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  • 1.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Monoamine oxidase A and B genes polymorphisms in Parkinson's diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by degeneration of nig:rostriatal dopaminergic neurons including the loss of cell bodies in the pars compacta of substantia nigra (SN). The mechanism for neurodegeneration is unknown, but the pathogenesis is considered to be multifactorial involving exposure for toxins, genetic inheritance, age, oxidative stress and mitochondrial electron transport chain defects. This study has been focused on polymorphisms in the genes for the enzymes monoamine oxidase A and B (MAO-A, MAO-B) and relation to smoking for the development of idiopathic Parkinson's disease. MAO enzymes are important in the dopamine metabolism and in the detoxification of neurotoxins. During metabolism of dopamine, MAO generates large amounts of free radicals and hydrogen peroxide, and may damage the neurons in substantia nigra, which has been suggested as a pathologic mechanism for PD.

    Blood samples were collected from 256 PD patients, age 30-80 years, and 582 unrelated control individuals, age 31 - 78 years, from southeastern Sweden.

    Two polymorphisms (exon 8 and exon 14) located in the MAO-A gene and one polymorphism located in the MA O-B gene were examined, with denatming HPLC, PCR-RFLP or DNA sequencing. Genotype and allele frequencies were determined for patients and controls. No statistical significant difference was revealed between any of the polymorphisms in the MAO-A and MAO-B genes and Parkinson's disease. Smoking displayed an enviromnental exposure with a strong decreased risk for both male (OR=0.40, 95% CI 0.25 - 0.63) and female (OR=0.48, 95% CI 0.25-0.89) PD without any interaction with MAO genotype.

    The polymorphisms in MAO genes might therefore not be acting as modifiers of risk for developing of PD either by itself or by interacting with smoking. With respect to the size of the study (256 PD patients and 582 controls) MAO polymorphisms do not represent any predisposing factor or a weak PD susceptibility factor.

  • 2.
    Andersson, Eva
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  • 4.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Törma, Hans
    Department of Medical Sciences, Section of Dermatology and Venereology, Uppsala University, Uppsala.
    Vahlquist, Anders
    Department of Medical Sciences, Section of Dermatology and Venereology, Uppsala University, Uppsala.
    Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytesManuscript (preprint) (Other academic)
    Abstract [en]

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

  • 5.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Törmä, H.
    Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
    Vahlquist, A.
    Department of Medical Sciences, Sect. of Dermatol. and Venereology, Uppsala University, Uppsala, Sweden.
    Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes1999In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 9, no 4, p. 339-346Article in journal (Refereed)
    Abstract [en]

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

  • 6.
    Andersson, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Törmä, Hans
    Vahlquist, Anders
    Differential effects of UV irradiation on nuclear retinoid receptor levels in cultured keratinocytes and melanocytes2003In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 12, no 5, p. 563-571Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Andersson, Eva
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Vahlquist, Anders
    Section of Dermatology and Venereology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    β-Carotene Uptake and Bioconversion to Retinol Differ Between Human Melanocytes and Keratinocytes2001In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 39, no 2, p. 300-306Article in journal (Refereed)
    Abstract [en]

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

  • 8.
    Andersson, T
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, M
    In vivo testing of the protective efficacy of gloves against allergen-containing products using an open chamber system.1999In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, p. 260-263Article in journal (Refereed)
  • 9.
    Andersson, T
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, M
    Björkner, B
    In vivo testing of the protection of gloves against acrylates in dentin-bonding systems on patients with known contact alllergy to acrylates.1999In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, p. 254-259Article in journal (Refereed)
  • 10.
    Andersson, Thomas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bruze, Magnus
    Gruvberger, Birgitta
    Björkner, Bert
    In vivo testing of the protection provided by non-latex gloves against a 2-hydroxyethyl methacrylate-containing acetone-based dentin-bonding product2000In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 80, no 6, p. 435-437Article in journal (Refereed)
    Abstract [en]

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

  • 11.
    Andersson, Thomas
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Johansson, Anders G.
    Kliniskt Mikrobiologiska Laboratoriet, Akademiska Sjukhuset, Uppsala.
    Westermark, Per
    Avdelningen för Genetik och Patologi, Enheten för Patologi, Akademiska Sjukhuset, Uppsala.
    Lundmark, Katarzyna
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Vanlig svamp gav ovanlig hudinfektion: Fallbeskrivning1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 45, p. 4926-4927Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

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

  • 12. Andreyev, HJN
    et al.
    Norman, AR
    Cunningham, D
    Oates, J
    Dix, BR
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Urosevic, N
    Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study2001In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 85, no 5, p. 692-696Article in journal (Refereed)
    Abstract [en]

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

  • 13. Boysen, Lene
    et al.
    Sörensen, Per
    Larsen, Morten
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Kristensen, Flemming
    Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs2002In: American Journal of Veterinary Research, ISSN 0002-9645, E-ISSN 1943-5681, Vol. 63, p. 565-569Article in journal (Refereed)
  • 14.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Andersson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Andersson, T.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Marcusson-Ståhl, Maritha
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    IL-10 production in primary PBMC cultures: an in vitro marker for nickel allergy?Manuscript (preprint) (Other academic)
    Abstract [en]

    Nickel (Ni) is one of the most known contact allergens and at present, patch test and clinical history constitute the two cornerstones in the diagnostic procedure. Since the patch test is inherited with in vivo provocation and subjective interpretation of the test result, a non-invasive in vitro method with objective interpretation of the test result has long been searched for. Unfortunately, in vitro diagnosis of Ni- allergy is hampered by the fact that Ni2+ is able to trigger in vitro proliferative responses in lymphocytes from both Ni-allergic and non-allergic subjects. This constitutes a problem when LTT (lymphocyte transformation test), the most frequently used in vitro test as a complement in the diagnosis of contact allergy, is considered for Ni allergy. However, other parameters in the in vitro response might be more useful. In this study, Ni2+-stimulated primary PBMC-cultures derived from Ni-allergic and non-allergic subjects were assessed for IFN-γ, IL-4, IL-10 and IL-17. Also, Ni2+ induced lymphoblasts from such cultures were characterized by their immunophenotype and T-cell receptor Vß-affiliation.

    We found a significantly higher release of IL-10 in Ni2+ treated cultures from allergic than from non-allergic subjects. The Ni2+-induced lymphoblasts from both groups were predominantly CD4+. Two of the allergic patients (n=5) showed a skewing towards TCR-Vß17, a Vß family earlier associated with Ni-allergy. A significant increase in CD134 and CD23 expression indicated that Ni2+ activates B-cells in vitro. In conclusion, IL-10 seems to be a promising marker for Ni-allergy using primary PBMC cultures. Further, flow cytometric screening of Ni2+ induced lymphoblasts can detect expanded TCR-Vß families that may be used for preparation of Ni-specific T cell clones.

  • 15.
    Emterling, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Skoglund, Johanna
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Schneider, José
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Evertsson, Sofia
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Clinicopathological significance of Nup88 expression in patients with colorectal cancer2003In: Oncology, ISSN 0890-9091, Vol. 64, no 4, p. 361-369Article in journal (Refereed)
    Abstract [en]

    Objective: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors.

    Materials and Methods: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases.

    Results: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02).

    Conclusions: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.

  • 16.
    Evertsson, Sofia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wallin, Åsa
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Rütten, Sabine
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Emterling, Anna
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Microsatellite instability and MBD4 mutation in unselected colorectal cancer2003In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 23, no 4, p. 3569-3574Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.

    PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.

    RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.

    CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.

  • 17. Faergemann, J
    et al.
    Diehl, U
    Bergfelt, L
    Brodd, A
    Edmar, B
    Hersle, K
    Lindemalm, B
    Nordin, P
    Ringdahl, IR
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Scalp psoriasis: synergy between the Malassezia yeasts and skin irritation due to calcipotriol2003In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 83, p. 438-441Article in journal (Refereed)
  • 18.
    Falk, Magnus
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances2003In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, p. 195-202Article in journal (Refereed)
    Abstract [en]

    Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

    Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

    Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

    Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

  • 19. Finlay, A
    et al.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Editorial. Training inspection visits - pushing up quality of training in Europe.2001In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 15, p. 193-193Article in journal (Refereed)
  • 20. Fullerton, A
    et al.
    Stücker, M
    Wilhelm, K-P
    Wårdell, K
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Fischer, T
    Nilsson, GE
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging. A report from the Standardization Group of the European Society of Contact Dermatitis* based upon the HIRELADO European community project2002In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 46, no 3, p. 129-140Article in journal (Refereed)
    Abstract [en]

    This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research. ⌐ Blackwell Munksgaard, 2002.

  • 21. Fullerton, AB
    et al.
    Rode, J
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Studies of cutaneous blood flow of normal forearm skin and irritated forearm skin based on high-resolution laser Doppler perfusion imaging (HR-LDPI)2002In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 8, p. 32-40Article in journal (Refereed)
  • 22. Fullerton, Ann
    et al.
    Rode, Birgitte
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Skin irritation typing and grading based on laser Doppler perfusion imaging2002In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 8, p. 23-31Article in journal (Refereed)
  • 23.
    Furubacke, A
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Lack of significant treatment effect of plasma exchange in the treatment of drug-induced toxic epidermal necrolysis? 1999In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 25, p. 1307-1310Article in journal (Refereed)
  • 24.
    Hillman, Jan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Milos, Peter
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Zhengquan, Yu
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Mellergård, Pekka
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Intracerebral microdialysis in neurosurgical intensive care patients utilising catheters with different molecular cut-off (20 and 100 kD)2006In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 148, no 3, p. 319-324Article in journal (Refereed)
    Abstract [en]

    Objective. To compare the properties of a new intracerebral micro-dialysis catheter with a high cut-off membrane (molecular cut-off 100 kDalton) with a standard catheter (CMA70, molecular cut-off 20 kDalton).

    Methods. Paired intracerebral microdialysis catheters were inserted in fifteen comatose patients treated in a neurosurgical intensive care unit following subarachnoid haemorrhage or traumatic brain injury. The high-cut-off catheter (D100) differed from the CMA 70 catheter by the length (20 mm) and cut-off properties of the catheter membranes (100 kDalton) and the perfusion fluids used (Ringer-Dextran 60). Samples were collected every 4–6 hours, analyzed bedside (for glucose, glutamate, glycerol, lactate, pyruvate and urea) and later in the laboratory (for total protein).

    Results. Fluid recovery was similar for the two types of catheters, but significantly more protein was recovered by the D100 catheter. The recovery of glycerol and pyruvate did not differ, while minor differences in recovery of glutamate and glucose were observed. The recovery of lactate was considerably lower in the D100 catheter (p < 0.01), influencing the lactate/pyruvate-ratio. The patterns of concentration changes over time were consistent for all metabolites, and independent of type of catheter.

    Conclusion. Microdialysis catheters with high cut-off membranes can be used in routine clinical practice in the NSICU, adding the possibility of macro-molecule sampling from the extracellular space during monitoring.

  • 25.
    Ilias, Michail A.
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Single exposure phototesting utilizing a divergent ultraviolet beam1999In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 5, no 4, p. 255-259Article in journal (Refereed)
    Abstract [en]

    Background/aims: Confident diagnosis of photosensitivity in patients with light dermatoses requires skin exposure to well determined ultraviolet (UV) light doses, most often from a solar simulator. The traditional test procedure results in a rough classification of skin sensitivity based on the minimal erythema dose (MED) found for each patient. The limited number of constant irradiance doses used during phototesting decreases the precision of the MED value. In the present study we aimed at developing the technical system for the determination of MED by using a single, centrifugally attenuating, UVB provocation.

    Methods: A divergent UV beam was achieved with the help of an optic lens. To investigate the irradiance profile, an irradiance acquisition system was built that produced three-dimensional intensity maps. In addition, a laser Doppler perfusion imaging (LDPI) system was introduced in the evaluation of the skin response along with visual readings of the same exposed areas, in order to add a quantitative aspect to the assessment of erythema. The procedure was used on one test subject.

    Results: The divergent UV beam showed the desired profile. With the current setup 20 different UV-dose levels could be discriminated. Relevant UV-dose levels were determined and tested on a subject, which in practice gave results in the form of visual assessment as well as LDPI-images. The visual or LDPI diameter gave the MED. Within the skin reaction, irradiance and the laser Doppler values could be compared mm for mm.

    Conclusions: A more accurate MED determination with a single UV exposure seems to be feasible by using the proposed method. Though further investigation is required, the technique appears to offer new possibilities for the association of dose to response. In addition LDPI is possibly a useful complement to the visual readings of the skin responses, since the method gives a quantification of the grade of erythema, as opposed to visual (+, ++, +++) readings that are subjective and at best semiquantitative.

  • 26.
    Ilias, Michail
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Single exposure phototesting: an adaptation to the CIE erythema action spectrum2002In: Proceedings on the 2nd European Medical and Biological Conference, 2002, p. 964-967Conference paper (Refereed)
    Abstract [en]

    In single exposure, divergent beam phototesting, an originally collimated ultraviolet beam is diverged by an optkal lens to give a circular ultraviolet light field with attenuating irradiance towards its periphery. The chromatic aberration, caused by the lens, and its influence on the erythemal effectiveness of the field has been investigated. Spectral measurements (250-400 nm) were performed along the 20 mm radius of the field in steps of 1 mm. The corresponding erythemal effectiveness was calculated after adjustment of the spectral irradiance according to the erythema action spectrum recommended by the Commission Internationale de l' Éclairage (CIE). The erythemal effectiveness of the irradiance field attenuated towards the periphery and stabilized at about 80% of the maximum value at the centre. Knowledge of this is important for dosimetry in skin photobiology and data interpretation. The divergent beam method was used in parallel with the traditional method on three volunteers.

  • 27.
    Ilias, Michail
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Falk, Magnus
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Phototesting based on a divergent beam: a study on normal subjects2001In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 17, no 4, p. 189-196Article in journal (Refereed)
    Abstract [en]

    In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

  • 28.
    Ilias, Michail
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Stücker, M.
    Department of Dermatology, Ruhr University, Bochum, Germany.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Assessment of pigmented skin lesions in terms of blood perfusion estimates2004In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 10, no 1, p. 43-49Article in journal (Refereed)
    Abstract [en]

    Background/aims: Cutaneous malignant melanoma is a disease of increasing clinical and economical importance. The prognosis is good with early diagnosis. The chief differential diagnosis is benign melanocytic naevus, a common lesion in Caucasians. Attempts have been made to use bioengineering techniques to aid in the initial diagnosis. The present study proposes a method of extracting possibly discriminative blood perfusion properties in pigmented skin lesions by combining information on the lesions' blood perfusion with optical or visual information of their spatial extent.

    Methods: A total of 46 blood perfusion measurements were performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three histologically proven malignant melanomas, four histologically proven benign naevi and fifteen naevi assessed by two specialist dermatologists as being benign. Laser Doppler perfusion imaging gave two different types of two-dimensional data sets (64×64 pixels), one representing the total backscattered light intensity at each measurement point (TLI image) and the second corresponding to perfusion values. The boundaries of each examined lesion were derived from the TLI image employing greyscale thresholding, thus resulting in an estimated region of interest (ROI) approximating the optical extent of the lesion. The ROI was superimposed on the perfusion image and extraction of perfusion features was then performed.

    Results: The processing of the TLI images was successful in delineating the lesions' boundaries. The first hypothesis that the mean perfusion quotients in MM and benign naevi are equal could not be rejected at the chosen 5% level of significance. The second hypothesis that the mean percent-age of elevated perfusion values (image pixels) within the ROI shows no difference between MM and benign naevi could be rejected at a 5% level of significance.

    Conclusions: This study has presented a method of extracting blood perfusion parameters of pigmented skin lesions by combining blood perfusion information with information on the lesion's optical extent. The proposed method of presenting data could prove to be a useful discriminative adjunct in the assessment of pigmented skin lesions.

  • 29.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital Hospital, Norrköping, Sweden.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer2003In: International Journal of Oncology, ISSN 1019-6439, Vol. 22, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins.

  • 30. Jerkegren, E
    et al.
    Sandrieser, L
    Brandberg, Y
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Sun-related behaviour and melanoma awareness among Swedish university students.1999In: European Journal of Cancer Prevention, ISSN 0959-8278, E-ISSN 1473-5709, Vol. 8, p. 27-34Article in journal (Refereed)
  • 31.
    Leahy, Martin J.
    et al.
    Department of Physics, University of Limerick Limerick, Ireland.
    O'Doherty, Jim
    Department of Physics, University of Limerick Limerick, Ireland.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology UHL.
    A new method for visualizing red blood cell content in the microcirculation2007In: Progress in Biomedical Optics and Imaging, ISSN 1605-7422, E-ISSN 1042-4687Article in journal (Other academic)
    Abstract [en]

    n/a

  • 32. Lindelöf, B
    et al.
    Sigurgeirsson, B
    Tegner, E
    Johannesson, A
    Berne, B
    Christensen, OB
    Andersson, T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Törngren, M
    Molin, M
    Nylander-Lundqvist, E
    Emtestam, L
    PUVA and cancer risk: the Swedish follow-up study.1999In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 141, p. 108-112Article in journal (Refereed)
  • 33. Lindén, Maria
    et al.
    Andersson, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Is vascular reactivity in skin predictable?2000In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 6, no 1, p. 27-30Article in journal (Refereed)
    Abstract [en]

    Background/aims: Cutaneous microdialysis can be used to follow the pharmacology and metabolism of an inflammatory reaction. It is assumed that an equilibration period compensates for the trauma of catheter insertion. Methods: In the present paper, the vascular reactivity of the skin to histamine was tested using assessment by laser Doppler perfusion imaging. In a group of six subjects, the provocation was preceded by insertion of a microdialysis catheter. In a second control group, histamine provocation alone was performed (six subjects). Results: The vascular response to histamine was greater in the microdialysis catheter group than the control group. The histamine provocation caused a greater response than catheter insertion. Further, there was a correlation between the response to catheter insertion and the histamine provocation. Conclusion: It appears that the insertion and/or presence of a microdialysis catheter increases vascular reactivity to subsequent provocation. The response to catheter insertion may predict skin reactivity in general in the individual subject. (C) Munksgaard, 2000.

  • 34.
    Lirvall, Margareta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Majeed, Meytam
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Höddelius, Pia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wasteson, Åke
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    UVB radiation increases EGF receptor mobility and trafficking in human melanocytesManuscript (preprint) (Other academic)
    Abstract [en]

    For the human skin, UVB-radiation (290-320nm) is a very potent injurious agent. UV radiation is absorbed in the epidermis and reaching the melanocytes leads to proliferation via activation of growth factor reccptors. This may play a key role in the clonal expansion of melanocytes and be a critical step in carcinogenesis. We show that UVB-irradiated human epidermal melanocytes display an increased mobility of epidermal growth factor receptors (EGF-R) in the plane of the cell membrane, and that UVB affects the intracellular EGF-R transport to the nucleus. Using fluorescence photobleaching technique we show a time and dose dependent increase in the diffusion coefficient and mobile fraction of EGF-R. EGF-Rdiffuse with a low rate within the cell membrane in control cells, and the mobility increases 4-fold after single physiologic doses of UVB. Three-dimensional confocal microscopy reveals that EGF-R display a strilting difference in receptor distribution and intracellular transport before and after UVB irradiation. The EGF-Rclearly eo-localize with clathrin-coated pits within the cells. These results indicate that already single physiologic doses of UVB affect growth factor receptor mobility in cell membranes and intracellular trafficlting. This may be an important early step in the ultraviolet radiation-induced signal transduction pathway leading to cell proliferation.

  • 35. Lodén, M
    et al.
    Andersson, A-C
    Andersson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Frödin, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Öhman, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Lindberg, M
    Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis2001In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 7, no 4, p. 209-213Article in journal (Refereed)
    Abstract [en]

    Background/aims: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin. Methods: Patients (n=109) with atopic dermatitis were treated for 30 days with a moisturiser in a randomised, parallel and double-blind fashion. Transepidermal water loss (TEWL) and skin capacitance were assessed instrumentally, and changes in the dryness of the skin were assessed by the dermatologist. Results: No difference in TEWL was found between glycerine treatment and its placebo, whereas a lower value was found in the urea-treated area compared to the glycerine-treated area. No difference in skin capacitance was found. The clinical assessment of dryness showed urea to be superior to glycerine in treating the condition. Conclusions: Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis.

  • 36.
    Rosdahl, Inger
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Andersson, Eva
    Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Törma, H.
    Department of Dermatology, University of Uppsala, Sweden.
    Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells1997In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 7, no 4, p. 267-274Article in journal (Refereed)
    Abstract [en]

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

  • 37.
    Rosdahl, Inger
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Finlay, Andrew
    Gollnick, Harald
    Lomuto, Michele
    Soyland, Elisabeth
    Guidelines for charter on visitation of training centres in dermatology and venereology: Report for the European board of dermatology and venereology, European Union of Medical Specialists.2001In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 15, p. 272-279Article in journal (Refereed)
  • 38.
    Said, Lilian
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Rebel, Carl
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Epidermal calcium release (ECR) in vivo sampled with a simple washout chamber technique. Experimental studies in normal and barrier pertubated skin2002In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 8, no 4, p. 219-226Article in journal (Refereed)
    Abstract [en]

    Background/aims: Epidermis forms the protective barrier of the skin by its outermost layer, stratum corneum. The purpose of this study was to investigate the epidermal barrier in view of epidermal calcium release (ECR), phosphate release, transepidermal water loss (TEWL) and skin surface pH. Calcium is mainly an intracellular ion. Calcium was sampled introducing a new and simple washout chamber technique for the study of epidermal release in vivo. Methods: Test sites on forearms of 13 healthy subjects were pre-treated with 24 h water occlusion, 24 h 2% sodium lauryl sulphate (SLS) or tape stripped. Both untreated and pretreated test sites were exposed to a water washout chamber with 200╡ deionized water as a solvent. Water washout chambers were removed after two hours and calcium and phosphate in the water was analyzed. Transepidermal water loss and pH were measured before and after the trial. Results: pH increased after tape stripping and after exposure to SLS. Transepidermal water loss increased significantly at all test sites. Calcium was significantly released from SLS-treated sites but not from tape stripped sites. There was generally a correlation between ECR, phosphate release, TEWL and pH. In this study ECR is showed to be a barrier marker of high reproducibility. Conclusions: Epidermal calcium release or ECR is found useful as an indicator of skin barrier function. Calcium release and increase of pH appear mainly to illustrate direct and corrosive damage to epidermal cells and functions contrasting TEWL, in this experiment probably reflecting intercellular damage of fracturing as exemplified by mechanical damage resulting from surface stripping. This new distinction of skin barrier damage into cellular damage resulting from a corrosive chemical trauma and intercellular damage and fracturing resulting from a mechanical trauma is exemplified in SLS provocative testing and tape stripping, the former characterized by increased ECR. The washout chamber technique was deemed technically reliable and reproducible, and has a major potential in experimental dermatology and skin pharmacology for the study of in vivo epidermal release of a range of endogenous and exogenous substances.

  • 39. Salahshor, S
    et al.
    Hou, H
    Diep, CB
    Loukala, A
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Liu, T
    Chen, J
    Iselius, L
    Rubio, C
    Lothe, RA
    Aaltonen, L
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Lindmark, G
    Lindblom, A
    A germline E-cadherin mutation in a family with gastric and colon cancer.2001In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 8, p. 439-443Article in journal (Refereed)
  • 40.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Hardware and measuring principles: The dermaflex A2001In: Bioengineering of the Skin: Skin Biomechanics, Volume V / [ed] Peter Elsner, Enzo Berardesca, Klaus P. Wilhelm and Howard I Maibach, CRC Press, 2001, p. 111-115Chapter in book (Other academic)
    Abstract [en]

    Since skin forms the interface between the human body and the environment, its mechanical properties are important in health and disease. Bioengineering of the Skin: Skin Biomechanics gives a thorough introduction in the biological basis of skin biomechanics. It explains the non-invasive methods that allow measurement of the mechanical properties of the skin focusing on commercially available instruments. Written by internationally leading experts in the field of non-invasive measurement technology of the skin, this volume describes the anatomy, biochemistry, physiology, and pathology of skin biomechanics. It explains in detail how to measure skin mechanic properties and how to use these measurements in the development of drugs and cosmetics.

  • 41.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Hardware and measuring principles: The dermaLab2001In: Bioengineering of the skin : skin biomechanics / [ed] Peter Elsner, Enzo Berardesca, Klaus-Peter Wilhelm, Linköping: Linköpings universitet , 2001, p. 117-121Chapter in book (Other academic)
    Abstract [en]

    Since skin forms the interface between the human body and the environment, its mechanical properties are important in health and disease. Bioengineering of the Skin: Skin Biomechanics gives a thorough introduction in the biological basis of skin biomechanics. It explains the non-invasive methods that allow measurement of the mechanical properties of the skin focusing on commercially available instruments. Written by internationally leading experts in the field of non-invasive measurement technology of the skin, this volume describes the anatomy, biochemistry, physiology, and pathology of skin biomechanics. It explains in detail how to measure skin mechanic properties and how to use these measurements in the development of drugs and cosmetics.

  • 42.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Mechanical properties of human skin: Elasticity parameters and their relevance2002In: Bioengineering of the skin. Skin biomechanics / [ed] Peter Elsner;, Linköpings universitet , 2002, p. 41-47Chapter in book (Other academic)
    Abstract [en]

    Since skin forms the interface between the human body and the environment, its mechanical properties are important in health and disease. Bioengineering of the Skin: Skin Biomechanics gives a thorough introduction in the biological basis of skin biomechanics. It explains the non-invasive methods that allow measurement of the mechanical properties of the skin focusing on commercially available instruments. Written by internationally leading experts in the field of non-invasive measurement technology of the skin, this volume describes the anatomy, biochemistry, physiology, and pathology of skin biomechanics. It explains in detail how to measure skin mechanic properties and how to use these measurements in the development of drugs and cosmetics.

  • 43.
    Sjögren, Florence
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Dermal cell trafficking: from microscopy to microdialysis2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The term dermal cell trafficking has been used to describe the dynamic nature of cell movement in the dermis reflecting the skin's role as an immunological organ. A light microscopic experimental model for qualitative and quantitative counting of the dermal inflammatory cell infiltrate in allergic, acute irritant and cumulative irritant contact reactions has been developed In human studies use of microdialysis technique has enabled observation of biochemical events in the skin, in vivo over a period of time. This method might allow measurement of cytokines and other inflammatory mediators in the intercellular space of the dermis without the need of multiple biopsies. For confirmation that cytokines detected/not detected in the dialysate are present /absent in the dermis, and to determine the possible cellular source of the cytokines, a return to biopsy technique at time points of special interest would be required.

    The general aims of this thesis have been to extend the experimental studies on skin reactions to immediate reaction types and to develop the use of microdialysis technique for the measurement of cytokines.

    Plastic embedding, thin sectioning and optimal staining were the basis for inflammatory cell counting. The immediate hypersensitivity reaction to ovalbumin and the non immunological immediate contact reaction to dimethyl sulfoxide were studied. The effect of topical glucocorticosteroid on delayed contact reaction types was also studied. A polyethersulfone membrane, with a cut-off value of 100,000 Daltons was used. Reliable sample volumes and high analyte recovery was achieved either by push pull pumping or standard pumping using a perfusate consisting of Ringer Dextran 60. ELISA and flow cytometry based analysis of polystyrene bead conjugated antibodies (suspension array) was used to estimate the levels of interleukins 1 beta, 2, 4, 5, 6, 8, 10, granulocyte monocyte colony stimulating factor, interferon gamma and tumor necrosis factor alpha in normal skin for up to 24 -28 hours. Tissue sections from the area of the microdialysis membrane were examined with double immunofluorescence for cytokines and resident dermal cells.

    The immediate Type 1 hypersensitivity reaction to ovalbumin showed an early phase with basophil granulocytes and a late lymphocytic phase. 100% DMSO gave a basophil rich non immunological immediate reaction while repeated applications of 12% DMSO gave a reaction most like the cumulative irritant reaction. Topical glucocorticosteroid and its acetone vehicle showed anti inflammatory effects most pronounced on the acute irritant reaction. Microdialysis showed IL6, IL8 and IL1b in response to insertion with a slow equilibration period. Other cytokines were detected less frequently and in smaller amounts. The biopsies revealed intracellular cytokines in general concordance with the microdialysis fmdings. Confocal microscopy using double immunofluorescence allowed demonstration of cytokines and cellular markers in the same preparation.

    The experimental model illustrates differences in dermal inflammatory histological patterns in various common reaction types. Findings are relevant for discussion of pathogenetic mechanisms and as background information for continued clinical studies. Microdialysis is well suited to chronological studies of cytokine patterns in vivo. Suspension array technique allows measurement of multiple cytokines and other analytes, the results of which need interpretation against background knowledge of the particular analyte. End point biopsy for immunofluorescence studies enable intracellular localization of cytokines and even speculation about cellular origin.

    List of papers
    1. The cellular dermal infiltrate in experimental immediate type cutaneous hypersensitivity
    Open this publication in new window or tab >>The cellular dermal infiltrate in experimental immediate type cutaneous hypersensitivity
    1995 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 75, no 6, p. 417-421Article in journal (Refereed) Published
    Abstract [en]

    A previously developed guinea pig model for the study of the dermal inflammatory cell infiltrate of allergic, toxic, and irritant reactions was adapted to the study of the immediate intradermal reaction to ovalbumin, Comparison of qualitative and quantitative counts of infiltrating cells at three levels in the dermis showed that counting 20 subepidermal fields starting from the injection point of the allergen gave reliable figures, The reaction showed microscopically two phases. The first was of rapid onset and characterized by a high proportion of neutrophils, unlike the picture seen in the previously studied (allergic and toxic) reaction types. In the second phase, which can be termed 'late phase' reaction, mononuclear cells and basophil granulocytes predominated. The late phase of the reaction bears similarities to the delayed allergic contact reaction at the same timepoint in that the response was rich in basophils. There were, however, other differences; e.g, eosinophils and neutrophils were more common.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84289 (URN)8651014 (PubMedID)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2017-12-07Bibliographically approved
    2. The spectrum of inflammatory cell response to dimethyl sulfoxide
    Open this publication in new window or tab >>The spectrum of inflammatory cell response to dimethyl sulfoxide
    2000 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 42, no 4, p. 216-221Article in journal (Refereed) Published
    Abstract [en]

    Dimethyl sulfoxide (DMSO), depending upon the concentration and mode of application to the skin, can induce either a non-immunological immediate contact urticaria or an irritant reaction. The dermal cellular infiltrate after open application of varying concentrations of DMSO has been studied in an experimental guinea pig model. The composition of the dermal cellular infiltrate showed a spectrum dependent on the concentration and number of applications of DMSO. The immediate reaction infiltrate 3 h after application of 100% DMSO consisted of 50% granulocytes, basophils being predominant. On the other hand, 12% DMSO applied 3 × daily for 3 days (cumulative insult) caused histologically a cellular reaction in which 80% of the infiltrate consisted of mononuclear cells. The present findings are compared to the microscopic findings in 3 other cutaneous reactions previously studied in this animal model, namely, the Type I immediate hypersensitivity reaction, the Type IV delayed hypersensitivity reaction, and the irritant reaction. Differing cellular infiltrate patterns are discernible at the same time points. The study illustrates the spectrum of inflammatory reactions seen in the skin and provides background information for future clinical studies, for instance, on the role of the basophil granulocyte in immediate contact reactions.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24852 (URN)10.1034/j.1600-0536.2000.042004216.x (DOI)9251 (Local ID)9251 (Archive number)9251 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Acetone has anti-inflammatory effects on experimental contact reactions
    Open this publication in new window or tab >>Acetone has anti-inflammatory effects on experimental contact reactions
    1999 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, no 1, p. 22-29Article in journal (Refereed) Published
    Abstract [en]

    The effects of a topically applied corticosteroid and its acetone vehicle on experimental allergic, toxic and irritant reactions are presented. The corticosteroid budesonide in acetone or acetone alone was applied to reactions immediately after and at different time intervals within the 1st h after provocation. Classical naked eye observation was performed and the dermal cellular infiltrate was differentiated and counted using a previously well-characterized method. “Treatment”, whether with the steroid in acetone or acetone alone, had anti-inflammatory effects. For all reaction types, erythema and oedema diminished and a significant decrease in mononuclear cells was seen, when application occurred within the first 5 min after provocation. The effects were most marked for the toxic reaction to croton oil, the steroid and the vehicle being anti-inflammatory to the same extent. Application up to 60 min after provocation had anti-inflammatory effects for this reaction type. The mechanisms of acetone's anti-inflammatory effects are at present unclear. One possible explanation is that intercellular lipid organisation and, by extension, cellular membrane lipid organisation, are altered, influencing membrane receptor function. Possible anti-inflammatory effects of acetone should be considered in experimental and perhaps even clinical situations. Further investigation of the therapeutic possibilities of the finding seems warranted.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24846 (URN)10.1111/j.1600-0536.1999.tb06203.x (DOI)9244 (Local ID)9244 (Archive number)9244 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis
    Open this publication in new window or tab >>Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis
    2002 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 146, no 3, p. 375-382Article in journal (Refereed) Published
    Abstract [en]

    Background  Cutaneous microdialysis in vivoin human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight.

    Objectives  To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis.

    Methods  Use of a polyethylenesulphone membrane, with a cut-off value of 100 000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter.

    Results  Reliable sample volumes and high analyte recovery were achieved either by push–pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments.

    Conclusions  Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24850 (URN)10.1046/j.1365-2133.2001.144003650_146_3.x (DOI)9249 (Local ID)9249 (Archive number)9249 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. Cytokine suspension array analysis of microdialysate samples from normal human skin during 24 hours after 100 kiloDalton cut of membrane catheter insertion
    Open this publication in new window or tab >>Cytokine suspension array analysis of microdialysate samples from normal human skin during 24 hours after 100 kiloDalton cut of membrane catheter insertion
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Cytokines play important roles in steering homeostatic and inflammtory activities in human tissues not the least skin. In vivo, human, large pore membrane microdialysis technique can be used to measure cytokines in human tissues such as skin, muscle and brain. The new analytical technique of flow cytometry based analysis of polystyrene bead conjugated antibodies (suspension array) allows the analysis of multiple cytokines or other proteins on the typically small sample volumes (10 - 15 ul) provided by microdialysis. Another challenge for microdialysis is the differentiation of observations due to the pathological process being studied from those caused by the insertion and presence in the tissue of the catheter itself.

    Objectives The objective of the present study was to use suspension array analysis of 10 cytokines to illustrate the chronology of the response of normal living human skin to the introduction of a microdialysis probe in-vivo.

    Methods CE-marked, commercially manufactured microdialysis catheters equipped with a 100 kiloDalton cut-off polyethersulphone membrane were introduced into the normal skin of the ventral forearm in 10 volunteers. Probes were perfused with Ringer Dextran Braun at a speed of 0.3 ul min-I. Samples were collected at 1 hour intervals for the first 7-8 hours, for a period of 9- 14 hours during the evening and during a 15-21 hours night period. Hourly sampling was again done the following morning until at least 24 hours after catheter insertion. Total protein was analysed by a protein assay kit. A cytokine suspension array was used to estimate the levels ofinterlenkin (IL) 1beta (b), 2, 4, 5, 6, 8, 10, granulocyte monocyte colony stimulating factor (GM-CSF), interferon gamma (IFNg) and turnor necrosis factor alpha (TNFa).

    Results All probes were in place as planned for 24-28 hours with a small and acceptable degree of discomfort to the subjects. Total protein levels confirmed that probes were functioning with high initial levels followed by a fall. The cytokines IL6, IL8 and IL-1 beta were detected in all patients at all time points after the first hour. IL-6 levels reached a peak at 5-8 hours, falling to levels between 25 - 820 pg ul-1 at 24 hours. IL-8 and IL-1b showed similar time courses. IL-2, GM-CSF and TNFalpha were detected at levels above the lowest standard for the technique at some time points in some subjects. IL-10, IL-5, and IL-4 were only detected in isolated samples in a few individuals. IFNg was not detected at any time point, in any of the ten subjects.

    Conclusions The previously observed elevation of IL-6 immediately after microdialysis catheter insertion into normal skin was confirmed with levels peaking at 5-8 hours and then falling to lower levels by 24 hours. IL-8 and IL-1b showed a similar time course though absolute levels at peak were lower. Other cytokines showed variable outcomes from similarly high levels, to variably low levels as well as absent levels. The cytokine spectrum was pro-inflammatory with a profile of non-Th2 character according to the Th1/Th2 paradigm. Suspension array represents a significant analytical advance in the applicability of in-vivo microdialysis whether it be experimental or clinical since most analytical capture molecules can be conjugated to the beads. The levels of cytokines seen after probe insertion provide a basis for normal biology and chronology of the cytokines as well as the interpretation of levels in the study of pathological reactions.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84290 (URN)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2012-10-03Bibliographically approved
    6. Immunofluorescence staining for cytokine and cellular localisation in 24 hour biopsies from the site of cutaneous microdialisys in normal human skin
    Open this publication in new window or tab >>Immunofluorescence staining for cytokine and cellular localisation in 24 hour biopsies from the site of cutaneous microdialisys in normal human skin
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Classically, participation of cytokines in a tissue process is demonstrated by biopsy, immunostaining and fluorescence microscopy or by PCR technique. If the chronology of a reaction is to be studied, multiple biopsies are required. This can pose practical and ethical problems. Cutaneous microdialysis is a technique which allows the qualitative and quantitative, chronological study of endogenous molecules including cytokines in living, human skin. For confumation that cytokines detected/not detected in the dialysate are present /absent in the dermis, and to determine the possible cellular source of the cytokines, a return to biopsy technique at time points of special interest is required.

    Objectives The first objective of the study was to use a single immunofluorescence staining technique to demonstrate the presence or absence of ten pro-inflammatory and lymphocyte regulatory cytokines in biopsies from the site of a microdialysis catheter. Findings were to be compared with analysis of the same cytokines in microdialysates from the same subjects immediately prior to the biopsy. A further objective was to investigate use of double immunostaining, confocal microscopy to compare the localisation of individual cytokines with cellular markers for four major candidate cell types -fibroblasts, endothelial cells, mast cells and dendritic/Langerhans cells.

    Methods In 10 volunteers studied by dermal microdialysis in normal skin for 24 -28 hours, a biopsy was taken from the area of the microdialysis membrane at the tip of the catheter. Biopsies were frozen in liquid nitrogen. Single immunostaining for interleukin (IL) I beta (b), 2, 4, 5, 6, 8, 10, granulocyte monocyte colony stimulating factor (GM-CSF), interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa), was performed and assessed semiquantitatively. Results were then compared with the microdialysis cytokine levels in the same subject innnediately prior to biopsy. Double immunostaining confocal microscopy for the cytokine and markers of the four main cell types in the dermis was performed on biopsies positive for the cytokines.

    Results Negative controls contained no fluorescence and there was reproducibility of results in multiple sections. Cellular localisation of cytokines was noted to varying degrees: IL8 was seen in all subjects; IL6 was seen in 70% of the subjects; TNFa in 50%; IL1b, IL2, GM-CSF and IFNg were seen in 30-40% of subjects; IL4, IL5 and IL10 were seen least often, 10 - 20% of subjects. At an individual subject level, concordance between positive or negative results for fluorescence microscopy and microdialysis was highest for IL8 (100%), lowest for TNFa (50%) with the remaining cytokines distributed between these two values. Double immunofluorescence and confocal microscopy enabled study of cytokine and cellular markers in the same section. Apparent co-localisation of the two markers was seen to varying degrees.

    Conclusions Fluorescence microscopy and microdialysis illustrate different aspects of cytokine presence in tissue reactions. Though individual variability can be seen in both methods and concordance of results was not seen in all subjects, the methodology was useful for better interpretation of microdialysis data. The individual concordance for the three main cytokines, IL8, IL6 and IL1b, seen after probe insertion were 100%, 80% and 60% respectively. Microdialysis fmdings in the 24 hours up to the biopsy bad suggested a non-Th2 cytokine pattern according to the Th1/Th2 paradigm. The immunofluorescence findings in the present paper indicate an even higher degree of positivity for TNFa and IFNg. Two important Th2 cytokines, IL4 and IL5 found in 1 of 10 subjects in microdialysis were not detected more frequently with immunofluorescence. The microdialysis and fluorescence findings together support a conclusion that dermal stimulation as reflected by catheter insertion creates a Th1 cytokine environment. The use of end point biopsy in the experimental design of microdialysis studies seems capable of producing worthwhlle data in regard to expression of cytokines and possible even cellular origin of cytokines.

    Keywords
    Immunostaining, cytokines, cutaneous microdialysis, confocal microscopy normal skin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84291 (URN)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2012-10-03Bibliographically approved
  • 44.
    Sjögren, Florence
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Light microscopic assessment of the dermal inflammatory cell infiltrate in experimental inflammatory reactions1999Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    In vivo experimental models have been used traditionally for the study of inflammatory contact reactions in the skin. The naked eye appearance and the histology of the skin reaction is in principle similar to that seen in man. More easily than in human experimentation, a cutaneous inflammatory reaction can, by the use of adequate group size, be studied histologically at many different time points. Plastic embedding and staining with May-GrUnewald Giemsa stains allow microscopic assessment of inflammatory cells infiltrating from the blood. Standardized, predetermined view-field selection and cellular criteria are necessary. Having previously studied the dermal infiltrate in contact reactions of delayed onset, the immediate Type I hypersensitivity reaction to ovalbumin and the non immunological immediate contact reaction to dimethyl sulfoxide (DMSO) were studied. Using the same experimental method, the effect of local application of the glucocorticosteroid, budesonide, on the delayed contact inflammatory reactions was also studied. The immediate Type I hypersensitivity reaction showed a dermal cellular infiltrate that was not uniformly distributed nor limited to the subepidermal area. The chronological study showed an influx of neutrophil and eosinophil granulocytes in the early phase and basophil granulocytes and mononuclear cells (chiefly lymphocytes) in the late phase. The non immunological immediate reaction to 100% DMSO showed the majority of the early infiltrating granulocytes to be basophils. One application of DMSO 12% gave no visible or microscopic reaction but repeated applications resulted in a delayed onset reaction with a predominant mononuclear cell infiltrate. Comparison of the two early reactions and the three previously studied reaction types showed differences and similarities at various time points in the dermal inflammatory cell infiltrate. Topically applied budesonide and its acetone vehicle showed anti inflammatory effects most pronounced on the toxic reaction to croton oil.

    The present model illustrates differences in dermal inflammatory histological patterns in various common model reaction types. The findings are relevant for the discussion of pathogenetic mechanisms and constitute background information for continued clinical studies.

  • 45.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Cytokine suspension array analysis of microdialysate samples from normal human skin during 24 hours after 100 kiloDalton cut of membrane catheter insertionManuscript (preprint) (Other academic)
    Abstract [en]

    Background Cytokines play important roles in steering homeostatic and inflammtory activities in human tissues not the least skin. In vivo, human, large pore membrane microdialysis technique can be used to measure cytokines in human tissues such as skin, muscle and brain. The new analytical technique of flow cytometry based analysis of polystyrene bead conjugated antibodies (suspension array) allows the analysis of multiple cytokines or other proteins on the typically small sample volumes (10 - 15 ul) provided by microdialysis. Another challenge for microdialysis is the differentiation of observations due to the pathological process being studied from those caused by the insertion and presence in the tissue of the catheter itself.

    Objectives The objective of the present study was to use suspension array analysis of 10 cytokines to illustrate the chronology of the response of normal living human skin to the introduction of a microdialysis probe in-vivo.

    Methods CE-marked, commercially manufactured microdialysis catheters equipped with a 100 kiloDalton cut-off polyethersulphone membrane were introduced into the normal skin of the ventral forearm in 10 volunteers. Probes were perfused with Ringer Dextran Braun at a speed of 0.3 ul min-I. Samples were collected at 1 hour intervals for the first 7-8 hours, for a period of 9- 14 hours during the evening and during a 15-21 hours night period. Hourly sampling was again done the following morning until at least 24 hours after catheter insertion. Total protein was analysed by a protein assay kit. A cytokine suspension array was used to estimate the levels ofinterlenkin (IL) 1beta (b), 2, 4, 5, 6, 8, 10, granulocyte monocyte colony stimulating factor (GM-CSF), interferon gamma (IFNg) and turnor necrosis factor alpha (TNFa).

    Results All probes were in place as planned for 24-28 hours with a small and acceptable degree of discomfort to the subjects. Total protein levels confirmed that probes were functioning with high initial levels followed by a fall. The cytokines IL6, IL8 and IL-1 beta were detected in all patients at all time points after the first hour. IL-6 levels reached a peak at 5-8 hours, falling to levels between 25 - 820 pg ul-1 at 24 hours. IL-8 and IL-1b showed similar time courses. IL-2, GM-CSF and TNFalpha were detected at levels above the lowest standard for the technique at some time points in some subjects. IL-10, IL-5, and IL-4 were only detected in isolated samples in a few individuals. IFNg was not detected at any time point, in any of the ten subjects.

    Conclusions The previously observed elevation of IL-6 immediately after microdialysis catheter insertion into normal skin was confirmed with levels peaking at 5-8 hours and then falling to lower levels by 24 hours. IL-8 and IL-1b showed a similar time course though absolute levels at peak were lower. Other cytokines showed variable outcomes from similarly high levels, to variably low levels as well as absent levels. The cytokine spectrum was pro-inflammatory with a profile of non-Th2 character according to the Th1/Th2 paradigm. Suspension array represents a significant analytical advance in the applicability of in-vivo microdialysis whether it be experimental or clinical since most analytical capture molecules can be conjugated to the beads. The levels of cytokines seen after probe insertion provide a basis for normal biology and chronology of the cytokines as well as the interpretation of levels in the study of pathological reactions.

  • 46.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    The spectrum of inflammatory cell response to dimethyl sulfoxide2000In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 42, no 4, p. 216-221Article in journal (Refereed)
    Abstract [en]

    Dimethyl sulfoxide (DMSO), depending upon the concentration and mode of application to the skin, can induce either a non-immunological immediate contact urticaria or an irritant reaction. The dermal cellular infiltrate after open application of varying concentrations of DMSO has been studied in an experimental guinea pig model. The composition of the dermal cellular infiltrate showed a spectrum dependent on the concentration and number of applications of DMSO. The immediate reaction infiltrate 3 h after application of 100% DMSO consisted of 50% granulocytes, basophils being predominant. On the other hand, 12% DMSO applied 3 × daily for 3 days (cumulative insult) caused histologically a cellular reaction in which 80% of the infiltrate consisted of mononuclear cells. The present findings are compared to the microscopic findings in 3 other cutaneous reactions previously studied in this animal model, namely, the Type I immediate hypersensitivity reaction, the Type IV delayed hypersensitivity reaction, and the irritant reaction. Differing cellular infiltrate patterns are discernible at the same time points. The study illustrates the spectrum of inflammatory reactions seen in the skin and provides background information for future clinical studies, for instance, on the role of the basophil granulocyte in immediate contact reactions.

  • 47.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Andersson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Immunofluorescence staining for cytokine and cellular localisation in 24 hour biopsies from the site of cutaneous microdialisys in normal human skinManuscript (preprint) (Other academic)
    Abstract [en]

    Background Classically, participation of cytokines in a tissue process is demonstrated by biopsy, immunostaining and fluorescence microscopy or by PCR technique. If the chronology of a reaction is to be studied, multiple biopsies are required. This can pose practical and ethical problems. Cutaneous microdialysis is a technique which allows the qualitative and quantitative, chronological study of endogenous molecules including cytokines in living, human skin. For confumation that cytokines detected/not detected in the dialysate are present /absent in the dermis, and to determine the possible cellular source of the cytokines, a return to biopsy technique at time points of special interest is required.

    Objectives The first objective of the study was to use a single immunofluorescence staining technique to demonstrate the presence or absence of ten pro-inflammatory and lymphocyte regulatory cytokines in biopsies from the site of a microdialysis catheter. Findings were to be compared with analysis of the same cytokines in microdialysates from the same subjects immediately prior to the biopsy. A further objective was to investigate use of double immunostaining, confocal microscopy to compare the localisation of individual cytokines with cellular markers for four major candidate cell types -fibroblasts, endothelial cells, mast cells and dendritic/Langerhans cells.

    Methods In 10 volunteers studied by dermal microdialysis in normal skin for 24 -28 hours, a biopsy was taken from the area of the microdialysis membrane at the tip of the catheter. Biopsies were frozen in liquid nitrogen. Single immunostaining for interleukin (IL) I beta (b), 2, 4, 5, 6, 8, 10, granulocyte monocyte colony stimulating factor (GM-CSF), interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa), was performed and assessed semiquantitatively. Results were then compared with the microdialysis cytokine levels in the same subject innnediately prior to biopsy. Double immunostaining confocal microscopy for the cytokine and markers of the four main cell types in the dermis was performed on biopsies positive for the cytokines.

    Results Negative controls contained no fluorescence and there was reproducibility of results in multiple sections. Cellular localisation of cytokines was noted to varying degrees: IL8 was seen in all subjects; IL6 was seen in 70% of the subjects; TNFa in 50%; IL1b, IL2, GM-CSF and IFNg were seen in 30-40% of subjects; IL4, IL5 and IL10 were seen least often, 10 - 20% of subjects. At an individual subject level, concordance between positive or negative results for fluorescence microscopy and microdialysis was highest for IL8 (100%), lowest for TNFa (50%) with the remaining cytokines distributed between these two values. Double immunofluorescence and confocal microscopy enabled study of cytokine and cellular markers in the same section. Apparent co-localisation of the two markers was seen to varying degrees.

    Conclusions Fluorescence microscopy and microdialysis illustrate different aspects of cytokine presence in tissue reactions. Though individual variability can be seen in both methods and concordance of results was not seen in all subjects, the methodology was useful for better interpretation of microdialysis data. The individual concordance for the three main cytokines, IL8, IL6 and IL1b, seen after probe insertion were 100%, 80% and 60% respectively. Microdialysis fmdings in the 24 hours up to the biopsy bad suggested a non-Th2 cytokine pattern according to the Th1/Th2 paradigm. The immunofluorescence findings in the present paper indicate an even higher degree of positivity for TNFa and IFNg. Two important Th2 cytokines, IL4 and IL5 found in 1 of 10 subjects in microdialysis were not detected more frequently with immunofluorescence. The microdialysis and fluorescence findings together support a conclusion that dermal stimulation as reflected by catheter insertion creates a Th1 cytokine environment. The use of end point biopsy in the experimental design of microdialysis studies seems capable of producing worthwhlle data in regard to expression of cytokines and possible even cellular origin of cytokines.

  • 48.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Andersson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Groth, O.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    The cellular dermal infiltrate in experimental immediate type cutaneous hypersensitivity1995In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 75, no 6, p. 417-421Article in journal (Refereed)
    Abstract [en]

    A previously developed guinea pig model for the study of the dermal inflammatory cell infiltrate of allergic, toxic, and irritant reactions was adapted to the study of the immediate intradermal reaction to ovalbumin, Comparison of qualitative and quantitative counts of infiltrating cells at three levels in the dermis showed that counting 20 subepidermal fields starting from the injection point of the allergen gave reliable figures, The reaction showed microscopically two phases. The first was of rapid onset and characterized by a high proportion of neutrophils, unlike the picture seen in the previously studied (allergic and toxic) reaction types. In the second phase, which can be termed 'late phase' reaction, mononuclear cells and basophil granulocytes predominated. The late phase of the reaction bears similarities to the delayed allergic contact reaction at the same timepoint in that the response was rich in basophils. There were, however, other differences; e.g, eosinophils and neutrophils were more common.

  • 49.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Groth, O.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Acetone has anti-inflammatory effects on experimental contact reactions1999In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 41, no 1, p. 22-29Article in journal (Refereed)
    Abstract [en]

    The effects of a topically applied corticosteroid and its acetone vehicle on experimental allergic, toxic and irritant reactions are presented. The corticosteroid budesonide in acetone or acetone alone was applied to reactions immediately after and at different time intervals within the 1st h after provocation. Classical naked eye observation was performed and the dermal cellular infiltrate was differentiated and counted using a previously well-characterized method. “Treatment”, whether with the steroid in acetone or acetone alone, had anti-inflammatory effects. For all reaction types, erythema and oedema diminished and a significant decrease in mononuclear cells was seen, when application occurred within the first 5 min after provocation. The effects were most marked for the toxic reaction to croton oil, the steroid and the vehicle being anti-inflammatory to the same extent. Application up to 60 min after provocation had anti-inflammatory effects for this reaction type. The mechanisms of acetone's anti-inflammatory effects are at present unclear. One possible explanation is that intercellular lipid organisation and, by extension, cellular membrane lipid organisation, are altered, influencing membrane receptor function. Possible anti-inflammatory effects of acetone should be considered in experimental and perhaps even clinical situations. Further investigation of the therapeutic possibilities of the finding seems warranted.

  • 50.
    Sjögren, Florence
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Ljunghusen, O
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Baas, A
    Coble, Britt-Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Stendahl, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Expression and function of beta-2 integrein CD11B/CD18 on leukocytes from patients with psoriasis. 1999In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 79, p. 105-110Article in journal (Refereed)
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