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PubMedDate not supplied

Integrating stratum-specific likelihood ratios with the analysis of ROC curves.

Data used to construct receiver operating characteristic (ROC) curves and to calculate the area under the curve (ROC AUC) can be used to derive stratum-specific likelihood ratios (SSLRs) with their 95% confidence intervals (95% CIs). The purpose of this study was to determine whether useful information can be obtained by adding SSLRs to the analysis of ROC curves. The authors analyzed four previously reported sets of data: 1) serum creatine kinase (SCK) for diagnosing acute myocardial infarction (AMI) in the coronary care unit (CCU); 2) SCK in the evaluation of chest pain in the emergency center (EC); 3) four predictor variables in the diagnosis of strep throat; and 4) the ordinal assessment of computed tomographic (CT) images. Use of SCK in the CCU produced four strata that had posttest probabilities that were highly discriminating, whereas SCK in the EC resulted in only two strata with limited discriminating ability. In either study the cutpoint at which the SSLR changed from less than to greater than 1.0 was higher than the reported upper normal for the test, thereby quantitating spectrum bias. The maximum number of strata of predictor signs and symptoms for strep throat was three rather than the five used in previous studies. With a larger sample size or pooling, four strata could probably be developed. With CT images, "definitely normal," "probably normal," and "questionable" were collapsed to one negative stratum. "Probably abnormal" became the true "questionable" stratum and "definitely abnormal" was the only positive stratum. The authors conclude that additional useful information is obtained by deriving stratum-specific likelihood ratios as part of the analysis of an ROC curve.

Humans↗
PubMed2003

Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis.

To clarify the functional relevance of sphingomyelin (SM) deacylase to the ceramide deficiency seen in atopic dermatitis (AD), we developed a new highly sensitive method and measured the metabolic intermediate sphingosylphosphorylcholine (SPC) that accumulates in the stratum corneum. SPC in intercellular lipids extracted from stratum corneum was reacted with [(14)C]acetic anhydride to yield [(14)C-C(2)]SM, which was then analyzed by TLC. In both the lesional and non-lesional stratum corneum obtained from patients with AD, there was a significant increase in the content of SPC over that of healthy control subjects. There was a reciprocal relationship between increases in SPC and decreases in ceramide levels of stratum corneum obtained from healthy controls, and from lesional and non-lesional skin from patients with AD. Comparison with other sphingolipids present in the stratum corneum demonstrated that there is a significant positive correlation between SPC and glucosylsphingosine, another lysosphingolipid derived from glucosylceramide by another novel epidermal enzyme, termed glucosylceramide deacylase. In contrast, there was no correlation between SPC and sphingosine, a degradative product generated from ceramide by ceramidase. These findings strongly suggest the physiological relevance of SM deacylase function in vivo to the ceramide deficiency found in the skin of patients with AD.

Adolescent↗
PubMed1992

Ontogeny of the epidermal barrier to water loss in the rat: correlation of function with stratum corneum structure and lipid content.

The mammalian epidermal permeability barrier is provided by highly hydrophobic lipids forming multiple membrane bilayers within the extracellular domains of the outer, cornified cell layers. To characterize the critical events associated with barrier maturation, we correlated the emergence of a competent barrier to transepidermal water loss with development of the lamellar body secretory system, the organization of stratum corneum membrane bilayers, and the lipid composition of these membranes in the perinatal rat. Whereas pups of 19 d estimated gestational age had no measurable barrier (transepidermal water loss greater than 10 mg/cm2/h), by 21 d the barrier was well established (mean transepidermal water loss 0.41 mg/cm2/h). Development of a functional barrier correlated with increasing thickness of the stratum corneum, as well as with development of a membrane pattern of lipid deposition, visualized with the hydrophobic fluorescent probe nile red. At 19 d estimated gestational age, the stratum corneum intercellular domains exhibited an abundance of secreted lamellar body contents, but they were not organized into basic bilayer unit structures. Lamellar unit structures became evident by 20 d and extended throughout the stratum corneum interstices by 22 d (term). The quantity of lipid in isolated stratum corneum increased significantly between 19 and 20 d (34.08 versus 50.08 mean micrograms lipid/cm2, respectively; p less than 0.02) and still further between 20 and 21 d estimated gestational age (74.49 micrograms lipid/cm2; p less than 0.001). This increase was due to progressive accumulation of neutral lipids, particularly cholesterol, as well as nonpolar ceramides, as shown by thin-layer chromatography/scanning densitometry. These studies imply that in the development of cutaneous barrier function in the fetal rat both the generation of sufficient quantities of hydrophobic lipids and the organization of these lipids into bilayer unit structures are required.

Age Factors↗
PubMed1997

Relationship between amount of beta-blockers permeating through the stratum corneum and skin irritation after application of beta-blocker adhesive patches to guinea pig skin.

We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a* -delta a*Placebo) values.

Acebutolol↗
PubMed2001

Effects of adhesive dressings on the stratum corneum of the skin.

Two human models were developed to quantify the stratum corneum removed by different adhesive dressings and to measure the peel force of dressing removal and relate this to stratum corneum removal. The first was an open study designed to compare the effects of applying Mepiform Safetac, Tielle and Duoderm Extra Thin to the skin of 12 normal volunteers aged 19-53 years. Treatments were applied once (one 24-hour application) or three times (three x 24-hour applications) to forearm skin which had been prestained with methylene blue. After dressing removal the dye left on the skin was sampled using the skin surface biopsy method and measured spectrophotometrically. The results show that, after one and three applications, the Mepiform Safetac sites had a higher level of dye than those on which the other dressings had been applied (p < 0.05, after three applications). Based on the assumption that the more dye is left on the skin, the less damage is caused, this suggests that Mepiform Safetac is less damaging to the skin surface than the other products tested. In the second study the peel force needed to remove adhesive dressings from prestained skin was measured and related to the amount of stratum corneum removed. Mepilex Border Safetac, Duoderm Extra Thin, Allevyn Adhesive, Biatain Adhesive and Tielle Hydropolymer Dressing were compared in 20 normal volunteers aged 23-64 years. Three consecutive 24-hour applications of each product were made, with measurements of peel force at 24, 48 and 72 hours. The amount of dye remaining on the skin at 72 hours was assessed by the surface biopsy method. Statistically significant differences between products were observed in terms of both peak force and steady state force of removal. Differences in the level of damage to the superficial stratum corneum were also detected. However, low levels of peel force were not always associated with low damage and, therefore, other factors must contribute to stratum corneum removal in this model.

Adhesives↗
PubMed1995

Immunolocalization of CD44 and heparan sulfate chains on the stratum intermedium and papillary layer in the rat enamel organ.

We studied the immunohistochemical localization of CD44 and heparan sulfate (HS) chains in rat enamel organ by confocal laser scanning microscopy and transmission electron microscopy. We also investigated the binding sites of basic fibroblast growth factor (bFGF), one of the heparin-binding growth factors (HBGF), on Microslicer-sections to clarify its role in the cell-cell interaction of HS. At the differentiation stage of ameloblast, weak immunoreactivity for CD44 was detected on the plasma membrane of the inner enamel epithelium, external enamel epithelium and the cells adjacent to the inner enamel epithelium. In accordance with the differentiation of preameloblasts into secretory ameloblasts, this immunoreactivity increased in stratum intermedium cells. At the secretory stage, stratum intermedium cells showed the most intense immunoreactivity in the enamel organ. At the maturation stage, strong immunoreactivity was seen on papillary layer cells. On the other hand, the lateral plasma membrane of ruffle-ended (RA) and smooth-ended ameloblast (SA) showed weak reactivity. No immunoreactivity was detected on the ruffled border of RA and the distal plasma membrane of SA. Immunolocalization of HS chains was similar to that of CD44. The binding activity of bFGF was also intense on stratum intermedium cells and papillary layer cells. These findings suggest that: 1) stratum intermedium cells and papillary layer cells express CD44 and HS chains in accordance with their differentiation; 2) HS chains on the plasma membrane of these cells may regulate calcium transport by their negative charge; and 3) HS chains on the stratum intermedium and papillary layer may play an important role in the differentiation and activity of ameloblasts by preserving HBGF.

Animals↗
PubMed1994

IgG-Fc receptors in stratum granulosum: an immunological defence in human skin?

Receptors for the Fc-part of IgG (Fc tau R) in stratum granulosum of normal human skin were examined using cryosections and indirect immunofluorescence staining with 1) soluble immune complexes and 2) monoclonal antibodies (MoAbs) against different types of Fc tau R, i.e. 32.2 (anti-Fc tau I-CD64), IV.3 (anti-Fc tau RII-CD32) and Leu 11b (anti-Fc tau RIII-CD16). The immune complexes gave staining corresponding to stratum granulosum in sections from all skin specimens. Inhibition experiments showed that pre-incubation of the sections with monomeric and heat-aggregated human IgG, periodic acid and formaldehyde inhibited the immune complex binding. F(ab')2 containing immune complexes did not bind to the skin sections. The MoAb 32.2 gave granular and Leu 11b linear staining corresponding to stratum granulosum. In addition, both IC, 32.2 and Leu 11b gave weaker staining of keratinocytes in other parts of the epidermis. IV.3 stained epidermal Langerhans' cells and were unreactive with other epidermal cells. Indirect immunofluorescence staining with MoAbs against IgG subclasses showed the presence of all IgG subclasses in stratum granulosum. The results show that granulosum cells express both high- and low-affinity IgG receptors and in vivo bound IgG. The data point to a role for stratum granulosum in cutaneous immunity.

Antibodies, Monoclonal↗
PubMed2000

[Effect of temperature, humidity and minor injury to the penetration of dermatophytes into human stratum corneum].

We evaluated the minimum period for penetration of Trichophyton mentagrophytes into human stratum corneum using an experimental model of tinea pedis. Fungal elements were applied to the surface of stratum corneum which were obtained from a healthy human heel, and samples were incubated under a designated condition of temperature and humidity. Thirty-five degrees, which is the approximate temperature of the surface of human skin, seemed more suitable for penetration than 27C. The result also indicated that humidity was a more significant factor than temperature. In the following examination using T. mentagrophytes and T. rubrum, the minimum period for penetration at 100% humidity was 1 day with the former and 1.5 days with the latter. At 95% humidity, T. mentagrophytes penetrated into human stratum corneum on day 1.5 and T. rubrum penetrated on day 4. Humidity of the 4th interdigital space in daily life was calculated to be below 95% using a hygro-thermometer. Therefore, to wash the feet daily can prevent development of tinea pedis. When we applied fungal elements to a cut side of stratum corneum, fungi penetrated within a day at 100% and 95% humidity. In addition, fungi were able to penetrate at below 85% humidity, which they were unable to do when applied them to the surface side. We stress that minor injury of stratum corneum is also a significant factor of the development of tinea pedis.

Humans↗
PubMed2002

[The stratum corneum].

Epidermal differentiation is a continuous process, constituting and renewing a protective layer at the skin surface: the stratum corneum, composed of cornified keratinocytes that is a barrier to water diffusion. Massive loss of physiologic liquids is one of the severest consequences of extensive burns. The stratum corneum also protects the subjacent tissues from xenobiotic aggression, ultraviolet radiation (70 p. cent of UVB absorption) and from mechanic aggression. The integrity of the stratum corneum depends on three elements: 1) the physico-chemical quality of the cornified cells, 2) the persistence of mechanical junctions uniting these cells and 3) the organization and composition of the lipid "mortar" in the intercellular spaces. Since all these components are issued from the keratinocyte differentiation process, any perturbation may, in time, induce modifications in the "barrier" function of the epidermis. The barrier quality varies, depending on its localization (soles of the feet, palms of the hands and transitional epidermis of the lips), during skin healing (priority to keratinocyte proliferation to the detriment of maturation) under the influence of treatment (retinoids, vitamin D derivatives), in the course of aging and diseases: ichtyosis and other keratinization genodermatoses, benign (including psoriasis) and malignant hyperproliferative diseases. Furthermore, the relative impermeability of the stratum corneum is an important factor limiting the penetration and diffusion of allergens, but also local drugs delivered with local and systemic trans-epidermal treatments. Further knowledge is required on the function of the epidermal barrier and the mechanism regulating cohesion/desquamation of the stratum corneum to understand certain hereditary diseases, improve efficacy of topical therapeutic products and optimize cosmetic formulations.

Body Water↗
PubMed1992

Physical methods for studying stratum corneum lipids.

The skin's barrier to water loss and drug transport is closely related to the biophysical properties of the stratum corneum lipids. A number of in vitro and in vivo methods have been used to evaluate the physical properties of stratum corneum lipids. Two particularly useful techniques, infrared spectroscopy and differential scanning calorimetry, have provided a wealth of information about stratum corneum structure and function. The results of these studies demonstrate that the alteration of stratum corneum lipid packing results in increased skin permeability. Furthermore, the magnitude of increased permeability can be predicted from these physical properties. Therefore, these results provide both insight into the mechanism of transport through the stratum corneum, as well as a useful paradigm for selection of agents that reversibly alter the permeability of the skin.

Animals↗
PubMed1990

[Stratum-structure of the spinal nerves in the understanding of body structure].

The main methodology employed in the progressive gross anatomy of today's Japan is typological anatomy (typologische Anatomie) as introduced by Seiho Nishi (1943; 1950; 1961). This typological methodology is sufficient to suggest the existence of a certain constancy between muscle phylogeny and innervation in spite of the classic theory of nerve-muscle specificity having been discredited. On the basis of findings obtained from the many recent Japanese studies including the author's study on the cervical plexus (Kida, 1987), it has been noted that the stratum-structure of the spinal nerves may be an important key for the phylogenetic understanding of animal body structure (Kida, 1988). 1) The stratum-structure of the spinal nerves was initially observed only in the limb plexus by Fürbringer (Schwalbe, 1981). At that time, it was accepted as the longitudinal strata corresponding to the portion occupied by nerve fibers to the flexors or the extensors (Bolk, 1902). This theory was effective for the systematic understanding of limb structure. 2) The stratum-structure of the spinal nerves was at first considered to be related to the concept of nerve-muscle specificity. After the review of Straus (1946) on the concept of nerve-muscle specificity, this concept was disproved and has since been generally regarded as a theory of the past, therefore stratum-structure is now treated independently of that concept. 3) However, recent Japanese studies have modified and progressed beyond the concept of the stratum-structure of the spinal nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1985

Interrelationship between water-barrier and reservoir functions of pathologic stratum corneum.

Scaly skin lesions are caused by decreased water content of the stratum corneum, despite the well-known fact that they usually show increased water passage. By performing simultaneous measurements of transepidermal water loss (TEWL) to check the water-barrier function of the stratum corneum and cutaneous conductance to the high-frequency electric current of 3.5 MHz, which is an indicator of skin-surface hydration state, in patients with psoriasis who had lesions of various grades of severity, we obtained data indicating that there is an inverse relationship between these functions of the stratum corneum. Furthermore, a time course study of TEWL and functional analysis of stratum corneum by an in vivo water sorption-desorption test performed on the experimentally induced scaly lesions after adhesive-tape stripping demonstrated that such pathologic stratum corneum is characterized by a water-holding defect that is associated with increased TEWL.

Adult↗
PubMed1979

[Influence of the stratum corneum on transepidermal water loss and Bioavailability of a new topical steroid, difluprednate: clinical implications (author's transl)].

Comparative study of experimental and theoretical curves obtained by plotting transepidermal water loss against stratum corneum thickness in man, shows that every layer in the stratum corneum acts as part of the epidermal barrier to water loss. Another function of the stratum corneum is to decrease the cutaneous penetration of topical corticosteroids like difluprednate and to modify their bioavailability ('corticosteroid reservoir'). Our data suggest that variations in stratum corneum thickness between subjects explain variation of transepidermal water loss and sensitivity difluprednate, as there is a close relationship between these two parameters. It is then conceivable than the phototype has clinical implications is there really exists a relationship between phototype, stratum corneum thickness and sensitivity to steroids.

Administration, Topical↗
PubMed1983

Human stratum corneum lipids: characterization and regional variations.

The lipids of mammalian stratum corneum are known to be important regulators of skin permeability. Since the human stratum corneum displays remarkable regional variations in skin permeability, we assessed the total lipid concentration, the distribution of all major lipid species, and the fatty acid composition in Bligh-Dyer extracts from four skin sites (abdomen, leg, face, and sole) that are known to display widely disparate permeability. Statistically significant differences in lipid weight were found at the four sites that were inversely proportional to their known permeability. In all four sites, among the polar lipids, the stratum corneum contained negligible phospholipids, but substantially more cholesterol sulfate (1-7%) than previously appreciated. As in the stratum corneum from other mammals, the bulk of the lipids consisted of neutral (60-80%) and sphingolipids (15-35%). Of the neutral lipids, free sterols (4- to 5-times greater than esterified sterols), free fatty acids, triglycerides, and highly nonpolar species (n-alkanes and squalene) predominated. n-Alkanes, which were present in greater quantities than previously appreciated, comprised a homologous series of odd- and even-chained compounds ranging from C19 to C34. The sphingolipids comprised over 80% ceramides vs. lesser quantities of glycosphingolipids. In all four sites, the sphingolipids were the major repository of long-chain, saturated fatty acids. The neutral lipid:sphingolipid ratio generally was proportional to the known permeability of each site: higher neutral lipids and lower sphingolipids generally were associated with superior barrier properties. These studies provide: 1) the first detailed, quantitative analysis of human stratum corneum lipids and 2) information about the variability in lipid composition at four skin sites with known differences in permeability. The latter results suggest that variations in neutral lipids, rather than sphingolipids, may underlie local variations in skin permeability.

Alkanes↗
PubMed1995

Characterization of stratum corneum structure in reconstructed epidermis by X-ray diffraction.

The intercellular lipid regions in the stratum corneum (SC), the outermost layer of the skin, form the major barrier for diffusion of substances through the skin. The barrier function of in vitro reconstructed epidermis is still impaired. With respect to further optimization of the model, it is necessary to characterize its stratum corneum lipid structure. In this study, small and wide angle X-ray diffraction were used to characterize the lipid organization in stratum corneum isolated from 14-day-old reconstructed epidermis. The measurements were carried out at room temperature, and subsequently as a function of temperature between 25 degrees C and 109 degrees C, followed by measurements after cooling to room temperature. The results of the X-ray diffraction measurements revealed the following in reconstructed epidermis. 1) The lamellar ordering of stratum corneum lipids was much lower than that observed in native stratum corneum. 2) Crystalline anhydrous cholesterol was present. 3) Orthorhombic packing was present, but the corresponding reflections were very weak. The orthorhombic packing disappeared between 30 degrees C and 45 degrees C. 4) A hexagonal packing was present and disappeared between 60 degrees C and 75 degrees C. 5) Soft keratin is present. 6) A higher extent of lamellar ordering could be achieved by heating to 109 degrees C and cooling down to room temperature. Analysis of SC lipids revealed the presence of high amounts of triglycerides, the level of which could be decreased by lowering the glucose content. However, modulation of culture medium composition did not significantly affect lipid lamellae structures or hydrocarbon chain packing.

Cells, Cultured↗
PubMedDate not supplied

Congenital ichthyosiform erythroderma (C.I.E.)--ultrastructural evidences of abnormal stratum corneum retention.

Congenital ichthyosiform erythroderma (C.I.E.) is a skin disorder which has been considered as a hyperkinetic hyperkeratosis. This study was performed in order to demonstrate that C.I.E. pathogenesis includes both basal cell hyperplasia and abnormal stratum corneum retention. Electron microscopic studies were carried out on 5 cases of C.I.E., clinically and histopathologically diagnosed. The following pathological changes were found in stratum corneum and stratum granulosum: persistence of desmosomes in outer layers of stratum corneum, increased volume of intercorneocyte material, loss of lamellar pattern of Odland bodies, important variability in size and shape of keratohyaline granules, abnormal aggregation of tonofilaments. These constitute ultrastructural evidences of abnormal stratum corneum retention in C.I.E. pathogenesis.

Cytoplasm↗
PubMed1978

Experimental cutaneous candidiasis in rodents; II. Role of the stratum corneum barrier and serum complement as a mediator of a protective infalmmatory response.

Of six species of Candida applied epicutaneously to rodents, only C albicans and C stellatoidea penetrate the stratum corneum and produce inflammation. The role of the stratum corneum and produce inflammation. The role of the stratum corneum in experimental murine Candida infections was studied, therefore, by intraepidermal injection of blastospores in mice that received a prior injection of staphylococcal epidermolysin. All six species caused accumulation of neutrophils if placed within an intraepidermal cleft in contact with viable epidermis. The role of serum complement in cutaneous candidiasis was also studied in vivo in rodents depleted of complement with cobra venom factor or deficient in the fifth component of complement. These animals failed to develop neutrophilic inflammatory responses to the six Candida species tested in contrast to control animals. Candida albicans, C stellatoidea, and C tropicalis developed extensive hyphal proliferation with invasion of the entire cutis and subcutis in these animals. The stratum corneum provides an effective barrier to some, but not all Candida species. When this barrier is penetrated, complement mediates an acute neutrophilic pustular response that resticts Candida proliferation and prevents deep invasion of tissue.

Animals↗
PubMed2004

Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response.

The skin is an important immunological organ with an outer protective layer, the stratum corneum forming a barrier between the skin-associated lymphoid tissue and the environment. We show that gently removing the stratum corneum with adhesive tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion by T cells from draining lymph nodes and high levels of specific IgE and IgG1 with no IgG2a showed that the immune responses induced following epicutaneous antigen exposure are strongly Th2 biased. Similar responses were obtained with different antigens and mouse strains. In contrast, subcutaneous immunization with antigen delivery into the dermis was less potent and gave predominantly Th1 responses. Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate. Rapid migration from epidermis to draining lymph node was obtained, however, by exposure to antigen after removal of the stratum corneum, suggesting that maturation and migration of Langerhans cells are independently regulated events. These results suggest that antigen presentation by Langerhans cells gives predominantly Th2 responses. This may provide an explanation for allergic sensitization to some antigens. It may also be a useful non-invasive, non-adjuvant-dependent method of vaccination.

Animals↗