Mcjm Dejong

Eczematous (irritant and allergic) reactions of the skin and barrier function as determined by water vapour loss

The aim of this study was to compare the influence of irritant and allergic reactions on the barrier function of the skin and to correlate disturbances of barrier function with macroscopically visible changes.

Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. II. Influence of season

Many atopic dermatitis (AD) patients have exacerbations of their skin disease in winter. These exacerbations may be caused by non‐immunological ‘non‐specific’ factors, such as low sun exposure and low temperature. To date, the influence of season on non‐specific skin reactivity in AD has not been studied. The aim of the present investigation was to assess the influence of season on two skin parameters which may be used as quantitative measures of non‐specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous irritant (sodium lauryl sulphate, SLS) exposure, and (ii) weal and flare responses to intracutaneous injection of bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin). Four of 16 AD patients had dermatitis which was more severe in November than in July. Susceptibility to SLS was increased in November, both in AD patients and in control subjects. AD patients were more susceptible to SLS than control subjects in both July and November, Pre‐exposure barrier function and skin hydration were reduced in November. The increased irritant susceptibility in November may be attributed to reduced barrier function, reduced skin hydration, and/or absence of the beneficial effects of ultraviolet light on cellular targets beneath the stratum corneurn, Flare responses to codeine, methacholine, substance P and trypsin were also increased in November compared with July, especially in AD patients. However, smaller Hares were observed in AD patients than in control subjects, in both July and November, Flare values were negatively correlated with dermatitis severity, probably because of down‐regulation. Weal responses did not show a clear seasonal variation. Hence, susceptibility to epicutaneous irritants and reactivity to intracutaneousty injected bioactive agents are parameters which may be used to monitor season dependent changes in non‐specific skin reactivity.

Protease activities in the spicule venom of Euproctis caterpillars.

The spicule venoms of Euproctis chrysorrhoea and Euproctis subflava were investigated for their capacity to hydrolyze chromogenic tripeptide substrates with selective affinities for various serine proteases. Seven substrates were assayed with affinities for trypsin and thrombin, trypsin and urokinase, serine proteases, chymotrypsin, glandular kallikrein, plasma kallikrein and plasmin. Venom material has a broad spectrum of affinities for the substrates with relative high plasma kallikrein activities. In E. chrysorrhoea venom, trypsin-like activities predominated, whereas E. subflava venom hydrolyzed, in preference, substrates with an affinity for chymotrypsin. The venoms were fractionated on Sephadex G-100, leading to three fractions, all having serine protease activity. The ratios of substrate specificities were markedly different, indicating that in both caterpillar venom preparations at least two separate serine proteases are present. In addition, in human plasma, inhibitor activity could be detected to the kallikrein activity of E. chrysorrhoea, but not of E. subflava. The trypsin-like activity was not inhibited by human plasma. These and earlier studies warrant the assumption that serine proteases, particularly kallikrein, are major factors in the elicitation of clinical symptoms observed after contact with caterpillar spicules.

Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. I. Influence of disease severity

The two main pathogenetic characteristics of atopic dermatitis (AD) are: (i) antigen‐dependent ‘specific’ reactivity, and (ii) altered non‐immimological ‘non‐specific’ reactivity. Our understanding of the role of non‐specific reactivity is hampered by the fact that methods available for its quantification are limited. The aim of the present study was to assess the usefulness of two parameters as quantitative measures of non‐specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous exposure to an irritant (sodium lauryl sulphate, SLS), assessed by visual scoring and transepidermal water loss(TEWL) measurement, and (ii) reactivity to intracutaneously injected bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin), assessed by measurement of weal and flare size. These two parameters were tested in a group of AD patients, subdivided according to the severity of their dermatitis, and a control group. The visual score and TEWL after SLS exposure tended to be higher in the AD group than in the control group. Furthermore, visual score and post‐exposure TEWL were positively correlated with the dermatitis severity score. Weal size following injection of codeine, histamine and substance P, and flare size following injection of all agents, except methacholine, were significantly lower in the AD group than in the control group. Negative correlations were found between weal and flare sizes and the dermatitis severity score. These findings can be explained by down‐regulation of structures involved in weal and flare reactions. In conclusion, we propose that epicutaneous irritant susceptibility and reactivity to intracutaneous bioactive agents may be useful indicators of non‐specific skin reactivity in AD.

A COMPARATIVE-STUDY OF THE SPICULE VENOM OF EUPROCTIS CATERPILLARS

Caterpillar spicule venoms were extracted and studied for the following activities: arginine ester (BAEE) hydrolase, tyrosine ester (ATEE) hydrolase, protease (casein digestion) and phospholipase A (indirect hemolytic activity). Crude spicule venom of E. chrysorrhoea preferably hydrolyzed BAEE in contrast to E. subflava venom, which hydrolyzed ATEE in preference to BAEE. This difference was confirmed by Sephadex G-100 elution profiles. The esterase activity in E. chrysorrhoea venom was separated into two peaks with average mol. wts. of 96,000 and 44,000. The first peak demonstrated optimal BAEE hydrolysis at pH 8.6 and 37 degrees C, whereas the second peak optimally hydrolyzed both BAEE and ATEE at pH 8.45 and pH 8.6 at 45 degrees C respectively. The esterase activity in E. subflava venom was separated into two peaks with average mol. wts of 63,000 and 32,000 showing optimal hydrolysis of BAEE at pH 8.9 and 37 degrees C, and of ATEE at pH 7.75 and pH 8.5 at 40 degrees C. The column fractions showed comparable proteolytic activity, irrespective of differences between their esterase activities. The presence of phospholipase A (PLA) enzyme in crude spicule venom of both species was evident from their indirect hemolytic activities. The PLA activity eluted with the void volume and seems to be associated with some high molecular weight protein. Under the assay conditions used, E. subflava venom contained 50-100 times less PLA activity than E. chrysorrhoea venom.

EPIDERMODYSPLASIA VERRUCIFORMIS - LANGERHANS CELLS, IMMUNOLOGICAL EFFECT OF RETINOID TREATMENT AND CYTOGENETICS

SummaryA case study is presented of a 44-year-old negroid male with epidermodysplasia verruciformis (EV), cutaneous carcinomas, and impaired cell-mediated immunity (CMI), infected with human papillomavirus type 8 and 17. Analysis was made of (a) T6+and HLA-DR+Langerhans cells (LCs) by immunoperoxidase staining in lesional and clinically normal skin before and during retinoid treatment, (b) the effect of retinoid treatment on CMI in vivo and in vitro, and (c) cytogenetic aspects related to chromosomal instability. The results showed the virtual absence of T6+and HLA-DR+LCs in koilocytic areas of epidermis involved with EV. Light-exposed, clinically normal skin also demonstrated microscopic EV lesions largely devoid of T6+and HLA-DR+LCs. Retinoid treatment with etretinate (Ro 10-9359) appeared both to increase the CMI response in vitro to T-cell mitogens and to influence the in situ pattern of T6+and HLA-DR+LCs. The cytogenetic study did not show evidence of spontaneous or UV-induced chromosomal instability.

DOES DNCB THERAPY POTENTIATE EPICUTANEOUS SENSITIZATION TO NON-RELATED CONTACT ALLERGENS

Nineteen patients suffering from alopecia areata were treated weekly with both 2,4‐dinitro‐chlorobenzene (DNCB) and dithranol applied to separate areas on the scalp.

IMMUNOFLUORESCENT LOCALIZATION OF ANTITHROMBIN-III IN HUMAN-SKIN

The presence in clinically normal human skin of the proteinase inhibitor antithrombin III (ATIII) has been studied by indirect immunofluorescence (IF) microscopy. The IF staining reaction for ATIII in skin tissue sections was most prominent in vessel wall structures. The simultaneous use of fluorescent staining techniques for nuclear DNA revealed that ATIII antigen tends to be concentrated at the level of the vascular cndothelial basement membrane, in contrast to the typical intra‐endothelial distribution of Factor VIII related antigen.