| 1. |
- Biro, T, et al.
(författare)
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How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches
- 2005
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 14:3, s. 225-225
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Tidskriftsartikel (refereegranskat)abstract
- While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.
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| 2. |
- Asplund, Anna, et al.
(författare)
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Genetic mosaicism in basal cell carcinoma
- 2005
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 14:8, s. 593-600
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Tidskriftsartikel (refereegranskat)abstract
- Human basal cell cancer (BCC) shows unique growth characteristics, including a virtual inability to metastasize, absence of a precursor stage and lack of tumour progression. The clonal nature of BCC has long been a subject for debate because of the tumour growth pattern. Despite a morphologically multifocal appearance, genetic analysis and three-dimensional reconstructions of tumours have favoured a unicellular origin. We have utilized the X-chromosome inactivation assay in order to examine clonality in 13 cases of BCC. Four parts of each individual tumour plus isolated samples of stroma were analysed following laser-assisted microdissection. In 12/13 tumours, the epithelial component of the tumour showed a monoclonal pattern suggesting a unicellular origin. Surprisingly, one tumour showed evidence of being composed of at least two non-related monoclonal clones. This finding was supported by the analysis of the ptch and p53 gene. Clonality analysis of tumour stroma showed both mono- and polyclonal patterns. A prerequisite for this assay is that the extent of skewing is determined and compensated for in each case. Owing to the mosaic pattern of normal human epidermis, accurate coefficients are difficult to obtain; we, therefore, performed all analyses both with and without considering skewing. This study concludes that BCC are monoclonal neoplastic growths of epithelial cells, embedded in a connective tissue stroma at least in part of polyclonal origin. The study results show that what appears to be one tumour may occasionally constitute two or more independent tumours intermingled or adjacent to each other, possibly reflecting a local predisposition to malignant transformation.
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| 3. |
- Backvall, H., et al.
(författare)
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Mutation spectra of epidermal p53 clones adjacent to basal cell carcinoma and squamous cell carcinoma
- 2004
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 13:10, s. 643-650
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Tidskriftsartikel (refereegranskat)abstract
- Foci of normal keratinocytes overexpressing p53 protein are frequently found in normal human skin. Such epidermal p53 clones are common in chronically sun-exposed skin and have been suggested to play a role in skin cancer development. In the present study, we have analyzed the prevalence of p53 mutations in epidermal p53 clones from normal skin surrounding basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Using laser-assisted microdissection, 37 epidermal p53 clones adjacent to BCC (21) and SCC (16) were collected. Genetic analysis was performed using a multiplex/nested polymerase chain reaction followed by direct DNA sequencing of p53 exons 2-11. In total, 21 of 37 analyzed p53 clones consisted of p53-mutated keratinocytes. The identified mutations were located in p53 exons 4-8, corresponding to the sequence-specific DNA-binding domain. All mutations were missense, and 78% displayed a typical ultraviolet signature. The frequency of p53 mutations was similar in skin adjacent to BCC compared to SCC. The presented data confirm and extend previous knowledge on the genetic background of epidermal p53 clones. The mutation spectra found in epidermal p53 clones resemble that of non-melanoma skin cancer. Approximately, 40% of the epidermal p53 clones lacked an underlying p53 mutation, suggesting that other genetic events in genes up- or downstream of the p53 gene can generate foci of normal keratinocytes overexpressing p53 protein.
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| 4. |
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| 5. |
- Larsson (Wäster), Petra, et al.
(författare)
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Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis
- 2005
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 14:2, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet (UV) radiation is an etiologic agent for malignant melanoma and non-melanoma skin cancer, but the spectral range responsible for tumor induction is still to be elucidated. In this study, we compared effects of UVA and UVB irradiation on normal human melanocytes (MCs) and keratinocytes (KCs) in vitro. We demonstrate that UVA irradiation induces immediate loss of reduced glutathione (GSH) in both MCs and KCs. Exposure to UVA also causes reduced plasma membrane stability, in both cell types, as estimated by fluorescein diacetate retention and flow cytometry. Furthermore, we noted reduction in proliferation and higher apoptosis frequency 24 h after UVA irradiation. UVB irradiation of KCs caused instant reduction of reduced GSH and impaired plasma membrane stability. We also found decline in proliferation and increased apoptosis after 24 h. In MCs, on the other hand, UVB had no effect on GSH level or plasma membrane stability, although increased apoptotic cell death and reduced proliferation was detected. In summary, MCs and KCs showed similar response towards UVA, while UVB had more pronounced effects on KCs as compared to MCs. These results might have implications for the induction of malignant melanoma and non-melanoma skin cancer.
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| 11. |
- Alexeyev, Oleg A.
(författare)
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Bacterial landscape of human skin : seeing the forest for the trees
- 2013
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Ingår i: Experimental dermatology. - : Wiley-Blackwell. - 0906-6705 .- 1600-0625. ; 22:7, s. 443-446
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Tidskriftsartikel (refereegranskat)abstract
- Skin harbours large communities of colonizing bacteria. The same bacterial species can exist in different physiological states: viable, dormant, non-viable. Each physiological state can have a different impact on skin health and disease. Various analytical methodologies target different physiological states of bacteria, and this must be borne in mind while interpreting microbiological tests and drawing conclusions about possible cause-effect relationships.
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| 15. |
- Andersson, Eva, 1946-, et al.
(författare)
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Differential effects of UV irradiation on nuclear retinoid receptor levels in cultured keratinocytes and melanocytes
- 2003
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 12:5, s. 563-71
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Tidskriftsartikel (refereegranskat)abstract
- 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 (RARalpha, RARgamma and RXRalpha) 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 4 h; protein levels minus 20-45% after 8 h), which was followed over the next 40 h by a variable response, leading to full normalization for RARalpha 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 approximately 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.
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| 16. |
- Andréasson, Kristofer, et al.
(författare)
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Limited impact of fibromodulin deficiency on the development of experimental skin fibrosis
- 2016
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705.
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Tidskriftsartikel (refereegranskat)abstract
- Excessive production of collagen is the hallmark of fatal diseases of fibrosis such as systemic sclerosis. Overexpression of the proteoglycan fibromodulin (FMOD) has been associated with improved wound healing and scarless repair. In this study we have investigated the consequences of FMOD deficiency on the development of experimental skin fibrosis. Using immunohistochemistry, we identified FMOD in both human and murine fibrotic skin. In the bleomycin model of skin fibrosis, FMOD(-/-) mice developed skin fibrosis to a similar degree compared to FMOD(+/+) mice. Analysis of skin ultrastructure using transmission electron microscopy revealed a significant reduction in collagen fibril diameter in FMOD(-/-) but not FMOD(+/+) mice following fibrosis. We conclude that impact of FMOD deficiency on the development of experimental skin fibrosis is limited. This article is protected by copyright. All rights reserved.
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| 17. |
- Bhardwaj, Vinay, et al.
(författare)
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A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face : Clinical evidence and mechanistic understanding by computational biology and optical biopsy
- 2024
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Ingår i: Experimental dermatology. - : John Wiley & Sons. - 0906-6705 .- 1600-0625. ; 33:4
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Tidskriftsartikel (refereegranskat)abstract
- Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflexTM), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.
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| 18. |
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| 19. |
- Bäckvall, Helena, et al.
(författare)
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Similar UV responses are seen in a skin organ culture as in human skin in vivo
- 2002
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 11:4, s. 349-356
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Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet radiation (UVR) plays an important role in the development of non-melanoma skin cancer. Most tumors develop in chronically sun-exposed skin, most often in cosmetically sensitive locations, where in vivo experiments may be difficult to perform. In this study, we describe a skin organ culture model with preserved normal morphology and intact response to UVR. Skin explants from chronically sun-exposed and non-sun-exposed skin were irradiated with artificial UVA+UVB with and without topical sunscreen. UV-induced DNA damage, epidermal p53 response and repair kinetics were analyzed using immunohistochemistry. Four hours after UV-irradiation epidermal keratinocytes showed a strong immunoreactivity for thymine-dimers. Gradual repair during an incubation time resulted in few residual thymine-dimers after 48 h. Repair appeared to be more efficient in chronically sun-exposed skin compared with non-sun-exposed skin. There was also an accumulation of p53 protein in epidermal keratinocytes, peaking at 4-24 h after irradiation. Large interindividual differences with respect to formation and repair of thymine-dimers as well as induction and duration of the p53 response were observed. Skin explants treated with topical sunscreen prior to UV-irradiation showed a clear reduction of thymine-dimers and p53 expression. The epidermal UV-responses and repair kinetics in organ-cultured skin were similar to what was found in vivo. Our data suggest that organ-cultured skin provides a valuable tool for studies of UV-induced epidermal responses in chronically sun-exposed skin.
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| 20. |
- Carlström, Maria, et al.
(författare)
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Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility
- 2012
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Ingår i: Experimental dermatology. - : John Wiley and Sons. - 0906-6705 .- 1600-0625. ; 21:12, s. 932-937
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Tidskriftsartikel (refereegranskat)abstract
- NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1 beta processing. The contribution of IL-1 beta in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domaincontaining protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohns disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan (R) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.11.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.
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| 25. |
- Collin, Mattias, et al.
(författare)
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The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodies.
- 2013
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 22:8, s. 511-514
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Tidskriftsartikel (refereegranskat)abstract
- IgG antibodies have one conserved N-glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro- or anti-inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N-acetyl-glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non-galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro-inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti-inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2 g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro-inflammatory immune responses, such as autoimmune reactions, primarily induce antigen-specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro- or anti-inflammatory effector functions obviously as immune complexes (IC) in an antigen-specific manner. Therefore, antigen-specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re-establishing tolerance against defined (self-) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen-specific IgG antibodies.
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