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Unaffected Skin (unaffected + skin)
Selected AbstractsInfiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin testEXPERIMENTAL DERMATOLOGY, Issue 5 2003M. Caproni Abstract:, In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-,), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22,57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-, showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [source] Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI)MICROCIRCULATION, Issue S1 2000MICHAEL JÜNGER ABSTRACT The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO2 and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo-null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d), and L-selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus-like changes in capillary morphology, a drop in the oxygen content (tcpO2) of the skin, increased permeability of the capillaries to low-molecular-weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA-1 and VLA-4 on lymphocytes, Mac-1 expression on the myeloid cell line, and L-selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L-selectin in blood cells collected at foot level in the controls (p = 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p < 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area. [source] Efficacy of 308-nm excimer light for Japanese patients with psoriasisTHE JOURNAL OF DERMATOLOGY, Issue 11 2009Yusuke NIWA Abstract Ultraviolet irradiation therapy, including psoralen and ultraviolet A therapy and narrow-band ultraviolet B (310,312 nm) therapy, is a widely used and highly efficient treatment modality for psoriasis. Therapy with 308-nm excimer light has been reported to be effective for the treatment of psoriasis vulgaris. To evaluate the efficacy of 308-nm excimer light therapy for Japanese psoriasis patients, seven patients (six men and one woman) with plaque-type psoriasis were treated with 308-nm excimer light at 7,14-day intervals. The Psoriasis Severity Index (PSI) was calculated for individual plaques in order to assess the effectiveness of the therapy. A 74.9% mean improvement in the PSI was observed after 10 treatment sessions. These results suggested that targeted irradiation with 308-nm excimer light leads to rapid and selective improvement in plaque-type psoriatic lesions without unnecessary radiation exposure to the surrounding unaffected skin. [source] Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: A quantitative comparative studyTHE JOURNAL OF DERMATOLOGY, Issue 6 2007Ayça Cordan YAZICI ABSTRACT Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase. [source] Alterations in the epidermal,dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skinBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006N. Ünver Summary Background, Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as , -melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. Objectives, To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. Methods, Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52,81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. Results, The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. Conclusions, In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed. [source] Comparison of the 308-nm excimer laser and a 308-nm excimer lamp with 311-nm narrowband ultraviolet B in the treatment of psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2005K. Köllner Summary Background, Psoriasis is a chronic, genetically determined inflammatory disease, characterized by an immunomediated pathogenesis, which affects approximately 1,3% of the population. Various modalities have been used for psoriasis treatment, including ultraviolet (UV) radiation. Narrowband UVB (311 nm) phototherapy is a well-established, widely used and highly efficient treatment for psoriasis, but a big disadvantage is that large areas of unaffected skin are irradiated along with the psoriatic lesions. Objectives, This investigation evaluates a 308-nm excimer laser and a 308-nm excimer lamp in comparison with 311-nm narrowband UVB in the treatment of patch psoriasis by using two different dose-increase schemes. Materials and methods, Fifteen patients with plaque psoriasis were enrolled in the study (first regime). Three different psoriatic lesions were treated with the 308-nm excimer laser, the 308-nm excimer lamp or 311-nm narrowband UVB three times per week. UVB doses were increased slowly and stepwise (1, 1, 2, 2, 3, 3, ,multiple MEDs). Sixteen patients were enrolled in the second regime. Two plaques were treated with the 308-nm excimer laser or with the 308-nm lamp with an accelerated scheme (2, 2, 4, 4, 6, 6, ,multiple MEDs) three times per week. We increased the UVB doses every second treatment (first and second regime) during the whole treatment. If blistering occurred, the blistered plaque was not treated on the next scheduled treatment. At every third visit and 1, 2 and 4 months after the last treatment a Psoriasis Severity Index (PSI) score was assigned in both regimes. Results, Using Friedman analysis, the PSI scores did not show a statistically significant difference (P > 0·05) comparing 308-nm laser therapy, 308-nm lamp therapy and 311-nm narrowband therapy after 10 weeks in the first regime. The mean number of treatments to achieve clearance was 24. With the accelerated scheme, clearance could be achieved with fewer treatments and with half the cumulative dose of the first regime. Nevertheless, the side-effects such as blistering and crusting were also increased. Conclusions, Both 308-nm light sources can clear patch psoriasis in a similar manner to standard phototherapy, with the advantage of the ability to treat exclusively the affected skin and with a reduced cumulative dose, thus perhaps reducing the long-term risk of carcinogenicity. [source] A Japanese case of segmental Darier's disease caused by mosaicism for the ATP2A2 mutationBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003T. Wada Summary Darier's disease is an autosomal dominant skin disorder that is characterized by multiple keratotic papules, focal loss of adhesion and abnormal keratinization. Mutations in the ATP2A2 gene encoding sarco/endoplasmic reticulum calcium pumping ATPase type 2 have been identified as the molecular basis of Darier's disease. Segmental Darier's disease is a rare type of Darier's disease in which there is characteristic localization of the keratotic papules in a linear pattern following Blaschko's lines. In this study we examined ATP2A2 mutations in a Japanese patient with segmental Darier's disease. The samples from affected skin, unaffected skin and peripheral leucocytes were subjected to polymerase chain reaction (PCR). Direct sequencing of the PCR products was performed. Sequence analysis revealed that the patient had 160A,G substitution mutation which predicts I54V. This novel mutation was present in the affected skin, but not in the unaffected skin or peripheral leucocytes. This is the first report of segmental Darier's disease caused by mosaicism for an ATP2A2 mutation in Japan. [source] |