Cornified envelopes in congenital disorders of keratinization

A morphological and biochemical analysis was made of cornified envelopes isolated from patients with different congenital disorders. Nomarski contrast microscopy of the envelopes showed that their morphology was not greatly altered in several types of keratoderma and parapsoriasis, but it was grossly modified in ichthyotic disorders. The various types of ichthyoses, keratoderma palmoplantare, KID syndrome and parapsoriasis showed, after cyanogen-bromide cleavage, peptide patterns similar to those obtained from healthy subjects. In contrast, envelopes from patients with Darier's disease, congenital pachyonychia and erythrokeratoderma variabilis showed markedly different peptide patterns.     

Cell kinetics in skin disorders with disturbed keratinization.

A relatively simple immunohistochemical method was developed and used on cryostat sections. The monoclonal antibody Ki67 was used as marker for actively cycling cells and Pab601 for germinative cells. Counts were expressed as Ki67- or Pab601-positive cells/mm. In order to improve our understanding of the pathogenetic mechanisms in skin disorders with disturbed keratinization we have measured cell kinetic values in dyskeratosis follicularis, pemphigus benigna familiaris chronica, autosomal dominant ichthyosis vulgaris, X-linked recessive ichthyosis, atopic dermatitis and psoriasis and compared them with previous values derived with autoradiography using tritiated thymidine. The results showed that microscopical acanthosis is related to an increase of the germinative population, while the increased epidermal turnover is associated with increased numbers of cycling cells. The cell kinetic changes seem to be all secondary except in psoriasis where a dysregulation in the epidermal growth may cause the epidermal changes. This simple method allows quick evaluation of drug efficacy which might be useful in atopic dermatitis and psoriasis.     

Molecular mechanisms of genetic disorders of keratinization.

An attempt is made to organize our current knowledge about genetically determined disorders of keratinized tissue, which primarily affect the epidermal structural proteins. Type I defects are those involving a change in a single amino acid and are analogous to sickle cell anemia. Type II defects are associated with abnormal retention of a normal structural protein intermediate. Type III defects are related to alterations in the normal post-translational cross-linking seen in keratinized tissues. Type IV defects are associated with altered proportions of fibrous proteins and are analogous to thalassemia. In type V defects, primary genetic disorders of other tissues profoundly affect keratinization in a secondary fashion. Examples from genetic disorders of the hair and epidermis are used to build this conceptual scheme.     

Involucrin expression in keratinization disorders of the skin--a preliminary study

We have studied the expression of involucrin in a variety of keratinization disorders, mostly of genetic origin using an avidin-biotin-peroxidase technique. In normal human epidermis 25% of the living epidermis was labelled. The diseases studied fell into two groups. Diseases with greatly increased involucrin staining including collodion baby (38%), Darier's disease (49%), Flegel's disease (56%), erythrokeratoderma variabilis (60%), epidermal naevus with epidermolytic hyperkeratosis (45%) and congenital bullous (58%) and non-bullous (44%) ichythyosiform erythroderma; and diseases with normal or slightly increased staining, including ichthyosis vulgaris (27%), X-linked ichthyosis (25%), confluent and reticulate papillomatosis (27%) and simple epidermal naevus (28%). These results demonstrate that involucrin expression is altered in some keratinization disorders and suggest that in such conditions cellular functions other than keratin metabolism are also affected.     

Fractionation and characterization of the human epidermal stratum corneum in keratinization disorders

Stratum corneum obtained from persons with a variety of keratinization disorders was fractionated into keratin fibers, water soluble proteins and cell membranes. SDS gel electrophoresis was used to study the keratin fibrous and water soluble fractions, and amino-acid analysis was employed for the membraneous fractions. Electrophoresis of the keratin fibrous fractions obtained from cases of epidermolytic hyperkeratosis and psoriasis vulgaris revealed a significant decrease in the 55,000 dalton subunit was observed. Similarly, a reduction of the 73,000 dalton subunit was observed in samples from a case of keratoma climacterium. Minor variations from the normal were recorded from cases of ichthyosis vulgaris, lamellar ichthyosis, and palmoplantar keratosis (which included a Vörner and punctate type, and one with corneal dystrophy). The water soluble fractions from all the cases of keratinization disorders studied exhibited different densities for the individual polypeptides after electrophoresis. The most impressive changes were revealed by amino-acid analysis of the membraneous fractions. Half-cystine and proline were uniformly reduced in cases of ichthyosis vulgaris, lamellar ichthyosis, punctate palmo-plantar keratosis, palmoplantar keratosis with corneal dystrophy and keratoma climacterium, and the presence of an abnormal amino-acid, ornithine, was characteristic of epidermolytic hyperkeratosis and psoriasis vulgaris.