PIXE analysis in uninvolved skin of atopic patients and aged skin.

PIXE (proton-induced X-ray emission) analysis was used to determine the elemental distribution in normal-appearing skin of patients suffering from atopic eczema and in the skin of elderly people. With this technique, elements with atomic numbers greater than or equal to 14 can be detected simultaneously in cryosections of skin biopsies down to a concentration of 1 ppm. Compared with a control group, the epidermal concentrations of Zn and Cu, which are constituent parts of a variety of enzymes, were increased in uninvolved skin of patients with atopic eczema. An increased concentration of these two metals might indicate that even in the epidermis of clinically normal skin of atopic patients, the content of certain enzymes is increased. In the epidermis of elderly people the level of K was lower and that of Ca was higher than in the epidermis of a younger age group. The decreased K level may reflect a reduction of the intracellular volume in the epidermis of aged skin. As high Ca concentrations inhibit the proliferation of and promote the differentiation of keratinocytes, elevated Ca levels may be of importance for the age-associated decrease in epidermal turnover rate.     

B-scanning evaluation with image analysis of psoriatic skin

Ten psoriatic plaques from different subjects were investigated by 20 MHz ultrasound B scanning. Lesions were evaluated before therapy, and after 7 and 15 days of topical treatment with anthralin. Recordings from lesional skin were compared with those from clinically non-involved contralateral skin. Images were assessed by means of a new image analysis program, allowing the conversion of the B-scan image color scale into a numerical amplitude scale, the selection and highlighting of amplitude bands, and the quantification of objects reflecting in a definite amplitude range. B-scanning evaluation of the psoriatic plaque revealed a thickening of the epidermis and dermis, the presence of parallel acoustic shadows in the dermis, and a characteristic hypo-echogenic band corresponding to the papillary dermis. Image processing allowed an exact quantification of the progressive reduction in thickness of the epidermis and dermis and of the hypo-echogenic band observed at skin sites which had been treated with topical substances. Thus, the echographic method with image analysis allows the evaluation of three different parameters of response to topical treatment of psoriatic skin.     

不同时期黄褐斑皮损三种皮肤影像的形态学分析

【摘要】 目的 运用三种皮肤影像技术探究女性黄褐斑不同时期皮损的形态。方法 2017年6月至2018年1月,在杭州市第三人民医院门诊收集女性黄褐斑患者253例。结合临床分期标准,应用反射式共聚焦显微镜（RCM）、VISIA皮肤图像检测仪、皮肤镜观察不同时期黄褐斑皮损,分析临床分期与树突状黑素细胞、亚临床黄褐斑、血管形态改变的相关性。采用SPSS19.0统计学软件,计数资料比较采用卡方检验及独立样本Mann?Whitney U检验。结果 253例患者中,进展期100例,稳定期153例。进展期患者中78例（78%）RCM下有树突状黑素细胞,稳定期中22例（14.4%）可见树突状黑素细胞,两组间差异有统计学意义（χ2 = 102.40,P＜0.01）。VISIA皮肤图像检测仪观察显示,进展期患者中78例（78%）有亚临床黄褐斑,稳定期患者25例有亚临床黄褐斑（16.3%）,进展期亚临床黄褐斑出现率高于稳定期（χ2 = 95.26,P＜0.01）。皮肤镜显示,进展期患者血管改变发生率为74%（74/100）,稳定期为68.6%（105/153）,两组差异无统计学意义（χ2 = 0.84,P = 0.39）。结论 RCM、VISIA皮肤图像检测仪下分别观察的树突状黑素细胞及亚临床表现可作为黄褐斑临床分期的参考指标。     

Keratinosomes in psoriatic skin.

Keratinosomes in psoriatic skin can be slightly larger than those in normal skin. Some seem to develop an unusual internal morphology, and some reach their full development while they are still within the immediate Golgi area. Observational evidence indicates that there may be more kerantinosomes in psoriatic skin than are generally found in normal skin. Keratinosomes appear extracellularly from the spinous layer through the horny layer. Some keratinosomes do not move to the outside of the cell and can be seen within cells of the horny layer. There appears to be an increased number of keratinosomes in and between the outer cells of sweat ducts. Keratinosomes are also present within the dark cells of the duct and the extracellular space between the dark cells contains material from keratinosomes.     

Quantitative enzyme-histochemical analysis of tryptase- and chymase-containing mast cells in psoriatic skin

Summary Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymaseand tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72–73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activitiy in the upper dermis may lead to an imbalance in the biochemical regulatory systems.     

Lectin binding of psoriatic skin

The aim of our study was the characterization of epidermal lectin binding pattern in psoriatic vs. non-psoriatic skin in order to reveal possible alterations of the glycocalyx composition of psoriatic keratinocytes. We used fluoroisothiocyanate-labeled lectins of Canavalia ensiformis (ConA), Phaseolus vulgaris (PHA), Lens culinaris (LCA), and Helix pomatia (HPA). The binding pattern of psoriatic (involved and non-lesional) skin did not differ from the control samples in ConA, PHA, and LCA. In psoriasis, there was a prominent HPA binding to the dermo-epidermal junction and to a lesser degree, intercellular epidermal near the uppermost cell layers. In seborrheic keratosis, in contrast, there was no fluorescence of the dermo-epidermal junction or the first layers of the epidermis. The most pronounced binding was observed perinuclear in the upper epidermis. The results are discussed in the light of an altered keratinocyte maturation in psoriasis.     

X-ray microanalysis of psoriatic skin

Electron probe x-ray microanalysis was used to study elemental distribution in uninvolved and involved skin from patients with psoriasis, and in skin from healthy controls. Significant differences were found between the involved and uninvolved psoriatic skin. In the involved skin, the concentrations of Mg, P, and K were higher in the stratum germinativum, spinosum, and granulosum, compared to the corresponding strata in uninvolved skin. Neither involved nor uninvolved psoriatic stratum germinativum differed markedly from nonpsoriatic control stratum germinativum. In uninvolved psoriatic skin only a lower level of K was noted. In comparison to uninvolved psoriatic skin, the elemental composition of the various strata of involved psoriatic skin shows a pattern typical for highly proliferative, nonneoplastic cells.     

Arginase is overactive in psoriatic skin

Background Psoriatic keratinocytes are poorly differentiated and hyperproliferative. Low concentrations of nitric oxide (NO) induce keratinocyte proliferation, while high concentrations induce differentiation. The NO‐producing enzyme inducible NO synthase is overexpressed in psoriatic skin, but so is arginase. The overexpressed arginase competes for arginine, the common substrate for both enzymes, and may reduce NO production. Objectives To determine whether arginase activity is elevated in psoriatic skin and whether exogenous NO will improve psoriatic plaques. Methods Tape strips were taken from healthy skin of eight control subjects and nonlesional skin of eight patients with psoriasis and l‐arginine, l‐citrulline and l‐ornithine concentrations measured by high‐performance liquid chromatography. In a second study, four psoriatic patients with a pair of similar symmetrical plaques were treated with an NO donor and vehicle control. Plaques were scored for size, erythema, induration and scaling at the start and after 6 weeks of treatment. Results Ornithine, the end‐product of arginase, was at higher concentrations in nonlesional psoriatic than in healthy skin (mean ± SEM 2·08 ± 0·98 vs. 1·13 ± 0·44 μg mg^?1 protein; P = 0·0002). Arginine, its substrate, was at lower concentrations. Topical application of an NO donor improved psoriatic plaques clinically [mean ± SD reduction in severity from baseline score (100%) to 35% ± 16% in active NO donor and to 93% ± 10% in control]. Conclusions Arginase is overactive in psoriatic skin, leading to a relative increase in the consumption of arginine. We therefore hypothesize a relative decrease in NO synthase‐derived NO production. NO donors may be effective topical treatments for psoriasis.     

Nucleolar ultrastructure in psoriatic skin lesions

Keratinocytes in psoriatic skin lesions were studied to provide more information on the nucleolar ultrastructure in these cells. In contrast to normal keratinocytes, nucleoli in the keratinocytes of the uppermost layer of stratum granulosum (intermedium) of psoriatic lesions were characterized by the absence of the segregation of nucleolar components. In addition, the keratinocytes without keratohyalin of the uppermost layer of stratum intermedium of psoriatic lesions did not contain degranulated nucleoli. Such observations indicate an alteration of the maturation processes in the keratinocytes of the psoriatic skin lesions and the characteristic nucleolar changes apparently represent the morphological expression of the altered inhibition of the nucleolar (preribosomal) RNA synthesis.     

Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin

Adhesion molecule expression in synovial membrane obtained from patients with psoriatic arthritis (PA) has previously been compared with rheumatoid arthritis (RA). Although expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was similar in both psoriatic and rheumatoid synovium, in contrast, little or no endothelial leucocyte adhesion molecule-1 (ELAM-1) was observed in psoriatic synovium. In the present study, the expression of ICAM-1. ELAM-1 and VCAM-1 was examined in the involved and uninvolved skin from patients with PA (n= 15), patients with psoriasis (Ps) but no arthritis (n= 5) and in normal skin (n= 4). ICAM-1 was intensely expressed on endothelium and keratinocytes of involved skin from patients with Ps with or without arthritis. There was constitutive expression of ICAM-1 on endothelium only in uninvolved and normal skin. In contrast, ELAM-1 expression was restricted to endothelial cells; it was widespread and intense in involved skin, but was minimal in uninvolved and normal skin. VCAM-1 was expressed on endothelium, and also on some dendritic cells in involved psoriatic skin. There was minimal VCAM-1 staining on endothelial cells in uninvolved and normal skin. In conclusion, in involved psoriatic skin from patients with and without arthritis ICAM-1, ELAM-1 and VCAM-1 expression is up-regulated on vascular endothelium, and ICAM-1 is expressed on keratinocytes. However, ELAM-1 and VCAM-1 expression seen in dermal vessels is not found in psoriatic synovial vessels. These differences suggest a mechanism for controlling cellular traffic in Ps and in PA.     

Origin of threshold behaviour in psoriatic skin

The mechanisms that lead to the psoriatic morphology are not fully elucidated. Several lines of evidence suggest that the positive feedback between keratinocytes and immunocytes plays a key role in the development of the lesions. On the other hand, little information is available on the negative regulatory controls that maintain a new homoeostasis level in psoriatic skin. We suggest here that the interplay of these two contrary feedbacks is likely to entail a hysteresis effect and that psoriasis is likely to be interpreted as a critical phenomenon characterized by a catastrophic shift of the skin from a normal to a hyperplastic state.     

Detection of inflammatory cytokines in psoriatic skin

Recent investigations have revealed the involvement of cytokines in the pathogenesis of psoriasis. This study examined the amount of inflammatory cytokines — interleukin-1 (IL-1), interleukin-6 (IL-6) and granulocyte macrophage colony-stimulating factor (GM-CSF) — released into the supernatants of organ cultures of involved and uninvolved skin from psoriatic patients and normal skin from healthy individuals. Bioassays were employed to detect the activities of IL-1 and IL-6. Enzyme-linked immunosorbent assay (ELISA) methods were used to quantitate immunoreactive IL-1, IL-1, IL-6 and GM-CSF. The activity of IL-1 in uninvolved psoriatic skin was found to be increased relative to that in involved and normal skin, while immunoreactive IL-1 was found only in involved skin. A neutralization experiment showed that bioactive IL-1 was mostly attributable to IL-1. Uninvolved psoriatic skin also secreted higher amounts of both bioactive and immunoreactive IL-6 compared with involved skin. Immunoreactive GM-CSF was detected in uninvolved skin only. These cytokines detected in uninvolved skin may have been released from epidermal or mesenchymal cells, since uninvolved skin contained fewer inflammatory infiltrates. Our results offer additional evidence that increased amounts of inflammatory cytokines in uninvolved skin may provide a preliminary condition and play important roles in the initial events in the evolution of psoriatic lesions.Part of this work was presented in abstract form at the Fifth International Psoriasis Symposium in San Fransisco, 10–14 July 1991