminiscens visar på dålig korrelation.

    Denna undersökning är en pilotstudie för att kunna gå vidare med frågeställningar som

    - kan man korrigera på något sätt för de olikheter som uppenbarligen finns mellan de olika mätmetoderna

    - kan man ta bort spädningssteget i fluoroimmunoassay-metoden för att därigenom kunna sänka referensgränsen

  • 188.
    Hägglöf, Christina
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Josefsson, Andreas
    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.
    Paulsson, Janna
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Östman, Arne
    Stromal PDGFRbeta expression in prostate tumors and non-malignant prostate tissue predicts prostate cancer survival2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 5, p. e10747-Article in journal (Refereed)
    Abstract [en]

    The study revealed a number of novel associations between stromal PDGFRbeta expression in prostate tumors and several important clinical characteristics, including survival.

  • 189.
    Höglund, K.
    et al.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Uppsala, Sweden..
    Lequarre, A. -S
    Ljungvall, I.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Uppsala, Sweden..
    Mc Entee, K.
    Univ Libre Bruxelles, Fac Med, Brussels, Belgium..
    Merveille, A. -C
    Wiberg, M.
    Univ Helsinki, Fac Vet Med, Helsinki, Finland..
    Gouni, V.
    Univ Paris Est Creteil, Ecole Natl Vet Alfort, Paris, France.;Hop Henri Mondor, INSERM, U955, Equipe 3, F-94010 Creteil, France..
    Willesen, J. Lundgren
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Hanås, S.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Uppsala, Sweden.;Evidensia Anim Clin, Vasteras, Sweden..
    Wess, G.
    Univ Munich, Munich, Germany..
    Sorensen, L. Mejer
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Tiret, L.
    Univ Paris Est Creteil, Ecole Natl Vet Alfort, Paris, France.;Hop Henri Mondor, INSERM, IMRB U955, Equipe BNMS 10, F-94010 Creteil, France..
    Kierczak, Marcin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Forsberg, S. K. G.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Uppsala, Sweden..
    Seppälä, E.
    Univ Helsinki, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst MIT & Harvard, Cambridge, MA USA..
    Lohi, H.
    Univ Helsinki, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Chetboul, V.
    Univ Paris Est Creteil, Ecole Natl Vet Alfort, Paris, France.;Hop Henri Mondor, INSERM, U955, Equipe 3, F-94010 Creteil, France..
    Fredholm, M.
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Häggstrom, J.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Uppsala, Sweden..
    Effect of Breed on Plasma Endothelin-1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs2016In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 30, no 2, p. 566-573Article in journal (Refereed)
    Abstract [en]

    Background: There are breed differences in several blood variables in healthy dogs.

    Objective: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration.

    Animals: Five-hundred and thirty-one healthy dogs of 9 breeds examined at 5 centers (2-4 breeds/center).

    Methods: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis.

    Results: Median ET-1 concentration was 1.29 (interquartile range [IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48-1.10) ng/mL/h in all dogs. Overall, breed differences were found in ET-1 and cortisol concentrations, and renin activity (P < .0001 for all). Pair-wise comparisons between breeds differed in 67% of comparisons for ET-1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET-1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET-1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers.

    Conclusions and Clinical Importance: Breed variation might be important to take into consideration when interpreting test results in clinical studies.

  • 190.
    Idberg, Anna
    et al.
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    Ulbaek, Lena
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    Äldre kvinnors sexuella välbefinnande2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Sexuality among older persons are just as important to quality of life as it is to younger people. The sexual ability and sexual needs will continue up in years. An active sex life is good for the sexual satisfaction.

    Objective: The objective was to examine factors that have a positive impact on older women's sexual satisfaction.

    Method: A quantitative method was used on already collected material, consisting of extensive surveys collected during the years of 2000-2003. The main variable sexual satisfaction has been tested against several relevant variables. The analytical methods used were chi-square test, univariate analysis and finally a multivariate analysis. We chose to examine the positive odds ratio, (POR), that affects the sexual satisfaction positively. Results: Among the respondents 25% estimated that they had very good sexual satisfaction. The results indicates to be appreciated at home and happy with ones own body affected the sexual satisfaction positively. Having a good mood and not have passed menopause also have a positive affect of the older womens sexual satisfaction.

  • 191. Ingvast-Larsson, C.
    et al.
    Högberg, M.
    Mengistu, U.
    Olsén, L.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Olsson, K.
    Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids2011In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 34, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, C(max) was 736 ± 184 ng/mL, T(max) was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.

  • 192. Ingvast-Larsson, C.
    et al.
    Svartberg, K.
    Hydbring-Sandberg, E.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Olsson, K.
    Clinical pharmacology of buprenorphine in healthy, lactating goats2007In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 30, no 3, p. 249-256Article in journal (Refereed)
    Abstract [en]

    The pharmacokinetics and the effects of the opioid buprenorphine on behavior, cardiovascular parameters, plasma concentrations of cortisol and vasopressin were studied in the goat. After intravenous injection at a dosage of 0.02 mg/kg bw, the terminal half-life was 73.8 ± 19.9 min (mean ± SD), the apparent volume of distribution 5.22 ± 1.01 L/kg, and total body clearance 79.1 ± 18.5 mL/min/kg. After intramuscular administration of buprenorphine at the same dosage, bioavailability was complete and clearance was 54.7 ± 16.6 mL/min/kg. Heart rate, blood pressure and concentrations of cortisol and vasopressin in plasma increased after drug administration. The goats became agitated and stopped ruminating. The effects were more pronounced the first time the animals received the drug, especially the influence on the hormone levels. The concentrations of cortisol and vasopressin in plasma remained unaffected after the second dose despite a wash-out period of 3–6 weeks. Buprenorphine may be an unsuitable drug in goats because of the profound inhibition of rumination and the agitation it causes. The short half-life of buprenorphine may limit its use if long-term analgesia is required but be advantageous if a short acting drug is desirable.

  • 193. Ingvast-Larsson, Carina
    et al.
    Holgersson, Anja
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Lagerstedt, Anne-Sofie
    Olsson, Kerstin
    Clinical pharmacology of methadone in dogs2010In: Veterinary Anaesthesia and Analgesia, ISSN 1467-2987, E-ISSN 1467-2995, Vol. 37, no 1, p. 48-56Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs. Study design Randomized, cross-over, experimental trial. Animals Nine adult dogs (beagle and beagle cross breeds), four males and five females. Methods Methadone hydrochloride, 0.4 mg kg-1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol. Results After IV administration, the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL-1 (mean +/- SD), the terminal half-life was 3.9 +/- 1.0 hours, the volume of distribution 9.2 +/- 3.3 L kg-1 and plasma clearance 27.9 +/- 7.6 mL minute-1 kg-1. After SC administration, time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL-1, the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic. Conclusion and clinical relevance When methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.

  • 194.
    Isoz, Isabelle
    Umeå University, Faculty of Medicine, Medical Biochemistry and Biophsyics.
    Role of yeast DNA polymerase epsilon during DNA replication2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Each cell division, the nuclear DNA must be replicated efficiently and with high accuracy to avoid mutations which can have an effect on cell function. There are three replicative DNA polymerases essential for the synthesis of DNA during replication in eukaryotic cells. DNA polymerase α (Pol α) synthesize short primers required for DNA polymerase δ (Pol δ) and DNA polymerase ε (Pol ε) to carry out the bulk synthesis. The role of Pol δ and Pol ε at the replication fork has been unclear. The aim of this thesis was to examine what role Pol ε has at the replication fork, compare the biochemical properties of Pol δ and Pol ε, and to study the function of the second largest and essential subunit of Pol ε, Dpb2.

    To identify where Pol ε replicates DNA in vivo, a strategy was taken where the active site of Pol ε was altered to create a mutator polymerase leaving a unique error-signature. A series of mutant pol ε proteins were purified and analyzed for enzyme activity and fidelity of DNA synthesis. Two mutants, M644F and M644G, exhibited an increased mutation rate and close to normal polymerase activity. One of these, the M644G gave rise to a specific increase of mismatch mutations resulting from T-dTMP mis-pairing during DNA synthesis in vitro. The M644G mutant was introduced in yeast strains carrying a reporter gene, URA3, on either side of an origin in different orientations. Mutations which inactivated the URA3 gene in the M644G mutant strains were analyzed. A strand specific signature was found demonstrating that Pol ε participates in the synthesis of the leading strand.

    Pol δ and Pol ε are both stimulated by the processivity clamp, PCNA, in in vitro replication assays. To clarify any differences they were challenged side by side in biochemical assays. Pol ε was found to require that single-stranded template (ssDNA) was entirely coated with RPA, whereas Pol δ was much less sensitive to uncoated ssDNA. The processivity of Pol δ was stimulated to a much higher degree by PCNA than of Pol ε. In presence of PCNA the processivity of Pol δ and Pol ε was comparable. In contrast, Pol ε was approximately four times slower than Pol δ when replicating a single-primed circular template in the presence of all accessory proteins and an excess of polymerase. The biochemical characterization of the system suggests that Pol ε and Pol δ are loaded onto the PCNA-primer-ternary complex by separate mechanisms. A model is proposed where the loading of Pol ε onto the leading strand is independent of the PCNA interaction motif which is required by enzymes acting on the lagging strand.

    The essential gene DPB2 encodes for the second largest subunit of Pol ε. We carried out a genetic screen in S.cerevisiae and isolated a lethal mutant allele of dpb2 (dpb2-200). When over-expressed together with the remaining three subunits of Polε, Pol2, Dpb3 and Dpb4, the dpb2-201 did not copurify. The biochemical property of Pol2/Dpb3/Dpb4 complex was compared with wild-type four-subunit Pol ε (Pol2/Dpb2/Dpb3/Dpb4) and a Pol2/Dpb2 complex in replication assays. The absence of Dpb2 in the complex did not significantly affect the specific activity or the processivity, but gave a slightly reduced efficiency in holoenzyme assays when compared to wild-type four-subunit Pol ε. We propose that Dpb2 is not essential for the enzyme activity of Pol ε.

  • 195.
    Ivarsson, Niklas
    Örebro University, School of Health and Medical Sciences.
    An inquiry to a possible fatty acid metabolism defect due to carnitine deficiency in patient fibroblast, analysed with a tritium release assay2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The formation of tritiated water from [9,10-3H]-palmitic acid has been recommended as an adequate screening method to detect patients with fatty acid oxidation disorders. Intact cultured fibroblasts from three patients (a young girl, the Mother and Grandfather) plus controls have been studied using this method with 3H-palmitic acid at the presence or absent of excess of carnitine. The patients were suspected to have an aberrant carnitine transport over the cell membrane, which probably could secondary affects the fatty acid metabolism.

    No differences were found in β-oxidation of 3H-palmytic acid between fibroblasts from patients compared to healthy controls. Excess of carnitine did not shown any effect on β-oxidation of 3H-palmytic acid either

    The results showed that the patients’ fibroblasts did not have a decreased β-oxidation capacity and no significant difference when treated with carnitine compared to the matched healthy controls. This study cannot link the patient’s symptoms with an aberrant carnitine transport over cell membrane or any defect in β-oxidation of fatty acid metabolism.

  • 196. Jacobsen, M
    et al.
    Kracht, S S
    Esteso, G
    Cirera, S
    Edfors, I
    Archibald, A L
    Bendixen, C
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fredholm, M
    Jørgensen, C B
    Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs2010In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 41, no 1, p. 21-25Article in journal (Refereed)
    Abstract [en]

    Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.

  • 197. Jacobsen, M
    et al.
    Kracht, SS
    Esteso, G
    Cirera, S
    Edfors, Inger
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Archibald, AL
    Bendixen, C
    Anderson, L
    Fredholm, M
    Jorgensen, CB
    Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs.2010In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 41, p. 21-25Article in journal (Refereed)
    Abstract [en]

    P>Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.

  • 198.
    Jakobsson, Christine
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Uppsala Centre for Sustainable Development, CSD Uppsala, The Baltic University Programme.
    Norrgren, Leif
    Swedish University of Agricultural Sciences.
    Karlsson, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Uppsala Centre for Sustainable Development, CSD Uppsala, The Baltic University Programme.
    Levengood, Jeffrey
    University of Illinois at Urbana-Champaign.
    Preface2012In: Sustainable Agriculture / [ed] Christine Jakobsson, Uppsala: Baltic University Press , 2012, 1, p. 8-10Chapter in book (Other (popular science, discussion, etc.))
  • 199.
    Jegefalk, Annelie
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Csiffary, Thomas
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Ökat kreatinintag = Ökad kraft: en träningsstudie om kreatinets prestationshöjande effekt och korrelationen mellan styrkeökning och kreatinupptag.2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet med studien var att undersöka kreatinets prestationshöjande effekt på styrka efter en sex dagars kreatinuppladdning samt undersöka om en korrelation mellan kreatinupptag och styrkeförändring förelåg. Frågeställningar var:

    Hur skiljer sig den statiska styrkan i biceps efter en sex dagar lång kreatinuppladdning?

    Hur skiljer sig den dynamiska styrkan i bänkpress efter en sex dagar lång kreatinuppladdning?

    Finns det någon korrelation mellan förändring av styrka och upptag av kreatin?

    Metod

    Studien genomfördes på 22 fysiskt aktiva friska svenska män och kvinnor (13 män, 9 kvinnor) som delades in i antingen en kreatingrupp (n=12) eller en kontrollgrupp (n=10). Båda grupperna genomförde tre testtillfällen (T1, T2, T3) där T1 syftades till att mäta upp deras 1RM. Vid T2 och T3 mättes deltagarnas statiska styrka i biceps (höger och vänster) samt deras dynamiska styrka i bänkpress. Mellan T2 och T3 gavs kreatingruppen 20 gram kreatin om dagen uppdelat vid 4 olika tillfällen i 6 dagar. En 24-timmars urininsamling genomfördes på samtliga deltagare i kreatingruppen under den andra dagen på kreatinuppladdningen för att mäta deras kreatinupptag.

    Resultat

    Kreatingruppens medelökning i bicepsövningen motsvarade som lägst 2,08 sekunder och som högst 9,33 sekunder där den största ökningen skedde under set 1 för höger arm. I den dynamiska bänkpressen visade kreatingruppen en ökning motsvarande 3,41 repetitioner. Inga signifikanta höjningar sågs för kontrollgruppen under något av seten. Inga korrelationer mellan kreatinupptag och styrkeförändring kunde påvisas i studien.

    Slutsats

    Resultaten från föreliggande studie indikerar på att ett oralt kreatinintag på 20 (4 tillfällen á 5 gram) gram kreatin om dagen i 6 dagar ger en förhöjd isometrisk prestation i biceps under tre set med 60 sekunders vila (p<0,05 under fem av sex set). Intaget tycks även resultera i en medelökning på 3,41 utförda repetitioner under det första setet i en dynamisk bänkpress (67 % av 1RM som belastning). Dessa resultat bör emellertid beskådas kritiskt sedan studien inte använde sig av något placebopreparat, vilket kan ha inneburit att en placeboeffekt förelåg.

  • 200.
    Jemtå, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Children and Adolescents Living with Mobility Impairment2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: This thesis aims to describe perceived overall well-being, coping strategies, experiences of intimacy and sexuality, and global and dimension-specific self-esteem among children and adolescents with mobility impairment.

    Methods: The study included 141 children and adolescents aged 7–18 years with mobility impairment. Data was gathered by comprehensive semi-structured interviews and the self-report inventories “Children’s Coping Strategies Checklist” (CCSC) and “I Think I am”. Perceived overall well-being was measured by the nine-grade visual “Snoopy scale”. Motor function and pain were measured by the BL motor assessment, and independence or dependence by Katz Index of Independence in Activities of Daily Living.

    Results: The majority reported a favourable level of perceived overall well-being and positive global and dimension-specific self-esteem. Lower global self-esteem was significantly related to: greater age, being a first-generation immigrant, having an acquired disease or injury and experience of pain, while lower level of perceived overall well-being was significantly related to all of these in addition to not living with both parents. Generally, children and adolescents identified themselves as sexual beings and most expressed future aspirations as living together with partner having children. However, many had limited or no experience of partner-related intimacy and sexual activities, and socio-demographic and disability characteristics had a marginal influence. A history of sexual abuse was reported by 7% in the age cohort 13–18 years. A four-dimensional model of coping strategies including “active coping”, “distraction”, “avoidance” and “support seeking” strategies provided an adequate fit to the CCSC data. Three of the four strategies, all except “avoidance”, were significantly related to several demographic and disability features. Well-being was not significantly related to coping strategies, although the higher the trust in the strategies, the higher the estimation of well-being.

    Conclusion: The understanding of vulnerability factors as well as identification of coping strategies among children and adolescents with mobility impairment is essential for providing proper care, treatment and support during childhood and adolescence.

1234567 151 - 200 of 444
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf