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  • 1.
    Akanda, Nesar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.

    Delarbeten
    1. Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli
    Öppna denna publikation i ny flik eller fönster >>Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli
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    2005 (Engelska)Ingår i: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 12, nr 8, s. 1134-1140Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Apoptotic cell death is an essential process in the development of the central nervous system and in the pathogenesis of its degenerative diseases. Efflux of K+ and Cl- ions leads to the shrinkage of the apoptotic cell and facilitates the activation of caspases. Here, we present electrophysiological and immunocytochemical evidences for the activation of a voltage-dependent anion channel (VDAC) in the plasma membrane of neurons undergoing apoptosis. Anti-VDAC antibodies blocked the channel and inhibited the apoptotic process. In nonapoptotic cells, plasma membrane VDAC1 protein can function as a NADH (-ferricyanide) reductase. Opening of VDAC channels in apoptotic cells was associated with an increase in this activity, which was partly blocked by VDAC antibodies. Hence, it appears that there might be a dual role for this protein in the plasma membrane: (1) maintenance of redox homeostasis in normal cells and (2) promotion of anion efflux in apoptotic cells.

    Nyckelord
    VDAC, voltage-dependent anion channel; STS, staurosporine; PS, phosphatidylserine
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14278 (URN)10.1038/sj.cdd.4401646 (DOI)
    Tillgänglig från: 2007-02-01 Skapad: 2007-02-01 Senast uppdaterad: 2018-01-25
    2. Voltage-dependent anion channels (VDAC) in the plasma membrane play a critical role in apoptosis in differentiated hippocampal neurons but not in neural stem cells
    Öppna denna publikation i ny flik eller fönster >>Voltage-dependent anion channels (VDAC) in the plasma membrane play a critical role in apoptosis in differentiated hippocampal neurons but not in neural stem cells
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    2008 (Engelska)Ingår i: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 7, nr 20, s. 3225-3234Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    microRNAs (miRNAs) are small non-coding RNAs that regulate a large variety of cellular processes including differentiation, apoptosis and proliferation. Several miRNAs display defective expression patterns in human tumors with the consequent alteration of target oncogene or tumor suppressor genes. Many of these miRNAs modulate the major proliferation pathways through direct interaction with critical regulators such as RAS, PI3K/PTEN or ABL, as well as members of the retinoblastoma pathway, Cyclin-CDK complexes or cell cycle inhibitors of the INK4 or Cip/Kip families. A complex interplay between miRNAs and MYC or E2F family members also exists to modulate cell cycle-dependent transcription during normal or tumoral proliferation. The ability of miRNAs to modulate these proliferation pathways may have relevant implications not only in physiological or developmental processes but also in tumor progression or cancer therapy.

    Nyckelord
    patch clamp, single-channel recordings, apoptosis, VDAC, hippocampal neurons, neural stem cells, sodium channels
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-47952 (URN)10.4161/cc.7.20.6831 (DOI)
    Tillgänglig från: 2009-10-11 Skapad: 2009-10-11 Senast uppdaterad: 2018-01-25
    3. Biophysical properties of the apoptosis-inducing plasma membrane voltage-dependent anion channel
    Öppna denna publikation i ny flik eller fönster >>Biophysical properties of the apoptosis-inducing plasma membrane voltage-dependent anion channel
    2006 (Engelska)Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 90, nr 12, s. 4405-4417Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Ion channels in the plasma membrane play critical roles in apoptosis. In a recent study we found that a voltage-dependent anion channel in the plasma membrane (VDACpl) of neuronal hippocampal cell line (HT22) cells was activated during apoptosis and that channel block prevented apoptosis. Whether or not VDACpl is identical to the mitochondrial VDACmt has been debated. Here, we biophysically characterize the apoptosis-inducing VDACpl and compare it with other reports of VDACpls and VDACmt. Excised membrane patches of apoptotic HT22 cells were studied with the patch-clamp technique. VDACpl has a large main-conductance state (400 pS) and occasionally subconductance states of µ28 pS and 220 pS. The small subconductance state is associated with long-lived inactivated states, and the large subconductance state is associated with excision of the membrane patch and subsequent activation of the channel. The open-probability curve is bell shaped with its peak around 0mV and is blocked by 30µM Gd3+. The gating can be described by a symmetrical seven-state model with one open state and six closed or inactivated states. These channel properties are similar to those of VDACmt and other VDACpls and are discussed in relation to apoptosis.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14280 (URN)10.1529/biophysj.105.080028 (DOI)
    Tillgänglig från: 2007-02-01 Skapad: 2007-02-01 Senast uppdaterad: 2018-01-25
    4. Sucrose reduces the current through plasma membrane voltage-dependent anion channels (VDACpl) mainly by reducing the open probability
    Öppna denna publikation i ny flik eller fönster >>Sucrose reduces the current through plasma membrane voltage-dependent anion channels (VDACpl) mainly by reducing the open probability
    Manuskript (Övrigt vetenskapligt)
    Identifikatorer
    urn:nbn:se:liu:diva-14281 (URN)
    Tillgänglig från: 2007-02-01 Skapad: 2007-02-01 Senast uppdaterad: 2010-01-13
  • 2.
    Amundin, Mats
    et al.
    Kolmården Wildlife Park.
    Hållsten, Henrik
    Filosofiska institutionen, Stockholms universitet.
    Eklund, Robert
    Linköpings universitet, Institutionen för kultur och kommunikation, Avdelningen för språk och kultur. Linköpings universitet, Filosofiska fakulteten.
    Karlgren, Jussi
    Kungliga Tekniska Högskolan.
    Molinder, Lars
    Carnegie Investment Bank, Swedden.
    A proposal to use distributional models to analyse dolphin vocalisation2017Ingår i: Proceedings of the 1st International Workshop on Vocal Interactivity in-and-between Humans, Animals and Robots, VIHAR 2017 / [ed] Angela Dassow, Ricard Marxer & Roger K. Moore, 2017, s. 31-32Konferensbidrag (Refereegranskat)
    Abstract [en]

    This paper gives a brief introduction to the starting points of an experimental project to study dolphin communicative behaviour using distributional semantics, with methods implemented for the large scale study of human language.

  • 3.
    Andersson, Anna
    Linköpings universitet, Hälsouniversitetet, Hälsouniversitetets läkarutbildning.
    Adjuvant and Down-Staging Treatment with Imatinib in Gastrointestinal Stromal Tumours2008Självständigt arbete på avancerad nivå (yrkesexamen), 10 poäng / 15 hpStudentuppsats
    Abstract [en]

    Background: GISTs are gastrointestinal mesenchymal tumours that express the type III receptor tyrosine kinase KIT. The KIT proto-oncogene encodes the receptor KIT. Most GISTs have gain-of-function mutations in the KIT or PDGFRA gene. The tyrosine kinase is therefore continuously activated leading to ligand-independent dimerization. Imatinib mesylate (Glivec®) is considered to be the first-line palliative treatment. The activated form of the KIT receptor tyrosine kinase is inhibited by imatinib. The aim of the study was to compare the survival of patients treated with either adjuvant or down-staging imatinib with historic controls treated with radical surgery (R0) only.

    Methods: A historic control group was chosen from a population-based series from western Sweden (population 1.6 million) that matched the adjuvant (n=23) and down-staging (n=7) groups respectively. Mutation analysis was performed in all cases with bidirectional direct sequencing. The recurrence-free survival was calculated.

    Results: There was only one recurrence (4 %) in the adjuvant group, and no recurrences in the down-staging study group, compared to 32/48 patients (67 %) in the control group. Tumour size decreased in diameter from 20 cm to 11 cm with down-staging treatment.

    Conclusion: Adjuvant imatinib improves recurrence-free survival in R0 resected patients. Down-staging treatment with imatinib is recommended for patients with large tumours or metastases. The importance of mutation analysis was established.

  • 4.
    Atikuzzaman, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Seminal Influence on the Oviduct: Mating and/or semen components induce gene expression changes in the pre-ovulatory functional sperm reservoir in poultry and pigs2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Internal fertilization occurs in birds and eutherian mammals. Foetal development, however, is either extra- respectively intra-corpore (egg vs uterus). In these animal classes, the female genital tract stores ejaculated spermatozoa into a restricted oviductal segment; the functional pre-ovulatory sperm reservoir, where they survive until ovulation/s occur. Paradoxically, this immunologically foreign sperm suspension in seminal fluid/plasma, often microbiologically contaminated, ought to be promptly eliminated by the female local immune defence which, instead, tolerates its presence. The female immune tolerance is presumably signalled via a biochemical interplay of spermatozoa, as well as the peptides and proteins of the extracellular seminal fluid, with female epithelial and immune cells. Such interplay can result in gene expression shifts in the sperm reservoir in relation to variations in fertility. To further aid our understanding of the underlying mechanisms, this thesis studied the proteome of the seminal fluid (using 2D SDS-PAGE and mass spectrometry) including cytokine content (using Luminex and/or ELISA) of healthy, sexually mature and fertile boars and cocks. As well, gene expression changes (using cDNA microarray) in the oviductal sperm reservoirs of sexually-mature females, mated or artificially infused with homologous sperm-free seminal fluid/plasma were studied. Pigs were of commercial, fertility-selected modern breeds (Landrace), while chicken belonged to the ancestor Red Junglefowl (RJF, low egg laying-capacity), a selected egg-layer White Leghorn (WL) and of their Advanced Intercross Line (AIL). Ejaculates were manually collected as single sample in cocks or as the sperm-rich fraction [SRF] and the post- SRF fraction in boars to harvest seminal fluid/plasma for proteome/cytokine and infusion-studies. Oviducts were retrieved for gene-expression analyses via microarray immediately post-mortem (chicken) or at surgery (pig), 24 h after mating or genital infusion. In pigs, the protein-rich seminal plasma showed the highest amounts of cytokines [interferon-γ, interferon gamma-induced protein 10 (IP-10/CXCL10), macrophage derived chemokine (MDC/CCL22), growth-regulated oncogene (GRO/CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemo-attractant protein-1 (MCP-1/ CCL2), interleukin (IL)-6, IL-8/CXCL8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-β1-3) in the larger, protein-rich and sperm-poor post-SRF, indicating its main immune signalling influence. Chicken showed also a plethora of seminal fluid proteins with serum albumin and ovotransferrin being conserved through selection/evolution. However, they showed fewer cytokines than pigs, as the anti-inflammatory/immune-modulatory TGF-β2 or the pro-inflammatory CXCL10. The RJF contained fewer immune system process proteins and lacked TGF-β2 compared to WL and AIL, suggesting selection for increased fertility could be associated with higher expression of immune-regulating peptides/proteins. The oviductal sperm reservoir reacted in vivo to semen exposure. In chicken, mating significantly changed the expression of immune-modulatory and pH-regulatory genes in AIL. Moreover, modern fertile pigs (Landrace) and chicken (WL), albeit being taxonomically distant, shared gene functions for preservation of viable sperm in the oviduct. Mating or SP/SF-infusion were able to change the expression of comparable genes involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12). The results of the thesis demonstrate that both mating and components of the sperm-free seminal fluid/plasma elicit gene expression changes in the pre-ovulatory female sperm reservoir of chickens and pigs, some conserved over domestication and fertility-selection.

    Delarbeten
    1. The Seminal Plasma of the Boar is Rich in Cytokines, with Significant Individual and Intra-Ejaculate Variation
    Öppna denna publikation i ny flik eller fönster >>The Seminal Plasma of the Boar is Rich in Cytokines, with Significant Individual and Intra-Ejaculate Variation
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    2015 (Engelska)Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, nr 6, s. 523-532Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Problem The boar, as human, sequentially ejaculates sperm-rich and sperm-poor fractions. Seminal plasma (SP) spermadhesins (PSP-I/PSP-II) induce a primary endometrial inflammatory response in female sows, similar to that elicited by semen deposition in other species, including human. However, the SP is also known to mitigate such response, making it transient to allow for embryo entry to a cleansed endometrium. Although cytokine involvement has been claimed, the exploration of cytokines in different SP fractions is scarce. This study determines Th1, Th2, Th17 and Th3 cytokine profiles in specific ejaculate SP fractions from boars of proven fertility. Methods SP samples from the sperm-rich fraction (SRF) and the sperm-poor post-SRF fraction (post-SRF) of manually collected ejaculates from eight boars (four ejaculates per boar) were analysed by commercial multiplex bead assay kits (Milliplex MAP, Millipore, USA) for interferon-gamma, interferon gamma-induced protein 10, macrophage-derived chemokine, growth-regulated oncogene, granulocyte-macrophage colony-stimulating factor, monocyte chemo-attractant protein-1, interleukins (IL)-6, IL-8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-beta 1-beta 3. Results Cytokine concentrations differed between the ejaculate fractions among boars, being highest in the post-SRF. Conclusion Boar SP is rich in Th1, Th2, Th17 and Th3 cytokines, with lowest concentrations in the sperm-peak-containing fraction, indicating its main immune influence might reside in the larger, protein-rich sperm-poor post-SRF.

    Ort, förlag, år, upplaga, sidor
    WILEY-BLACKWELL, 2015
    Nyckelord
    Ejaculate fractions; immunomodulatory molecules; pig; seminal plasma peptides
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-124497 (URN)10.1111/aji.12432 (DOI)000367669300006 ()26412440 (PubMedID)
    Anmärkning

    Funding Agencies|MINECO Madrid (Spain) [AGL2012-39903]; FEDER funds (EU); Formas (Stockholm, Sweden); MECD (Madrid, Spain); Seneca Foundation (Murcia, Spain)

    Tillgänglig från: 2016-02-02 Skapad: 2016-02-01 Senast uppdaterad: 2017-11-30
    2. Selection for higher fertility reflects in the seminal fluid proteome of modern domestic chicken
    Öppna denna publikation i ny flik eller fönster >>Selection for higher fertility reflects in the seminal fluid proteome of modern domestic chicken
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    2017 (Engelska)Ingår i: Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics, ISSN 1744-117X, E-ISSN 1878-0407, Vol. 21, s. 27-40Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The high egg-laying capacity of the modern domestic chicken (i.e. White Leghorn, WL) has arisen from the low egg-laying ancestor Red Junglefowl (RJF) via continuous trait selection and breeding. To investigate whether this long-term selection impacted the seminal fluid (SF)-proteome, 2DE electrophoresis-based proteomic analyses and immunoassays were conducted to map SF-proteins/cytokines in RJF, WL and a 9th generation Advanced Intercross Line (AIL) of RJF/WL-L13, including individual SF (n = 4, from each RJF, WL and AIL groups) and pools of the SF from 15 males of each group, analyzed by 2DE to determine their degree of intra-group (AIL, WL, and RJF) variability using Principal Component Analysis (PCA); respectively an inter-breed comparative analysis of intergroup fold change of specific SF protein spots intensity between breeds. The PCA clearly highlighted a clear intra-group similarity among individual roosters as well as a clear inter-group variability (e.g. between RJF, WL and AIL) validating the use of pools to minimize confounding individual variation. Protein expression varied considerably for processes related to sperm motility, nutrition, transport and survival in the female, including signaling towards immunomodulation. The major conserved SF-proteins were serum albumin and ovotransferrin. Aspartate aminotransferase, annexin A5, arginosuccinate synthase, glutathione S-transferase 2 and l-lactate dehydrogenase-A were RJF-specific. Glyceraldehyde-3-phosphate dehydrogenase appeared specific to the WL-SF while angiotensin-converting enzyme, γ-enolase, coagulation factor IX, fibrinogen α-chain, hemoglobin subunit α-D, lysozyme C, phosphoglycerate kinase, Src-substrate protein p85, tubulins and thioredoxin were AIL-specific. The RJF-SF contained fewer immune system process proteins and lower amounts of the anti-inflammatory/immunomodulatory TGF-β2 compared to WL and AIL, which had low levels- or lacked pro-inflammatory CXCL10 compared to RJF. The seminal fluid proteome differs between ancestor and modern chicken, with a clear enrichment of proteins and peptides related to immune-modulation for sperm survival in the female and fertility.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2017
    Nyckelord
    Rooster seminal fluid proteome, Cytokines, Egg-laying capacity, Red Junglefowl, White Leghorn, Advanced intercross line, Chicken
    Nationell ämneskategori
    Biokemi och molekylärbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Genetik och förädling
    Identifikatorer
    urn:nbn:se:liu:diva-132624 (URN)10.1016/j.cbd.2016.10.006 (DOI)000395224100004 ()27852008 (PubMedID)
    Anmärkning

    Funding agencies: Research Council FORMAS, Stockholm, Sweden [221-2011-512]; Ministerio de Ciencia e Innovacion (Madrid, Spain) [BFU2013-42833-P]

    Tillgänglig från: 2016-11-17 Skapad: 2016-11-17 Senast uppdaterad: 2018-05-02Bibliografiskt granskad
    3. Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens
    Öppna denna publikation i ny flik eller fönster >>Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens
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    2015 (Engelska)Ingår i: Reproduction, Vol. 150, nr 6, s. 473-483Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The female chicken, as with other species with internal fertilization, can tolerate the presence of spermatozoa within specialized sperm-storage tubuli (SST) located in the mucosa of the utero-vaginal junction (UVJ) for days or weeks, without eliciting an immune response. To determine if the oviduct alters its gene expression in response to sperm entry, segments from the oviduct (UVJ, uterus, isthmus, magnum and infundibulum) of mated and unmated (control) hens, derived from an advanced inter-cross line between Red Junglefowl and White Leghorn, were explored 24 h after mating using cDNA microarray analysis. Mating shifted the expression of fifteen genes in the UVJ (53.33% immune-modulatory and 20.00% pH-regulatory) and seven genes in the uterus, none of the genes in the latter segment overlapping the former (with the differentially expressed genes themselves being less related to immune-modulatory function). The other oviductal segments did not show any significant changes. These findings suggest sperm deposition causes a shift in expression in the UVJ (containing mucosal SST) and the uterus for genes involved in immune-modulatory and pH-regulatory functions, both relevant for sperm survival in the hen's oviduct.

    Ort, förlag, år, upplaga, sidor
    Bioscientifica, 2015
    Nationell ämneskategori
    Genetik
    Identifikatorer
    urn:nbn:se:liu:diva-122573 (URN)10.1530/REP-15-0253 (DOI)000365344400004 ()26370241 (PubMedID)
    Anmärkning

    Funding agencies: Research Council FORMAS, Stockholm [221-2011-512]; FORMAS [221-2012-667]; VR [621-2011-4802]

    Tillgänglig från: 2015-11-09 Skapad: 2015-11-09 Senast uppdaterad: 2017-02-20
  • 5.
    Avall Lundqvist, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Nordström, L
    Sjövall, K
    Eneroth, P
    Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.1989Ingår i: European journal of gynaecological oncology, ISSN 0392-2936, Vol. 10, nr 6, s. 395-405Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

  • 6.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Atikuzzaman, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Measurement of Activity and Concentration of Paraoxonase 1 (PON-1) in Seminal Plasma and Identification of PON-2 in the Sperm of Boar Ejaculates2015Ingår i: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 82, nr 1, s. 58-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r=-0.763; Pless than0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r=-0.726, Pless than0.05), but positively correlated with sperm concentration (r=0.654, Pless than0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r=0.773; Pless than0.01), but negatively correlated with PON-1 concentration (r=-0.709; Pless than0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters. Mol. Reprod. Dev. 82: 58-65, 2015. (c) 2014 Wiley Periodicals, Inc.

  • 7.
    Bednarska, Olga
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Peripheral and Central Mechanisms in Irritable Bowel Syndrome: in search of links2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.

    This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.

    In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.

    In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.

    In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.

    In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.

    Delarbeten
    1. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
    Öppna denna publikation i ny flik eller fönster >>Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
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    2017 (Engelska)Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, nr 4, s. 948-+Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.

    Ort, förlag, år, upplaga, sidor
    W B SAUNDERS CO-ELSEVIER INC, 2017
    Nyckelord
    Intestinal Permeability; Bacteria; Ketotifen; Inflammation
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:liu:diva-142158 (URN)10.1053/j.gastro.2017.06.051 (DOI)000411835200024 ()28711627 (PubMedID)
    Anmärkning

    Funding Agencies|Stiftelsen Halsofonden, County Council of Ostergotland; Diarrheal Disease Research Centre, Linkoping University; AFA research foundation; Bengt-Ihre fonden, County Council of Ostergotland; Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [FI12/00254]; NIH [R01 DK048351]; [CP10/00502]; [PI13/00935]; [MV16/00028]; [CIBEREHD CB06/04/0021]

    Tillgänglig från: 2017-10-24 Skapad: 2017-10-24 Senast uppdaterad: 2019-11-11
    2. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
    Öppna denna publikation i ny flik eller fönster >>Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
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    2019 (Engelska)Ingår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 21, artikel-id 101602Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2019
    Nyckelord
    Irritable bowel syndrome; Gut epithelial permeability; Resting state fMRI; Brain-gut interactions; Default mode network; Coping skills
    Nationell ämneskategori
    Neurovetenskaper
    Identifikatorer
    urn:nbn:se:liu:diva-155612 (URN)10.1016/j.nicl.2018.11.012 (DOI)000460337700015 ()30472166 (PubMedID)2-s2.0-85056893948 (Scopus ID)
    Anmärkning

    Funding Agencies|AFA FOrskning [AFA140417]; County Council of Ostergotland [SLS-693541, SLS-503411]; Region Ostergotland [LIO-700871, LIO-606201, LIO-536281, LIO-514271]; Deutsche Forschungsgemeinschaft [DFG IC 81/1-1]; Bengt-Ihre Fonden

    Tillgänglig från: 2019-03-20 Skapad: 2019-03-20 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
    3. Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
    Öppna denna publikation i ny flik eller fönster >>Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
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    2019 (Engelska)Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, nr 9, s. 2004-2012Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

    Ort, förlag, år, upplaga, sidor
    Lippincott Williams & Wilkins, 2019
    Nyckelord
    Irritable bowel syndrome, Functional magnetic resonance imaging, Quantitative magnetic resonance spectroscopy, Insula, Visceral pain, Coping
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-160012 (URN)10.1097/j.pain.0000000000001589 (DOI)31045748 (PubMedID)
    Tillgänglig från: 2019-09-02 Skapad: 2019-09-02 Senast uppdaterad: 2019-09-09Bibliografiskt granskad
  • 8.
    Dahlström, Örjan
    et al.
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Institutet för handikappvetenskap (IHV). Linköpings universitet, Filosofiska fakulteten.
    Zetterqvist, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Lundh, Lars-Gunnar
    Department of Psychology, Lund University, Lund, Sweden..
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents2015Ingår i: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 27, nr 1, s. 302-313Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Given that nonsuicidal self-injury (NSSI) is prevalent in adolescents, structured assessment is an essential tool to guide treatment interventions. The Functional Assessment of Self-Mutilation (FASM) is a self-report scale that assesses frequency, methods, and functions of NSSI. FASM was administered to 3,097 Swedish adolescents in a community sample. With the aim of examining the underlying factor structure of the functions of FASM in this sample, the adolescents with NSSI who completed all function items (n = 836) were randomly divided into 2 subsamples for cross-validation purposes. An exploratory factor analysis (EFA) was followed by a confirmatory factor analysis (CFA) using the mean and variance adjusted weighted least squares (WLSMV) estimator in the Mplus statistical modeling program. The results of the EFA suggested a 3-factor model (social influence, automatic functions, and nonconformist peer identification), which was supported by a good fit in the CFA. Factors differentiated between social/interpersonal and automatic/intrapersonal functions. Based on learning theory and the specific concepts of negative and positive reinforcement, the nonconformist peer identification factor was then split into 2 factors (peer identification and avoiding demands). The resulting 4-factor model showed an excellent fit. Dividing social functions into separate factors (social influence, peer identification, and avoiding demands) can be helpful in clinical practice, where the assessment of NSSI functions is an important tool with direct implications for treatment.

  • 9.
    du Preez, Marinus
    et al.
    North-West University, South Africa.
    Govender, Danny
    South African National Parks, South Africa.
    Kylin, Henrik
    Linköpings universitet, Institutionen för tema, Tema Miljöförändring. Linköpings universitet, Filosofiska fakulteten.
    Bouwman, Hindrik
    North-West University, South Africa.
    Metallic elements in Nile Crocodile eggs from the Kruger National Park, South Africa2018Ingår i: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 148, s. 930-941Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Nile Crocodile is the largest predator on the African continent. Recent mass mortalities in the Kruger National Park (KNP) raised concerns about possible influence of pollution. We analysed eggs and their eggshells collected from nests inside the KNP and from a crocodile farm for metallic elements. We found that mercury, selenium, and copper occurred at levels of concern. Eggshells had very high concentrations of iron. Apart from toxicological implications associated with elevated concentrations in eggs, we found iron possibly contributing towards thicker eggshells. Thicker shells may act as a barrier to gas and water exchange, as well as possibly increasing the effort required for the hatchling to emerge from tightly packed shells under sand. Pollutants are transported into the KNP via rivers, and possibly via air. Mercury and copper pollution are waste-, industrial- and mining-related; ecotoxicological concern should therefore be extended to all areas where the four African crocodile species occur. Reptiles are under-represented in ecotoxicological literature in general, and especially from Africa. We know of only one previous report on metals and metalloids in crocodile eggs from Africa (Zimbabwe), published 30 years ago. Reduced fitness, endocrine disruption and effects on behaviour are other possible sub-lethal effects associated with metallic elements that may only become apparent decades later in a long-lived species such as the Nile Crocodile. In the face of habitat destruction, pollution, human population increases, and climate change, further research is needed regarding pollutant concentrations and effects in all African reptiles . The rivers that carry water from outside the park sustain its aquatic life, but also transport pollutants into the KNP. Therefore, improved source mitigation remains an important task and responsibility for all involved.

  • 10.
    Dórea, Fernanda C.
    et al.
    Department of Disease Control and Epidemiology, National Veterinary Institute, Sweden.
    Vial, Flavie
    Epi-Connect, Skogås, Sweden.
    Hammar, Karl
    Linköpings universitet, Institutionen för datavetenskap, Interaktiva och kognitiva system. Linköpings universitet, Tekniska fakulteten. Department of Computer Science and Informatics, Jönköping University, Sweden.
    Lindberg, Ann
    Department of Disease Control and Epidemiology, National Veterinary Institute, Sweden.
    Lambrix, Patrick
    Linköpings universitet, Institutionen för datavetenskap, Databas och informationsteknik. Linköpings universitet, Tekniska fakulteten.
    Blomqvist, Eva
    Linköpings universitet, Institutionen för datavetenskap, Interaktiva och kognitiva system. Linköpings universitet, Tekniska fakulteten.
    Revie, Crawford W.
    Atlantic Veterinary College, University of Prince Edward Island, Canada.
    Drivers for the development of an Animal Health Surveillance Ontology (AHSO)2019Ingår i: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 166, nr 1, s. 39-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Comprehensive reviews of syndromic surveillance in animal health have highlighted the hindrances to integration and interoperability among systems when data emerge from different sources. Discussions with syndromic surveillance experts in the fields of animal and public health, as well as computer scientists from the field of information management, have led to the conclusion that a major component of any solution will involve the adoption of ontologies. Here we describe the advantages of such an approach, and the steps taken to set up the Animal Health Surveillance Ontological (AHSO) framework. The AHSO framework is modelled in OWL, the W3C standard Semantic Web language for representing rich and complex knowledge. We illustrate how the framework can incorporate knowledge directly from domain experts or from data-driven sources, as well as by integrating existing mature ontological components from related disciplines. The development and extent of AHSO will be community driven and the final products in the framework will be open-access.

  • 11.
    Foyer, Pernilla
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten. Department of Military Studies, Military-Technology Division, Swedish Defence University, Stockholm, Sweden.
    Svedberg, Anna-Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Emma
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Wilsson, Erik
    Swedish Armed Forces Dog Training Unit, Märsta, Sweden.
    Olsen Faresjö, Åshild
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Behavior and cortisol responses of dogs evaluated in a standardized temperament test for military working dogs2016Ingår i: Journal of Veterinary Behavior: Clinical Applications and Research, ISSN 1558-7878, E-ISSN 1878-7517, Vol. 11, s. 7-12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Military and police working dogs are often exposed to stressful or threatening events, and an improper response, e.g., fear, may implicate both reduced working efficiency and welfare. Therefore, identifying individuals that display a favorable response to potentially threatening situations is of great interest. In the present study, we investigated behavior responses of 85 prospective military working dogs in 4 subtests in a standardized temperament test used to select working dogs for the Swedish Armed Forces. Our goal was to evaluate behavioral responses in specific subtests and cortisol responses of candidate dogs. After dogs were rated as approved or nonapproved based on the test leader’s assessment of the full test result, we independently analyzed video recordings of 4 subtests. In addition, for 37 dogs, we analyzed pretest and posttest salivary cortisol levels. Dogs which were approved by the test leader for further training scored higher in the video recordings on emotionality and, in particular, fear-related behavior during a subset of the test and had higher levels of cortisol both before and after the test, than nonapproved dogs. Although this may actually reflect the desired traits, it could also indicate a bias in the selection procedure, which may pose limitations on the attempts to recruit the most suitable working dogs.

  • 12.
    Garcia, Emanuell
    et al.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Hultgren, Jan
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Fällman, Pontus
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Geust, Johanna
    Nötcenter Viken, Vikens Egendom, Falköping, Sweden.
    Algers, Bo
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Stilwell, George
    Centro de Investigação Interdisciplinar em Sanidade Animal, Universidade Técnica de Lisboa, Lisboa, Portugal.
    Gunnarsson, Stefan
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Hälsouniversitetet. Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Intensity of Oestrus Signalling Is the Most Relevant Indicator for Animal Well-Being in High-Producing Dairy Cows2011Ingår i: Veterinary Medicine International, ISSN 2090-8113, E-ISSN 2042-0048, Vol. 2011, artikel-id 540830Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Full signalling of oestrous behaviour is vital for proper timing of AI and good reproductive performance, currently jeopardized by shorter observations of oestrus behaviour. Alternative indicators including progesterone (P4) recordings on-farm are tested. Oestrous intensity of 37 heifers (H) and 30 1st-parity dairy cows (C1) either Swedish Red (32) or Swedish Holstein (35) with high genetic potential for milk production, was studied in relation to AI. P4-levels in blood or milk were monitored on-farm at 0, 7, and 20 d post-AI with a portable ELISA reader (eProCheck800). Avoidance distance and body condition were scored at day 7, and pregnancy diagnosed by P4 (day 20) and trans-rectal palpation (day 50). More heifers (46%) than C1-cows (10%) showed standing oestrus (strongest intensity, 𝑃<0.05), leading to higher pregnancy rate at d50 (72% versus 37% for C1, 𝑃<0.01) and calving rate (H: 64%, C1: 33%, 𝑃<0.05). Avoidance distances were short (<1 m), reflecting good human-animal interaction. Visually-recorded standing oestrus yielded 4.8 fold higher odds of pregnancy, respectively 4.6-fold higher odds of calving. On-farm P4-recordings had complementary value yet less accuracy. Intensity of oestrus signalling relates to animal well-being, reflected in pregnancy-to-term being a good indicator for optimal welfare in high-producing dairy cattle.

  • 13.
    Ghareh Baghi, Ghareh Baghi
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.

    This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.

    The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.

    The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.

    Delarbeten
    1. A pattern recognition framework for detecting dynamic changes on cyclic time series
    Öppna denna publikation i ny flik eller fönster >>A pattern recognition framework for detecting dynamic changes on cyclic time series
    2015 (Engelska)Ingår i: Pattern Recognition, ISSN 0031-3203, E-ISSN 1873-5142, Vol. 48, nr 3, s. 696-708Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This paper proposes a framework for binary classification of the time series with cyclic characteristics. The framework presents an iterative algorithm for learning the cyclic characteristics by introducing the discriminative frequency bands (DFBs) using the discriminant analysis along with k-means clustering method. The DFBs are employed by a hybrid model for learning dynamic characteristics of the time series within the cycles, using statistical and structural machine learning techniques. The framework offers a systematic procedure for finding the optimal design parameters associated with the hybrid model. The proposed  model is optimized to detect the changes of the heart sound recordings (HSRs) related to aortic stenosis. Experimental results show that the proposed framework provides efficient tools for classification of the HSRs based on the heart murmurs. It is also evidenced that the hybrid model, proposed by the framework, substantially improves the classification performance when it comes to detection of the heart disease.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2015
    Nyckelord
    Hybrid model, cyclic time series, time series, phonocardiogram, systolic murmurs
    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110177 (URN)10.1016/j.patcog.2014.08.017 (DOI)000347747000008 ()
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. Detection of systolic ejection click using time growing neural network
    Öppna denna publikation i ny flik eller fönster >>Detection of systolic ejection click using time growing neural network
    2014 (Engelska)Ingår i: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 36, nr 4, s. 477-483Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In this paper, we present a novel neural network for classification of short-duration heart sounds: the time growing neural network (TGNN). The input to the network is the spectral power in adjacent frequency bands as computed in time windows of growing length. Children with heart systolic ejection click (SEC) and normal children are the two groups subjected to analysis. The performance of the TGNN is compared to that of a time delay neural network (TDNN) and a multi-layer perceptron (MLP), using training and test datasets of similar sizes with a total of 614 normal and abnormal cardiac cycles. From the test dataset, the classification rate/sensitivity is found to be 97.0%/98.1% for the TGNN, 85.1%/76.4% for the TDNN, and 92.7%/85.7% for the MLP. The results show that the TGNN performs better than do TDNN and MLP when frequency band power is used as classifier input. The performance of TGNN is also found to exhibit better immunity to noise.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2014
    Nyckelord
    Systolic ejection click; Time growing neural network; Time delay neural network; Heart sound
    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:liu:diva-106865 (URN)10.1016/j.medengphy.2014.02.011 (DOI)000334976800008 ()
    Tillgänglig från: 2014-05-28 Skapad: 2014-05-23 Senast uppdaterad: 2017-12-05
    3. A novel method for discrimination between innocent and pathological heart murmurs
    Öppna denna publikation i ny flik eller fönster >>A novel method for discrimination between innocent and pathological heart murmurs
    2015 (Engelska)Ingår i: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, nr 7, s. 674-682Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2015
    Nyckelord
    Growing-time support vector machine, support vector machine, phonocardiogram signal, heart murmurs, innocent murmurs.
    Nationell ämneskategori
    Medicinteknik
    Identifikatorer
    urn:nbn:se:liu:diva-117825 (URN)10.1016/j.medengphy.2015.04.013 (DOI)000357354400007 ()26003286 (PubMedID)
    Anmärkning

    At the time for thesis presentation publication was in status: Manuscript

    Tillgänglig från: 2015-05-08 Skapad: 2015-05-08 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    4. An Automatic Tool for Pediatric Heart Sounds Segmentation
    Öppna denna publikation i ny flik eller fönster >>An Automatic Tool for Pediatric Heart Sounds Segmentation
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    In this paper, we present a novel algorithm for pediatric heart sound segmentation, incorporated into a graphical user interface. The algorithm employs both the Electrocardiogram (ECG) and Phonocardiogram (PCG) signals for an efficient segmentation under pathological circumstances.First, the ECG signal is invoked in order to determine the beginning and end points of each cardiac cycle by using wavelet transform technique. Then, first and second heart sounds within the cycles are identified over the PCG signal by paying attention to the spectral properties of the sounds. The algorithm is applied on 120 recordings of normal and pathological children, totally containing 1976 cardiac cycles. The accuracy of the segmentation algorithm is 97% for S1 and 94% for S2 identification while all the cardiac cycles are correctly determined.

    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110179 (URN)
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2014-09-04Bibliografiskt granskad
    5. Severity assessments of aortic stenosis using intelligent phonocardiography
    Öppna denna publikation i ny flik eller fönster >>Severity assessments of aortic stenosis using intelligent phonocardiography
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objectives: To study capabilities of the intelligent phonocardiography (IPCG) in automatic grading severity of the aortic stenosis (AS).

    Methods: Phonocardiogram signals were recorded from the patients with AS, as diagnosed by echocardiography. The patient group is comprised of signals, recorded from 5 patients (2 recordings from each), mostly elderly referrals (>60 years) with mild to severe AS. An advanced processing algorithm, consisted of the wavelet transform and the stepwise regression analysis, characterizes the systolic murmur caused by the AS in order to predict the 5 indicators; mean pressure gradient over the aortic valve (MPG), maximum jet velocity (MJV), aortic valve area (AVA), velocity time integral and the ejection period. The automatic assessment is performed by an artificial neural network using the predicted values of the indicators as the input data. Reliability of the IPCG is validated by applying repeated random sub-sampling (RRSS) with 70%/30% of the training/testing data, and calculating the accuracy. The RRSS is also employed to validate reproducibility of the IPCG by using 70% of the signals for training and the second recording of the same individuals for  testing.

    Results: Accuracy of the IPCG is estimated to be and (95% confidence interval) for the reliability and the reproducibility, respectively. Linear correlation between the characterized systolic murmur and the MPG (r>0.81), the MJV (r>0.82) and the AVA (r>0.85) is observed.

    Conclusions: The IPCG has the potential to objectively serve as a clinical tool for grading severity of the aortic stenosis.

    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110181 (URN)
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2014-09-04Bibliografiskt granskad
  • 14.
    Girvan, Pilar
    Linköpings universitet, Institutionen för tema, Tema Genus.
    Clearing up the bullshit: Deconstructing 'feminisation', gender stereotypes and gender biases within UK veterinary surgery2019Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    This thesis explores ‘feminisation’ discourse(s) within the UK veterinary profession, including the ways in which gender stereotypes and biases also influence such discourses and experiences of working within the field. Drawing upon and combining a range of sociological, organisational and feminist theories such as Witz’s (1992) theory of gendered professional projects and Butler’s (1990) highly influential notion of performativity, I am able to contextualise and expand upon the ‘doing’ of the veterinary profession as well as being able to frame ‘feminisation’ discourses as paradoxes, potentially producing the effects they articulate. My analysis is divided into two parts; the first deals with results of a 463 participant survey of veterinary workers regarding definitions, perceptions and observations of ‘feminisation’ and gender difference, highlighting the significance of this subject matter within their professional lives. The second part incorporates a deeper thematic analysis of particular everyday realities, emerging from four semi-structured interviews which also aimed to explore in greater detail individual perceptions and observations regarding ‘feminisation’ and gender biases and stereotypes, encouraging participants themselves to reflect upon their experiences. A number of conclusions emerged during the analysis, including an intriguing insight that those who tended to draw most strongly on gender stereotypes and biases to outline their perceptions and observations were paradoxically those who most vehemently believed gender was irrelevant. Fundamentally however this study concludes that the concept of ‘feminisation’ is a fluid conceptualisation, a cultural process and not just empirical category of ‘empty rhetoric’ as commonly utilised and applied to the veterinary profession; as such it has the potential to be utilised extensively to progress the profession in terms of wider inclusiveness, equality, transformation, in offering reconceptualised ways of considering what it means to be part of a ‘profession’ not predicated on patriarchal structures, and to ultimately reperceive how gender can be (re/un)enacted in transformative ways alongside progressively rearticulated ‘feminisation’ discourses.

  • 15.
    Gizejewski, Z
    et al.
    Institute of Animal Breeding and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
    Söderquist, L
    Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Sciences, SLU, Uppsala, Sweden.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Hälsouniversitetet.
    Genital and sperm characteristics of wild, free rangingred deer stags (Cervus elaphus L) hunted in different regions of Poland2010Ingår i: Wildlife Biology in Practice, ISSN 1646-1509, E-ISSN 1646-2742, Vol. 6, nr 2, s. 81-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an attempt to establish reference values for sperm morphology in wild red deer, genital tracts were collected from thirty-six 3-11 years old free-ranging, wild red deer stags (Cervus elaphus L) shot down during 3 consecutive mating seasons (1996-1998) at three different environmental regions of Poland, defining two major ecotypes: (i) highland (outer eastern Carpathian range, Bieszczady mountains) and, (ii) lowland (Mazuria and Pomerania) and studied within 4.5h-49h after death for testis (T), epididymides (E) and vesicular gland (VG) variables. Spermatozoa collected from the E-cauda were examined for motility and morphology (light and electron microscopy levels). Both T size and weight and VS-weight differed with age (P<0.05-0.01) while habitat influenced T size and weight (P<0.01) a well as sperm motility (P<0.05). Neither sperm numbers nor morphology showed significant differences, mostly owing to

    the large variation recorded among stags (range 1-72%). Domain-grouped sperm morphological deviations were <5%, the mean total proportion of abnormal spermatozoa ranging 7.2-17.5%. Although variation was present, the values ought to be used as reference for spermiogrammes.

  • 16.
    Havarinasab, Said
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Effect of thimerosal on the murine immune system: especially induction of systemic autoimmunity2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Dose-response study of thimerosal-induced murine systemic autoimmunity
    Öppna denna publikation i ny flik eller fönster >>Dose-response study of thimerosal-induced murine systemic autoimmunity
    2004 (Engelska)Ingår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, Vol. 194, nr 2, s. 169-179Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury.

    A.SW mice were exposed to 1.25–40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 μg Hg/kg bw and a concentration of 21 and 1.9 μg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose–response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury.

    Nyckelord
    Thimerosal, Ethylmercury, Mice, Autoimmunity
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13815 (URN)10.1016/j.taap.2003.09.006 (DOI)
    Tillgänglig från: 2006-04-21 Skapad: 2006-04-21 Senast uppdaterad: 2009-08-18
    2. Immunosuppressive and autoimmune effects of thimerosal in mice
    Öppna denna publikation i ny flik eller fönster >>Immunosuppressive and autoimmune effects of thimerosal in mice
    Visa övriga...
    2005 (Engelska)Ingår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, Vol. 204, nr 2, s. 109-121Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2s) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 μg Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-γ mRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-1-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2s strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell co-stimulatory molecule CD28 (B10.S–CD28−/−), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2s strains with targeted mutations, we found that IFN-γ and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 81 μg Hg/g. EtHg made up 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.

    Nyckelord
    Thimerosal; Ethylmercury; Mice; Immunosuppression; Autoimmunity
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13816 (URN)10.1016/j.taap.2004.08.019 (DOI)
    Tillgänglig från: 2006-04-21 Skapad: 2006-04-21
    3. The autoimmunogen effect of the organic mercury species methyl mercury and ethyl mercury
    Öppna denna publikation i ny flik eller fönster >>The autoimmunogen effect of the organic mercury species methyl mercury and ethyl mercury
    Manuskript (Övrigt vetenskapligt)
    Identifikatorer
    urn:nbn:se:liu:diva-13817 (URN)
    Tillgänglig från: 2006-04-21 Skapad: 2006-04-21 Senast uppdaterad: 2010-01-13
    4. Alteration of the spontaneous systemic autoimmune disease in (NZB x NZW)F1 mice by treatment with thimerosal (ethyl mercury)
    Öppna denna publikation i ny flik eller fönster >>Alteration of the spontaneous systemic autoimmune disease in (NZB x NZW)F1 mice by treatment with thimerosal (ethyl mercury)
    2006 (Engelska)Ingår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, Vol. 214, nr 1, s. 43-54Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Inorganic mercury may aggravate murine systemic autoimmune diseases which are either spontaneous (genetically determined) or induced by non-genetic mechanisms. Organic mercury species, the dominating form of mercury exposure in the human population, have not been examined in this respect. Therefore, ethyl mercury in the form of thimerosal, a preservative recently debated as a possible health hazard when present in vaccines, was administered in a dose of 0.156–5 mg/L drinking water to female (NZB × NZW)F1 (ZBWF1) mice. These mice develop an age-dependent spontaneous systemic autoimmune disease with high mortality primarily due to immune-complex (IC) glomerulonephritis. Five mg thimerosal/L drinking water (295 μg Hg/kg body weight (bw)/day) for 7 weeks induced glomerular, mesangial and systemic vessel wall IC deposits and antinuclear antibodies (ANA) which were not present in the untreated controls. After 22–25 weeks, the higher doses of thimerosal had shifted the localization of the spontaneously developing renal glomerular IC deposits from the capillary wall position seen in controls to the mesangium. The altered localization was associated with less severe histological kidney damage, less proteinuria, and reduced mortality. The effect was dose-dependent, lower doses having no effect compared with the untreated controls. A different effect of thimerosal treatment was induction of renal and splenic vessel walls IC deposits. Renal vessel wall deposits occurred at a dose of 0.313–5 mg thimerosal/L (18–295 μg Hg/kg bw/day), while splenic vessel wall deposits developed also in mice given the lowest dose of thimerosal, 0.156 mg/L (9 μg Hg/kg bw/day). The latter dose is 3- and 15-fold lower than the dose of Hg required to induce vessel wall IC deposits in genetically susceptible H-2s mice by HgCl2 and thimerosal, respectively. Further studies on the exact conditions needed for induction of systemic IC deposits by low-dose organic mercurials in autoimmune-prone individuals, as well as the potential effect of these deposits on the vessel walls, are warranted.

    Nyckelord
    Thimerosal; Mice; Autoimmunity; Immune-complex; (NZB × NZW)F1 mice
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13818 (URN)10.1016/j.taap.2005.12.004 (DOI)
    Tillgänglig från: 2006-04-21 Skapad: 2006-04-21
  • 17.
    Henriksson, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    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 intake2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Body-composition development during early childhood and energy expenditure in response to physical activity in 1.5-y-old children
    Öppna denna publikation i ny flik eller fönster >>Body-composition development during early childhood and energy expenditure in response to physical activity in 1.5-y-old children
    Visa övriga...
    2012 (Engelska)Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, nr 3, s. 567-573Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: The prevalence of childhood overweight and obesity has increased recently, but the mechanisms involved are incompletely known. Previous research has shown a correlation between the percentage of total body fat (TBF) and physical activity level (PAL). However, the PAL values used may involve a risk of spurious correlations because they are often based on predicted rather than measured estimates of resting energy metabolism. less thanbrgreater than less thanbrgreater thanObjectives: We studied the development of body composition during early childhood and the relation between the percentage of TBF and PAL on the basis of the measured resting energy metabolism. less thanbrgreater than less thanbrgreater thanDesign: Body composition was previously measured in 108 children when they were 1 and 12 wk old. When 44 of these children (21 girls and 23 boys) were 1.5 y old, their total energy expenditure and TBF were assessed by using the doubly labeled water method. Resting energy metabolism, which was assessed by using indirect calorimetry, was used to calculate PAL. less thanbrgreater than less thanbrgreater thanResults: Significant correlations were shown for TBF (r = 0.32, P = 0.035) and fat-free mass (r = 0.34, P = 0.025) between values (kg) assessed at 12 wk and 1.5 y of age. For TBF (kg) a significant interaction (P = 0.035) indicated a possible sex difference. PAL at 1.5 y was negatively correlated with the percentage of TBF (r = -0.40, P = 0.0076) and the increase in the percentage of TBF between 12 wk and 1.5 y (r = 0.38, P = 0.0105). less thanbrgreater than less thanbrgreater thanConclusions: The results indicate that body fatness and physical activity interact during early childhood and thereby influence obesity risk. Our results are based on a small sample, but nevertheless, they motivate additional studies in boys compared with girls regarding the development of body composition during early life.

    Ort, förlag, år, upplaga, sidor
    American Society for Nutrition, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84341 (URN)10.3945/ajcn.111.022020 (DOI)000307863800016 ()
    Anmärkning

    Funding Agencies|Swedish Research Council|15402|AFA Insurance||Medical Faculty, Linkoping University||County Council of Ostergotland||Crown Princess Lovisa Foundation||

    Tillgänglig från: 2012-10-05 Skapad: 2012-10-05 Senast uppdaterad: 2019-06-28
    2. Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age
    Öppna denna publikation i ny flik eller fönster >>Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age
    Visa övriga...
    2015 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    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.

    Nyckelord
    Body composition, energy expenditure, physical activity, children, doubly labelled water
    Nationell ämneskategori
    Klinisk vetenskap Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:liu:diva-117418 (URN)
    Tillgänglig från: 2015-04-27 Skapad: 2015-04-27 Senast uppdaterad: 2019-06-28Bibliografiskt granskad
    3. Evaluation of Actiheart and a 7d activity diary for estimating free-living total and activity energy expenditure using criterion methods in 1 center dot 5- and 3-year-old children
    Öppna denna publikation i ny flik eller fönster >>Evaluation of Actiheart and a 7d activity diary for estimating free-living total and activity energy expenditure using criterion methods in 1 center dot 5- and 3-year-old children
    2014 (Engelska)Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, nr 10, s. 1830-1840Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Accurate and easy-to-use methods to assess free-living energy expenditure in response to physical activity in young children are scarce. In the present study, we evaluated the capacity of (1) 4d recordings obtained using the Actiheart (mean heart rate (mHR) and mean activity counts (mAC)) to provide assessments of total energy expenditure (TEE) and activity energy expenditure (AEE) and (2) a 7d activity diary to provide assessments of physical activity levels (PAL) using three sets of metabolic equivalent (MET) values (PAL(Torun), PAL(Adolph) and PAL(Ainsworth)) in forty-four and thirty-one healthy Swedish children aged 1 center dot 5 and 3 years, respectively. Reference TEE, PAL(ref) and AEE were measured using criterion methods, i.e. the doubly labelled water method and indirect calorimetry. At 1 center dot 5 years of age, mHR explained 8% (P=0 center dot 006) of the variation in TEE above that explained by fat mass and fat-free mass. At 3 years of age, mHR and mAC explained 8 (P=0 center dot 004) and 6 (P=0 center dot 03)% of the variation in TEE and AEE, respectively, above that explained by fat mass and fat-free mass. At 1 center dot 5 and 3 years of age, average PAL(Ainsworth) values were 1 center dot 44 and 1 center dot 59, respectively, and not significantly different from PAL(ref) values (1 center dot 39 and 1 center dot 61, respectively). By contrast, average PAL(Torun) (1 center dot 5 and 3 years) and PAL(Adolph) (3 years) values were lower (Pless than0 center dot 05) than the corresponding PAL(ref) values. In conclusion, at both ages, Actiheart recordings explained a small but significant fraction of free-living energy expenditure above that explained by body composition variables, and our activity diary produced mean PAL values in agreement with reference values when using MET values published by Ainsworth.

    Ort, förlag, år, upplaga, sidor
    Cambridge University Press (CUP), 2014
    Nyckelord
    Heart rate recording; Activity diary; Doubly labelled water; Accelerometer
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-106669 (URN)10.1017/S0007114513004406 (DOI)000334172400012 ()
    Tillgänglig från: 2014-05-21 Skapad: 2014-05-19 Senast uppdaterad: 2019-06-28
    4. A New Mobile Phone-Based Tool for Assessing Energy and Certain Food Intakes in Young Children: A Validation Study
    Öppna denna publikation i ny flik eller fönster >>A New Mobile Phone-Based Tool for Assessing Energy and Certain Food Intakes in Young Children: A Validation Study
    Visa övriga...
    2015 (Engelska)Ingår i: JMIR mhealth and uhealth, E-ISSN 2291-5222, Vol. 3, nr 2, artikel-id e38Artikel i tidskrift (Refereegranskat) Published
    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.

    Ort, förlag, år, upplaga, sidor
    JMIR publications, 2015
    Nyckelord
    Cell phone, digital camera, food intake, energy intake, child, DLW, FFQ
    Nationell ämneskategori
    Klinisk vetenskap Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:liu:diva-117419 (URN)10.2196/mhealth.3670 (DOI)25910494 (PubMedID)
    Tillgänglig från: 2015-04-27 Skapad: 2015-04-27 Senast uppdaterad: 2019-06-28Bibliografiskt granskad
  • 18.
    Henriksson, Hanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Löf, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. 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 Study2015Ingår i: JMIR mhealth and uhealth, E-ISSN 2291-5222, Vol. 3, nr 2, artikel-id e38Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Henriksson, Hanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Britt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Forsum, Elisabet
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Flinke Carlsson, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Löf, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age2015Manuskript (preprint) (Övrigt vetenskapligt)
    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.

  • 20.
    Henriksson, Pontus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    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 infants2015Manuskript (preprint) (Övrigt vetenskapligt)
    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.

  • 21.
    Henriksson, Pontus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    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 girls2015Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, nr 5, s. 491-497Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Hilborn, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer: Impact on tamoxifen treatment2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
    Öppna denna publikation i ny flik eller fönster >>C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
    Visa övriga...
    2014 (Engelska)Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 145, nr 1, s. 73-82Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P less than 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.

    Ort, förlag, år, upplaga, sidor
    Springer Verlag (Germany), 2014
    Nyckelord
    CXCL10; CXCR3; Endocrine treatment; Prognosis; Tamoxifen
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-106833 (URN)10.1007/s10549-014-2933-7 (DOI)000334519400007 ()
    Tillgänglig från: 2014-05-28 Skapad: 2014-05-23 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
    Öppna denna publikation i ny flik eller fönster >>Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
    Visa övriga...
    2016 (Engelska)Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, nr 3, s. 248-255Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P &lt; 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

    Ort, förlag, år, upplaga, sidor
    NATURE PUBLISHING GROUP, 2016
    Nyckelord
    Androgen receptor; breast cancer; tamoxifen; oestrogen receptor; triple-negative breast cancer
    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:liu:diva-125675 (URN)10.1038/bjc.2015.464 (DOI)000369223600003 ()26742006 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish research council [A0346701]; Swedish cancer foundation [13 0435]

    Tillgänglig från: 2016-03-02 Skapad: 2016-02-29 Senast uppdaterad: 2017-05-03
  • 23.
    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.1997Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, nr 3, s. 499-502Artikel i tidskrift (Refereegranskat)
    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%.

  • 24.
    Kernell, Kristina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Cardiac disease in pregnancy and consequences for reproductive outcomes, comorbidity and survival2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background

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

    Aims

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

    Methods

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

    Results and conclusions

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

    Delarbeten
    1. Reproductive patterns and pregnancy outcomes in women with congenital heart disease - a Swedish population-based study
    Öppna denna publikation i ny flik eller fönster >>Reproductive patterns and pregnancy outcomes in women with congenital heart disease - a Swedish population-based study
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    2011 (Engelska)Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, nr 6, s. 659-665Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective. To study women diagnosed with congenital heart disease (CHD) with respect to characteristics related to their own births, their subsequent likelihood of giving birth and the obstetric and neonatal outcomes of their pregnancies. Design. Population-based register study. Population. All women born in 1973-1983 who were alive and living in Sweden at 13 years of age (n=500 245). Methods. Women diagnosed with CHD (n=2 216) were compared with women without CHD (n=492 476). A total of 188 867 mother-firstborn-offspring pairs were identified and available for analysis. Results. Mothers of women with CHD were more often older and single/unmarried. Women with CHD were more often born preterm or small-for-gestational age (SGA) than women without CHD, more likely to have been born with a cesarean section, to have given birth during the study period, and to be younger at the time of their first pregnancy. Women with CHD were also more prone to give birth to children preterm or SGA and their babies were more often delivered by cesarean section with a higher frequency of congenital abnormality. Conclusions. Women with CHD were more likely to have been born preterm or SGA and these outcomes were repeated in the next generation. Women with CHD should not be discouraged from pregnancy. Prenatal diagnostics should be discussed and offered to these women, as there is an increased risk for congenital abnormalities.

    Ort, förlag, år, upplaga, sidor
    Wiley, 2011
    Nyckelord
    Congenital heart disease; reproduction; high-risk pregnancy
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-69887 (URN)10.1111/j.1600-0412.2011.01100.x (DOI)000291433600016 ()
    Tillgänglig från: 2011-08-09 Skapad: 2011-08-08 Senast uppdaterad: 2019-06-28
    2. Congenital heart disease in men - birth characteristics and reproduction: a national cohort study.
    Öppna denna publikation i ny flik eller fönster >>Congenital heart disease in men - birth characteristics and reproduction: a national cohort study.
    Visa övriga...
    2014 (Engelska)Ingår i: BMC pregnancy and childbirth, ISSN 1471-2393, Vol. 14, s. 187-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Women with congenital heart disease (CHD) are more often born preterm or small-for-gestational age and with a caesarean section. This pattern together with an increased risk of congenital anomalies seems to be repeated in the next generation. Information on the effect of paternal CHD on their offspring is sparse. In this study we investigated if men with CHD differ from those who do not have CHD with respect to characteristics related to their own births, their reproductive patterns and the neonatal outcomes of their children.

    METHODS: In this national cohort study data were derived from Swedish population-based registries. The population consists of all men born in 1973-1983 who were alive and living in Sweden at 13 years of age (n = 522 216). The index group is men with CHD (n = 2689). Men diagnosed with CHD were compared with men without CHD. The CHD were also divided into two groups, complex and simple CHD and comparisons between the groups were made.

    RESULTS: Men with CHD are more likely to have been born preterm (p < 0.001), small-for gestational-age (p < 0.001) or large-for-gestational-age (p < 0.001) than men without CHD. They are also more likely to have been the result of a twin pregnancy (p < 0.001) and to have been delivered by caesarean section (p < 0.001). Men with CHD have a decreased likelihood to become fathers compared to non-CHD men and in this study their offspring do not have a higher incidence of CHD than offspring to non-CHD fathers. The neonatal outcomes of children of men with CHD do not differ from the outcomes of children of non-CHD men.

    CONCLUSIONS: Men with CHD were more often born with non-optimal characteristics compared to men without the condition. However, the increased risk does not repeat itself in the next generation. This knowledge can lead to improved preconception counselling for couples in which the father has a CHD.

    Ort, förlag, år, upplaga, sidor
    BioMed Central, 2014
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-115269 (URN)10.1186/1471-2393-14-187 (DOI)000338566400002 ()24890365 (PubMedID)2-s2.0-84905053219 (Scopus ID)
    Tillgänglig från: 2015-03-11 Skapad: 2015-03-11 Senast uppdaterad: 2019-06-28Bibliografiskt granskad
  • 25.
    Klasson, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet.
    MRI Contrast Enhancement using Gd2O3 Nanoparticles2008Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

    Delarbeten
    1. High Proton Relaxivity for Gadolinium Oxide Nanoparticles
    Öppna denna publikation i ny flik eller fönster >>High Proton Relaxivity for Gadolinium Oxide Nanoparticles
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    2006 (Engelska)Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 19, nr 4, s. 180-186Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd2O3 nanocrystals.

    Materials and methods: Gd2O3 nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd2O3 was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).

    Results: Results showed a considerable relaxivity increase for the Gd2O3–DEG particles compared to Gd-DTPA. Both T 1 and T 2 relaxivities in the presence of Gd2O3–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T1-weighted spin echo sequence.

    Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd2O3–DEG nanocrystals as contrast agent. The high T 1 relaxation rate at low concentrations of Gd2O3 nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.

    Nyckelord
    Gd2O3, Nanoparticle, Contrast agent, Relaxivity, MRI
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12943 (URN)10.1007/s10334-006-0039-x (DOI)000241584400002 ()
    Tillgänglig från: 2008-02-21 Skapad: 2008-02-21 Senast uppdaterad: 2017-12-13
    2. Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals: A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties
    Öppna denna publikation i ny flik eller fönster >>Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals: A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties
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    2009 (Engelska)Ingår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 113, nr 17, s. 6913-6920Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Ultrasmall gadolinium oxide nanoparticles doped with terbium ions were synthesized by the polyol route and characterized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. The structural, optical, and magnetic properties of the organic-acid-capped and PEGylated Gd2O3:Tb3+ nanocrystals were studied by HR-TEM, XPS, EDX, IR, PL, and SQUID. The luminescent/fluorescent property of the particles is attributable to the Tb3+ ion located on the crystal lattice of the Gd2O3 host. The paramagnetic behavior of the particles is discussed. Pilot studies investigating the capability of the nanoparticles for fluorescent labeling of living cells and as a MRI contrast agent were also performed. Cells of two cell lines (THP-1 cells and fibroblasts) were incubated with the particles, and intracellular particle distribution was visualized by confocal microscopy. The MRI relaxivity of the PEGylated nanoparticles in water at low Gd concentration was assessed showing a higher T-1 relaxation rate compared to conventional Gd-DTPA chelates and comparable to that of undoped Gd2O3 nanoparticles.

    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12944 (URN)10.1021/jp808708m (DOI)000265529700009 ()
    Anmärkning

    On the day of the defence date the status of this article was Submitted

    Tillgänglig från: 2008-02-21 Skapad: 2008-02-21 Senast uppdaterad: 2018-10-29Bibliografiskt granskad
    3. Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
    Öppna denna publikation i ny flik eller fönster >>Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
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    2008 (Engelska)Ingår i: Contrast Media and Molecular Imaging, ISSN 1555-4309, Vol. 3, nr 3, s. 106-111Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s-1 mm-1 for cell culture medium. The r2 was 17.4 and 12.9 s-1 mm-1, respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.

    Nyckelord
    gadolinium oxide, nanoparticles, contrast agent, THP-1 cells, magnetic resonance imaging
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12945 (URN)10.1002/cmmi.236 (DOI)000257982000002 ()
    Tillgänglig från: 2008-02-21 Skapad: 2008-02-21 Senast uppdaterad: 2017-09-22Bibliografiskt granskad
  • 26.
    Lee, Francis
    Linköpings universitet, Institutionen för tema, Tema teknik och social förändring. Linköpings universitet, Filosofiska fakulteten.
    Purity and interest: on relational work and epistemic value in the biomedical sciences2015Ingår i: Value practice in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, oxford: Oxford University Press, 2015, s. 207-223Kapitel i bok, del av antologi (Refereegranskat)
  • 27.
    Lerner, Henrik
    Linköpings universitet, Institutionen för kultur och kommunikation, Centrum för tillämpad etik. Linköpings universitet, Filosofiska fakulteten.
    Transeminarium om eutanasi för människa och av djur2010Ingår i: Svensk Veterinärtidning, ISSN 0346-2250, Vol. 62, nr 10, s. 23-25Artikel, forskningsöversikt (Övrigt vetenskapligt)
  • 28.
    Liedberg, Gunilla
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Hälsa, Aktivitet, Vård (HAV). Linköpings universitet, Hälsouniversitetet.
    Women with fibromyalgia: Employment and daily life2004Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

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

    Delarbeten
    1. Factors of Importance for Work Disability in Women with Fibromyalgia
    Öppna denna publikation i ny flik eller fönster >>Factors of Importance for Work Disability in Women with Fibromyalgia
    2000 (Engelska)Ingår i: Journal of Rheumatology, ISSN 0315-162X, Vol. 27, nr 5, s. 1271-1276Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: To identify factors of importance for women with fibromyalgia (FM) to continue working despite the limitations imposed by the symptoms.

    METHODS: A mail questionnaire with questions regarding social background, symptoms, sickness benefits, work situation, work conditions and adjustments, opinions regarding own work ability, and satisfaction with the situation was sent to 218 consecutive women seen at a university pain or rheumatology clinic. Answers were obtained from 176 women.

    RESULTS: Pain, poor quality sleep, abnormal tiredness, muscle stiffness, and increased pain after muscle exertion were frequently reported symptoms. Fifty percent of the women were employed, 15% full-time. Twenty-three percent reported FM as the reason for not working. The work situation had been changed for 58% of the working women, and 80% counted on being able to continue working.

    CONCLUSION: Work disability is a serious concern in FM, and the majority of women with FM have limitations in their ability to work. Our results indicate that individual adjustments in the work situation need to be made and that women who have found a level matching their ability may continue to work and find it satisfactory. Early intervention in the work situation is recommended.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13639 (URN)
    Tillgänglig från: 2004-05-21 Skapad: 2004-05-21 Senast uppdaterad: 2009-05-18
    2. Factors of Importance for Work Disability in Women with Fibromyalgia: An Interview Study
    Öppna denna publikation i ny flik eller fönster >>Factors of Importance for Work Disability in Women with Fibromyalgia: An Interview Study
    2002 (Engelska)Ingår i: Arthritis Care and Research, ISSN 1529-0131, Vol. 47, nr 3, s. 266-274Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: Fibromyalgia symptoms such as continuous pain, tiredness, hyperalgesia, and allodynia limit gainful employment. The present study examines which factors influence the decision to remain in a work role for women with fibromyalgia. This information is important for the individual and for public finances.

    Methods: Qualitative interviews were performed with 39 women, 19 of whom were gainfully employed and 20 who had stopped working. The transcribed interviews were analyzed and divided into categories and subcategories.

    Results: Four categories appear, at societal and individual levels, that were regarded as important by the women for remaining in a work role.

    Conclusions: The ability to remain at work depends not only on limitations in work capacity, but also on the capacity of society to adjust work environments and work tasks. More individual solutions are needed to allow women with fibromyalgia to maintain work roles.

    Nyckelord
    Work role, Employment, Work disability, Qualitative method
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13640 (URN)
    Tillgänglig från: 2004-05-21 Skapad: 2004-05-21 Senast uppdaterad: 2009-05-18
    3. The Impact of Fibromyalgia on Employment Status of Newly-Diagnosed Young Women
    Öppna denna publikation i ny flik eller fönster >>The Impact of Fibromyalgia on Employment Status of Newly-Diagnosed Young Women
    2005 (Engelska)Ingår i: Journal of Musculoskeletal Pain, ISSN 1058-2452, Vol. 13, nr 2, s. 31-41Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: To describe employment loss in young women with newly diagnosed fibromyalgia syndrome [FMS] and to identify variables that may explain early loss of employment.

    Methods: In this pilot studsy, 94 young women [18-39 years old] in the United States [USA] and Sweden completed demographics, global rating scales, and standardized questionnaires, including the Fibromyalgia Impact Questionnaire, SF-36 General Health Subscale, Beck Depression Inventory, Beck Anxiety Inventory, Arthritis Self-Efficacy Scale, Arthritis Impact Measurement Scales II Social Support Subscale, and Job Flexibility Scale, three times during the first 12 to 15 months after diagnosis.

    Results: At the time of diagnosis, 60 percent were in paid employment [USA 71 percent, Sweden 49 percent]. When the participants entered the study, within three months of diagnosis, only 46 percent were working [USA 56 percent, Sweden 37 percent]. Twelve months later, 41 percent were working [USA 55 percent, Sweden 28 percent]. Younger age, poorer physical functioning, and lower self-efficacy for pain management along with higher symptom interference with ability to do any work, and pain severity predicted unemployment with 75 percent accuracy.

    Conclusions: An early and notable decrease in the percentage of young women diagnosed with FMS and working in paid employment was seen in this pilot study. Because most of the job loss was associated with FMS symptoms, a larger study of strategies to control or ameliorate these symptoms in the work setting should be undertaken.

    Nyckelord
    Fibromyalgia; women; employment; disability; outcomes
    Nationell ämneskategori
    Samhällsvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13641 (URN)10.1300/J094v13n02_05 (DOI)
    Tillgänglig från: 2004-05-21 Skapad: 2004-05-21 Senast uppdaterad: 2009-05-07
    4. Young women with fibromyalgia in the United States and Sweden: Perceived difficulties during the first year after diagnosis
    Öppna denna publikation i ny flik eller fönster >>Young women with fibromyalgia in the United States and Sweden: Perceived difficulties during the first year after diagnosis
    2006 (Engelska)Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 28, nr 19, s. 1177-1185Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose. The major symptoms of fibromyalgia (FM) - pain, tiredness, disrupted sleep, and muscle weakness - severely impact everyday activities, including the paid work role of women who have had FM for a long time. There are no prospective studies on young and newly diagnosed women with FM. The aim of the present study was to describe and compare difficulties young and newly diagnosed women in Sweden and the United States experienced during their first year after diagnosis.

    Method. Three interviews, 6 months apart, were conducted, with 49 Swedish and 45 US women between the ages of 18 and 39. Five open-ended questions were asked concerning physical, psychological and social difficulties and limitations, and factors that increased or decreased their difficulties and limitations. At interviews 2 and 3 the women were also asked about ways of preventing their difficulties. The answers were written down and analysed by a content analysis approach.

    Results. Consistent categories of difficulties were reported: symptoms, movements, activities, moods, social network, external factors and coping strategies. More US women were working outside their homes than were their Swedish counterparts and they expressed more difficulties compared with the Swedish women.

    Conclusions. In general, difficulties decreased and coping strategies increased over the 1-year period in both groups of newly diagnosed, young women.

    Nyckelord
    Activities of daily living; qualitative method; content analysis; physical; psychological; social
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13642 (URN)10.1080/09638280600551534 (DOI)
    Tillgänglig från: 2004-05-21 Skapad: 2004-05-21 Senast uppdaterad: 2017-12-13
    5. Time Use and Activity Patterns in Women with Long-term Pain
    Öppna denna publikation i ny flik eller fönster >>Time Use and Activity Patterns in Women with Long-term Pain
    2004 (Engelska)Ingår i: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, Vol. 11, nr 1, s. 26-35Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Earlier studies of people with fibromyalgia have shown that pain, tiredness, and sleep disruption seriously affect their daily performance and their ability to maintain life roles. A time-geographic diary method was used to study activities and time use in the daily lives of women with long-term pain. The results of the diaries were also used to evaluate activity changes over time. Sixteen women wrote diaries over seven days, and after three months for another four days. The diaries were analysed in a computer program. After considering the results of the first diary, the women formulated goals to be met in the following three months. The results showed that working women spent significantly less time on “Care for others”, “Care for oneself”, Rest, and “Procure and prepare food” compared with non-working women. Further, working women used time in a manner similar to that of the Swedish female population. The diary method gave a clear picture of the women's daily lives. Visualized in graphs and tables, it will serve as an educational tool in rehabilitation and can be used as a framework for discussing adjustment and coping strategies.

    Nyckelord
    activities of daily living, fibromyalgia, occupational therapy, qualitative research, rehabilitation, work
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13643 (URN)10.1080/11038120410019081 (DOI)
    Tillgänglig från: 2004-05-21 Skapad: 2004-05-21 Senast uppdaterad: 2009-08-19
  • 29.
    Lindehammar, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Neurofysiologiska kliniken US.
    Muscle function in Juvenile Idiopathic Arthritis: A two-year follow-up2004Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

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

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

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

    No patient had signs of neuropathy.

    Delarbeten
    1. Muscle function in Juvenile Chronic Arthritis
    Öppna denna publikation i ny flik eller fönster >>Muscle function in Juvenile Chronic Arthritis
    1995 (Engelska)Ingår i: Journal of Rheumatology, ISSN 0315-162X, Vol. 22, nr 6, s. 1159-1165Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE. Muscle strength and thickness were studied in children with juvenile chronic arthritis (JCA) to evaluate their muscle function. METHODS. We studied voluntary isometric, isokinetic, and nonvoluntary isometric muscle strength, as well as muscle thickness, in 20 children with JCA. Thickness of the quadriceps muscle was measured by ultrasound. Results were compared with reference values for healthy children and a matched control group. RESULTS. Isometric muscle strength in knee extensors, elbow flexors, and wrist dorsiflexors was reduced in children with JCA. In muscles near an inflamed joint, the strength was 45-65% of expected value. In muscles without adjacent arthritis, the strength was slightly decreased (80-90% of expected value). Isometric and isokinetic strength in ankle dorsiflexors was reduced only in children with ankle arthritis. Nonvoluntary muscle strength in thumb adductors during electrical stimulation of the ulnar nerve was reduced in children with arthritis in the hand. Thickness of the quadriceps muscle was reduced both in children with and without knee arthritis (75 and 90% of expected). CONCLUSION. Children with JCA have reduced muscle strength and thickness, which is most pronounced in muscles near an inflamed joint.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13644 (URN)
    Tillgänglig från: 2004-05-27 Skapad: 2004-05-27 Senast uppdaterad: 2009-08-19
    2. Measurement of Quadriceps Muscle Strength and Bulk in Juvenile Chronic Arthritis: A Prospective, Longitudinal, 2 Year Survey
    Öppna denna publikation i ny flik eller fönster >>Measurement of Quadriceps Muscle Strength and Bulk in Juvenile Chronic Arthritis: A Prospective, Longitudinal, 2 Year Survey
    1998 (Engelska)Ingår i: Journal of Rheumatology, ISSN 0315-162X, Vol. 25, nr 11, s. 2240-2248Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: In a prospective survey over a 2-year period we studied strength and bulk of the quadriceps muscle in the thighs of children with juvenile chronic arthritis (JCA). METHODS: Every third month for 2 years we measured isometric muscle strength in knee extensors with a hand-held dynamometer in 20 children with JCA. Ultrasound equipment was used to measure thigh muscle bulk. A joint evaluation was made using a standard severity score. The children had their ordinary medical treatment and physiotherapy during the observation period. RESULTS: Children with high severity scores in the knee or hip had least strength and muscle bulk. In the 4 children with the highest severity scores muscle strength was reduced to half of that expected. In 10 of the children there were clear variations in severity scores during the study period, for either better or worse. In these children an increase in the severity score correlated significantly with reduction in muscle strength and bulk (p < 0.05). The muscle strength and bulk changed in parallel in these children. Other factors, although not independent, such as polyarticular JCA, long duration of disease, and steroid treatment, also reduced muscle strength. CONCLUSION: The presence and intensity of local arthritis is one important factor affecting muscle function in JCA. Normal muscle strength and bulk is rapidly lost near an inflamed joint. It is difficult to maintain or achieve normal muscle function in the presence of active arthritis despite medical and physical treatment. We assume that the muscle weakness is in part caused by atrophy of the muscle, which is influenced by local arthritis.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13645 (URN)
    Tillgänglig från: 2004-05-27 Skapad: 2004-05-27 Senast uppdaterad: 2009-08-19
    3. Hand strength in juvenile chronic arthritis: a two-year follow-up
    Öppna denna publikation i ny flik eller fönster >>Hand strength in juvenile chronic arthritis: a two-year follow-up
    2003 (Engelska)Ingår i: Acta Paediatrica, ISSN 0001-656X, Vol. 92, nr 11, s. 1291-1296Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    AIM: To describe changes in muscle strength in the hands of children with juvenile chronic arthritis (JCA) and to examine the relationship between muscle strength, presence of local arthritis and disease subtype.

    METHODS: Twenty children (10 girls and 10 boys) with JCA aged 7 to 18 y were followed for two years. Isometric muscle strength in wrist dorsiflexors and handgrip strength were measured repeatedly. The results were compared with reference values for the same methods. Arthritis severity in the hand was scored every third month. Nerve conduction velocities were measured twice.

    RESULTS: Seven out of 20 patients had initially low or decreasing strength in one or both of the two tests. Five out of 20 children had reduced strength (more than two standard deviations below the mean of the reference group) in at least one test. Four children showed a significant reduction in muscle strength in at least one test during the observation time. The greatest reduction in strength was measured in four children with polyarticular disease. These children also had local arthritis in the hand. A greater proportion of children with polyarthritis had low or decreasing strength compared with children with oligoarthritis. The same was true for children with active arthritis in the hand. Nerve conduction velocities were normal in all cases and did not change.

    CONCLUSION: The majority of children with JCA have normal strength in the hand. Some children, especially those with polyarthritis and hand arthritis, have reduced muscle strength in the hand. Risk factors for low or decreasing strength are polyarthritis and/or active arthritis in the hand.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13646 (URN)10.1080/08035250310006340 (DOI)
    Tillgänglig från: 2004-05-27 Skapad: 2004-05-27 Senast uppdaterad: 2009-08-19
    4. Muscle involvement in juvenile idiopathic arthritis
    Öppna denna publikation i ny flik eller fönster >>Muscle involvement in juvenile idiopathic arthritis
    2004 (Engelska)Ingår i: Rheumatology, ISSN 1462-0324, Vol. 43, nr 12, s. 1546-1554Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: An observational study of changes in muscle structure and the relation to muscle strength in juvenile idiopathic arthritis (JIA).

    METHODS: Fifteen children and teenagers (eight girls and seven boys) with JIA, aged 9-19 yr (mean age 16.1), were studied. Muscle biopsies were obtained from the anterior tibial muscle and were examined using histopathological and immunohistochemical methods. Muscle fibre types were classified and fibre areas measured. As markers of inflammation, the major histocompatibility complex (MHC) class I and class II and the membrane attack complex (MAC) were analysed. Results were compared with biopsies from the gastrocnemius muscle in 33 young (19-23 yr) healthy controls. Isometric and isokinetic muscle strengths were measured in ankle dorsiflexion. Strength was compared with reference values for healthy age-matched controls. Nerve conduction velocities were recorded in the peroneal and sural nerves.

    RESULTS: Four of the 15 muscle biopsies were morphologically normal. Eleven biopsies showed minor unspecific changes. Two of these also showed minor signs of inflammation. MHC class II expression was found in 4/15 patients, which was significantly more than in the healthy controls (P = 0.0143). The expression of MHC class I and MAC did not differ from that in the controls. The mean area of type I fibres was lower than that of type IIA fibres in 12/13 biopsies. Muscle strength was significantly reduced in the patient group. There was a significant positive correlation between muscle fibre area and muscle strength. Nerve conduction studies were normal in all cases.

    CONCLUSIONS: Changes in leg muscle biopsies appear to be common in children and teenagers with JIA. The presence of inflammatory cells in the muscle and expression of MHC class II on muscle fibres may be a sign of inflammatory myopathy. There are no findings of type II muscle fibre hypotrophy or neuropathy, as in adults with RA.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13647 (URN)10.1093/rheumatology/keh381 (DOI)
    Tillgänglig från: 2004-05-27 Skapad: 2004-05-27 Senast uppdaterad: 2009-08-19
  • 30.
    Lönnqvist, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Applications of human skin in vitro2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

    Delarbeten
    1. Biodegradable Gelatin Microcarriers Facilitate Re-Epithelialization of Human Cutaneous Wounds - An In Vitro Study in Human Skin
    Öppna denna publikation i ny flik eller fönster >>Biodegradable Gelatin Microcarriers Facilitate Re-Epithelialization of Human Cutaneous Wounds - An In Vitro Study in Human Skin
    2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, s. e0128093-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds.

    Ort, förlag, år, upplaga, sidor
    Public Library of Science, 2015
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-120232 (URN)10.1371/journal.pone.0128093 (DOI)000355979500074 ()26061630 (PubMedID)
    Tillgänglig från: 2015-07-21 Skapad: 2015-07-20 Senast uppdaterad: 2017-12-04
    2. Tracing human keratinocytes and melanocytes with carboxyfluorescein hydroxysuccinimidyl ester (CFSE) staining
    Öppna denna publikation i ny flik eller fönster >>Tracing human keratinocytes and melanocytes with carboxyfluorescein hydroxysuccinimidyl ester (CFSE) staining
    2015 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Burn treatment and conditions of hypopigmentation may require autologous transplantation of keratinocytes and melanocytes. The tracing of transplanted cells presents a challenge. We report a methodology based on passive staining with carboxyfluorescein hydroxysuccinimidyl ester (CFSE) that enables localising cells in tissue sections to investigate the fate of transplanted cells in wound re-epithelialisation. CFSE-stained keratinocytes and CFSE-stained melanocytes were transplanted to human full thickness in vitro wounds either as cell suspension for keratinocytes, or with the aid of  macroporous gelatin microcarriers for both cells types in single and co-culture. Viability and migration of CFSE-stained keratinocytes and melanocytes were investigated, and proliferation of the cells cultured on microcarriers was measured with flow cytometry. Wounds with transplanted cells were harvested after seven, 14 and 21 days in culture, cryosectioned and investigated using fluorescence microscopy. Sections from wounds with transplanted co-cultured keratinocytes and melanocytes were stained for pancytokeratin to distinguish double stained keratinocytes. The CFSE-staining of keratinocytes and melanocytes did not affect the viability, migration or proliferation of the cells. Transplanted cells were traced in tissue sections after 21 days and wound re-epithelialisation was not affected. We propose a novel application of CFSE-staining in transplantation studies here presented with primary human keratinocytes and melanocytes.

    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-123310 (URN)
    Tillgänglig från: 2015-12-10 Skapad: 2015-12-10 Senast uppdaterad: 2015-12-10Bibliografiskt granskad
    3. Influence of acidic pH on keratinocyte function and re-epithelialisation of human in vitro wounds
    Öppna denna publikation i ny flik eller fönster >>Influence of acidic pH on keratinocyte function and re-epithelialisation of human in vitro wounds
    2015 (Engelska)Ingår i: Journal of Plastic Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 49, nr 6, s. 346-352Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Chronic wounds are one of the greatest challenges for the healthcare system. Today, a plethora of dressings are used in the treatment of these wounds, each with specific influence on the wound environment. Due to differences in the permeability of the dressings the use will result in differences in the pH balance in the wound bed. However, little is known about how changes in the pH in the wound environment affect the different phases of the healing process. Aim: The aim of the present study was to investigate the effects of acidic pH on the regeneration phase by studying keratinocyte function in vitro and re-epithelialisation in an in vitro model of human skin. Results:In vitro assays showed reduced viability and migration rates in human keratinocytes when pH was lowered. Real time PCR revealed differential expression of genes related to wound healing and environmental impairment. Tissue culture showed no re-epithelialisation of wounds subjected to pH 5.0 and moderate re-epithelialisation at pH 6.0, compared to controls at pH 7.4. Conclusion: The results indicate that lowering pH down to pH 5.0 in wounds is counterproductive in aspect of keratinocyte function which is crucial for successful wound healing.

    Ort, förlag, år, upplaga, sidor
    Taylor & Francis, 2015
    Nyckelord
    Keratinocyte; pH; re-epithelialisation; wound model
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-123140 (URN)10.3109/2000656X.2015.1053397 (DOI)000364409400006 ()26051107 (PubMedID)
    Tillgänglig från: 2015-12-07 Skapad: 2015-12-04 Senast uppdaterad: 2017-12-01Bibliografiskt granskad
    4. Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds
    Öppna denna publikation i ny flik eller fönster >>Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds
    2016 (Engelska)Ingår i: Toxicology Mechanisms and Methods, ISSN 1537-6516, E-ISSN 1537-6524, Vol. 26, nr 2, s. 82-87Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R2 = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.

    Ort, förlag, år, upplaga, sidor
    Taylor & Francis, 2016
    Nyckelord
    Human full thickness skin, in vitro model, SDS
    Nationell ämneskategori
    Farmakologi och toxikologi
    Identifikatorer
    urn:nbn:se:liu:diva-123312 (URN)10.3109/15376516.2015.1091537 (DOI)000373528000002 ()26446981 (PubMedID)
    Tillgänglig från: 2015-12-10 Skapad: 2015-12-10 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
  • 31.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Studies for Better Treatment of Patients with Glioma2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.

    The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.

    The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).

    The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.

    The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.

    In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.

    Delarbeten
    1. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Öppna denna publikation i ny flik eller fönster >>Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Visa övriga...
    2012 (Engelska)Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, nr 9, s. 916-926Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84333 (URN)10.1016/S1470-2045(12)70265-6 (DOI)000308425600019 ()
    Anmärkning

    Funding Agencies|Merck||Lions Cancer Research Foundation||University of Umea||Swedish Cancer Society||Schering-Plough||University of Umea, Sweden||Cancer Fonden, Sweden||

    Tillgänglig från: 2012-10-05 Skapad: 2012-10-05 Senast uppdaterad: 2019-11-06
    2. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Öppna denna publikation i ny flik eller fönster >>Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Visa övriga...
    2017 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 12, s. 1776-1785Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

    Ort, förlag, år, upplaga, sidor
    TAYLOR & FRANCIS LTD, 2017
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:liu:diva-144005 (URN)10.1080/0284186X.2017.1332780 (DOI)000418118800016 ()28675067 (PubMedID)
    Anmärkning

    Funding Agencies|Merck; Linkoping University Hospital for Neuro-research; Lions Cancer Foundation; Cancer Foundation Norrland, Umea, Sweden; LIUCancer; South-East Sweden FORSS

    Tillgänglig från: 2018-01-02 Skapad: 2018-01-02 Senast uppdaterad: 2019-11-06
    3. Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Öppna denna publikation i ny flik eller fönster >>Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Visa övriga...
    2019 (Engelska)Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Ort, förlag, år, upplaga, sidor
    Oxford: Oxford University Press, 2019
    Nationell ämneskategori
    Medicinsk biovetenskap Klinisk laboratoriemedicin
    Identifikatorer
    urn:nbn:se:liu:diva-160808 (URN)10.1093/nop/npz039 (DOI)
    Tillgänglig från: 2019-10-09 Skapad: 2019-10-09 Senast uppdaterad: 2019-11-06Bibliografiskt granskad
  • 32.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Winther Kristensen, Bjarne
    Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark.
    Hovey, Elizabeth
    Department of Medical Oncology, Nelune Comprehensive Cancer Centre, Prince of Wales Hospital , Randwick, Sydney, NSW, Australia University of New South Wales , Sydney, Australia.
    Henriksson, Roger
    Department of Radiation Sciences, University of Umeå , Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma2019Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Publikationen är tillgänglig i fulltext från 2020-09-25 08:00
  • 33.
    Martinez, Cristina Alicia
    et al.
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Cambra, Josep Miquel
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Parrilla, Inmaculada
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Lucas, Xiomara
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Martinez, Emilio Arsenio
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Izpisua, Juan Carlos
    Salk Institute for Biological Studies, La Jolla, CA, USA.
    Cuello, Cristina
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Gil, Maria Antonia
    University of Murcia, Murcia, Spain; Campus de Ciencias de la Salud, Murcia, Spain.
    Three-to-5-day weaning-to-estrus intervals do not affect neither efficiency of collection nor in vitro developmental ability of in vivo-derived pig zygotes2019Ingår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 141, s. 48-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An efficient system to collect large numbers of vital zygotes is a pre-requisite for application of zygote genome-editing technology, including development of efficient models for xenotransplantation using pigs. Owing to the sub-optimal in vitro production of zygotes in pigs, efficient collection of in vivo developed zygotes is required. Timing of ovulation is a key factor to sustain efficiency since the interval between pronuclear formation and the first division is very short in pigs. The weaning-to-estrus interval can, due to its inverse relation with length of estrus and time of ovulation, interfere with ovulation and make it asynchronous, which reduces the probability of obtaining zygotes. This retrospective study compared the effects of three weaning-to-estrus intervals of 3, 4 or 5 days on zygote collection efficiency in a total of 17 trials over a 3-year period including 223 sows. Donor sows in groups of 10–15 animals were super-ovulated with eCG 24 h after weaning and those in estrus at 48–72 h post-eCG were immediately treated with hCG, followed by insemination 6 and 24 h thereafter. Collected structures during laparotomy on Day 2 (Day 0: onset of estrus) were morphologically evaluated and only those with a single cell and two visible polar bodies were considered as zygotes. Zygotes were injected with CRISPR-Cas9 editor mixture and cultured for 6 days to evaluate their developmental ability against non-injected control zygotes. Of all recovered structures (N = 5,468), 67.4%, 30.8% and 1.8% were zygotes, 2-cell embryos and oocytes-degenerated embryos, respectively. The different weaning-to-estrus intervals did not affect either the percentages of collected zygotes (range: 64.1%–70.0%) or the percentages of sows with zygotes at collection time (range: 69.0%–73.3%). The weaning-to-estrus intervals did not affect the in vitrodevelopmental ability of zygotes. After 24 h of culture, 78.1 ± 2.0% and 95.1 ± 0.6 (P < 0.05) of injected (N = 2,345) and non-injected (N = 335) zygotes, respectively, developed to 2-to-4-cell embryo stage. The total efficiency of the system was 64.1 ± 2.2% and 85.8 ± 1.5% (P < 0.05) for injected and non-injected zygotes, respectively. In conclusion, the results indicate that neither the efficiency of collecting in vivo derived porcine zygotes from superovulated sows nor the zygote ability to develop to blastocyst after cytoplasmic genome-editing injection were affected by a weaning-to-estrus interval between 3-to-5 days.

  • 34.
    Martínez-Pastor, Felipe
    et al.
    Department of Molecular Biology (Cell Biology), Universidad de León, Spain; INDEGSAL, Universidad de León, León, Spain.
    Álvarez, Mercedes
    INDEGSAL, Universidad de León, León, Spain; Department of Medicine, Surgery and Veterinary Anatomy, Universidad de León, León, Spain.
    Guerra, Camino
    Department of Animal Health and Anatomy, Veterinary Faculty, Universitat Autònoma de Barcelona, Barcelona, Spain.
    Chamorro, César A
    Department of Medicine, Surgery and Veterinary Anatomy, Universidad de León, León, Spain; Department of Animal Health and Anatomy, Veterinary Faculty, Universitat Autònoma de Barcelona, Barcelona, Spain.
    Anel-López, Luis
    INDEGSAL, Universidad de León, León, Spain; Department of Medicine, Surgery and Veterinary Anatomy, Universidad de León, León, Spain.
    de Paz, Paulino
    Department of Molecular Biology (Cell Biology), Universidad de León, Spain; INDEGSAL, Universidad de León, León, Spain.
    Anel, Luis
    INDEGSAL, Universidad de León, León, Spain; Department of Medicine, Surgery and Veterinary Anatomy, Universidad de León, León, Spain.
    Alvarez-Rodriguez, Manuel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. INDEGSAL, Universidad de León, León, Spain; Department of Animal Health and Anatomy, Veterinary Faculty, Universitat Autònoma de Barcelona, Barcelona, Spain.
    Extender osmolality, glycerol and egg yolk on the cryopreservation of epididymal spermatozoa for gamete banking of the Cantabric Chamois (Rupicapra pyrenaica parva)2019Ingår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 125, s. 109-114, artikel-id S0093-691X(18)30573-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Germplasm banking is a key technology enabling the ex-situ conservation of wild species. However, cryopreservation protocols must be tested to assure the applicability of the banked material. The objective of this study was defining a range of parameters for the composition of a semen extender for Cantabrian chamois epididymal spermatozoa (post-mortem collection). The freezing extender was based in a TES-Tris-fructose buffer, modifying its composition in three experiments: Osmolality of the buffer (320, 380 or 430 mOsm/kg, 8% glycerol, 15% egg yolk), glycerol (4 or 8%, 430 mOsm/kg, 15% egg yolk), egg yolk (10 or 15%, 430 mOsm/kg, 4% glycerol). Sperm was extended at 100 mill. spermatozoa/ml, cooled at 5 °C and frozen at -20 °C/min. Sperm quality was assessed pre and post-thawing (CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability and acrosomal damage by flow cytometry). Freezability was good overall, with total motility of 65.5% ± 2.4 initial and 55.8% ± 2.4 post-thawing. The extenders affected the post-thaw sperm quality marginally. Whereas osmolalities and glycerol concentrations seemed not to differ, 430 mOsm/kg and 4% glycerol might be preferred. Egg yolk concentrations only differed on sperm velocity (VCL: 84.0 ± 6.7 μm/s in 10% vs. 70.7 ± 6.2 μm/s in 15%, P < 0.05). Our results suggest a good cryotolerance of chamois epididymal spermatozoa, with a preferred extender composition of hyperosmotic buffer, glycerol in the 4% range and lower egg yolk (10% range) than other ruminants.

  • 35.
    Midhagen, Gunnar
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken.
    Adult Coeliac Disease in Clinical Practice2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

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

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

    Delarbeten
    1. Adult coeliac disease within a defined area in Sweden: A study of prevalence and associated diseases
    Öppna denna publikation i ny flik eller fönster >>Adult coeliac disease within a defined area in Sweden: A study of prevalence and associated diseases
    1988 (Engelska)Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 23, nr 8, s. 1000-1004Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    An epidemiologic study of coeliac disease in a geographically defined area of Sweden showed that the prevalence was 95.5/105 inhabitants aged 15 years or more. The highest prevalence, 178/105 inhabitants, was found in the age group 65-74 years. The lowest prevalence, 39/105 inhabitants, was found in patients aged 15-24 years. Among the associated diseases an especially high incidence of associated thyroid disease was observed: thyrotoxicosis occurred in 5.0% and hypothyroidism in 5.8% of the patients.

    Nyckelord
    Coeliac disease, dermatitis herpetiformis, epidemiology, thyroid disease
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-13985 (URN)10.3109/00365528809090160 (DOI)