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  • 51. Amini, Rose-Marie
    et al.
    Enblad, Gunilla
    Gustavsson, Anita
    Ekman, Tor
    Erlanson, Martin
    Haapaniemi, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Glimelius, Bengt
    Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience.2000In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 65, p. 379-389Article in journal (Refereed)
  • 52.
    Ander, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Preservation of parathyroid function in thyroid and parathyroid surgery1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Preservation of normal parathyroid function and calcium homeostasis after operations on the thyroid and parathyroid glands is a difficult assignment in endocrine surgery, and it is crucial to minimise the risks of permanent postoperative hypoparathyroidism. The aim of this thesis was to study the vascular supply of the parathyroid glands and the revascularisation, growth, and function of transplanted parathyroid tissue, in order to add new information about parathyroid preservation.

    The microcirculation and blood supply of normal, hyperplas~c and adenomatous parathyroid glands were studied with laser Doppler flowmetry in 103 patients during operations on the thyroid and parathyroid glands. In normal parathyroid glands the blood flow was higher compared with that in hyperplastic glands and adenomas. Occlusion of the main trunks of the inferior and superior thyroid arteries reduced the blood flow by 35% and 25%, respectively. The reduction was similar in normal, hyperplastic, and adenomatous parathyroid glands. In 12 patients with single parathyroid adenomas, the increased concentration of parathyroid hormone (PTH) remained mainly unchanged despite appreciable reduction in blood flow. In 16 patients the microcirculation and macroscopic appearance of normal parathyroid glands located anteriorly on the thyroid lobe were analysed before and after dissection for in situ preservation. There was a poor correlation between reduction in blood flow and macroscopic appearance of the glands. Laser Doppler flowmetry (LDF) showed that the disturbed microcirculation often recovered 30-60 minutes after dissection for preservation.

    Parathyroid tissue obtained from 47 patients operated on for hyperparathyroidism was implanted subcutaneously in athymic mice. The processes of revascularisation, morphology, cell proliferation, and function of normal, hyperplastic, and adenomatous parathyroid tissue were studied at 2 and 4 days and 1, 4, 7 and 12 weeks after transplantation. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. The transplanted tissues were examined by light and electron microscopy and by autoradiography after continuous infusion of tritiated thymidine. The relative amount of viable tissue was assessed with a computer image-analysing program. Graft function was judged by measuring human iPTH in mouse serum.

    Over 90% of the transplants took and the original structure of the tissue was well preserved. Confluent areas of parathyroid tissue could be seen in 80% of the transplants. The mean loss of viable tissue in all three groups was 45%.

    Immunohistochemical examination showed ingrowth of vessels from the host into the transplant. The sprouts matured gradually into vessels with thin endothelial linings and capillary fenestrations in adenomatous and hyperplastic transplants but not in transplants of normal tissue.

    In normal parathyroid tissue the proliferation of parathyroid parenchyma! cells increased only slightly in contrast to the advancing proliferative capacity in adenomatous tissue. In contrast to adenomas, parenchyma! cell proliferative capacity in hyperplastic tissue decreased at 12 week.

    Concentrations of iPTH were raised at one week in hyperplastic and adenomatous tissue. Twelve weeks after transplantation iPTH concentrations in relation to the amount of transplanted tissue and relative area of viable tissue were comparable in all three groups of transplanted tissue.

    We conclude that, LDF is a feasible method to study physiological blood flow in human parathyroid glands. Parathyroid blood supply is not as dependent on the inferior thyroid artery as was previously suggested. LDF showed that blood flow recovered in parathyroid glands dissected for in situ preservation and any decision about autografting should be delayed until the end of the operation. Parathyroid transplants re vascularise from host vessels and this is more pronounced and proceeds faster in hyperplastic and adenomatous tissue than in normal transplants. In contrast to nonnal and hyperplastic transplants, adenomatous tissue has a greater and increasing proliferative capacity. The iPTH concentration as an expression of parathyroid function correlates poorly with parenchyma! cell proliferation.

  • 53.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Cutaneous microdialysis: Is it worth the sweat?2006In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 126, no 6, p. 1207-1209Article in journal (Other academic)
    Abstract [en]

    Microdialysis is a minimally invasive technique for chronological study of metabolic, biochemical, and pharmacological events in living tissue. In the skin, probes are placed in the dermis or subcutis for research in two main areas, percutaneous penetration and various aspects of inflammation. Advances in technique, and the concept of data generation and analysis are leading to new areas of application.

  • 54.
    Anderson, Chris
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Lindén, Maria
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    High resolution laser Doppler perfusion imaging for visualisation of changes in skin circulation after microdialysis probe insertion1996In: Jadassohn Centenary Congress,1996, 1996Conference paper (Other academic)
  • 55.
    Anderson, Chris
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Analysis of laser Doppler perfusion images from contact reactions1996In: Jadassohn Centenary Congress,1996, 1996Conference paper (Other academic)
  • 56.
    Anderson, Emma
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Oligodendrocytens nyckelroll2000In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, p. 3265-3268Article in journal (Other (popular science, discussion, etc.))
  • 57.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cordManuscript (preprint) (Other academic)
    Abstract [en]

    As observed by Del Rio-Hortega (1928), the oligodendroglial population includes Type I and 11 cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. AI the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Against this background, the present study examines the 3D anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker 04 showed that a few positive cells are at hand at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases some 4x, from 50 µm to over 200 flm, while the length of the spinal cord increases 36% only. Hence, early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

  • 58.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphology of early developing oligodendrocytes in the ventrolateral spinal cord of the chicken2003In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 32, no 9, p. 1045-1053Article in journal (Refereed)
    Abstract [en]

    The oligodendroglial population includes Type I and II cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord, oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. At the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Based on these findings, the present study examines more thoroughly the anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker O4 showed that a few positive cells are present at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases about 4×, from 50 µm to over 200 µm, while the length of the spinal cord increases 36% only. This indicates that early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

  • 59.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    The type IV Oligodendrocyte: experimental studies on chicken white matter2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In mammals, islet amyloid polypeptide (IAPP) is co-produced with insulin in pancreatic ß-cells. In the chicken, the expression of IAPP in the brain is more than 10-fold higher than in the pancreas. We made the fortuitous finding that a polyclonal rabbit antiserum raised against chicken IAPP did not recognise the immunogen, but labelled a subpopulation of oligodendroglia! cells in chicken white matter. The hitherto unknown antigen was called T4-O (Type 4 Oligodendrocyte) since it was localised to the Schwann cell-like Type IV oligodendrocyte of Del Rio-Hortega (1928). This formed a starting point for the present thesis, which is centred on the Type IV oligodendrocyte in chicken white matter.

    Biochemical analysis of chicken spinal cord showed that the T4-O molecule is a protein with a molecular weight of approximately 100 kDa and an isoelectric point of about 4. Further characterisation has not yet been possible.

    Immunohistochemical studies on frozen sections revealed that the white matter oligodendrocytes exhibit subpopulations expressing T4-O immunoreactivity strongly, weakly or not at all. Strongly T4-O immunoreactive (IR) oligodendrocytes are co-localised with thick myelinated fibres in the ventral (VF) and lateral funiculi of the spinal cord. A corresponding T4-O immunoreactivity is not found in the fish, the frog, the turtle, the rat and the rabbit.

    To find out when the T4-0 antigen first appears during development we examined sections from embryonic and post-hatching chicken spinal cords by immunohistochemistry. This showed that the T4-O molecule is first expressed in the VF at embryonic day (E)15, after which the number of IR cells increases with age. Oligodendrocytes cultivated in vitro without or with neurons do not develop a T4-O IR phenotype.

    These findings called for a closer analysis of the structural development of chicken VF white matter. Electron microscopic (EM) examination revealed a developmental sequence of events principally similar to the development of mammalian white matter, but with a more rapid time course. As seen in the electron microscope the first compact myelin has appeared by E12, when most oligodendrocytes are multipolar. By E15 it seems that these cells have developed a Type IV phenotype, possibly by eliminating some sheaths.

    Histochemical analysis of Vibratome sections showed that Marchi-positive myelinoid bodies are enriched in white matter areas containing many T4-O IR oligodendrocytes and many large myelinated axons.

    Examination of the three-dimensional (3D) anatomy of early VF oligodendrocytes in Vibratome slices after 04 labelling or after intracellular injection of a fluorescent dye revealed that these units indeed are Schwann cell-like, with a start length of around 50 µm. We also found that these sheaths expand very rapidly, reaching lengths exceeding 200 µm in three days (E12- E15). The 3D data conformed to our EM evidence that the early oligodendrocytes develop a unipolar Schwann cell-like Type IV anatomy through elimination of some sheaths.

    To my knowledge the present observations represent the first evidence for an oligodendroglia! heterogeneity in the chicken spinal cord. Differences among oligodendrocytes might, conceivably, explain why inherited disorders of myelin metabolism such as Krabbe's disease, affect some CNS areas more than others.

    List of papers
    1. Molecular heterogeneity of oligodendrocytes in chicken white matter
    Open this publication in new window or tab >>Molecular heterogeneity of oligodendrocytes in chicken white matter
    1999 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 27, no 1, p. 15-21Article in journal (Refereed) Published
    Abstract [en]

    The classical studies by Del Rio Hortega (Mem. Real. Soc. Espan. Hist. Nat. 14:40–122, 1928) suggest that the oligodendrocyte population includes four morphological subtypes. Recent data from the cat and the rat show that the anatomy of oligodendrocytes related to early myelinating prospective large fibers differs from that of oligodendrocytes related to late myelinating prospective small fibers. After application of a polyclonal antiserum to cryostat sections from the chicken CNS, we noted that glial cells in the spinal cord white matter had become labeled. Analysis of the occurrence and cellular localization of this immunoreactivity—the T4-O immunoreactivity—in the CNS of the adult chicken showed that T4-O immunoreactive cells are enriched in the ventral funiculus and superficially in the lateral funiculus of the spinal cord, where they are co-localized with large fibers. Double staining with T4-O antiserum and anti-GFAP or the lectin BSI-B4 revealed that T4-O immunoreactive cells are not astrocytes or microglia. Staining with anti-HSP108, a general marker for avian oligodendrocytes, showed that T4-O immunoreactivity defines an oligodendroglial subpopulation. A search for T4-O immunoreactivity in spinal cord white matter of some other vertebrates revealed that T4-O immunoreactive cells are not present in sections from fish, frog, turtle, rat, and rabbit spinal cord white matter. These results suggest the presence of a fiber size-related molecular heterogeneity among chicken white matter oligodendrocytes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24854 (URN)10.1002/(SICI)1098-1136(199907)27:1<15::AID-GLIA2>3.0.CO;2-I (DOI)9254 (Local ID)9254 (Archive number)9254 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro
    Open this publication in new window or tab >>Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro
    Show others...
    2000 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 284, no 1-2, p. 21-24Article in journal (Refereed) Published
    Abstract [en]

    Accumulating data suggest that the oligodendrocyte population includes morphological and biochemical subtypes. We recently reported that a polyclonal antiserum against an unknown antigen, the T4-O molecule, labels a subpopulation of chicken oligodendrocytes, obviously representing the type IV variety of Del Rio Hortega. The present study examines the developmental expression of the T4-O molecule in situ and in vitro. The results show that T4-O immunoreactive cells first appear at E15 in the ventral funiculus. But, oligodendrocytes cultured in vitro with or without neurones do not develop a T4-O immunoreactivity. We conclude that oligodendrocytes in the spinal cord of chicken embryos first express the T4-O molecule some time after onset of myelination, and that the T4-O immunoreactive phenotype does not develop in vitro.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24853 (URN)10.1016/S0304-3940(00)00989-7 (DOI)9253 (Local ID)9253 (Archive number)9253 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Myelination of prospective large fibres in chicken ventral funiculus
    Open this publication in new window or tab >>Myelination of prospective large fibres in chicken ventral funiculus
    2000 (English)In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 29, no 10, p. 755-764Article in journal (Refereed) Published
    Abstract [en]

    In mammals, the oligodendrocyte population includes morphological and molecular varieties. We reported previously that an antiserum against the T4-O molecule labels a subgroup of oligodendrocytes related to large myelinated axons in adult chicken white matter. We also reported that T4-O immunoreactive cells first appear in the developing ventral funiculus (VF) at embryonic day (E)15, subsequently increasing rapidly in number. Relevant fine structural data for comparison are not available in the literature. This prompted the present morphological analysis of developing and mature VF white matter in the chicken. The first axon-oligodendrocyte connections were seen at E10 and formation of compact myelin had started at E12. Between E12 and E15 the first myelinating oligodendrocytes attained a Schwann cell-like morphology. At hatching (E21) 60% of all VF axons were myelinated and in the adult this proportion had increased to 85%. The semilunar or polygonal oligodendrocytes associated with adult myelinated axons contained many organelles indicating a vivid metabolic activity. Domeshaped outbulgings with gap junction-like connections to astrocytic profiles were frequent. Oligodendrocytes surrounded by large myelinated axons and those surrounded by small myelinated axons were cytologically similar. But, thick and thin myelin sheaths had dissimilar periodicities and Marchi-positive myelinoid bodies occurred preferentially in relation to large myelinated axons. We conclude that early oligodendrocytes contact axons and form myelin well before the first expression of T4-O and that emergence of a T4-O immunoreactivity coincides in time with development of a Type IV phenotype. Our data also show that oligodendrocytes associated with thick axons are cytologically similar to cells related to thin axons. In addition, the development of chicken VF white matter was found to be similar to the development of mammalian white matter, except for the rapid time course.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-49235 (URN)10.1023/A:1010994505741 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
    4. Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cord
    Open this publication in new window or tab >>Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cord
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    As observed by Del Rio-Hortega (1928), the oligodendroglial population includes Type I and 11 cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. AI the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Against this background, the present study examines the 3D anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker 04 showed that a few positive cells are at hand at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases some 4x, from 50 µm to over 200 flm, while the length of the spinal cord increases 36% only. Hence, early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81479 (URN)
    Available from: 2012-09-17 Created: 2012-09-17 Last updated: 2012-09-17Bibliographically approved
  • 60.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eriksson, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Westermark, Gunilla
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro2000In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 284, no 1-2, p. 21-24Article in journal (Refereed)
    Abstract [en]

    Accumulating data suggest that the oligodendrocyte population includes morphological and biochemical subtypes. We recently reported that a polyclonal antiserum against an unknown antigen, the T4-O molecule, labels a subpopulation of chicken oligodendrocytes, obviously representing the type IV variety of Del Rio Hortega. The present study examines the developmental expression of the T4-O molecule in situ and in vitro. The results show that T4-O immunoreactive cells first appear at E15 in the ventral funiculus. But, oligodendrocytes cultured in vitro with or without neurones do not develop a T4-O immunoreactivity. We conclude that oligodendrocytes in the spinal cord of chicken embryos first express the T4-O molecule some time after onset of myelination, and that the T4-O immunoreactive phenotype does not develop in vitro.

  • 61.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Myelination of prospective large fibres in chicken ventral funiculus2000In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 29, no 10, p. 755-764Article in journal (Refereed)
    Abstract [en]

    In mammals, the oligodendrocyte population includes morphological and molecular varieties. We reported previously that an antiserum against the T4-O molecule labels a subgroup of oligodendrocytes related to large myelinated axons in adult chicken white matter. We also reported that T4-O immunoreactive cells first appear in the developing ventral funiculus (VF) at embryonic day (E)15, subsequently increasing rapidly in number. Relevant fine structural data for comparison are not available in the literature. This prompted the present morphological analysis of developing and mature VF white matter in the chicken. The first axon-oligodendrocyte connections were seen at E10 and formation of compact myelin had started at E12. Between E12 and E15 the first myelinating oligodendrocytes attained a Schwann cell-like morphology. At hatching (E21) 60% of all VF axons were myelinated and in the adult this proportion had increased to 85%. The semilunar or polygonal oligodendrocytes associated with adult myelinated axons contained many organelles indicating a vivid metabolic activity. Domeshaped outbulgings with gap junction-like connections to astrocytic profiles were frequent. Oligodendrocytes surrounded by large myelinated axons and those surrounded by small myelinated axons were cytologically similar. But, thick and thin myelin sheaths had dissimilar periodicities and Marchi-positive myelinoid bodies occurred preferentially in relation to large myelinated axons. We conclude that early oligodendrocytes contact axons and form myelin well before the first expression of T4-O and that emergence of a T4-O immunoreactivity coincides in time with development of a Type IV phenotype. Our data also show that oligodendrocytes associated with thick axons are cytologically similar to cells related to thin axons. In addition, the development of chicken VF white matter was found to be similar to the development of mammalian white matter, except for the rapid time course.

  • 62.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Department of Neurosciences, Lerner Research Institue, Cleveland Clinic Foundation, Cleveland, Ohio.
    Westermark, Gunilla
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Molecular heterogeneity of oligodendrocytes in chicken white matter1999In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 27, no 1, p. 15-21Article in journal (Refereed)
    Abstract [en]

    The classical studies by Del Rio Hortega (Mem. Real. Soc. Espan. Hist. Nat. 14:40–122, 1928) suggest that the oligodendrocyte population includes four morphological subtypes. Recent data from the cat and the rat show that the anatomy of oligodendrocytes related to early myelinating prospective large fibers differs from that of oligodendrocytes related to late myelinating prospective small fibers. After application of a polyclonal antiserum to cryostat sections from the chicken CNS, we noted that glial cells in the spinal cord white matter had become labeled. Analysis of the occurrence and cellular localization of this immunoreactivity—the T4-O immunoreactivity—in the CNS of the adult chicken showed that T4-O immunoreactive cells are enriched in the ventral funiculus and superficially in the lateral funiculus of the spinal cord, where they are co-localized with large fibers. Double staining with T4-O antiserum and anti-GFAP or the lectin BSI-B4 revealed that T4-O immunoreactive cells are not astrocytes or microglia. Staining with anti-HSP108, a general marker for avian oligodendrocytes, showed that T4-O immunoreactivity defines an oligodendroglial subpopulation. A search for T4-O immunoreactivity in spinal cord white matter of some other vertebrates revealed that T4-O immunoreactive cells are not present in sections from fish, frog, turtle, rat, and rabbit spinal cord white matter. These results suggest the presence of a fiber size-related molecular heterogeneity among chicken white matter oligodendrocytes.

  • 63. Anderson, Kristina
    et al.
    Rusterholz, Corinne
    Månsson, Robert
    Jensen, Christina T
    Bacos, Karl
    Sasan, Zandi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Sasaki, Yutaka
    Nerlov, Claus
    Sigvardsson, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Jacobsen, Sten Eirik W
    Ectopic expression of PAX5 promotes maintenance of biphenotypic myeloid progenitors coexpressing myeloid and B-cell lineage-associated genes2007In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 109, no 9, p. 3697-3705Article in journal (Refereed)
    Abstract [en]

    The transcription factor PAX5 is a critical regulator of B-cell commitment and development. Although normally not expressed in myeloid progenitors, PAX5 has recently been shown to be frequently expressed in myeloid malignancies and to suppress expression of myeloid differentiation genes, compatible with an effect on the differentiation or maintenance of myeloid progenitors. However, previous studies in which PAX5 was ectopically expressed in normal myeloid progenitors in vivo and in vitro provided conflicting results as to the effect of PAX5 on myeloid development. Herein, we demonstrate that on ectopic expression of PAX5 in bone marrow multipotent stem/progenitor cells, cells with a biphenotypic B220+GR-1/MAC-1+ phenotype are produced. These remain cytokine-dependent, but unlike control-transduced cells they sustain long-term generation of myeloid progenitors in vitro and remain capable of myeloid differentiation. Notably, PAX5+B220+GR-1/MAC- 1+ myeloid progenitors coexpress, at the single-cell level, myeloid genes and otherwise B-cell-specific PAX5 target genes. These findings establish that ectopic expression of PAX5 introduces extensive self-renewal properties in otherwise short-lived myeloid progenitors. Along with the established ectopic expression of PAX5 in acute myeloid leukemia, this motivates a careful investigation of the potential involvement of ectopic PAX5 expression in myeloid and biphenotypic leukemias. © 2007 by The American Society of Hematology.

  • 64.
    Andersson, Eva
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences.
    Studies on cellular vitamin A metabolism and effects of UV irridation in human keratinocytes and melanocytes1998Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Reinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation in a variety of cell types, including epidermal cells. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to the acid form retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors inducing gene transcriptions. Using high-performance liquid chromatography we have investigated the endogenous ROH and ddROH concentrations and the metabolism of [3H]ROH in cultures of keratinocytes, melanocytes, Hela cells, melanoma cell and two cell lines of non human origin (CV-1 and F9). Cellular retinoid-binding proteins (CRABP I, CRABP II) were also determined by radioligand binding technique and RT-PCR.

    Keratinocytes and melanocytes contained high concentrations of ROH and ddROH, Hela- and melanoma cells contained intermediate amounts of retinoids, while in the cell of non human origin only ROH was detected. Analysis of CRABP Il showed a correlation to the cells' ability to accumulate ddROH, suggesting a role for this protein in the 3,4-didehydro metabolic pathway. In melanocytes CRABP I was highly expressed and in melanoma cells CRABP Il dominated. CV-1 and F9 contained low levels of CRABP Il.

    Incubation with [3H]ROH for 1-24 hours resulted in a rapid appearance of [3H]ddROH in keratinocytes and toa lesser extent in Hela cells,  melanocytes and melanoma cells. At the end of the incubation the amount of [3H]ddROH corresponded to 30% of the total cellular radioactivity in the Hela cells, 10% in the keratinocytes, 4% in melanocytes and only 1 % in the melanoma cells. The cell types of non human origin did not produce [3H]ddROH from [3H]ROH. These findings support the concept that ddROH production is cell and tissue specific.

    Another purpose of this study was to examine the influence of ultraviolet radiation (UVR) on cellular metabolism of retinoids. A physiological dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in cell cultures by 20-50%. The concentration retumed to control levels in about 1-2 days. The uptake of [3H]ROH which was almost 3-fold higher in melanocytes than in keratinocytes, did not much differ between irradiated and control cells. Also, the formation of [3H]ddROH from [3H]ROH was unaffected by UVR. However, the accumulation of the metabolite all-trans [3H]RA was 60% higher in irradiated than unirradiated keratinocytes and melanocytes. Our data indicate that restoration of cellular vitamin A after UVR is mainly accomplished by a retarded metabolism of RA to less active compounds and indicate that the homeostatic control of RA production isa priority after UVR. Failure of this control may be an important factor in UV-induced carcinogenesis in vivo.

  • 65.
    Andersson, Eva
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Retinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors, which induce gene transcriptions. A perturbed ROH metabolism is observed in several dermatoses and iu non-melanoma skin cancer. Dietary ß-carotene has been considered to play a critical role in the natural defence against cancer. Whether ß-carotene is converted to ROH in the skin has been debated.

    We have investigated ß-carotene and retinoid metabolism, retinoid binding proteins and retinoid receptors in human keratinocytes (KCs) and melanocytes (MCs) in vitro. Similar studies of vitamin A have been done in human malignant epithelial cells (HeLa) and malignant melanoma cells. The influence of ultraviolet radiation (UVR) on retinoid metabolism and receptor expression was specially focused upon this thesis. KCs and MCs contained high concentrations of ROH, ddROH, while HeLa- and melanoma cells contained lower levels. KCs contained the highest level of the retinoid-binding proteins CRBP I and CRABP II compared to MCs, HeLa and melanoma cells. High CRABP II levels showed a correlation with the ability to accumulate ddROH. In MCs, CRABP I was highly expressed, but in melanoma cells CRABP II dominated. The difference between MCs and melanoma cells in receptor levels was most pronounced for RARß, which was highly expressed in melanoma cells. Such dissimilarities between benign and malignant MCs might play a role in differentiation and growth regulation. The uptake of [3H]ROH, [3H]RA and ß-carotene was significantly higher in MCs than in KCs. We were able to demonstrate that [14C]ß-carotene was converted to [14C]ROH in both these cell types. This suggests that this local storage of ß-carotene might serve as au alternative supply for vitamin A in the skin.

    A moderate dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in KCs and MCs by 20-50%. The concentration returned to starting levels in 1-2 days, and could be explained by a retarded metabolism of RA, the biologically most active metabolite. When KCs and MCs were exposed to UVR, the mRNA and protein levels of the three nuclear retinoid receptors (RARα, RARγ and RXRα) decreased rapidly. In MCs these levels were close to normal 3 days postirradiation. In KCs only the RARα mRNA and protein levels returned to baseline within 3 days. This thesis has increased our knowledge of the effects of UVR on retinoid metabolism and retinoid receptors in human cells. Further studies are needed to understand the role of ß-carotene and retinoid signaling in UV induced skin cancer.

    List of papers
    1. The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression
    Open this publication in new window or tab >>The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression
    1994 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1224, no 3, p. 349-354Article in journal (Refereed) Published
    Abstract [en]

    Conversion of retinol to 3,4-didehydroretinol is probably a rate-limiting step in the formation of 3,4-didehydroretinoic acid, a candidate ligand for nuclear retinoid receptors in human epidermal keratinocytes. To investigate whether this metabolic pathway also exists in other cell systems, we compared the retinoid concentrations and the bioconversion of [3H]retinol to [3H]3,4-didehydroretinol in human primary keratinocytes, human cervical carcinoma (HeLa) cells, human melanoma (JKM86-4) cells, monkey kidney epithelium (CV-1) cells, and murine teratocarcinoma (F9) cells. The cellular retinol concentration ranged from 2.33 to 99.1 pmol/mg protein with the highest values observed in keratinocytes. 3,4-Didehydroretinol was only detected in cells of human origin and its concentration ranged from 0.24 pmol/mg in HeLa to 34.6 pmol/mg in the keratinocytes. Incubation with [3H]retinol for 1–24 h resulted in a rapid appearance of [3H]3,4-didehydroretinol in human keratinocytes, and to a lesser extent in HeLa and melanoma cells, but not in the other cells. Analysis of cellular retinol- and retinoic acid-binding protein concentrations showed a correlation to the cells' ability to accumulate 3,4-didehydroretinol, suggesting a role for these proteins in the 3,4-didehydro metabolic pathway. The combined results suggest that although 3,4-didehydroretinol is most typical for human keratinocytes, studies of its metabolism are also feasible in HeLa cells which contain low levels of retinoid-binding proteins.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81440 (URN)10.1016/0167-4889(94)90267-4 (DOI)
    Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2017-12-07Bibliographically approved
    2. β-Carotene Uptake and Bioconversion to Retinol Differ Between Human Melanocytes and Keratinocytes
    Open this publication in new window or tab >>β-Carotene Uptake and Bioconversion to Retinol Differ Between Human Melanocytes and Keratinocytes
    2001 (English)In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 39, no 2, p. 300-306Article in journal (Refereed) Published
    Abstract [en]

    β-Carotene is one of the carotenoids that has been considered to play a role in the natural defense against ultraviolet-induced skin cancer. It is not known whether epidermal cells are able to accumulate β-carotene and, subsequently, convert it to vitamin A. We used normal cultured human keratinocytes and melanocytes to study the uptake, and possible bioconversion to retinol, of authentic or [14C]β-carotene. The uptake was much higher in melanocytes than in keratinocytes, corresponding to a fivefold difference in the intracellular fraction after two days of incubation. An increased level of cellular retinol was noted after one day of β-carotene incubation. The conversion of [C]β-carotene to [14C]retinol peaked at 24 hours of incubation in keratinocytes and melanocytes. The results suggest that β-carotene can function as a local supply of vitamin A in the skin and that melanocytes are especially likely to store β-carotene.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-49078 (URN)10.1207/S15327914nc392_21 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
    3. Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells
    Open this publication in new window or tab >>Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells
    1997 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 7, no 4, p. 267-274Article in journal (Refereed) Published
    Abstract [en]

    Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo- and hyperpigmentation. Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation. We detected messenger RNA transcripts for the cellular retinol- and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes. In the melanoma cell lines the major transcript was CRABP II. Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells. The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]RA. Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81443 (URN)10.1097/00008390-199708000-00001 (DOI)
    Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2017-12-07Bibliographically approved
    4. Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes
    Open this publication in new window or tab >>Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes
    1999 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 9, no 4, p. 339-346Article in journal (Refereed) Published
    Abstract [en]

    Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans [3H]retinoic acid in cultured human keratinocytes and melanocytes exposed to UVR, using high performance liquid chromatography. Before UVR the retinoid content was similar in keratinocytes and melanocytes, but the uptake of [3H]retinol was three-fold higher and the uptake of [3H]retinoic acid was 10-fold higher in the melanocytes. In both cell types, UVR (UVA 360 mJ/cm2 plus UVB 140 mJ/cm2) instantaneously reduced the concentration of retinol by about 50% and that of 3,4-didehydroretinol by about 20%. The retinoid concentrations returned to normal within 1-2 days post-irradiation, despite there being no overt increase in the uptake of [3H]retinol or the biosynthesis of 3,4- didehydroretinol. However, in both types of irradiated cells, the accumulation of the biologically most active metabolite, all-trans [3H]retinoic acid, was about 60% higher than in control cells. Furthermore, the metabolism of authentically supplied [3H]retinoic acid was reduced, especially in irradiated keratinocytes, which probably contributed to the restoration of retinoid levels after UV exposure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24867 (URN)10504051 (PubMedID)9269 (Local ID)9269 (Archive number)9269 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytes
    Open this publication in new window or tab >>Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytes
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Skin cancer is the most common malignancy in man. A major risk factor is UV irradiation, which not only damages DNA but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to study the effects of UV radiation on the expression of the retinoid receptors RARα, RARβ, RARγ and RXRα. By real-time PCR and Western blot technique, the mRNA and protein levels were monitored, before and up to 4 days following 50 mJ/cm2 UVB. In keratinocytes, UVB caused a rapid drop in all four mRNA levels (minus 50-70% the first 8 h) and protein levels dropped by 30-40% followed by a gradual increase, but full normalization was ouly reached for RARα within the study period. ln melanocytes, UVB caused a quick drop both in the receptor mRNA and protein levels (minus 50-60% after 4 h), followed by normalization of the protein levels for all receptors within 2-3 days. The UV-induced depletion of vitamin A and retinoid receptors might abrogate the retinoid signaling, which subsequently might promote tumor development.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81447 (URN)
    Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2012-09-14Bibliographically approved
  • 66.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Björklind, Carina
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Törma, Hans
    Department of Dermatology, University Hospital, Uppsala, Sweden.
    Vahlquist, Anders
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression1994In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1224, no 3, p. 349-354Article in journal (Refereed)
    Abstract [en]

    Conversion of retinol to 3,4-didehydroretinol is probably a rate-limiting step in the formation of 3,4-didehydroretinoic acid, a candidate ligand for nuclear retinoid receptors in human epidermal keratinocytes. To investigate whether this metabolic pathway also exists in other cell systems, we compared the retinoid concentrations and the bioconversion of [3H]retinol to [3H]3,4-didehydroretinol in human primary keratinocytes, human cervical carcinoma (HeLa) cells, human melanoma (JKM86-4) cells, monkey kidney epithelium (CV-1) cells, and murine teratocarcinoma (F9) cells. The cellular retinol concentration ranged from 2.33 to 99.1 pmol/mg protein with the highest values observed in keratinocytes. 3,4-Didehydroretinol was only detected in cells of human origin and its concentration ranged from 0.24 pmol/mg in HeLa to 34.6 pmol/mg in the keratinocytes. Incubation with [3H]retinol for 1–24 h resulted in a rapid appearance of [3H]3,4-didehydroretinol in human keratinocytes, and to a lesser extent in HeLa and melanoma cells, but not in the other cells. Analysis of cellular retinol- and retinoic acid-binding protein concentrations showed a correlation to the cells' ability to accumulate 3,4-didehydroretinol, suggesting a role for these proteins in the 3,4-didehydro metabolic pathway. The combined results suggest that although 3,4-didehydroretinol is most typical for human keratinocytes, studies of its metabolism are also feasible in HeLa cells which contain low levels of retinoid-binding proteins.

  • 67.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Törma, Hans
    Department of Medical Sciences, Section of Dermatology and Venereology, Uppsala University, Uppsala.
    Vahlquist, Anders
    Department of Medical Sciences, Section of Dermatology and Venereology, Uppsala University, Uppsala.
    Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytesManuscript (preprint) (Other academic)
    Abstract [en]

    Skin cancer is the most common malignancy in man. A major risk factor is UV irradiation, which not only damages DNA but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to study the effects of UV radiation on the expression of the retinoid receptors RARα, RARβ, RARγ and RXRα. By real-time PCR and Western blot technique, the mRNA and protein levels were monitored, before and up to 4 days following 50 mJ/cm2 UVB. In keratinocytes, UVB caused a rapid drop in all four mRNA levels (minus 50-70% the first 8 h) and protein levels dropped by 30-40% followed by a gradual increase, but full normalization was ouly reached for RARα within the study period. ln melanocytes, UVB caused a quick drop both in the receptor mRNA and protein levels (minus 50-60% after 4 h), followed by normalization of the protein levels for all receptors within 2-3 days. The UV-induced depletion of vitamin A and retinoid receptors might abrogate the retinoid signaling, which subsequently might promote tumor development.

  • 68.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Törmä, H.
    Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
    Vahlquist, A.
    Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
    Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes1999In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 9, no 4, p. 339-346Article in journal (Refereed)
    Abstract [en]

    Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans [3H]retinoic acid in cultured human keratinocytes and melanocytes exposed to UVR, using high performance liquid chromatography. Before UVR the retinoid content was similar in keratinocytes and melanocytes, but the uptake of [3H]retinol was three-fold higher and the uptake of [3H]retinoic acid was 10-fold higher in the melanocytes. In both cell types, UVR (UVA 360 mJ/cm2 plus UVB 140 mJ/cm2) instantaneously reduced the concentration of retinol by about 50% and that of 3,4-didehydroretinol by about 20%. The retinoid concentrations returned to normal within 1-2 days post-irradiation, despite there being no overt increase in the uptake of [3H]retinol or the biosynthesis of 3,4- didehydroretinol. However, in both types of irradiated cells, the accumulation of the biologically most active metabolite, all-trans [3H]retinoic acid, was about 60% higher than in control cells. Furthermore, the metabolism of authentically supplied [3H]retinoic acid was reduced, especially in irradiated keratinocytes, which probably contributed to the restoration of retinoid levels after UV exposure.

  • 69.
    Andersson, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Törmä, Hans
    Vahlquist, Anders
    Differential effects of UV irradiation on nuclear retinoid receptor levels in cultured keratinocytes and melanocytes2003In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 12, no 5, p. 563-571Article in journal (Refereed)
    Abstract [en]

    A major risk factor for skin cancer is UV irradiation, which not only damages DNA and other photosensitive compounds like vitamin A, but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to examine the effects of UV irradiation on the expression of the predominant retinoid receptors in the human skin (RARa, RAR? and RXRa) and the AP-1 protein c-Jun, mRNA levels were studied by real-time PCR and protein levels by Western blot. In keratinocytes, a single dose of UVB (50 mJ/cm2) caused a rapid drop in the expression of all three receptors (mRNA levels minus 35-50% after 4h, protein levels minus 20-45% after 8h), which was followed over the next 40 h by a variable response, leading to full normalization for RARa only. In contrast, the levels of c-Jun did not change significantly after UV exposure. In melanocytes, UVB caused a similar drop of the retinoid receptor levels as in keratinocytes but this was soon followed by an increased expression leading to a complete normalization of all receptor levels within 1-3 days. The c-Jun levels in melanocytes increased 1 day after UV exposure and remained high (plus 50%) thereafter. In both cell types, a ~3-fold increase in apoptosis (measured by DNA fragmentation) was observed 8-48 h after UVB irradiation. In conclusion, a depletion of vitamin A and retinoid receptors by UV irradiation, together with unchanged or even increased c-Jun levels, might seriously interfere with retinoid signaling and thus promote future tumor development, especially in keratinocytes. ⌐ Blackwell Munksgaard, 2003.

  • 70.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Vahlquist, Anders
    Section of Dermatology and Venereology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    β-Carotene Uptake and Bioconversion to Retinol Differ Between Human Melanocytes and Keratinocytes2001In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 39, no 2, p. 300-306Article in journal (Refereed)
    Abstract [en]

    β-Carotene is one of the carotenoids that has been considered to play a role in the natural defense against ultraviolet-induced skin cancer. It is not known whether epidermal cells are able to accumulate β-carotene and, subsequently, convert it to vitamin A. We used normal cultured human keratinocytes and melanocytes to study the uptake, and possible bioconversion to retinol, of authentic or [14C]β-carotene. The uptake was much higher in melanocytes than in keratinocytes, corresponding to a fivefold difference in the intracellular fraction after two days of incubation. An increased level of cellular retinol was noted after one day of β-carotene incubation. The conversion of [C]β-carotene to [14C]retinol peaked at 24 hours of incubation in keratinocytes and melanocytes. The results suggest that β-carotene can function as a local supply of vitamin A in the skin and that melanocytes are especially likely to store β-carotene.

  • 71.
    Andersson, Peter
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Surgery and anorectal function in Crohn's colitis2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The study concerns surgery in Crohn's disease, particularly Crohn's colitis, its relation to medical treatment, symptomatic load, perceived health, quality of life, outcome on anorectal function and also anorectal physiologic conditions.

    Four hundred and thirty-two patients treated at the University Hospital, Linköping from 1970 to 1997 were included in the study. Operations and medical treatment were retrospectively reviewed, whereas symptomatic load, perceived health, quality of life, function outcome and anorectal physiology were prospectively evaluated.

    In a cross-sectional analysis of all patients surveilled 1995 the annual incidence of surgery was 5.7% in a population-based cohort and 10.3% in referred patients. Medical maintenance treatment was used in 61 and 55% respectively. This led to 89% of the patients being in clinical remission or having only mild symptoms and to a large proportion with a perception of good health. The treatment was paralleled by a low rate of septic and surgical complications.

    Surgical treatment of Crohn's colitis prior to 1990 mainly implied colectomy or proctocolectomy and thereafter almost exclusively segmental resection. The creation of a permanent stoma decreased and was rarely needed at the end of the study period when the annual risk was 0.23%. This development was basically due to a deliberate change in surgical attitude aiming at introducing similar treatment principles as for small bowel Crohn's disease With limited resections and preservation of transanal defecation. The reduced colectomy rate may have been facilitated by the introduction of immunosuppressive medical treatment as a reduction of colectomies tended to be associated with medical maintenance treatment during the later part of the study. Time from diagnosis to surgery was prolonged and stricture replaced active disease as the major indication for surgery. Symptomatic load and anorectal function outcome were better after segmental resection without the expense of an increased reresection rate. Seventy percent of patients with Crohn's colitis were in clinical remission and these patients scored quality of life similar to the general population but patients with active disease scored worse in all indexed aspects. The need of immunosuppression or previous surgery was not related to quality of life except when operated with a permanent stoma which negatively influenced psychological well being.

    Anorectal physiology in Crohn's disease differed from controls with increased anal resting pressures and increased rectal sensitivity. This provides possible prerequisites for later development of anal pathology such as fissures and fistulas.

    The study indicates that the concept oflimited surgery is applicable also in Crohn's colitis with obvious benefits for the patients. A treatment concept including medical maintenance treatment and limited resections implies that the vast majority of patients with Crohn's disease may live with only minor symptoms and minimal risk of having a permanent stoma, factors associated with a quality of life similar to that of the general population.

    List of papers
    1. Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments
    Open this publication in new window or tab >>Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments
    Show others...
    1998 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 33, no 4, p. 423-429Article in journal (Refereed) Published
    Abstract [en]

    Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.

    Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.

    Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.

    Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.

    Place, publisher, year, edition, pages
    Informa Healthcare, 1998
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81922 (URN)10.1080/00365529850171062 (DOI)9605265 (PubMedID)
    Available from: 2012-09-25 Created: 2012-09-25 Last updated: 2017-12-07
    2. Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the replacement of total colectomy by segmental resection
    Open this publication in new window or tab >>Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the replacement of total colectomy by segmental resection
    Show others...
    2002 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 1, p. 68-73Article in journal (Refereed) Published
    Abstract [en]

    Background: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced.

    Methods: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods.

    Results: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% ( P < 0.01) while stricture as an indication increased from 9% to 50% ( P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years ( P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery ( P = 0.017), permanent stoma ( P < 0.01) and total colectomy ( P < 0.01). Findings were similar in the population-based cohort.

    Conclusions: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.

    Keywords
    Colectomy, Colitis, Crohn Disease, Population-BASED, Stoma, Surgery
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24873 (URN)10.1080/003655202753387383 (DOI)9275 (Local ID)9275 (Archive number)9275 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Segmental resection or subtotal colectomy in Crohn's colitis?
    Open this publication in new window or tab >>Segmental resection or subtotal colectomy in Crohn's colitis?
    2002 (English)In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 45, no 1, p. 47-53Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Segmental resection for Crohn's colitis is controversial. Compared with subtotal colectomy, segmental resection is reported to be associated with a higher rate of re-resection. Few studies address this issue, and postoperative functional outcome has not been reported previously. This study compared segmental resection to subtotal colectomy with anastomosis with regard to re-resection, postoperative symptoms, and anorectal function.

    METHODS: Fifty-seven patients operated on between 1970 and 1997 with segmental resection (n = 31) or subtotal colectomy (n = 26) were included. Reoperative procedures were analyzed by a life-table technique. Segmentally resected patients were also compared separately with a subgroup of subtotally colectomized patients (n = 12) with similarly limited colonic involvement. Symptoms were assessed according to Best's modified Crohn's Disease Activity Index and an anorectal function score.

    RESULTS: The re-resection rate did not differ between groups in either the entire study population (P = 0.46) or the subgroup of patients with comparable colonic involvement (P = 0.78). Segmentally resected patients had fewer symptoms (P = 0.039), fewer loose stools (P = 0.002), and better anorectal function (P = 0.027). Multivariate analysis revealed the number of colonic segments removed to be the strongest predictive factor for postoperative symptoms and anorectal function (P = 0.026 and P = 0.013, respectively).

    CONCLUSION: Segmental resection should be considered in limited Crohn's colitis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24878 (URN)10.1007/s10350-004-6113-4 (DOI)9280 (Local ID)9280 (Archive number)9280 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Health related quality of life in Crohn's proctocolitis does not differ from a general population when in remission
    Open this publication in new window or tab >>Health related quality of life in Crohn's proctocolitis does not differ from a general population when in remission
    Show others...
    2003 (English)In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 5, no 1, p. 56-62Article in journal (Refereed) Published
    Abstract [en]

    Objective  All treatment in Crohn's disease, although palliative, aims at restoring full health. The objective of this study was to compare health-related quality of life and psychosocial conditions in patients with Crohn's proctocolitis with a general population.

    Patients and methods  One hundred and twenty-seven patients with Crohn's proctocolitis (median age 44 years, 44.1% men) were compared with 266 controls (median age 45 years, 50.7% men). A questionnaire consisting of the Short Form-36 (SF-36), the Psychological General Well-Being Index (PGWB) and a visual analogue scale (VAS) evaluating general health as well as questions regarding psychosocial conditions was used. Disease activity was evaluated by Best's modification of the classical Crohn's Disease Activity Index.

    Results  Patients in remission had a health related quality of life similar to controls according to the SF-36 apart from general health where scores were lower (P < 0.01). Patients with active disease scored lower in all aspects of the SF-36 (P < 0.001 or P < 0.0001) as well as the PGWB (P < 0.0001). In a model for multiple regression including age, gender, concomitant small bowel disease, permanent stoma, previous colonic surgery, disease activity, duration, and aggressiveness, disease activity was the only variable negatively predicting all 8 domains of the SF-36 in the patient group (P < 0.001). The mean annual sick-leave for patients and controls were 33.9 and 9.5 days (P < 0.0001), respectively. Sixty-eight percent of the patients and 78.4% of the controls (P = 0.04) were married or cohabited, 67.7% and 78.0% (P = 0.04), respectively, had children.

    Conclusion  The health related quality of life for patients with Crohn's proctocolitis in remission does not differ from the general population. The disease has, however, a negative impact on parenthood, family life and professional performance.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24877 (URN)10.1046/j.1463-1318.2003.00407.x (DOI)9279 (Local ID)9279 (Archive number)9279 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. Increased anal resting pressure and rectal sensitivity in Crohn's disease
    Open this publication in new window or tab >>Increased anal resting pressure and rectal sensitivity in Crohn's disease
    Show others...
    2003 (English)In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 46, no 12, p. 1685-1689Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Anal pathology occurs in 20 to 80 percent of patients with Crohn's disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn's disease compared with healthy controls.

    METHODS: Twenty patients with Crohn's disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations.

    RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025).

    CONCLUSIONS: This study demonstrates how patients with Crohn's disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.

    Keywords
    Crohn's disease, anorectal manometry, manovolumetry, anal pathology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24876 (URN)10.1007/BF02660776 (DOI)9278 (Local ID)9278 (Archive number)9278 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 72.
    Andersson, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Gustafsson, T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells.1999In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 163, no 2, p. 281-288Article in journal (Refereed)
    Abstract [en]

    We have investigated the expression and secretion of insulin-like growth factor binding proteins (IGFBPs-1 to -6) in human vascular smooth muscle cells (hVSMCs) cultured from human renal arteries. Solution hybridization was used to determine IGFBP nRNA levels and Western immunoblot to detect the corresponding peptides. The hVSMCs expressed mRNAs for IGFBPs-2 to -6, IGFBP-1 mRNA was not detected. IGFBPs-3, -4 and -6 mRNAs were the most abundant, IGFBP-5 was also highly expressed, whereas the IGFBP-2 mRNA was just above the limit of detection. Serum starvation for 48 h significantly decreased the mRNA levels of IGFBPs-2 to -5 and tended to decrease IGFBP-6 mRNA also. IGFBPs-2, -4, -5 and -6 peptides could be detected in conditioned medium, but IGFBP-3 peptide was not detected. IGFBP-4 was the only peptide detected without any concentration step. Low-molecular-mass immunoreactive degradation products were found for IGFBPs-2 and -4. Exogenous IGFBPs-1, -3 and -4 in concentrations of 50 ng/ml inhibited DNA synthesis induced by 1 nM IGF-I, whereas IGFBPs-2, -5 and -6 had no significant inhibitory effects at this concentration. We conclude from these results that all IGFBPs except IGFBP-1 are expressed in hVSMC. Our results indicate that locally produced, in addition to circulating,, IGFBPs may have an important role in the regulation of hVSMC.

  • 73.
    Andersson, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Kullman, Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Halldestam, Ingvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Einarsson, Curt
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Bouveret's syndrome followed by gallstone entrapment in the stomach: An uncommon cause of upper gastrointestinal bleeding and gastric retention2000In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166, no 2, p. 183-185Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 74.
    Andersson, Peter
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Bendtsen, Preben
    Linköping University, Faculty of Health Sciences.
    Myrelid, Pär
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Health related quality of life in Crohn's proctocolitis does not differ from a general population when in remission2003In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 5, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    Objective  All treatment in Crohn's disease, although palliative, aims at restoring full health. The objective of this study was to compare health-related quality of life and psychosocial conditions in patients with Crohn's proctocolitis with a general population.

    Patients and methods  One hundred and twenty-seven patients with Crohn's proctocolitis (median age 44 years, 44.1% men) were compared with 266 controls (median age 45 years, 50.7% men). A questionnaire consisting of the Short Form-36 (SF-36), the Psychological General Well-Being Index (PGWB) and a visual analogue scale (VAS) evaluating general health as well as questions regarding psychosocial conditions was used. Disease activity was evaluated by Best's modification of the classical Crohn's Disease Activity Index.

    Results  Patients in remission had a health related quality of life similar to controls according to the SF-36 apart from general health where scores were lower (P < 0.01). Patients with active disease scored lower in all aspects of the SF-36 (P < 0.001 or P < 0.0001) as well as the PGWB (P < 0.0001). In a model for multiple regression including age, gender, concomitant small bowel disease, permanent stoma, previous colonic surgery, disease activity, duration, and aggressiveness, disease activity was the only variable negatively predicting all 8 domains of the SF-36 in the patient group (P < 0.001). The mean annual sick-leave for patients and controls were 33.9 and 9.5 days (P < 0.0001), respectively. Sixty-eight percent of the patients and 78.4% of the controls (P = 0.04) were married or cohabited, 67.7% and 78.0% (P = 0.04), respectively, had children.

    Conclusion  The health related quality of life for patients with Crohn's proctocolitis in remission does not differ from the general population. The disease has, however, a negative impact on parenthood, family life and professional performance.

  • 75.
    Andersson, Peter
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Arvidsson, M.
    Dabrosin-Söderholm, J.
    Nyström, Per-Olof
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Smedh, K.
    Ström, Magnus
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments1998In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 33, no 4, p. 423-429Article in journal (Refereed)
    Abstract [en]

    Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.

    Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.

    Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.

    Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.

  • 76.
    Andersson, Peter
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Nyström, Per-Olof
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the replacement of total colectomy by segmental resection2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 1, p. 68-73Article in journal (Refereed)
    Abstract [en]

    Background: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced.

    Methods: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods.

    Results: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% ( P < 0.01) while stricture as an indication increased from 9% to 50% ( P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years ( P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery ( P = 0.017), permanent stoma ( P < 0.01) and total colectomy ( P < 0.01). Findings were similar in the population-based cohort.

    Conclusions: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.

  • 77.
    Andersson, Peter
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Boeryd, Bernt
    Östergötlands Läns Landsting, Centre for Laboratory Medicine.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Increased anal resting pressure and rectal sensitivity in Crohn's disease2003In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 46, no 12, p. 1685-1689Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Anal pathology occurs in 20 to 80 percent of patients with Crohn's disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn's disease compared with healthy controls.

    METHODS: Twenty patients with Crohn's disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations.

    RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025).

    CONCLUSIONS: This study demonstrates how patients with Crohn's disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.

  • 78.
    Andersson, Peter
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Segmental resection or subtotal colectomy in Crohn's colitis?2002In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 45, no 1, p. 47-53Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Segmental resection for Crohn's colitis is controversial. Compared with subtotal colectomy, segmental resection is reported to be associated with a higher rate of re-resection. Few studies address this issue, and postoperative functional outcome has not been reported previously. This study compared segmental resection to subtotal colectomy with anastomosis with regard to re-resection, postoperative symptoms, and anorectal function.

    METHODS: Fifty-seven patients operated on between 1970 and 1997 with segmental resection (n = 31) or subtotal colectomy (n = 26) were included. Reoperative procedures were analyzed by a life-table technique. Segmentally resected patients were also compared separately with a subgroup of subtotally colectomized patients (n = 12) with similarly limited colonic involvement. Symptoms were assessed according to Best's modified Crohn's Disease Activity Index and an anorectal function score.

    RESULTS: The re-resection rate did not differ between groups in either the entire study population (P = 0.46) or the subgroup of patients with comparable colonic involvement (P = 0.78). Segmentally resected patients had fewer symptoms (P = 0.039), fewer loose stools (P = 0.002), and better anorectal function (P = 0.027). Multivariate analysis revealed the number of colonic segments removed to be the strongest predictive factor for postoperative symptoms and anorectal function (P = 0.026 and P = 0.013, respectively).

    CONCLUSION: Segmental resection should be considered in limited Crohn's colitis.

  • 79.
    Andersson, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Controversies in surgical treatment of inflammatory bowel disease2001Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 80. Andersson, R
    et al.
    Hugander, A
    Ghazi, SH
    Ravn, H
    Offenbartl, K
    Nyström, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Diagnostic value of disease history, clinical presentation, and inflammatory parameters of appendicitis.1999In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 23, p. 133-140Article in journal (Refereed)
  • 81. Andersson, RE
    et al.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Tysk, C
    Ekbom, A
    Appendectomy and protection against ulcerative colitis2001In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 344, no 11, p. 808-814Article in journal (Refereed)
    Abstract [en]

    Background: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. Methods:We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. Results: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87], for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90], and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06, 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). Conclusions: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.

  • 82.
    Andersson, Roland
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Appendicitis: Epidemiology and diagnosis1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The study concerns appendicitis, its epidemiology and diagnosis, and the outcome of appendectomy. A population based cohort of 9,274 patients undergoing appendectomy in 1969 to 1990 in Jönköping County was retrospectively studied, and 502 patients admitted for suspected appendicitis to the hospitals in Jönköping and Eksjö between October 1992 and December 1993 were prospectively studied.

    Appendicitis was found to occur in outbreaks and space-time clusters, indicating an infectious etiology. The incidence of non-perforating appendicitis was strongly age-dependent, with a peak in adolescence, whereas the incidence of perforating appendicitis was stable at all ages. This suggests that perforating and non-perforating appendicitis are separate entities.

    There was a high rate of negative appendectomies, but during the study period an increasing diagnostic accuracy and decreasing incidence of negative appendectomies was observed, indicating a trend towards a more restrictive attitude to exploration in patients with suspected appendicitis. This was accompanied by a decreasing incidence of non-perforating appendicitis, whereas the incidence of perforating appendicitis was stable. An analysis of population based studies showed a strong relation between surgeons' attitude to exploration and the incidence of non-perforating ap9endicitis, whereas the incidence of perforating appendicitis was unrelated. This is consistent with a high proportion of potentially resolving appendicitis.

    A conservative management decreases the munber of negative explorations and saves a number of patients with resolving appendicitis from an unnecessary operation. This leads to a high proportion of perforations among the operated patients but the number of perforations is not increased. The perforation rate, therefore, should not be used as a quality measure of the management of patients with suspected appendicitis.

    The rate of negative explorations is higher in women. This gender difference is found at all ages and is not due to gynecological diseases alone. The explanation is the larger number of women attending for nonsurgical abdominal pain, whereas the rate of diagnostic errors among these patients is similar in men and women.

    Patients with a negative appendectomy are characterized by high intensity of pain and tenderness without signs of a systemic inflammatory response. Surgeons pay too much attention to pain and tenderness in their decision to operate, and underestimate the importance of temperature, laboratory variables and duration of symptoms.

    No single clinical or laboratory variable has sufficiently high discriminating power to be used as a true diagnostic test. The inflammatory variables are as important predictors as the clinical findings, and they are especially important in advanced appendicitis. Their diagnostic value is higher at a repeat examination after a few hours of observation.

    The study show for a need of an improved management of patients with suspected appendicitis, and the potential for improved clinical diagnosis. Inflammatory variables should be given more attention, and pain and tenderness should be interpreted more cautiously. An expectant management, with repeated clinical and laboratory examinations, is advisable once advanced appendicitis has been ruled out.

  • 83. Andersson, Roland
    et al.
    Hugander, Anders
    Ravn, Hans
    Offenbartl, Karsten
    Ghazi, Sam
    Nyström, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Repeated clinical and laboratory examinations in patients with an equivocal diagnosis of appendicitis2000In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 24, no 4, p. 479-485Article in journal (Refereed)
    Abstract [en]

    In-hospital observation with repeated clinical examinations is commonly used in patients with an equivocal diagnosis of appendicitis. It is not known if repeated measurements of temperature and laboratory examinations have any diagnostic importance in this situation. The importance of repeated measurements of the body temperature, white blood cell (WBC) and differential cell counts, C-reactive protein concentration (CRP) and of the surgeon's repeated assessments was prospectively analyzed in 420 patients with an equivocal diagnosis of appendicitis at admission who were reexamined after a median of 6 hours of observation. The final diagnosis was appendicitis in 137 patients. After observation the inflammatory response was increasing among patients with appendicitis and decreasing among patients without appendicitis. The variables discriminating power for appendicitis consequently increased, from an area under the receiver operating characteristic (ROC) curve of 0.56 to 0.77 at admission, to 0.75 to 0.85 after observation. The ROC area of the surgeons' clinical assessment increased from 0.69 to 0.89. The WBC and differential cell counts were the best discriminators at the repeat examination. The change in the variables between the observations had weak discriminating power and had no additional importance in addition to the actual level at the repeat examination. To conclude, the diagnostic information of the temperature and laboratory examinations increased after observation. Repeated controls of the body temperature and laboratory examinations are therefore useful in the management of patients with equivocal signs of appendicitis, but the result of the examinations must be integrated with the clinical assessment.

  • 84. Andersson, Roland
    et al.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Tysk, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Ekbom, Anders
    Appendectomy is followed by increased risk of Crohn's disease2003In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 124, no 1, p. 40-46Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. Methods: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. Results: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37, 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. Conclusions: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.

  • 85.
    Andersson, Roland
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Petzold, MG
    Nonsurgical treatment of appendiceal abscess or phlegmon: A systematic review and meta-analysis2007In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 246, no 5, p. 741-748Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A systematic review of the nonsurgical treatment of patients with appendiceal abscess or phlegmon, with emphasis on the success rate, need for drainage of abscesses, risk of undetected serious disease, and need for interval appendectomy to prevent recurrence. SUMMARY BACKGROUND DATA: Patients with appendiceal abscess or phlegmon are traditionally managed by nonsurgical treatment and interval appendectomy. This practice is controversial with proponents of immediate surgery and others questioning the need for interval appendectomy. METHODS: A Medline search identified 61 studies published between January 1964 and December 2005 reporting on the results of nonsurgical treatment of appendiceal abscess or phlegmon. The results were pooled taking the potential clustering on the study-level into account. A meta-analysis of the morbidity after immediate surgery compared with that after nonsurgical treatment was performed. RESULTS: Appendiceal abscess or phlegmon is found in 3.8% (95% confidence interval (CI), 2.6-4.9) of patients with appendicitis. Nonsurgical treatment fails in 7.2% (CI: 4.0-10.5). The need for drainage of an abscess is 19.7% (CI: 11.0-28.3). Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3, CI: 1.9-5.6, P < 0.001). After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6-1.7) and an important benign disease in 0.7% (CI: 0.2-11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7-11.1). CONCLUSIONS: The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon. © 2007 Lippincott Williams & Wilkins, Inc.

  • 86.
    Andersson, T
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, M
    In vivo testing of the protective efficacy of gloves against allergen-containing products using an open chamber system.1999In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, p. 260-263Article in journal (Refereed)
  • 87.
    Andersson, T
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, M
    Björkner, B
    In vivo testing of the protection of gloves against acrylates in dentin-bonding systems on patients with known contact alllergy to acrylates.1999In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, p. 254-259Article in journal (Refereed)
  • 88.
    Andersson, Thomas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, Magnus
    Gruvberger, Birgitta
    Björkner, Bert
    In vivo testing of the protection provided by non-latex gloves against a 2-hydroxyethyl methacrylate-containing acetone-based dentin-bonding product2000In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 80, no 6, p. 435-437Article in journal (Refereed)
    Abstract [en]

    In dentistry, allergic contact dermatitis to acrylates and allergic contact urticaria to latex are important occupational hazards. There is a need to identify, non-latex gloves which are suitable for dental work but at the same time provide adequate protection against acrylate monomers. In a previous study, a new open-chamber system was used for testing the in vivo protection of 6 different gloves against an acrylate-containing ethanol-based dental adhesive. A nitrile glove gave the best protection among the gloves suitable for dental work. In the present study, the test model was used to investigate the in vivo protection of 7 non-latex gloves against a dental bonding product containing 2-hydroxyethyl methacrylate (2-HEMA) in an acetone/water vehicle. Eight 2-HEMA-allergic patients participated. Two neoprene gloves gave the best protection. The protection of the poorest glove was comparable to that of the positive control (no glove). The study produced in vivo data useful in the implementation of individual preventative measures against contact allergy to acrylates.

  • 89.
    Andersson, Thomas
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Johansson, Anders G.
    Kliniskt Mikrobiologiska Laboratoriet, Akademiska Sjukhuset, Uppsala.
    Westermark, Per
    Avdelningen för Genetik och Patologi, Enheten för Patologi, Akademiska Sjukhuset, Uppsala.
    Lundmark, Katarzyna
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Vanlig svamp gav ovanlig hudinfektion: Fallbeskrivning1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 45, p. 4926-4927Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Vid opportunistisk svampinfektion i huden är diagnosen sällan självklar. Ett samarbete mellan dermatolog, patolog och mykolog kan behövas, som i detta fall av kutan alternarios. Denna typ av svampinfektion innefattas i begreppet feohyfomykos.

  • 90.
    Andin, Josefine
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics.
    Hallbeck, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Mohammed, Abdul H
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1174, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.

  • 91. Andius, Patrik
    et al.
    Damm, Ole
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Holmäng, Sten
    Prognostic factors in patients with carcinoma in situ treated with intravesical bacille Calmette-Guérin2004In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 38, no 4, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Objective: To report prognostic factors and follow-up data for an unselected group of patients with carcinoma in situ (CIS) of the urinary bladder treated with bacille Calmette-Guérin (BCG). Material and Methods: The clinical records of patients with CIS treated with BCG were reviewed. All 173 patients treated between 1986 and 1997 in four hospitals in two Swedish cities were included. The median follow-up period was 72 months (range 6-154 months). The impact of 18 variables on the times to recurrence and progression was studied using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. Results: No pre-treatment variables, including type of CIS and T1G3 tumour, had prognostic value in terms of time to progression. The result of the first cystoscopy had a very strong prognostic importance: 44% of patients with a positive first cystoscopy progressed in stage, 59% were BCG failures and 35% died from urothelial cancer. The corresponding values for patients with a negative first cystoscopy were 11%, 18% and 8%. Fourteen patients (8%) were diagnosed with an upper urinary tract tumour but no variable had prognostic significance. The diagnoses of the upper urinary tract tumours were evenly distributed during follow-up. Conclusions: We were not able to predict which patients would respond favourably to BCG. Cystectomy should be strongly considered even after a positive first cystoscopy. The accumulated incidence of patients with bladder CIS and a subsequent upper urinary tract tumour is rather high but it is questionable whether the prognosis will improve if routine follow-up urographies are performed.

  • 92. Andreen Sachs, Magna
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Övergripande kvalitetsindikatorer framtagna för hälso- och sjukvården2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 797-803Article in journal (Other academic)
  • 93.
    Andreen-Sachs, Magna
    et al.
    Hälso- och sjukvårdsnämndens stab, Stockholms läns landsting.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Overgripande kvalitetsindikatorer framtagna for halso- och sjukvarden2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 797-803Article in journal (Other academic)
  • 94. Andreyev, HJN
    et al.
    Norman, AR
    Cunningham, D
    Oates, J
    Dix, BR
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Urosevic, N
    Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study2001In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 85, no 5, p. 692-696Article in journal (Refereed)
    Abstract [en]

    Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.

  • 95.
    Angsten, G
    et al.
    Univ Childrens Hosp, Dept Paediat Surg, SE-75185 Uppsala, Sweden Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden Linkoping Univ, Dept Biomed & Surg, Linkoping, Sweden Univ Uppsala Hosp, Dept Anaesthesiol, Uppsala, Sweden.
    Boberg, M
    Cederblad, Gitten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Meurling, S
    Univ Childrens Hosp, Dept Paediat Surg, SE-75185 Uppsala, Sweden Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden Linkoping Univ, Dept Biomed & Surg, Linkoping, Sweden Univ Uppsala Hosp, Dept Anaesthesiol, Uppsala, Sweden.
    Stiernstrom, H
    Univ Childrens Hosp, Dept Paediat Surg, SE-75185 Uppsala, Sweden Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden Linkoping Univ, Dept Biomed & Surg, Linkoping, Sweden Univ Uppsala Hosp, Dept Anaesthesiol, Uppsala, Sweden.
    Metabolic effects in neonates receiving intravenous medium-chain triglycerides2002In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 91, no 2, p. 188-197Article in journal (Refereed)
    Abstract [en]

    The effects of two lipid emulsions, one with 5017( each of medium-chain and long-chain triglycerides, and a long-chain triglycerides lipid emulsion as a control, were evaluated for lipid and carnitine metabolism and respiratory quotient when given to neonates after major surgery during a short period of total parenteral nutrition. Each group included 10 neonates, and all tolerated the total parenteral nutrition well. The relative contents of linoleic acid and)alpha-linolenic acid increased in all lipid esters in plasma and adipose tissue in both groups, indicating that the content of these fatty acids is sufficient even in the medium-chain triglycerides emulsion. The serum concentration of ketones was within normal limits. Free fatty acids in plasma did not increase in either group. The total plasma carnitine concentration decreased in both groups but the distribution of free carnitine and acylcarnitine did not change. The total muscle carnitine did not change significantly but the ratio of acylcarnitine to free carnitine tended to increase in muscle in the treatment group, probably an effect of the medium-chain triglyceride supplementation. Conclusions: The two groups displayed the same fatty acid pattern in plasma and adipose tissue and the same respiratory quotient during the treatment period. Regarding carnitine status, essentially the same changes were seen in the two groups. However, discrete changes were seen in muscle tissue in the treatment group.

  • 96.
    Angsten, G.
    et al.
    Department of Paediatric Surgery, University Children's Hospital, S-751 85 Uppsala, Sweden.
    Cederblad, Gitten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Meurling, S.
    Department of Paediatric Surgery, University Children's Hospital, S-751 85 Uppsala, Sweden.
    Reference ranges for muscle carnitine concentration in children2003In: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 40, no 4, p. 406-410Article in journal (Refereed)
    Abstract [en]

    Background: We investigated muscle and plasma carnitine concentrations in children to establish reference intervals for use following biopsy of skeletal muscle. Methods: The study comprised 50 children from newborns up to 14 years of age, all undergoing elective surgery. They were divided into six age groups, the youngest 0-2 days and the oldest 11-14 years. The samples were taken at the beginning of surgery. Results: Gestational age was a major determinant of the total muscle carnitine concentration in newborns (Spearman's rs= 0.692, P<0.01). This concentration was low during the first year, but subsequently did not differ between age groups. In neonates the median value (range) for total carnitine concentration in skeletal muscle was 5.9 (2.2-15.9) µmol/g dry weight and the free to total carnitine ratio was 62 (31-81)%. In children 1-12 months old the corresponding figures were 6.0 (3.5-7.9) µmol/g dry weight and 51 (28-71)% and in those 1-14 years they were 12.1 (6.6-17.4) µmol/g dry weight and 76 (42-92)%. Conclusion: This study shows that muscle carnitine concentrations in newborns are dependent on gestational age. The data suggest that there is an accretion of carnitine in skeletal muscle during the first year of life. Reference intervals are given.

  • 97.
    Aniansson Zdolsek, Helena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Holt, Patrick G.
    TVW Telethon Institute for Child Health Research, Perth, Australia.
    Nilsson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.

    Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.

    Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.

    Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.

  • 98. Arber, N
    et al.
    Kuwada, S
    Leshno, M
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Hultcrantz, R
    Rex, D
    Sporadic adenomatous polyp regression with exisulind is effective but toxic: A randomised, double blind, placebo controlled, dose-response study2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 3, p. 367-373Article in journal (Refereed)
    Abstract [en]

    Background and aim: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. Patients and methods: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. Results: A total of 281 patients were enrolled and randomised, 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p = 0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p = 0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. Conclusion: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.

  • 99.
    Arbman, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Colorectal cancer in Östergötland: risk factors, diagnosis, and quality of treatment1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this investigation colorectal cancer in the county of Östergötland has been studied with emphasis on risk factors, diagnostic efforts, and the results of treatment.

    In two case-control studies on food and colorectal cancer, a decreased risk was associated with a high intake of cereal fibre, total fibre, and calcium per unit energy consumed as well as a high intake of raw vegetables. Processed meat was associated with an increased lisk for colon cancer and alcohol with an increased risk for rectal cancer. Drug consumption was also found to influence the cancer risk.

    In a case-control study on occupational factors and the risk for colorectal cancer, some occupations seemed to influence the risk for colon and rectal cancer in different ways. Twenty years of physically active work significantly decreased the risk for left-sided colon cancer but increased the risk for rectal cancer. Accordingly, twenty year of sedentary work significantly decreased the risk for rectal cancer.

    Known risk factors were found in 12% of colorectal cancer patients, though previous cholecystectomy did not turn out to be a risk factor.

    The symptoms of colon cancer are vague and unspecific, whereas bleeding is prominent and a dominating symptom in rectal cancer. Conflicting results have been presented regarding the importance of a short delay between onset of symptoms and treatment. In our study, a more favourable stage distribution was found for rectal cancer with a very short delay between start of symptoms and treatment, but not for colon cancer.

    Results of treatment for colorectal cancer show considerable variation in different series, which can be due to differences in selection and classification as well as in treatment. A computerized system for quality assurance of colorectal cancer was introduced in Östergötland in 1984. All cases diagnosed 1984-1986 were registered in this system, making it possible to study outcome of treatment for an unselected population. The results of treatment in terms of postoperative mortality and five year survival were comparable to the results from specialised international centres, but local recunence rate after operation for rectal cancer was high (20%).

    To reduce this local recurrence rate, the technique of total mesorectal excision was introduced in three of the surgical departments in the county. Using the system for quality assurance, the local recunence rate during a three year period before the change in technique was compared with a three year period when the new technique was used. The local recunence rate was significantly reduced in the later period without any change in postoperative complications.

    In conclusion this study shows an environmental influence on cancer-risk that may be different for colon and rectal cancer. The usefulness of a continuous quality assurance system to detect shmtcomings in diagnosis and treatment and to evaluate new techniques is also shown. Finally, total mesorectal excision reduces the local recurrence rate for rectal cancer in an unselected population treated in different kinds of hospital.

  • 100. Arnelo, Urban
    et al.
    Herrington, Margery
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Adrian, Thomas
    Reidelberger, Roger
    Larsson, Jörgen
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Strömmer, Lisa
    Ding, Xianzhong
    Permert, Johan
    Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.2000In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 887, p. 391-398Article in journal (Refereed)
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