Electron microscopic observations of concentric lamellar bodies within mesenchymal cells of anagen hair dermal papilla

The presence of 2 forms of the concentric lamellar bodies was observed in the mesenchymal cells within dermal papilla of normal scalp anagen hairs. They are those composed of agranular membrane arrays in association with beta-glycogen particles (glycogen bodies) and those of smooth-surfaced endoplasmic reticulum (smooth-surfaced lamellar bodies). On rare occasions these 2 forms of the concentric lamellar bodies were simultaneously present within the same cells. Transitional forms between the smooth-surfaced lamellar bodies and phagosegresomal granules were also encountered.     

Characteristics and modulation of dithranol (anthralin)-induced skin irritation in the mouse ear model

Summary Dithranol-induced skin irritation and the modulatory effects of different pharmacological agents were studied using the mouse ear model. A single topical application of dithranol caused a dose-dependent skin irritation which resulted in delayed swelling of the mouse ear with two separate peak responses, 1–2 and 6–10 days after application. The irritation was most effectively and persistently inhibited by topical treatment with corticosteroids, the free radical scavenger DL--tocopherol (DLAT) and the serotonin antagonist metergoline. The effect of corticosteroids, however, was slightly diminished during the second peak irritation. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), the dual lipoxygenase and cyclo-oxygenase inhibitor tolfenamic acid and the cyclo-oxygenase inhibitor indomethacin as well as trifluoperazine retained their inhibitory activity. Of these compounds, indomethacin was active only during the first irritation peak, NDGA during both peaks and trifluoperazine principally during the second peak. Retinoic acid did not inhibit the ear swelling. The results confirm and extend the observations that the formation of free radicals is essential for dithranol inflammation. The inflammation can also be suppressed by inhibiting the formation of arachidonic acid or its pro-inflammatory metabolites.     

Electron microscopy of the effects of dithranol on healthy and on psoriatic skin

The fine structure of healthy and of psoriatic skin was studied after dithranol irritation. Following a minimum erythematogenic or a moderate-to-considerable irritant reaction of healthy skin with dithranol, all epidermal cell types were focally affected. The Langerhans' cells (LC) were most sensitive, reacting with strongly swollen mitochondria with broken cristae, and sometimes by forming branched and circular Birbeck granules. More often than is normal, the Birbeck granules showed continuity with the LC cytomembrane. Also, melanocytes were more sensitive than keratinocytes. Most of the more strongly affected keratinocytes became cytolytic with edemic cytoplasm, but scattered cells underwent dyskeratosis (apoptosis) resulting in colloid bodies in the upper dermis. High amounts of lipid droplets developed in the basal keratinocytes, LCs, melanocytes, and dermal cells. Lipid droplets also developed in the keratinocytes at the stratum granulosum/stratum corneum interface concomitantly with a decrease in keratohyalin. Ten days after challenge, keratohyalin granules were normal again, but otherwise many changes in epidermis persisted, with increased numbers of exocytic cells and LC-mononuclear cell contacts in the epidermis and immunocompetent cells crossing the dermal-epidermal junction. These findings indicate that an irritant reaction could predispose to sensitization via nonspecifically activated immunocompetent cells. A single half-hour contact treatment with dithranol caused negligible changes in the psoriatic skin, while 24 hours' occlusion caused moderate-to-massive changes in mitochondria of keratinocytes, resulting in giant perinuclear mitochondria with broken cristae. Dithranol affects all cell types in the skin and morphologically it cannot be concluded which effect is the important one in clearing the psoriatic lesions.     

Autoradiographic in vitro-examination of psoriatic skin before,during and after dithranol treatment

Summary Autoradiographic in vitro-examination of normal and of psoriatic skin, using the double labelling technique (1 µC thymidine-2-C¹⁴ and 10 µC thymidine-methyl-H³), revealed the usual increase of proliferative activity in psoriatic skin, approximately four times greater than normal. The cell cycle time was shortened. According to the data obtained by the double labelling technique a shortening of the DNA synthesis time was not found in vitro. Treatment with a dithranol-salicylic acid (10%)-petrolatum ointment (DSP) normalized the cell cycle in accordance with the degree of clinical improvement. The findings seem to indicate that DSP has an effect on the DNA-synthesis.

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Zusammenfassung Autoradiographische in vitro-Untersuchungen gesunder und psoriatisch veränderter Haut mit dem Doppelmarkierungsverfahren (1 µC C-14-Thymidin und 10 µC H-3-Thymidin) ergaben bei unbehandelter psoriatischer Haut einen entsprechend der gesteigerten Proliferationsaktivität auf durchschnittlich 8,83% erhöhten Thymidinmarkierungsindex. Die Generationszeit war verkürzt. Unter der durchgeführten Dithranol-Saliclysäure (10%)-Vaseline-Behandlung (DSP) kam es entsprechend dem klinischen Verlauf zu einer Normalisierung des Markierungsindex und zu einer Verlängerung bzw. Normalisierung der Dauer des Zellcyclus. Nach den erhaltenen Ergebnissen scheint ein Einfluß der Dithranol-Salbe auf die DNS-Synthese zu bestehen.

     

Light and electron microscopic differentiation of amyloid and colloid or hyaline bodies.

Hyaline or colloid bodies (Civatte bodies) and amyloid are sometimes confused because of their similar appearance under the light microscope. A differentiation can be made by histochemical means (DMAB-Nitrite method) and by fluorescence or polarization microscopy. At the ultrastructural level hyaline or colloid bodies as well as amyloid exhibit a fibrillar structure, but can be differentiated by the diameter and arrangement of fibrils and the localization of the aggregations. A clearcut differentiation between hyaline or colloid bodies and amyloid seems of great importance in any dicussion of the epidermal origin of amyloid and the classification of fibrillar aggregations associated with skin tumours.     

Differential staining of skin-limited amyloid and colloid bodies with immunofluorescence after pretreatments

We examined whether immunoglobulin (Ig) and complement (C) components of amyloid and colloid bodies were inherent parts of these substances or were present due to nonspecific absorption only. In direct immunofluorescence (IF) studies without pretreatment, skin-limited and systemic amyloid and colloid bodies in all cases showed positive staining for Ig or C. When these sections were pretreated with 0.1 M glycine buffer (pH 7.2) or 0.05% Tween-20 solution, Ig and C in skin-limited amyloid deposits were negative or weakly positive. In contrast, positive fluorescence of colloid bodies and systemic amyloid masses was not influenced by pretreatment. Existence of amyloid masses before and after pretreatment were confirmed by Thioflavin-T and Dylon stains. In addition, pretreatment did not alter disulfide bonds by DACM staining or the reactivities of amyloid with monoclonal antikeratin antibody EKH4. These results suggest that skin-limited amyloid can be differentiated from systemic amyloid or colloid bodies by these methods. We can infer from the present studies that most of the Ig and C in skin-limited amyloid masses are a result of nonspecific absorption due to penetration of serum, which is different from Ig in systemic amyloid and colloid bodies in as much as in these conditions immunobinding is specific.     

Carcinosarcoma of the skin: Immunohistochemical and electron microscopic observations

A rapidly growing, hemorrhagic, exophytic tumor on the upper back of a 44-year-old male patient was investigated. Histological, immunohistochemical, and electron microscopic studies revealed both basal cell carcinoma-like and spindle cell sarcoma-like structures intermingled in the same tumor. Clinical consequences to this patient were mainly dependent on the sarcomatous element.     

Electron microscopic microanalysis of prickle cell carcinoma, basaloma, malignant melanoma and normal skin

EMMA has been used in Dermatology since 10 years. In 1981, Fisher established the Cu/Zn index as a parameter for the prognosis of malignant melanoma. We tested the EMMA technique as a means to determine the Cu/Zn index in basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and normal skin. Our preliminary conclusions are: EMMA may be useful to determine the Cu/Zn index in skin tumors; it is possible to obtain useful data from tumors already fixed in paraffin; (c) the highest Cu/Zn index was found in normal skin, the lowest one in malignant melanoma.     

Comparison of human skin irritation patch test data with in vitro skin irritation assays and animal data

Background: Efforts to replace the rabbit skin irritation test have been underway for many years, encouraged by the EU Cosmetics Directive and REACH. Recently various in vitro tests have been developed, evaluated and validated. Objective: A key difficulty in confirming the validity of in vitro methods is that animal data are scarce and of limited utility for prediction of human effects, which adversely impacts their acceptance. This study examines whether in vivo or in vitro data most accurately predicted human effects. Methods: Using the 4‐hr human patch test (HPT) we examined a number of chemicals whose EU classification of skin irritancy is known to be borderline, or where in vitro methods provided conflicting results. Results: Of the 16 chemicals classified as irritants in the rabbit, only five substances were found to be significantly irritating to human skin. Concordance of the rabbit test with the 4‐hr HPT was only 56%, whereas concordance of human epidermis models with human data was 76% (EpiDerm) and 70% (EPISKIN). Conclusions: The results confirm observations that rabbits overpredict skin effects in humans. Therefore, when validating in vitro methods, all available information, including human data, should be taken into account before making conclusions about their predictive capacity.     

Fibrinoid necrosis and downward motion of colloid bodies in lichen planus (apoptosis).

Fibrinoid necrosis which in previous investigations was demonstrated in the epithelial cells of the skin and of the liver in certain disorders, may also appear in the colloid bodies in lichen planus. Trichrome stainings were positive for fibrinoid, staining reactions with haematoxylin variants indicated the presence of keratin and precursors, and investigations in Wood's light permitted conclusions concerning the appearance of mixed proteins, of which keratofibrinoid seems to be the most important. Circulatory disturbances are emphasized as having an important role. The colloid bodies are extruded from the epidermis, according to the observations of Kerr et al., following the rules of apoptosis.     

Electron microscopic observations on the lesions of herpes zoster with topical application of interferon

The lesions of herpes zoster in three patients were investigated electron microscopically before and after topical application of interferon. In the blister, on the 5th to 7th day after its formation, the following were seen: acantholytic cells with virus particles in the nucleus and cytoplasm, multinucleated cells derived from keratinocytes, edematous and degenerated keratinocytes containing virus particles and tonofibrillar materials, macrophages with many large vacuoles, neutrophils, lymphocytes and Langerhans's cells. After the first application of interferon, the findings for keratinocytes were the same as those of before application and keratinocytes were frequently found adjacent to macrophages. The macrophages were large and had numerons large vacuoles in the cytoplasm. After the second application of interferon, virus particles were often seen in the vacuoles of the macrophages in comparison with that before application. In the cytoplasm of macrophages, acantholytic keratinocytes and tonofibrillar materials were phagocytized. Many virus particles were seen in the vacuoles of some acantholytic keratinocytes. It was concluded from these findings that the macrophages accelerated the phagocytotic activity of the virus particles.     

白癜风皮损边缘黑素细胞线粒体超微结构的电镜观察

【摘要】 目的 探讨白癜风患者皮损边缘黑素细胞线粒体结构的变化。方法 在透射电镜下观察健康对照、进展期白癜风及稳定期白癜风患者皮损边缘黑素细胞形态,体视学方法测量线粒体体密度（Vv）、表面积密度（Sv）、数密度（Nv）等参数。结果 健康对照组黑素细胞可见大量黑素小体（28.57 ± 3.21）,以Ⅲ、Ⅳ期为主,线粒体规则分布在细胞内,结构正常、嵴密集,部分细胞胞质内可见自噬小体。进展期和稳定期白癜风黑素细胞内黑素小体数量减少,单位细胞内黑素小体数量分别为22 ± 6.16和17.43 ± 6.24,其中,Ⅲ期黑素小体显著减少,线粒体大小不一、形态多样,大部分线粒体明显肿胀,嵴模糊、排列紊乱甚至断裂,呈空泡状改变,未见线粒体自噬现象。线粒体形态结构定量研究显示,健康对照组Nv、Vv、Sv分别为（7.194 ± 1.434） μm－3、（4.8 ± 1.2）%、（2.42 ± 0.86） μm－1;进展期白癜风组Nv、Vv、Sv分别为（4.055 ± 0.906） μm－3、（7.4 ± 2.1）%、（3.58 ± 1.15） μm－1;稳定期白癜风组Nv、Vv、Sv分别为（5.311 ± 0.873） μm－3、（6.5 ± 1.4）%和（2.82 ± 0.94） μm－1,组间差异有统计学意义（P ＜ 0.05）。结论 白癜风皮损边缘黑素细胞线粒体受损,且进展期损伤程度大于稳定期。 【关键词】 白癜风; 黑素细胞; 线粒体; 显微镜检查,电子,透射