bromochloroacetic-acid and Keratosis

Keratin (KRT), a natural fibrous structural protein, can be classified into two categories: "soft" cytosolic KRT that is primarily found in the epithelia tissues (e.g., skin, the inner lining of digestive tract) and "hard" KRT that is mainly found in the protective tissues (e.g., hair, horn). The latter is the predominant form of KRT widely used in biomedical research. The oxidized form of extracted KRT is exclusively denoted as keratose (KOS) while the reduced form of KRT is termed as kerateine (KRTN). KOS can be processed into various forms (e.g., hydrogel, films, fibers, and coatings) for different biomedical applications. KRT/KOS offers numerous advantages over other types of biomaterials, such as bioactivity, biocompatibility, degradability, immune/inflammatory privileges, mechanical resilience, chemical manipulability, and easy accessibility. As a result, KRT/KOS has attracted considerable attention and led to a large number of publications associated with this biomaterial over the past few decades; however, most (if not all) of the published review articles focus on KRT regarding its molecular structure, biochemical/biophysical properties, bioactivity, biocompatibility, drug/cell delivery, and in vivo transplantation, as well as its applications in biotechnical products and medical devices. Current progress that is directly associated with KOS applications in tissue regeneration and drug delivery appears an important topic that merits a commentary. To this end, the present review aims to summarize the current progress of KOS-associated biomedical applications, especially focusing on the in vitro and in vivo effects of KOS hydrogel on cultured cells and tissue regeneration following skin injury, skeletal muscle loss, peripheral nerve injury, and cardiac infarction.

Topics: Biocompatible Materials; Hair; Humans; Hydrogels; Keratins; Keratosis

Topics: Adult; Female; Humans; Keratins; Keratosis; Scalp Dermatoses; Warts

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Keratoacanthoma; Keratosis; Photography; Skin Neoplasms; Warts

Topics: Cells, Cultured; Epithelium; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Keratosis; Mutation; Skin Diseases, Vesiculobullous

The last ten years has revealed some of the key players in the development and differentiation of the hair follicle and the epidermis in general. In this review, we discuss how our current understanding of these processes has been made possible by the elucidation of the molecular basis of human inherited diseases and mouse mutants which display defects in the hair and epidermis. For examples, the study of ectodermal dysplasias and the basal cell carcinoma predisposition disease Gorlin syndrome have allowed the determination of signalling hierarchies critical in the formation of the hair follicle. Epidermolytic diseases and hyperkeratoses have focussed attention on the importance of the programs of keratin expression, while ichthyoses provide insight in the final stage of epidermal development, cornification. Finally, the increasing range of diseases and mouse models exhibiting alopecias are revealing the critical pathways in control of the hair follicle cycle.

Topics: Alopecia; Animals; Basal Cell Nevus Syndrome; Cell Differentiation; Epidermis; Forecasting; Genetic Predisposition to Disease; Humans; Keratins; Keratosis; Mice; Mice, Transgenic; Models, Biological; Mutation; Skin; Skin Diseases; Skin Neoplasms

Keratins are obligate heterodimer proteins that form the intermediate filament cytoskeleton of all epithelial cells. Keratins are tissue and differentiation specific and are expressed in pairs of types I and II proteins. The spectrum of inherited human keratin diseases has steadily increased since the causative role of mutations in the basal keratinocyte keratins 5 and 14 in epidermolysis bullosa simplex (EBS) was first reported in 1991. At the time of writing, mutations in 15 epithelial keratins and two trichocyte keratins have been associated with human diseases which include EBS, bullous congenital ichthyosiform erythroderma, epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, diffuse and focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita and monilethrix. Mutations in extracutaneous keratins have been reported in oral white sponge naevus and Meesmann's corneal dystrophy. New subtleties of phenotype-genotype correlation are emerging within the keratin diseases with widely varying clinical presentations attributable to similar mutations within the same keratin. Mutations in keratin-associated proteins have recently been reported for the first time. This article reviews clinical, ultrastructural and molecular aspects of all the keratin diseases described to date and delineates potential future areas of research in this field.

Topics: Animals; Hair Diseases; Humans; Intermediate Filaments; Keratins; Keratosis; Multigene Family; Mutation; Nail Diseases; Nevus; Pseudogenes; Skin Abnormalities

There have been a number of major discoveries recently in the field of dermatological science which have enabled us to determine the causes of inherited skin diseases of previously unknown etiology. In this paper we will review some important aspects of the biology of epidermal differentiation and the recent advances in understanding of the molecular mechanism underlying genetic diseases of keratinization.

Topics: Epidermis; Humans; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Keratosis

A clinically and genetically heterogeneous group of disorders, known collectively as the palmoplantar keratodermas, are unified by the phenotypic characteristic of a thickening of the skin over the palms and soles. Although spectacular progress has been made in understanding the basis of many genodermatoses, the genetic defects causing many of the keratodermas are still largely unknown. These unusual phenotypes are beginning to capture the attention of investigators in epidermal biology, and several compelling lines of evidence point to the cornified cell envelope and structural components of the desmosome as potential underlying targets of disease. It is anticipated that understanding the molecular basis of the keratodermas will underscore the importance of the integrity of the cell envelope and the desmosome, and provide new insights into the mechanisms of epidermal differentiation and related disorders.

Topics: Animals; Autoantibodies; Cell Differentiation; Cell Membrane; Desmosomes; Epidermal Cells; Esophageal Neoplasms; Genetic Linkage; Humans; Keratins; Keratoderma, Palmoplantar; Keratoderma, Palmoplantar, Diffuse; Keratosis; Membrane Proteins; Mice; Mice, Transgenic; Pemphigus; Protein Precursors

It is widely accepted that radicular cysts (apical periodontal cysts) are commonly lined with stratified squamous epithelium without keratin formation. However, we identified a case of maxillary radicular cyst with remarkable keratinization and atypical proliferation of the lining epithelium among the 207 radicular cyst cases seen at our department. Histopathological and clinical findings of these cysts were reviewed.

Topics: Cell Division; Cytoplasmic Granules; Epithelium; Fibrosis; Granulation Tissue; Humans; Hyalin; Keratins; Keratosis; Male; Maxillary Diseases; Middle Aged; Radicular Cyst

Harlequin ichthyosis is an inherited skin disorder that usually results in death shortly after birth. Although the clinical features of this disorder are well described, the underlying molecular basis is not understood. In this article, we discuss the results of the latest histologic, immunochemical, and Western immunoblotting studies done in our laboratory and propose a hypothesis for molecular basis of this disorder.. Previous experiments done in our laboratory show suggestive evidence for defective lipid synthesis and protein dephosphorylation in harlequin ichthyosis. Our latest study shows that the catalytic subunit of one of the most prevalent protein phosphatase, type 2A protein phosphatase, appears to be altered in some cases of type 2 harlequin ichthyosis.. Based on these observations and the known functions of protein phosphatase in keratinocytes, we hypothesize that the underlying molecular basis of harlequin ichthyosis may be related to mutations affecting protein dephosphorylation. We further describe approaches by which this hypothesis can be tested.

Topics: Cells, Cultured; Humans; Ichthyosis; Ichthyosis, Lamellar; Infant, Newborn; Keratinocytes; Keratins; Keratosis; Molecular Biology; Mutation; Phosphoprotein Phosphatases; Skin

Topics: Adult; Humans; Keratins; Keratolytic Agents; Keratosis; Male; Microscopy, Electron

Topics: Cell Differentiation; Cell Membrane; Chemical Phenomena; Chemistry; Epidermal Cells; Epidermis; Humans; Ichthyosis; Keratins; Keratosis; Lipid Metabolism

Topics: Adrenal Cortex Hormones; Cell Cycle; Cyclic AMP; Epidermis; Humans; Keratins; Keratosis; Protein Binding; Protein Precursors; Psoriasis

Topics: Acrodermatitis; Amino Acid Metabolism, Inborn Errors; Basal Cell Nevus Syndrome; Epidermolysis Bullosa; Hair Diseases; Humans; Ichthyosis; Keratins; Keratosis; Neurofibromatosis 1; Psoriasis; Refsum Disease; Skin; Skin Diseases; Skin Neoplasms; Tuberous Sclerosis; Tyrosine; Warts; Xeroderma Pigmentosum

Topics: Adolescent; Adult; Age Factors; Aged; Candidiasis, Oral; Child; Female; Follow-Up Studies; Humans; Hyperplasia; Keratins; Keratosis; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Nicotine; Precancerous Conditions; Retrospective Studies; Sex Factors; Smoking; Stomatitis

In a 14-day test with 50 probands, the effects of a heat-curing resin and a self-curing resin on the palatal mucosa of the test persons were tested by means of exfoliative cytology. It was shown that the keratinization index increased considerably during wearing the plates. It was not possible to demonstrate differences in the effect of heat-curing resins and that of self-curing resins. The different isolation with alginate film or tinfoil did not, in general, have any influence on the cytogram either. Roughness of the surface resulted in a slight increase of the intermediary cells.

Topics: Acrylic Resins; Densitometry; Denture Bases; Humans; Keratins; Keratosis; Mouth Mucosa; Palate; Surface Properties

Bowen disease, one of the common skin cancers, is defined as squamous cell carcinoma in situ, characterized by atypical keratinocytes occupying the full thickness of the epidermis, and predominantly occurs on sun-protected skin. There is no existing data on the impact of tumour and immune cell interactions or cytokeratin expression on the pathology of Bowen disease.. We analysed dynamic changes in cytokeratin expression and immune cell composition during the development and progression of Bowen disease.. Analysis was performed using immunohistochemistry and electron microscopy for samples from 140 patients with Bowen disease and 20 patients with invasive squamous cell carcinoma. We evaluated cytokeratin expression, the number of infiltrating immune cells and amyloid deposition by immunohistochemistry, and the ultrastructural relationship between tumour cells and immune cells by electron microscopy.. The results showed that the expression of CK14 is associated with tumour progression, keratotic status and amyloid deposition and that the expression of CK10 is associated with accumulation of immune cells in Bowen disease. The findings of electron microscopy indicated repeated battles involving immune cells in response to tumour invasion.. The expression of cytokeratins, hyperkeratosis, inflammatory infiltration and amyloid deposition are useful findings indicating the "stage" in Bowen disease.

Topics: Anus Neoplasms; Bowen's Disease; Carcinoma, Squamous Cell; Humans; Keratins; Keratosis

Keratins are a class of intermediate filament proteins that can be obtained from numerous sources including human hair. Materials fabricated from keratins offer desirable characteristics as scaffolds for tissue engineering, including intrinsic cell adhesion sequences and tunable degradation kinetics. The capacity to create 3D printed constructs from keratin-based bio-inks generates unique opportunities for spatial control of scaffold physicochemical properties to direct scaffold functions in ways not readily achieved through other means. The aim of this study was to leverage the controllable rheological properties of keratin hydrogels to create a strategy for extrusion 3D printing of keratin bio-inks without the use of exogenous rheological modifiers, crosslinking agents, or photocurable resins. The rheological properties of keratin hydrogels were tuned by varying two parameters: (a) the ratio of keratose (obtained by oxidative extraction of keratin) to kerateine (obtained by reductive extraction of keratin); and (b) the weight percentage of total keratin protein in the gel. A computational model of the dispensing nozzle for a commercially available extrusion 3D printer was developed to calculate the needed pneumatic printing pressures based on the known rheological properties of the gels. Keratin hydrogel constructs, of varying keratose/kerateine ratios and total keratin weight percentages, were 3D printed in cylindrical geometries via extrusion 3D printing. Rheology and degradation studies showed that gels with greater relative kerateine content exhibited greater flow resistance and slower degradation kinetics when submerged in phosphate buffered saline solution at 37 °C, owing to the presence of cysteine residues in kerateine and the capability of forming disulfide bonds. Total keratin weight percentage was found to influence gel yield stress, with possible implications for tuning filament fidelity. Findings from this work support the use of keratose/kerateine ratio and total keratin weight percentage as handles for modulating rheological characteristics of keratin hydrogels to enhance printability and control scaffold properties.

Topics: Bioprinting; Humans; Hydrogels; Keratins; Keratosis; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds

Pachyonychia congenita (PC) refers to a group of autosomal dominant disorders caused by mutations in five keratin genes (KRT16,KRT6A,KRT17,KRT6B or KRT6C). Current disease classification is based on the gene harbouring disease-causing variants.. We harnessed the International Pachyonychia Congenita Research Registry (IPCRR) containing both clinical and molecular data on patients with PC worldwide, to identify genetic variants predicting disease severity.. We ascertained 815 individuals harbouring keratin mutations registered in the IPCRR. We looked for statistically significant associations between genetic variants and clinical manifestations in a subgroup of patients carrying mutations found in at least 10% of the cohort. Data were analysed using χ. We identified five mutations occurring in at least 10% of the patients registered in the IPCRR. The KRT16 p.L132P mutation was significantly associated with younger age of onset, presence of palmar keratoderma oral leucokeratosis and a higher number of involved nails. By contrast, the KRT16 p.N125S and p.R127C mutations resulted in a milder phenotype featuring a decreased number of involved nails and older age of onset. Patients carrying the p.N125S mutation were less likely to develop palmar keratoderma while p.R127C was associated with an older age of palmoplantar keratoderma onset. Moreover, the KRT17 p.L99P mutation resulted in an increased number of involved fingernails and patients demonstrating 20-nail dystrophy, while the opposite findings were observed with KRT17 p.N92S mutation.. We have identified novel and clinically useful genetic predictive variants in the largest cohort of patients with PC described to date.

Topics: Age of Onset; Case-Control Studies; Child, Preschool; Cohort Studies; Genetic Variation; Heterozygote; Humans; Infant; Keratin-16; Keratin-17; Keratin-6; Keratins; Keratoderma, Palmoplantar; Keratosis; Leukoplakia, Oral; Mutation; Nail Diseases; Nails, Malformed; Pachyonychia Congenita; Phenotype; Predictive Value of Tests; Registries; Severity of Illness Index

Topics: Child, Preschool; Dermoscopy; Female; Forearm; Humans; Keratins; Keratosis; Rare Diseases

Symmetrical acrokeratoderma (SAK) is characterized by brown to black hyperkeratotic patches on acral regions. Although epidermal hyperkeratosis and acanthosis are consistent pathological changes, the nature of epidermal hyperplasia is unknown.. To evaluate epidermal proliferation and differentiation and melanocytic density in skin lesions of SAK.. Expression of keratin 10 (K10), K14, K16, involucrin, filaggrin, Ki-67, and Melan-A was detected by immunohistochemistry in eight patients with SAK, seven patients with ichthyosis vulgaris (IV) and six healthy controls (HCs).. Expression of K14, K16, involucrin and filaggrin was upregulated in patients with SAK compared with patients with IV and the HCs (P < 0.01-0.05), but K10 expression was similar for the three groups (P > 0.05). Numbers of Ki-67+ and Melan-A+ cells were higher in patients with SAK than in patients with IV and the HCs (P < 0.05).. These results demonstrate that excessive keratinocyte proliferation and abnormal differentiation contribute to epidermal hyperplasia, while melanocytic proliferation is responsible for the pigmented lesions in SAK.

Topics: Adolescent; Adult; Cell Differentiation; Cell Proliferation; Epidermal Cells; Epidermis; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Ki-67 Antigen; Male; Melanocytes; Protein Precursors; Skin; Up-Regulation; Young Adult

Topics: Biomarkers; Cell Differentiation; Cell Proliferation; Erythema; Female; Hand Dermatoses; Humans; Keratins; Keratosis; Middle Aged

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

Topics: Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lichen Planus, Oral; Merkel Cells; Microscopy, Confocal; Mouth Mucosa; Nerve Endings; Neurites

A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7) demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

Topics: Animals; Cell Differentiation; Cytoskeleton; Disease Models, Animal; Gene Expression; Human papillomavirus 16; Humans; Keratin-14; Keratins; Keratosis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Papillomavirus E7 Proteins; Promoter Regions, Genetic; Skin; Transplantation, Homologous

A 30-year-old man presented with lesions on his oral mucosa and soles. There were no similar complaints in his family members. The dermatological examination revealed follicular hyperkeratosis on his trunk and upper extremities and flesh-colored, firm cystic lesions on his axillae. He had focal, painful, hyperkeratotic areas sited particularly on both his soles and palms. In addition to these, leukokeratosis and ulcerative areas on buccal, labial mucosa, tongue, and at corners of the mouth, and complete loss of teeth was observed. The proximal layering was revealed on all of his nails. The laboratory investigations produced normal results except the deficiency of immunoglobulin A. The psychiatric examination revealed mild mental retardation. Keratin gene (KRT6a, KRT6b, KRT16, and KRT17) mutations for pachyonychia congenita were negative. He got removable dental prosthesis because of inadequate alimentation. Squamous cell cancer developed on lower lip mucosa during follow-up. We present an individual who had different nail dystrophy, epidermal cysts, mental retardation, blepharitis, complete loss of teeth, and negative keratin gene mutations for pachyonychia congenita and developed squamous cell cancer on the oral leukokeratosis lesions. We think that the present case may be an unusual new type of pachyonychia congenita.

Topics: Adult; Carcinoma, Squamous Cell; Epidermal Cyst; Humans; Intellectual Disability; Keratins; Keratosis; Leukoplakia, Oral; Lip Neoplasms; Male; Mouth, Edentulous; Oral Ulcer; Pachyonychia Congenita; Syndrome

Topics: Aminolevulinic Acid; Biopsy; Diagnosis, Differential; Ear Diseases; Ear, External; Epithelial Cells; Female; Humans; Keratins; Keratosis; Middle Aged; Miliaria; Photochemotherapy; Photosensitizing Agents

Epidermal keratinization disorders comprise a heterogeneous group of skin diseases that share the common feature of abnormal epidermal maturation, often leading to a disturbed stratum corneum.. To describe two cases of an unusual disorder of epidermal keratinization.. The clinical features of two unrelated patients with a long-standing widespread cutaneous eruption are described. Histopathologic examination and immunohistochemical studies were performed on skin biopsy specimens.. The eruption was characterized by symmetric erythematous, flat, discrete papules with a polygonal shape and fine scaling. The papules covered most of the skin surface and, in some areas of the trunk, they were arranged along the lines of cleavage, parallel to the ribs. There was no facial, mucosal, nail, or palmoplantar involvement; the teeth and hair were normal. The first patient had a sister with an identical eruption, and a brother of the second patient was said to have similar skin lesions. Histopathology revealed well-demarcated areas of compact eosinophilic orthokeratotic hyperkeratosis overlying a slightly acanthotic epidermis. Lesional skin showed weaker immunoexpression for connexin 43 compared with normal skin.. Only two patients and one sibling were investigated.. We propose the name "saurian papulosis" to describe this newly described clinicopathologic entity.

Topics: Adult; Aged, 80 and over; Female; Humans; Immunohistochemistry; Keratins; Keratosis; Male; Skin

To investigate the clinical and histologic features of frictional keratoses located exclusively on the facial attached gingiva and establish whether these belong to the category of leukoplakia.. Over a period of 15 years, 159 patients presenting with oral keratotic plaques, located exclusively on the facial attached gingival mucosa, excluding the edentulous alveolar ridge and retromolar pad area, were retrospectively selected. Clinical and histologic features and the symptoms and progression of these lesions were carefully assessed.. The presence of oral frictional keratosis located exclusively on the facial attached gingival mucosa was clinically and immunohistologically diagnosed in 14 of 159 patients (8.8%). Eleven patients (78.5%) showed unilateral involvement, whereas 3 patients (21.5%) had bilateral involvement. The disappearance of the lesions was accomplished in only 9 of 14 patients, resulting from discontinuation of bad habits. Clinically, these lesions appeared as distinct, sharply demarcated, isolated, asymptomatic, homogeneous whitish-plaques that were neither removable nor painful. The plaques did not create discomfort, change shape, or develop into malignancy. Histologically, these plaques showed features superimposable to those present in benign alveolar ridge keratoses.. The results highlighted that frictional keratoses on the facial attached gingival mucosa 1) are rare findings, 2) clinically appear as "true leukoplakia" but histologically have the same features as benign alveolar ridge keratoses, 3) have no propensity for malignant transformation, 4) have a good prognosis, and 5) have a specific cause, and resolution is accomplished if the frictional element is eliminated. Thus, these must be removed from the category of leukoplakia.

Topics: Adult; Diagnosis, Differential; Epithelium; Female; Fluorescent Antibody Technique, Direct; Follow-Up Studies; Friction; Gingiva; Gingival Diseases; Humans; Keratins; Keratosis; Leukoplakia, Oral; Male; Middle Aged; Retrospective Studies; Toothbrushing

Topics: Aged; Cholesteatoma, Middle Ear; Diagnosis, Differential; Ear Canal; Ear Diseases; Earache; Female; Hearing Loss, Conductive; Humans; Keratins; Keratosis

To assess periodontal health of individuals with a lateral lower lip piercing and describe associated periodontal, dental and mucosal complications.. A split-mouth study was performed in a sample of 50 patients with a lateral lower lip piercing who attended the Periodontal Pathology and Surgery Unit of the Dental School of the University of Barcelona. The patients underwent periodontal, dental and mucosal examination on both the piercing and the control sides.. Piercing users were predominantly women (78%), with a mean age of 21.3 years (SD=4.4). The amounts of keratinized and attached gingiva were significantly lower on the piercing side, and the prevalence of gingival recession was higher (p=0.012). The canine and first bicuspid teeth were the most affected. Tooth fractures and cracks were more frequent on the piercing side (20%) when compared with the control (4%). Mucosal alterations were found in seven patients.. The use of lateral lower lip piercings enhances gingival recession and reduces the amounts of keratinized and attached gingiva. These ornaments are also associated with tooth fractures and cracks.

Topics: Analysis of Variance; Body Piercing; Cross-Sectional Studies; Female; Functional Laterality; Gingiva; Gingival Diseases; Humans; Keratins; Keratosis; Lip; Male; Statistics, Nonparametric; Young Adult

Acquired digital fibrokeratomas (ADF) are benign and uncommon lesions consisting of collagenous papules and nodules covered by hyperkeratotic epidermis. These tumors occur mainly on the fingers and toes and infrequently on the palms and soles. They may possibly be triggered by a reaction to a trauma, ADF usually present as small and solitary dome-shaped lesions with a collarete of slightly raised skin at the base. We report a rare case of fibrokeratoma of the heel, presenting as a large and pedunculated nodule.

Topics: Collagen; Heel; Humans; Keratins; Keratosis; Male; Middle Aged; Treatment Outcome

A 60-year-old female and a 59-year-old male each presented with a solitary circumscribed patch of depressed skin of the right thenar palm and right sole, respectively. Both lesions were present for approximately 30 years without a history of trauma or other inciting incident. Histologically, the lesions showed a well-demarcated abrupt decrease in the thickness of the stratum corneum with a central area of thinned stratum corneum and hypogranulosis. Inflammation was absent. Ultrastructurally, keratin filaments were evident in the stratum corneum, and a diminished granular cell layer was apparent. There was a decrease in maturation of the keratinocytes, however, no defects in corneodesmosomes or other ultrastructural components were identified. No evidence of human papilloma virus was detected by in situ hybridization studies. Based on these 2 cases and the 25 cases reported in the literature to date, this entity seems to represent a chronic localized non-inflammatory defect in keratinization on acral sites.

Topics: Alphapapillomavirus; Female; Hand Dermatoses; Humans; In Situ Hybridization; Keratinocytes; Keratins; Keratosis; Middle Aged; Skin

Circumscribed palmar or plantar hypokeratosis (CPH) is a rare skin disorder only recently described.. To determine the diagnostic features and to provide insight into the pathogenesis of CPH, with analysis of two new Japanese cases.. Dermoscopy, immunohistochemistry, electron microscopy, polymerase chain reaction amplification for human papillomavirus (HPV) DNA and 16S microbial rRNA gene profiling were conducted.. Dermoscopy showed characteristic features using both dry and jelly immersion observation; step-like desquamation and a homogeneous erythema with regularly distributed whitish spots. Immunohistochemistry revealed strong staining with anti-pankeratin antibody (AE1+AE3) and anti-keratin 16 antibody, and decreased expression of keratin 2e. EM revealed a breakage of the corneocytes within their cytoplasm, but structures for cell attachment were intact. HPV and lesion-specific bacteria were not detected.. The number of cases analyzed was two.. Hyperproliferative epidermal state along with enhanced corneocyte fragility may account for the unique features in CPH.

Topics: Aged; Bacteria; DNA, Viral; Female; Hand Dermatoses; Humans; Immunohistochemistry; Keratin-2; Keratins; Keratosis; Microscopy, Electron; Middle Aged; Papillomaviridae; Polymorphism, Restriction Fragment Length; RNA, Ribosomal, 16S; Staining and Labeling

Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression.

Topics: Animals; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Connexin 26; Connexin 30; Connexins; Epidermis; Hemangioma; Humans; Keratinocytes; Keratins; Keratosis; Liver; Melanoma; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms; Warts

Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expressed in stratified epithelia (including skin), due to the RFP reporter driven by the promoter of the zebrafish keratin 18 gene. We titrated doses of inorganic arsenite for zebrafish embryos and found that arsenite exposure at 50 microM for 120 h was suitable for mimicking a long-term, chronic effect. When embryos derived from Tg(k18(2.9):RFP) adults were treated with this arsenite dose and time of exposure, abnormal phenotypes were not noticeable under the light microscope. However, arsenic keratosis was visible in the epithelial cells under the fluorescent microscope. Morphological defects became more severe with increased dose and exposure duration, suggesting that the severity of skin lesions was dose- and time-dependent. Histochemical examination of keratosis after 4',6'-diamidino-2-phenylindole hydrochloride (DAPI) staining showed that the epithelial cells overproliferated after treatment with arsenite. Therefore, this Tg(k18(2.9):RFP) zebrafish line is an excellent model for studying toxicity induced by inorganic arsenite and may have potential for studying other environmental pollutants.

Topics: Animals; Animals, Genetically Modified; Arsenites; Cell Proliferation; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Epithelial Cells; Keratin-18; Keratins; Keratosis; Linear Models; Luminescent Proteins; Microscopy, Fluorescence; Models, Animal; Promoter Regions, Genetic; Random Allocation; Red Fluorescent Protein; Skin; Teratogens; Toxicity Tests; Zebrafish; Zebrafish Proteins

Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties.. Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed.. Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease.. An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases.

Topics: Bowen's Disease; Diagnosis, Differential; Humans; Keratins; Keratosis; Neoplasms, Glandular and Epithelial; Paget Disease, Extramammary; Paget's Disease, Mammary; Regression Analysis; Skin Neoplasms; Sweat Gland Neoplasms

The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Fusion; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Karyotyping; Keratinocytes; Keratins; Keratoacanthoma; Keratosis; Kidney Transplantation; Male; Reverse Transcriptase Polymerase Chain Reaction; Skin Diseases; Skin Neoplasms; Stem Cells; Tissue Donors; Transplantation, Homologous

Focal palmoplantar and gingival keratosis is a rare autosomal dominant disease whose clinical features, and in particular, pathologic alterations and molecular etiology remain to be well defined. Recently we observed a German family affected by the disease in at least 3 consecutive generations. The 4 patients examined showed circumscribed and painful hyperkeratosis at the weight-bearing plantar skin since infancy, rather mild palmar hyperkeratosis, and continuous leukokeratosis confined to the maxillary and mandibulary attached gingiva. There were no nail changes, subungeal keratoses, or follicular hyperkeratosis. Light and electron microscopy of the plantar and gingival lesions revealed alterations of epidermolytic hyperkeratosis. Mutations in the known keratin genes were excluded by linkage analysis using microsatellite markers. We conclude that focal palmoplantar and gingival keratosis is a clinically distinct palmoplantar ectodermal dysplasia that is pathologically characterized by epidermolytic alterations, but is most probably not caused by a mutation in a keratin gene.

Topics: Adult; Child; Ectodermal Dysplasia; Female; Genetic Linkage; Genotype; Gingival Diseases; Humans; Keratins; Keratoderma, Palmoplantar; Keratosis; Male; Middle Aged; Mutation; Pedigree

Topics: Adult; Amino Acid Sequence; Ectodermal Dysplasia; Female; Humans; Keratins; Keratoderma, Palmoplantar; Keratosis; Mouth Diseases; Mutation, Missense; Nails, Malformed; Proline; Syndrome

Topics: Adolescent; Base Sequence; DNA Mutational Analysis; Follow-Up Studies; Foot Dermatoses; Genetic Predisposition to Disease; Hand Dermatoses; Humans; Japan; Keratins; Keratoderma, Palmoplantar, Diffuse; Keratosis; Male; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Risk Assessment; Severity of Illness Index

Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti-Ted-H-1 monoclonal antibody (mAb), but not with antifilaggrin mAb or antiloricrin polyclonal antibody (pAb). This finding indicated that the Ted-H-1 antigenic protein is a haematoxylin-stainable protein in KHG.. To clarify the identity of the major component protein of the large KHG in solar keratosis, another disorder in which large KHG are observed.. An enzyme immunohistochemical study was performed using antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb. Immunofluorescent double staining and immunoelectron microscopic analyses were performed using anti-Ted-H-1 mAb and antiloricrin pAb.. Antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb reacted with normal KHG in nonlesional skin of solar keratosis, while only anti-Ted-H-1 mAb reacted with the large KHG in the lesions of solar keratosis. Antifilaggrin mAb did not react with large KHG. Antiloricrin pAb reacted with the cell membrane of the stratum granulosum, but not with large KHG.. These findings suggest that the haematoxylin-stainable protein in the large KHG would be a Ted-H-1 antigen protein which was neither filaggrin nor loricrin.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Cytoplasmic Granules; Female; Filaggrin Proteins; Fluorescent Antibody Technique; Hematoxylin; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Keratosis; Male; Membrane Proteins; Microscopy, Immunoelectron; Middle Aged; Skin; Sunlight

Human papillomavirus type 16 (HPV16) has been known as a major causative factor for the development of uterine cervical carcinomas. To investigate the in vivo activity of HPV16 expressed in squamous epithelia, transgenic mice harboring HPV16 E6/E7 with human keratin 14 (hK14) promoter were generated. Grossly, hK14 driven HPV16 E6/E7 transgenic mice exhibited multiple phenotypes, including wrinkled skin that was apparent prior to the appearance of hair in neonates, thickened ears, and loss of hair in adults. Transgenic mice with phenotype exhibiting severe wrinkled skin and a lack of hair growth died at the age of 3-4 weeks. Histological analysis revealed that in transgenic mice survived beyond the initial 3-4 weeks, HPV16 E6/E7 causes epidermal hyperplasia in multiple transgenic lineages with high incidence of transgene penetration. This epithelial hyperplasia was characterized by an expansion of the proliferating compartment and keratinocytes, and was associated with hyperkeratosis. Such activities were significantly higher in the skin of transgenic mice than that of the normal mice. Thus, these transgenic mice appeared to be useful for the expression of HPV16 E6/E7 gene and subsequent analysis on hyperkeratosis.

Topics: Animals; Humans; Keratin-14; Keratins; Keratosis; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Promoter Regions, Genetic; Repressor Proteins; Skin Neoplasms

Cannon's disease or white sponge naevus is a relatively rare genetically determined skin disorder. It is inherited as an autosomal dominant trait that displays a high degree of penetrance and expressivity. This article describes cases of Cannon's disease in a mother and her son.

Topics: Adult; Burns, Chemical; Candidiasis, Oral; Child, Preschool; Diagnosis, Differential; Female; Genetic Diseases, Inborn; Humans; Keratins; Keratosis; Leukoplakia, Oral; Male; Mouth Diseases; Mouth Mucosa; Mutation; Pedigree

The antibody 34-betaE12 stains selectively the keratins of basal cells. The aim of this study is to investigate the staining pattern of 34-betaE12 in borderline (keratoacanthomas and solar keratosis), and benign lesions (seborrheic keratoses). The proliferation index Ki-67 staining was also evaluated in these and also in malignant (basal and squamous cell carcinomas) cases. The staining pattern where the 34-betaE12 positive cells found in the basal, suprabasal epidermal layers was called "focal"; and the staining in all layers including upper spinous layer was called "diffuse". Mean proliferation index and the distribution pattern of Ki-67 immunohistochemical expression were assessed. Basal and suprabasal expression of 34-betaE12 significantly predominated in the normal parts of the epidermis, in eight out of 11 seborrheic keratoses (%73), one out of the 19 keratoacanthomas (%5), two out of 11 solar keratosis (18%). Statistical analysis revealed significant differences between mean level of Ki-67 expression of malignant (squamous cell carcinoma, basal cell carcinoma), benign (seborrheic keratoses) and premalignant (solar keratoses, keratoacanthomas) lesions (p<0.01). The distribution of staining pattern for Ki-67 paralleled to the staining pattern of 34-betaE12. Basal cell status assessment completed by 34-betaE12 may resolve some, but not all of the problems in terms of determining the presence of dysplasia.

Topics: Cell Division; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Keratosis; Keratosis, Seborrheic; Ki-67 Antigen; Precancerous Conditions; Skin

A 5-year-old girl presented with extensor hyperkeratotic papules and subungual hyperkeratosis with nail-plate discoloration affecting all twenty nails. The mother reported that her daughter had natal teeth. By report, the father has a similar history and constellation of clinical findings. The patient's clinical presentation and history was consistent with pachyonychia congenita, which is a genodermatosis linked to mutations in the genes encoding keratins 6, 16, and 17.

Topics: Child, Preschool; Female; Genes, Dominant; Humans; Keratins; Keratosis; Mutation; Nail Diseases

Onychomatricoma (OM) is a tumor of the nail matrix typified histologically by multiple distal fibroepithelial projections and a thick keratogenous zone forming multiple V-shaped invaginations at the level of epithelial ridges, with the formation of a thick nail plate. In its proximal portion, the thickness of the nail looks like a spur originating from the ventral part of the nail plate. In its distal part, beyond the lunula, the nail plate is globally thickened and filled with cavities containing serous fluid. Often, however, the pathologist is not provided with the nail plate. The diagnosis then rests on the presence of a fibroepithelial tumor. In this article the histologic criteria of OM without nail plate are refined and OM is characterized immunohistochemically using three tumors fixed in liquid nitrogen and examined separately from the nail plate. On longitudinal section OM without nail plate appears as a unique pedunculated fibroepithelial tumor i.e., the multiple distal epithelial digitations arranged along a transversal plane are not seen. The feature is reminiscent of fibrokeratoma. When OM is visualized in longitudinal section, 3 main criteria differentiate OM from fibrokeratoma: the presence of epithelial-lined invaginations around optical cavities, a stroma organized in 2 layers, and the absence of horny corn. Patterns of expression of cytokeratins and integrins in OM are identical to that observed in the normal nail matrix. Involucrin finds expression from the basal layer through to the top of the epithelium, where it is more marked and where transglutaminase 1 is restricted. Merkel cells detected by CK 20 are increased in number and sometimes disposed in clusters. The fibrous component of OM is composed of 2 layers: a superficial stroma made of numerous fines fibrils of collagen IV intermingled with collagen I, and deep stroma made principally of collagen I. Antibody AE13, specific to trichocytic keratins Ha 1-4, represent a good potential marker of OM. Its V-shaped expression in epithelium ridges offers early identification of the keratogenous zone of OM, on tumors separated from their nail plates and limited to their fibroepithelial components.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Fibroma; Fluorescent Antibody Technique, Indirect; Humans; Integrins; Keratins; Keratosis; Microscopy, Fluorescence; Nail Diseases; Skin Neoplasms

The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen's disease were completely negative. Compatible with this result, the basal cells in Bowen's disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14), which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen's disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen's disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen's disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen's disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly indicate that the basal cells in Bowen's disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis.

Topics: Actins; Bowen's Disease; DNA, Neoplasm; Humans; Immunoenzyme Techniques; Interphase; Keratins; Keratosis; Microscopy, Electron; Proliferating Cell Nuclear Antigen; Reticulin; Silver Nitrate; Skin; Skin Neoplasms; Staining and Labeling; Tumor Suppressor Protein p53

To investigate anti-crypt keratin (CK) immunologic histochemical changes in children with chronic tonsillitis.. Removed tonsilla were fixed by 10% formaldehyde. Immunologic histochemical method was used to determine the changes of anti-broad spectrum (KD 68, 56, 56, 50) CKSP.. In 230 cases, obvious keratosis was 90.9%, no keratosis was 9.1%, 3 cases were found with fungus filaments and bacteria in the bottom of crypts. Anti-broad spectrum and hypermolecule CK of tonsil cryptic epithelium were positive reaction, anti-broad spectrum CK of cryptic keratosis in all cases was positive reaction.. During the period of episode, cryptic epitheliums of tonsilla was destroyed repeatly, therefore, immunoglobulin production was reduce. Because the immune function of tonsilla was reduced, bacteria and virus might be invade into organism. This reduplicative malignant circles must be interrupted or blocked only by tonsillectomy.

Topics: Adolescent; Antibodies; Child; Child, Preschool; Chronic Disease; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Keratosis; Male; Palatine Tonsil; Tonsillitis

Granular parakeratosis is a histologic phenomenon that produces a characteristic clinical picture with multiple brownish and hyperkeratotic papules. In all 6 published cases of localized axillary parakeratosis, excessive use of different topical preparations (cream-type products, deodorants that include roll-on and stick types, antiperspirants, shampoos, bath soaps) was reported by the authors. The exact pathogenic causal relationships have not yet been resolved. In the case reported below, we demonstrate for the first time that the macro- and micromorphological entities can also occur in the submammary region.

Topics: Adult; Breast Diseases; Cell Nucleus; Dermatologic Agents; Epidermis; Female; Humans; Hyalin; Keratinocytes; Keratins; Keratosis; Parakeratosis; Skin Care; Therapeutic Irrigation

c-Myc overexpression has been associated with several types of human cancers. To study the role of c-myc in epidermal differentiation and carcinogenesis, a transgenic mouse model was created to overexpress c-Myc in the epidermis. Human c-myc 2 cDNA was subcloned into a 6.5 kb mouse loricrin expression vector, ML.myc2. This loricrin promoter primarily directs expression in the epidermis in both proliferating and differentiated keratinocytes. On day 4, ML.myc2 transgenic pups develop a hyperkeratotic phenotype, which progressively worsens until day 7. Upon histological analysis, both hyperplasia and hyperkeratosis were evident. Bromodeoxyuridine (BrdU) incorporation revealed that transgenic mice had a threefold increase in the number of proliferating cells as compared with a normal littermate. Proliferative cells in the ML.myc2 epidermis were also found to be suprabasal, suggesting an inhibition of terminal differentiation in keratinocytes. Inhibition of terminal differentiation by c-Myc overexpression was further suggested by aberrant expression of differentiation markers, keratin 1, keratin 6, loricrin, and filaggrin in ML.myc2 transgenic mice. Interestingly, ML.myc2 keratinocytes exhibit a reduced sensitivity to UV-B induced apoptosis, in vivo. In vitro studies reveal the reduced sensitivity of ML.myc2 keratinocytes to UV-B irradiation is growth factor dependent. These findings provide evidence that overexpression of c-Myc in the epidermis induces proliferation, inhibits terminal differentiation and decreases the sensitivity of keratinocytes to UV-B induced apoptosis.

Topics: Animals; Animals, Newborn; Apoptosis; Biomarkers; Cell Differentiation; Cell Division; Epidermis; Female; Filaggrin Proteins; Genes, myc; Growth Substances; Humans; Hyperplasia; Intermediate Filament Proteins; Keratins; Keratosis; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Mice, Inbred Strains; Mice, Transgenic; Ultraviolet Rays

To determine the role of protein kinase Cdelta in mouse skin carcinogenesis, we have developed transgenic FVB/N mouse lines expressing in the epidermis an epitope-tagged protein kinase Cdelta (T7-PKCdelta) regulated by the human keratin 14 promoter. The untreated T7-PKCdelta mice displayed excessive dryness in the skin of the tail with a variable penetrance over time. Histologically, the tail skin showed hyperplasia with evidence of hyperkeratosis. The epidermis of the rest of the T7-PKCdelta mouse was unremarkable. Despite this mild phenotype, the effects of PKCdelta overexpression on mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) were dramatic. Two independent lines of T7-PKCdelta mice (16 and 37) expressing the T7-PKCdelta transgene were examined for responsiveness to skin tumor promotion by 7,12-dimethylbenz[a]anthracene and TPA. By immunoblot analysis, the T7-PKCdelta-16 and T7-PKCdelta-37 mice showed an 8- and 2-fold increase of PKCdelta protein. The T7-PKCdelta-16 mice averaged 300% more T7-PKCdelta activity than the T7-PKCdelta-37 mice did. The T7-PKCdelta-37 mice did not manifest any difference in tumor burden or incidence. However, the reduction in papilloma burden at 25 weeks of promotion for the T7-PKCdelta-16 mice relative to wild-type mice averaged 72 and 74% for males and females, respectively. The T7-PKCdelta-16 mice reached 50% papilloma incidence between 12 and 13 weeks of promotion compared with 8 weeks for wild-type mice. Furthermore, the carcinoma incidence was also reduced in T7-PKCdelta-16 mice. Carcinoma incidence at 25 weeks of promotion treatment was: wild-type females, 78%; T7-PKCdelta16 females, 37%; wild-type males, 45%; and T7- PKCdelta-16 males, 7%. Thus, PKCdelta when expressed at sufficient levels can suppress skin tumor promotion by TPA.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Female; Humans; Isoenzymes; Keratin-14; Keratins; Keratosis; Male; Mice; Mice, Transgenic; Neoplasm Proteins; Papilloma; Protein Kinase C; Protein Kinase C-delta; Sex Factors; Signal Transduction; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

Nevoid hyperkeratosis of the nipple and areola is a rare dermatosis with unknown etiology, (Perez-Izquierdo JM, Vilata JJ, Sanchez JL, et al. Retinoic acid treatment of nipple hyperkeratosis. Arch Dermatol 1990;126:687-688). Only 40 cases have been reported until 1997 (Alpsoy E, Yilmaz E, Aykol A. Hyperkeratosis of the nipple: report of two cases. J Dermatol 1997;24:43-45). The disease has a benign course and may only be a cosmetic problem. Different modalities have been used in the treatment of NHNA. In our case treatment with topical retinoic acid induced an acceptable response.

Topics: Administration, Cutaneous; Adult; Breast Diseases; Female; Humans; Hyperpigmentation; Keratins; Keratolytic Agents; Keratosis; Nipples; Tretinoin; Warts

This case report describes a unique palatal tumor with features of a dermal neoplasm. Microscopically, the lesion appeared similar to a trichoepithelioma and trichoadenoma.. Light microscopic and immunohistochemical studies were performed to arrive at the final diagnosis.. The lesion arose from the surface epithelium and had features of a dermal tumor.. The case report describes a unique benign palatal neoplasm.

Topics: Adenoma, Pleomorphic; Adult; Diagnosis, Differential; Epithelial Cells; Epithelium; Female; Humans; Hyalin; Immunohistochemistry; Keratins; Keratosis; Mouth Mucosa; Neoplasms, Basal Cell; Palatal Neoplasms; Palate, Soft; Skin

Reactive perforating collagenosis is characterised by trans-epidermal elimination of collagen and is hypothesized to be both autosomally dominant and recessive. We report a family in which two brothers and a sister had lesions of reactive perforating collagenosis.

Topics: Adolescent; Child; Child, Preschool; Collagen; Collagen Diseases; Epithelium; Facial Dermatoses; Female; Genes, Dominant; Genes, Recessive; Hand Dermatoses; Humans; Hypopigmentation; Keratins; Keratosis; Male; Skin; Skin Diseases, Papulosquamous

Topics: Acne Vulgaris; Aged; Diagnosis, Differential; Hair Follicle; Humans; Keratins; Keratosis; Male; Skin; Skin Diseases

Topics: Aged; Aged, 80 and over; Ear Diseases; Ear, External; Epidermis; Follow-Up Studies; Humans; Keratins; Keratosis; Male

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Elastic Tissue; Erythema; Female; Humans; Infrared Rays; Keratins; Keratosis; Male; Mitosis; Neoplasms, Multiple Primary; Skin Aging; Skin Neoplasms; Ultraviolet Rays

A case report of twenty-nail dystrophy in a 21-year-old woman is presented. All her finger nails were affected with numerous small superficial pits. The histological findings showed the focal spongiotic change in the nail matrix reflecting the clinical appearance of the nail plate surface.

Topics: Adult; Female; Fingers; Humans; Keratins; Keratosis; Nail Diseases; Nails; Toes

We have previously reported 18 cases of an ichthyosiform contact dermatitis caused by antiseptic solutions containing 3% cetrimide and 0.3% chlorhexidine. The reaction was traced to cetrimide, a mixture of quaternary ammonium compounds that are widely used as disinfectants and detergents. Quaternary ammonium compounds are known irritants. To elucidate the pathogenesis of the abnormal keratinization caused by cetrimide, electron microscopy was performed on biopsied lesions from five patients and on specimens from rabbits in which a mild reaction had been induced by closed patch with Savlon, cetrimide, and chlorhexidine. The patients' samples revealed hyperkeratosis with striking vesiculation of lamellar bodies in the granular cells and upper spinous cells, premature secretion of lamellar bodies, and abundant remnants of lamellar bodies and retention of desmosomes between the corneocytes. Similar lamellar bodies changes were induced in rabbit skin after 48 hours of closed patch with Savlon 1:30 and cetrimide 0.1%, but not with chlorhexidine 3%-further indication that cetrimide was the cause of the dermatitis. We conclude that the abnormal keratinization can be attributed, at least in part, to dysfunction of lamellar bodies resulting from the direct effects of cetrimide on the lipids and enzymes of lamellar bodies. Vesiculation with dysfunction of lamellar bodies may be an important pathogenetic mechanism in irritant dermatitis caused by quaternary ammonium compounds.

Topics: Animals; Anti-Infective Agents, Local; Anti-Inflammatory Agents, Non-Steroidal; Blister; Cetrimonium; Cetrimonium Compounds; Chlorhexidine; Cytoplasmic Granules; Dermatitis, Contact; Dermatitis, Irritant; Desmosomes; Drug Combinations; Epidermis; Humans; Ichthyosis; Keratinocytes; Keratins; Keratosis; Lipid Metabolism; Microscopy, Electron; Organelles; Patch Tests; Rabbits; Skin

The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies.. Our purpose was to determine Glut1 expression in cutaneous neoplasms.. A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia.. All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses.. Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

Topics: Antibodies; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Division; Cicatrix; Dermatitis, Seborrheic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Keratosis; Melanoma; Monosaccharide Transport Proteins; Neoplasm Invasiveness; Nevus; Regeneration; Skin Neoplasms

Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes.. Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA.. We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment.. In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective.. LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Amyloid; Amyloidosis; Antipruritics; Chronic Disease; Collagen; Disease; Female; Histamine H1 Antagonists; Humans; Keratinocytes; Keratins; Keratosis; Leg Dermatoses; Male; Middle Aged; Necrosis; Neurodermatitis; Pruritus; Remission Induction; Skin; Skin Diseases

Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta-related growth factors. In the developing epidermis, expression of BMP-6 coincides with the onset of stratification. Expression persists perinatally but declines after day 6 postpartum, although it can still be detected in adult skin by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. We constitutively overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter. All mice expressing the transgene developed abnormalities in the skin, indicating an active transgene-derived factor. Depending on the pattern of transgene expression, the effects on proliferation and differentiation were completely opposite. Strong and uniform expression of the BMP-6 transgene resulted in severe repression of cell proliferation in embryonic and perinatal epidermis but had marginal effects on differentiation. Weaker and patchy expression of the transgene evoked strong hyperproliferation and parakeratosis in adult epidermis and severe perturbations of the usual pattern of differentiation. These perturbations included changes in the expression of keratins and integrins. Together with an inflammatory infiltrate both in the dermis and in the epidermis, these aspects present all typical histological and biochemical hallmarks of a human skin disease: psoriasis.

Topics: Acanthosis Nigricans; Animals; Animals, Newborn; Antigens, CD; Bone Morphogenetic Protein 6; Bone Morphogenetic Proteins; Cell Differentiation; Cell Division; Epidermal Cells; Epidermis; Gene Expression Regulation, Developmental; Humans; Integrin alpha6; Keratin-10; Keratins; Keratosis; Mice; Mice, Transgenic; Mouth Mucosa; Promoter Regions, Genetic; Psoriasis; RNA, Messenger; Skin; Stomach

Kindler syndrome is a genodermatosis that combines clinical features of hereditary epidermolysis bullosa and poikiloderma congenitale. The ultrastructural level of blister formation has not been well characterized.. Two brothers with Kindler syndrome had a history of primarily acral blistering since infancy as well as photosensitivity. Blister formation was found through the basal layer. Marked tonofilament clumping was found in intact keratinocytes adjacent to the blisters. The younger brother (aged 21 years) had actinic keratoses, which have not been previously described in Kindler syndrome.. The findings of basal layer separation in both spontaneous and induced blisters in Kindler syndrome suggest this is the true level of blister formation. The finding of actinic keratoses in a young patient with Kindler syndrome suggests that some patients may be at increased risk for early solar-induced skin disease. The presence of clumped tonofilaments in keratinocytes adjacent to blistered areas suggests an abnormality of keratin 5 or 14 could be present and may play a role in blister formation in patients with Kindler syndrome.

Topics: Adult; Blister; Epidermolysis Bullosa; Humans; Intermediate Filaments; Keratinocytes; Keratins; Keratosis; Male; Photosensitivity Disorders; Rothmund-Thomson Syndrome; Skin; Syndrome

The odontogenic keratocyst (OKC) is a locally aggressive neoplasm with rates of recurrence reported as high as 60%. Correlation between histopathology and the likelihood of recurrence remains a subject of controversy. In this review of the authors' experience in treating 50 patients with OKC between 1977 and 1993, 58 specimens were studied to correlate the likelihood of recurrence with the presence of the following histologic features--parakeratosis, orthokeratosis, satellite cysts, epithelial rests, or epithelial proliferation. Orthokeratinized cysts were associated with a higher recurrence rate than in previously reported studies. Disruption of the epithelial lining in the resected specimen was found to be a primary determinant of recurrence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Division; Child; Epithelium; Female; Follow-Up Studies; Humans; Inflammation; Keratins; Keratosis; Male; Mandibular Diseases; Maxillary Diseases; Middle Aged; Odontogenic Cysts; Radiography; Recurrence

The purpose of this study was to characterize a spontaneous disease condition causing hyperkeratosis in nude mice and to explore the etiologic role of a particular species of coryneform bacteria in this disease, colloquially known as "scaly skin disease." The study was divided into two parts. In the first phase, a series of inoculation experiments was conducted with a field isolate of the coryneform species used to study the clinical and histopathologic development of the disease syndrome. Athymic nude mice (4 to 5 weeks old) were inoculated on the skin of the back with a suspension of a pure culture of the coryneform bacterium that had been isolated from a field case. The culture was applied with a sterile cotton swab in concentrations varying from 6.1 x 10(4)/ml to 5.0 x 10(7)/ml. All inoculated mice became persistently infected throughout the 33 days of the experiment. Clinically evident hyperkeratosis in inoculated animals developed more frequently in mice housed in a microisolator cage than in a semi-rigid isolator and more frequently in mice inoculated with higher numbers of organisms. In all animals in which hyperkeratosis developed, it was first noted on day 7 after inoculation. The second series of experiments was designed to determine the success of various housing methods in excluding the infection, mechanisms of transmission, susceptibility of other stocks and strains of mice to the organism, and whether the other strains might serve as a source of the organism. Results of the study in various strains indicated that both immunocompetent and immunodeficient mice, whether glabrous or hirsute, could be infected with the organism, but only glabrous animals developed hyperkeratosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Corynebacterium; Corynebacterium Infections; Epidermis; Fatty Acids; Female; Keratins; Keratosis; Lactams; Macrolides; Male; Mice; Mice, Nude; Microbial Sensitivity Tests; Rodent Diseases; Skin Diseases, Bacterial

Transgenic mice that expressed v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos) developed preneoplastic epidermal hyperplasia and hyperkeratosis after long latency and an associated wound promotion stimulus. To assess the requirements for papilloma formation and malignant conversion and determine the sensitivity to a chemical promotion stimulus, HK1.fos mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). HK1.fos mice were sensitive to TPA promotion but developed papillomas only after long latency (20-30 weeks of promotion) and in relatively few numbers per animal, suggesting the necessity of an additional genetic event prior to overt lesion formation. Consistent with this idea, at 60 weeks, on cessation of TPA promotion, these HK1.fos TPA-papillomas were found to be autonomous, TPA-independent tumors which persisted, grew larger, and converted to malignancy. Analysis of HK1.fos tumor RNA and DNA identified endogenous c-rasHa mutations at codons 12 and 61 in papillomas and carcinomas; however, no p53 tumor suppressor gene mutations were detected. These data indicate that epidermal expression of v-fos induces sensitivity to TPA promotion, but since additional genetic events, such as endogenous c-rasHa activation, appear to be required in tumorigenesis, v-fos may predominantly play a role in the mechanism of promotion to achieve papilloma autonomy and TPA independence. Furthermore, spontaneous malignant conversion in this model does not appear to involve mutations in the p53 tumor suppressor gene.

Topics: Animals; Base Sequence; Biomarkers; Carcinoma; Cell Differentiation; Cell Transformation, Neoplastic; DNA, Neoplasm; Epidermis; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, p53; Genes, ras; Hyperplasia; Keratins; Keratosis; Mice; Mice, Transgenic; Molecular Sequence Data; Mutation; Oncogene Proteins v-fos; Papilloma; ras Proteins; RNA, Neoplasm; Tetradecanoylphorbol Acetate

A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.

Topics: Arm; Epidermis; Female; Filaggrin Proteins; Follow-Up Studies; Humans; Hyperpigmentation; Ichthyosiform Erythroderma, Congenital; Infant; Infant, Newborn; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Leg; Lichenoid Eruptions; Protein Precursors; Syndrome

Of 291 immunosuppressed renal transplant recipients (RTRs) with surviving allografts attending the Royal London Hospital, 171 patients (59%) were found to have warty keratoses. On histological analysis, the lesions in 50 patients (17%) showed partial-thickness dysplasia, and 34 (12%) had one or more invasive squamous cell carcinoma (SCC) and/or one or more in situ SCC or full-thickness dysplasia. We examined the claim that squamoproliferative lesions in RTRs possess distinctive histopathological features that differ from those of similar lesions occurring sporadically in the nonimmunosuppressed population. We compared 40 squamoproliferative lesions from RTRs with 40 matched squamoproliferative lesions from nonimmunosuppressed patients; lesions were coded and their source was unknown to the assessors. Two dermatopathologists independently assessed the cases and gave scores for 11 histological features that have been reported to be characteristic of such lesions in the immunosuppressed population. These included a warty architecture, koilocytes, and multinucleate giant cells. Using these criteria, it was not possible to distinguish lesions of immunosuppressed patients from those of immunocompetent people.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Epithelium; Female; Giant Cells; Graft Survival; Humans; Hyalin; Immunocompetence; Immunosuppression Therapy; Keratins; Keratosis; Kidney Transplantation; Male; Neoplasm Invasiveness; Papilloma; Skin Neoplasms; Transplantation, Homologous; Warts

We report the case of a second patient with the extraordinary ultrastructural findings of vacuolated structures intermingled with membranes in the perinuclear part of the upper epidermal cells. Clinical, light microscopic, and electron microscopic features of this particular presentation of ichthyosis congenita type III have already been presented by K. M. Niemi and L. Kanerva in 1989. Although our patient has more or less the same light and electron microscopic findings, the clinical picture is more severe. The patient was born as a collodion baby. Later, he showed signs of generalized severe involvement with large scales, erythrodermia, and itching. Successful therapy with retinoids resulted in complete removal of the hyperkeratosis but left the striking reticulate skin pattern. Noting the heterogeneous clinical presentation, the specific electron microscopic findings are diagnostic. No biochemical data on this disease are known.

Topics: Adult; Cell Nucleus; Cytoplasmic Granules; Dermatitis, Exfoliative; Dermatologic Agents; Epidermis; Humans; Hyalin; Ichthyosis; Keratins; Keratosis; Male; Microscopy, Electron; Mitochondria; Pruritus; Retinoids; Skin; Vacuoles

The present study was conducted to determine the patterns of immunohistochemical characterization of keratin (K) and involucrin in solar keratosis and Bowen's disease in order to clarify the abnormal differentiation or maturation of the tumor cells in these precancerous epithelial dermatoses. Seventeen human anti-cytokeratin antibodies and an anti-involucrin antibody were used to examine 15 cases of solar keratosis and 18 cases of Bowen's disease. Formalin-fixed and paraffin-embedded sections were stained with these antibodies by the avidin-biotin-peroxidase technique. In solar keratosis, keratin and involucrin distribution was similar to that in normal epidermis, whereas in Bowen's disease the keratin distribution varied among individual cases. The dyskeratotic cells in Bowen's disease showed a reduction or loss of staining with these antibodies, and they were occasionally positive for keratin 19. These observations suggest that there is a difference in keratin and involucrin expression between solar keratosis and Bowen's disease and that the atypical cells of Bowen's disease exhibit a diversity of differentiation.

Topics: Aged; Aged, 80 and over; Bowen's Disease; Cell Differentiation; Cellular Senescence; Epidermis; Female; Fixatives; Formaldehyde; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Keratosis; Male; Middle Aged; Paraffin Embedding; Precancerous Conditions; Protein Precursors; Skin Neoplasms; Sunlight

Nail pathology shares some common features with skin pathology, but it also has its own peculiar aspects. The anatomical and physiological characteristics of the nail unit probably play a major role in determining these pathological differences. Although the presence of keratohyaline granules is a normal feature of the skin, there is no granular layer in the normal nail matrix. As a consequence, nail matrix hypergranulosis should be considered a separate entity from skin hypergranulosis. In our review of 150 longitudinal nail biopsy specimens, keratohyaline granules were seen in the nail matrix of 24 cases of lichen planus, 29 cases of spongiotic trachyonychia, 10 cases of psoriasis, and three cases of Hallopeau acrodermatitis. In all cases, the presence of keratohyaline granules was associated with the absence of the normal keratogenous zone. Similar nail matrix features were detectable in three cases of malignant melanoma, two cases of primary systemic amyloidosis, and one case of histiocytoid hemangioma compressing the nail matrix. Our data suggest that inflammatory and compressive insults to the nail matrix cause both disappearance of the keratogenous zone and matrix keratinization with the formation of keratohyaline granules. Skin hypergranulosis reflects a hyperplasia of a normal skin component. In the nail matrix, however, hypergranulosis represents the appearance of structures not normally present. Nail matrix hypergranulosis should be considered a pattern of nail matrix reaction to different inflammatory insults. It is therefore more analogous to epidermal parakeratosis than to epidermal hypergranulosis.

Topics: Acrodermatitis; Amyloidosis; Biopsy; Epidermis; Epithelium; Hemangioma; Humans; Hyalin; Hyperplasia; Keratins; Keratosis; Lichen Planus; Melanoma; Nail Diseases; Nails; Onychomycosis; Psoriasis

Monospecific antibodies to individual keratin polypeptides can be used to examine the tissue and cellular coexpression of members of keratin pairs. Monospecific monoclonal and polyclonal antibodies have been raised to keratins 1 and 10 using both crude cytoskeletal extracts and synthetic peptides. The tissue distribution of these keratins has been determined against a panel of freshly frozen normal tissues from humans, rodents and pigs. Epidermal expression has been examined in psoriatic plaques, and healing wounds, as examples of epidermal hyperproliferation. Cultured keratinocytes in monolayer (low calcium), stratified (high calcium), and complex cultures, transformed keratinocytes, and tumour cell lines, have been examined for the in vitro expression of these keratins. The sensitivity and precise localization of reactivity with these monospecific antibodies gives a highly accurate picture of individual cell expression. There is confirmation of coexpression of keratins 1 and 10 in epidermal and mucosal sites, and with keratin 16 in hyperproliferative states. These monospecific antibodies provide an important means of examining keratin expression in epidermal tumours and keratinizing disorders, and of seeking keratin mutations in cell lines and in skin diseases.

Topics: Adult; Animals; Antibodies, Monoclonal; Biomarkers; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; Epidermal Cells; Epidermis; Gene Expression Regulation; Humans; Infant, Newborn; Keratinocytes; Keratins; Keratosis; Mice; Mice, Inbred BALB C; Mucous Membrane; Psoriasis; Skin; Skin Neoplasms; Swine; Wound Healing

The clinico-pathologic, immunohistochemical and radiological features of 12 jaw cysts with a prominent orthokeratinized epithelial lining were studied and compared with those of typical odontogenic keratocysts and dentigerous cysts. They differed significantly from odontogenic keratocysts in terms of biologic behavior and histopathologic findings. Although immunohistochemical staining of the epithelial linings for cytokeratins, EMA, CEA and involucrin has not shed any light on the histogenesis of these lesions, staining patterns for these markers were significantly different from those of odontogenic keratocysts and non-keratinized dentigerous cysts. Radiologically, nine cases appeared as dentigerous cysts; two cases, one with sebaceous differentiation, as non-dentigerous unilocular cysts, and the remaining one was exceptional as it showed multiple epidermal cysts with prominent dermal appendages histologically. It is suggested that most of the orthokeratinized jaw cysts may belong to clinico-pathological entities different from odontogenic keratocysts with the majority representing dentigerous cysts with orthokeratinization. The possibility of the existence of rare central dermoid or epidermoid cysts is also to be considered.

Topics: Adolescent; Adult; Child; Child, Preschool; Dentigerous Cyst; Dermoid Cyst; Female; Humans; Immunohistochemistry; Jaw Cysts; Keratins; Keratosis; Male; Odontogenic Cysts

Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS.. In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members.. An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

Topics: Adult; Aged; Atrophy; Cicatrix; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Neck; Skin Diseases

The regulatory elements of the human keratin K1 gene have been used to target expression of the v-Ha-ras oncogene exclusively in the epidermis of transgenic mice. We developed 12 transgenic mouse lines that express the HK1.ras transgene, producing epidermal hyperplasia in neonates and hyperkeratosis in juveniles. Eventually this skin phenotype diminished but with time adult animals developed papillomas that could persist or regress. The rate and frequency of tumorigenesis appeared to be limited, which suggests that v-Ha-ras requires a second or even third event to elicit and maintain a benign phenotype in transgenic mice. Since in certain transgenic lines papillomas appeared at wound sites, it appears that the promotion stimulus from wounding may be a second event. We envision that such transgenic mice that express v-Ha-ras in the epidermis will become a powerful model for assessing how environmental and molecular factors affect the process of multistage skin carcinogenesis in vivo, as well as a model for evaluating novel therapeutic protocols.

Topics: Aging; Animals; Bacteriophage lambda; Base Sequence; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Fluorescent Antibody Technique; Gene Expression; Gene Expression Regulation, Neoplastic; Genes, ras; Genetic Techniques; Hyperplasia; Keratins; Keratosis; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Polymerase Chain Reaction; Regulatory Sequences, Nucleic Acid; RNA, Neoplasm; Skin Neoplasms

Four cases of either combined occurrence of ameloblastoma and odontogenic keratocyst or a rare keratinising variant of ameloblastoma are presented. The cardinal histomorphologic characteristics are simultaneous occurrence of ameloblastomatous epithelial islands with central keratinisation and multiple keratinising cysts. Immunohistochemically the tumour elements were keratin positive and occasionally S-100 protein and desmin positive. Major differential diagnosis of these neoplasms are discussed.

Topics: Adult; Ameloblastoma; Connective Tissue; Desmin; Epithelium; Female; Humans; Keratins; Keratosis; Male; Mandibular Diseases; Mandibular Neoplasms; Maxillary Diseases; Maxillary Neoplasms; Odontogenic Cysts; S100 Proteins

Two patients suffering from ichthyosis with unusual ultrastructural features were examined. One was a 14-year-old boy with ichthyotic skin since birth. The ichthyosis was initially erythrodermic and later presented as follicular hyperkeratosis. The other patient was an ichthyotic child who died 2 days after birth of respiratory distress syndrome. Although apparently not consanguineous, both families came from the same relatively isolated rural area and autosomal recessive inheritance seems likely. Light microscopy did not yield diagnostic features, but the ultrastructural findings in the granular and horny cells showed diagnostic lamellar membrane packages. Identical ultrastructural features have previously been published in one prematurely born baby who died soon after birth and once in a prenatal diagnosis in the same family; the disease was termed "ichthyosis congenita type IV".

Topics: Adolescent; Cell Nucleus; Cytoplasm; Epidermis; Genes, Recessive; Hair; Humans; Hyalin; Ichthyosis, Lamellar; Infant, Newborn; Keratins; Keratosis; Langerhans Cells; Male; Microtubules; Scalp; Skin

A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appeared at other epidermal sites, most notably in the axilla and inguinal areas. This indicates that a second promoting event, such as wounding or friction, is required to elicit these pathological changes. Highly keratotic benign ear lesions and benign squamous papillomas appeared after long latency at sites of phenotypic epidermis. These data suggest that v-fos may be interfering with c-fos function in normal keratinocyte differentiation, but by itself is insufficient to elicit overt benign lesions.

Topics: Alopecia; Animals; Base Sequence; Cell Differentiation; Epidermis; Gene Expression Regulation, Neoplastic; Genes, fos; Hyperplasia; Keratins; Keratosis; Mice; Mice, Transgenic; Molecular Sequence Data; Oncogene Proteins v-fos; Proto-Oncogene Proteins c-fos; Skin Neoplasms

The various cytokeratin polypeptides in oral epithelia are expressed in dependence on site and formation of a stratum corneum. Certain cytokeratins occur permanently and others occasionally. In fibrous hyperplasia and Lichen ruber planus, patterns of cytokeratins did not deviate significantly from normal. In some but not all cases of squamous cell carcinoma and leukoplakia studied, marked aberrations of pattern were characterized by (i) appearance of cytokeratin No. 19, (ii) somewhat more frequent occurrence of cytokeratins Nos. 8 and 18, (iii) proteolytic modifications of cytokeratins, and (iv) partial loss of a few site-specific cytokeratins. The aberrations may be taken as additional diagnostic criteria for differentiation between non-aggressive and potentially aggressive leukoplakic lesion, even if they are not correlated with the conventional histological grading of dysplasia.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Female; Gingiva; Humans; Hyperplasia; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Molecular Weight; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms

Localized absence of epithelial Langerhans cells (LC) has been shown to affect systemic immune responses, allow microbial colonization and play a possible role in carcinogenesis. Because use of smokeless tobacco is associated with abnormal oral mucosal changes and development of carcinoma, we examined lesion and control specimens from 17 current users of smokeless tobacco to determine whether lesions showed changes in LC number or antigen expression. We identified LC by immunohistochemistry with antibodies to the antigens T6, HLA-DR, HLA-DQ, and HLA-DP. Lesion specimens contained fewer LC (means of 6 LC/mm and 10 LC/mm2) than did the corresponding control specimens (means of 14 LC/mm and 30 LC/mm2), and in each pair of lesion and autologous control specimens the reduction in LC was on average 58% (range, 3% to 95%). There were no apparent differences between lesion and control specimens in the number of LC expressing each of the four marker antigens. Reductions in LC occurred in all types of smokeless tobacco-associated lesions, regardless of increased epithelial thickness or changes in keratinization. Our data indicate that smokeless tobacco reduces the number of Langerhans cells at its site of contact with the oral mucosa.

Topics: Antigens, Surface; Cell Count; Cell Nucleus; Epithelium; HLA-DP Antigens; HLA-DQ Antigens; Humans; Hyperplasia; Keratins; Keratosis; Langerhans Cells; Leukoplakia, Oral; Male; Mouth Mucosa; Plants, Toxic; Tobacco, Smokeless; Vacuoles

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) has been said to represent a widely dilated, keratin-plugged acrosyringium and dermal duct. We have observed in a case of congenital PEODDN a normal-appearing, acrosyringium-like duct that traverses vertically the entire length of the parakeratotic column. Also, in its lower course, it stained positively for carcinoembryonic antigen, while the inner borders of the invagination from which the parakeratotic column arose stained negatively. This leads us to suggest that the epithelial structure in PEODDN is an abnormally keratinizing epidermal invagination through which an acrosyringium-like duct traverses, rather than an abnormally dilated, parakeratotically plugged acrosyringium and dermal duct.

Topics: Adult; Carcinoembryonic Antigen; Eccrine Glands; Epidermis; Epithelium; Hand; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Keratosis; Male; Nevus, Pigmented; Skin Neoplasms

Topics: Biomarkers; Cell Differentiation; Humans; Keratinocytes; Keratins; Keratosis

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.

Topics: Cell Count; Cell Cycle; Humans; Immunohistochemistry; Keratins; Keratosis; Kinetics; Skin; Skin Diseases

Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) has been suggested to be a separate disease entity. However, the distinction from linear psoriasis has been discussed in the literature over recent decades. The aim of the present study was to investigate, in addition to the clinical and histological criteria, the immunohistochemical aspects of inflammation, epidermal proliferation and keratinization. From a clinical and histological point of view, ILVEN and psoriasis, according to the established criteria, have been proved to overlap. The immunohistochemical study suggests that the following procedures have an additional diagnostic impact: assessment of elastase-positive cells, assessment of keratin 16 and of keratin 10.

Topics: Adult; Aged; Antibodies, Monoclonal; Chromoblastomycosis; Diagnosis, Differential; Humans; Keratins; Keratosis; Male; Middle Aged; Nevus; Pancreatic Elastase; Psoriasis; Skin Neoplasms

Porokeratoses are known to give rise to squamous and basal cell carcinomas. In this study, we examined 15 lesions of porokeratosis immunohistochemically for evidence of aberrant keratinization using several markers of keratinocyte (KC) maturation and differentiation, including involucrin, filaggrin, cytokeratins, and the growth activation marker psi-3. The staining patterns obtained were compared with several non-premalignant parakeratotic skin lesions including psoriasis, pityriasis rosea, pityriasis rubra pilaris, irritated seborrheic keratosis, atopic dermatitis, seborrheic dermatitis, and verruca vulgaris. The centers of porokeratoses stained in a pattern identical to that observed in other premalignant keratinocytic lesions including actinic keratoses, recessive dystrophic epidermolysis bullosa, and nonhealing wounds. KCs beneath the cornoid lamella (CL) stained in a pattern similar to that observed in squamous cell carcinomas. KCs peripheral to the CL in the epidermis showed a normal staining pattern. The control non-premalignant parakeratotic lesions displayed a variety of staining patterns, but none showed a pattern identical to that observed in porokeratosis. The failure of KCs in porokeratoses to mature and differentiate normally may be related to the increased incidence of carcinomas associated with these lesions.

Topics: Epidermis; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Protein Precursors; Skin Neoplasms

The mechanisms of comedogenesis and comedolysis were investigated at the ultrastructural level after applying oleic acid (OA) only, or oleic acid together with vitamin A acid (VAA), to rabbit ears daily for two weeks. 1) In the follicular epithelium of the experimentally-induced comedo (EIC) by OA, several ultrastructural changes similar to those in human comedo were observed. EIC in rabbit ears appeared to be induced both by the hyperkeratinization of the follicular epithelium and by the delayed desquamation of horny cells due to the persistence of intercellular binding apparatus. 2) VAA strongly inhibited the formation of EIC. In the follicular epithelium, two different types of changes, non-cohesive hyperkeratinization and inhibition of keratinization, were observed. These represent the cell injury and recovery stages, respectively. VAA induced the disturbance of follicular epithelial keratinization and reduction of intercellular bindings between horny cells. These effects might prevent the cohesion and accumulation of horny cells and inhibit EIC formation. 3) The number of Odland bodies (Ods) showed an inverse correlation with the cohesion of horny layer. These findings support the theory that Ods have a desquamating function as extracellular lysosomes. The change in Ods would also contribute to both EIC formation by OA and the inhibition by VAA. In addition, VAA caused a characteristic increase in Ods with lamellar structures. It is suggested that Ods with lamellar structures have a desquamating function.

Topics: Acne Vulgaris; Animals; Cytoplasmic Granules; Desmosomes; Hair; Hyalin; Keratins; Keratosis; Male; Microscopy, Electron; Oleic Acid; Oleic Acids; Rabbits; Vitamin A

A monoclonal antibody (ES3A) was raised against a mouse graft-versus-host reaction (GVHR) model. This antibody was against basal cell cytoplasm and reacted with an acidic (pI 6.2) 50 kDa keratin of human epidermis. However, ES3A reacted with several lower layers of epidermal cells in psoriasis and seborrhoeic keratosis. Acanthotic seborrhoeic keratosis showed varying patterns even in a single lesion. If combined with FACS analysis, ES3A-positive cells could be quantified. Normal skin showed 28%, while psoriasis and seborrhoeic keratosis showed 44% and 51%, respectively. ES3A-positive compartments of the acanthotic type of seborrhoeic keratosis were larger than those of the hyperkeratotic type. ES3A may be suitable for quantification of germinative or proliferative cells.

Topics: Animals; Antibodies, Monoclonal; Cell Fusion; Cell Separation; Dermatitis, Seborrheic; Disease Models, Animal; Epidermal Cells; Flow Cytometry; Fluorescent Antibody Technique; Graft vs Host Reaction; Humans; Immunoblotting; In Vitro Techniques; Keratins; Keratosis; Mice; Propidium; Psoriasis

In weanling rats, after receiving a zinc-deficient diet (less than 1 ppm) for 4 wk, the buccal mucosa appears hyperplastic. This study determines changes at earlier stages of the lesion. After 9 days of deficiency, the keratin layer had partially converted to parakeratosis and thickened, and the size of the capillary bed was increased. After 18 days, the keratin layer was fully parakeratotic and thickened further. The cellular layer was thickened. The mitotic rate was doubled and rete ridges were convoluted. After 27 days, the keratin and cellular layers were further thickened, and the mitotic rate remained elevated. The rete ridges were further convoluted. The number of mast cells was doubled and the size of the vascular bed had increased further. These findings suggest early and late interactions between the epithelium and lamina propria. After four days on a control diet following 27 days of zinc deficiency, the mucosa returned normal.

Topics: Animals; Capillaries; Cell Count; Connective Tissue; Cytoplasmic Granules; Epithelium; Hyalin; Keratins; Keratosis; Male; Mast Cells; Mitosis; Mouth Mucosa; Rats; Rats, Inbred Strains; Time Factors; Zinc

While some cutaneous squamous cell carcinomas (SCC) arise from predisposing conditions such as burn scars, draining sinuses, and chronic, nonhealing wounds, the vast majority of these tumors arise from actinically damaged epidermis. It has been shown previously that keratinocytes within healing wounds show an "activated" immunophenotype when stained with antibodies to psi-3, involucrin, filaggrin, and cytokeratins. A similar pattern has been seen in keratinocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), in whom the incidence of cutaneous SCC is markedly increased. We tested the hypothesis that actinic keratoses (AK), recognized as precursors in the development of the majority of SCC, would show a similar activated immunophenotype when stained with the antibody panel described above. We examined 10 AK, biopsied from the facies and extremities of ten patients, ages 60 to 80, with antibodies to psi-3, involucrin, filaggrin, and AE1. All lesions examined had an immunostaining pattern indistinguishable from that seen in keratinocytes from patients with RDEB or within healing wounds. There was suprabasilar staining of keratinocytes with antibodies to psi-3 and AE1. Involucrin and filaggrin was expressed by all keratinocytes above the midstratum spinosum. Within the acrosyringia and acrotrichia, the staining pattern was that of the normal epidermis, i.e., AE1 staining of basal keratinocytes, granular layer staining of involucrin and filaggrin, and absence of psi-3 expression. These data suggest that an activated keratinocyte phenotype is a unifying feature in conditions which predispose to development of cutaneous SCC.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermis; Female; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Male; Middle Aged; Phenotype; Precancerous Conditions; Protein Precursors; Skin Neoplasms; Sunburn

Seborrheic keratoses were investigated by means of histo- and biochemical techniques in order to define the epidermal differentiation and proliferation of this most common epithelial tumor in adults. The following markers have been used in our study: cytokeratins, epidermal proteins binding zinc, insulin receptors, tissue plasminogen activator (tPA), as well as calmodulin (immunohistochemical and quantitative evaluation). Immunohistochemical investigation of seborrheic keratoses revealed a decreased tPA expression; their epidermal concentration of calmodulin was doubled. The differentiation markers failed to show any significant deviation from normal skin. Thus, seborrheic keratoses are associated with normal epidermal differentiation in spite of morphogenic alterations. Pathogenetically, we have to consider epidermaldermal interactions.

Topics: Calmodulin; Carrier Proteins; Dermatitis, Seborrheic; Humans; Immunohistochemistry; Keratins; Keratosis; Receptor, Insulin; Skin; Tissue Plasminogen Activator

Cultured epidermal sheets were examined before and at various times after grafting on skin ulcer beds. Before grafting, the sheet consisted of four to five layers of keratinocytes with incomplete differentiation. Ten days after grafting, graft recipient sites showed compact hyperkeratosis, a normal-appearing epidermis, and a flat dermoepidermal junction. At 6 months, the stratum corneum had a basket-weave appearance but the dermoepidermal junction remained flat. Monoclonal antibodies to keratins 14 and 10 showed normal basal and suprabasal localization, respectively. Electron microscopy showed a normal basement membrane with anchoring fibrils. LH7:2, a monoclonal antibody that binds to the type VII collagen molecule, stained the dermoepidermal junction in all biopsy specimens. AE-1, an antibody that stains suprabasal cells in hyperproliferative skin, was expressed suprabasally for up to 12 weeks after healing (16 weeks after grafting), but expression was confined to the basal layer at 18 weeks after healing (6 months after grafting). Anti-involucrin staining was found in the deeper layers of the epidermis up to 12 weeks after healing (16 weeks after grafting) but had receded to a normal distribution in upper spinous and granular layers at 18 weeks (6 months after grafting). Overall, the histologic patterns observed in recipient sites during the first 4 months after grafting resembled those observed for 10 to 14 days in newly healed epidermis and in hyperproliferative states such as psoriasis. In four sex-mismatched graft sites, specimens were reacted with a biotinylated probe to the Y chromosome by in situ hybridization. Lack of Y chromosome-positive cells suggested that host keratinocytes had replaced the allografts. Multilocus DNA analysis in one patient confirmed this observation. Our data suggest that an altered state of epithelial maturation persists for several months after culture grafting, with restoration of the normal pattern by 6 months. No differences were detected between autografted and allografted sites.

Topics: Cells, Cultured; DNA; DNA Probes; Female; Graft Survival; Humans; Keratins; Keratosis; Skin; Skin Transplantation; Skin Ulcer; Wound Healing

The present investigation was based on the postulate, first proposed by Reed and Leone in 1970, that porokeratosis lesions represent clonal growth of epidermal cells. Comparative studies using immunocytochemical staining, epidermal cell culture, and non-equilibrium pH gradient (NEpHG) gel electrophoresis analysis of the keratins extracted were carried out on five patients with various types of porokeratosis. Positive type IV collagen staining on the stratum corneum was found in lesional skin specimens of all patients, but not in normal controls. A search for connections between type IV collagen in the basement membrane of epidermis and the skin surface disclosed infrequent intra-epidermal streaking of type IV collagen and one positively stained trans-epidermal acrosyringium. Positive intra-epidermal laminin staining in porokeratosis lesions confirmed the trans-epidermal passage of basement-membrane materials. Epidermal cells cultured from lesional skin showed low plating efficiency, and all colonies exhibited intracytoplasmic vacuole formation and excessive top cell shedding. NEpHG gel electrophoresis of keratins extracted showed that lesional profiles not only contained keratins normally present in glabrous skin, but also possibly K9 and some additional proteins. K9 had been immunolocalized to periductal cells in previous studies. Our findings, taken together, strongly suggest that porokeratosis epidermis consists of epithelial cells with lumen-forming ability.

Topics: Blotting, Western; Cells, Cultured; Epidermis; Humans; Immunohistochemistry; Keratins; Keratosis; Male; Reference Values; Skin

We report on two cases of pachyonychia congenita, Jadassohn-Lewandowsky type, in a father and daughter. Histopathological examination revealed thickened, aggregated bundles of tonofilaments and an increased number of atypical keratohyalin granula, which is suggestive of an altered keratinization. Immunohistological staining with antibodies to cytokeratins (A45-B/B3, A51-B/H4, A53-B/A2, RPN 1161) was unchanged. Filaggrin could not be detected. Basal cells immunoreactive for calmodulin were markedly reduced or even absent in the rete ridges. Staining with a monoclonal antibody against Ki67 made epidermal cell hyperproliferation seem unlikely. The epidermal lectin binding was normal. C3 was detectable in vessel walls mainly of the stratum reticulare. The findings are discussed with reference to pachyonychia pathogenesis.

Topics: Adolescent; Adult; Autoantibodies; Female; Filaggrin Proteins; Humans; Hyperhidrosis; Immunohistochemistry; Keratins; Keratosis; Male; Nails, Malformed; Syndrome

Among carcinomas, signet-ring morphologic characteristics have been regarded as pathognomonic of adenocarcinoma. This report presents the case of a poorly differentiated cutaneous squamous cell carcinoma with a monodispersed, invasive signet-ring component. Kreyberg stains had negative results for mucin. Immunohistochemical analysis demonstrated that concentric rings in the signet-ring cells were composed of keratin. To the best of the authors' knowledge, this is the first report of signet-ring squamous cell carcinoma. Another feature that bears emphasis is that this squamous cell carcinoma led to the death of the patient, even though it originated in a field of actinic keratosis.

Topics: Adenocarcinoma, Mucinous; Aged; Carcinoma, Squamous Cell; Forehead; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Keratosis; Neoplasm Recurrence, Local; Skin Neoplasms; Staining and Labeling

The final alpha-keratin compositions attained in the outer horny layer of 16 dyskeratoses have been compared with the series of compositions which is produced during normal epidermal differentiation. In each case, the abnormal outer horny layer composition corresponded with that of normal basal, spinous, granular or inner horny cells, with, in some cases, the addition of alpha-keratins characteristic of hyperproliferating/regenerating keratinocytes. The results have implications for the aetiology of these diseases. In addition, the distinction between the alpha-keratin patterns in certain of the conditions was sufficiently clear to allow the use of the technique as a non-invasive aid to diagnosis.

Topics: Epidermis; Female; Humans; Keratins; Keratosis; Middle Aged

A case of a 70-year-old man with several dome-shaped tumors with acantholysis was reported. The histopathological findings of these black-brownish colored tumors on the back were compatible with seborrheic keratosis, consisting of basaloid and squamoid cells. Although three cases reported by Tagami et al. (1978) and Uchiyama et al. (1986) showed intraepidermal epithelioma-like tumor nests in the acanthotic lesions, our case was thought to correspond to another variant of seborrheic keratosis with acantholysis.

Topics: Acantholysis; Aged; Biopsy; Dermatitis, Seborrheic; Humans; Keratins; Keratosis; Male; Skin Diseases

Corneal intraepithelial neoplasia (CIN) is the term applied by some authors to the spectrum of disease ranging from mild dysplasia to carcinoma in situ. Such lesions usually are associated with dysplastic or neoplastic processes at the limbus or adjacent conjunctiva; isolated corneal dysplasia is rare. Clinically, CIN appears as a geographic, gray, translucent thickening of the epithelium with fimbriated or scalloped borders and lesions often contain scattered white dots. We report a case of intraepithelial neoplasia limited to the cornea that had the unusual clinical appearance of a white plaque, which prompted the misdiagnosis of a calcific scar. Histopathologic examination of the debrided tissue revealed intraepithelial neoplasia and marked hyperkeratosis as the cause of the opacification.

Topics: Corneal Diseases; Epithelial Cells; Eye Neoplasms; Fixatives; Humans; Keratins; Keratosis; Male; Middle Aged; Visual Acuity

We used an avidin-biotin complex immunoperoxidase technique with various monoclonal antibodies to determine Langerhans cell densities, class II antigen expression on keratinocytes, and phenotypes of other infiltrating cells in several malignant and benign epithelial tumors of the skin. Our observations indicate (1) there are few Langerhans cells in nests of basal cell carcinoma and squamous cell carcinoma; (2) there are increased Langerhans cell densities in seborrheic keratoses, verrucous epidermal nevus, and Bowen's disease; (3) there is an expression of class II molecules on the keratinocytes and cancer cells of basal cell carcinoma, squamous cell carcinoma, Bowen's disease, seborrheic keratosis, and verrucous epidermal nevus; and (4) there is a netlike staining of the keratinocyte surface with OKM5 in the epidermal lesion of seborrheic keratosis, verrucous epidermal nevus, and Bowen's disease, as well as in the epidermis adjacent to the basal cell carcinoma and squamous cell carcinoma nests.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Female; Histocompatibility Antigens Class II; Humans; Keratins; Keratosis; Langerhans Cells; Male; Middle Aged; Skin Neoplasms

We investigated immunohistochemically 20 basal cell carcinomas (BCC), five pilomatricomas, and nine seborrheic keratoses using anti-BCC keratin monoclonal antibody (BKN-1) and anti-hair keratin monoclonal antibodies (HKN-2, HKN-4- -7). The neoplastic cells in all the cases of BCC were always uniformly stained by BKN-1, HKN-2, and HKN-4, indicating that the BCC cells display a constant antigenicity of keratin, which may be different from that of the normal epidermis. Although no fluorescence by HKN-6 or HKN-7 was seen in any cases of BCC, HKN-5 partially but strongly stained the neoplastic nests in most cases of BCC; BCC may have differentiation toward the lower part of hair follicular epithelium. In pilomatricoma, all the anti-keratin monoclonal antibodies showed a similar staining pattern; the differentiating neoplastic cells undergoing transition from basaloid to eosinophilic were positively stained by each antibody in all the cases. This finding of pilomatricoma corresponds to that of the differentiating cells in the inner hair layers, especially in the hair cortex. In seborrheic keratoses, no fluorescence was recognized with HKN-5- -7, which stain the lower follicular cells in the normal human skin. The staining patterns of seborrheic keratosis by BKN-1, HKN-2, and HKN-4 were similar to those of the normal interfollicular epidermis. These anti-keratin monoclonal antibodies seem to be useful for the investigation of the direction of differentiation of skin adnexal neoplasms.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Dermatitis, Seborrheic; Humans; Immunohistochemistry; Keratins; Keratosis; Skin Neoplasms

The purpose of this study is to examine the ultrastructure of leukoplakia and lichen planus. The light and examine electron-microscopical observations were made in the specimens of leukoplakia and lichen planus as dyskeratosis in oral mucosa which were diagnosed as benign lesions clinically and histopathologically. The results were as follows: 1. Light microscopical findings: Leukoplakia exhibited orthokeratinization and the thickening of prickle and corneal cell layers was seen. The clear and unclear granular layers were seen. Lichen planus was classified as the type of parakeratinizing region or the mixed type of orthokeratinizing and parakeratinizing region, but the former was more abundant. The thickened prickle and corneal cell layers were seen and the granular layer was unclear in the parakeratinized cell regions. Various cells were observed in expanded intercellular spaces of basal cell and prickle cell layers. The infiltration of inflammatory cells in the lamina propria was more marked in lichen planus than in leukoplakia. 2. Electron microscopical findings: 1) The melanocyte and histiocyte-like cell were seen in the expanded intercellular spaces of basal and prickle cell layers in lichen planus, while they were not observed in leukoplakia. 2) The aggregation and scattering of the discharged desmosomes into the expanded intercellular spaces of prickle cell layers were observed in leukoplakia. The number of desmosome was decreased in the orthokeratinization process from granular layer to corneal layer. An increase in the width of intercellular contact layer and the disappearance of attachment plaque were observed. In lichen planus, the desmosome of parakeratinized regions were decreased in number toward the superficial layer, but the structure was clear even in the superficial part. 3) Small number of Odland bodies in the cytoplasm of superficial layer of prickle cell layer were seen. They increased in the granular layer and were discharged into the intercellular spaces in the most superficial layer of granular layer. The lamellar pattern of Odland bodies was not clear in the more superficial layer.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Mouth Diseases; Mouth Mucosa

Spreading pigmented actinic keratosis is a rarely reported premalignant, pigmented, epidermal tumor that can be difficult to distinguish clinically from other benign and malignant pigmented lesions. In an attempt to determine the cause of clinical hyperpigmentation, seven lesions from five patients were examined by light microscopy. Three of these lesions were also examined using electron microscopy. Findings from these studies indicate that hyperpigmentation is due to enhanced melanosome formation and distribution and not to a melanocyte-keratinocyte melanosome transfer block.

Topics: Aged; Cryosurgery; Epidermis; Female; Humans; Keratins; Keratosis; Male; Melanocytes; Microscopy, Electron; Middle Aged; Skin Pigmentation

Lectin application is used to study 12 cases of ichthyosis, 8 cases of Darier's disease and two of acrokeratosis verruciformis, establishing comparative patterns with normal skin.

Topics: Darier Disease; Humans; Ichthyosis; Keratins; Keratosis; Lectins; Skin; Staining and Labeling

Lectins are used to study four cases of keratosis pilaris, four of lichen spinulosus, 11 of porokeratosis, 8 of striated lichen and one case of pityriasis rubra pilaris, with the aim of providing data to improve knowledge of the histogenesis of these processes.

Topics: Humans; Keratins; Keratosis; Lectins; Phytohemagglutinins; Pityriasis Rubra Pilaris; Ricin; Skin Diseases

Topics: Adult; Aged; Epidermal Cells; Epidermis; Humans; Keratins; Keratosis; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged

We compared morphologic features of keratohyalin granules (KHG) that were directly related to keratinization in oral mucosa (tongue, cheek, gums, palate; n = 4) with those in parakeratotic epidermis (psoriasis, n = 2; pityriasis rubra pilaris, n = 1; acute dermatitis, n = 1) and normal orthokeratotic epidermis. Among others, the ultrastructural features of globular KHG were observed in the cheek, nonspecialized tongue mucosa, and parakeratotic epidermis occurring in psoriasis, pityriasis rubra pilaris, and acute dermatitis, whereas gums and palate showed a mixture of characteristics, also resembling stellate KHG as seen in normal skin. From literature as well as from our studies, the impression was gained that globular KHG were found especially in quickly dividing epithelia and could easily be distinguished from the irregular or stellate KHG that were found in slowly dividing normal epidermis. Therefore, we studied keratinization features on days 3, 7, and 14 after autografting normal human skin (n = 4), thus inducing high cell turnover. Stellate KHG, present in granular cells of normal skin, were almost absent on the third day. Active cell division on the seventh day resulted in sparse keratohyalin formation inside globular granules of low electron density, whereas numerous, rather electron-translucent lipid droplets occurred in upper spinous and horny cells. These two phenomena seemed to be interrelated. After 14 days, round and increasingly electron-dense KHG were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cytoplasmic Granules; Epidermis; Humans; Hyalin; Keratins; Keratosis; Mouth Mucosa; Parakeratosis; Skin Transplantation

Topics: Adult; Cyclic AMP; Etretinate; Female; Humans; Keratins; Keratosis; Male; Microscopy, Electron; Middle Aged; Skin

A 30-year-old woman with erythrokeratodermia variabilis was treated with oral isotretinoin for four months. Clinical and light and electron microscopic observations were made before and after treatment. A characteristic electron microscopic feature was subnormal numbers of keratinosomes within the stratum granulosum of hyperkeratotic plaques. Isotretinoin therapy resulted in almost complete clinical clearing of these plaques and restoration of normal numbers of epidermal keratinosomes. In addition, distinctive dyskeratotic cells containing clumped tonofilaments were observed within the stratum granulosum by electron microscopy. These cells persisted after retinoid treatment.

Topics: Adult; Biopsy; Epidermal Cells; Erythema; Female; Humans; Isotretinoin; Keratins; Keratoderma, Palmoplantar; Keratosis; Microscopy, Electron; Skin; Time Factors; Tretinoin

Seventy-six skin biopsies of proliferative lesions were studied by using 4 different lectins and an avidin-biotin-peroxidase complex. In solar keratosis, Bowen's disease and squamous cell carcinoma, malignant-appearing keratinocytes exhibited loss of membrane staining with Concanavalia ensiformis agglutinin (Con A), but revealed cytoplasmic staining. When incubated with peanut agglutinin (PNA), the malignant keratinocytes did not stain. However, the PNA binding sites were not absent, but masked by sialic acid. Following cleavage of the sialic acid with neuraminidase, free PNA binding sites could be demonstrated in the plasma membranes. In contrast, the keratinocytes in keratoacanthomas showed membrane staining with Con A and also contained free PNA binding sites. These histochemical findings confirm and extend our earlier observations regarding cell surface carbohydrates in premalignant and malignant epidermal lesions.

Topics: ABO Blood-Group System; Binding Sites; Bowen's Disease; Carbohydrate Metabolism; Carcinoma, Squamous Cell; Cell Membrane; Concanavalin A; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Neuraminic Acids; Peanut Agglutinin; Plant Lectins; Skin; Skin Neoplasms; Sunlight; Wheat Germ Agglutinins

Colloid keratosis is characterized by homogeneous eosinophilic masses of variable size and number within the upper layers of squamous epithelia, including epidermis. It has been observed as the characteristic feature of many onychoses and inflammatory conditions of oral epithelium, and as an incidental finding in neoplastic and nonneoplastic lesions in the skin and respiratory tract. Its nature remains obscure, but knowledge at present suggests that it may represent a disorder of an early phase of keratinization. Current evidence supports the hypothesis that colloid keratosis represents a nonspecific cellular reaction pattern of squamous epithelium.

Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Colloids; Eosinophilia; Epithelium; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling

Inverted follicular keratosis, a benign tumor of the skin believed to arise from the infundibular portion of the hair follicle that can involve perioral skin, has a unique histologic picture. It can be confused with forms of skin cancer; with knowledge of this entity, oral and maxillofacial surgeons may be able to avoid unnecessary surgery. The clinical and microscopic findings of 12 cases of inverted follicular keratosis are reported.

Topics: Adult; Aged; Darier Disease; Diagnosis, Differential; Epithelium; Facial Dermatoses; Facial Neoplasms; Humans; Keratins; Keratosis; Lip Diseases; Male; Middle Aged

Parakeratosis (PK) is a common feature of the abnormal epidermis in several disorders of keratinization. Tar phenols, retinoids and steroids which cause the inhibition of PK and the restoration of orthokeratosis (OK) are used for treating psoriasiform conditions. In this work, we studied two experimental models of the drug-induced inhibition of PK: (1) the suppression of the normal development of PK in the infant mouse tail and (2) the OK conversion of established PK in the adult tail. Two markers of OK were studied: the histological evaluation of the granular layer and the expression of cytoplasmic antigens linked to OK differentiation. It was demonstrated that high-boiling tar phenols cause a more potent inhibition of PK than betamethasone valerate. Most importantly, immunofluorescence showed that the switch to OK differentiation was located in the cells situated in a suprabasal position. The use of these immunological markers to investigate and anti-parakeratotic mechanisms has revealed that these drugs act at stages of keratinocyte differentiation which are distinct from those previously suggested.

Topics: Acids; Age Factors; Animals; Animals, Newborn; Antibodies; Betamethasone; Betamethasone Valerate; Cell Differentiation; Coal Tar; Keratins; Keratosis; Male; Mice; Time Factors

The immunofluorescent staining patterns of oral lesions of discoid lupus erythematosus were examined by use of monoclonal antibodies AE1, AE2 and AE3. AE1 and AE2 showed suprabasal staining, whereas AE3 stained all cell layers of the epithelium. This pattern is consistent with that of other benign hyperkeratinized lesions of the oral mucosa. Occasionally, however, the most basally positioned epithelial cells stained positive with AE1. The morphology of these cells was similar to stratum spinosum cells. Colloid bodies in the epithelium as well as in the connective tissue stained positive with AE1 and AE3, demonstrating their epithelial origin. Few bodies in the connective tissue staining positive with IgM were negative for keratin. These structures may be Russell bodies or may be derived from the basement membrane zone.

Topics: Antibodies, Monoclonal; Colloids; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Keratins; Keratosis; Lupus Erythematosus, Discoid; Mouth Mucosa; Staining and Labeling

In humans, the skin is a particularly sensitive target for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and certain halogenated analogs. Reported lesions include a thickening of the epidermis (acanthosis), hyperkeratosis, and squamous metaplasia of the epithelial lining of the sebaceous glands. In this report we describe ongoing studies on the actions of TCDD on cultured human epidermal cells. This system has been established as an in vitro model for interfollicular epidermal hyperkeratinization. Treatment of newly confluent cultures with TCDD results in enhanced differentiation as judged by histologic examination of the cultures, a decrease in the number of basal proliferating cells, and an increase in the number of envelope competent (differentiating) cells and terminally differentiated cells with highly cross-linked cornified envelopes. Changes in the differentiation program are preceded by a decrease in epidermal growth factor (EGF) binding. The concentration dependence and stereospecificity for these responses suggest the involvement of the Ah receptor. We propose that TCDD modulates normal patterns of epidermal differentiation through direct actions on proliferating basal cells, modulating the responsiveness of these cells to growth factors such as EGF.

Topics: Cell Differentiation; Cell Line; Cells, Cultured; Clone Cells; Dioxins; Epidermal Cells; Epidermal Growth Factor; Epidermis; Humans; Keratins; Keratosis; Male; Polychlorinated Dibenzodioxins; Protein Precursors; Receptors, Aryl Hydrocarbon; Receptors, Drug

Seventy-six cases of tumorlike and neoplastic lesions from epidermis and oral epithelium were analyzed by a histochemical technique for the demonstration of keratin. Formalin-fixed paraffin sections were reacted with rabbit antihuman keratin antiserum (dilution of 1:40). The types of distribution of keratin in cells of lesions were classified into five categories: (1) regional, as found in normal squamous epithelia and benign hyperkeratinized lesions, and papilloma, and keratinized squamous cell carcinoma; (2) total, as seen in intensely keratinized lesions, such as verruca vulgaris and highly keratinized squamous cell carcinoma; (3) negative, as displayed by basal cell carcinoma; (4) scattered, as in the most poorly differentiated squamous cell carcinomas; and (5) mixed cellular, as found in both poorly and moderately differentiated squamous cell carcinomas.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermatitis, Seborrheic; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Mouth Neoplasms; Papilloma; Protein Binding; Skin Neoplasms; Warts

In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibroepitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (Mr 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Condylomata Acuminata; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Keratoacanthoma; Keratosis; Molecular Weight; Molluscum Contagiosum; Papilloma; Peptides; Skin; Skin Neoplasms; Warts

Topics: Adult; Carcinoma; Female; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nicotiana; Plants, Toxic; Precancerous Conditions

We report an interesting case of generalized papular and nodular lesions with central keratinous plugs and severe hyperkeratotic-acanthotic histopathology with arthritis in a 19-year-old male patient who had suffered from a similar disease 2 years earlier. Papules and nodules erupted a few days after the arthritis and this was noticed during both episodes. On healing, nodules fell spontaneously leaving behind insignificant hyperpigmented scars.

Topics: Adult; Arthritis; Humans; Keratins; Keratoacanthoma; Keratosis; Male; Skin; Skin Diseases

Topics: Aged; Darier Disease; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Keratosis; Male; Microscopy, Electron

Three cases of trichilemmal keratosis (horn) were light microscopically examined and all showed numbers of U- or V-shaped epidermal proliferations which keratinized in a fashion either identical or similar to trichilemmal keratinization. Electron microscopy revealed both uneven and linear borders between the keratinized and the keratinizing cells with a few keratohyalin droplets, remnants of desmosomes, no marginal band in the horny layer, perinuclear vacuolation, few spherical bodies in the intercellular spaces (ICS) of the upper epidermis, and widening of the ICS of the lower epidermis. A number of electron dense spherical particles, 40-50 nm in diameter, were observed in nuclei of the upper epidermis. This suggests that ultrastructure of trichilemmal keratosis is similar rather to viral warts than to trichilemmal cysts, although there are close similarities between trichilemmal keratosis and cyst.

Topics: Adult; Aged; Cysts; Desmosomes; Diagnosis, Differential; Epidermis; Epithelium; Humans; Keratins; Keratosis; Male; Middle Aged; Skin; Skin Diseases; Skin Neoplasms

Topics: Amino Acids; Electrophoresis; Humans; Keratins; Keratosis

Topics: Aged; Amino Acids; Electrophoresis, Polyacrylamide Gel; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Molecular Weight; Skin

The ultrastructural study of the senile epidermis without an apparent lesion, in the phase of cicatrization of a traumatic lesion and in a state of hyperkeratosic transformation in comparison with those performed in the normal epidermis, reveals decrease in the number of clear keratinocytes (only compensated in the process of cicatrization) it is in concord with the most recent theory of the aging of cells of Gelfant and Smith. The increase of clear suprabasal cells in the epidermis degenerative process with a constant of the percentage of clear and dark basal cells suggest a liberation of bloqued cells, which constituted probably the direct source of neoplasic differentiation.

Topics: Aged; Aging; Cell Transformation, Neoplastic; Epidermis; Humans; Keratins; Keratosis; Middle Aged; Wound Healing

Ten patients with disorders of keratinization were treated with oral isotretinoin (13-cis-retinoic acid) on an investigational protocol to test the efficacy, safety, and optimal dosage schedule for using the drug in these rare disorders. Elevations of serum triglyceride levels above the highest normal levels developed in seven of the ten patients, while they maintained normal levels of serum cholesterol. This effect was found to be dose and/or time related and reversible. Moderate elevations of serum triglyceride levels have not been clearly established as a risk factor for the development of coronary artery disease. High levels, however, may precipitate acute pancreatitis. For this reason, the conditions of patients receiving retinoids must be carefully monitored for triglyceride abnormalities throughout their courses of treatment.

Topics: Administration, Oral; Adolescent; Adult; Child; Cholesterol; Darier Disease; Female; Humans; Isotretinoin; Keratins; Keratosis; Male; Middle Aged; Skin; Skin Diseases; Tretinoin; Triglycerides

Topics: Candidiasis, Oral; Carcinoma in Situ; Diagnosis, Differential; Epithelium; Erythroplasia; Humans; Keratins; Keratosis; Leukoedema, Oral; Leukoplakia, Oral; Lichen Planus; Lupus Erythematosus, Discoid; Melanins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nevus; Precancerous Conditions; Risk; Sebaceous Glands; Smoking; Stomatitis

The fibrous proteins of the malpighian layer of human epidermis (prekeratin) have been isolated with citrate buffer, pH 2.65, and shown to consist of 7 polypeptide chains varying in molecular weight from 45,000 daltons to 67,000. Some variation in the number and amount of the components was observed in prekeratin prepared from the epidermis of different individuals. The fibrous proteins of the stratum corneum were isolated with Tris buffer, pH 9.0, containing 6 M urea and 0.1 M mercapto-ethanol and were found to have a pattern similar to prekeratin but not identical to it. However, fibrous protein isolated from the superficial layers of the stratum showed a considerably different pattern indicating that there was post-translational modification of the protein in the late stages of keratinization. These data show that human keratin has the same heterogeneity which was observed previously in cow epidermis. This was further confirmed by studying the polypeptide chain content of prekeratin from a large number of lesions showing benign epidermal hyperplasia, where considerable variation in composition was observed.

Topics: Animals; Cattle; Electrophoresis, Polyacrylamide Gel; Epidermis; Humans; Keratins; Keratosis; Proteins

Hamster cheek pouches were painted thrice weekly with 50% v/v turpentine in liquid paraffin over periods ranging from 1 day to 16 weeks. Pouch mucosa was examined histologically for changes and measurements of epithelial thickness were made with a calibrated eyepiece micrometer. An increase in epithelial thickness was first observed 48 hrs. after a single painting and was accompanied by inflammatory changes in both epithelium and connective tissue. Maximal epithelial thickening occurred after 9 weeks of thrice weekly painting. Cheek pouches of animals left without further treatment for up to 1 year following 9 weeks painting were indistinguishable from controls. The epithelial response to treatment with turpentine is that of a reversible benign epithelial hyperplasia with hyperkeratosis.

Topics: Animals; Connective Tissue; Cricetinae; Epithelium; Hyperplasia; Keratins; Keratosis; Male; Models, Biological; Mouth Mucosa; Stomatitis; Time Factors; Turpentine

The radiologic finding of innumerable fine ridges in the outer soft tissues of a patient with severe generalized epidermolytic hyperkeratosis is presented as a sign of the disease. The radiodensity results from the density of keratin and low water content in the scales of epidermolytic hyperkeratosis.

Topics: Child; Female; Humans; Keratins; Keratosis; Radiography; Water

We saw three patients with inflammatory linear verrucose epidermal nevus (ILVEN). The purpose of this study is to better delineate the histopathologic features of this type of nevus. In fact, in all three cases very particular, specific histologic lesions have been noted that permit us to better distinguish this recently outlined entity. The histologic features were depressed, cup-like areas of hyper-granulosis with overlying orthokeratotic hyperkeratosis, alternating (with sharp dermacation) with raised, level areas of agranulosis with overlying parakeratotic hyperkeratosis.

Topics: Adult; Child; Female; Humans; Infant; Keratins; Keratosis; Male; Nevus, Pigmented; Parakeratosis; Skin Neoplasms

Topics: Adult; Cytoplasmic Granules; Humans; Hyalin; Keratins; Keratosis; Male; Skin

Topics: Humans; Keratins; Keratosis; Skin Diseases

Electron microscopic analyses of basaloid cell papillomas of the solid and papillomatous types are reported. The submicroscopic organization is described. Some of the ultrastructural findings, e.g. an increased number of mitochondria, a certain mitochondrial polymorphismus, the occurrence of irregularly shaped intracytoplasmic vesicles, the abundance of endoplasmic reticulum hypertrophy and the remarkable presence of microtubule-like structures, an unusual finding in a material fixed at the temperature used, are indicating an altered metabolic activity. The alternating presence and absence of keratohyalin is found to be submicromorphologically related to the formation of A- respectively B-cells. This is compared with the formation of parakeratosis in psoriatic lesions without keratohyalin. A formation of orthokeratosis as seen by the light microscopical procedure seems possible without preceeding occurrence of keratohyalin.

Topics: Carcinoma, Basal Cell; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Humans; Hyalin; Keratins; Keratosis; Microscopy, Electron; Microtubules; Mitochondria; Parakeratosis; Ribosomes; Skin Neoplasms; Temperature

It is proposed that oral keratoses appear white because of the ability of abnormal oral keratin to evenly reflect the visible light spectrum because of the hydration of the keratin layer in a manner similar to the reaction of the stratum corneum of the epidermis to water. Thickening of the keratin layer per se or the over-all thickness of the epithelium does not appear to be the primary factor in causing an intraoral lesion to appear white. The white appearance is related to thickness only insofar as it takes a certain amount of abnormal keratin to be clinically evident. It appears that an accumulation of only 10 to 20 microns of abnormal keratin is sufficient to cause a lesion to appear very white. This is about the amount seen on the normal human palate. It seems likely that, when a normally nonkeratinized area, such as the buccal mucosa or floor of the mouth, is stimulated to produce keratin, the keratin thus produced would be different from normally occurring oral keratin. This difference apparently manifests itself clinically as hydration of the keratin layer. A more complete understanding of why white lesions are white awaits further elucidation in regard to the role of lipids, keratohyaline granules, membrane-coating granules, and intercellular cement. Characterization of the oral keratins as to their amino acid residues and types of bondings, as well as insight into the events transpiring when the prickle cell becomes keratinized, may not only shed light on the etiology of these lesions but also have prognostic implications.

Topics: Animals; Color; Cytoplasm; Cytoplasmic Granules; Dogs; Epithelium; Haplorhini; Humans; Hyalin; Keratins; Keratosis; Mouth Diseases; Mouth Mucosa; Swine

The activity of ICDH(NAD) was measured in subcorneal and basal epidermal layers in 8 patients with psoriasis and in 7 healthy controls treated once a day with 0.15% dithranol in white petrolatum for 2 weeks. Skin biopsies were taken before and on days 2, 6, and 14 of the treatment. Lowry's microtechniques were used in conjunction with a bioluminescent system (bacterial luciferase) for enzymatic assays. The enzymic activity could be related to the type of keratinization present in the stratum corneum overlying the epidermal areas under study. In orthokeratotic areas from the controls, in noninvolved, and in treated involved skin the activity was low. In parakeratotic areas, as found in treated noninvolved and in involved psoriatic skin, the enzymic activity was increased to a level at least twice that found in orthokeratosis. Since ICDH(NAD) activity reflects an aspect of mitochondrial function, the results suggest that mitochondrial activity may be important in control of keratinization.

Topics: Adolescent; Adult; Anthracenes; Anthralin; Humans; Isocitrate Dehydrogenase; Keratins; Keratosis; Middle Aged; Mitochondria; NAD; Parakeratosis; Psoriasis; Skin

A correlative histocytological study for keratinization was done in 446 cases of oral leukoplakia. Cytologically, keratinization could be correctly identified in 91% of leukoplakias exhibiting orthokeratosis, 73% of leukoplakias exhibiting parakeratosis, and 78% of cases showing both types of keratinization. Cytologically, orthokeratosis was present in 83% of individuals with homogeneous leukoplakia and in 69% with ulcerated leukoplakia, while parakeratosis was present in 7% of homogeneous leukoplakias and in 19% of ulcerated leukoplakias. A higher frequency of dysplasia was observed in smears and their corresponding histological sections for those cases which had revealed only parakeratosis in the cytological examination and for both orthokeratosis and parakeratosis as compared to those showing only orthokeratosis. It is suggested that the cytological method is a reliable method for studying oral keratinization and is of value to the clinician in identifying the type of leukoplakias which may need to be biopsied for further surveillance.

Topics: Cytoplasmic Granules; Humans; Keratins; Keratosis; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Parakeratosis

The alveolar mucosa in the upper jaw from 12 patients suffering from severe denture stomatitis was examined histologically and microradiographically using ultrasoft X-rays. Pathological changes of the epithelial cell layers were observed in all cases. In 10 of the 12 cases examined no keratinization was found. A reduction in the number of epithelial cell layers was commonly observed. In most cases the connective tissue showed signs of moderate to severe inflammation. The inflammatory reaction and the degenerative changes of the tissue were presumably due to a combined effect of microorganisms and mechanical trauma.

Topics: Alveolar Process; Cell Nucleus; Connective Tissue; Connective Tissue Cells; Cytoplasm; Cytoplasmic Granules; Epithelial Cells; Epithelium; Female; Humans; Keratins; Keratosis; Male; Microradiography; Middle Aged; Mouth Mucosa; Stomatitis; Stomatitis, Denture

Weanling rats were fed a zinc-deificient diet, 1.3 ppm zinc, for four weeks. Parakeratotic changes of the buccal epithelium were studied by electron microscopy. The incomplete disintegration of the nucleus and cytoplasmic organelles in the horny layer is deemed to be due to insufficient function of zinc-related lytic enzymes.

Topics: Animals; Cell Nucleus; Chromatin; Cytoplasmic Granules; Epithelial Cells; Epithelium; Keratins; Keratosis; Male; Mouth Mucosa; Organoids; Parakeratosis; Rats; Ribosomes; Zinc

Topics: Carcinoma; Erythroplasia; Histocytochemistry; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Melanins; Smoking

Topics: Adult; Aged; Female; Foot Dermatoses; Genes, Dominant; Humans; Keratins; Keratosis; Male; Microscopy, Electron; Organoids; Skin

Topics: Adolescent; Adult; Carcinoma, Squamous Cell; Cell Membrane; Cell Nucleus; Child; Child, Preschool; Collagen; Cytoplasm; Female; Fibroblasts; Foot Dermatoses; Hand Dermatoses; Humans; Keratins; Keratosis; Leg; Male; Melanocytes; Microscopy, Electron; Middle Aged; Skin; Syndrome

Topics: Biopsy, Needle; Carcinoma; Female; Humans; Jaw Neoplasms; Keratins; Keratosis; Male; Mandibular Neoplasms; Maxillary Neoplasms; Mitosis; Neoplasm Recurrence, Local; Odontogenic Cysts; Radiography

Topics: Acid Phosphatase; Animals; Esterases; Histocytochemistry; Keratins; Keratosis; Male; Mouth Diseases; Mouth Mucosa; Muramidase; Rats; Sulfhydryl Compounds; Sulfides; Vitamin A Deficiency

The smoking habits of 345 Danish and 184 Hungarian leukoplakia patients were analysed against the histopathology of the leukoplakias, i.e. type of keratinization, epithelial thickness, epithelial dysplasia and inflammation. In spite of the reasonable size of the numbers forming the basis for the analysis, no statistically significant differences were found between smokers and non-smokers. However, it was found that the frequency of epithelial dysplasia is not higher among smokers than among non-smokers.

Topics: Atrophy; Denmark; Epithelium; Female; Humans; Hungary; Hyperplasia; Inflammation; Keratins; Keratosis; Leukoplakia, Oral; Male; Smoking

Topics: Adolescent; Biopsy; Cell Nucleus; Cytoplasmic Granules; Female; Golgi Apparatus; Humans; Inclusion Bodies; Keratins; Keratosis; Langerhans Cells; Lipids; Lysosomes; Macrophages; Microscopy; Microscopy, Electron; Neutrophils; Organoids; Phagocytosis; Psoriasis; Skin

Topics: Animals; Cell Differentiation; Cholesterol; Cytoplasmic Granules; Female; Guinea Pigs; Humans; Keratins; Keratosis; Male; Mice; Microscopy, Electron; Organoids; Skin; Sterols; Triparanol

Topics: Cell Membrane Permeability; Humans; Keratins; Keratosis; Microscopy, Electron, Scanning; Psoriasis; Skin

Topics: Animals; Animals, Newborn; Cell Differentiation; Disulfides; Growth Substances; Keratins; Keratosis; Oxygen Consumption; Proteins; Skin; Submandibular Gland; Sulfhydryl Compounds

Topics: Biopsy; Gingiva; Humans; Keratins; Keratosis; Methods; Staining and Labeling

Topics: Adenosine Triphosphatases; Adult; Aged; Dermatitis, Seborrheic; Dihydroxyphenylalanine; Female; Histocytochemistry; Humans; Keratins; Keratosis; Langerhans Cells; Male; Melanocytes; Middle Aged; Skin; Warts

Topics: Alveolar Process; Animals; Autoradiography; Gingiva; Gingivitis; Haplorhini; Keratins; Keratosis; Mitosis; Mouth Diseases; Mouth Mucosa; Thymidine; Tritium

In biopsies from the oral mucosa of 235 cases in which the diagnosis was lichen planus, keratosis or leukoplakia, mitotic values were calculated for the stratum basale (M.V. basal) and the stratum spinosum (M.V. spinous). The mean M.V. basal was significantly different from the mean M.V. spinous in the keratosis and leukoplakia groups, but not in the lichen planus group. Within the keratosis and leukoplakia groups, M.V. basal and M.V. spinous were significantly correlated. When each of the mean M.V.s was compared with the M.V.s for the other diagnostic groups, various significant differences were found. The M.V.s were examined in relation to the type of keratinization, the presence of acanthosis or atrophy, and the patient's age, but the M.V.s were not significantly related to these features.

Topics: Acantholysis; Age Factors; Atrophy; Epithelium; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Mitosis; Mouth Diseases; Mouth Mucosa

Topics: Alopecia; Biomechanical Phenomena; Elasticity; Female; Genetic Diseases, Inborn; Hair; Homocystinuria; Humans; Hyperthyroidism; Hypothyroidism; Ichthyosis; Keratins; Keratosis; Male; Oxidation-Reduction; Skin Diseases; Ultrasonography; X-Ray Diffraction

Topics: Glycosaminoglycans; Histocytochemistry; Humans; Intercellular Junctions; Keratins; Keratosis; Nails; Nails, Malformed; Skin

Topics: Blister; Dermatitis, Atopic; Dermatitis, Exfoliative; Extremities; Facial Dermatoses; Foot Dermatoses; Genes, Dominant; Genes, Recessive; Hand Dermatoses; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Ribosomes; Scalp Dermatoses; Sex Chromosomes; Skin; Thorax

Topics: Basement Membrane; Carcinoma; Dermatology; Diagnosis, Differential; Esterases; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Keratins; Keratoacanthoma; Keratosis; Lupus Erythematosus, Discoid; Mast-Cell Sarcoma; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Sweat Glands; Urticaria

Topics: Cell Differentiation; Cell Division; Culture Techniques; Epithelium; Histocytochemistry; Humans; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Lichen Planus; Metaplasia; Mouth Mucosa; Mouth Neoplasms; Organ Culture Techniques

Topics: Adult; Female; Formaldehyde; Gingiva; Humans; Keratins; Keratosis; Male; Massage; Mouthwashes; Periodontal Diseases; Toothbrushing

Topics: Child; Hair; Humans; Keratins; Keratosis; Kwashiorkor; Pellagra; Protein Binding; Water

Topics: Humans; Keratins; Keratosis; Lysosomes; Microscopy, Electron; Skin; Sunburn; Time Factors; Ultraviolet Rays

Topics: Cell Membrane; Cell Nucleus; Cheek; Cytoplasmic Granules; Epithelium; Glycogen; Histocytochemistry; Humans; Inflammation; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Lichen Planus; Microscopy, Electron; Mouth Mucosa; Mouth Neoplasms; Smoking

Sixty-two "leukoplakias" from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the "intensity" of the habit.

Topics: Adult; Aged; Areca; Biopsy; Connective Tissue; Epithelium; Humans; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Middle Aged; Mitosis; Mouth Mucosa; Mouth Neoplasms; Plants, Medicinal

Topics: Adult; Biopsy; Child; Female; Hair; Histocytochemistry; Humans; Keratins; Keratosis; Middle Aged; Skin; Staining and Labeling; Sweat Glands

Topics: Adult; Gingiva; Glycogen; Histocytochemistry; Humans; Keratins; Keratosis; Male

Topics: Adult; Epithelium; Fetus; Histidine; Histocytochemistry; Humans; Keratins; Keratosis; Skin

Topics: Carcinoma, Basal Cell; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Mitochondria; Psoriasis; Skin Neoplasms

Topics: Autopsy; Dermatitis, Seborrheic; Humans; Hyperplasia; Keratins; Keratosis; Pigmentation Disorders

Topics: Animals; Epithelial Cells; Epithelium; Hyperplasia; Keratins; Keratosis; Microscopy, Electron; Rats; Urinary Bladder; Vitamin A Deficiency

Topics: Aging; Birefringence; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemistry Techniques, Analytical; Humans; Keratins; Keratosis; Microscopy, Polarization; Skin; Skin Neoplasms; Staining and Labeling

Topics: Adult; Female; Gingival Hyperplasia; Glycogen; Humans; Keratins; Keratosis; Leukoplakia; Male; Middle Aged

Topics: Adolescent; Biopsy; Female; Humans; Ichthyosis; Keratins; Keratosis; Male; Microscopy, Electron

Topics: Adolescent; Adult; Aged; Aging; Atrophy; Child; Collagen; Glycogen; Humans; Keratins; Keratosis; Middle Aged; Mouth Mucosa; Polysaccharides

Topics: Humans; Keratins; Keratosis

Topics: Alkanes; Body Weight; Guinea Pigs; Hydrocarbons; Hyperplasia; Keratins; Keratosis; Keratosis, Actinic; Metabolism; Pharmacology; Research; Skin; Toxicology; Water

Topics: Biomedical Research; Electrons; Epidermis; Histology; Humans; Keratins; Keratosis; Keratosis, Actinic; Melanins; Microscopy; Microscopy, Electron; Skin; Ultraviolet Rays

Topics: Alkalies; Digestion; Enzymes; Hair; Humans; Keratins; Keratosis; Pepsin A; Sulfides

Topics: Humans; Keratins; Keratosis; Keratosis, Actinic