Reversal by retinoids of keratinization induced by benzo[alpha]pyrene in normal hamster tracheal explants: comparison with the assay involving organ culture of tracheas from vitamin A-deficient hamsters

In a defined culture system for hamster tracheal explants, the activity of 12 different retinoids was evaluated for reversal of keratinization induced by exposure to the carcinogen, benzo[a]pyrene (BP-HTOC assay). The effects of retinoids in this system were compared to those in a defined culture system for tracheal explants from vitamin A-deficient hamsters (standard-HTOC assay). In both assays, all-trans-retinoic acid (RA) and 13-cis-RA were the most active retinoids. For RA and 13-cis-RA, the values of ED₅₀ determined in the BP-HTOC bioassay were 4 × 10⁻¹² and 1 × 10⁻¹¹ M, respectively, whereas the corresponding values in the standard HTOC assay were 2 × 10⁻¹¹ and 3.3 × 10⁻¹⁰ M. For all 12 retinoids, the ED₅₀ values from the BP-HTOC were lower than those from the standard-HTOC assay, and there was also a statistically significant correlation between the rank-ordering of ED₅₀ values from the 2 assays. Among 3 N-(retinoyl)amino acids examined in both assays, N-(retinoyl)leucine was the most active, N-(retinoyl)phenylalanine the least active, and N-(retinoyl)alanine intermediate. Among a novel series of bifunctional retinoic acid analogues, the dicarboxyl derivative was the most active. On the basis of these results, the BP-HTOC assay appears to be one of the most sensitive assays for retinoids yet developed. This assay is an appropriate model for evaluating the chemopreventive potential of new retinoids in vitro.     

Granular layer induction following the topical application of proliferating agents

Summary 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.     

阿维A治疗儿童角化性疾病的研究现状

阿维A为第二代维A酸,是阿维A酯的代谢活性酸,具有较高的生物利用度及较短的半衰期,已广泛治疗各种角化性皮肤病,而这些角化性疾病大多是遗传性疾病。这些疾病主要见于儿童和青少年,因此,阿维A与儿童和青少年角化性疾病有着重要的联系,但阿维A除治疗作用外,该类药物对人类从妊娠到儿童的肝脏、骨骼生长及生殖系统等亦有一定的潜在不良影响,又因为用药经验不足,造成用药时有所顾虑,特别是国内对其在儿童角化性疾病的研究不多。     

Retinoic acid alters the keratinization of cultured rat sublingual keratinocytes in vitro

Summary A multilayered, continuously proliferating keratinocyte cell culture has been produced from rat sublingual epithelium. The rate of growth of the cultures was stable throughout long-term culture. Retinoic acid (3.3 M) inhibited the keratinization of these cultures. Morphological changes included total loss of tonofilaments within 7 days, decrease in desmosomes, an increase in intercellular spaces, absence of thickened plasma membranes, and elongated and more numerous cytoplasmic projections. Exposure to retinoic acid (3.3 M) for 33 days did not affect the growth rates of the cultures, as estimated from the protein and DNA content per flask. Retinoic acid (3.3 M) reduced the polyacrylamide gel electrophoresis protein profile within 3 days of treatment and produced reductions in the incorporation of amino acids into keratins of molecular weights 62,000 and 60,000 within 24 h. All five keratin polypeptides showed a reduced incorporation rate after treatment for 3 days. This inhibition was reversible. Protein synthesis of nonkeratins was not detectably affected by retinoid treatment.     

无毛小鼠不同年龄皮肤结构的比较研究

采用组织学方法对１月龄、２月龄、老龄豫医无毛小鼠皮肤结构进行了比较，结果发现，各年龄段表皮均有一层角化过度的角质层，毛干消失，毛球结构不正常，毛囊被一些角化物质充填。但真皮层差别很大。１月龄皮肤为肉色偏红，切片可见表皮层较厚，真皮内没有包囊；２月龄皮肤为肉色，表皮层较１月龄薄，毛囊腔大，真皮深层及皮下组织内有一些大小不等的包囊；老龄鼠皮肤为淡黄色，头部和体侧形成特别皱纹和褶痕，皮肤脆性大，易撕裂，表皮层薄，角化严重，真皮层被包囊扩张。包囊直径约为２月龄的４倍，内含一些角化物和脂肪样物质     

Hipoqueratosis circunscrita palmar o plantar. Conocimientos y controversias tras 10 años de su descripción

This review of the literature on palmoplantar hypokeratosis, a process that was first indentified only 10 years ago, discusses the current state of our understanding, the therapeutic options available, and the debate about etiology. Forty-four publications reporting 69 cases were found. Palmar or plantar hypokeratosis occurs mainly in women (76.8%) and age at the time of a first visit to a physician ranges from 42 to 84 years. Most cases present between the ages of 51 and 70 years. The majority of patients have had solitary lesions usually located on the right palm, particularly in the regions of the thenar (in 44/79 lesions [55.7%]) or hypothenar eminences (in 11/79 lesions [13.9%]). In only 8 cases was there a history of prior trauma at the site. Studies using polymerase chain reaction techniques to identify human papillomavirus involvement were negative in most cases. These hypokeratotic lesions are localized epidermal depressions formed by an abrupt thinning of the stratum corneum, providing a singular histopathologic feature. This condition can currently be considered a localized keratinization disorder affecting zones where there is a thick stratum corneum. The precipitating cause is unknown and a definitive treatment remains to be found. The mechanism would be the localized failure of a clone of keratinocytes during differentiation toward normal palmoplantar hyperkeratinization.     

Ultrastructural study of the skin in Sjögren — Larsson syndrome

Summary The ichthyosiform skin and the uninvolved skin of a 5-year-old Japanese female with Sjögren — Larsson syndrome were examined by light and electron microscopy to elucidate the keratinization disorder. Light microscopically, the epidermis of the ichthyosiform skin showed acanthosis, papillomatosis and hyperkeratosis. The horny cells had a basket-weave appearance. The granular cell layer was slightly thickened. Slight round cell infiltration and vascular dilatation were seen in the upper dermis. The uninvolved skin was histologically normal. Electron microscopically, in both ichthyosiform and uninolved skin, abnormal lamellar or membranous inclusions were present in the cytoplasm of horny cells of the epidermis. These inclusions appeared to be derived from some of the lamellar bodies and/or abnormal membranous structures found in the cytoplasm of spinous and granular cells. Mitochondria in the epidermal basal cells were more numerous in the ichthyosiform skin than in the uninvolved skin. These findings indicate that, whether the skin is involved or not, the epidermis of the patient with this disorder may always have a structural abnormality, which may be genetically determined. Local environmental factors may play a role in inducing the acanthosis and papillomatosis of the epidermis.     

Prognostic significance of keratinization in squamous cell cancer of uterine cervix: a population based study

Purpose  To determine the influence of keratinization on prognosis in squamous cell cancer (SCC) of the uterine cervix. Methods  Patients with keratinized squamous cell carcinoma (KSCC) and non-keratinized squamous cell carcinoma (NKSCC) of the cervix were identified from the Limited Use SEER database from 1988 to 2004. A subgroup of patients who did not have radiation or surgery formed the basis to study the natural history of the disease. Data were analyzed using Pearson Chi-square, Student’s T tests. Kaplan–Meier and Cox Regression Proportional Hazards survival analysis was conducted in SPSS and SEER-Stat software. Results  The KSCC group had 3,102 and the NKSCC had 3,751 patients with mean age being 51 and 49 years, respectively (P = 0.001). In general, patients with KSCC were more likely to have advanced stage (FIGO III and IV) disease while patients with NKSCC were more likely to have poorly differentiated neoplasms (P < 0.001). The prevalence of lymph node metastasis remained similar in both histology types (P > 0.05). Overall, the 5-year survival in KSCC was 63.4% as compared to 65.3% in the NKSCC group (P = 0.04). Patients treated by surgery had no difference in survival; however, patients treated by radiation had a median survival in KSCC of 33 months (n = 928, 95% CI 27.7–38.3) as compared to 38 months (n = 1,140, 95% CI 32.1–43.8) in NKSCC (P = 0.03). A total of 165 KSCC and 147 NKSCC patients did not receive treatment. Within this subgroup, the median survival was 10 months (95% CI 5.93–14.07) as compared to 28 months (95% CI 17.9–38.0; P = 0.001) respectively for the two cohorts. In multivariate analysis stage, treatment status, nodal metastasis and keratinization were independent predictors of survival (P < 0.05). Conclusion  This is the largest study reporting on the prognostic importance of keratinization in SCC. KSCC may be less radiosensitive and associated with shorter overall survival. Also, in the natural history of the SCC, keratinization signifies striking reduction in survival.     

Bicomponent keratohyalin in normal human ridged skin

Summary Up to now, bicomponent keratohyalin has only been described for rat epithelium and human intraepidermal sweat ducts and fetal nail organ cells. In normal human interductal epidermis, the keratohyalin appears homogeneous, osmiophilic and stellate in shape. Under pathological conditions, bicomponent keratohyalin has been observed in different palmoplantar keratoses and has therefore been thought to be associated with abnormal keratosis. We studied the keratinization process in normal human plantar epidermis, in which keratohyalin was found to exhibit several morphological differences as compared to that seen in non-ridged skin. The most striking feature was seen in upper granular cells, where the keratohyalin granules consisted of two components of differing electron density. The electron-dense component formed the main part of the composite granule and was found in the cytoplasm of lower and upper granular cells. The less-electron-dense component was attached to the main component and appeared in the cytoplasm of upper granular cells, forming the convex contact zone. No intranuclear osmiophilic inclusions were present. The respective electron densities of the two keratohyalin components of ridged skin were obviously different to that of the bicomponent keratohyalin granules seen in the epidermal sweat-duct cells of the same specimen. These findings indicate the presence of at least two different types of keratohyalin proteins in normal human ridged skin. They can be distinguished at the electron-microscope level and differ from the keratohyalin of human non-ridged skin as well as from bicomponent keratohyalin granules derived from human epidermal sweat-duct cells or from rat epithelium.