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The measurement of the rate of desquamation is an important parameter for epidermal cell kinetic considerations. In order to obtain such information, we have compared 2 existing techniques with a new one and with a modification of a little-used technique for determining the rate of cell loss from the stratum corneum. We have also studied regional and age variations in desquamation in normal skin. The results of the studies performed show there was a strong positive correlation between the "chamber" technique (which measures passive desquamation) and the "scrub" technique (measuring forced desquamation). There was similar strong negative correlation for the "scrub" technique and the dansyl chloride fluorescence method which measures stratum corneum renewal. [ABSTRACT FROM AUTHOR]

Measurement of intracorneal cohesion in vivo should provide quantitative information concerning the process of desquamation. In this investigation three techniques have been employed to measure the internal binding forces within the stratum corneum in vivo. The first technique, cohesography, directly measures the force required to remove stratum corneum of partial thickness from a known area of skin. Sex and site differences were detected using this method. A second technique employs a surfometer to measure the surface contours of the internal face of skin surface biopsies. Quantitative assessment of surfometer tracings reflects both internal structure of stratum corneum and its cohesive property. Positive correlations were found using these two techniques on the forearms of 16 normal subjects. A scrub technique has also been used which can deliver a controllable and measurable stimulus to the skin surface to release corneocytes. Counting the number of corneocytes released provides a further measure of internal cohesion of the stratum corneum but the results did not correlate with the other two techniques. It is suggested that the use of all three techniques might provide a profile of the cohesive property of the stratum corneum. [ABSTRACT FROM AUTHOR]

Two in vivo techniques which are rapid, inexpensive, and reproducible have been investigated. The first is a standardized radiological (xerographic) technique which we have shown is capable of detecting small degrees of dermal atrophy after the application of topical corticosteroid preparations for only one month. The second technique employs the Harpenden Skinfold Caliper used in an unconventional manner so as to exclude subcutaneous fat. We have shown that this too is capable of detecting dermal atrophy from the application of topical corticosteroids and that there is a strong correlation between the two techniques (r = 0.82, p < 0.001). Histometric techniques, on the other hand, give inaccurate and erroneous results for dermal thickness. [ABSTRACT FROM AUTHOR]

Scales from patients with psoriasis sehorrheic dermatitis, and pityriasis rubra pilaris characteristically have microvilli on their surface when examined by scanning electron microscopy. The experiments reported here were designed to investigate the relationships between the development of parakeratotic scale, the appearance of the scale with scanning electron microscopy, and the proliferative state of the epidermis producing the scale. The villous pattern appeared in scale taken from areas that had developed a high mitotic index and appeared to be related to the proliferative state of the epidermis as well as to the appearance of parakeratosis. A " ridge" pattern was found in some specimens examined and this was thought to represent an intermediary stage between the normal pattern and the villous pattern of the hyperproliferative epidermis. [ABSTRACT FROM AUTHOR]

The effects of 0.5% triamcinolone under occlusion on adult human epidermis for short periods of time has been examined in 10 subjects. An in vitro method was used employing thin sheets of skin removed with a Castroviejo keratotome. Treated skin was found to have a decreased uptake of tritiated thymidine but no consistent effect was found on cytidine, proline or histidine incorporation although occlusion by itself might cause increased cytidine incorporation. [ABSTRACT FROM AUTHOR]

Epidermal dimensions, replication, and anabolic activity have been studied before and after treatment in 10 patients with thyrotoxicosis and 7 patients with hypothyroidism. Following treatment of thyrotoxicosis there was a significant decrease in epidermal thickness, and also in cell replication as measured by an autoradiographic labeling index technique. The rates of anabolic activity in the epidermis, as estimated by measuring the rates of incorporation of tritiated precursor compounds, were significantly reduced after treatment in the thyrotoxic group. There were increases in these same measurements in the hypothyroid group following treatment although their magnitude was not as great as that seen after treatment of thyrotoxicosis. There was a significant positive correlation between serum triiodothyronine and epidermal thickness, labeling index and proline incorporation, but no correlation could be detected between serum thyroxine iodine and any of the epidermal measurements. These finding indicates that the epidermis changes in structure and activity in thyroid disease, and than the changes are rapidly reversible. Furthermore, the correlations we have found suggest that the receptors for thyroid hormone in human skin are specific for triiodothyronine. [ABSTRACT FROM AUTHOR]

The article discusses the clinical evaluation of patients with skin disease in 1979. There appears to be a communication barrier between researchers and clinicians which is not improving. With rare exception, patients with skin disease are managed in much the same way as they were 50 years ago. This applies particularly to the diagnosis and continuous assessment of the chronic scaling dermatoses. The clinical diagnosis of psoriasis is hardly sufficient guidance for treatment and/or prognosis. Rarely an attempt is made to estimate the intensity of the disease by estimating its extent and its severity. Yet intensity may be the most important determinant as to treatment and outcome.

The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.

Dermal collagen fiber bundles (DCFB) are the major constructional element in the dermis. Although degenerative alterations of DCFB have been reported in chronologically aged skin, changes in photodamaged skin have not been fully investigated. We report ultrastructural alterations of DCFB, and their relation to skin elasticity using photodamaged human skin and UV-irradiated hairless mouse skin. The degree to which DCFB were intact and closely packed was evaluated and scored blindly. Exposed skin (outer forearm) exhibited marked ultrastructural degeneration. In UV-irradiated hairless mouse skin, the intact ultrastructural appearance of DCFB was gradually lost with increasing UV dosage; however, marked alterations in DCFB ultrastructure were absent in either human inner upper arm (unexposed) skin or nonirradiated age-matched control mouse skin. Skin mechanical properties were measured using a Cutometer SEM 474 suction extensometer, recording Ue* immediate deformation, Uv* viscous deformation, Uf* final deformation, and Ur* immediate contraction, all normalized for skin thickness. Uf*, Ue*, Uv*, and Ur/Uf were significantly decreased in exposed compared with unexposed skin. Significant positive correlations between degenerative alterations of DCFB and the decrease in Uf*, Ue*, and Uv* were seen. Changes of "% area of wrinkles" in UV-irradiated mouse skin was significantly correlated with degenerative changes of DCFB. Based on these results, we confirm observations made by others that chronic photodamage may have more severe effects on degeneration of DCFB than that of chronologic aging alone. Furthermore, degeneration of DCFB as detected ultrastructurally may, by its effect on skin elasticity, result in an increase in the appearance of wrinkles.

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin condition with features similar to epidermolytic hyperkeratosis (EH). Clinical symptoms are characterized by mild hyperkeratosis with an acral distribution. Histology shows epidermolysis of upper spinous and granular cells, whereas ultrastructurally, tonofilaments form perinuclear aggregates. IBS has been linked to the type II keratin cluster on chromosome 12q, and K2e mutations have recently been identified in IBS patients. We have studied genomic DNA from two IBS families and in both cases heterozygous point mutations were found in the 2B helical domain of K2e. One family had an established mutation in codon 493 (E493K), whereas the other had an unreported mutation in the adjacent codon (E494K). Both mutations were confirmed by allele-specific PCR. These data reinforce the hypothesis that mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin filament network integrity and provide further evidence for the involvement of K2e mutations in IBS.

Heat shock induces in cells the synthesis of specific proteins called heat-shock proteins. We have compared the induction of these proteins in human keratinocytes, skin fibroblasts, and a human epithelial tumor cell line following exposure to weak and strong inducing agents (heat, cadmium sulphate, and sodium arsenite). The induction of heat shock proteins was measured in cells by one-dimensional gel electrophoresis of [35S] methionine-labeled proteins and by immunofluorescence using a specific HSP72 monoclonal antibody. Both HSP90 and HSP116 were constitutively expressed in these cell types. Exposure of these cells to weak inducing agents such as heat or cadmium sulphate resulted in the synthesis of HSP72 and HSP90, whereas HSP28 and HSP116 synthesis was detected in keratinocytes and fibroblasts following exposure to the strong inducing agent sodium arsenite. In addition, sodium arsenite induced the synthesis of HSP46 in human keratinocytes. Immunofluorescence demonstrated a rapid and reversible accumulation of the 72-kD heat shock protein within the nucleolus of heat-stressed human keratinocytes and fibroblasts.

Although callosities of the plantar skin are common and often disabling, little is known of their pathology or the reasons for their persistence. In this study plantar epidermal structure and cell renewal were investigated in patients with callosities and normal, age-, sex- and site-matched control subjects. Tritiated thymidine autoradiographic labeling indices were increased in the calluses but the dansyl chloride fluorescence clearance time was prolonged, reflecting the increased thickness of the stratum corneum. The number of corneocytes that could be removed from the surface of callosities by a standardized stimulus was considerably increased compared to controls but after adhesive tape stripping no such increase was observed. The density of corneocytes as measured on Percoll gradients was decreased in corneocytes from callus compared to normal plantar skin, and their volume was increased. These observations suggest that there are differences in epidermal differentiation due to an increased rate of epidermal cell production in plantar skin affected by callosity.

Nonionic detergent-soluble (NIDS) proteins from human stratum corneum have been prepared by the combined action of detergent and mechanical stimulation of normal human skin. SDS-polyacrylamide gel electrophoresis studies revealed approximately 15 components falling into the molecular weight ranges of 10,000-15,000, 24,000-37,000, and 44,000-68,000. Immunization of rabbits with this material gave antisera which demonstrated 3 or 4 antigenic components using 2-dimensional immunoelectrophoresis. Studies with 125I-labeled NIDS protein indicated that the main precipitate on 2-dimensional immunoelectrophoresis was associated with SDS-polyacrylamide gel components of molecular weight 15,000 and 30,000. Indirect immunofluorescence studies on human skin sections revealed localization of NIDS protein antigens throughout the suprabasal epidermis but concentrated in the stratum granulosum and stratum corneum. Localization studies using strips of stratum corneum obtained by the skin surface biopsy technique revealed a pericellular type of distribution of the NIDS protein antigens.

After UV irradiation of human skin there is an increase in epidermal and stratum corneum thickness and an increase in the thymidine autoradiographic labeling index. Previously we have demonstrated that persistent exposure to ultraviolet radiation (UVR) alters the distribution and activities of glucose-6-phosphate dehydrogenase (G-6-PDH) and succinic dehydrogenase (SDH) within the epidermis; G-6-PDH activity is increased over the whole epidermis and SDH activity is diminished in the granular cell area but increased in the basal layer. When skin is protected by an efficient sunscreen and irradiated with UVB, there is almost complete inhibition of the erythema normally seen following UVR exposure. In this study we have investigated the cytochemical, cell kinetic, and histometric changes that take place in the epidermis after UVB irradiation, with and without two different types of sunscreen. Some of the histometric and metabolic changes associated with UVB exposure were still evident despite sunscreen protection and the successful blocking of the erythema response. The implications of these findings are discussed together with the use of sunscreens to prevent development of solar damage.

Solar keratoses (SKs) may show basal cell liquefactive degeneration (BLD) and, when extensive, this can result in a superficial resemblance to lichen planus. The frequency of these phenomena and involvement of immune mechanisms in them have been investigated in this study. The prevalence of lichenoid keratosis (LK) was 6.1% in 212 SKs examined retrospectively and 10.7% in 28 examined prospectively. Histologic features were scored on analogue scales and their interrelationships examined. BLD could not be correlated with epidermal atypia, acanthosis, acantholysis, or inflammatory cellular infiltrate; a negative correlation occurred with parakeratosis. Immunoglobulins and/or fibrin and complement were found by immunofluorescence in 78.8% of the 28 specimens examined prospectively. Three LKs showed similar immunofluorescence findings to ordinary SKs. No circulating antibodies to epidermal structures were detected in patients with SKs. It is concluded that (1) no feature of SKs investigated predisposed to lichenoid change, (2) BLD was a frequent feature in SKs whereas full development of LK occurred much less frequently, and (3) immunoprotein deposits were not related to the development of BLD. Clinically, LKs could not be distinguished from ordinary SKs.

The effect of a factor XIII preparation on active epidermal cell migration in vitro has been studied using both floating and attached types of human skin explants in short-term maintenance cultures. In both types of experiment the factor XIII preparation proved to have an inhibitory effect on epidermal cell migration in a dose-dependent fashion. This effect was shown to be independent of both the presence of fibrin and the concentration of calcium ion in the medium. The preparation also showed inhibition of the proliferation of epidermal cells in cell culture.

The epidermal metabolic activity of a patient with a marked generalized ichthyosis associated with heredopathia atactica polyneuritiformis has been investigated. Both the in vivo labeling index and the in vitro rates of incorporation of radioactively labeled thymidine, proline, histidine and acetate were increased relative to normal indicating a high rate of epidermopoiesis. Thin-layer chromatographic analysis of 14C-acetate containing lipid extracts revealed qualitative changes compared with normal. In particular, altered proportions of radioactivities were incorporated into the triglyceride and phospholipid moieties. However, as abnormal patterns of lipogenesis are also seen in autosomal dominant ichthyosis, these changes are probably a reflection of disordered keratinization.

Damage to the microvasculature occurs commonly in autoimmune diseases affecting the skin. There has been little investigation of immune mechanisms other than immune complex deposition as a major cause of microvascular damage. We have investigated the potential of antibody-dependent cellular cytotoxicity (ADCC) to cause vascular destruction in an in vitro model consisting of human dermal microvascular endothelial cells to which were added antibody and leukocytes. Severe damage was induced by antibody and lymphocytes. Monocytes or neutrophils were not able to mediate cytotoxicity although activated neutrophils caused endothelial detachment. The cytotoxic cells were OKT3-, Leu 11+ and were identified as K cells. ADCC was not inhibited by human serum or aggregated IgG. These results imply that ADCC may have a role in causing the vascular destruction observed in some human autoimmune skin diseases.

We have demonstrated previously that following UVB irradiation to normal volunteers there is an increase in epidermal and stratum corneum thickness and an increase in the thymidine autoradiographic labeling index. These changes are coupled with alterations in epidermal glucose-6-phosphate dehydrogenase and succinic dehydrogenase activities, despite the absence of erythema clinically. The use of a sunscreen did not completely prevent these changes. In this study, we have examined the effects of repeated irradiation of human skin with either UVB or UVA alone in order to compare the changes produced in the epidermis and to ascertain whether UVA irradiation could cause these. Irradiation with either UVB or UVA alone was found to increase the mean epidermal thickness, the mean stratum corneum thickness, and mean keratinocyte height significantly. Glucose-6-phosphate dehydrogenase activity was significantly increased throughout the epidermis, and succinic dehydrogenase activity was significantly decreased. The autoradiographic labeling index was significantly increased following UVB irradiation but not following UVA irradiation. These results demonstrate that UVA alone can have a direct effect on epidermal morphology and metabolism, suggesting that protection of skin from UV radiation should include adequate protection from UVA.

Biochemical changes taking place in desmosomes during differentiation have been studied. Bovine muzzle epidermis was sliced horizontally into 6 layers, 0.2 mm thick, and desmosomes were isolated from each layer. These were then analyzed by polyacrylamide gel electrophoresis. The electrophoretic patterns of desmosomal proteins from the 6 layers were found to be qualitatively similar to each other, but there was an increase in the ratio of the amount of 150 kD glycoprotein (desmoglein I) relative to 240 and 210 kD proteins (desmoplakins) in the upper layers of the epidermis. This finding was supported by the similar increase observed in electrophoretic patterns of proteins extracted directly from each layer of the epidermis in electrophoretic sample buffer. In order to study the fate of desmosomal components in the stratum corneum, serial skin surface biopsies were stained with antisera against desmosomal components using indirect immunofluorescence techniques. This experiment showed that desmosomal proteins and glycoproteins persist in the stratum corneum but quantitatively decrease in the outer layers. This decrease may play a significant role in desquamation.

A pulsed ultrasound technique was shown to have a high degree of correlation with the established xeroradiographic method for the determination of dermal thickness both in normal skin and corticosteroid treated skin, although xeroradiography consistently gave a higher value than ultrasound. Using the pulsed ultrasound technique, an early onset of dermal thinning could be detected 2 days following treatment with creams containing 0.05% clobetasol propionate and 0.1% beta-methasone 17-valerate. The amount of dermal thinning produced by the clobetasol propionate preparation was significantly greater than that produced by cream base, clobetasone butyrate 0.05% cream and hydrocortisone 1% cream as determined by both techniques. The pulsed ultrasound technique is an accurate, noninvasive and safe method for determining dermal thickness.