PubMed HealthSearch

Biomedical subjects

R Wrench

Publications and source records attributed to R Wrench.

11 recordsLinked to original sources

Antibodies to orthokeratotic keratinocytes in monitoring the drug-induced inhibition of parakeratotic differentiation in adult and infant mice.

Parakeratosis (PK) is a common feature of the abnormal epidermis in several disorders of keratinization. Tar phenols, retinoids and steroids which cause the inhibition of PK and the restoration of orthokeratosis (OK) are used for treating psoriasiform conditions. In this work, we studied two experimental models of the drug-induced inhibition of PK: (1) the suppression of the normal development of PK in the infant mouse tail and (2) the OK conversion of established PK in the adult tail. Two markers of OK were studied: the histological evaluation of the granular layer and the expression of cytoplasmic antigens linked to OK differentiation. It was demonstrated that high-boiling tar phenols cause a more potent inhibition of PK than betamethasone valerate. Most importantly, immunofluorescence showed that the switch to OK differentiation was located in the cells situated in a suprabasal position. The use of these immunological markers to investigate and anti-parakeratotic mechanisms has revealed that these drugs act at stages of keratinocyte differentiation which are distinct from those previously suggested.

Acids

Expression of cytoplasmic antigens linked to orthokeratosis during the development of parakeratosis in newborn mouse tail epidermis.

An unusual example of two different types of epidermal differentiation occurs side by side in adult mouse tail. The neonate shows only orthokeratotic differentiation, but develops parakeratotic scales in precise patterns over the first two weeks of life, retaining orthokeratotic differentiation at the necks of hair follicles. Certain human IgG antibodies from patients receiving bone marrow transplants bind only to cytoplasmic components of orthokeratotic epithelium. As markers of orthokeratotic differentiation in indirect immunofluorescent studies, these antibodies allowed the timing and location of the change in epidermal differentiation. A specific loss of 'orthokertotic' antigens in the natural switch from orthokeratosis to parakeratosis was demonstrated. The sequence of the orthokeratotic antigens disappearance suggested that the switch to parakeratotic differentiation occurred at a supra-basal level.

Animals

Langerhans cell.

Explore the source record for details and available documents.

Animals

Scale prophylaxis. A new antiparakeratotic assay.

This article describes a new animal model for the evaluation of drugs that may prevent the development of parakeratosis. The advantages of this model are simplicity, economy, and the opportunity to observe the possible occurrence of acute systemic toxic reactions. High-boiling coal tar acids (phenols), vitamin A (retinyl acetate), and hydrocortisone butyrate (Locoid) were assayed. Only tar phenols consistently prevented scale development. Vitamin A was not properly screened because of toxic effects that resulted in premature termination of the experiment.

Animals

Epidermal thinning: evaluation of commercial corticosteroids.

Epidermal thinning of mouse tail skin was compared for commercial preparations of clobetasol propionate (Dermovate), clobetasone butyrate (Eumovate), fluocinonide (Metosyn), and hydrocortisone butyrate (Locoid). The thickness measurements were ranked with those for hydrocortisone (1%), betamethasone valerate (Betnovate), triamcinolone acetonide (Ledercort), fluocinolone acetonide (Synlar), and prednisolone stearoylglycolate (Sinistrone) obtained in a previous study (Spearman and Jarrett, 1975). All steroids caused epidermal thinning, except clobetasone butyrate. Some cream and ointment vehicles were also assayed. Epidermal thickening was caused by the cream and ointment vehicles used for Eumovate and also by the cream employed for Locoid formulation.

Administration, Topical

Granular layer induction following the topical application of proliferating agents.

Evidence is provided for a possible dermal influence on the epidermis. Topical vitamin A stimulates a number of dermal cells with different enzyme reactions, and these invade the epidermis at about the time a granular layer is induced in mouse tail scale epidermis. N-hexadecane also induced a granular layer formation in the tail scale epidermis but the application of this agent only results in the invasion of the epidermis by non-specific esterase cells. These non-specific esterase cells are present in the follicular zone where a granular layer is usually present. It appears that dendritic cells may be responsible for the formation of a granular layer and that these cells in some way influence the keratinocytes to discharge their lyosomal enzymes and thus form a granular layer. It appears unlikely that the dendritic cells actually contribute their own acid hydrolases to the cell cytolysis necessary for the production of granular layer.

Acid Phosphatase

Evaluation of coal tar fractions for use in psoriasiform diseases using the mouse tail test. (I) High and low temperature tars and their constituents.

'High' and 'low' temperature tars were evaluated on parakeratotic mouse tail skin, which was used as a model for the psoriatic keratinization process. The skin was examined histologically for signs of induced granular layers in previously scaly areas; epidermal thicknesses were also measured. It appears that the acidic (phenolic) fractions of coal tars induce granular layers and cause epidermal thickening, whereas neutral constituents alone only cause thickening. It is suggested that tar acids should be further investigated for anti-psoriatic activity.

Animals

Evaluation of coal tar fractions for use in psoriasiform diseases using the mouse tail test. III. High boiling tar oil acids.

Twelve phenolic fractions of creosote and anthracene oils derived from a high temperature tar were applied in an ointment base to mouse tail skin. After treatment with the higher boiling acids, formerly parakeratotic scale areas underwent granular layer induction and 'basket-weave' keratin was produced. Changes in distribution of acid phosphatase and in horny layer fluorescence were consistent with the conversion to an orthokeratotic state. It is suggested that some of these phenols may be of value in the treatment of chronic psoriasis.

Acid Phosphatase