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  • 51.
    Larsson (Wäster), Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Andersson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Johansson, Uno
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis2005In: Experimental Dermatology, ISSN 0906-6705, Vol. 14, no 2, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) radiation is an etiologic agent for malignant melanoma and non-melanoma skin cancer, but the spectral range responsible for tumor induction is still to be elucidated. In this study, we compared effects of UVA and UVB irradiation on normal human melanocytes (MCs) and keratinocytes (KCs) in vitro. We demonstrate that UVA irradiation induces immediate loss of reduced glutathione (GSH) in both MCs and KCs. Exposure to UVA also causes reduced plasma membrane stability, in both cell types, as estimated by fluorescein diacetate retention and flow cytometry. Furthermore, we noted reduction in proliferation and higher apoptosis frequency 24 h after UVA irradiation. UVB irradiation of KCs caused instant reduction of reduced GSH and impaired plasma membrane stability. We also found decline in proliferation and increased apoptosis after 24 h. In MCs, on the other hand, UVB had no effect on GSH level or plasma membrane stability, although increased apoptotic cell death and reduced proliferation was detected. In summary, MCs and KCs showed similar response towards UVA, while UVB had more pronounced effects on KCs as compared to MCs. These results might have implications for the induction of malignant melanoma and non-melanoma skin cancer.

  • 52.
    Larsson Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Ultraviolet (UV) A- and UVB-induced redox alterations and activation of nuclear factor-kappaB in human melanocytes - protective effects of alpha-tocopherol2006In: British Journal of Dermatology, ISSN 0007-0963, Vol. 155, no 2, p. 292-300Article in journal (Refereed)
    Abstract [en]

    Background Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge concerning reaction pathways and signalling transduction in melanocytes is still limited.

    Objectives To evaluate the protective capacity of α-tocopherol and β-carotene during UVA and UVB irradiation of human melanocytes in vitro.

    Methods Primary cultures of normal human melanocytes were irradiated by different wavelengths within the UV spectrum (UVA 6 J cm−2, UVB 60 mJ cm−2). Redox alterations and apoptosis were studied and the protective potential of α-tocopherol and β-carotene was evaluated.

    Results UVA and UVB irradiation decreased the intracellular concentration of reduced glutathione and activated the transcription factor nuclear factor (NF)-κB, detected as the increased level of the p65 subunit and translocation to the nucleus. This coincided with a rise in the level of γ-glutamyl-cysteine-synthetase, the rate-limiting enzyme of the glutathione synthesis. UVA and UVB caused apoptotic cell death as detected by nuclear fragmentation and caspase activation 24 h postirradiation. Pretreatment with α-tocopherol prevented UVA- and UVB-induced glutathione loss, NF-κB translocation and diminished apoptosis, but β-carotene did not show a similar protective capacity. Further, exposure to α-tocopherol by itself reduced cell proliferation rate.

    Conclusions UVA and UVB irradiation affected the intracellular redox state and increased the frequency of apoptosis in human melanocytes in vitro. α-Tocopherol might be a useful substance in protecting melanocytes from UV-induced damage.

  • 53.
    Lens, Marko
    et al.
    Kings College London.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Newton-Bishop, Julia
    St James Hospital.
    Cutaneous Melanoma During Pregnancy: Is the Controversy Over?2009In: American Journal of Clinical Oncology, ISSN 0277-3732, E-ISSN 1537-453X, Vol. 27, no 19, p. E11-E12Article in journal (Other academic)
    Abstract [en]

    n/a

  • 54. Lens, MB
    et al.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Ahlbom, A
    Farahmand, BY
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Boeryd, B
    Bishop, JAN
    Effect of pregnancy on survival in women with cutaneous malignant melanoma2004In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 22, no 21, p. 4369-4375Article in journal (Refereed)
    Abstract [en]

    Purpose An adverse influence of pregnancy on the risk of death in women with cutaneous melanoma was suggested historically by anecdotal reports. Previous studies included small numbers of women observed for short periods. Methods Using data from the Swedish National and Regional Registries, we performed a retrospective cohort study of all Swedish women who were diagnosed with cutaneous melanoma during their reproductive period, from January 1, 1958, to December 31, 1999. The relationship between pregnancy status at the diagnosis of melanoma and overall survival was examined in multivariable proportional-hazards models. Results The cohort comprised 185 women (3.3%) diagnosed with melanoma during pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with melanoma while not pregnant. There was no statistically significant difference in overall survival between pregnant and nonpregnant groups (log-rank chi(2)1 [r] = 0.84, P =.361). Pregnancy status at the time of diagnosis of melanoma was not related to survival in a multivariable Cox model in the 2,101 women (hazard ratio for death in the pregnant group was 1.08, 95% Cl, 0.60 to 1.93). In the multivariable analysis, pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58, 95% Cl, 0.32 to 1.05). Conclusion The survival of pregnant women with melanoma is not worse than the survival of nonpregnant women with melanoma. Pregnancy subsequent to the diagnosis of primary melanoma was not associated with an increased risk of death. (C) 2004 by American Society of Clinical Oncology.

  • 55.
    Loden, Marie
    et al.
    Research and Development, ACO HUD Nordic AB, Upplands Väsby, Sweden, ACO Hud Nordic AB, Box 622, SE-194 26 Upplands Väsby, Sweden.
    Ungerth, Louise
    Stockholm Consumer Cooperative Society, Stockholm, Sweden.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Changes in European legislation make it timely to introduce a transparent market surveillance system for cosmetics2007In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 87, no 6, p. 485-492Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Marketing of cosmetics often makes strong claims linked to active ingredients. This is especially so for anti-ageing products, where the presentation and content of "active" ingredients may create new difficulties in their classification as cosmetics or medicinal products. A recent change in European legislation classifies a product as medicinal by virtue of its "function", in addition to the previous definition of "presentation" (i.e. marketing linked to diseases). Thus, formulations that also restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action should henceforth be covered by the Medicinal Products Directive. A cosmetic product must be suitable for its purpose and should not lead to adverse reactions that are disproportional in relation to its intended effect. However, the forthcoming ban on animal testing of cosmetic ingredients and the new European regulation, REACH (Registration, Evaluation and Authorisation of Chemicals), which aims to ensure a high level of chemical safety to protect human health and the environment, will probably have limited impact on the safety assessment of cosmetics. In order to enable consumers to make informed purchasing decisions, greater transparency in the process of assessing the performance of cosmetics is needed. Introduction of a more transparent system, enabling consumers and professionals to examine the scientific evidence for the claimed effect and the safety assessment of cosmetics, is therefore timely. Lack of transparency increases the risk of consumers wasting money on cosmetics that do not deliver the desired effects. This may jeopardize public trust in the cosmetic industry.

  • 56.
    Magnusson, B.M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Intra- and inter-individual variability in the development of erythema after application of methyl nicotinate evaluated by polarization spectroscopy imaging2010In: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 801-801, ISSN: 002-3573, Pharmaceutical Press , 2010, Vol. 62, no 6, p. 801-801Conference paper (Refereed)
    Abstract [en]

    The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.

  • 57.
    Manifold, R N
    et al.
    Department of Dermatology, Royal Adelaide Hospital, Adelaide .
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Increased cutaneous oxygen availability by topical application of hydrogen peroxide cream enhances the photodynamic reaction to topical 5-aminolevulinic acid-methyl ester2011In: ARCHIVES OF DERMATOLOGICAL RESEARCH, ISSN 0340-3696, Vol. 303, no 4, p. 285-292Article in journal (Refereed)
    Abstract [en]

    Topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) of skin lesions is an accepted treatment for skin tumours but success rates need improvement. The effectiveness of PDT is influenced by availability of oxygen. The aim of this study was to demonstrate, in normal skin, whether a decrease in skin oxygen tension reduces the photodynamic reaction (PDR); and whether the addition of topical hydrogen peroxide can reverse the effect. Topical MAL and red light were administered to the inner forearms of 40 healthy volunteers. Skin oxygen availability was lowered during the illumination phase of the PDT, by applying blanching pressure with a plastic slide. Topical hydrogen peroxide was applied under the pressure slide, immediately prior to illumination, to reverse the effect. Erythema was assessed by naked eye and laser Doppler perfusion imaging (LDPI), at baseline and at 1, 5, 24 and 48 h following illumination. Decreasing oxygen availability by pressure altered the PDR with a larger number of subjects (17.5%) not demonstrating any visible erythema at any time point after plastic slide pressure compared to a PDR Control site (7.5%). The addition of topical hydrogen peroxide during pressure application, restored the number of subjects showing no visible erythema compared to that of PDR Control. LDPI data showed that there was a decrease in mean perfusion after plastic slide pressure when comparing the change from baseline to 24 h (P andlt; 0.05) with the PDR Control. The addition of hydrogen peroxide not only restored but also increased the mean perfusion compared to that of PDR Control when comparing the change from baseline to 5 h and the change from baseline to 24 h (P andlt; 0.001). Increasing oxygen availability increased the PDR in normal skin. The possibility that addition of topical hydrogen peroxide to PDT protocols for non-melanoma skin cancer may increase reactivity and, thus, be relevant for outcomes warrants further study.

  • 58.
    McNamara, Paul N
    et al.
    University of Limerick, Ireland.
    O'Doherty, Jim
    Royal Surrey County Hospital, Guildford, UK.
    O'Connell, Marie-Louise
    University of Limerick.
    Fitzgerald, Barry W
    University of Limerick, Ireland.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Toll, Rani
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Leahy, Martin J
    University of Limerick, Ireland.
    Tissue viability (TiVi) imaging: temporal effects of local occlusion studies in the volar forearm2010In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 3, no 1-2, p. 66-74Article in journal (Refereed)
    Abstract [en]

    Tissue Viability (TiVi) imaging is a promising new technology for the assessment of microcirculation in the upper human dermis. Although the technique is easily implemented and develops large amounts of observational data, its role in the clinical workplace awaits the development of standardised protocols required for routine clinical practice. The present study investigates the use of TiVi technology in a human, in vivo, localized, skin blood flow occlusion protocol. In this feasibility study, the response of the cutaneous microcirculation after provocation on the volar surface of the forearm was evaluated using a high temporal-low spatial resolution TiVi camera. 19 healthy subjects - 10 female and 9 male - were studied after a localized pressure was applied for 5 different time periods ranging from 5 to 25 seconds. Areas corresponding to 100 x 100 pixels (2.89 cm(2)) were monitored for 60 seconds prior to, during and after each occlusion period. Our results demonstrated the removal of blood from the local area and a hyperaemic response supporting the suitability of TiVi imaging for the generation of detailed provocation response data of relevance for the physiological function of the skin microcirculation in health and disease.

  • 59.
    Mellergard, Pekka
    et al.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Release of VEGF and FGF in the extracellular space following severe subarachnoidal haemorrhage or traumatic head injury in humans2010In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 24, no 3, p. 261-267Article in journal (Refereed)
    Abstract [en]

    Microdialysate fluid from 145 severely injured NSICU-patients, 88 with subarachnoidal haemorrage (SAH), and 57 with traumatic brain injury (TBI), was collected by microdialysis during the first 7 days following impact, and levels of the neurotrophins fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) were analysed. The study illustrates both similarities and differences in the reaction patterns of the 2 inflammatory proteins. The highest concentrations of both FGF2 and VEGF were measured on Day 2 (mean (+/- SE) values being 47.1 +/- 15.33 and 116.9 +/- 41.85 pg/ml, respectively, in the pooled patient material). The VEGF concentration was significantly higher in TBI-patients, while the FGF2 showed a tendency to be higher in SAH-patients. This is the first report presenting in some detail the human cerebral response of FGF2 and VEGF following SAH and TBI. Apart from increasing the understanding of the post-impact inflammatory response of the human brain, the study identifies potential threshold values for these chemokines that may serve as monitoring indicators in the NSICU.

  • 60.
    Mellergard, Pekka
    et al.
    Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury2012In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, no 1, p. 112-118Article in journal (Refereed)
    Abstract [en]

    Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1 beta, IL-6, IL-10, IL-8, MIP-1 beta, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group (andgt;= 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 mu mol/L (25-44 year) to 252 mu mol/L (andgt;= 65 years; p andlt; 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L (p andlt; 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients andgt;= 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients andgt;= 65 years old, significantly higher compared to all other age groups (p andlt; 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

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  • 61.
    Mellergård, Pekka
    et al.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Säberg, Carina
    Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Differences in Cerebral Extracellular Response of Interleukin-1 beta, Interleukin-6, and Interleukin-10 After Subarachnoid Hemorrhage or Severe Head Trauma in Humans2011In: NEUROSURGERY, ISSN 0148-396X, Vol. 68, no 1, p. 12-19Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Microdialysis has become a routine method for biochemical surveillance of patients in neurosurgical intensive care units. OBJECTIVE: To analyze the intracerebral extracellular levels of 3 interleukins (ILs) during the 7 days after major subarachnoid hemorrhage or traumatic brain injury). METHODS: Microdialysate from 145 severely injured neurosurgical intensive care unit patients (88 with subarachnoid hemorrhage, 57 with traumatic brain injury) was collected every 6 hours for 7 days. The concentrations of IL-1 beta and IL-6 were determined by fluorescence multiplex bead technology, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: Presented are the response patterns of 3 ILs during the first week after 2 different types of major brain injury. These patterns are different for each IL and also differ with respect to the kind of pathological impact. For both IL-1 beta and IL-6, the initial peaks (mean values for all patients at day 2 being 26.9 +/- 4.5 and 4399 +/- 848 pg/mL, respectively) were followed by a gradual decline, with IL-6 values remaining 100-fold higher compared with IL-1 beta. Female patients showed a stronger and more sustained response. The response of IL-10 was different, with mean values less than 23 pg/mL and with no significant variation between any of the postimpact days. For all 3 ILs, the responses were stronger in subarachnoid hemorrhage patients. The study also indicates that under normal conditions, IL-1 beta, IL-6, and IL-10 are present only at very low concentrations or not at all in the extracellular space of the human brain. CONCLUSION: This is the first report presenting in some detail the human cerebral response of IL-1 beta, IL-6, and IL-10 after subarachnoid hemorrhage and traumatic brain injury. The 3 ILs have different reaction patterns, with the response of IL-1 beta and IL-6 being related to the type of cerebral damage sustained, whereas the IL-10 response was less varied.

  • 62.
    Mellergård, Pekke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Sjögren, Florence
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology .
    Pettersson, P.
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Changes in Extracellular Concentrations of Some Cytokines, Chemokines, and Neurotrophic Factors After Insertion of Intracerebral Microdialysis Catheters in Neurosurgical Patients2008In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, no 1, p. 151-157Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The extracellular levels of eight different inflammatory agents were analyzed during the initial 36 hours after insertion of microdialysis catheters in patients. METHODS: Cerebral extracellular fluid from 38 patients who were treated in a neurosurgical intensive care unit for severe brain injury was collected every 6 hours for 36 hours. The concentration of interleukin (IL)-1ß, IL-6, IL-8, macrophage inflammatory protein-1ß, regulated on activation, normal T-cell expressed and secreted (RANTES), fibroblast growth factor-2, and vascular endothelial growth factor was determined by a multiplex assay, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: This is the first report regarding the presence of IL-10, IL-8, macrophage inflammatory protein-1ß, regulated on activation, T-cell expressed and secreted, vascular endothelial growth factor, and fibroblast growth factor-2 in the tissue level proper of the living human brain. The study also provides new information regarding the response of IL-1ß and IL-6 after insertion of a microdialysis catheter. The study confirms that the intriguing patterns of interplay between different components of the inflammatory response studied in laboratory settings are present in the human brain. This was most clearly observed in the variations in response between the three different chemokines investigated, as well as in the rapid and transient response of fibroblast growth factor-2. CONCLUSION: The data presented illustrate the opportunity to monitor biochemical events of possible importance in the human brain and indicate the potential of such monitoring in neurosurgical intensive care. The study also underlines that any analysis of events in the brain involving mechanical invasiveness needs to take into account biochemical changes that are directly related to the manipulation of brain tissue.

  • 63.
    Newton Bishop, Julia A.
    et al.
    ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, U.K..
    Bradburn, M.
    Karlsson, Pia
    Altman, D. G.
    Cancer Research Fund Medical Statistics Group, Oxford, U.K..
    Bergman, W.
    Department of Dermatology, Leiden University Medical Center, The Netherlands.
    Østerlind, A.
    Danish Cancer Society and Department of Dermatology, Gentofte University Hospital, Hellerup, Denmark.
    Pinney, E.
    ICRF Maths Statistics and Epidemiology, London, U.K. .
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Scerri, L.
    Department of Dermatology, Southampton University Hospitals NHS Trust, U.K..
    Weichenthal, M.
    Arbeitsgemeinschaft Dermatologische Pravention, Hamburg, Germany.
    Mant, D.
    Department of Primary Medical Care, University of Southampton, U.K..
    Breitbart, E. W.
    Arbeitsgemeinschaft Dermatologische Pravention, Hamburg, Germany.
    Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study2000In: British Journal of Dermatology, ISSN 0007-0963, Vol. 142, no 2, p. 331-337Article in journal (Refereed)
    Abstract [en]

    The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94·5% (kappa 0·70, P < 0·0001). The kappa scores in different countries ranged from 0·65 to 0·77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

  • 64.
    Nilsson, Gert
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Leahy, M.
    Department of Physics University of Limeric, Ireland.
    O´Doherty, J.
    Department of Physics University of Limerick, Ireland.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of tissue viability by polarization spectroscopy2008In: Opto-Electronics Review, ISSN 1230-3402, E-ISSN 1896-3757, Vol. 16, no 3, p. 309-313Article in journal (Refereed)
    Abstract [en]

    A new and versatile method for tissue viability imaging based on polarization spectroscopy of blood in superficial tissue structures such as the skin is presented in this paper. Linearly polarized light in the visible wavelength region is partly reflected directly by the skin surface and partly diffusely backscattered from the dermal tissue matrix. Most of the directly reflected light preserves its polarization state while the light returning from the deeper tissue layers is depolarized. By the use of a polarization filter positioned in front of a sensitive CCD-array, the light directly reflected from the tissue surface is blocked, while the depolarized light returning from the deeper tissue layers reaches the detector array. By separating the colour planes of the detected image, spectroscopic information about the amount of red blood cells (RBCs) in the microvascular network of the tissue under investigation can be derived. A theory that utilizes the differences in light absorption of RBCs and bloodless tissue in the red and green wavelength region forms the basis of an algorithm for displaying a colour coded map of the RBC distribution in a tissue. Using a fluid model, a linear relationship (cc. = 0.99) between RBC concentration and the output signal was demonstrated within the physiological range 0–4%. In-vivo evaluation using transepidermal application of acetylcholine by the way of iontophoresis displayed the heterogeneity pattern of the vasodilatation produced by the vasoactive agent. Applications of this novel technology are likely to be found in drug and skin care product development as well as in the assessment of skin irritation and tissue repair processes and even ultimately in a clinic case situation.

  • 65.
    Nyström Kronander, Ulla
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Urtikaria – utredning och behandling2010In: Allergi i Praxis, ISSN 0806-5462Article in journal (Other academic)
  • 66.
    O'doherty, Jim
    et al.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Leahy, Martin J.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation2007In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, no 4, p. 472-484Article in journal (Refereed)
    Abstract [en]

    Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

    Methods: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced.

    Results: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi index) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation.

    Conclusions: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.

  • 67.
    O'Doherty, Jim
    et al.
    Royal Surrey County Hospital, Guildford, United Kingdom.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Enfield, Joey
    University of Limerick, Ireland.
    Nilsson, Gert E
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Leahy, Martin J.
    University of Limerick, Ireland.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation2011In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 303, no 2, p. 79-87Article in journal (Refereed)
    Abstract [en]

    In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.

  • 68.
    O'Goshi, K.-I.
    et al.
    Department of Dermatology, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Inter-instrumental variation of skin capacitance measured with the Corneometer®2005In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 11, no 2, p. 107-109Article in journal (Refereed)
    Abstract [en]

    Background/purpose: Measurement of skin surface and stratum corneum (SC) hydration during clinical and/or experimental trials needs devices with acceptable reproducibility and sensitivity under conditions ranging from increased and normal to low hydration. A previous study comparing Corneometer® instruments (European group for Efficacy Measurement of Cosmetics and Other products - EEMCO) used for measurement of electrical capacitance of skin indicated a major difference among Corneometer® instruments. The aim of this study was to assess threee inter-instrumental similar Corneometer® instruments (two pieces of CM820 and one CM810) in normal skin. We named them CM-A(CM820), CM-B(CM820), and CM-C(CM810). Methods: The hydration state of SC measured as electrical capacitance of six body sites were measured in 53 subjects with three Corneometer® instruments. Result: We found that the Corneometer® instruments displayed close capacitance levels. When one Corneometer® was plotted against another the regression line indicated a good correlation among instruments albeit a major and random disagreement could appear in individual sites as an exception. Conclusion: Three Corneometer® instruments evaluated in this study gave close measurements and correlated well. Nevertheless, pretest validation of instruments should be undertaken in multicenter studies where capacitance data are compared or pooled, and concordance among instruments should be documented prior to study. © Blackwell Munksgaard, 2005.

  • 69.
    Ring, L.
    et al.
    Uppsala University, Sweden.
    Kettis-Lindblad, A.
    Uppsala University, Sweden.
    Kjellgren, Karin
    The Sahlgrenska Academy at Göteborg University, Sweden.
    Kindell, Y.
    Uppsala University, Sweden.
    Maroti, M.
    Ryhov Hospital, Jönköping, Sweden.
    Serup, Jörgen
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Living with skin diseases and topical treatment: patients' and providers' perspectives and priorities2007In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 18, no 4, p. 209-218Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Relationship-centred care stresses the importance of taking both patients' and health-care providers' values, expectations and preferences into account to improve health outcomes. The aim of this qualitative study was to identify patients' and providers' views and experiences of skin disease and topical treatment.

    METHODS:

    Two types of focus group were used: (i) patients with chronic dermatological diseases and (ii) doctors, nurses and pharmacists working in dermatological care.

    RESULTS:

    Three major categories emerged: (i) problems related to the disease, (ii) problems related to the treatment and (iii) strategies for improving everyday life for patients.

    CONCLUSION:

    Patients and providers made several suggestions for improving everyday life. Future research needs to focus on how to achieve preference-matched shared decision-making, or concordance, between patients and health-care providers, taking different perspectives into account and how to evaluate the effect of the final, clinical, economical and humanistic outcomes of care and treatment. More seamless care and an increasingly shared understanding between patients and providers of their values, expectations and preferences for care and treatment may contribute to better health and better daily lives for patients.

  • 70.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Magnusson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Implications for critical care of a new in vivo human vascular microdosing technique for giving noradrenaline and nitroglycerine by microdialysisManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion. Little is known, however, about the metabolic consequences seen in skin secondary to hyporperfusion, particularly when the effects of vasoactive drugs are involved. The aims of this study were: to develop an in vivo, human microdosing model based on microdialysis in skin; and to investigate the effects on blood flow and metabolism of administering noradrenaline and nitroglycerine locally.

    Method: Nine healthy volunteers each had two or three microdialysis catheters placed intradermally in the volar surface of the lower arm. After a stabilisation period, the catheters were perfused with buffers containing noradrenaline 0.5 or 5 μg/ml for 60 minutes, and after a second period of equilibrium of 60 minutes, all catheters were perfused with buffer containing nitroglycerine (0.5mg/ml). Changes in the blood flow in the skin were measured by laser Doppler imaging urea and ethanol clearance. Simultaneous changes in tissue glucose, lactate, and pyruvate concentrations were recorded.

    Results: Perfusing skin with noradrenaline and nitroglycerine induced appreciable changes in all variables studied, depending on time and dose. The changes in glucose and lactate concentrations correlated with the change in blood flow assessed by either laser Doppler imaging or urea clearance. The changes in glucose and lactate that were induced by vasoconstriction (noradrenaline) continued until vasodilatation was induced by nitroglycerine.

    Conclusion: Noradrenaline given by microdialysis in healthy volunteers induced reproducible and dose-dependent hypoperfusion and ischaemia with simultaneous metabolic consequences. Among these, we particularly note that: tissue glucose concentrations responded rapidly to hypoperfusion but remained considerably higher than zero, which suggests an energy-dependent deficiency in cellular uptake; and vasoconstriction remained after cessation of the noradrenaline perfusion, implicating vasospasm and a lack of autoregulatory (recovery) capacity in skin. These findings are particularly interesting from the critical care perspective, where noradrenaline is used extensively for circulatory support. The metabolic consequences may be underestimated and our results suggest that further investigations are warranted.

  • 71.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Magnusson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 7, p. 975-983Article in journal (Refereed)
    Abstract [en]

    Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.

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  • 72. Sander, B.
    et al.
    Karlsson, Pia
    Linköping University, Department of Computer and Information Science. Linköping University, The Institute of Technology.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Westermark, P.
    Boeryd, B.
    Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological: study of 130 cases1999In: International Journal of Cancer, ISSN 0020-7136, Vol. 80, no 5, p. 646-651Article in journal (Refereed)
    Abstract [en]

    To assess whether there has been a change in histological features and prognostic factors of primary cutaneous malignant melanoma (CMM) in young individuals in Sweden, an unselected, population-based study was undertaken; 177 cases of primary CMM in persons below 20 years of age were reported to the Swedish National Cancer Registry between 1973 and 1992. In 87% of the cases, original tumor tissue was available for histo-pathological review. The original diagnosis was verified in 88% (n = 126) of these cases. All tumors had histological features similar to adult CMM; 17% had an associated precursor lesion. Superficial spreading melanoma (SSM) was the most common sub-type, constituting 20/36 cases in the first decade and 59/90 in the second. Corresponding figures for nodular melanoma (NM) were 11/36 and 23/90. Only 5 melanomas in situ were diagnosed. In girls, the mean thickness of SSM decreased from 1.5 to 0.6 mm (p < 0.001). Overall mortality was 10%, 22% in the group with CMM diagnosed 0-15 years of age and 8% in individuals 15-19 years. Fatal CMM cases diagnosed below 15 years of age (n = 4) were NM >1.6 mm thick and in subjects 15-19 years (n = 9) 44% of fatal tumors were NM with a mean thickness of 2.2 mm. Breslow index was the single most important prognostic factor. However, when known prognostic factors were adjusted for in a Cox regression analysis, young age remained an independent risk factor, with a relative death rate of 0.21 for individuals aged 15-19 compared with children <15 years of age.

  • 73.
    Seifert, Oliver
    et al.
    Ryhov Hospital, Sweden .
    Matussek, Andreas
    Ryhov Hospital, Sweden .
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Geffers, Robert
    Helmholtz Centre Infect Research, Germany .
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions2012In: Journal of Inflammation, ISSN 1476-9255, E-ISSN 1476-9255, Vol. 9, no 43Article in journal (Refereed)
    Abstract [en]

    Background: Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. less thanbrgreater than less thanbrgreater thanMethods: Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. less thanbrgreater than less thanbrgreater thanResults: Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. less thanbrgreater than less thanbrgreater thanConclusion: The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.

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  • 74.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Efficacy testing of cosmetic products2001In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 7, no 3, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Background/aims: Regulations for cosmetic products primarily address safety of the products that may be used by large populations of healthy consumers. Requirements for documentation of efficacy claims are only fragmentary. This synopsis aims to review and conclude a set of standards that may be acceptable to the European Community, and the cosmetic industry, as a legal standard for efficacy documentation in Europe in the future. Methods and Results: Ethical, formal, experimental, statistical and other aspects of efficacy testing are described, including validation, quality control and assurance. The importance of user relevant clinical end points, a controlled randomized trial design and evidence-based cosmetic product documentation, validation of methods, statistical power estimation and proper data handling, reporting and archiving is emphasized. The main principles of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) good clinical practice (GCP) should be followed by the cosmetics industry in a spirit of good documentation standard and scientific soundness, but full GCP is not considered mandatory in the field of cosmetics. Documentation by validated bio-instrumental methods may be acceptable, but efficacy documentation based on information about raw materials, reference to literature and laboratory experiments are only acceptable in exceptional cases. Conclusions: Principles for efficacy substantiation of cosmetic products in Europe, as described in this synopsis, are officially proposed by the Danish Ministry of Environment and Energy to the European Community as a basis for an amendment to the Cosmetics Directive or otherwise implemented as a European Community regulation.

  • 75.
    Serup, Jörgen
    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.
    Kettis Lindblad, Åsa
    Department of Pharmacy, Uppsala University, Uppsala, Sweden.
    Maroti, Marianne
    Ryhov Hospital, Jönköping, Sweden.
    Kjellgren, Karin I
    Institute of Nursing Faculty of Health and Caring Sciences, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Niklasson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Ring, Lena
    Department of Pharmacy, Uppsala University, Uppsala, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    To follow or not to follow dermatological treatment: A review of the literature2006In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 86, no 3, p. 193-197Article, review/survey (Refereed)
    Abstract [en]

    Creams, ointments and solutions applied to the skin surface by patients as part of a daily routine might be expected to provide a more variable dosage than do standard tablets. However, adherence to treatment in dermatology has been little studied. This article reviews recent publications in the field. These are dominated by questionnaire-based studies, which tend to over-estimate adherence. Reduced adherence to dermatological treatment is noted in 34-45% of patients. It is likely that the percentage of patients who practice truly optimal treatment in their daily life is even lower considering the variable practice of self-treatment. Self-reported psychiatric morbidity contributes to poor adherence to dermatological treatment, while a well-functioning doctor-patient interaction is a major determinant of good adherence, as is patient satisfaction. In conclusion, adherence to dermatological treatment is unsatisfactory and there is a need for intervention and change in clinical routines. The therapeutic and economic benefits may be considerable. The immediate challenge is to stimulate a change in patient behaviour and improve self-treatment at home. © 2006 Acta Dermato-Venereologica.

  • 76.
    Shubbar, Emman
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Vegfors, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Carlström, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Petersson, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Enerbäck, Charlotta
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 134, no 1, p. 71-80Article in journal (Refereed)
    Abstract [en]

    Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasin increased proliferation comparable to that of recombinant VEGF protein. No change in proliferation was seen when endothelial cells were infected with psoriasin-expressing adenoviruses, suggesting that the proliferative effect of psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting the receptor for advanced glycation end products (RAGE), thus inhibited endothelial cell proliferation and tube formation enhanced by recombinant psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein abolished the effect of psoriasin on endothelial cell proliferation. Our data suggest that psoriasin expression in mammary epithelial cells leads to increased endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may therefore play a role in breast cancer progression by promoting oxidative stress response and angiogenesis.

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  • 77.
    Sjögren, Florence
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Sterile trauma to normal human dermis invariably induces IL1beta, IL6 and IL8 in an innate response to "danger".2009In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 89, no 5, p. 459-465Article in journal (Refereed)
    Abstract [en]

    Microdialysis allows the study of the local production and temporal resolution of cytokines in living skin. Samples were taken from the normal skin of 10 healthy subjects for 24-28 h after insertion of a concentric microdialysis catheter, and analysed with a Luminex bead-based assay. Interleukin-1 beta (IL1b), IL6 and IL8 were seen in all subjects at all time-points after the first hour. Levels peaked at 5-8 h, equilibrating to lower levels at 24 h. Immunohistological double staining for human leukocyte antigen (HLA)-DR and intracellular cytokines on biopsies taken after catheter removal showed many stained cells in the dermis, in contrast to the few cells stained in the epidermis. This study demonstrates the reactive capability of the dermis when provoked separately from the epidermis. The production of IL1b, IL6 and IL8 occurs invariably in what can be termed an innate, dermal response to "danger"; in this case in the form of sterile needle trauma.

  • 78.
    Sjögren, Florence
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Are cutaneous microdialysis cytokine findings supported by end-point biopsy immunohistochemistry findings?2010In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 12, no 4, p. 741-749Article in journal (Refereed)
    Abstract [en]

    Insertion of a cutaneous microdialysis catheter into normal dermis has been shown to induce the production of IL1b, IL6 and IL8 in an innate response to minimal trauma. In the present study, skin biopsy for immunohistochemistry has been performed at the site of the microdialysis catheter to compare the findings with that of the microdialysis findings 24 h after insertion. Of the three named cytokines, concordance between the two investigated technologies was highest for IL8 (100%) followed by IL6 (70%) and IL1b (50%). For seven other pro-inflammatory and T cell-relevant cytokines studied, concordance ranged between 50% and 80%. The total number of positive (microdialysis or immunofluorescence) findings was similar between the two methodologies. Technical and biological phenomenon can explain the differences. We conclude that both methodologies illustrate important features of tissue biology and that a combination of the two methods in clinical research can provide the chronology of soluble mediator participation and the more classic, but also more invasive, biopsy-based methodology at a point which constitutes the end of the observation period. We conclude further that at the 24-h time period here studied, microdialysis catheters are still functional and thus capable of producing relevant data which can be corroborated and extended by the “end point biopsy”.

  • 79.
    Sjögren, Florence
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Davidsson, Karin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöström, Michael
    Umeå University.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Cutaneous Microdialysis: Cytokine Evidence for Altered Innate Reactivity in the Skin of Psoriasis Patients?2012In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 14, no 2, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Cutaneous microdialysis demonstrates cytokine production in living human skin. In the present study, microdialysis samples taken from uninvolved and lesional skin in three test subjects with psoriasis over 24 h have been investigated for cytokine content with a bead-based multiplex immunoassay from Luminex. Concentration curves for a set of Th1/Th2 and pro-inflammatory cytokines measured differed from a reference group of ten subjects without psoriasis. The time to return to near baseline values after innate insertion reactivity is between 9 and 16 h. Post-equilibration levels (17-24 h) for the three main cytokines elevated in the reference group were differentially elevated outside the range of the reference group for interleukin-1 beta (IL1 beta) and IL8 but not so for IL6. Two further cytokines, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha not generally elevated in the reference group, showed elevated values in the test subjects. Multivariate time series analysis (chemometry) showed that cytokine patterns for the individual test subjects often fell outside the 99% confidence intervals of a model generated from the reference group. In a clinical research situation, cutaneous microdialysis is feasible, gives generally higher cytokine levels than in the blood and generates interpretable data on an individuals reactivity compared with a reference group. This may well prove useful in delineation of pathogenetic issues, selection of appropriate therapy and monitoring of subsequent response in inflammatory dermatoses such as psoriasis.

  • 80.
    Sjöwall, Johanna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases.
    Fryland, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Nordberg, Marika
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Garpmo, Ulf
    Kalmar Hospital.
    Jansson, Christian
    Aland Borrelia Grp.
    Carlsson, Sten-Anders
    Aland Borrelia Grp.
    Bergstrom, Sven
    Umea University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Nyman, Dag
    Aland Borrelia Grp.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans2011In: PLOS ONE, ISSN 1932-6203, Vol. 6, no 3, p. 0018220-Article in journal (Refereed)
    Abstract [en]

    Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

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  • 81.
    Suihko, Christian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Serup, Jorgen
    Bispebjerg Hospital, Denmark .
    Fluorescent fibre-optic confocal imaging of lesional and non-lesional psoriatic skin compared with normal skin in vivo2012In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 18, no 4, p. 397-404Article in journal (Refereed)
    Abstract [en]

    Background/aims Fibre-optic confocal imaging (FOCI) allows non-invasive visualization of live skin in vivo. A contrast agent, a fluorophore, is injected in the dermis. FOCI images are optical sections from a horizontal (en face) view. The aim was to study epidermis and the cellular structure of keratinocytes of psoriatic plaques and adjacent non-lesional with healthy skin as a reference. Methods Twelve patients with stable plaque psoriasis were studied and compared with a control group of eight healthy individuals. Fluorescein sodium was used as fluorophore. A hand held fibre-optic laser scanner (Stratum (R); Optiscan Pty., Melbourne, Australia) was used. The study included morphometric analyses. Results The confocal in vivo images demonstrated characteristic features of epidermis and keratinocytes in lesional and non-lesional skin vs. healthy skin. Morphometry based on FOCI demonstrated an approximately 30% increased width of keratinocytes of psoriatic skin vs. healthy control, and the number of keratinocytes per viewing field was reduced. FOCI allowed non-invasive visualization of cell nuclei and parakeratosis of psoriatic epidermis. The horizontal width of dermal papillae of psoriatic skin was increased by approximately 50% as compared with healthy skin, and the flow of erythrocytes in the papillar vessels could be observed in real-time. Conclusion FOCI can directly visualize essential epidermal structures of plaque psoriasis in vivo, in real-time and with cellular resolution without the need of taking biopsies and thus without disturbing the natural state of the skin. FOCI is a versatile future tool for non-invasive microscopic diagnosis and therapy follow-up of psoriasis.

  • 82.
    Suihko, Christian
    et al.
    Linköping University, Faculty of Health Sciences.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Fluorescence confocal laser scanning microscopy for in vivo imaging of epidermal reactions to two experimental irritants2008In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, no 4, p. 498-503Article in journal (Refereed)
    Abstract [en]

    Background: Fibre-optic fluorescence confocal laser scanning microscopy (CLSM) is a novel non-invasive technique for in vivo imaging of skin. The cellular structure of the epidermis can be studied. A fluorophore, e.g. fluorescein sodium, is introduced by an intradermal injection or applied to the skin surface before scanning. Images are horizontal optical sections parallel to the skin surface. Fluorescence CLSM has hitherto not been applied to experimental contact dermatitis. Objective: The aim was to study the applicability of fluorescence CLSM for in situ imaging of irritant contact dermatitis reactions caused by established model irritants, e.g. sodium lauryl sulphate (SLS) and pelargonic acid (PA). Methods: Twelve healthy individuals volunteered. The flexor aspect of the right and the left forearm was exposed to SLS in water and PA in isopropanol and occluded under Finn Chambers for 24h. The reactions were rated clinically and, following epicutaneous and intra-dermal application of fluorescein sodium, studied by fluorescence CLSM, magnification ×1000. Results: Both irritants disturbed the epidermal intercellular borders, which became blurred, thickened and variably altered. This was interpreted as being a result of chemical damage to cellular membranes. Cell borders might show a double contour as a result of inter-cellular oedema. PA might increase the size of individual keratinocytes interpreted as a result of intra-cellular disturbance with oedema. SLS-exposed sites showed clusters of keratinocytes with visible nuclei in the outer layers of the epidermis, e.g. a parakeratotic shift supposed to be due to increased cell proliferation elicited by SLS. The isopropanol vehicle and PA did not interfere with the CLSM imaging technique or the experimental procedures. SLS, being a detergent, however, modified the physico-chemical properties of the skin surface and both disturbed epicutaneous labelling with the flurophore and immersion oil coupling between the skin surface and the optical system. Thus, SLS was technically more difficult to study by CLSM than PA. Conclusions: This preliminary study demonstrated the applicability of fluorescence CLSM for a detailed study of experimental skin irritants in vivo. Essential findings were disturbed and widened cell borders, swelling of keratinocytes by PA and induction of a parakeratotic shift by SLS with clusters of keratinocytes holding nuclei in the epidermis. Fluorescence CLSM offers a unique opportunity to study the inter- and intracellular water compartments directly in the epidermis in situ and an opportunity to visualize cell proliferation manifested as parakeratosis. Fibre-optic fluorescence CLSM of irritant reactions is, however, technically more complicated than reflectance CLSM and may not be applicable to any irritant. SLS applied epicutaneously interacted with the skin surface and coupling to the microscope and was thus found to be more difficult to study technically than PA. PA dissolved in isopropanol is for technical reasons, and with SLS as alternative, considered the preferred model irritant. © Journal compilation © 2008 Blackwell Munksgaard.

  • 83.
    Sun, Xiao-Feng
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Zhang, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas1997In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 74, no 6, p. 600-604Article in journal (Refereed)
    Abstract [en]

    Heat shock proteins (hsp) are molecular chaperones that are increased by various environmental and patho-physiological stimuli. Hsp can bind to mutant/wild-type p53 in tumors and, consequently, could not only regulate p53 accumulation or localization but also modulate its biological effects on cells. However, there is little information available on the significance of hsp expression in colorectal cancer. The aim of our study was to investigate the relationship of hsp to p53 expression, clinico-pathological factors and prognosis in a series of 256 patients with colorectal adenocarcinomas, using immuno-histochemistry. Seventy-five cases exhibited hsp expression in the cytoplasm, with 11 presenting both cytoplasmic and nuclear staining. Hsp expression was related positively to cytoplasmic p53 expression but not to nuclear p53 expression. In the subgroup of rectal tumors, hsp over-expression appeared to predict unfavorable survival, though its prognostic value diminished using multivariate analysis. There were no significant relationships of hsp with patient sex or age, tumor site, Duke's stage, growth pattern or differentiation.

  • 84.
    Synnerstad, Ingrid
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Ternesten-Bratel, A
    Capio Diagnost AB.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Low risk of melanoma in patients with atopic dermatitis2008In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 22, no 12, p. 1423-1428Article in journal (Refereed)
    Abstract [en]

    Background: There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper-reactive state of the immune system. Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment.

    Objective: This study aims to investigate the melanoma risk in a retrospective cohort of AD patients compared with the population.

    Study design: 6280 AD patients born 1935–1979 visited five Dermatology clinics during 1986–2004. Mean follow-up time was 36.7 years (SD 6.9) corresponding to 230 742 person-years at risk. The cohort file was linked to the National Cancer register.

    Results: Six AD patients with melanoma were identified, and the Poisson regression analysis adjusted for age group, sex and year resulted in an incidence rate ratio of 0.49 (95% confidence interval: 0.27–1.35, P = 0.08) for the AD group compared with the total population in the region.

    Conclusion: A low risk to develop melanoma was found in AD patients. However, the results must be interpreted with caution since the small number of expected cases of melanoma makes the risk estimate sensitive to chance effects. We hypothesize that formation of naevi and progression to melanoma is counteracted by the inflammatory process in the skin of AD patients.

  • 85.
    Tagami, H.
    et al.
    Department of Dermatology, Tohoku University, Tohoku, Japan.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Hachiro Tagami, MD: Japanese dermatologist in a global community2003In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 9, no 1Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 86.
    Tinghög, Gustav
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    How costly is skin cancer for society?2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 1, p. 12-14Article in journal (Other academic)
    Abstract [en]

    The annual cost of skin cancer in Sweden in 2005 was estimated to be -142.4 million (-15/inhabitant). When comparing direct costs only cost associated with medical consumption, skin cancer is more costly than the equivalent costs of both multiple sclerosis and brain tumours, and is close to the cost of breast cancer.

  • 87.
    Tinghög, Gustav
    et al.
    Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Carlsson, Per
    Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Societal Cost of Skin Cancer in Sweden 20052008In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 88, no 5, p. 467-473Article in journal (Refereed)
    Abstract [en]

    Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. This study aims to estimate the total societal cost of skin cancer in Sweden 2005, using a prevalence based cost-of-illness approach. The total cost of skin cancer was estimated to € 142.4 million (€ 15 per inhabitant), of which € 79.6 million (€ 8 per inhabitant) were spent on health services and € 62.8 million (€ 7 per inhabitant) were due to production loss. The main cost driver was resource utilisation in outpatient care, amounting to 42.2% of the total cost. Melanoma was the most costly skin cancer diagnosis. Non-melanoma skin cancer was however the main cost driver for health services alone. In the future it is important to establish effective preventive measures to avoid increasing costs and suffering caused by skin cancer.

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  • 88.
    Ulff, E.
    et al.
    Ryhov Hospital, Jönköping, Sweden.
    Maroti, M.
    Ryhov Hospital, Jönköping, Sweden.
    Kettis-Lindblad, A.
    Uppsala University, Sweden.
    Kjellgren, Karin
    Sahlgrenska Academy, Göteborg University, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Ring, L.
    Uppsala University, Sweden.
    Serup, Jörgen
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Single application of a fluorescent test cream by healthy volunteers: assessment of treated and neglected body sites2007In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 156, no 5, p. 974-978Article in journal (Refereed)
    Abstract [en]

    Background: Management of dermatological self-treatment is demanding. Imperfect application of creams and ointments and poor adherence to topical treatment are common, resulting in unsatisfactory treatment outcome. Objectives: To assess the technique and precision of test subjects' self-application of a test cream. Treated and neglected skin sites were measured after intended widespread single application of a fluorescent test cream. Methods: Twenty healthy volunteers (10 women, 10 men) were included. They were asked to treat their whole skin surface with the fluorescent test cream, except the head and neck and skin covered by underwear. Treated and untreated sites were subsequently measured under Wood's ultraviolet radiation. Results: Thirty-one per cent of the skin surface that was a target for application did not show any fluorescence and thus was assumed to have been untreated. Typical neglected sites included the central back, the upper breast, the axilla with surrounding skin, the legs and the feet, particularly the sole. The posterior aspect of both trunk and extremities, not easily inspected, was more often neglected. In the treated sites the fluorescence was typically uneven. Conclusions: Qualified and motivated persons with no obvious physical limitations practised imperfect self-application of a test cream mimicking a therapeutic cream product. As much as 31% of the skin surface was neglected. Sites especially prone to nonapplication were identified. This might imply that dermatological patients on long-term self-treatment may practise local application very poorly, a problem of major therapeutic and economic importance. A fluorescent test cream can be used for research, and as an educational tool in the training of dermatological patients on how to apply local treatment.

  • 89.
    Ulff, Eva
    et al.
    Ryhov County Hospital, Sweden .
    Maroti, Marianne
    Ryhov County Hospital, Sweden .
    Serup, Jörgen
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology in Östergötland.
    Fluorescent cream used as an educational intervention to improve the effectiveness of self-application by patients with atopic dermatitis2013In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 24, no 4, p. 268-271Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to assess if a fluorescent cream, in a self-application educational session, could increase the effectiveness of cream application in practice and serve as a therapeutic intervention. Methods: 30 adults with atopic dermatitis were enrolled. They applied a fluorescent test cream on two occasions. Effectiveness of application was checked under ultraviolet illumination. At baseline, the patients greased their skin as they normally do. After 2 weeks, the patients were instructed to grease the whole body area. The results were commented on and visualised to the patients on both occasions. Results: At the baseline visit, 29% of the target skin was untreated, and at the follow-up visit after education, this improved to 13.6% (mean values, p andlt; 0.05). Women performed better than men at baseline; however, men performed similar to women at the follow-up visit. Conclusions: The Fluorescent-cream Educational Session (FES) is an educational instrument for therapeutic intervention based on interaction between patient and provider. It includes hard endpoints, that is, visualisation and measurement of treated area, time spend on treatment and amount of cream used.

  • 90.
    Ulff, Eva
    et al.
    Ryhov County Hospital, Sweden .
    Maroti, Marianne
    Ryhov County Hospital, Sweden .
    Serup, Jörgen
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Falkmer, Ursula
    Ryhov County Hospital, Sweden .
    A potent steroid cream is superior to emollients in reducing acute radiation dermatitis in breast cancer patients treated with adjuvant radiotherapy. A randomised study of betamethasone versus two moisturizing creams2013In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 108, no 2, p. 287-292Article in journal (Refereed)
    Abstract [en]

    Background and purpose: The aim was to investigate whether treatment with potent local steroids can reduce signs and symptoms of acute radiation dermatitis in breast cancer patients undergoing adjuvant radiotherapy (RT) compared to emollient creams. less thanbrgreater than less thanbrgreater thanMaterial and methods: The study was randomised and double-blinded. Patients with breast cancer who had undergone mastectomy or breast-conserving surgery were included when they started adjuvant 3D planned RT. In all, 104 patients were randomised 2:1:1 to three treatment groups, i.e. betamethasone + Essex (R) cream, Essex (R) cream or Canoderm (R) cream. The patients themselves treated the irradiated area during the radiation period (5 weeks) and two weeks after cessation of RT. Signs of RT dermatitis were measured qualitatively with RTOG clinical scoring and quantitatively by colorimeter. In addition, the patients symptoms were recorded as well as the Fitzpatrick skin type. less thanbrgreater than less thanbrgreater thanResults: There was a statistically significant difference (p = 0.05) in skin reactions when assessed with RTOG in favour of the group treated with the potent steroid. Patient-related symptoms did not differ between the treatment groups. The effect of the steroid was prominent in three subgroups, i.e. (i) patients treated with ablation of the breast, (ii) patients receiving RT to the armpit and the supraclavicular fossa, and (iii) patients with Fitzpatrick skin type 1. less thanbrgreater than less thanbrgreater thanConclusions: Treatment with betamethasone cream is more efficient than moisturizers for the control of acute RT dermatitis in patients treated with adjuvant RT for breast cancer.

  • 91.
    Varol, Alexandra L
    et al.
    Liverpool Hospital.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    A minimally invasive human in vivo cutaneous wound model for the evaluation of innate skin reactivity and healing status2010In: ARCHIVES OF DERMATOLOGICAL RESEARCH, ISSN 0340-3696, Vol. 302, no 5, p. 383-393Article in journal (Refereed)
    Abstract [en]

    Individual variability in skin reactivity and healing capacity after trauma are important clinical issues. The aims were to develop an in vivo, human wound model based on a standardised minimal skin injury and to demonstrate therapeutic effect of simple wound therapies in terms of morphological wound outcome with changes in skin blood perfusion as a quantified indicator of wound healing. In a series of experiments, wounds were induced on the normal forearm skin of volunteers using a blood collection lancet. This was well tolerated. Wounds were assessed by naked eye examination or laser Doppler perfusion imaging (LDPI) at baseline and at up to 6 further time points up to 96 h in control wounds and wounds treated by commonly used occlusive dressing options. Assessment by clinical observation with 10x magnification showed over 96 h a progression of erythema, surface crust, a new keratinisation layer and finally healed areas. LDPI quantifying wound erythema showed a peak at 24 h and near normal levels at 96 h. Inter-individual variability was evident but intra-individual variability was much less pronounced. Wounds treated with occlusion showed a statistically significant more rapid return to baseline blood perfusion as measured by LDPI compared to controls supported by favourable healing parameters in the clinical assessment. The paper exemplifies use of non-invasive, bioengineering technique for quantification of individual innate variability in skin reactivity, wound healing capacity and therapeutic effect in a well-tolerated in vivo, human, minimal skin trauma model.

  • 92.
    Varol, Alexandra
    et al.
    Liverpool Hospital.
    Seifert, Oliver
    Ryhov Hospital.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    The skin pathergy test: innately useful?2010In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 302, no 3, p. 155-168Article, review/survey (Refereed)
    Abstract [en]

    Pathergy is the term used to describe hyper-reactivity of the skin that occurs in response to minimal trauma. A positive skin pathergy test (SPT), characterised by erythematous induration at the site of the needle stick with a small pustule containing sterile pus at its centre, is among the criteria required for a diagnosis of Beh double dagger ets disease (BD) and in certain population has been shown to be highly specific for this condition. Problems with standardising the induction manoeuvre for the SPT as well as the method of assessment of the response have limited the usefulness of the SPT in the clinical setting. Extensive investigation into histopathological and immunological aspects of pathergy has led to a number of hypotheses relating to the aetiology of the skin pathergy reaction and the disease itself, but the cause is considered to be unknown. Pathergy lesions, the development of new skin lesions or the aggravation of existing ones following trivial trauma, are also reported in pyoderma gangrenosum and has been noted in other neutrophilic dermatoses such as Sweets syndrome. The response of such patient groups to the systematic application of the SPT has not been described. We propose that a new way of considering the pathergy reaction is to see it as an aberration of the skins innate reactivity from a homeostatic reactive mode closely coupled to tissue healing to an abnormal destructive/inflammatory mode. Our understanding of BD and other similar conditions would profit by more detailed mechanistic knowledge of skin homeostasis to minimal trauma in both health and disease through a more structured and systematic use of the SPT.

  • 93.
    Verma, Deepti
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Farahani, Ensieh
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Enerbäck, Charlotta
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma2012In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 25, no 4, p. 506-513Article in journal (Refereed)
    Abstract [en]

    Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1 beta. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish casecontrol study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.273.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.336.30), which intensified in male patients (OR 4.03, CI 1.4011.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.043.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.3325). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.

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  • 94. Order onlineBuy this publication >>
    Wäster Larsson, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    UVA/B induced redox alterations and apoptosis in human melanocytes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Malignant melanoma is one of the most rapidly increasing cancers and accounts for about three-quarter of all skin cancer deaths worldwide. Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge how various wavelength spectra affect the balance between proliferation and apoptosis controlling the homeostasis of the melanocyte population is still limited. The aim of this thesis was to elucidate the regulation of UVA/B induced apoptotic signaling in human epidermal melanocytes in vitro in relation to redox alterations and antioxidant photoprotection.

    UVA irradiation induced changes in plasma membrane stability, decreased cell proliferation and increased apoptosis. In comparison, melanocyte plasma membrane was markedly resistant to UVB irradiation although apoptosis was triggered. Thus, UVA irradiation should not be overlooked as an etiologic factor in melanoma development. Further, after irradiation with UVA/B we found alterations in redox state manifested by a reduction of intracellular GSH levels, translocation of nuclear factor-κB from the cytosol to the nucleus, an increase of γ-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and an increased apoptosis frequency. α-Tocopherol provided photoprotection through several modes of action affecting redox alterations and signaling, stabilizing the plasma membrane, and decreased proliferation and apoptosis rate, while β-carotene did not show the same protective capacity. Altogether, α-tocopherol might be a useful substance in protecting melanocytes from UV induced damage.

    We demonstrate UVA/B irradiation to activate the intrinsic pathway of apoptosis in melanocytes where translocation of Bcl-2 family proteins to the mitochondria modulates the apoptosis signal. Interestingly, the anti-apoptotic Bcl-2 family proteins generally thought to be attached to membranes, were localized in the cytosol before UV irradiation and translocated to the mitochondria in the surviving population, which might be a critical event in preventing apoptotic cell death. Lysosomal cathepsins were released to the cytosol acting as pro-apoptotic mediators upstream of activation and translocation of Bax to the mitochondria. When melanocytes were exposed to UVA, p53 participated in apoptosis regulation through interaction with Bcl-2 family proteins, while UVB induced p53-transcriptional activity and apoptosis involving lysosomal membrane permeabilization. Thus, depending on the UV wavelength p53 mediated apoptosis in melanocytes by transcriptional dependent or independent activity. These results emphasize p53 as an important pro-apoptotic component in the regulation of apoptosis.

    This thesis gives new insight in the harmful and various effects of different wavelengths within the UV spectrum on human melanocytes in vitro. Improved knowledge of the apoptosis regulatory systems in melanocytes might lead to a better understanding of the formation of pigment nevi and malignant melanoma and, in the future, provide better strategies to prevent and eliminate tumor development and progression.

    List of papers
    1. Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis
    Open this publication in new window or tab >>Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis
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    2005 (English)In: Experimental Dermatology, ISSN 0906-6705, Vol. 14, no 2, p. 117-123Article in journal (Refereed) Published
    Abstract [en]

    Ultraviolet (UV) radiation is an etiologic agent for malignant melanoma and non-melanoma skin cancer, but the spectral range responsible for tumor induction is still to be elucidated. In this study, we compared effects of UVA and UVB irradiation on normal human melanocytes (MCs) and keratinocytes (KCs) in vitro. We demonstrate that UVA irradiation induces immediate loss of reduced glutathione (GSH) in both MCs and KCs. Exposure to UVA also causes reduced plasma membrane stability, in both cell types, as estimated by fluorescein diacetate retention and flow cytometry. Furthermore, we noted reduction in proliferation and higher apoptosis frequency 24 h after UVA irradiation. UVB irradiation of KCs caused instant reduction of reduced GSH and impaired plasma membrane stability. We also found decline in proliferation and increased apoptosis after 24 h. In MCs, on the other hand, UVB had no effect on GSH level or plasma membrane stability, although increased apoptotic cell death and reduced proliferation was detected. In summary, MCs and KCs showed similar response towards UVA, while UVB had more pronounced effects on KCs as compared to MCs. These results might have implications for the induction of malignant melanoma and non-melanoma skin cancer.

    Keywords
    apoptosis, keratinocyte, melanocyte, oxidative stress, UV irradiation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14497 (URN)10.1111/j.0906-6705.2005.00238.x (DOI)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-08-30
    2. Ultraviolet (UV) A- and UVB-induced redox alterations and activation of nuclear factor-kappaB in human melanocytes - protective effects of alpha-tocopherol
    Open this publication in new window or tab >>Ultraviolet (UV) A- and UVB-induced redox alterations and activation of nuclear factor-kappaB in human melanocytes - protective effects of alpha-tocopherol
    2006 (English)In: British Journal of Dermatology, ISSN 0007-0963, Vol. 155, no 2, p. 292-300Article in journal (Refereed) Published
    Abstract [en]

    Background Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge concerning reaction pathways and signalling transduction in melanocytes is still limited.

    Objectives To evaluate the protective capacity of α-tocopherol and β-carotene during UVA and UVB irradiation of human melanocytes in vitro.

    Methods Primary cultures of normal human melanocytes were irradiated by different wavelengths within the UV spectrum (UVA 6 J cm−2, UVB 60 mJ cm−2). Redox alterations and apoptosis were studied and the protective potential of α-tocopherol and β-carotene was evaluated.

    Results UVA and UVB irradiation decreased the intracellular concentration of reduced glutathione and activated the transcription factor nuclear factor (NF)-κB, detected as the increased level of the p65 subunit and translocation to the nucleus. This coincided with a rise in the level of γ-glutamyl-cysteine-synthetase, the rate-limiting enzyme of the glutathione synthesis. UVA and UVB caused apoptotic cell death as detected by nuclear fragmentation and caspase activation 24 h postirradiation. Pretreatment with α-tocopherol prevented UVA- and UVB-induced glutathione loss, NF-κB translocation and diminished apoptosis, but β-carotene did not show a similar protective capacity. Further, exposure to α-tocopherol by itself reduced cell proliferation rate.

    Conclusions UVA and UVB irradiation affected the intracellular redox state and increased the frequency of apoptosis in human melanocytes in vitro. α-Tocopherol might be a useful substance in protecting melanocytes from UV-induced damage.

    Keywords
    α-tocopherol, β-carotene, melanocyte nuclear factor-κB, reduced glutathione (GSH), ultraviolet A, ultraviolet B
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14498 (URN)10.1111/j.1365-2133.2006.07347.x (DOI)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-08-30
    3. UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Open this publication in new window or tab >>UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Show others...
    2006 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 126, no 5, p. 1119-1127Article in journal (Refereed) Published
    Abstract [en]

    We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-XL were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14400 (URN)10.1038/sj.jid.5700124 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2017-08-30
    4. UVA/B mediate divergent p53 apoptosis signaling both dependent and independent of its transcriptional activity in human melanocytes
    Open this publication in new window or tab >>UVA/B mediate divergent p53 apoptosis signaling both dependent and independent of its transcriptional activity in human melanocytes
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14500 (URN)
    Available from: 2007-05-21 Created: 2007-05-21 Last updated: 2010-01-13
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  • 95.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    UVA/B-induced redox alterations and apoptosis in human melanocytes2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 1, p. 26-27Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 96.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Gilmore, Brendan F.
    Queens University Belfast, UK.
    Seifert, Oliver
    Ryhov Hospital, Jönköping.
    Ultraviolet exposure of melanoma cells induces fibroblast activation protein-alpha in fibroblasts: Implications for melanoma invasion2011In: International Journal of Oncology, ISSN 1019-6439, Vol. 39, no 1, p. 193-202Article in journal (Refereed)
    Abstract [en]

    Fibroblast activation protein-alpha (FAP-alpha) promotes tumor growth and cell invasiveness through extracellular matrix degradation. How ultraviolet radiation (UVR), the major risk factor for malignant melanoma, influences the expression of FAP-alpha is unknown. We examined the effect of UVR on FAP-alpha expression in melanocytes, keratinocytes and fibroblasts from the skin and in melanoma cells. UVR induces upregulation of FAP-alpha in fibroblasts, melanocytes and primary melanoma cells (PM) whereas keratinocytes and metastatic melanoma cells remained FAP-alpha negative. UVA and UVB stimulated FAP-alpha-driven migration and invasion in fibroblasts, melanocytes and PM. In co-culture systems UVR of melanocytes, PM and cells from regional metastases upregulated FAP-alpha in fibroblasts but only supernatants from non-irradiated PM were able to induce FAP-alpha in fibroblasts. Further, UV-radiated melanocytes and PM significantly increased FAP-alpha expression in fibroblasts through secretory crosstalk via Wnt5a, PDGF-BB and TGF-beta 1. Moreover, UV radiated melanocytes and PM increased collagen I invasion and migration of fibroblasts. The FAP-alpha/DPPIV inhibitor Gly-ProP(OPh)(2) significantly decreased this response implicating FAP-alpha/DPPIV as an important protein complex in cell migration and invasion. These experiments suggest a functional association between UVR and FAP-alpha expression in fibroblasts, melanocytes and melanoma cells implicating that UVR of malignant melanoma converts fibroblasts into FAP-alpha expressing and ECM degrading fibroblasts thus facilitating invasion and migration. The secretory crosstalk between melanoma and tumor surrounding fibroblasts is mediated via PDGF-BB, TGF-beta 1 and Wnt5a and these factors should be evaluated as targets to reduce FAP-alpha activity and prevent early melanoma dissemination.

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  • 97.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Redox-Dependent Translocation of p53 to Mitochondria or Nucleus in Human Melanocytes after UVA- and UVB-Induced Apoptosis2009In: JOURNAL OF INVESTIGATIVE DERMATOLOGY, ISSN 0022-202X, Vol. 129, no 7, p. 1769-1781Article in journal (Refereed)
    Abstract [en]

    The p53 protein is an important transcription factor and tumor suppressor that is induced in response to many forms of cellular stress. UVA irradiation of human melanocytes caused generation of reactive oxygen species, which altered the intracellular redox balance and was accompanied by translocation of p53 to mitochondria. In contrast, UVB did not affect the redox status and p53 was translocated to the nucleus. Although different intracellular location of p53, UVA/B induced apoptosis through the intrinsic pathway detected as translocation of Bax to mitochondria, release of cytochrome c, and activation of caspases. These events were all prevented by inhibition of p53 with pifithrin-alpha. Furthermore, inhibition of p53 prevented lysosomal membrane permeabilization, detected as translocation of cathepsins to the cytosol, after UVB exposure, whereas UVA-induced lysosomal release was unaffected by inhibition of p53. In control cells, p53 coimmunoprecipitated with the antiapoptotic proteins Bcl-2 and Bcl-x(L) and upon UVA exposure the interaction was replaced by binding to the proapoptotic proteins Bax, Noxa, and Puma. Our findings suggest that UVA-induced apoptosis is caused by extensive oxidative damage leading to p53-regulated mitochondrial release, whereas UVB induces DNA damage and apoptosis signaling upstream of lysosomal membrane permeabilization.

  • 98.
    Zhao, Zeng-Ren
    et al.
    Department of General Surgery Hebei Medical University, Shijiazhuang 050031, P.R. China.
    Zhang, Zhiyong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology .
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology .
    Jiang, Li
    Department of Pathology Tangshan Gongren Hospital, Tangshan 063000, P.R. China.
    Wang, Ming-Wei
    Laboratory Centre Hebei Medical University, Shijiazhuang 050031, P.R. China.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Overexpression of Id-1 protein is a marker in colorectal cancer progression2008In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 19, no 2, p. 419-424Article in journal (Refereed)
    Abstract [en]

    The inhibitor of differentiation/DNA binding 1 (Id-1), a negative regulator of basic helix-loop-helix transcription factors, plays an important role in the regulation of cell proliferation and differentiation. We examined the Id-1 expression by immunohistochemistry in 9 adenomas, 79 primary colorectal adenocarcinomas matched with 40 adjacent normal mucosa specimens and its relationship with clinicopathological factors. The Id-1 expression was increased in the carcinoma compared to the adjacent normal mucosa either in the unmatched and matched samples or to the adenoma. There was no significant difference in the Id-1 expression between normal mucosa and adenoma. The Id-1 expression of carcinoma was increased from Dukes' stages A to B, to C and to D. The cases with lymph node metastasis had a higher rate of a stronger Id-1 expression than those without lymph node metastasis. In conclusion, Id-1 overexpression plays an important role in colorectal cancer progression.

12 51 - 98 of 98
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