Suprabasal Layers (suprabasal + layer)

Distribution by Scientific Domains


Selected Abstracts


Genotype,phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1

EXPERIMENTAL DERMATOLOGY, Issue 2 2002
T. Hamada
Abstract: We report a 42-year-old Japanese man with an unusual autosomal recessive genodermatosis. The clinical features comprised normal skin at birth, loss of scalp hair at 3-months of age after a febrile illness, progressive nail dystrophy during infancy, palmoplantar keratoderma starting around the age of 18 years and trauma-induced skin fragility and blisters noted from the age of 20 years. Skin biopsy of rubbed non-lesional skin revealed widening of spaces between adjacent keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a reduction in intercellular staining for the desmosome component plakophilin 1. Mutation analysis revealed a homozygous intron 11 donor splice site mutation in the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT-PCR, using RNA extracted from the skin biopsy, provided evidence for residual low levels of the full-length wild-type transcript (,8%) as well as multiple other near full-length transcripts, one of which was in frame leading to deletion of 17 amino acids from the 9th arm-repeat unit of the plakophilin 1 tail domain. Thus, the molecular findings help explain the clinical features in the patient, who has a similar but milder phenotype to previously reported patients with skin fragility-ectodermal dysplasia syndrome associated with complete ablation of plakophilin 1 (OMIM 604536). This new ,mitis' phenotype provides further clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell,cell adhesion and ectodermal development. [source]


Expression of ,-catenin in external auditory canal cholesteatoma (EACC)

BIOFACTORS, Issue 3-4 2003
Ramin Naim
Abstract External auditory canal cholesteatoma (EACC) is a chronic inflammation of the external auditory canal and is composed of hyperproliferative epithelium. The upward migration of the epithelial cells requires permanent breakdown and reformation of intercellular connection. This is established by the modulation of the adherent junctions consisting of an E-Cadherin-,-catenin complex. Dissociated ,-catenin intranuclearly enables persistent activation of downstream transcription and growth factors and decreases the integrity of tissue. In our study we examined EACC and normal meatal auditory skin taken from 16 patients between 23 and 74 years of age. Immunostaining for ,-catenin was used for semiquantitative description of the specimens after assessing hematoxylin-eosin-stained slides. ,-catenin was expressed in all layers of AMS-epithelium, whereas in EACC only basal layer of the matrix epithelium showed positive immunostaining for ,-catenin. In the suprabasal layer of the epithelium only faint reactivity was detectable. The immunostaining was restricted to the membrane of the cells. We assumed that either the content of membranous ,-catenin was decreased or ,-catenin was changed due to molecular modification. It is known that stimulation of endothelial cells by certain growth factors, ,-catenin is maximally phosphorylated. In regard to the increased loss of immunoreactivity for ,-catenin in the suprabasal layers of the hyperplastic EACC-matrix, we assumed bio-molecular modification or loss of ,-catenin decreasing the cell-cell-integrity. Furthermore, this might result in desquamation of keratinocytes and accumulation of dead keratin debrids. In sum, this study should be understood as a descriptive analysis of ,-catenin expression in EACC. [source]


Hypermelanocytic guttate and macular segmental hypomelanosis

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004
W. Westerhof
Summary We report two sisters, 27 and 30 years of age, with a cutaneous pigmentary anomaly, which seems to be a new entity. At the age of 26 years the elder sister developed an asymptomatic and persistent rash consisting of discrete, grouped, round to oval, guttate and nummular, hypopigmented macules, 0·2,5 cm in diameter. The distribution of the lesions was unilateral. They were located on the right side of the thorax with a moderately sharp demarcation in the mid-line and ran in a segmental distribution over the right arm, hand and fingers. Microscopic examination of lesional skin scrapings was negative for fungi. Examination with Wood's light accentuated the lesions from the surrounding normal skin. The younger sister had experienced identical, mostly guttate, skin lesions for many years, which at examination were distributed on all extremities and buttocks, and to a lesser degree on the trunk, but here in a segmental distribution. Histological examination (Masson,Fontana staining) of lesional skin of both sisters was identical. A slightly thinned epidermis and a marked decrease in pigmentation of the epidermal basal layer was seen. Electron microscopic examination of lesional skin showed an overall linear increase of morphologically and cytologically normal melanocytes just above the epidermal basal membrane. At many places the density of melanocytes was so high that the keratinocytes were displaced from the basal layer. The melanocytic dendrites extended into the suprabasal layer. The keratinocytes of lesional skin showed a decreased number of melanosomes. It is paradoxical that a hypomelanotic macule shows a histological picture of an increase in normal functioning melanocytes. In all probability a deficient melanosome transfer is responsible for this unexpected phenomenon. [source]


Cell kinetic studies in murine ventral tongue epithelium: cell cycle progression studies using double labelling techniques

CELL PROLIFERATION, Issue 2002
C. S. Potten
Abstract. The dorsal and ventral epithelia on the murine tongue exhibit very pronounced circadian rhythms in terms of the cell cycle. These rhythms are such that three injections of tritiated thymidine 3 h apart spanning the circadian peak in S phase cells labelled between 40 and 50% of the basal cells. Injection of bromodeoxyuridine generally gave slightly lower labelling indices. Approximately the same proportion (54% of the basal cells) could be accumulated in metaphase over a 24-h period using vincristine as a stathmokinetic agent. The experiments reported here using mouse ventral tongue epithelium use double-labelling approaches to address the question: what proportion of the approximately 50% of the basal cells that are proliferating have a 24-h cell cycle and can therefore be labelled by a similar labelling protocol the following day? The results suggest a heterogeneity amongst the proliferating basal cells, similar to the heterogeneity proposed for the dorsal tongue epithelium. Although not all the basal component has been accounted for, the data presented here suggest that about 20% of the basal cells may have a cell cycle time of 24 h, about 30% appear to have a longer cell cycle time (48 or 72 h), while about 20% of the basal cells appear to be postmitotic maturing G1 cells, awaiting the appropriate signals for migration into the suprabasal layer. [source]


Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens

EXPERIMENTAL DERMATOLOGY, Issue 1 2000
Y. Suga
Abstract: Ichthyosis bullosa of Siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype,genotype correlation in these families. [source]


Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblasts

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008
Briana C. Gleason
Background:, The mechanisms whereby melanocytes populate the epidermis and developing hair follicles during embryogenesis are incompletely understood. Recent evidence implicates an intermediate mesenchymal stage in this evolutionary process in which HMB-45-positive melanocyte precursors (,melanoblasts') exist both in intradermal as well as intraepithelial and intrafollicular compartments. The melanocyte master transcriptional regulator, microphthalmia transcription factor (MITF), identifies mature melanocytes as well as melanocyte precursor stem cells that reside in the bulge region of the hair follicle. Methods:, To better define the use of MITF expression in the evaluation of melanocyte ontogeny, human embryonic and fetal skin samples (n = 28) at 6,24 weeks gestation were studied immunohistochemically for expression of MITF and Mart-1. Adjacent step sections were evaluated to correlate staining patterns with cell localization in the intraepidermal, intrafollicular and intradermal compartments. Results:, At 6,8 weeks, MITF and Mart-1-positive cells were primarily intradermal with only rare positive cells in the epidermis. By 12,13 weeks, most of these cells had migrated into the epidermis, predominantly the suprabasal layers. Between 15,17 weeks, these cells localized to the basal layer and colonized developing hair follicles. Rare intradermal MITF and Mart-1 positive cells were found as late as week 20. At 18,24 weeks, MITF and Mart-1 positive cells were identified in the outer root sheath, bulge, and follicular bulge epithelium, in addition to the epidermis. Unexpectedly, weak but diffuse nuclear MITF expression was also present in the keratinocytes of the bulge area. Conclusions:, The in situ migratory fate of MITF/Mart-1-expressing cells in fetal skin involves a well-defined progression from intradermal to intraepidermal to intrafollicular localization. Occasional intradermal melanocytes may persist after the intraepithelial stages are completed, a finding of potential significance to melanocytic proliferations that may arise de novo within the dermis. Because MITF may play a role in stem cell maintenance, the presence of MITF in bulge epithelial cells suggests that it may be a novel marker for follicular stem cells of both epithelial and melanocytic lineage. [source]


Lupus erythematosus: clinical and histopathological study of oral manifestations and immunohistochemical profile of epithelial maturation

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2006
Silvia Vanessa Lourenço
Background:, Lupus erythematosus (LE) is an autoimmune disease of unknown cause. Prevalence of oral involvement in patients with LE is uncertain but may vary from 9 to 45% in patients with systemic disease and from 3 to 20% in patients with chronic cutaneous involvement. Methods:, Incidence of oral lesions of LE and their clinical aspects were investigated. Their histopathologic features were analyzed, and the status of epithelial maturation was assessed through the expression patterns of cytokeratins. Results:, Twenty-six patients (from 188 examined) presented oral lesions of LE. Most of them were females (19) with systemic disease (11). Clinical aspects of these lesions varied, and lips and buccal mucosa were most affected. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers only. Conclusions:, Oral lesions of LE show a variety of aspects, and their microscopic features are of a lichenoid mucositis with deep inflammatory infiltrate. Cytokeratins expression patterns are of hyperproliferative epithelium, and this phenomenon must be analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease. [source]


The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2000
Karin Nylander
Abstract: Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview of the p53 molecule and evaluates its possible prognostic role in SCCHN. Today it is clear that the p53 pathway is very important in SCCHN biology and potentially in its treatment. The function and importance of a few other cell cycle proteins connected to p53 are also discussed. [source]


Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia

JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2006
S. Hatakeyama
Background and Objective:, The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Material and Methods:, Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. Results:, In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell,cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. Conclusion:, These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier. [source]


Paederus dermatitis in Egypt: a clinicopathological and ultrastructural study

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010
M Assaf
Abstract Background, Outbreaks of paederus dermatitis (PD) have been observed in different parts of the world, yet the histopathological and ultrastructural changes and their relationship to pederin toxin have not been described. Objective, To describe the clinical presentations of PD in Egypt and to study the effects of pederin toxin on the skin by evaluating the histopathological and ultrastructural changes of some representative cases. Methods, One hundred and thirteen patients with PD were studied clinically and epidemiologically. Skin biopsies were taken from 40 patients for histopathological examination and from 20 patients for electron microscopic (EM) examination. Results, Clinically, the most common presentation comprised erythematous plaques with micropustules. Blisters exhibited a linear configuration in 40% of the patients and kissing lesions were observed in 13%. Multiple lesions occurred in 78% of the patients and the face was the most commonly involved site (48%). The insect was identified as Paederus alfierii. Histopathological examination revealed features of acute irritant dermatitis in the upper epidermis. Mitotic figures and apoptotic changes such as chromatin condensation and DNA fragmentation were identified in the basal and suprabasal layers. These features were confirmed by EM. Conclusions, Clinical, histopathological and, for the first time, ultrastructural characteristics of paederus dermatitis are described. The pathological abnormalities of the upper epidermis are caused by the irritant effect of pederin toxin. The presence of apoptosis within the lower epidermis can be related to this toxin, a point that needs further research, hoping for its future implications in the management of hyperproliferative disorders. [source]


A novel model of wound healing in the SCID mouse using a cultured human skin substitute

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2009
Martin L Windsor
SUMMARY Studies of skin graft behaviour in rodent excisional wound models are limited by the dominance of wound contracture and graft sloughing as primary healing responses. To slow skin contraction, polytetrafluoroethylene (Teflon) rings were inserted into dorso-lateral full-thickness wounds in SCID mice. Cultured skin substitutes (OrCel), composed of cultured human keratinocytes and fibroblasts in a bovine collagen sponge, were implanted within the rings. Examination and histology of grafts 14 days later showed graft take in four of six recipients, with 90% epithelialization and wound contraction of 31,47%. Immunohistochemical studies, using human-specific antisera to distinguish graft from host tissues, showed that regenerated tissue was predominantly human. Staining with anticytokeratin, revealed a multilayered, stratified neoepidermis. HBG were identified in keratinocytes in all epidermal layers. Langerhans cells were absent. Antihuman vimentin, used as a fibroblast marker, confirmed that cells of the neodermis were primarily of human origin. Neoepidermal keratinocytes, primarily in the basal and suprabasal layers, were also stained. Results suggest that the poly(tetrafluoroethylene) ring inhibited graft sloughing and provided a more favourable environment for the skin substitute to regenerate a substantially normal human skin. [source]


Expression of ,-catenin in external auditory canal cholesteatoma (EACC)

BIOFACTORS, Issue 3-4 2003
Ramin Naim
Abstract External auditory canal cholesteatoma (EACC) is a chronic inflammation of the external auditory canal and is composed of hyperproliferative epithelium. The upward migration of the epithelial cells requires permanent breakdown and reformation of intercellular connection. This is established by the modulation of the adherent junctions consisting of an E-Cadherin-,-catenin complex. Dissociated ,-catenin intranuclearly enables persistent activation of downstream transcription and growth factors and decreases the integrity of tissue. In our study we examined EACC and normal meatal auditory skin taken from 16 patients between 23 and 74 years of age. Immunostaining for ,-catenin was used for semiquantitative description of the specimens after assessing hematoxylin-eosin-stained slides. ,-catenin was expressed in all layers of AMS-epithelium, whereas in EACC only basal layer of the matrix epithelium showed positive immunostaining for ,-catenin. In the suprabasal layer of the epithelium only faint reactivity was detectable. The immunostaining was restricted to the membrane of the cells. We assumed that either the content of membranous ,-catenin was decreased or ,-catenin was changed due to molecular modification. It is known that stimulation of endothelial cells by certain growth factors, ,-catenin is maximally phosphorylated. In regard to the increased loss of immunoreactivity for ,-catenin in the suprabasal layers of the hyperplastic EACC-matrix, we assumed bio-molecular modification or loss of ,-catenin decreasing the cell-cell-integrity. Furthermore, this might result in desquamation of keratinocytes and accumulation of dead keratin debrids. In sum, this study should be understood as a descriptive analysis of ,-catenin expression in EACC. [source]


Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006
S. Benoit
Summary Background, The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives, We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods, Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results, A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705 ± 120 ng mL,1 (mean ± SEM, n = 18), those with a PASI of ,15 showed levels of 1315 ± 150 ng mL,1 (n = 32) while controls presented with 365 ± 50 ng mL,1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. Conclusions, Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions. [source]


Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism,

CANCER, Issue 5 2006
Ramy Ibrahim M.D.
Abstract BACKGROUND To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them. METHODS The authors tested the expression of FASL on the surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify apoptotic cells. An in vitro functional assay was then done to test if the FASL expressed on the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues. RESULTS Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of FasL in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS The findings of the current study support the authors' hypothesis that persistent expression of FasL plays a role in the ability of cervical carcinoma cells to escape from the immune system. Cancer 2006. Published 2006 by the American Cancer Society. [source]


P-cadherin expression reduced in squamous cell carcinoma of the oral cavity

CANCER, Issue 5 2005
An indicator of poor prognosis
Abstract BACKGROUND The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E-cadherin (E-cad) and P-cadherin (P-cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC). METHODS The authors used immunohistochemical methods to analyze the expression pattern of E-cad and P-cad in healthy oral mucosa, in oral carcinoma in situ (CIS), and in surgical samples of 50 patients with the early stages (Stages I,II) of OSCC. RESULTS E-cad showed weak expression in the basal layer of the healthy oral mucosa and reduced expression in patients with oral CIS. P-cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS. In the group of patients with OSCC, univariate analysis demonstrated that reduced expression of E-cad or P-cad correlated significantly with locoregional disease recurrence in the follow-up (P = 0.03 and P = 0.01, respectively). However, only the reduction in the expression of P-cad emerged as an independent prognostic marker in the multivariate analysis (P = 0.04, hazard ratio = 8.06). CONCLUSIONS These findings suggested that a decrease in E-cad and/or P-cad expression may contribute to the invasive potential of early OSCC. According to the current data, P-cad expression may be a potential independent prognostic factor in patients with OSCC. Cancer 2005. © 2005 American Cancer Society. [source]