bromochloroacetic-acid and Skin-Diseases
bromochloroacetic-acid has been researched along with Skin-Diseases* in 376 studies
Reviews
80 review(s) available for bromochloroacetic-acid and Skin-Diseases
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Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa.
PubMed searches reveal much literature regarding lipids in barrier function of skin and less literature on lipids in barrier function of the oral mucosa. In terrestrial mammals, birds, and reptiles, the skin's permeability barrier is provided by ceramides, fatty acids, and cholesterol in the outermost layers of the epidermis, the stratum corneum. This layer consists of about 10-20 layers of cornified cells embedded in a lipid matrix. It effectively prevents loss of water and electrolytes from the underlying tissue, and it limits the penetration of potentially harmful substances from the environment. In the oral cavity, the regions of the gingiva and hard palate are covered by keratinized epithelia that much resemble the epidermis. The oral stratum corneum contains a lipid mixture similar to that in the epidermal stratum corneum but in lower amounts and is accordingly more permeable. The superficial regions of the nonkeratinized oral epithelia also provide a permeability barrier. These epithelial regions do contain ceramides, cholesterol, and free fatty acids, which may underlie barrier function. The oral epithelial permeability barriers primarily protect the underlying tissue by preventing the penetration of potentially toxic substances, including microbial products. Transdermal drug delivery, buccal absorption, and lipid-related disease are discussed. Topics: Administration, Cutaneous; Humans; Keratins; Lipids; Mouth Mucosa; Mucous Membrane; Permeability; Skin; Skin Diseases | 2021 |
Mechanical forces in skin disorders.
Mechanical forces are known to regulate homeostasis of the skin and play a role in the pathogenesis of skin diseases. The epidermis consists of keratinocytes that are tightly adhered to each other by cell junctions. Defects in keratins or desmosomal/hemidesmosomal proteins lead to the attenuation of mechanical strength and formation of intraepidermal blisters in the case of epidermolysis bullosa simplex. The dermis is rich in extracellular matrix, especially collagen, and provides the majority of tensile force in the skin. Keloid and hypertrophic scar, which is the result of over-production of collagen by fibroblasts during the wound healing, are associated with extrinsic tensile forces and changes of intrinsic mechanical properties of the cell. Increasing evidences shows that stiffness of the skin environment determines the regenerative ability during wound healing process. Mechanotransduction pathways are also involved in the morphogenesis and cyclic growth of hair follicles. The development of androgenetic alopecia is correlated to tensile forces generated by the fibrous tissue underlying the scalp. Acral melanoma predominantly occurs in the weight-bearing area of the foot suggesting the role of mechanical stress. Increased dermal stiffness from fibrosis might be the cause of recessive dystrophic epidermolysis bullosa associated squamous cell carcinoma. Strategies to change the mechanical forces or modify the mechanotransduction signals may lead to a new way to treat skin diseases and promote skin regeneration. Topics: Collagen; Desmosomes; Extracellular Matrix; Fibroblasts; Fibrosis; Humans; Keratinocytes; Keratins; Mechanotransduction, Cellular; Skin; Skin Diseases; Wound Healing | 2018 |
Molecular basis of the skin barrier structures revealed by electron microscopy.
The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis and their relevance to skin disease. Topics: Animals; Desmosomes; Epidermal Cells; Epidermis; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Lipids; Lysosomes; Membrane Proteins; Mice; Microscopy, Electron; Skin; Skin Diseases; Skin Physiological Phenomena; Tight Junctions | 2018 |
The Molecular Revolution in Cutaneous Biology: Identification of Skin Disease Genes.
Topics: Animals; Blister; DNA; Ectodermal Dysplasia; Genome, Human; Humans; Keratins; Mice; Mice, Transgenic; Microsatellite Repeats; Molecular Biology; Mutation; Phenotype; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Skin; Skin Diseases | 2017 |
The Molecular Revolution in Cutaneous Biology: Keratin Genes and their Associated Disease: Diversity, Opportunities, and Challenges.
The abundance of keratin proteins and the filaments they form in surface epithelia has long been appreciated. This said, the remarkable diversity of keratin proteins and the notion that they are encoded by one of the largest gene families in the human genome has come to the fore relatively recently, coinciding with the sequencing of whole genomes. This complexity has generated some practical challenges, notably in terms of nomenclature and tractability. More importantly, however, studies of keratin have seeded the discovery of the genetic basis for a large number of genodermatoses and continue to provide a unique perspective on and insight into epithelial cells and tissues, whether normal or diseased. Topics: Animals; Epithelial Cells; Genome, Human; Humans; Keratins; Skin; Skin Diseases | 2017 |
Autoinflammatory keratinization diseases.
Topics: Humans; Inflammation; Keratins; Skin Diseases | 2017 |
Revertant mosaicism in genodermatoses.
Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual's lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this "natural gene therapy". Topics: Epidermis; Humans; Keratins; Mosaicism; Mutation; Phenotype; Skin Diseases | 2017 |
Pathogenesis and Treatment of Callus in the Diabetic Foot.
Diabetic foot is one of the most common long term complications of diabetes. The risk of developing a foot ulcer is significantly increased when a patient presents with a callus. Callus develops due to various reasons, of which, the most important in people with diabetes is peripheral neuropathy. Motor neuropathy leads to deformity and sensory neuropathy causes lack of sensation, which results in persistent abnormal pressure on the foot. The cells of skin react to it by increasing keratinization and turns into a callus, which predisposes to foot ulceration. However, there is a lack of research in the field of callus. The link between hyperkeratosis, insulin and hyperglycaemia is not fully explored. There is also a lack of research on the relationship between genetic defects of hyperkeratosis, and the risk of developing a diabetic foot ulcer. There is scope for further research in this area, such as exploring whether development of callus is an individual risk factor, and whether glycaemic control or its treatment has any relationship with callus formation. The research around the genetic defects of hyperkeratosis may lead to identification of those, with diabetes, who may have increased risk of developing a foot ulcer. Topics: Bony Callus; Diabetic Foot; Diabetic Neuropathies; Foot Ulcer; Humans; Keratins; Skin; Skin Diseases | 2016 |
Keratins and skin disease.
Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal disorders. Cutaneous disorders include epidermolysis bullosa simplex, palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita. Both clinical and laboratory observations confirm a major role for keratins in maintaining epidermal cell-cell adhesion. When normal tissue homeostasis is disturbed, for example, during wound healing and cancer, keratins play an important non-mechanical role. Post-translational modifications including glycosylation and phosphorylation of keratins play an important role in protection of epithelial cells from injury. Keratins also play a role in modulation of the immune response. A current focus in the area of keratins and disease is the development of new treatments including small inhibitory RNA (siRNA) to mutant keratins and small molecules to modulate keratin expression. Topics: Animals; Biomechanical Phenomena; Hair Diseases; Humans; Keratins; Mutation; Skin Diseases | 2015 |
Harnessing neuroendocrine controls of keratin expression: a new therapeutic strategy for skin diseases?
Human skin produces numerous neurohormones and neuropeptides. Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ. Since selected keratins are now understood to exert important regulatory functions beyond mechanical stability, we argue that neuroendocrine pathways of keratin regulation are important for maintaining skin and hair follicle homeostasis. This invites innovative neuroendocrine therapeutic interventions for skin disorders characterized by abnormal keratin expression, ranging from psoriasis to genodermatoses, and for promoting skin wound healing and hair growth. This strategy can be probed in simple, but instructive and readily available human skin and hair follicle organ culture assays as ideal models for exploring this new neuroendocrine frontier in translational epithelial biology. Topics: Animals; Gene Expression Regulation; Humans; Keratins; Neurosecretory Systems; Neurotransmitter Agents; Skin Diseases; Skin Physiological Phenomena; Wound Healing | 2014 |
How do keratinizing disorders and blistering disorders overlap?
Inherited keratinizing disorders are caused by mutations in the genes encoding cornified cell envelope proteins, enzymes and their inhibitors, adhesion molecules, cytoskeletal proteins and others in the epidermis. These molecules are known to regulate differentiation, proliferation and cell adhesions. Intriguingly, some keratinizing disorders show blistering skin lesions, while some inherited blistering disorders show abnormal keratinization. Therefore, hereditary keratinizing and blistering diseases are closely related and show overlapping genetic backgrounds. In this review, we overviewed keratinizing and blistering disorders in terms of overlapping of the two disease groups. Gene mutations in desmosomal components cause striate keratoderma, Naxos disease, epidermolytic palmoplantar keratoderma and plakophilin deficiency, which first show skin fragility and blisters and later hyperkeratosis. Gene mutations in hemidesmosomal components cause various forms of epidermolysis bullosa, some of which show hyperkeratosis on the nails, palms and soles, in addition to blister formation. Diseases with gene mutations in calcium pump proteins are Darier disease and Hailey-Hailey disease, which show clinicopathological overlaps and develop both keratinizing and blistering skin lesions. Finally, gene mutations in epidermal keratins cause epidermolysis bullosa simplex, epidermolytic ichthyosis, superficial epidermolytic ichthyosis, epidermolytic palmoplantar keratoderma and pachyonychia congenita/focal palmoplantar keratoderma, which show thickening of the palms and soles with underlying blister formation. In general, responsible proteins for diseases developing both keratinizing and blistering conditions are adhesion molecules, calcium pump proteins and keratins, but not connexins, cornified cell envelop proteins, enzymes or inhibitors. It is still unknown how particular keratinizing diseases develop blisters and vice versa. Topics: Arrhythmogenic Right Ventricular Dysplasia; Blister; Calcium; Cell Differentiation; Epidermis; Epidermolysis Bullosa; Hair Diseases; Humans; Hyperkeratosis, Epidermolytic; Keratins; Keratoderma, Palmoplantar; Mutation; Pemphigus, Benign Familial; Skin Diseases | 2013 |
The expanding significance of keratin intermediate filaments in normal and diseased epithelia.
Intermediate filaments are assembled from a diverse group of evolutionary conserved proteins and are specified in a tissue-dependent, cell type-dependent, and context-dependent fashion in the body. Genetic mutations in intermediate filament proteins account for a large number of diseases, ranging from skin fragility conditions to cardiomyopathies and premature aging. Keratins, the epithelial-specific intermediate filaments, are now recognized as multi-faceted effectors in their native context. In this review, we emphasize the recent progress made in defining the role of keratins towards the regulation of cytoarchitecture, cell growth and proliferation, apoptosis, and cell motility during embryonic development, in normal adult tissues, and in select diseases such as cancer. Topics: Animals; Apoptosis; Cell Movement; Cell Nucleus; Embryonic Development; Epithelium; Homeostasis; Humans; Intermediate Filaments; Keratins; Neoplasms; Skin Diseases; Stress, Physiological | 2013 |
Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases.
Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process. Topics: Adult; Aged; Amyloid; Amyloidosis; Dermis; Ear; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases | 2012 |
Keratin gene mutations in disorders of human skin and its appendages.
Keratins, the major structural protein of all epithelia are a diverse group of cytoskeletal scaffolding proteins that form intermediate filament networks, providing structural support to keratinocytes that maintain the integrity of the skin. Expression of keratin genes is usually regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Amongst the 54 known functional keratin genes in humans, about 22 different genes including, the cornea, hair and hair follicle-specific keratins have been implicated in a wide range of hereditary diseases. The exact phenotype of each disease usually reflects the spatial expression level and the types of mutated keratin genes, the location of the mutations and their consequences at sub-cellular levels as well as other epigenetic and/or environmental factors. The identification of specific pathogenic mutations in keratin disorders formed the basis of our understanding that led to re-classification, improved diagnosis with prognostic implications, prenatal testing and genetic counseling in severe keratin genodermatoses. Molecular defects in cutaneous keratin genes encoding for keratin intermediate filaments (KIFs) causes keratinocytes and tissue-specific fragility, accounting for a large number of genetic disorders in human skin and its appendages. These diseases are characterized by keratinocytes fragility (cytolysis), intra-epidermal blistering, hyperkeratosis, and keratin filament aggregation in severely affected tissues. Examples include epidermolysis bullosa simplex (EBS; K5, K14), keratinopathic ichthyosis (KPI; K1, K2, K10) i.e. epidermolytic ichthyosis (EI; K1, K10) and ichthyosis bullosa of Siemens (IBS; K2), pachyonychia congenita (PC; K6a, K6b, K16, K17), epidermolytic palmo-plantar keratoderma (EPPK; K9, (K1)), monilethrix (K81, K83, K86), ectodermal dysplasia (ED; K85) and steatocystoma multiplex. These keratins also have been identified to have roles in apoptosis, cell proliferation, wound healing, tissue polarity and remodeling. This review summarizes and discusses the clinical, ultrastructural, molecular genetics and biochemical characteristics of a broad spectrum of keratin-related genodermatoses, with special clinical emphasis on EBS, EI and PC. We also highlight current and emerging model tools for prognostic future therapies. Hopefully, disease modeling and in-depth understanding of the molecular pathogenesis of the diseases may lead to the development of novel therap Topics: Animals; Disease Models, Animal; Humans; Keratins; Mutation; Skin; Skin Diseases | 2011 |
[Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering].
Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea. Topics: Adult; Animals; Cell Culture Techniques; Cell-Matrix Junctions; Cells, Cultured; Cornea; Corneal Diseases; Endothelial Cells; Epithelial Cells; Extracellular Matrix; Humans; Infant, Newborn; Keratinocytes; Keratins; Mesenchymal Stem Cells; Mice; Skin; Skin Diseases; Tissue Engineering; Transplantation, Autologous; Vibrissae | 2009 |
Diseases of epidermal keratins and their linker proteins.
Epidermal keratins, a diverse group of structural proteins, form intermediate filament networks responsible for the structural integrity of keratinocytes. The networks extend from the nucleus of the epidermal cells to the plasma membrane where the keratins attach to linker proteins which are part of desmosomal and hemidesmosomal attachment complexes. The expression of specific keratin genes is regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Progress in molecular characterization of the epidermal keratins and their linker proteins has formed the basis to identify mutations which are associated with distinct cutaneous manifestations in patients with genodermatoses. The precise phenotype of each disease apparently reflects the spatial level of expression of the mutated genes, as well as the types and positions of the mutations and their consequences at mRNA and protein levels. Identification of specific mutations in keratinization disorders has provided the basis for improved diagnosis and subclassification with prognostic implications and has formed the platform for prenatal testing and preimplantation genetic diagnosis. Finally, precise knowledge of the mutations is a prerequisite for development of gene therapy approaches to counteract, and potentially cure, these often devastating and currently intractable diseases. Topics: Animals; Desmosomes; DNA Mutational Analysis; Epidermis; Gene Expression Regulation; Humans; Intermediate Filaments; Keratinocytes; Keratins; Mutation; Skin Diseases | 2007 |
Inherited disorders of the skin in human and mouse: from development to differentiation.
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 | 2004 |
The stratum corneum barrier: the final frontier.
The stratum corneum (SC) is the differentiated end product of the mammalian epidermis. It is vital to constancy of the milieu interieur (the environment within) because it prevents water loss and the penetration by potentially toxic xenobiotics, damaging radiation, and pathogenic microbes. The intercorneocyte space contains complex nonpolar lipids that constitute the water barrier. The formation of the SC in the process of keratinization is complex providing multiple opportunities for disorders to arise. The final act of keratinization is desquamation and for this to occur the controlled release of single corneocytes is required in which proteases play an important role. Tests and techniques are described that measure the structure and function of the SC. Topics: Animals; Epidermis; Humans; Keratins; Skin; Skin Diseases | 2004 |
Keratins and skin disorders.
The association of keratin mutations with genetic skin fragility disorders is now one of the best-established examples of cytoskeleton disorders. It has served as a paradigm for many other diseases and has been highly informative for the study of intermediate filaments and their associated components, in helping to understand the functions of this large family of structural proteins. The keratin diseases have shown unequivocally that, at least in the case of the epidermal keratins, a major function of intermediate filaments is to provide physical resilience for epithelial cells. This review article reflects on the variety of phenotypes arising from mutations in keratins and the reasons for this variation. Topics: Corneal Dystrophies, Hereditary; Cytoskeleton; Epidermolysis Bullosa Simplex; Hair; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mutation; Nevus; Phenotype; Skin Diseases | 2004 |
The cytoskeleton and disease.
Cytoskeletal research in recent years has revolutionized cell biology and biomedicine. The cytoskeleton spans the cytoplasm and interconnects the cell nucleus with the extracellular matrix, thereby forming a structural link between molecules involved in cell communication on the one hand, and gene expression on the other. Since the cytoskeleton is involved in virtually all cellular processes, abnormalities in this essential cellular component frequently result in disease. In this introduction, the basic structure of the cytoskeleton is briefly outlined. Furthermore, the disease processes in which the cytoskeleton plays a decisive role, and which are reviewed in detail in the papers in this issue, are briefly introduced. The advances in our understanding of the cytoskeleton and its function in disease will lead to new diagnostic and therapeutic applications in the foreseeable future. Topics: Actins; Cell Nucleus; Cytoskeletal Proteins; Cytoskeleton; Hematologic Diseases; Humans; Intestinal Diseases; Keratins; Liver Diseases; Lymphatic Diseases; Muscular Diseases; Neurodegenerative Diseases; Skin Diseases | 2004 |
Lessons from disorders of epidermal differentiation-associated keratins.
A number of diseases have been associated with mutations in genes encoding keratin intermediate filaments. Several of these disorders have skin manifestations, in which histological changes highlight the role of various different keratins in epidermal differentiation. For example, mutations in either K1 or K10 (the major keratin pair expressed in differentiated keratinocytes) usually lead to clumped keratin filaments and cytolysis. Furthermore, the precise nature of the mutation has direct implications for disease phenotype. Specifically, mutations in the H1 and alpha-helical rod domains of K1/K10 result in bullous congenital ichthyosiform erythroderma, underscoring the critical role for this keratin filament domain in maintaining cellular integrity. However, a lysine to isoleucine substitution in the V1 domain of K1 underlies a form of palmoplantar keratoderma, which has different cell biological implications. Keratins are cross-linked into the cornified cell envelopes through this particular lysine residue and the consequences of the mutation lead to changes in keratin-desmosome association and cornified cell morphology, suggesting a role for this keratin subdomain in cornified cell envelope formation. Recently, to extend genotype-phenotype correlation, a frameshift mutation in the V2 region of the K1 tail domain was identified in ichthyosis hystrix (Curth-Macklin type), in which keratin filaments show a characteristic shell-like structure and fail to form proper bundles. In this case, the association of desmosomes with loricrin was also altered, implicating this keratin domain in organizing the intracellular distribution of loricrin during cornification. Collectively, these mutations in K1/K10 provide a fascinating insight into both normal and abnormal processes of epidermal differentiation. Topics: Animals; Cell Differentiation; Epidermis; Humans; Keratinocytes; Keratins; Skin Diseases | 2002 |
Corneocyte desquamation.
Corneocyte desquamation at the skin surface is a complex biologic event which is normally regulated for providing an inconspicuous shedding of single corneocytes. When altered, the process gives rise to xerotic and ichthyotic conditions. The present review focusses on important biologic and molecular aspects responsible for normal and altered corneocyte desquamation. There is a complex relationship between epidermal cell production, maturation and desquamative loss. Corneocyte hydration, stratum corneum barrier function and enzymatic corneodesmolysis are involved in a dynamic interrelationship. Many physiological and environmental factors acting in a different time frame influence desquamation. Topics: Cell Adhesion; Dermatologic Agents; Desmosomes; Epidermal Cells; Epidermis; Humans; Keratins; Lipid Metabolism; Membrane Glycoproteins; Skin Diseases; Skin Physiological Phenomena | 2000 |
Immunoelectron microscopy links molecules and morphology in the studies of keratinization.
It is impossible to understand keratinization disorders without knowing what is going on at molecular levels. We and others have been analyzing the issues of keratinization by means of (immuno)electron microscopy and found that this is quite a useful tool for molecular pathology. We summarize the recent advances in the biology and pathology of keratinization at ultrastructural and molecular levels. Tonofilaments, a morphological hallmark of keratinocytes, are composed of keratins. Epidermolytic hyperkeratosis, a genetic disease of keratin K1/K10, shows clumped tonofilaments that are shown to be actually composed of K1/K10 by immunoelectron microscopy. Distribution of profilaggrin and its derivatives has also been revealed by immunoelectron microscopy. Defective interaction between keratin and filaggrin is seen in epidermolytic hyperkeratosis. Transient nuclear localization of N-terminal domains of profilaggrin is observed in the transitional cells of normal epidermis. Unique distribution of trichohyalin was detected in psoriasis. Distribution of various components of cornified cell envelopes including involucrin and loricrin in normal and abnormal keratinization can also be detected with this technique. Premature formation of involucrin-rich cell envelopes are observed in psoriasis vulgaris. Defects in cross-linking of loricrin are detected in transglutaminase 1 knockout mice, the animal model of lamellar ichthyosis. Abnormal distribution of loricrin has been detected in genetic diseases of loricrin (loricrin keratoderma). By combining immunoelectron microscopy and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling (TUNEL) methods, the nature of TUNEL positive cells has also been unravelled. Topics: DNA Fragmentation; Filaggrin Proteins; Humans; In Situ Nick-End Labeling; Keratins; Microscopy, Immunoelectron; Skin; Skin Diseases | 2000 |
Cutaneous ciliated cyst of the right lower leg.
A 23-year-old Japanese woman with a cutaneous ciliated cyst on her right lower leg is reported. A subcutaneous cyst, measuring 2.5 cm in diameter with papillary projections into the lumen, was lined with ciliated cuboidal to columnar epithelia with partial stratification, histologically. These lining cells did not produce mucin. Immunohistochemically, the ciliated lining cells of the cyst were diffusely positive to epithelial membrane antigen and cytokeratin. In addition, positive immunoreaction with anti-desmin monoclonal antibody was observed in the body of the cilia. Less than 10% of the epithelial cells revealed positive immunoreaction to S-100 protein and estrogen receptor. Topics: Adult; Cilia; Cysts; Desmin; Female; Humans; Immunohistochemistry; Keratins; Leg; Mucin-1; Skin Diseases | 1999 |
Using transgenic models to study the pathogenesis of keratin-based inherited skin diseases.
In the past decade, the production of transgenic animals whose genome is modified to contain DNA transgenes of interest has significantly contributed to expand our understanding of the molecular etiology and pathobiology of several inherited skin diseases. This technology has led to the discovery that mutations affecting specific keratin genes are responsible for a wide spectrum of inherited bullous diseases, which are collectively characterized by blistering after minor trauma. Type I and type II keratin proteins are restricted to, and very abundant in, epithelial cells, where they occur as a pancytoplasmic network of cytoskeletal filaments. Although it had long been suspected that a primary function of keratin filaments may be to contribute to the physical strength of epithelial sheets, a formal demonstration came from studies of transgenic mouse models and patients suffering from keratin-based blistering diseases. Here we review the basic characteristics of keratin gene and their proteins and relate them to the molecular pathogenesis of relevant inherited skin blistering diseases. A particular emphasis is placed on the role of transgenic mouse models in the past, current, and future studies of these genodermatoses. Topics: Animals; Disease Models, Animal; Keratins; Mice; Mice, Transgenic; Skin Diseases | 1999 |
Human epidermal keratinocyte: keratinization processes.
Topics: Biomarkers; Cell Differentiation; Hormones; Humans; Keratinocytes; Keratins; Microscopy, Electron; Molecular Structure; Phenotype; Proteins; Receptors, Cell Surface; Skin Diseases; Stem Cells; Transglutaminases; Vitamins | 1997 |
Protein chains in hair and epidermal keratin IF: structural features and spatial arrangements.
Over the past decade the progress made in characterising the structural hierarchy of both the hard and the epidermal keratin intermediate filaments has exceeded all expectations. The origin of much of this progress can be traced back to the quantity of amino acid sequence data that became available in the early/mid 1980s, and their interpretation in terms of a heterodimeric molecular structure. Subdomains were subsequently identified in both the rod and terminal domains, and now the roles of most of these have been determined in principle, if not yet fully in detail. TEM and STEM, together with very revealing crosslinking analyses have also allowed details to be determined of the mechanism by which molecules assemble into oligomers and oligomers into IF. It remains for the three-dimensional packing of keratin molecules in the IF to be elucidated, but even here progress is being made. A particularly exciting development over the last two or three years has been the establishment of the link between keratinopathies and single point nucleotide mutations in keratin genes. Furthermore, the clustering of mutation sites in regions involved in a key structural mode of molecular aggregation has provided, for the first time, an understanding of keratin diseases at the molecular level. Topics: Amino Acid Sequence; Animals; Epidermis; Hair; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Molecular Sequence Data; Molecular Structure; Mutation; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Skin Diseases | 1997 |
Genetic approaches to understanding the keratinopathies.
Genetic methods (both statistical and laboratory based), along with close clinical scrutiny, have led to the recent discovery that abnormal keratin genes underlie several disorders of cornification (Table 3). The ability to classify diseases based on the specific underlying gene mutation has now become a reality (e.g., the ability to distinguish IBS from EHK and to correlate palmoplantar hyperkeratosis in EHK with keratin 1 mutations vs. the lack of palmoplantar hyperkeratosis with keratin 10 mutations). Understanding how specific keratin mutations cause their associated clinical phenotypes will lead to better appreciation of the function of KIFs in epidermis in normal and disease states. Topics: Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Epidermolysis Bullosa Simplex; Genetic Linkage; Hamartoma; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Mutation; Nail Diseases; Skin Diseases | 1997 |
Keith R. Porter Lecture, 1996. Of mice and men: genetic disorders of the cytoskeleton.
Since the time when I was a postdoctoral fellow under the supervision of Dr. Howard Green, then at the Massachusetts Institute of Technology, I have been interested in understanding the molecular mechanisms underlying growth, differentiation, and development in the mammalian ectoderm. The ectoderm gives rise to epidermal keratinocytes and to neurons, which are the only two cell types of the body that devote most of their protein-synthesizing machinery to developing an elaborate cytoskeletal architecture composed of 10-nm intermediate filaments (IFs). Our interest is in understanding the architecture of the cytoskeleton in keratinocytes and in neurons, and in elucidating how perturbations in this architecture can lead to degenerative diseases of the skin and the nervous system. I will concentrate on the intermediate filament network of the skin and its associated genetic disorders, since this has been a long-standing interest of my laboratory at the University of Chicago. Topics: Animals; Cytoskeleton; Epidermolysis Bullosa Simplex; Genetic Diseases, Inborn; Humans; Keratins; Mice; Nervous System Diseases; Skin Diseases | 1997 |
Restrictive dermopathy: report and review.
Restrictive dermopathy (RD) is a lethal autosomal recessive genodermatosis (MIM No. 275210) in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence (FADS). Polyhydramnios with reduced fetal movements is followed by premature delivery at around 31 weeks gestation. Manifestations include a tightly adherent, thin, translucent skin with prominent vessels, typical facial changes, generalized joint contractures, enlarged fontanelles, dysplasia of clavicles, respiratory insufficiency, and an enlarged placenta with short umbilical cord. Histologic abnormalities of the skin include thin dermis with paucity and hypoplasia of the appendages and abnormally arranged collagen bundles. Elastic fibers are nearly missing. The subcutaneous fat is slightly increased. These skin findings usually appear after 22 or 24 weeks of gestation, which is why prenatal diagnosis with skin biopsy may fail. This disease is easily differentiated from other congenital FADS, such as Pena-Shokeir syndrome, COFS syndrome, Parana hard-skin syndrome, etc. We report on an affected boy of consanguineous parents and 30 previous cases are reviewed. Topics: Calcification, Physiologic; Chromosome Inversion; Chromosomes, Human, Pair 9; Collagen; Contracture; Fatal Outcome; Female; Fetal Growth Retardation; Genes, Recessive; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Karyotyping; Keratins; Kyphosis; Male; Natal Teeth; Pregnancy; Skin Diseases; Syndrome | 1997 |
The future of vitamin D in dermatology.
Vitamin D3 analogs have been found to be effective in treating psoriasis.. We attempted to identify the targets and actions of vitamin D3 in the skin and to explore the availability of synthetic vitamin D3 analogs with selective actions on particular cell types or cell functions.. A review of the literature focused on the cellular targets of vitamin D3 in the skin and within the immune system. Furthermore, the use of novel vitamin D3 analogs in skin diseases other than psoriasis was reviewed.. The vitamin D receptor has been detected in most skin cells, which means that keratinization, hair growth, melanogenesis, fibrogenesis, angiogenesis, and immune-mediated processes are potential targets for vitamin D3. Vitamin D3 analogs have been synthesized with a higher therapeutic index or a higher degree of selectivity than the natural form of vitamin D3.. Vitamin D3 analogs with wide-ranging clinical applications may become available for dermatology. Topics: Adjuvants, Immunologic; Biological Availability; Cholecalciferol; Connective Tissue; Dermatologic Agents; Forecasting; Hair; Humans; Immunity, Cellular; Keratins; Melanins; Neovascularization, Physiologic; Psoriasis; Receptors, Calcitriol; Skin; Skin Diseases | 1997 |
Keratins and skin disorders.
The epidermal keratinocytes express two major pairs of keratin polypeptides. One pair (K5/K14) expressed specifically in basal generative compartment and the other (K1/K10) expressed specifically in the differentiating suprabasal compartment. The switch in the expression of the keratins from proliferating to differentiating compartment indicates the changes that occur in the keratin filament organization which in turn influences the functional properties of the epidermis. Proper regulation of keratin gene expression and the filament organization are absolutely necessary for normal functioning of the skin. Keratin gene mutations can influence the filament integrity thereby causing several heritable blistering disorders of the skin such as epidermolysis bullosa, bullous icthyosiform erythroderma, etc. Changes in the keratin gene expression may lead to incomplete differentiation of the epidermal keratinocyte, causing hyperproliferative diseases of the skin such as psoriasis, carcinomas, etc. This review briefly describes the changes in keratin structure or gene expression that are known to result in various disorders of the skin. Topics: Gene Expression; Humans; Keratins; Skin Diseases | 1996 |
The genetics of human skin diseases.
Molecular genetic analyses during the past half-decade have brought unexpected insights into the molecular defects underlying a wide variety of abnormal skin phenotypes. Highlights of the efforts in the past year include the identification of mutations in an epidermal transglutaminase gene in lamellar ichthyosis as well as mutations in an additional five keratin genes causing four different abnormal phenotypes, and mutations in beta 4 integrin and bullous pemphigoid antigen 2 genes in junctional epidermolysis bullosa and in the p16NK-4a gene in 50% of kindreds with familial melanoma. Topics: Epidermolysis Bullosa, Junctional; Humans; Ichthyosis, Lamellar; Keratins; Melanoma; Skin Diseases; Skin Neoplasms | 1996 |
Human keratin diseases: hereditary fragility of specific epithelial tissues.
Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining t Topics: Animals; Epithelium; Genes, Recessive; Genotype; Humans; Keratins; Phenotype; Point Mutation; Pseudogenes; Skin Diseases | 1996 |
Hair keratinization in health and disease.
The cells of the epidermis and its derivative, the hair follicle, undergo processes of terminal differentiation that involves the synthesis and assembly of classes of protein and enzymes to form the stratum corneum of the epidermis, and the hair fiber and its cuticle. Using genetic linkage and DNA sequencing methods, we now know that mutations in several genes encoding epidermal keratins or a transglutaminase enzyme cause ichthyosis-related diseases. Similar methods have now suggested that mutations in hair keratin genes underlie some cases of monilethrix, and a deficiency in a cuticle lipid metabolizing enzyme causes maple syrup urine disease. It is to be expected that further application of these methods will elucidate the molecular bases of other genetic hair diseases. Topics: Animals; Epidermal Cells; Epidermis; Genetic Linkage; Hair; Hair Diseases; Humans; Keratinocytes; Keratins; Maple Syrup Urine Disease; Mutation; Reference Values; Skin; Skin Diseases; Skin Physiological Phenomena | 1996 |
The latest fashions in skin disease.
The complex nature of epidermal tissue homeostasis is borne out by the range of diseases affecting this tissue. Indeed, mutations in proteins involved in intracellular integrity and cell-cell or cell-matrix adhesion can cause disease in an appropriate epidermal compartment. The most important realization in epidermal disease in the last two years has been that point mutations in key structural genes can result in filaments collapsing, cell cytolysis, or cell adhesion defects; and that these defects can result in severe human skin disease. Now that these associations have been made, the important next step will be to alleviate the suffering of these patients. Animal models will be an important part of these investigations; many molecules including growth factors, oncogenes, and cell adhesion molecules have been targeted to the epidermis of transgenic mice to investigate their role in disease. Such animal models should also elucidate the causes of diseases like psoriasis, a very common skin disease, the molecular basis of which remains elusive. Gene therapy involving the replacement of defective genes or local delivery of therapeutic molecules will be one of the main goals in alleviating these known epidermal diseases. Such protocols in the epidermis are aided by the relative accessibility of the skin and the presence of the "stem cells" in relatively accessible compartments. Indeed, as the last few years have shed much light on the genetic causes of epidermal disease, it is hoped that the next several years will prove as illuminating in the alleviation of these diseases. Topics: Animals; Cell Adhesion; Cell Adhesion Molecules; Humans; Kalinin; Keratins; Mice; Mice, Transgenic; Skin; Skin Diseases; Skin Physiological Phenomena | 1995 |
Keratins and the skin.
Keratins are the major structural proteins of the vertebrate epidermis and its appendages, constituting up to 85% of a fully differentiated keratinocyte. Together with actin microfilaments and microtubules, keratin filaments make up the cytoskeletons of vertebrate epithelial cells. Traced as far back in the evolutionary kingdom as mollusks, keratins belong to the superfamily of intermediate filament (IF) proteins that form alpha-helical coiled-coil dimers which associate laterally and end-to-end to form 10-nm diameter filaments. The evolutionary transition between organisms bearing an exoskeleton and those with an endoskeleton seemed to cause considerable change in keratin. Keratins expanded from a single gene to a multigene family. Of the approximately 60 IF genes in the human genome, half encode keratins, and at least 18 of these are expressed in skin. Vertebrate keratins are subdivided into two sequence types (I and II) that are typically coexpressed as specific pairs with complex expression patterns. The filament-forming capacity of a pair is dependent upon its intrinsic ability to self-assemble into coiled-coil heterodimers, a feature not required of the invertebrate keratins (Weber et al 1988). Approximately 20,000 heterodimers of type I and type II keratins assemble into an IF. Mutations that perturb keratin filament assembly in vitro can cause blistering human skin disorders in vivo. From studies of these diseases, an important function of keratins has been unraveled. These filaments impart mechanical strength to a keratinocyte, without which the cell becomes fragile and prone to rupturing upon physical stress. In this review, studies on the pattern of expression, structure, and function of skin keratins are summarized, and new insights into the functions of these proteins and their involvement in human disease are postulated. Topics: Amino Acid Sequence; Animals; Base Sequence; Embryo, Mammalian; Embryo, Nonmammalian; Epidermolysis Bullosa Simplex; Gene Expression Regulation; Hair; Humans; Hyperkeratosis, Epidermolytic; Keratins; Mammals; Molecular Sequence Data; Multigene Family; Nevus; Oligodeoxyribonucleotides; Point Mutation; Protein Structure, Secondary; Skin; Skin Diseases; Skin Neoplasms; Skin Physiological Phenomena; Vertebrates | 1995 |
Keratin and keratinization.
A flood of new knowledge and discoveries in the basic science of keratins and keratinization has appeared in the past several years. This review summarizes this recent information with a focus on the epithelial keratin polypeptides, keratin intermediate filaments, keratohyaline granule proteins, cell envelope formation and cell envelope proteins, "soft" keratinization, true disorders of keratinization (i.e., epidermolysis bullosa simplex and epidermolytic hyperkeratosis), and disease and drug effects on keratinization. Topics: Adult; Animals; Betamethasone; Cells, Cultured; Cyclosporine; Epidermolysis Bullosa Simplex; Humans; Hyperkeratosis, Epidermolytic; Keratins; Retinoids; Skin; Skin Diseases; Wound Healing | 1994 |
Intermediate filaments and disease: mutations that cripple cell strength.
Topics: Animals; Cell Survival; Genetic Diseases, Inborn; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Mutation; Skin Diseases | 1994 |
Keratin diseases.
The recent discovery that epidermal fragility syndromes can be caused by mutations in the genes for keratin intermediate filaments has been a turning point for research into these structural proteins. Clustering of pathogenic mutations implies differential structural sensitivity along the keratin molecule, and implications for filament function require a new look at culture assay systems, plus a reassessment of structural defects in epithelial and other tissues. Topics: Amino Acid Sequence; Humans; Keratins; Models, Biological; Molecular Structure; Mutation; Phenotype; Skin Diseases | 1994 |
Structural features of keratin intermediate filaments.
The first step in the assembly of a keratin intermediate filament (KIF) is the formation of a type I/type II heterodimer molecule in which two chains become aligned in parallel and close axial registration to form a flexible segmented alpha-helical coiled-coil rope 46 nm long. The segments of coiled-coil are interspersed by sequences that introduce irregularities of unknown structure. Here we have modeled two of these, the link L2 and the heptad discontinuity located near the middle of segment 2B. In a model for L2, the orientation of the coiled-coil structure is turned through about 180 degrees over the eight residue stretch constituting this link segment. In contrast, the heptad discontinuity in segment 2B would seem to result in only minimal distortion of the coiled-coil rope, contrary to previous expectations. Little is known about how the neighboring molecules are aligned and packed within the assembled KIF. Crosslinking experiments with KIF have determined that two neighboring molecules are aligned anti-parallel and axially in three ways, and predict that similarly-directed molecules could be overlapped by about 1 nm. The two-dimensional surface lattice resulting from these data predicts an axial periodicity of 22.6 nm, which in fact is visible by electron microscopy of shadowed KIF. Interestingly, most of the amino acid substitutions resulting from mutations in the keratin genes found in genodermatoses are clustered in this molecular overlap region. Although we do not yet know how the rows of antiparallel molecules fold in three dimensions to form an intact KIF, certain of the observed crosslinks could also occur between nearest neighbor parallel molecules across a four-molecule strand; that is, KIF may be built from bundles or protofibrils. These insights on molecular structure and molecular packing provide new constraints on models for KIF structure. Topics: Amino Acid Sequence; Animals; Genetic Linkage; Humans; Intermediate Filaments; Keratins; Models, Molecular; Models, Structural; Molecular Sequence Data; Multigene Family; Mutation; Skin Diseases | 1994 |
Ultrastructural identification of basic abnormalities as clues to genetic disorders of the epidermis.
The present article discusses specific, directly gene-dependent ultrastructural markers of dominantly inherited epidermal disorders that serve as clues to their underlying molecular genetic abnormalities. These are epidermolysis bullosa simplex Koebner and Weber-Cockayne with rupture or non-assembly of basal cell keratins and point mutations in keratins 5 and 14. Clumping of basal cell keratins is pathognomonic of EB Dowling-Meara and caused by mutations in hot spots of the rod domain of K5 and K 14. Clumps and aggregates of basal keratins occur side by side in the same cell and thus do not indicate specific different types of mutations. Similar clumping of suprabasal keratins in bullous CIE Brocq and in palmoplantar keratoderma Voerner have been assigned to identical types of mutations in the same critical position of the rod domain in K 1, K 10, and K 9, respectively. Highly unusual tubular keratins are pathognomonic of another dominant palmoplantar keratoderma type the genetic basis of which still awaits elucidation. Shell formation of (low molecular weight?) keratins in ichthyosis hystrix Curth-Macklin is not linked to the keratin gene clusters on chromosomes 12 and 17 and might be related to regulatory genes of keratin expression. Suprabasal shells in congenital reticular ichthyosiform erythroderma do not consist of keratins but resemble glycoprotein networks. Finally, the keratohyalin abnormality in ichthyosis vulgaris was the clue for the identification of a filaggrin deficiency, at the same time giving evidence to the heterogeneity of keratohyalin proteins. Topics: Epidermis; Filaggrin Proteins; Genetic Markers; Humans; Hyalin; Keratins; Microscopy, Electron; Skin Diseases | 1994 |
Keratin gene mutations in human skin disease.
Topics: Animals; Epidermolysis Bullosa; Gene Expression; Humans; Hyperkeratosis, Epidermolytic; Intermediate Filaments; Keratins; Keratoderma, Palmoplantar, Diffuse; Mice; Mice, Transgenic; Point Mutation; Skin Diseases | 1994 |
The epidermis: rising to the surface.
At the skin surface, the epidermis serves an important protective function which it manifests by building an extensive cytoskeletal architecture of keratin filaments, spanning from the nuclear envelope to hemidesmosomes and desmosomes. Recent studies on epidermal proteins and their interactions have provided insights into human skin diseases, including genetic disorders of keratins, laminins, and collagen. Explorations into the regulatory mechanisms underlying epidermal genes have underscored the importance of transcription factors AP-1 and AP-2, retinoic acid receptors, and POU proteins. Transgenic and gene ablation experiments on TGF-alpha and TGF-beta genes have yielded clues as to how the epidermis maintains a balance of growing and differentiating cells. Topics: Animals; Base Sequence; Cell Differentiation; Cell Division; DNA; Epidermal Cells; Epidermis; Gene Expression Regulation, Developmental; Humans; Keratins; Molecular Sequence Data; Skin Diseases; Stem Cells; Transcription Factors | 1994 |
[Biochemistry of keratin proteins].
Topics: Animals; Cells, Cultured; Humans; Keratins; Mice; Molecular Structure; Point Mutation; Skin Diseases; Tretinoin | 1993 |
Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats.
Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were investigated by light microscopy in order to clarify the nomenclature and classification of these lesions. The structure of benign keratinizing cystic squamous cell tumours of the lung was compared to that of cystic squamous lesions in the skin of rats, with consideration of data from the literature. We conclude that the reviewed keratinizing cystic squamous cell lesions of the lung are true neoplasms and that the growth pattern of these cystic lesions is inconsistent with that of a simple cyst. In the development of squamous lung cancer, a continuum of proliferation from exaggerated metaplasia through benign cystic tumours to invasive squamous cell carcinomas can be observed. Topics: Animals; Epidermal Cyst; Keratins; Keratoacanthoma; Lung Neoplasms; Rats; Skin Diseases; Terminology as Topic | 1993 |
Genetic skin diseases caused by mutations in keratin intermediate filaments.
Keratin intermediate filaments are the major differentiation products of epithelial cells such as the epidermis. The filaments are highly dynamic entities involved in the maintenance of the structural integrity of both the individual cells and the entire tissue. Recent biochemical studies suggest that the keratin proteins overlap each other in several key locations when packed together in filaments. Interestingly, mutations that introduce inappropriate amino acid substitutions in at least some of these overlap regions cause defective keratin filaments that result in at least three classes of autosomal dominant skin disease. Topics: Amino Acid Sequence; Animals; Humans; Intermediate Filaments; Keratins; Molecular Sequence Data; Mutation; Skin Diseases | 1993 |
Transgenic models of skin diseases.
Transgenic animals have greatly enhanced our understanding of the contribution of various structural and regulatory components to epidermal biology. The expression of mutant versions of these components in the epidermis of transgenic mice has generated animal models of specific human skin diseases.. The expression of mutant keratin genes has produced animal models of epidermolysis bullosa simplex and epidermolytic hyperkeratosis and, in doing so, has focused attention on the genetics of keratins in these and other skin disorders. Similarly, the generation of mice overexpressing growth factors and/or oncogenes, exclusively in the epidermis, has identified the role of these factors in normal skin and produced models of disease states where the regulation of these factors is perturbed.. These models of keratin disorders and other diseases not only enable the determination of the cause of these disorders, but also allow evaluation of novel therapeutic techniques for the amelioration of these skin diseases. Topics: Animals; Animals, Newborn; Epidermal Growth Factor; Gene Expression; Genes, Dominant; Genes, fos; Genes, ras; Humans; Keratins; Mice; Mice, Transgenic; Models, Biological; Mutation; Phenotype; Skin; Skin Diseases; Skin Neoplasms; Transforming Growth Factor alpha; Transforming Growth Factor beta | 1993 |
Intermediate filament structure.
In the past year, several new developments concerning the structure of intermediate filament proteins and their assembly into intact intermediate filaments have been made: the coiled-coil structure of a rod domain has been elucidated; the basis of the chain interaction and its role in intermediate filament assembly has been specified; the organization of nearest-neighbour molecules in keratin intermediate filaments has been determined; and the glycine loop structures of the terminal domains of epidermal keratin chains have been defined. In addition, mutations in intermediate filament chains that promote pathology have been reported for the first time. Topics: Animals; Humans; Intermediate Filaments; Keratins; Mutagenesis, Site-Directed; Skin Diseases | 1992 |
Eruptive vellus hair cysts: case report and review of the literature.
A 6-year-old Caucasian girl had dozens of asymptomatic, flesh-colored, 2- to 5-mm eruptive vellus hair cysts. These papules on the buttocks, thighs, and groin increased in number for three months. Histologic examination revealed poorly defined, keratin-filled cysts in the upper middermis, containing numerous transversely or obliquely cut portions of vellus hair. The histopathologic differential diagnosis with other epithelial cysts containing hair shafts is debated, and new clinical differential diagnoses are proposed. Review of the literature suggests that eruptive vellus hair cyst is not a rare disorder, but its frequency is probably underestimated due to paucity of symptoms. Nevertheless, the clinical relevance of some of the differential diagnoses should convince clinicians to obtain histologic confirmation. Topics: Buttocks; Child; Epidermal Cyst; Epithelium; Female; Groin; Hair; Humans; Keratins; Skin Diseases; Thigh | 1992 |
Of mice and men: genetic skin diseases of keratin.
Topics: Amino Acid Sequence; Animals; DNA Mutational Analysis; Humans; Intermediate Filaments; Keratins; Mice; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Skin Diseases | 1992 |
[The keratinocyte].
This review summarizes recent data on the keratinocyte, the major cell type in the epidermis. A two-state model is proposed: in the "resting" state, the keratinocyte is committed to a program of terminal differentiation focusing on production of an efficient barrier, the stratum corneum, and of the epidermal basement membrane; the activated state, first discovered in cell culture studies, occurs in vivo during epidermal wound healing and inflammatory skin diseases. Topics: Cell Differentiation; Epidermal Cells; Epidermis; Filaggrin Proteins; Humans; Interleukin-1; Intermediate Filament Proteins; Keratinocytes; Keratins; Protein Precursors; Skin Diseases; Transglutaminases; Wound Healing | 1992 |
Follicular hybrid cysts. An expanded spectrum.
Currently it is well established that each of the three parts of the hair follicle (infundibulum, isthmus, and the inferior portion) originates different types of cutaneous cysts. Thus, follicular cysts include infundibular, trichilemmal, and matricial cysts. Brownstein in 1983 described a mixed type of cutaneous cyst combining epidermoid, infundibular, and trichilemmal types of keratinization. We review and illustrate the different combinations of follicular hybrid cysts reported to date: infundibular and trichilemmal cyst, infundibular and pilomatricoma cyst, trichilemmal and pilomatricoma cyst, eruptive vellus hair cyst and steatocystoma, and eruptive vellus hair cyst and trichilemmal cyst. Therefore, the concept of hybrid cyst should not be restricted to those composed of infundibular and trichilemmal cysts, because any cyst arising from the various parts of the pilosebaceous unit can combine with others to form a large series of follicular hybrid cysts. Topics: Diagnosis, Differential; Follicular Cyst; Hair; Hair Diseases; Humans; Keratins; Skin Diseases | 1991 |
Keratin genes, epidermal differentiation and animal models for the study of human skin diseases.
The examples shown here illustrate the power of gene targeting to the epidermis as a means of developing animal models for the study of human skin diseases. In this short review, I have focused on contributions which stem predominantly from my own laboratory [31, 32, 34, 37, 47]. However, other laboratories have also contributed heavily to the development of this technology [28-30, 35, 36]. The opportunities for these models are vast: there are a myriad of human skin diseases which have been characterized extensively at a biological level, but whose aetiology is presently unknown. A combined knowledge of (a) the biochemistry of epidermal differentiation; (b) epidermal-specific gene expression; and (c) transgenic mouse technology has provided the foundation for these and future studies in this area. Topics: Animals; Disease Models, Animal; Humans; Keratins; Mice; Mice, Transgenic; Mutation; Skin; Skin Diseases; Transcription, Genetic; Transforming Growth Factor alpha | 1991 |
[Cytokeratins--survey of incidence in normal and diseased skin. II. Cytokeratin expression in diseased skin].
The distribution patterns of cytokeratins demonstrated by different authors in benign and malignant tumours of the skin are presented and the resulting possibilities for histological differentiation are discussed. The monoclonal antibody A53-B/A2 made in GDR may be useful in the diagnosis of Merkel cell tumours or of the extramammary Morbus Paget. -For different dermatoses, especially some disease with abnormal types of keratinization, the expressed polypeptides are described. Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Peptides; Skin; Skin Diseases; Skin Neoplasms | 1990 |
[Amyloid K].
Electron-microscopic, histochemical and immunological studies have shown that the deposits of primary and secondary localized cutaneous amyloid (amyloid K) consist mainly of keratin filament material. The amyloid P component is the second most significant constituent. Pathogenetically, defective keratinocyte apoptosis is the most likely mechanism of generation for amyloid K. Apoptosis is a distinct mode of cell death according to which individual basal keratinocytes disintegrate in physiological and pathological conditions to form membrane-bound "apoptotic" bodies consisting mainly of keratin filament aggregates. These lose their protective membrane and drop into the upper dermis, where they present as keratin (Civatte, cytoid) bodies, which are regularly coated with immunoglobulins. Overproduction of keratin bodies and/or a defect in their degradation by enzymatic digestion or phagocytosis by macrophages and fibroblasts, followed by conversion into amyloid fibrils, may be responsible for the generation of deposits of amyloid K. Topics: Amyloid; Amyloidosis; Humans; Keratins; Microscopy, Electron; Monocytes; Phagocytosis; Serum Amyloid P-Component; Skin; Skin Diseases | 1988 |
[Use of the cell culture method in genetic dermatoses].
Topics: Amniotic Fluid; Cell Differentiation; Cells, Cultured; Epidermal Cells; Female; Fibroblasts; Genetic Carrier Screening; Humans; Keratins; Pregnancy; Prenatal Diagnosis; Skin Diseases | 1988 |
Morphogenesis and malformations of the skin NICHD/NIADDK research workshop.
Developmentally caused skin malformations constitute a spectrum of birth defects, some of which can be recognized prenatally by morphologic or biochemical means. The number of prenatally diagnosable skin diseases could be greatly expanded with an increased understanding of the molecular and cellular bases of skin development and the mechanisms that result in the generation of skin defects. The National Institute of Child Health and Human Development and the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, therefore, sponsored a workshop that recommended basic biologic studies combined with clinical investigations of normal and abnormal cutaneous development set forth in this article. Investigations resulting from these research recommendations are intended to contribute to the knowledge that should aid in the prevention of developmentally caused skin deformities. Topics: Adult; APUD Cells; Cell Differentiation; Cytoskeletal Proteins; Desmoplakins; Epidermal Cells; Epidermis; Extracellular Matrix; Fetus; Filaggrin Proteins; Gene Expression Regulation; Humans; Intermediate Filament Proteins; Keratins; Langerhans Cells; Lipids; Melanocytes; Membrane Proteins; Microbial Collagenase; National Institutes of Health (U.S.); Skin; Skin Abnormalities; Skin Diseases; Skin Physiological Phenomena; United States | 1987 |
Immunopathology of cutaneous graft-versus-host disease.
Graft-versus-host disease (GVHD) occurs when lymphoid cells from an immunocompetent donor are introduced into a histoincompatible recipient that is incapable of rejecting them. GVHD is seen most commonly as a complication of therapeutic bone marrow transplantation, and the skin is a primary target organ. As GVHD mimics several important skin diseases both clinically and histologically, it provides a useful model for studying the immunopathologic features of epidermal cell-lymphocyte interactions. Topics: Animals; Epidermis; Graft vs Host Disease; HLA-D Antigens; Humans; Keratins; Langerhans Cells; Skin Diseases; T-Lymphocytes | 1987 |
Expression and modification of keratins during terminal differentiation of mammalian epidermis.
Topics: Animals; Cell Differentiation; Cells, Cultured; Epidermal Cells; Epidermis; Foot; Gene Expression Regulation; Hair; Hand; Humans; Keratins; Nails; Phosphorylation; Protein Processing, Post-Translational; Skin Diseases | 1987 |
Fanconi anemia, dyskeratosis congenita, and WT syndrome.
The association of congenital anomalies and pancytopenia is encountered in several clinical syndromes. Among these, Fanconi anemia is by far the most prevalent, and consequently best known. As a result, other similar conditions, such as dyskeratosis congenita and particularly WT syndrome, are often mistaken for Fanconi anemia. However, at a closer look, the type of congenital anomalies, the mode of inheritance, cytogenic and other laboratory findings allow clear differentiation between these 3 syndromes. Topics: Abnormalities, Multiple; Anemia, Aplastic; Diagnosis, Differential; Fanconi Anemia; Female; Humans; Keratins; Male; Pancytopenia; Skin Diseases; Syndrome | 1987 |
Epidermal effects of retinoids: supramolecular observations and clinical implications.
Retinoids, synthetic vitamin A analogs, stimulate mucous metaplasia and gap-junction proliferation in embryonic and neoplastic epidermis. Such effects demonstrate that vitamin A has potent effects on epidermal differentiation. Oddly, however, retinoid action in normal postnatal tissues, where these drugs are used clinically, appears to be quite different. In animals and humans, both topical and systemic retinoids produce acanthosis, hypergranulosis, and a relative (but not absolute) decrease in the thickness of the stratum corneum. These changes reflect the distinct boost in cell turnover that results from retinoid treatment. On the ultrastructural level, desmosomes are actively shed by cells of the spinous layer, resulting in many fewer attachment points along the cell membranes of the outer epidermis. Loss of desmosomes, coupled with decreased tonofilaments, enhanced keratinocyte autolysis, and intercellular deposition of glycoconjugates (not mucin), cause loosening and fragility of the stratum corneum (so-called anti-keratinizing effects). The biochemical basis of retinoid activity, in addition to stimulating increased cell turnover, appears to be a global enhancement of glycoconjugate synthesis and the generation of less mature keratins. The epidermal effects of retinoids can be exploited therapeutically: to cause loosening of thickened stratum corneum, for example in psoriasis or ichthyosis; to enhance penetration of pharmacologic agents such as 5-fluorouracil across hypertrophic actinic keratoses; and to normalize differentiation in neoplastic epidermis involving mucous metaplasia and gap-junction proliferation. Topics: Animals; Cell Differentiation; Desmosomes; Epidermis; Humans; Intermediate Filaments; Keratins; Retinoids; Skin Diseases | 1986 |
[Basal cell antigens of normal epidermal tissues and in pathology].
Topics: Animals; Antibodies; Antigens; Cell Differentiation; Epidermal Cells; Epidermis; Humans; Immunization; Keratins; Reference Values; Skin Diseases | 1986 |
Monoclonal antibody studies of mammalian epithelial keratins: a review.
Topics: Animals; Antibodies, Monoclonal; Cell Differentiation; Cells, Cultured; Epithelium; Humans; Keratins; Models, Biological; Molecular Weight; Skin; Skin Diseases; Vitamin A Deficiency | 1985 |
Etretinate therapy in children with severe keratinization defects.
Keratinization defects can be very severe and disfiguring diseases. The development of retinoids such as etretinate has provided us with an effective symptomatic form of oral therapy for these skin conditions. Based on our own experience, we briefly outline the therapeutic potential of etretinate in various keratinization defects (lamellar ichthyosis, Netherton syndrome, Sjögren-Larsson syndrome, mal de Meleda and juvenile pityriasis rubra pilaris). The toxicology of etretinate is reviewed with special regard to the treatment of children. Bone changes such as premature closure of the growth line or other unacceptable side-effects have so far not been observed. Guidelines for patient selection and for the safe treatment of children are given. Topics: Adolescent; Bone and Bones; Chemical Phenomena; Chemistry; Child; Etretinate; Female; Humans; Keratins; Male; Skin Diseases | 1985 |
Progress on cutaneous amyloidoses.
Topics: Amyloid; Amyloidosis; Disulfides; Histocytochemistry; Humans; Immunoglobulin G; Immunologic Techniques; Keratins; Maleimides; Microscopy, Electron; Skin Diseases; Staining and Labeling | 1984 |
Retinoids: a review.
The retinoids are synthetic derivatives of vitamin A. Isotretinoin (13-cis-retinoic acid) is now being widely used in the United States for severe acne and etretinate is available in Europe and other countries for psoriasis. These drugs are also effective for a number of other skin diseases. This is an attempt to review basic knowledge of retinoids with which the practicing dermatologist should be familiar, to review the current status of studies, and to speculate on the present and future roles of these drugs in dermatology. Topics: Acne Vulgaris; Etretinate; Humans; Inflammation; Isotretinoin; Keratins; Psoriasis; Retinoids; Sebum; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases; Tretinoin; Vitamin A | 1984 |
Pathology of granulomatous diseases. Foreign body granulomas.
Topics: Animals; Diagnosis, Differential; Foreign Bodies; Gout; Granuloma; Hair; Humans; Insecta; Keratins; Lipids; Oils; Plants; Silicon Dioxide; Skin; Skin Diseases; Sutures; Tattooing | 1984 |
Dermatologic birth defects and congenital skin disease.
Topics: Alopecia Areata; Child; Collagen Diseases; DNA; Genetic Counseling; Humans; Keratins; Male; Nevus; Pharmaceutical Preparations; Pharmacogenetics; Research; Skin Abnormalities; Skin Diseases; Skin Diseases, Vesiculobullous; Skin Neoplasms; Syndrome | 1984 |
Immunohistochemistry of adnexal neoplasms.
Topics: Animals; Antibodies, Monoclonal; Carcinoembryonic Antigen; Female; Goats; Humans; Immunoenzyme Techniques; Keratins; Mice; Pregnancy; Protein Precursors; Rabbits; S100 Proteins; Skin Diseases; Skin Neoplasms | 1984 |
Flow cytometry of keratinocytes.
A prerequisite for using flow cytometry (FCM) is the availability of isolated single cells. Procedures for separation and isolation of keratinocytes from animals and man are available, and the resulting single cell suspensions have been subjected to FCM measurements. The major advantage of the method is the accuracy and speed with which a variety of cellular constituents can be quantified. FCM of keratinocytes has, hitherto, been mainly confined to measurements of nuclear DNA for estimation of cell-cycle distributions and for ploidy studies. In mouse epidermis, cell-cycle distributions were estimated from sequentially obtained DNA histograms and evaluated with other cell kinetic measurements, resulting in new information about epidermal cell-cycle progression, not achievable by any of the methods alone. The best way, therefore, to increase our knowledge of keratinocyte proliferation, is the combined use of DNA FCM and other cell kinetic methods. DNA FCM has also been applied to healthy and diseased human epidermis, and may add valuable information to the classification of skin disease in selected cases. It is believed that further progress in the characterization of keratinocyte growth and development will depend on parameters other than DNA alone. Topics: Animals; Cell Cycle; Cell Separation; Circadian Rhythm; Cricetinae; DNA; Epidermal Cells; Epidermis; Epithelium; Flow Cytometry; Humans; In Vitro Techniques; Keratins; Mice; Mice, Hairless; RNA; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1983 |
Retinoids in keratinizing diseases and acne.
Topics: Acne Vulgaris; Adolescent; Child; Child, Preschool; Darier Disease; Etretinate; Female; Humans; Ichthyosis; Infant; Isomerism; Isotretinoin; Keratins; Keratoderma, Palmoplantar; Male; Pityriasis Rubra Pilaris; Psoriasis; Skin Diseases; Skin Diseases, Vesiculobullous; Tretinoin | 1983 |
Advances in genetics in dermatology.
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 | 1982 |
The cytoskeleton in pathologic conditions.
Topics: Actomyosin; Animals; Cytoskeleton; Desmin; Glial Fibrillary Acidic Protein; Hepatitis, Alcoholic; Humans; Intermediate Filament Proteins; Keratins; Liver; Mice; Microtubules; Protein Precursors; Skin Diseases; Vimentin | 1982 |
Lipids and the epidermal permeability barrier.
Topics: Animals; Biological Transport; Epidermis; Fatty Acids, Essential; Freeze Fracturing; Keratins; Lipids; Mice; Permeability; Skin; Skin Diseases; Solvents | 1981 |
Lipid composition and metabolism in normal and diseased epidermis.
Topics: Fatty Acids; Fatty Acids, Essential; Humans; Hydrocarbons; Ichthyosis; Keratins; Lipid Metabolism; Lipids; Phospholipids; Psoriasis; Skin; Skin Diseases; Skin Physiological Phenomena; Sphingolipids; Sterols; Subcellular Fractions; Waxes | 1981 |
[Cutaneous cysts and cystic skin tumors].
The nomenclature and pathogenesis of cutaneous cysts is discussed along the lines of their pathological properties. On the basis of histological and experimental evidence it is concluded that most cysts represent benign neoplasms derived from pluripotential cells. Topics: Adenoma, Sweat Gland; Cysts; Dermoid Cyst; Epidermal Cyst; Hamartoma; Humans; Keratins; Pilonidal Sinus; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases | 1979 |
Lysosomes and the skin.
Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Fabry Disease; Inflammation; Keratins; Langerhans Cells; Light; Lysosomes; Melanophores; Microscopy, Electron; Peptide Hydrolases; Phagocytosis; Pigmentation; Protease Inhibitors; Sebaceous Glands; Skin; Skin Diseases; Skin Neoplasms; Vitamin A | 1975 |
Vitamin A and keratinization.
Topics: Animals; Cell Division; Humans; Keratins; Lysosomes; Membranes; Mucins; Protein Biosynthesis; Rats; RNA; Skin; Skin Diseases; Vitamin A; Vitamin A Deficiency | 1972 |
Sulphur metabolism in relation to cutaneous disease.
Topics: Chondroitin; Dermatitis, Exfoliative; Glycosaminoglycans; Hair; Homocystinuria; Humans; Keratins; Methionine; Psoriasis; Skin Diseases; Sulfates; Sulfur | 1969 |
Trials
6 trial(s) available for bromochloroacetic-acid and Skin-Diseases
Article | Year |
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Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases.
Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process. Topics: Adult; Aged; Amyloid; Amyloidosis; Dermis; Ear; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases | 2012 |
Clinical application of multiphoton tomography in combination with high-frequency ultrasound for evaluation of skin diseases.
The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments. Topics: Adult; Aged; Aged, 80 and over; Coenzymes; Collagen; Elastin; Female; Fluorescence; Humans; Keratins; Lasers; Male; Melanins; Microscopy, Fluorescence, Multiphoton; Middle Aged; Skin; Skin Diseases; Skin Neoplasms; Tomography, Optical; Ultrasonics | 2010 |
Comparative effects of retinoic acid, glycolic acid and a lipophilic derivative of salicylic acid on photodamaged epidermis.
Studies comparing purported antiaging compounds are rare.. To compare in a randomized, placebo-controlled double-blind study 10% glycolic acid (GA), 2% 2-hydroxy-5-octanoyl benzoic acid (beta-lipohydroxy acid, LSA) and 0.05% all-trans-retinoic acid (RA).. Women volunteers treated one forearm twice daily with one of the active products and the other one with the vehicle. Comparative evaluations of efficacy were made using histochemistry and quantitative immunohistochemistry.. Improvement in the various epidermal compartments was the most prominent finding at the RA-treated site. The LSA-treated site also exhibited similar positive changes, although to a lesser degree. GA showed no significant effect.. In the presently tested concentrations and formulations, RA had a beneficial impact upon the aging epidermis. LSA mimicked RA but with somewhat lesser efficacy. By contrast, GA appeared almost inactive. Topics: Double-Blind Method; Epidermis; Female; Filaggrin Proteins; Glycolates; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Keratolytic Agents; Ki-67 Antigen; Lectins; Middle Aged; Plant Lectins; Salicylates; Skin; Skin Diseases; Transglutaminases; Treatment Outcome; Tretinoin | 1999 |
Bacteriology of inflamed and uninflamed epidermal inclusion cysts.
To determine whether inflamed and uninflamed epidermoid cysts differ in the number and/or type of bacteria inhabiting them.. A controlled study. We obtained aerobic and anaerobic bacterial culture specimens from 25 inflamed and 25 uninflamed epidermoid cysts.. A university medical center.. Nonimmunocompromised adults without recent systemic use of antibiotics.. The 2 groups did not differ significantly with respect to number of bacterial isolates, "no growth" cultures, and aerobic, anaerobic, or potential pathogens cultured.. The microbiological milieu of inflamed epidermoid cysts is similar to that of uninflamed cysts. Possible mechanisms for inflammation are discussed. Topics: Adult; Aged; Bacteria, Aerobic; Bacteria, Anaerobic; Colony Count, Microbial; Cysts; Erythema; Female; Gram-Positive Bacterial Infections; Humans; Inflammation; Keratins; Male; Middle Aged; Peptostreptococcus; Skin Diseases; Staphylococcal Infections; Staphylococcus aureus; Suppuration | 1998 |
Systemic retinoids in dermatology.
Orally administered retinoids are synthetic derivatives of vitamin A. This new group of drugs (not yet available for general use in the United States) has been effective in experimental trials for treatment of a wide range of skin diseases. The current status of two of these drugs, isotretinoin (13-cis-retinoic acid) and etretinate (Ro 10-9359), is herein reviewed. Topics: Acne Vulgaris; Administration, Oral; Child; Clinical Trials as Topic; Facial Dermatoses; Female; Humans; Isomerism; Isotretinoin; Keratins; Keratitis; Neoplasms; Psoriasis; Skin Diseases; Tretinoin; Xerostomia | 1982 |
The use of isotretinoin in disorders of keratinization.
Topics: Clinical Trials as Topic; Humans; Isomerism; Isotretinoin; Keratins; Skin Diseases; Tretinoin | 1982 |
Other Studies
291 other study(ies) available for bromochloroacetic-acid and Skin-Diseases
Article | Year |
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LC-MS/MS and immuno-electron subtyping combined with genetics show that OSMR mutations cause amyloid deposition of keratins 5/14 in familial primary localized cutaneous amyloidosis.
Topics: Amyloidosis, Familial; Chromatography, Liquid; Humans; Keratins; Mutation; Oncostatin M Receptor beta Subunit; Skin Diseases; Skin Diseases, Genetic; Tandem Mass Spectrometry | 2022 |
Subungual Pigmented Squamous Cell Carcinoma in a Dog.
An 11-year-old spayed female Miniature Schnauzer dog was presented with loss of a claw caused by a nail bed mass. Histopathological evaluation revealed that the mass comprised neoplastic squamous cells with abundant cytoplasmic melanin pigment. Immunohistochemically, the neoplastic cells were positive for cytokeratin and negative for vimentin and ionized calcium-binding adaptor molecule 1, supporting a diagnosis of pigmented squamous cell carcinoma. To our knowledge, this is the first report of subungual pigmented squamous cell carcinoma in animals. Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Keratins; Nail Diseases; Skin Diseases; Skin Neoplasms | 2022 |
Sargassum horneri extract containing polyphenol alleviates DNCB-induced atopic dermatitis in NC/Nga mice through restoring skin barrier function.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction. Sargassum horneri (S. horneri) is a brown alga that has been widely used in traditional medicine of eastern Asian countries. Recent studies proved that a brown alga S. horneri has anti-inflammatory activity. In this study, we investigated the effect of S. horneri ethanol extract (SHE) against AD in 2,4-dinitrobenzene (DNCB) induced AD in NC/Nga mice. We observed that SHE treatment decreased the epidermal thickness and epidermal hyperplasia that had been worsened through DNCB application. Moreover, SHE significantly inhibited the proliferation of mast cells and decreased the expression of IL-13 on CD4⁺ cells prompted by elevated thymic stromal lymphopoietin (TSLP) expression in DNCB-induced AD in mice. We also demonstrated that SHE directly inhibited the expression of keratinocyte-produced TSLP known to exacerbate skin barrier impairment. Especially, the decrease of filaggrin, an integral component of proper skin barrier function through a function in aggregating keratin filaments, observed in DNCB-induced AD mice was significantly improved when treated with SHE. More importantly, we proved that SHE was able to decrease the serum levels of IgG₁ and IgG₂ₐ, two crucial factors of AD, indicating the protective effect of SHE. Taken together, our findings suggest that SHE may protect NC/Nga mice against DNCB-induced AD via promoting skin barrier function. Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrobenzenes; Immunoglobulin G; Interleukin-13; Keratins; Mice; Plant Extracts; Polyphenols; Sargassum; Skin; Skin Diseases | 2022 |
Autoinflammatory Keratinization Diseases (AiKDs): Expansion of Disorders to Be Included.
Topics: Animals; Autoimmunity; Humans; Immunity, Innate; Inflammation; Keratins; Phenotype; Signal Transduction; Skin; Skin Diseases | 2020 |
Editorial: Autoinflammatory Keratinization Disease (AiKD).
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Inflammation; Inflammation Mediators; Keratins; Signal Transduction; Skin; Skin Diseases | 2020 |
Trichodysplasia spinulosa mimicking lichen nitidus in a renal transplant patient.
Trichodysplasia spinulosa (TS) is a rare cutaneous condition associated with the TSPyV and characterized by skin-colored, folliculocentric papules with keratin spicule formation. TS is seen almost exclusively in immunosuppressed individuals, often presenting in patients with a history of solid organ transplantation or chemotherapy for a lymphoreticular malignancy. We report a case of widespread TS in a 9-year-old girl with a history of renal transplantation complicated by BK viremia, which is also caused by a polyomavirus, BKPyV. The clinical presentation of TS in this case morphologically resembled the more common, harmless skin condition known as "lichen nitidus," and was more extensive than expected for TS, creating a diagnostic challenge. This case illustrates an important presentation of severe TS of which transplant teams, oncologists, primary care providers, and dermatologists should be aware. Topics: BK Virus; Child; Congenital Abnormalities; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Keratins; Kidney; Kidney Diseases; Kidney Transplantation; Lichen Nitidus; Polyomavirus; Polyomavirus Infections; Postoperative Complications; Skin; Skin Diseases; Tumor Virus Infections | 2019 |
Fabrication and characterization of chicken feather keratin/polysaccharides blended polymer coated nonwoven dressing materials for wound healing applications.
In this research work, three kinds of nonwoven wound dressings were developed from chicken feather keratin (CFK-NW), keratin‑sodium alginate (CFK-SA-NW) and keratin-chitosan (CFK-CS-NW) and characterized using FTIR and SEM. The physical characteristics such as air permeability, thickness and areal density test results revealed the suitability of fabricated materials for wound dressing applications. CFK-SA-NW and CFK-CS-NW indicated a positive antibacterial effect against Gram's positive Staphylococcus aureus and Gram's negative Klebsiella pneumoniae and Escherichia coli bacteria with the zone of inhibition enhanced over >2.0 cm. Moreover, the biomedical potentials of dressing materials has been investigated by cell viability and cytotoxicity tests. Further, the wound healing ability was demonstrated using in vivo model (Albino Wistar rat). The fabricated materials exhibited good support for cell viability and a strong cytocompatibility. Furthermore, the hundred percent wound healing ability of CFK-CS-NW, CFK-SA-NW, CFK-NW and untreated control rats was observed at 15, 17, 21 and 23 days, respectively, Moreover, the wound healing potential of CFK-CS-NW and CFK-SA-NW was found to be better than that of CFK-NW and control group of rats. The outcome of the present study discloses the prospective applications of the developed materials as wound dressing biomaterial. Topics: Alginates; Animals; Bandages; Biocompatible Materials; Cell Line; Cell Survival; Chickens; Chitosan; Feathers; Glucuronic Acid; Gram-Negative Bacteria; Gram-Positive Bacteria; Hexuronic Acids; Keratins; Male; Mice; Polymers; Polysaccharides; Rats; Rats, Wistar; Skin Diseases; Wound Healing | 2018 |
Indurated plaque on the eyebrow.
Topics: Adnexa Uteri; Adnexal Diseases; Carcinoma; Cysts; Diagnosis, Differential; Eyebrows; Female; Humans; Keratins; Middle Aged; Skin; Skin Diseases | 2017 |
Topical application of probiotics in skin: adhesion, antimicrobial and antibiofilm in vitro assays.
When skin dysbiosis occurs as a result of skin disorders, probiotics can act as modulators, restoring microbial balance. Several properties of selected probiotics were evaluated so that their topical application could be considered.. Adhesion, antimicrobial, quorum sensing and antibiofilm assays were carried out with several probiotic strains and tested against selected skin pathogens. All tested strains displayed significant adhesion to keratin. All lactobacilli with the exception of Lactobacillus delbrueckii, showed antimicrobial activity against skin pathogens, mainly due to organic acid production. Most of them also prevented biofilm formation, but only Propioniferax innocua was able to break down mature biofilms.. This study demonstrates that although all tested probiotics adhered to human keratin, they showed limited ability to prevent adhesion of some potential skin pathogens. Most of the tested probiotics successfully prevented biofilm formation, suggesting that they may be successfully used in the future as a complement to conventional therapies in the treatment of a range of skin disorders.. The topically used probiotics may be a natural, targeted treatment approach to several skin disorders and a complement to conventional therapies which present many undesirable side effects. Topics: Anti-Infective Agents; Bacterial Adhesion; Biofilms; Dysbiosis; Humans; Keratins; Lactobacillus; Probiotics; Quorum Sensing; Skin; Skin Diseases | 2017 |
Trichodysplasia Spinulosa in a 7-Year-Old Boy Managed Using Physical Extraction of Keratin Spicules.
Trichodysplasia spinulosa (TS) is an uncommon skin disease characterized by a folliculocentric papular eruption and keratin spine formation, classically appearing on the central face and ears. It occurs in immunosuppressed patients and is linked to a viral etiology. Diagnostic tests including polymerase chain reaction (PCR) are available for detection of the TS-associated polyomavirus. Effective treatment options include topical cidofovir and oral valganciclovir. We present a case diagnosed using PCR with skin scrapings and treated using physical extraction of the keratin spicules. Significant improvement was noted, suggesting a safe, cost-effective treatment alternative. Topics: Child; Humans; Keratins; Male; Polyomavirus Infections; Skin Diseases | 2017 |
Clinicopathological features and expression of four keratins (K10, K14, K17 and K19) in six cases of eruptive vellus hair cysts.
Six cases of eruptive vellus hair cysts (EVHC) were evaluated for histopathology and the immunohistochemical profile of Ki-67 and four keratins (K10, K14, K17 and K19). The pathological hallmark of EVHC was the existence of vellus hair shafts within the cystic cavity, but atypical pathological changes included two or three cysts and a foreign-body granuloma in three cases. Our results demonstrate that atypical pathological changes are not uncommon in EVHC, and indicate that based on keratin expression, it is likely that EVHC is derived from the infrainfundibulum and sebaceous duct. Topics: Adolescent; Adult; Epidermal Cyst; Female; Hair Diseases; Humans; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases; Young Adult | 2014 |
Keratin 76 is required for tight junction function and maintenance of the skin barrier.
Keratins are cytoskeletal intermediate filament proteins that are increasingly being recognised for their diverse cellular functions. Here we report the consequences of germ line inactivation of Keratin 76 (Krt76) in mice. Homozygous disruption of this epidermally expressed gene causes neonatal skin flaking, hyperpigmentation, inflammation, impaired wound healing, and death prior to 12 weeks of age. We show that this phenotype is associated with functionally defective tight junctions that are characterised by mislocalization of the integral protein CLDN1. We further demonstrate that KRT76 interacts with CLDN1 and propose that this interaction is necessary to correctly position CLDN1 in tight junctions. The mislocalization of CLDN1 has been associated in various dermopathies, including the inflammatory disease, psoriasis. These observations establish a previously unknown connection between the intermediate filament cytoskeleton network and tight junctions and showcase Krt76 null mice as a possible model to study aberrant tight junction driven skin diseases. Topics: Animals; Claudin-1; Cytoskeleton; Epidermis; Humans; Intermediate Filaments; Keratinocytes; Keratins; Mice; Psoriasis; Skin Diseases; Tight Junctions | 2014 |
Knock-down of filaggrin does not affect lipid organization and composition in stratum corneum of reconstructed human skin equivalents.
Human skin mainly functions as an effective barrier against unwanted environmental influences. The barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which is composed of corneocytes embedded in an extracellular lipid matrix. The importance of a proper barrier function is shown in various skin disorders such as atopic dermatitis (AD), a complex human skin disorder strongly associated with filaggrin (FLG) null mutations, but their role in barrier function is yet unclear. To study the role of FLG in SC barrier properties in terms of SC lipid organization and lipid composition, we generated an N/TERT-based 3D-skin equivalent (NSE) after knock-down of FLG with shRNA. In these NSEs, we examined epidermal morphogenesis by evaluating the expression of differentiation markers keratin 10, FLG, loricrin and the proliferation marker ki67. Furthermore, the SC was extensively analysed for lipid organization, lipid composition and SC permeability. Our results demonstrate that FLG knock-down (FLG-KD) did not affect epidermal morphogenesis, SC lipid organization, lipid composition and SC permeability for a lipophilic compound in NSEs. Therefore, our findings indicate that FLG-KD alone does not necessarily affect the functionality of a proper barrier function. Topics: Cell Proliferation; Dermatitis, Atopic; Epidermis; Fibroblasts; Filaggrin Proteins; Gene Knockdown Techniques; Heterozygote; Humans; Inflammation; Intermediate Filament Proteins; Keratin-10; Keratins; Ki-67 Antigen; Lipids; Membrane Proteins; Permeability; Phenotype; Skin; Skin Diseases | 2013 |
Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs.
In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children. Topics: Animals; Desmosomes; Disease Models, Animal; DNA Primers; Dogs; Ectodermal Dysplasia; Gene Expression Regulation; Keratins; Microscopy, Electron; Microscopy, Electron, Transmission; Mutation; Phenotype; Plakophilins; Sequence Analysis, DNA; Skin; Skin Diseases | 2012 |
Amyloidosis cutis dyschromica.
Amyloidosis cutis dyschromica is a rarely documented variant of cutaneous amyloidosis. To date, only 26 cases have been reported.. The purpose of this study was to improve the clinical and histopathological data for this variant of amyloidosis and to highlight the immunohistochemical features of the disease. The published cases were also reviewed.. We performed a retrospective review of patients with amyloidosis cutis dyschromica in a single centre. The clinical, histopathological and immunohistochemical features were documented and analysed.. We described 10 cases of amyloidosis cutis dyschromica. Six of them were female. Five patients were from the same family, and the other 5 were sporadic. The distinguishing features of the clinical presentation included generalised mottled hyper- and hypopigmented macules, which were asymptomatic or mild pruritic. The typical onset of the lesions occurred in childhood (n = 7) and occasionally after puberty (n = 3). No evidence of systemic amyloidosis deposition was observed in these cases of amyloidosis cutis dyschromica. Amyloid deposits were observed in the papillary dermis and were positive for the Congo red stain. An immunohistochemical study showed that the amyloid expresses cytokeratins CK34βE12 and CK5/6.. We described the largest series of amyloidosis cutis dyschromica to date and reviewed the published patients. This rare disease is featured by generalised mottled hyper- and hypopigmented lesions, and it is a rare variant of primary cutaneous amyloidosis without evidence of systemic amyloid deposition. Positive staining for the cytokeratins CK34βE12 and CK5/6 in amyloidosis cutis dyschromica suggests that the amyloid is derived from keratinocytes. Topics: Adolescent; Adult; Aged; Amyloidosis; Congo Red; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Keratinocytes; Keratins; Male; Middle Aged; Pigmentation Disorders; Retrospective Studies; Skin Diseases; Young Adult | 2012 |
Comparative immunohistochemical analyses on the modes of cell death/keratinization in epidermal cyst, trichilemmal cyst, and pilomatricoma.
Keratinization is a kind of cell death called terminal differentiation and includes various patterns such as epidermal keratinization (EK), trichilemmal keratinization (TK), and shadow cell differentiation (SCD), whereas these have not been comparatively investigated from a standpoint of cell death. In the present study, surgically extirpated specimens of epidermal cyst, trichilemmal cyst, and pilomatricoma (10 cases in each) were subjected to immunohistochemistry for single-strand DNA (ssDNA), gamma-H2AX, cleaved caspase-3, cleaved lamin A, caspase-14, and CD138 to compare the modes of cell death and keratinization pattern. Transitional cells in pilomatricoma were immunoreactive, although not in whole part, for ssDNA and gamma-H2AX, and negative for cleaved caspase-3 and cleaved lamin A. Epidermal and trichilemmal cyst were negative for these 4 markers, except for ssDNA or cleaved lamin A in a small number of parakeratotic cells in a few cases. The keratinizing component showed caspase-14(+)/CD138(-) in epidermal cyst, caspase-14(-)/CD138(+) in trichilemmal cyst, and caspase-14(-)/CD138(-) in pilomatricoma. These results indicate that EK, TK, and SCD have a common property of apoptosis-like programmed cell death without caspase-3 activation or nuclear fragmentation. Meanwhile, they show different characteristics one another as follows: (A), DNA double-strand breaks occur in the transitional cells of SCD but not in EK/TK; and (B), EK, TK, and SCD can be distinguished by expression pattern of caspase-14 and CD138 in the keratinizing component. Topics: Biomarkers, Tumor; Caspase 14; Cell Death; Cell Differentiation; DNA Breaks, Double-Stranded; Epidermal Cyst; Hair Diseases; Humans; Immunohistochemistry; Keratins; Pilomatrixoma; Skin Diseases; Skin Neoplasms; Syndecan-1 | 2011 |
Biopsy of a 5 mm cystic lesion on the right heel of a 48-year-old woman.
An excisional biopsy of an asymptomatic cystic lesion that had been present for several years on the right heel of a 48-year-old woman revealed a subcutaneous cyst lined by ciliated columnar epithelium. On immunostaining, the epithelial cells were positive for Pan-cytokeratin (CK AE 1/3), estrogen receptor (ER) and progesterone receptor (PR), but negative for carcinoembryonic antigen (CEA), suggesting Mullerian type of epithelium. Cutaneous ciliated cyst of Mullerian type occurs almost exclusively on the lower extremity of premenopausal women. The lesion is benign and excision is curative. Topics: Biopsy; Cysts; Female; Heel; Humans; Keratins; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Skin Diseases; Treatment Outcome | 2011 |
A revaluation of folliculosebaceous cystic hamartoma: the histopathological and immunohistochemical features.
The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the origin of the frequently associated adipocytes and other mesenchymal components, remains unclear. There are controversial problems regarding FSCH, such as the relationship between FSCH and trichofolliculoma (TF), and the exact concept of sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the histopathology and studied for immunohistochemical profile of various cytokeratins, hair follicular stem cell markers, and others. The nestin expression was partly upregulated in the sebaceous duct structures and the proliferating spindle cells in the surrounding connective tissue in some lesions. S-100 protein staining clarified the presence of lipogenesis in these nestin-expressed lesions, and the nestin-positive spindle cells were also seen around the immature adipocytes. Some FSCHs showed the focal follicular differentiation, where no signs of catagen or telogen stage were seen. One peculiar case showed both FSCH and TF features equally. The possibility that the adipocytes and other mesenchymal components in FSCHs originated from the nestin-positive multipotent stem cells was suggested. It is not convincing that FSCH and TF represent a chronological change in the spectrum of the same condition. Each FSCH and TF is therefore considered to be a distinctive entity. They may develop under a similar pathogenesis differing from each other in the direction of fundamental differentiation. In contrast to the TF lesions, the unusual upregulation of nestin expression is occasionally seen in FSCH lesions, including their stromas, which may thus result in the production of various kinds of mesenchymal components in FSCHs. Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Female; Hair Follicle; Hamartoma; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Nerve Tissue Proteins; Nestin; Retrospective Studies; S100 Proteins; Skin Diseases | 2010 |
AGE-modified collagens I and III induce keratinocyte terminal differentiation through AGE receptor CD36: epidermal-dermal interaction in acquired perforating dermatosis.
To clarify the molecular mechanism underlying the transepidermal extrusion of dermal collagen in acquired perforating dermatosis (APD) associated with diabetes mellitus and renal failure, we studied the interaction between advanced glycation end product (AGE)-modified extracellular matrix proteins and keratinocytes (KCs) in a cell culture system. The expression of involucrin (INV) and keratin 10 was significantly enhanced in normal human KCs grown on AGE-modified collagen I or III compared with cells grown on unmodified collagen I or III. Glycated collagens I and III preferentially induced the expression of AGE receptor CD36, but not of other AGE receptors. KCs induced to terminal differentiation demonstrated markedly elevated CD36 expression. Glycated collagen I- and III-induced INV expression was partially blocked by the anti-CD36 antibody (Ab). These substrates also induced epidermal matrix metalloproteinase 9 (MMP-9) expression. Lesional skin from APD patients reacted moderately or strongly with the anti-CD36 Ab as well as the anti-MMP-9 Ab in the epidermal cells surrounding the collagenous materials being eliminated. These results suggest that exposing KCs to AGE-modified interstitial collagen (types I and III) by scratching induces terminal differentiation of KCs via the AGE receptor (CD36), leading to the upward movement of KCs together with glycated collagen. Topics: Adult; Aged; CD36 Antigens; Cell Differentiation; Collagen Type I; Collagen Type III; Dermis; Epidermis; Female; Glycation End Products, Advanced; Humans; Keratinocytes; Keratins; Male; Matrix Metalloproteinase 9; Middle Aged; Models, Biological; Skin Diseases | 2010 |
Rethinking the prosaicism of mosaicism; is it in us?
Exponential advances in the quantitation of DNA variation and epigenetic states seem poised to convert much of biological research into a statistical exercise. But these developments also invite us to reimagine well-worn biological concepts on a grander scale. Somatic mosaicism refers to postzygotic mutations persisting in the individual, occasionally conspicuous to dermatologists as Blaschkoid, checkerboard, phylloid and patchy morphologies. A thoughtful examination of cutaneous mosaicism suggests, however, that virtually all of us may be somatic mosaics. Such genetic variability within individuals might explain localized presentations of disease and implies that some tissues literally evolve throughout life. We discuss here (i) the likely ubiquity of somatic mosaicism, (ii) the broad range of possible biological consequences and (iii) how experimentalists and clinicians may begin establishing genotype-to-phenotype correlates. Topics: Cell Lineage; Clone Cells; Disease; Genetic Association Studies; Humans; Keratins; Mosaicism; Mutation; Neoplasms; Nevus; Sequence Analysis, DNA; Skin; Skin Diseases | 2010 |
Folliculosebaceous cystic hamartoma differentiates toward the infundibulum, sebaceous duct and sebaceous cells: immunohistochemical study of keratins and filaggrin.
Topics: Aged; Diagnosis, Differential; Epidermal Cyst; Facial Neoplasms; Filaggrin Proteins; Hamartoma; Humans; Intermediate Filament Proteins; Keratins; Male; Sebaceous Glands; Skin Diseases | 2009 |
Comparative analysis of the expression of cytokeratins (1, 10, 14, 16, 4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions.
Epidermodysplasia verruciformis (EV) is a rare genodermatosis with susceptibility to human papillomavirus (HPV) infection, and high risk of skin cancer considered a model of viral oncogenesis.. Fifteen cases of EV plane wart (PW)-type lesions (EV) and 14 cases of PW in healthy individuals were subjected to immunohistochemical technique for cytokeratins (K) 1, 10, 14, 16, 4, involucrin, filaggrin and e-cadherin.. K1/10 showed retarded or negative expression in EV, being substituted by K14. Expression of K14 occurred in the basal and suprabasal layers in both groups, but in EV, its expression was observed up to the more superficial layers. Both groups showed positivity for K16 and K4, involucrin expression in lower levels of the spinous layer and unaltered filaggrin expression. E-cadherin expression was diminished at the koilocytotic foci of both lesions, more superficially in EV.. Infection by HPV may alter the differentiation status of the epidermis, leading to a major expression of K14, delayed or absent expression of K1/10 and earlier involucrin expression, especially in EV. It also stimulates the expression of K16 and K4. Filaggrin expression is not altered, and e-cadherin is diminished in superficial koilocytotic cells' foci in EV. Topics: Adult; Cadherins; Epidermodysplasia Verruciformis; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Papillomavirus Infections; Protein Precursors; Skin Diseases | 2009 |
Multiple epidermal cysts occurring in a tattoo.
In decorative tattooing, pigment is introduced into the skin with needles or a tattoo gun to create a picture, motif or symbol. Various skin reactions have been reported in association with tattoos. These include acute inflammatory reactions, eczematous hypersensitivity reactions, pseudolymphomatous reactions and skin infections. We present a 24-year-old Malay man who developed multiple epidermal cysts a month after tattooing. To the best of our knowledge, this is the first case in the literature of epidermal cysts occurring after skin tattooing. Topics: Adult; Biopsy; Cysts; Dermis; Epidermis; Humans; Keratins; Macrophages; Male; Skin Diseases; Tattooing | 2009 |
Keratoacanthoma occurring within the red dye of a tattoo.
Keratoacanthoma (KA) is a common keratinizing squamous cell neoplasm of unknown origin characterized by rapid growth and spontaneous involution. Trauma-induced forms have been observed with various types of skin injury. To our knowledge, reports of KA arising at tattoo sites are scarce in the literature. A 41-year-old woman with no medical history presented for a rapidly growing nodule confined to the red part of a tattoo located on the scapula. Histology showed a keratin-filled cuplike crater with an epithelial proliferation (hyperkeratosis, parakeratosis, no keratinocyte atypia). An inflammatory infiltrate in the dermis composed of lymphocytes and histiocytes intermixed with red ink-related exogenous pigments was noted. Lack of papillomatosis and viral inclusions ruled out the diagnosis of viral wart, absence of granulomatous reaction ruled out deep fungal or mycobacterial infection and lack of cytological atypia and frank architectural abnormalities did not favour a squamous cell carcinoma. KA should be included in the list of cutaneous complications related to tattooing. Diagnosis can be challenging as differential diagnoses include pseudoepitheliomatous hyperplasia and squamous cell carcinoma. Removal of the entire area, thorough histological examination and careful follow up are mandatory. Topics: Adult; Carcinoma, Squamous Cell; Coloring Agents; Diagnosis, Differential; Female; Histiocytes; Humans; Keratinocytes; Keratins; Keratoacanthoma; Lymphocytes; Skin Diseases; Skin Neoplasms; Tattooing | 2008 |
KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare autosomal dominant disorder characterized by loss of dermatoglyphics, reticulate hyperpigmentation of the skin, palmoplantar keratoderma, abnormal sweating, and other developmental anomalies of the teeth, hair, and skin. We recently demonstrated that NFJS is caused by heterozygous nonsense or frameshift mutations in the E1/V1-encoding region of KRT14, but the mechanisms for their deleterious effects in NFJS remain elusive. In this study, we further expand the spectrum of NFJS-causing mutations and demonstrate that these mutations result in haploinsufficiency for keratin 14 (K14). As increased apoptotic activity was observed in the epidermal basal cell layer in NFJS patients and as previous data suggested that type I keratins may confer resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in epithelial tissues, we assessed the effect of down-regulation of KRT14 expression on apoptotic activity in keratinocytes. Using a HaCaT cell-based assay, we found that decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis. This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling. Collectively, our results indicate that NFJS results from haploinsufficiency for K14 and suggest that increased susceptibility of keratinocytes to pro-apoptotic signals may be involved in the pathogenesis of this ectodermal dysplasia syndrome. Topics: Apoptosis; Cell Line; Child; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Keratin-14; Keratinocytes; Keratins; Mutation; Skin Abnormalities; Skin Diseases; Syndrome; Tumor Necrosis Factor-alpha | 2008 |
Milia en plaque on the forehead.
Topics: Adult; Epidermal Cyst; Female; Forehead; Humans; Keratins; Skin Diseases | 2008 |
Scrotal calcinosis results from calcification of cysts derived from hair follicles: a series of 20 cases evaluating the spectrum of changes resulting in scrotal calcinosis.
Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The etiology of this entity is speculative largely as a result of the paucity of larger series.This study of 20 patients with scrotal calcinosis was undertaken to critically analyze the histology with a view to assess the probable etiology of this lesion. Two thirds of the patients were young adults. Of these, 11 patients (55%) were asymptomatic and 9 complained of symptoms related to the breakdown of these lesions (eg, discharge, itching, or heaviness in the scrotum). All cases showed classical histologic features of scrotal calcinosis with a variable amount of calcification in the dermis. In 14 cases the etiology of this calcification could be traced to originate from dilated epidermal cysts. The spectrum of changes probably started with the cystic dilation of the hair follicle, then calcification around and within this cyst. Finally the epithelial elements disappeared, leaving behind residual areas of calcification. The remaining 6 cases did not have epithelial cysts in the vicinity. Based on these observations we conclude that scrotal calcinosis results from calcification of hair follicular or epidermal cysts, but as most of the cases report, this epithelium disappears and may not be seen. Topics: Adult; Calcinosis; Disease Progression; Epidermal Cyst; Genital Diseases, Male; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Scrotum; Skin Diseases | 2007 |
Proliferating trichilemmal cyst of the eyelid.
To report a case of proliferating trichilemmal cyst in a 55-year-old woman.. Observational case report.. A 55-year-old woman sought treatment for a mass in the right upper eyelid. The lesion was excised twice previously, and recurred. The mass was reexcised and examined histopathologically.. Light microscopy showed a cystic lesion lined by stratified squamous epithelium with a compact layer of eosinophilic keratin without granular cell layer. There was no atypia, mitosis, or stromal invasion.. Although proliferating trichilemmal cyst shows benign histopathologic features, clinical manifestations may mimic those of more aggressive tumors with local recurrences or distant metastasis. Wide excision of the lesion and close long-term follow-up is recommended. Topics: Cell Proliferation; Eosinophils; Epidermal Cyst; Eyelid Diseases; Female; Humans; Keratins; Middle Aged; Mitosis; Skin Diseases | 2007 |
DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis.
Desmosterolosis is an autosomal recessive disorder due to mutations in the 3beta-hydroxysterol-Delta24 reductase (DHCR24) gene that encodes an enzyme catalyzing the conversion of desmosterol to cholesterol. To date, only two patients have been reported with severe developmental defects including craniofacial abnormalities and limb malformations. We employed mice with targeted disruption of DHCR24 to understand the pathophysiology of desmosterolosis. All DHCR24-/- mice died within a few hours after birth. Their skin was wrinkleless and less pliant, leading to restricted movement and inability to suck (empty stomach). DHCR24 gene was expressed abundantly in the epidermis of control but not of DHCR24-/- mice. Accordingly, cholesterol was not detected whereas desmosterol was abundant in the epidermis of DHCR24-/- mice. Skin histology revealed thickened epidermis with few and smaller keratohyaline granules. Aberrant expression of keratins such as keratins 6 and 14 suggested hyperproliferative hyperkeratosis with undifferentiated keratinocytes throughout the epidermis. Altered expression of filaggrin, loricrin, and involcrin were also observed in the epidermis of DHCR24-/-. These findings suggested impaired skin barrier function. Indeed, increased trans-epidermal water loss and permeability of Lucifer yellow were observed in DHCR24-/- mice. DHCR24 thus plays crucial role for skin development and its proper function. Topics: Animals; Apoptosis; Caveolin 1; Cell Differentiation; Cell Proliferation; Ceramides; Cholesterol; Desmosterol; Fatty Acids, Nonesterified; Immunohistochemistry; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Nerve Tissue Proteins; Oxidoreductases Acting on CH-CH Group Donors; Permeability; Skin; Skin Diseases | 2006 |
In vivo drug screening in human skin using femtosecond laser multiphoton tomography.
The novel femtosecond laser multiphoton imaging system DermaInspect forin vivotomography of human skin was used to study the diffusion and intradermal accumulation of topically applied cosmetic and pharmaceutical components. Near-infrared 80 MHz picojoule femtosecond laser pulses were employed to excite endogenous fluorophores and fluorescent components of a variety of ointments via a two-photon excitation process. In addition, collagen was imaged by second harmonic generation. A high submicron spatial resolution and 50 ps temporal resolution was achieved using galvoscan mirrors and piezodriven focusing optics together with a time-correlated single-photon counting module with a fast microchannel plate detector. Individual intratissue cells, intracellular mitochondria, melanosomes, and the morphology of the nuclei as well as extracellular matrix elements were clearly visualized due to NAD(P)H, melanin, elastin, and collagen imaging and the calculation of fluorescence lifetime images. Nanoparticles and intratissue drugs were detected by two-photon-excited fluorescence. In addition, hydration effects and UV effects were studied by monitoring modifications of cellular morphology and autofluorescence. The system was used to observe the diffusion through the stratum corneum and the accumulation and release of functionalized nanoparticles along hair shafts and epidermal ridges. The novel noninvasive 4-D multiphoton tomography tool provides high-resolution optical biopsies with subcellular resolution, and offers for the first time the possibility to study in situ the diffusion through the skin barrier, long-term pharmacokinetics, and cellular response to cosmetic and pharmaceutical products. Topics: Adult; Aged; Collagen; Cosmetics; Dermatologic Agents; Dermis; Diffusion; Drug Evaluation, Preclinical; Endoscopy; Fluorescence; Humans; Infrared Rays; Keratins; Lasers; Middle Aged; Nanostructures; Ointments; Photons; Skin; Skin Diseases; Ultraviolet Rays; Water | 2006 |
Overcoming functional redundancy to elicit pachyonychia congenita-like nail lesions in transgenic mice.
Mutations affecting the coding sequence of intermediate filament (IF) proteins account for >30 disorders, including numerous skin bullous diseases, myopathies, neuropathies, and even progeria. The manipulation of IF genes in mice has been widely successful for modeling key features of such clinically distinct disorders. A notable exception is pachyonychia congenita (PC), a disorder in which the nail and other epithelial appendages are profoundly aberrant. Most cases of PC are due to mutations in one of the following keratin-encoding genes: K6, K16, and K17. Yet null alleles obliterating the function of both K6 genes (K6alpha and K6beta) or the K17 gene, as well as the targeted expression of a dominant-negative K6alpha mutant, elicit only a subset of PC-specific epithelial lesions (excluding that of the nail in mice). We show that newborn mice null for K6alpha, K6beta, and K17 exhibit severe lysis restricted to the nail bed epithelium, where all three genes are robustly expressed, providing strong evidence that this region of the nail unit is initially targeted in PC. Our findings point to significant redundancy among the multiple keratins expressed in hair and nail, which can be related to the common ancestry, clustered organization, and sequence relatedness of specific keratin genes. Topics: Alleles; Animals; Cells, Cultured; Disease Models, Animal; Epithelium; Fluorescent Antibody Technique, Indirect; Genes, Dominant; Genotype; Homozygote; Keratinocytes; Keratins; Mice; Mice, Transgenic; Models, Genetic; Mutagenesis; Mutation; Nail Diseases; Phenotype; Skin; Skin Diseases; Tongue; Transgenes | 2005 |
Skin carcinoma arising from donor cells in a kidney transplant recipient.
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 | 2005 |
Cutaneous keratocyst arising independently of the nevoid basal cell carcinoma syndrome.
Topics: Basal Cell Nevus Syndrome; Diagnosis, Differential; Epidermal Cyst; Humans; Keratins; Leg; Male; Middle Aged; Skin Diseases | 2005 |
Clinical and immunohistochemical study of the effect of a cosmetic product in patients with asteatotic eczema.
Cutaneous xerosis is a common clinical condition associated with an altered barrier function of the stratum corneum. Xerotic skin appears dry, rough and slightly scaling. Patients complain of pruritus and stinging. Our aim was to investigate the clinical effects of a cosmetic ointment (Scherilan) in patients with circumscribed senile xerosis (also called asteatotic eczema). Moreover, variations in expression of epidermal proteins such as keratin (K)-5 and involucrin, detected by immunohistochemistry, were also evaluated before and after topical treatment. We enrolled 30 patients (11 males, 19 females) with asteatotic eczema. We examined dryness, roughness and desquamation and symptoms such as itching and dryness. A score of 0 to 3 was assigned to each of these parameters. A biopsy was performed in seven patients before and after a 21-day topical treatment. All skin specimens were then immunostained with antibodies to K5 and involucrin. At day 7 or 21 of treatment all signs of xerosis and pruritus were significantly reduced; furthermore, the reduction increased with the duration of therapy. Before treatment K5 was strongly expressed in stratum basale (SB) and stratum spinosum (SS), while involucrin was strongly expressed in stratum granulosum (SG) and the upper portion of SS. In contrast, after treatment immunostaining for K5 was restricted to SB and the lower part of SS, while involucrin showed intense staining in SG. We highlight the importance of treating cutaneous xerosis with an ointment such as this one, which probably induces an increase of lipid content of the SC intercellular matrix. Topics: Aged; Biopsy; Cell Proliferation; Cosmetics; Eczema; Epidermis; Female; Glycolates; Humans; Immunohistochemistry; Keratin-5; Keratins; Lipid Metabolism; Lipids; Male; Middle Aged; Ointments; Protein Precursors; Pruritus; Skin Diseases; Time Factors; Treatment Outcome; Vitamin E | 2005 |
Xerosis in primary Sjögren syndrome: immunohistochemical and functional investigations.
Topics: Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Middle Aged; Protein Precursors; Sjogren's Syndrome; Skin Diseases | 2005 |
Genetic diseases affecting the epidermis.
Topics: Animals; Epidermis; Genetic Diseases, Inborn; Humans; Keratins; Skin Diseases | 2005 |
A heritable keratinization defect of the superficial epidermis in norfolk terriers.
Although well-characterized in man, abnormal cornification secondary to heritable superficial keratin defects is rarely reported in animals. This report describes a mild cornification defect in seven related Norfolk terrier dogs. Lesions were present at birth and pedigree analysis suggested an autosomal recessive mode of inheritance. The affected dogs had hyperpigmented skin with scaling following mild trauma. The lesions were generalized but most prominent in the glabrous skin of the axillary and inguinal regions-areas where the epidermis is not protected by hair and is subject to frequent trauma. The most striking histological change was vacuolation in the upper epidermis, which often resulted in epidermolysis and blister formation. All of the affected dogs showed similar gross and histological changes. Ultrastructural changes included abnormal keratin filament clumping, prominent clear spaces in the cytoplasm of suprabasal keratinocytes, and abnormal keratohyaline granules. Immunohistochemical labelling for keratin 10 demonstrated a lack of expression in the superficial epidermis of affected dogs. All of the morphological changes noted in the Norfolk terriers were consistent with a mild form of a heritable defect in superficial keratin synthesis. Topics: Animals; Dogs; Epidermis; Female; Immunohistochemistry; Keratin-10; Keratins; Male; Microscopy, Electron; Pedigree; Skin Diseases | 2004 |
Cytokeratin expression in lichen amyloidosus and macular amyloidosis.
To understand the role of epidermal cells in the pathogenesis of lichen amyloidosus (LA) and macular amyloidosis (MA).. We carried out immunohistochemical investigations on cytokeratins (CKs) in amyloid deposits in formalin-fixed and paraffin-embedded tissue specimens from eight persons with LA and 12 with MA. The primary antibodies of CK1-8 (AE3), CK10 (DEK-10), CK14 (LL002), CK17 (E3), CK18 (DC10), CK19 (KS19.1), CK5/6/18 (LP34) and CK8/18 (5D3) were used in the study.. In amyloid deposits, immunoreactivity with only two monoclonal antibodies (CK1-8 and CK5/6/18) was observed in 14 cases (eight LA and six MA), confirming the hypothesis that epidermal cells participate in amyloid formation of LA and MA.. All of the CKs detected in amyloid deposits were basic type (type II). It seems plausible either that acidic CKs might be degraded faster than basic types in amyloidogenesis or that paraffin-embedded tissue specimens are less sensitive than frozen tissue sections. The results of our study suggest that when paraffin-embedded specimens are investigated by immunohistochemical methods, CK5 antibody is useful in the diagnosis of LA and MA. Topics: Adult; Aged; Amyloid; Amyloidosis; Biopsy, Needle; Cohort Studies; Culture Techniques; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Serum Amyloid A Protein; Severity of Illness Index; Skin Diseases | 2004 |
A study of cytokeratin profiles in localized cutaneous amyloids.
The major component of localized cutaneous amyloids may be derived from cytokeratin (CK). However, the CK profiles of primary cutaneous amyloidosis (PCA) and secondary cutaneous amyloidosis (SCA) remain obscure. Paraffin-embedded sections of skin tissue from 64 patients with PCA, 111 with SCA and 3 with systemic amyloidosis were analyzed immunohistochemically using 12 different polyclonal or monoclonal anti-CK antibodies (34betaE12, MNF116, LP34, AE1/AE3, anti-CK1, CK5, CK6, CK7, CK10, CK14, CK16 and CK17). In addition, frozen skin tissues from 12 patients with PCA were analyzed for comparison with the paraffin-embedded tissue. In all 64 PCA paraffin sections, the amyloid deposits were immunopositive for anti-CK5 antibody and 34betaE12. In all 12 frozen sections of PCA, the amyloid deposits were immunopositive for anti-CK5 antibody, 34betaE12, MNF116 and LP34, and seven (58.3%), three (25%) and one (8.3%) were immunopositive for anti-CK1, CK14, and CK10 antibodies, respectively. In all SCA sections, the amyloid deposits were immunopositive for CK5 and 34betaE12. In addition, MNF116 immunolabeled amyloids of all sections from patients with basal cell carcinoma and trichoepithelioma, and MNF116 and LP34 immunolabeled amyloids of sections from patients with porokeratosis. Our results indicate that CK5 is the major CK present in the amyloid deposits of PCA and SCA, and "amyloid-K" is mainly derived from basal keratinocytes. Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Female; Humans; Immunohistochemistry; Keratin-5; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases | 2004 |
Induction of GVHD-like skin disease by passively transferred CD8(+) T-cell receptor transgenic T cells into keratin 14-ovalbumin transgenic mice.
To understand the mechanisms involved in immunological tolerance to skin-associated antigens, we have developed transgenic (Tg) mice that express a model self-antigen, membrane-bound chicken ovalbumin (OVA), under the control of a keratin 14 (K14) promoter. K14-mOVA Tg mice express OVA mRNA in the epidermis, and appear normal. K14-mOVA Tg mice failed to mount T cell and delayed type hypersensitivity reactions to OVA, suggesting that the Tg mice were tolerant to OVA. Skin dendritic cells, including Langerhans cells, may contribute to the tolerance induction because migratory skin DC derived from K14-mOVA efficiently activated CD8(+) T cells from OVA-specific T-cell receptor (Va2/Vb5) Tg (OT-I) mice. OT-I cells expanded and accumulated in skin-draining lymph nodes after intravenous injected into K14-mOVA mice and exhibited activation markers. Graft-versus-host disease-like skin lesions appeared in K14-mOVA mice by day 7 after injection of OT-I cells. These studies demonstrate that K14-mOVA Tg mice are susceptible to an autoimmunelike skin disease induced by passively transferred naïve CD8(+) OVA T-cell receptor Tg T cells, and serve as a good model for understanding self-tolerance and for the investigation of the pathogenesis, treatment and potential prevention of cell-mediated autoimmune reactions in skin. Topics: Adoptive Transfer; Animals; Autoantigens; CD8-Positive T-Lymphocytes; Cell Movement; Gene Expression; Graft vs Host Disease; Hypersensitivity, Delayed; Keratin-14; Keratins; Mice; Mice, Transgenic; Ovalbumin; Promoter Regions, Genetic; Skin Diseases; Transgenes | 2004 |
Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state.
TCR transgenic mice that express a peptide antigen in keratinocytes develop a lethal CD8 T cell-dependent autoimmune disease. We employed an adoptive transfer system to understand this disease and show that transfer of low numbers of naive CD8 T cells into peptide transgenic mice caused chronic skin disease. The antigen-presenting cell that initiated this response was the epidermal Langerhans cell. Naive CD8 T cells proliferated extensively, migrated to tissues, developed effector function, and were capable of making a recall response. These features are very different from the abortive activation of CD8 T cells that occurred in response to the same antigen presented by APC from other tissues. Furthermore, tolerance was dominant when the antigen was presented by both Langerhans cells and other APC. These data suggest that Langerhans cells do not have tolerogenic properties in the steady state. Topics: Adoptive Transfer; Animals; Antigen Presentation; Autoantigens; Autoimmune Diseases; CD8-Positive T-Lymphocytes; Cell Movement; Disease Models, Animal; Humans; Immune Tolerance; Keratin-14; Keratins; Langerhans Cells; Lymphocyte Activation; Mice; Mice, Transgenic; Ovalbumin; Promoter Regions, Genetic; Skin Diseases | 2004 |
[A de nono I462S mutation in the KRT6A gene is associated with pachyonychia congenita type I].
To analyze the KRT6A gene mutation and mutating patterns in a sporadic Chinese patient with Pachyonychia congenita (PC)-1 so as to provide a basis for gene diagnosis and genetic counseling of this disorder.. Genomic DNA was extracted from whole blood by standard methods from a female patient with PC-1 and her parents, and from 50 normal, unrelated individuals. Primers for specific amplification of the structural KRT6A gene without co amplification of homologous genes were designed and synthesized. All exons of the gene and their flanking intronic sequences were amplified using polymerase chain reaction (PCR) and subjected to automatic DNA sequencing. The mutation was confirmed by Mbo I restriction digestion of the KRT6A-specific PCR products.. Direct sequencing of the PCR products revealed a novel heterozygous missense mutation, I462S in the KRT6A gene, which resulted from T to G transversion at nucleotide 1385 (1385T > G) in exon 7 was detected in the patient. This mutation would result in the substitution of Isoleucine by Serine at codon 462 (I462S) located in the end 2B domain of keratin 6A. No such mutation was found in the patient's parents by sequencing of PCR products and this mutation was confirmed in the patient and excluded from both parents and 50 normal, unrelated controls by restriction analysis of PCR fragments using Mbo I enzyme.. A de novo missense mutation in the KRT6A gene, I462S, has been found in a sporadic PC-1 patient. The identification of this novel mutation in the KRT6A gene provides further evidence that mutation in the KRT6A gene causes PC-1 phenotype. Topics: Base Sequence; Child, Preschool; Ectodermal Dysplasia; Exons; Female; Genome, Human; Humans; Keratins; Keratins, Hair-Specific; Molecular Sequence Data; Mutation, Missense; Nails, Malformed; Point Mutation; Skin Diseases | 2004 |
A case of epidermal cyst with pilomatrical differentiation.
A 20-year-old Japanese woman with an epidermal cyst on the back is described. Physical examination revealed a deep blue and round shaped cystic lesion measuring 10 min in diameter. A comedo-like keratotic plug also could be seen at the center. Histologically, the inner surface of the cyst was clearly separated of two types of the cells. The one was layers of epidermal keratinocytes and the other looked like a basal layer of epidermis, which immunohistochemically stained by S-100, HMB-45, cytokeratin (CK19) and Fontana-Masson staining. We diagnosed this case as epidermal cyst with pilomatrical differentiation. Topics: Adult; Cell Differentiation; Epidermal Cyst; Epidermis; Female; Hair Follicle; Humans; Immunohistochemistry; Keratinocytes; Keratins; S100 Proteins; Silver Nitrate; Skin Diseases; Staining and Labeling; Treatment Outcome | 2004 |
Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts.
Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation-specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC-2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC-2, but they usually occur at puberty.. To report a Chinese pedigree of PC-2 with unusually early onset sebaceous cysts and to explore the genetic mutation and its phenotype.. Exon 1 of keratin 17 was amplified by polymerase chain reaction (PCR) from genomic DNA from the three patients in the pedigree, the proband, his half-sister and his younger son, two unaffected members in the pedigree and 50 unrelated and unaffected people. PCR products were directly sequenced to detect the mutation.. Direct sequencing of the PCR products revealed a heterozygous 275A-->G mutation in all three affected members. This mutation predicts the substitution of asparagine by serine in codon 92 (N92S) located in the 1A domain of keratin 17.. Mutation in the 1A domain of keratin 17 underlies the affected members' phenotype, PC-2 with early onset sebaceous cysts and late-onset thickened fingernails and toenails. The onset of the cysts is very early in some people within this family and the age at onset of thickened fingernails and toenails is variable within the family, implying the existence of modifying factors. Topics: Adolescent; Age of Onset; China; Ectodermal Dysplasia; Epidermal Cyst; Female; Humans; Infant; Keratins; Male; Mutation; Nails, Malformed; Pedigree; Phenotype; Polymerase Chain Reaction; Skin Diseases | 2003 |
Blue light inhibits the growth of skin tumors in the v-Ha-ras transgenic mouse.
12-O-Tetradecanoylphorbol-13-acetate (TPA) was applied to the back skin of v-Ha-ras (TG-AC) female transgenic mice at a dose of 2.5 microg/200 microl twice a week for 9 weeks. The back skin was then exposed to blue light (wavelength, 470 nm; irradiance, 5.7 mW/cm2) for 1 h daily for 9 weeks. The mice to which TPA was applied developed skin tumors at 6 weeks after the start of application. The tumor incidence rates at 6, 7, 8 and 9 weeks after the start of application were 70%, 80%, 100% and 100%, respectively, and the numbers of tumors 1 mm or more in diameter were 1, 5, 10 and 19, respectively. In the mice that were exposed to blue light after TPA application, the tumor incidence rates were 10%, 40%, 60% and 80%, respectively, and the numbers of tumors 1 mm or more in diameter were 0, 2, 5 and 9, respectively. Histopathological examination of the skin revealed that TPA application induced diffuse hyperplasia, exaggerated keratinization, and papillomas in all 10 mice. A localized form of epidermal hyperplasia was also observed in 4 mice. The incidence rate of papillomas in the mice that were exposed to blue light after TPA application was lower and the degree of exaggerated keratinization was greater. Exaggerated keratinization was considered to represent a regressive change following exposure. These findings suggest that exposure to blue light may be a promising new approach in the treatment of skin tumors. Topics: Animals; Epidermis; Female; Genes, ras; Hyperplasia; Keratins; Mice; Mice, Transgenic; Oncogene Protein p21(ras); Papilloma; Phototherapy; Precancerous Conditions; Recombinant Fusion Proteins; Skin Diseases; Skin Neoplasms; Tetradecanoylphorbol Acetate; Weight Gain | 2003 |
IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity.
p40, the common subunit of the proinflammatory cytokines IL-12 and IL-23, is produced by resident skin cells. Whereas the in vivo effects of IL-12 are well established, little is known about the role of IL-23 in cutaneous immune responses. In this study we show that p40 transgenic (TG) mice constitutively produce IL-23 (p19/p40), but not IL-12 (p35/p40), in basal keratinocytes by cosecretion of TG p40 with endogenous p19. Repeated injections of rIL-23 in littermate (LM) mice result in an inflammatory skin disease similar to that of p40 TG mice, confirming the proinflammatory activity of IL-23. Furthermore, IL-23 secretion by p40 TG keratinocytes induces elevated numbers of Langerhans cells (LC) with a marked up-regulation of costimulatory molecules, indicating advanced maturation of keratin 14 (K14)/p40 LC when compared with LM LC. At the functional level, freshly isolated K14/p40 LC greatly exceeded LC from LM animals in their capacity to stimulate allogeneic T cell proliferation. To assess whether IL-23 regulates cutaneous immune responses in vivo, we used an allogeneic skin transplantation model. Full thickness skin grafts from K14/p40 donors (H-2(q)) transplanted across a MHC class I and class II barrier onto BALB/c (H-2(d)) recipients were rejected in a significantly accelerated fashion (mean survival time: 8.8 days) when compared with skin grafts from non-TG LM (H-2(q)) (mean survival time: 10.7 days, p < 0.01). Based on these results we propose that IL-23-induced changes of LC may be an important mechanism in directing the outcome of cutaneous immune responses. Topics: Animals; Cell Count; Cell Movement; Cells, Cultured; Female; Graft Rejection; Immunity, Cellular; Immunophenotyping; Inflammation; Injections, Subcutaneous; Interleukin-12; Interleukin-12 Subunit p40; Interleukin-23; Interleukin-23 Subunit p19; Interleukins; Interphase; Keratin-14; Keratins; Langerhans Cells; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Transgenic; Organ Culture Techniques; Protein Subunits; RNA, Messenger; Skin; Skin Diseases; Skin Transplantation | 2003 |
Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability.
Ablation of the desmosomal plaque component plakophilin 1 underlies the autosomal recessive genodermatosis, skin fragility-ectodermal dysplasia syndrome (OMIM 604536). Skin from affected patients is thickened with increased scale, and there is loss of adhesion between adjacent keratinocytes, which exhibit few small, poorly formed desmosomes. To investigate further the influence of plakophilin 1 on keratinocyte adhesion and desmosome morphology, we compared plakophilin 1-deficient keratinocytes (vector controls) with those expressing recombinant plakophilin 1 introduced by retroviral transduction. We found that plakophilin 1 increases desmosomal protein content within the cell rather than enhancing transcriptional levels of desmosomal genes. Re-expression of plakophilin 1 in null cells retards cell migration but does not alter keratinocyte cell growth. Confluent sheets of plakophilin 1-deficient keratinocytes display fewer calcium-independent desmosomes than do plakophilin 1-deficient keratinocytes expressing recombinant plakophilin 1 or keratinocytes expressing endogenous plakophilin 1. In addition electron microscopy studies show that re-expression of plakophilin 1 affects desmosome size and number. Collectively, these results demonstrate that restoration of plakophilin 1 function in our culture system influences the transition of desmosomes from a calcium-dependent to a calcium-independent state and this correlates with altered keratinocyte migration in response to wounding. Thus, plakophilin 1 has a key role in increasing desmosomal protein content, in desmosome assembly, and in regulating cell migration. Topics: 3T3 Cells; Animals; beta Catenin; Cadherins; Calcium; Cell Adhesion; Cell Adhesion Molecules; Cell Division; Cell Movement; Cells, Cultured; Cytoskeletal Proteins; Desmoglein 3; Desmoplakins; Desmosomes; Female; Humans; Keratinocytes; Keratins; Male; Mice; Microscopy, Electron; Plakophilins; Proteins; RNA, Messenger; Skin; Skin Diseases; Trans-Activators | 2003 |
Multiphoton microscopy: an optical approach to understanding and resolving sulfur mustard lesions.
Sulfur mustard (SM; 2,2(')-dichloroethyl sulfide) is a percutaneous alkylating agent first used as a chemical weapon at Ypres, Belgium, in World War I. Despite its well-documented history, the primary lesions effecting dermal-epidermal separation and latent onset of incapacitating blisters remain poorly understood. By immunofluorescent imaging of human epidermal keratinocytes (HEK) and epidermal tissues exposed to SM (400 microM for 5 min), we have amassed unequivocal evidence that SM disrupts adhesion complex molecules, which are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Images of keratin 14 (K14) in control cells showed tentlike filament networks linking the HEK's basolateral anchoring sites to the dorsal surface of its nuclei. Images from 6-h postexposure profiles revealed early disruption ( Topics: Cell Adhesion Molecules; Cells, Cultured; Chemical Warfare Agents; Culture Techniques; Epidermis; Imaging, Three-Dimensional; Integrin alpha6beta4; Keratin-14; Keratinocytes; Keratins; Laminin; Microscopy, Fluorescence; Microscopy, Fluorescence, Multiphoton; Mustard Gas; Skin; Skin Diseases; Tissue Distribution; Tomography, Optical | 2003 |
Dilated pore: a case report and an immunohistochemical study of cytokeratin expression.
We report a 71-year-old Japanese female with a dilated pore in the form of a nodule above her right eyebrow. Histologic examination revealed a flask-shaped, keratinous cystic structure that was continuous with the surface epidermis and had numerous elongated rete ridges in the lower portion. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins (CKs) and involucrin detected CK1 and CK10 in the suprabasal cells of the cystic structure. CK8 and CK19 expression was observed in the outermost layer of some elongated rete ridges; it was composed of pallisading columnar cells. Most parts of the outermost layer of the cystic structure stained positively with AE1 antibody. From these immunohistochemical findings, we speculated that the dilated pore in our case was an isolated clinical entity is a follicular tumor differentiating mainly toward the infundibulum and partly toward the isthmus. Topics: Aged; Biopsy, Needle; Epidermal Cyst; Epidermis; Eyebrows; Female; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Skin Diseases | 2003 |
[A novel keratin 17 gene mutation in a Chinese pedigree of delayed-onset pachyonychia congenita type II].
To detect the keratin 17 gene mutation in a Chinese pedigree of typical delayed-onset pachyonychia congenita type II (PC-II) and to explore the relationship between the genetic mutation and the phenotype of PC-II.. The DNA was extracted from the blood samples of 19 patients with PC-II in four generations in the pedigree, 1 unaffected member of the pedigree, and 50 un-related normal persons. Nested PCR was used to amplify the mutation hot spot in the exon 1 of keratin 17 gene. The PCR products were directly sequenced to detect the mutation.. Sequencing of the PCR products revealed that the codon 109 (AAC) was mutated as GAC in the nine affected members of the pedigree, causing the substitution of asparagine by aspartic acid in codon 109 (N109D) located in the 1A domain of keratin 17 gene. No such mutation was found in the unaffected member of the pedigree and the 50 unrelated controls.. The novel missense mutation (N109D) located in the second half of 1A domain of keratin 17 gene underlies the affected members' phenotype, delayed-onset pachyonychia congenita type II. Topics: Age of Onset; Ectodermal Dysplasia; Humans; Keratins; Male; Middle Aged; Mutation; Pedigree; Polymerase Chain Reaction; Skin Diseases | 2003 |
Cutaneous ciliated cyst of the abdominal wall.
Topics: Abdominal Muscles; Adolescent; Cilia; Epidermal Cyst; Female; Humans; Immunohistochemistry; Keratins; Skin Diseases; Treatment Outcome | 2002 |
Disorders of skin barriers: clinical implications.
Topics: Dermatitis, Atopic; Humans; Intermediate Filaments; Keratins; Skin Diseases; Skin Physiological Phenomena | 2002 |
Retinoids strongly and selectively correlate with keratin 13 and not keratin 19 expression in cutaneous warts of renal transplant recipients.
To compare the expression of keratin (K) 13 and K19 in cutaneous warts of renal transplant recipients (RTRs) and immunocompetent individuals (ICIs).. Retrospective, nonrandomized immunohistochemical study.. Specimens from cutaneous warts of RTRs and ICIs were retrieved from the archives of the Department of Pathology, University Medical Center St Radboud, Nijmegen, the Netherlands. Twenty-one warts from RTRs and 21 from ICIs were examined. Nine RTRs (10 specimens) received either systemic acitretin or topical all-trans retinoic acid, and their effect on both keratins was assessed.. Frequency and expression patterns of K13 and K19 in warts of RTRs vs ICIs and the effect of retinoids.. A significantly higher percentage of warts of RTRs expressed K13 compared with warts of ICIs (86% vs 14%, 18 vs 3 cases, respectively; P<.001). In warts of RTRs, retinoid treatment correlated significantly with a particularly strong, segmental K13 expression pattern, which we termed zebroid. Without use of retinoids, K13 was mostly restricted to suprabasal single cells. Keratin 19 was absent in all warts of both patient groups.. Retinoids strongly correlate with K13 in a characteristic zebroid pattern in warts of RTRs, making K13 a sensitive marker for retinoid bioactivity in skin (lesions) of RTRs. In non-retinoid-treated RTRs, K13 is also frequently found in warts but without the dramatic zebroid pattern noted in retinoid-treated warts. Topics: Acitretin; Adult; Aged; Confidence Intervals; Culture Techniques; Female; Humans; Immunohistochemistry; Keratins; Kidney Transplantation; Male; Middle Aged; Probability; Reference Values; Retrospective Studies; Sensitivity and Specificity; Skin Diseases; Warts | 2002 |
A novel point mutation in the keratin 17 gene in a Japanese case of pachyonychia congenita type 2.
Topics: Adult; Asian People; Cysts; Hair; Humans; Japan; Keratins; Keratoderma, Palmoplantar; Male; Nail Diseases; Point Mutation; Skin Diseases | 2002 |
Cytokeratin expression in steatocystoma multiplex.
Topics: Adult; Aged; Biomarkers; Epidermal Cyst; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sebaceous Glands; Skin Diseases | 2002 |
Tricholemmal carcinoma in continuity with trichoblastoma within nevus sebaceus.
A nodule arising within the nevus sebaceus on the vertex of the scalp of a 68-year-old woman was histopathologically and immunohistochemically investigated. We also used immunohistochemistry to investigate the cytokeratin (CK) distribution of the outer root sheaths of normal terminal hair follicles. The nodule consisted of two parts, a main exophytic part with a lobular proliferation and a small peripheral part with the features of trichoblastoma. The main exophytic lesion consisted of lobular aggregations composed of both or either basaloid cells and clear cells with the silhouette and cytology of malignancy. The columnar clear cells were aligned in a palisade at the periphery of the aggregations of clear cells, and the aggregations located in the superficial dermis were connected to the follicular infundibular structures. Almost all of the neoplastic aggregations were diffusely positive for CK7 (OV/TLR/30), and the innermost or inner cells of the neoplastic aggregations were positive for CK17; a similar staining pattern to that in the lower portion of the outer root sheath between the A and B fringes in normal terminal hair follicles. The exophytic part of the lesion was a malignant neoplasm with differentiation mainly toward the lower segment of the outer sheath between the A and B fringes of the terminal hair follicle, namely tricholemmal carcinoma. Our case may represent a collision of two distinctive neoplasms (tricholemmal carcinoma and trichoblastoma), however, an intimate relationship between these two neoplasms also should be considered. Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Hair Follicle; Hamartoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Nevus; Scalp; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms | 2002 |
Radiology quiz case. Epidermal inclusion cyst with intracystic keratin debris.
Topics: Adult; Diagnosis, Differential; Epidermal Cyst; Head and Neck Neoplasms; Humans; Keratins; Magnetic Resonance Imaging; Male; Skin Diseases | 2002 |
Identification of the etiological agent for necrotizing scute disease in the Texas tortoise.
Epidermal lamellae (scutes) of the Texas tortoise, Gopherus berlandieri, from southern Texas (USA) were observed to be in various stages of necrosis, ranging from localized whitish blemishes to complete degradation of the external portion of the scute. Fusarium semitectum was consistently isolated from slivers of infected scute from tortoises. The fungus was not isolated from tortoises exhibiting no lesions. Confocal microscopy confirmed the presence of septate mycelia inside the scutes, and isolates of F. semitectum grown in the laboratory were successfully transferred to non-infected tortoises. Twenty-four tortoises maintained by two rehabilitators in southern Texas exhibited lesions; however, only one of 27 tortoises from Dimmit and Zavala counties was infected. Topics: Animal Diseases; Animals; Epidermis; Fusarium; Keratins; Male; Mycoses; Necrosis; Skin Diseases; Texas; Turtles | 2001 |
Atrichia with papular lesions: electron microscopic observations of cystic lesions.
Atrichia with papular lesions is a rare inherited skin disorder characterized by congenital atrichia with numerous papules. We describe a 27-year-old woman with atrichia, who had numerous papules on her scalp, nape, and axillae. Histologically, many keratinous cysts were seen in the middermis of a skin specimen from the nape. Electron microscopy showed that the developing keratinocytes in the walls of some cysts were rich in glycogen granules and had epidermoid keratinization with formation of keratohyaline granules and that laminated bodies were formed before keratinization. Langerhans cells were often seen in the walls of the cysts. In addition, a broad glassy vitreous layer surrounded the cyst wall. From these findings, it was suggested that the cystic lesions might have originated from immature or incomplete hair follicles. In particular, the structure of the cyst wall corresponded well to infundibular and/or isthmal portions of the outer root sheath of the hair follicle. Topics: Adult; Alopecia; Cysts; Female; Humans; Keratinocytes; Keratins; Microscopy, Electron; Skin; Skin Diseases | 2001 |
Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.
The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation. Topics: Aging; Alopecia; Animals; Antigens, CD; Cadherins; Cell Differentiation; Cell Division; Dermatitis; Desmocollins; Desmosomes; Epidermis; Eyelids; Gene Targeting; Immunohistochemistry; Integrin beta4; Keratins; Ki-67 Antigen; Membrane Glycoproteins; Mice; Mice, Transgenic; Phenotype; Protein Isoforms; Recombination, Genetic; Skin Diseases | 2001 |
Sebaceous carcinoma, trichoblastoma, and sebaceoma with features of trichoblastoma in nevus sebaceus.
A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case. Topics: Aged; Carcinoma; Carcinoma, Skin Appendage; Ear Neoplasms; Ear, External; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms | 2001 |
[Keratin 17 gene mutation in patients with steatocystoma multiplex].
To study the relationship between steatocystoma multiplex (SCM) and keratin 17 gene mutation.. The keratin 17 gene mutation in the cDNA of cystic tissue of 5 patients of SCM and in the DNA in peripheral blood of 25 patients with SCM from a SCM family was studied by direct sequencing of the RT-PCR products, nested PCR, and restricted fraction length polymorphism (RFLP) analysis. Thirty-nine blood specimens from the unaffected members of that family were collected and tested too. Ten DNA pool specimens and other 2000 DNA pool specimens of normal individuals outside that SCM family were used as controls.. In the base 428, 94(th) codon in keratin 17 gene in the cDNA of patients' cystic tissue, R94C mutation, a G-->A mutation, was detected Nested PCR, and restricted enzyme Acil polymorphism analysis showed that in the DNA specimens of peripheral blood of patients a mutated allele lacking enzyme cutting locus was detected, thus causing an uncut band with 200 bp while the corresponding allele was cut and caused two bands with 108 bp and 92 bp. In the DNA pool specimens of normal controls only these two bands with 108 bp and 92 bp were observed.. The R94C mutation in keratin 17 gene is one of the genetic bases of SCM in Chinese. The results of this study provide scientific data for genetic diagnosis and counseling of SCM. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Epidermal Cyst; Female; Humans; Keratins; Male; Middle Aged; Point Mutation; Skin Diseases | 2001 |
Novel mechanism of steroid action in skin through glucocorticoid receptor monomers.
Glucocorticoids (GCs), important regulators of epidermal growth, differentiation, and homeostasis, are used extensively in the treatment of skin diseases. Using keratin gene expression as a paradigm of epidermal physiology and pathology, we have developed a model system to study the molecular mechanism of GCs action in skin. Here we describe a novel mechanism of suppression of transcription by the glucocorticoid receptor (GR) that represents an example of customizing a device for transcriptional regulation to target a specific group of genes within the target tissue, in our case, epidermis. We have shown that GCs repress the expression of the basal-cell-specific keratins K5 and K14 and disease-associated keratins K6, K16, and K17 but not the differentiation-specific keratins K3 and K10 or the simple epithelium-specific keratins K8, K18, and K19. We have identified the negative recognition elements (nGREs) in all five regulated keratin gene promoters. Detailed footprinting revealed that the function of nGREs is to instruct the GR to bind as four monomers. Furthermore, using cotransfection and antisense technology we have found that, unlike SRC-1 and GRIP-1, which are not involved in the GR complex that suppresses keratin genes, histone acetyltransferase and CBP are. In addition, we have found that GR, independently from GREs, blocks the induction of keratin gene expression by AP1. We conclude that GR suppresses keratin gene expression through two independent mechanisms: directly, through interactions of keratin nGREs with four GR monomers, as well as indirectly, by blocking the AP1 induction of keratin gene expression. Topics: Gene Expression Regulation; Glucocorticoids; HeLa Cells; Humans; Keratinocytes; Keratins; Promoter Regions, Genetic; Receptors, Glucocorticoid; Skin; Skin Diseases | 2000 |
Keratinocyte expression of transgenic hepatocyte growth factor affects melanocyte development, leading to dermal melanocytosis.
Using the epidermis-specific cytokeratin 14 promoter to deliver HGF exclusively from epidermal keratinocytes, we have examined the potential of hepatocyte growth factor (HGF) secreted from the normal environment to control morphogenesis. The transgenic mice displayed a significant increase of the number of melanocytes and their precursors in embryos starting not later than 16.5 dpc, and then after birth an explosive increase of dermal melanocytes started within 1 week, and these melanocytes were maintained throughout the entire life of the mice. Thus, HGF acts as a paracrine agent to promote survival, proliferation and differentiation of melanocyte precursors in vivo, and eventually causes melanocytosis. Loss of E-cadherin expression in dermal melanocyte precursors suggests that HGF caused dermal localization of melanocytes and their precursors by down-regulation of E-cadherin molecules. Topics: Animals; Animals, Newborn; Cadherins; Ear, External; Gene Expression Regulation, Developmental; Hepatocyte Growth Factor; Intramolecular Oxidoreductases; Keratinocytes; Keratins; Melanocytes; Mice; Mice, Transgenic; Promoter Regions, Genetic; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-met; Skin; Skin Diseases; Skin Pigmentation; Stem Cell Factor | 2000 |
A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus.
Palmoplantar keratodermas are a group of heterogeneous diseases characterized by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes: diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All forms are genetic diseases inherited as autosomal dominant disorders. We studied a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fit into any classes already described. We sequenced the keratin 16 cDNA derived from skin biopsy material from affected and non affected palms. The keratin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletion (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypeptide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygotic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, "unilateral palmoplantar verrucous nevus", rather than localized or focal epidermolytic palmoplantar keratodermas, as the lesions are present only on one side of the body and follow Blaschko's lines. This study is a report of a mosaic mutation in keratin 16 and also the association of a mutation in the V1 domain of a type I keratin associated with a human disease. Topics: Adolescent; DNA Mutational Analysis; Female; Gene Expression; Hamartoma; Humans; Keratins; Keratoderma, Palmoplantar; Mutation; Protein Structure, Tertiary; Skin Diseases | 2000 |
Effects of plant-induced hypervitaminosis D on cutaneous structure, cell differentiation and cell proliferation in cattle.
Solanum glaucophyllum (Sg) (synonym S. malacoxylon) is a plant toxic to cattle due to its high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives. Sg causes a disease characterized by wasting and calcification of soft tissues. The effects of vitamin D are not only important in calcium homeostasis, but also in immune regulation, cell growth and cell differentiation. Skin samples in Sg-intoxicated and control heifers were studied histologically. Cellular differentiation and proliferation were analysed by immunohistochemical expression of cytokeratins, involucrin and proliferating cell nuclear antigen (PCNA). The results were obtained by image processing and analysis and were statistically evaluated. Sg-intoxicated cattle showed atrophy of epidermis and severe involution of hair follicles and of sebaceous and sweat glands. As judged by PCNA expression, cellular proliferation was reduced, even though the reduction was not statistically significant. The analysed markers of differentiation, e.g. involucrin and cytokeratins 10 and 11, changed in relation to Sg-poisoning. The possible pathogenesis of the skin lesions is discussed. Topics: Animals; Antibodies, Monoclonal; Argentina; Body Weight; Cattle; Cattle Diseases; Cell Differentiation; Cell Division; Female; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Plant Poisoning; Proliferating Cell Nuclear Antigen; Protein Precursors; Skin Diseases; Solanaceae; Solanaceous Alkaloids; Vitamin D | 2000 |
A mutation detection strategy for the human keratin 6A gene and novel missense mutations in two cases of pachyonychia congenita type 1.
Pachyonychia congenita type 1 (PC-1) is an autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy, focal non-epidermolytic palmoplantar keratoderma and variable features of oral leukokeratosis and follicular keratosis. Previously, we have shown that this disease can be caused by mutations in type I keratin K16 and one mutation has been reported in its type II keratin expression partner, K6a. Mutation analysis for K6a has been hampered by the presence of multiple copies of the K6 gene in the human genome, of which some are expressed and others are pseudogenes. Here, we describe a mutation detection strategy where the entire KRT6A gene, approximately 7 kb, is specifically amplified by long-range PCR. Using this technique, we have detected two novel mutations in the 1A domain of the K6a polypeptide, N171K and F174S. Mutations were confirmed in the affected individuals and were excluded from 50 unaffected unrelated individuals by restriction enzyme analysis of KRT6A PCR products. Additionally, mutation N171K was confirmed by RT-PCR in mRNA derived from lesional palmoplantar epidermis of an affected individual, confirming the specificity of the genomic PCR for the functional K6a gene. This, together with a similar strategy which we have developed for the K16 gene, provide a robust system for mutation detection and prenatal diagnosis for patients with PC-1. Topics: Amino Acid Substitution; Base Sequence; Ectodermal Dysplasia; Exons; Female; Genome, Human; Humans; Keratins; Male; Multigene Family; Mutation, Missense; Nails, Malformed; Pedigree; Skin Diseases | 1999 |
Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot.
Pachyonychia congenita (PC) is a rare, autosomal dominant, ectodermal dysplasia characterized most distinctly by the presence of symmetric nail hypertrophy. In the Jadassohn-Lewandowsky form, or PC-1, additional cutaneous manifestations may include palmoplantar hyperkeratosis, hyperhidrosis, follicular keratoses, and oral leukokeratosis. Mutations have previously been identified in the 1A helix initiation motif of either keratin 6 or keratin 16 in patients with PC-1. In the current study, we have identified 2 sporadic, heterozygous mutations in the 1A helix region of the K6 isoform (K6a). The first mutation identified was a 3 base pair deletion (K6adelta N171). The second mutation was a C-to-A transversion resulting in an amino acid substitution (K6a N171K). These data, in combination with previous reports, provide further evidence that this location is a mutational hot spot. Topics: Amino Acid Sequence; Amino Acid Substitution; Base Sequence; DNA; DNA Primers; Ectodermal Dysplasia; Female; Genetic Carrier Screening; Humans; Infant; Keratins; Male; Nails, Malformed; Pedigree; Point Mutation; Polymerase Chain Reaction; Protein Structure, Secondary; Skin Diseases | 1999 |
Milia en plaque.
Topics: Aged; Ear Diseases; Ear, External; Epidermal Cyst; Female; Humans; Keratins; Skin Diseases | 1999 |
Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice.
To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens. Topics: Administration, Oral; Animals; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Disease Progression; DNA Replication; Ear; Eflornithine; Epidermis; Gene Expression Regulation; Genes, Viral; Keratin-14; Keratins; Mice; Mice, Transgenic; Neoplasm Proteins; Organ Specificity; Ornithine Decarboxylase Inhibitors; Papilloma; Papillomaviridae; Precancerous Conditions; Putrescine; Skin Diseases; Skin Neoplasms; Thorax; Transgenes | 1999 |
Primary localized cutaneous amyloidosis--lichen amyloidosus. A case report.
We report a case of primary localized cutaneous amyloidosis-lichen amyloidosus in a 55-year-old man. Immunohistochemistry using antibodies against cytokeratin and AL immunoglobulins revealed the presence of both components in amyloid foci located subepidermally, mainly in dermal papillae. The results of histochemical reactions confirm the keratin-derived nature of amyloid in primary cutaneous amyloidosis. Topics: Amyloid; Amyloidosis; Capillaries; Dermis; Humans; Immunoenzyme Techniques; Immunoglobulin Light Chains; Keratins; Male; Middle Aged; Skin; Skin Diseases | 1999 |
Overexpression of protein kinase C-alpha in the epidermis of transgenic mice results in striking alterations in phorbol ester-induced inflammation and COX-2, MIP-2 and TNF-alpha expression but not tumor promotion.
Protein kinase Calpha (PKCalpha) is one of six PKC isoforms expressed in keratinocytes of mouse epidermis. To gain an understanding of the role of epidermal PKCalpha, we have localized its expression to specific cells of normal mouse skin and examined the effect of keratin 5 (K5) promoter directed expression of PKCalpha in transgenic mice. In normal mouse skin, PKCalpha was extensively expressed in the outer root sheath (ORS) keratinocytes of the anagen hair follicle and weakly expressed in keratinocytes of interfollicular epidermis. K5-targeted expression of PKCalpha to epidermal basal keratinocytes and follicular ORS keratinocytes resulted in a tenfold increase in epidermal PKCalpha. K5-PKCalpha mice exhibited no abnormalities in keratinocyte growth and differentiation in the epidermis. However, a single topical treatment with the PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a striking inflammatory response characterized by edema and extensive epidermal infiltration of neutrophils that formed intraepidermal microabscesses in the epidermis. Compared to TPA-treated wild-type mice, the epidermis of TPA-treated K5-PKCalpha mice displayed increased expression of cyclooxygenase-2 (COX-2), the neutrophil chemotactic factor macrophage inflammatory protein-2 (MIP-2) mRNA and the proinflammatory cytokine TNFalpha mRNA but not IL-6 or IL-1alpha mRNA. To determine if K5-PKCalpha mice display an altered response to TPA-promotion, 7, 12-dimethylbenz[a]anthracene-initiated K5-PKCalpha mice and wild-type mice were promoted with TPA. No differences in papilloma incidence or multiplicity were observed between K5-PKCalpha mice and wild-type littermates. These results demonstrate that the overexpression of PKCalpha in epidermis increases the expression of specific proinflammatory mediators and induces cutaneous inflammation but has little to no effect on epidermal differentiation, proliferation or TPA tumor promotion. Topics: Abscess; Animals; Cattle; Chemokine CXCL2; Chemotactic Factors; Cyclooxygenase 2; Edema; Enzyme Activation; Epidermis; Gene Expression Regulation; Hair; Inflammation; Isoenzymes; Keratinocytes; Keratins; Mice; Mice, Transgenic; Monokines; Neutrophils; Promoter Regions, Genetic; Prostaglandin-Endoperoxide Synthases; Protein Kinase C; Protein Kinase C-alpha; RNA, Messenger; Skin; Skin Diseases; Tetradecanoylphorbol Acetate; Transcription, Genetic; Tumor Necrosis Factor-alpha | 1999 |
Expression of MK6a dominant-negative and C-terminal mutant transgenes in mice has distinct phenotypic consequences in the epidermis and hair follicle.
Mouse keratin 6a (MK6a) is constitutively expressed in a single cell layer of the outer root sheath (ORS) of hair follicles, but its synthesis can be induced in interfollicular epidermis including the basal cell layer in response to perturbing stimuli. A basally inducible human K6 (HK6) isoform has not been described, and it is not clear which of the known HK6 isoforms is expressed in the ORS. In this study we show that expression of a dominant-negative MK6a construct (Delta2B-P) in the interfollicular epidermis caused severe blistering and neonatal lethality, suggesting that mutations in a yet to be identified basally expressed HK6 isoform might result in a severe blistering phenotype. Surviving Delta2B-P animals showed transgene expression only in isolated epidermal cells and not in all cells of the ORS, but nevertheless developed severe alopecia. Expression of two different C-terminal mutant transgenes also caused alopecia while a third C-terminal mutant had no phenotypic conse- quences. Electron microscopy revealed that Delta2B-P expression resulted in the collapse of keratin filaments, while destruction of hair follicles in the two phenotypic C-terminal mutant lines occurred in the absence of filament abnormalities. The latter finding indicates that the innermost ORS cells are uniquely sensitive to expression of even slightly altered K6 proteins, suggesting that mutations affecting an HK6 isoform expressed in this cell layer could result in alopecia in humans as well. Topics: Age of Onset; Alopecia; Amino Acid Sequence; Animals; Animals, Newborn; Epidermis; Gene Expression; Genes, Dominant; Hair Follicle; Keratins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Mutagenesis, Site-Directed; Phenotype; Protein Isoforms; Skin Diseases; Time Factors; Transgenes | 1999 |
Immunohistochemical observation of cytokeratins in keratinous cysts including plantar epidermoid cyst.
Sixteen cases of epidermal cyst (EC) (6 cases of conventional EC and 10 cases of plantar epidermoid cyst (PEC)) and 9 cases of trichilemmal cyst (TC) were examined by an immunohistochemical technique using various antibodies against cytokeratins and human papilloma virus (HPV) in order to clarify their histogenesis. There was no difference in immunoreactivities between EC and PEC with or without HPV infection. In TC, the inner layers of the cyst wall were stained with the antibody E3 (CK17), and the outermost layer was stained with the antibodies 4.1.18 (CK8) and 170.2.14 (CK19). In PEC and EC, however, the cyst wall didn't react with these antibodies, and differentiation-specific cytokeratins were expressed in the inner layer. These results confirmed that the immunoreactivities of PEC and EC were identical to those of normal epidermis or infundibulum, and that those of TC were similar to the outer root sheath between the lower infundibulum and isthmus. Although PEC has been recently reported to originate from eccrine ducts, there was a significant difference in immunoreactivities between PEC and eccrine ducts. Furthermore, on the basis of the fact that sole skin has no hair follicles, PEC was speculated to originate from epidermal implantation. Topics: Adolescent; Adult; Aged; Epidermal Cyst; Female; Foot Dermatoses; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Papillomaviridae; Skin Diseases | 1999 |
Disseminated superficial porokeratosis with dermal amyloid deposits: case report and immunohistochemical study of amyloid.
The association of porokeratosis with dermal amyloid deposits is extremely rare, only three cases are reported in the literature. We describe a case of disseminated superficial porokeratosis (DSP) with clear histologic evidence of amyloid deposition in the upper dermis. The amyloid was typed with an original immunohistochemical assay based on three anticytokeratin antibodies (MNF 116, CK1, KER B). The epidermal origin of the substance (K amyloid) was demonstrated by its strong positivity for MNF 116 and KER B. Topics: Aged; Amyloidosis; Humans; Immunohistochemistry; Keratins; Male; Porokeratosis; Skin Diseases | 1998 |
Not all black follicular plugs are comedones!
Topics: Acne Vulgaris; Aged; Diagnosis, Differential; Hair Follicle; Humans; Keratins; Keratosis; Male; Skin; Skin Diseases | 1998 |
Cytokeratins in primary cutaneous amyloidosis.
The expression of keratins was investigated immunohistochemically on formalin-fixed and snap-frozen primary cutaneous amyloidosis tissue with a panel of monospecific and polyspecific antikeratin antibodies, with recognized keratins K1, K5, K6, K7, K8, K10, K14, K16, K17, K18 and K19. Amyloid deposits in frozen sections of seven cases of macular amyloidosis and lichen amyloidosus always reacted with antibodies LP34 (labelling K5, K6 and K18), MNF 116 (labelling K5, K6, K8, K10, K17 and K18), and RCK 102 (labelling K5 and K8); frozen sections in one case each of the seven cases also reacted with antibodies LL001 (labelling K14), LP1K (labelling K7 and K17), and LP2K (labelling K19). In formalin-fixed sections of 13 cases of macular amyloidosis and lichen amyloidosus, amyloid deposits were labelled with LP34 in three sections, MNF 116 in four sections, LL020 (labelling keratins K5 and K6) in one section, and LP2K in two sections. In nodular primary cutaneous amyloidosis, amyloid deposits were not labelled with any antikeratin antibodies. These data confirm that amyloid in macular amyloidosis and lichen amyloidosus contains keratin epitopes, and suggests derivation of the fibrillar component from keratin intermediate filaments. Several different keratins appear to undergo conversion to amyloid. LP34, MNF 116 and RCK 102 antibodies, which have in common the labelling of keratin K5, may be useful in the diagnosis of macular and papular amyloidosis with frozen tissue sections. Topics: Amyloidosis; Antibodies, Antinuclear; Biomarkers; Culture Techniques; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Skin Diseases | 1998 |
A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2.
Type I and type II keratins form the heteropolymeric intermediate filament cytoskeleton, which is the main stress-bearing structure within epithelial cells. Pachyonychia congenita (PC) is a group of autosomal dominant disorders whose most prominent phenotype is hypertrophic nail dystrophy accompanied by other features of ectodermal dysplasia. It has been shown previously that mutations in either K16 or K6a, which form a keratin expression pair, produce the PC-1 variant (MIM 184510). Mutations in K17 alone, an unpaired accessory keratin, result in the PC-2 phenotype (MIM 184500). Here, we describe a family with PC-2 in which the K17 locus on 17q was excluded and linkage to the type II keratin locus on 12q was obtained (Z max 3.31 at straight theta = 0). Mutation analysis of candidate keratins revealed the first reported missense mutation in K6b, implying that this keratin is the previously unknown expression partner of K17, analogous to the K6a/K16 pair. Co-expression of these genes was confirmed by in situ hybridization and immunohistochemical staining. These results reveal the hitherto unknown role of the K6b isoform in epithelial biology, as well as genetic heterogeneity in PC-2. Topics: Female; Gene Expression; Genetic Linkage; Genotype; Humans; Keratins; Male; Mutation, Missense; Nail Diseases; Pedigree; Phenotype; Skin Diseases | 1998 |
Towards defining the pathogenesis of the hairless phenotype.
Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen-associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen. Topics: Alkaline Phosphatase; Animals; Female; Gene Expression; Hair; Immunohistochemistry; In Situ Hybridization; Keratins; Ki-67 Antigen; Mice; Mice, Hairless; Mice, Inbred C57BL; Neural Cell Adhesion Molecules; Phenotype; RNA, Messenger; Skin; Skin Diseases | 1998 |
The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE.
Epidermal thickening is a phenomenon common to many genodermatoses but little is known about the underlying causes. We have recently created a mouse model for the human skin disease bullous congenital ichthyosiform erythroderma by gene targeting. Mice heterozygous for a truncated keratin 10 gene exhibit acanthosis and hyperkeratosis as seen in the human disease. The degree of epidermal thickening is highly variable, offering a novel opportunity to investigate how epidermal homeostasis is modulated in keratin disorders by comparing epidermis from different body regions. We have performed bromodeoxyuridine labeling experiments and detected proliferation antigens by immunohistochemical means to compare proliferation in the epidermis of wild-type and heterozygous mice. These results have been compared with the expression of epidermal differentiation markers and of the "hyperproliferation associated" keratins K6 and K16. These experiments indicated that hyperproliferation is only partly responsible for the morphologic changes and that other mechanisms such as decreased desquamation are likely to be involved. Topics: Animals; Back; Biomarkers; Cell Division; Disease Models, Animal; Ear; Epidermis; Esophagus; Foot; Gene Expression; Histocytochemistry; Hyperkeratosis, Epidermolytic; Immunohistochemistry; Integrin beta1; Keratins; Ki-67 Antigen; Mice; Mice, Knockout; Proliferating Cell Nuclear Antigen; Skin; Skin Diseases | 1998 |
Pachyonychia congenita type 2: keratin 17 mutation in a Japanese case.
Topics: Adult; Alleles; Humans; Japan; Keratins; Male; Mutation; Nail Diseases; Pedigree; Polymerase Chain Reaction; Sequence Analysis; Skin Diseases | 1998 |
Apolipoprotein E is present in primary localized cutaneous amyloidosis.
Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis. Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Antigen-Antibody Reactions; Apolipoproteins E; Female; Humans; Immunoblotting; Immunohistochemistry; Keratins; Lichenoid Eruptions; Male; Microscopy, Electron; Middle Aged; Skin Diseases | 1998 |
Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2.
Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an autosomal dominant disorder characterized by hypertrophic nail dystrophy, mild focal keratoderma, multiple pilosebaceous cysts and other features of ectodermal dysplasia. Keratin 17 (K17) is a differentiation-specific keratin expressed in the nail bed, hair follicle, sebaceous gland and other epidermal appendages. Previously, we have demonstrated that PC-2 is caused by mutations in K17 and that similar mutations in this gene can present as steatocystoma multiplex with little or no nail dystrophy. Here, we describe three unrelated kindreds carrying K17 mutations. Two of these families have identical missense mutations (R94C) in the 1A domain of K17. However, while affected members of one kindred have the classical features of PC-2, affected persons in the other family have the steatocystoma multiplex phenotype. In a third family with PC-2, mutation N92S was detected, bringing the total number of distinct mutations reported in K17 thus far to 11. These results demonstrate that K17 mutations commonly underlie both PC-2 and steatocystoma multiplex and that the alternate phenotypes which arise from these genetic lesions in K17 are independent of the specific mutation involved. Topics: Adolescent; Adult; Cysts; DNA Mutational Analysis; Female; Humans; Keratins; Mutation; Mutation, Missense; Nail Diseases; Pedigree; Phenotype; Polymerase Chain Reaction; Skin Diseases | 1998 |
[Childhood plaque milia of the inner canthus].
Milia en plaque is an uncommon skin condition usually seen in adult women, typically in the retroauricular region. We report a new localization in a young child.. A 6-year-old girl with an uneventful history had developed over the last 7 months an erythematous plaque with numerous whitish-yellow microcysts on the left internal canthus. No local or general favoring factor was found. Skin biopsy showed numerous cystic cavities with an epidermal lining containing layers of keratin within a moderately inflammatory infiltration. The lesion resolved after enucleation of the cysts and no recurrence has been observed after 9 months follow-up.. Milia en plaque is a charateristic erythematous lesion covered with cysts. The usual localization is the retroauricular region, but other localizations have been reported, mainly on the head. This is the first report involving the internal canthus and also in such a young child. One case of a 15-year-old boy has been discribed. Milia en plaque is often a primary condition as in our case although local or general factors may rarely be inductive. Our case illustrates the different localizations possible for milia en plaque, with predominance on the head, and the possibility of childhood cases. We prefer the term milia en plaque rather than retroauricular milia en plaque. Topics: Child; Diagnosis, Differential; Epidermal Cyst; Erythema; Facial Dermatoses; Female; Follow-Up Studies; Humans; Keratins; Skin Diseases | 1998 |
Milia en plaque in a bilateral submandibular distribution.
Milia en plaque typically occurs in the retroauricular area. We report the case of an 84-year-old woman with this disorder occurring bilaterally in the submandibular region. The diagnosis was confirmed by histological examination. Topics: Aged; Aged, 80 and over; Cysts; Female; Humans; Keratins; Skin Diseases; Submandibular Gland Diseases | 1998 |
Evaluation of cross-reacting anti-human antibodies in the euthymic hairless guinea pig model (HGP) suggests that the HGP may be a model for the study of proliferative skin disease.
Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis. Topics: Actins; Animals; Antibodies; Antibody Specificity; Apoptosis; CD3 Complex; Cell Division; Collagen; Cross Reactions; Disease Models, Animal; Fibronectins; Guinea Pigs; Humans; Immunohistochemistry; Keratinocytes; Keratins; Ki-67 Antigen; Male; Proliferating Cell Nuclear Antigen; S100 Proteins; Skin; Skin Diseases; Tumor Suppressor Protein p53; Vimentin; von Willebrand Factor | 1997 |
Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts.
We compared the patterns of keratin 10 (K10) and keratin 17 (K17) expression in epidermoid cysts, trichilemmal cysts, eruptive vellus hair cysts, and steatocystoma multiplex. Epidermoid cysts expressed K10 and eruptive vellus hair cysts expressed K17, whereas trichilemmal cysts and steatocystoma multiplex showed expression of both K10 and K17. Our findings support the opinion that eruptive vellus hair cysts, which stained negative for K10, and steatocystoma multiplex are distinct entities and not variants of one disorder. Topics: Cysts; Epidermal Cyst; Hair; Humans; Immunohistochemistry; Keratin-10; Keratins; Skin Diseases | 1997 |
Microcystic adnexal carcinoma with extensive sebaceous differentiation.
We report two cases of microcystic adnexal carcinoma showing extensive sebaceous differentiation. Multiple cellular nests and strands within a moderately sclerotic stroma involving the full thickness of the dermis were observed. Clusters of basaloid cells with extensive sebaceous differentiation were present. Foci of sebaceous ductal differentiation were observed in the more superficial areas. Neither strikingly atypical cells nor mitotic figures were present. Perineural invasion was present in the deep areas of both tumors. Clinically, the lesions were solitary whitish-pink papules with a central dell on the faces of 2 men (aged 78 and 73 years old). We propose a relationship between these tumors and other cytologically bland but locally aggressive adnexal carcinomas. Sebaceous differentiation itself in a poorly circumscribed neoplasm does not indicate conventional extraocular sebaceous carcinoma. We propose a simple classification of locally aggressive adnexal carcinomas that takes into account the full range of adnexal differentiation that can occur in such lesions. Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Skin Appendage; Cell Differentiation; Elastic Tissue; Epidermis; Facial Neoplasms; Follow-Up Studies; Glycosaminoglycans; Humans; Keratins; Male; Mitosis; Neoplasm Invasiveness; Neurons; S100 Proteins; Sclerosis; Sebaceous Glands; Skin Diseases; Skin Neoplasms | 1997 |
Steatocystoma multiplex and oligosymptomatic pachyonychia congenita of the Jackson-Sertoli type.
A family with affected members, previously reported to carry an R94H mutation of keratin K17, and characterized by a variable and oligosymptomatic form of pachyonychia congenita of the Jackson-Sertoli type with steatocystoma multiplex, is described in detail. Topics: Adult; Epidermal Cyst; Female; Humans; Keratins; Keratoderma, Palmoplantar; Male; Middle Aged; Mutation; Nail Diseases; Pedigree; Phenotype; Skin Diseases | 1997 |
Effects of xerosis and ageing on epidermal proliferation and differentiation.
The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age. Topics: Adult; Aged; Aging; Body Water; Cell Differentiation; Cell Division; Electrophoresis, Gel, Two-Dimensional; Epidermis; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Protein Precursors; Skin Diseases; Water Loss, Insensible | 1997 |
Keratin and the skin: past, present and future.
Topics: Epidermolysis Bullosa Simplex; Humans; Keratins; Mutation; Skin Diseases | 1997 |
Combined neuroendocrine carcinoma of the skin (Merkel cell tumor) and trichilemmal cyst.
We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium. Topics: Aged; Biomarkers, Tumor; Carcinoma, Merkel Cell; Cell Nucleolus; Cell Nucleus; Chromatin; Cytoplasm; Epidermal Cyst; Epithelium; Female; Humans; Keratins; Neoplastic Stem Cells; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin; Skin Diseases; Skin Neoplasms | 1997 |
Lichen amyloidosus: a consequence of scratching.
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 | 1997 |
Repair kinetics in pig epidermis: an analysis based on two separate rates of repair.
Pig skin was irradiated using 90Sr/90Y plaques and the dose-related incidence of induced moist desquamation was determined. The repair of radiation-induced sublethal damage (SLD) was studied by fitting these response data to the generalized LQ equation for incomplete repair using quasilikelihood methods with binomial statistics, and either a Poisson or logistic link to relate the probability of response to the covariates. A Poisson response analysis based on the assumption that SLD was governed by two repair processes gave estimated repair half-times of 0.20 [(95% confidence limits) 0.12, 0.34] and 6.6 [4.3, 10.0] h. The estimates of the short and long repair half-times were significantly different, although there was no significant difference between the results using the Poisson and logistic modes of analyses. The partition coefficient for the longer repair process was 0.5 [0.34, 0.71] indicating that about 33% of SLD-derived lethal damage is associated with the longer repair process in the case of 'complete repair' protocols. However, this proportionation is, in general, protocol dependent for incomplete repair protocols. A chi2 test on the residual deviance showed that the assumption of two repair processes for SLD gave a superior fit to the data than a single repair process at a significance level >99%. The radiation dose to the assumed target cell population depends upon their depth from the skin surface, due to the relatively short range of the electron emission from the 90Sr/90Y plaques. However, further modelling analyses have shown that the estimated repair half-times were independent of the assumed target cell distribution in the skin. This is in contrast with the alpha/beta ratio, where different (clinically significant) estimates can be obtained depending upon the assumed target cell distribution. If the target cells were at 16 micrometer depth from the surface of the skin, the estimated value for the alpha/beta ratio using the biphasic repair model would be 4.6[3.6, 5.6] Gy(Poisson analysis). However, the estimates decrease with the assumed depth (distribution) of the target cells. Topics: Animals; Dose-Response Relationship, Radiation; Keratins; Mathematical Computing; Models, Biological; Radiation Injuries, Experimental; Skin; Skin Diseases; Skin Physiological Phenomena; Swine | 1996 |
The insulin-like growth factor 1 receptor is expressed by epithelial cells with proliferative potential in human epidermis and skin appendages: correlation of increased expression with epidermal hyperplasia.
Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (alpha-IR3) that binds to the alpha-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the follicular outer root sheath, sebaceous glands, and the hair matrix. There was minimal IGF-1 receptor expression in differentiating outer root sheath, hair shaft, and sebaceous epithelial cells. IGF-1 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells. Topics: Cell Division; Eccrine Glands; Epidermal Cells; Epidermis; Epithelial Cells; Epithelium; Humans; Hyperplasia; Immunohistochemistry; In Vitro Techniques; Keratinocytes; Keratins; Receptor, IGF Type 1; Skin; Skin Diseases | 1996 |
Rate of keratinization of the wall segment of the hoof and its relation to width and structure of the zona alba (white line) with respect to claw disease in cattle.
To determine contribution of the wall segment of bovine cattle hoof to horn production, and relevance of structural differences of the wall segment and its horn production rate to claw disease.. Epidermis and papillary body of the wall segment were examined by mesoscopy, light microscopy, and transmission and scanning electron microscopy. Morphometry of the entire length of the zona alba was examined, and the horn production rate of the wall segment was calculated.. Mixed-breed, dual purpose (beef and dairy) cattle of either sex, and young (20 months) Holstein-Friesian beef bulls.. Blocks of a strip of the hoof from the coronary segment to the sole margin, including epidermis and dermis, were prepared for light and transmission electon microscopy. Prepared specimens of the wall-sole border were examined by scanning electron microscopy. Morphometry was performed on the outer, middle, and inner parts of the zona alba structures on unfixed horn specimens of beef bull claws. After removal of the zona alba specimens, the claw was removed and the proximodistal extent of the epidermal leaflets was measured and analyzed statistically.. Horn production increased in the distal half of the wall segment, was greatest at the wall-sole border, and highest above the abaxial end of the zona alba. High horn production resulted in an incompletely keratinized, softer horn.. High horn production at the zona alba increases susceptibility to vascular disturbance. Claw dyskeratoses appear first in areas of high horn production, areas which are also subject to a greater frequency of claw lesions. Topics: Animals; Cattle; Cattle Diseases; Epidermal Cells; Epidermis; Female; Foot Diseases; Hoof and Claw; Keratins; Male; Skin; Skin Diseases | 1996 |
Differentiation-associated localization of small proline-rich protein in normal and diseased human skin.
The expression of SPRR (small proline-rich protein) was investigated in normal human skin and in diseased skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, naevus pigmentosus, ichthyosis vulgaris and several inflammatory skin diseases, by immunohistochemical staining. A polyclonal antibody was raised against a synthetic peptide for a C-terminal common region for SPRR1 and SPRR3. In immunoblot analysis, a positive band of 18 kDa was detected, which showed the presence of SPRR1 in human epidermal keratinocytes. In normal epidermis, positive staining for SPRR was observed in keratinocytes in the granular layer and the uppermost or two spinous cell layers, with no staining of the other spinous or basal layers. The staining was obvious at the cell periphery, weak at the cytoplasm, and absent in the nucleus. Staining was observed in several outer layers of the follicular infundibulum to the isthmus. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, eccrine duct, melanocytes, Langerhans cells or fibroblasts. The arrectores pilorum, striated muscles, muscle layers of vessels, and myoepithelia of eccrine gland, were weakly stained. In psoriatic skin, stained keratinocytes were distributed in the spinous cell layers except for the basal layer. In ichthyosis vulgaris, SPRR was barely expressed in the uppermost living cell layers of the epidermis. In epidermolytic hyperkeratosis, degenerated squamous cells widely expressed SPRR. In Darier's disease, dyskeratotic cells were clearly stained. In squamous cell carcinoma, staining was observed in keratotic cells around horny pearls. In basal cell epithelioma, naevus pigmentosus, and malignant melanoma, the tumour cells or naevus cells were not stained. The distribution of SPRR was similar to that of involucrin in normal and several diseased skin, except for ichthyosis vulgaris. We conclude that SPRR is expressed in close association with epidermal differentiation in normal skin and skin diseases. The alteration of the expression of the proteins correlated to terminal differentiation, and differs from disease to disease. Topics: Adult; Aged; Amino Acid Sequence; Cell Differentiation; Cornified Envelope Proline-Rich Proteins; Dermatitis; Epidermis; Female; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Molecular Sequence Data; Proteins; Psoriasis; Skin; Skin Diseases; Skin Neoplasms | 1996 |
Intermediate- and low-molecular-weight keratin detection with the monoclonal antibody MNF116. An immunohistochemical study on 232 paraffin-embedded cutaneous lesions.
Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and tumors composed of basaloid keratinocytes in paraffin sections of formalin-fixed tissue. We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely-processed skin lesions with MNF116 and compared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a leiomyosarcoma) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly-differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas. We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Melanoma; Molecular Weight; Paraffin Embedding; Prospective Studies; Retrospective Studies; Skin Diseases; Skin Neoplasms | 1996 |
Mucinous syringometaplasia. An immunohistochemical and ultrastructural study of a case.
Mucinous syringometaplasia (MS) is an unusual skin lesion of unknown etiology, characterized histologically by epidermal invaginations lined by mucin-laden goblet-like cells and by nonkeratinized squamous cells. The present case study was performed to elucidate further the characteristics of this lesion using immunohistochemistry and electron microscopy. The mucin-laden cells in the MS lesion stained positively for carcinoembryonic antigen, epithelial membrane antigen, and low molecular weight keratins. The ultrastructural examination, which was performed on deparaffined sections, revealed two morphological variants of mucous granules. Electron-dense mucous granules predominated in the mucus-containing cells, which were situated among the keratinocytes adjacent to the epidermal invaginations, mostly in the lower parts of the epidermis. Larger, electron-lucent granules containing flocculent material were found more abundantly in the cells lining the epidermal invaginations. Also, some of the mucus-containing cells showed bundles of tonofilaments; structures that appeared to be isolated short, stubby microvilli; and attachments to adjacent mucus-containing cells and keratinocytes by desmosomes. The ultrastructural and immunohistochemical findings in our case suggest that the mucinous changes occurred as a metaplastic process in the resident epidermal cells and were accompanied by changes in cellular antigen expression resembling those of simple secretory epithelium. Topics: Adult; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Microscopy, Electron; Skin Diseases | 1996 |
Subcutaneous cysts: another cause of "failed" spinal anesthesia?
Spinal anesthesia continues to be one of the major techniques in the arsenal of the modern anesthesiologist. Inadequate anesthesia may follow a spinal anesthetic for a variety of reasons. We report a case in which entry of a spinal needle into a subcutaneous cyst mimicked the free flow of cerebrospinal fluid seen with dural puncture. This was confirmed by microscopic examination of the fluid, which was consistent with the contents of a subcutaneous cyst. This represents an unusual cause for failure of spinal anesthesia. Such a possibility should be borne in mind, especially when "clear fluid" return occurs through a spinal needle placed at a relatively superficial depth. Topics: Adult; Anesthesia, Spinal; Cerebrospinal Fluid; Cysts; Exudates and Transudates; Humans; Keratins; Male; Needles; Punctures; Skin Diseases | 1996 |
Evaluation of retinoid lactones as topical therapeutic agents in dermatology.
Optimization of the therapeutic ratio of analogs of the topically active 11-cis, 13-cis-12-hydroxymethylretinoic acid, delta-lactone (1) relative to antihyperproliferation and antihyperkeratinization vs. toxicity.. Nine analogs of 1, in which variations were made in the lipophilic cyclohexenyl moiety or in the lactone ring, were evaluated for topical activity against hyperkeratinization, inhibition of TPA-induced DNA synthesis and for skin irritation.. Although more potent lactones than the parent lactone 1 were identified, none possessed the favorable therapeutic ratio associated with 1.. The delta-lactone 1 possesses unique molecular features responsible for its desirable therapeutic ratio as an antihyperproliferative and antihyperkeratotic agent. In view of its very low systemic retinoid toxicity and the absence of any systemic toxicity, this lactone may be a good candidate for use in the topical treatment of acne. Topics: Administration, Topical; Animals; Drug Evaluation, Preclinical; Keratins; Lactones; Mice; Retinoids; Skin; Skin Diseases; Tretinoin | 1995 |
[New research findings raises hope for patients with hard-to-treat skin diseases].
Topics: Collagen; Humans; Keratins; Skin Diseases | 1995 |
HLA-linked skin disease: classical HLA genes or novel genes within HLA?
Topics: Alleles; Epidermis; Genes, MHC Class I; HLA-C Antigens; Humans; Keratinocytes; Keratins; Membrane Glycoproteins; Psoriasis; Serine; Skin Diseases; Vitronectin | 1995 |
Cutaneous ciliated cyst: a case report.
We report a case of a cutaneous ciliated cyst in the buttock of a 16-year-old girl. We describe the pathological and immunohistochemical data on this very uncommon skin lesion, whose histogenesis remains a matter of controversy. Topics: Adolescent; Cilia; Epidermal Cyst; Female; Humans; Keratins; Skin Diseases | 1995 |
Basal cell carcinoma associated with a giant comedone.
Topics: Aged; Carcinoma, Basal Cell; Cysts; Humans; Keratins; Male; Skin Diseases; Skin Neoplasms | 1995 |
[Inherited abnormalities of the epidermis caused by mutation of keratins].
The recent identification of keratin mutations as a cause of hereditary disorders of keratinization stresses the importance of an intact cytoskeleton of keratinocytes. Four disorders have reported to be caused by keratin mutations so far: epidermolysis bullosa simplex, bullous congenital ichthyosiform erythroderma, ichthyosis bullosa and epidermolytic palmoplantar hyperkeratosis. Molecular genetic diagnosis of keratin disorders is being introduced into the clinical routine and prenatal diagnosis is possible after 10 weeks of gestation. Topics: Epidermis; Female; Humans; Keratinocytes; Keratins; Male; Molecular Biology; Mutation; Pregnancy; Prenatal Diagnosis; Skin Diseases | 1995 |
Milium-like syringoma in the perianal region.
We report a case of syringoma clinically presenting as milia in the perianal region. Milium-like syringoma is an unusual clinical variant of the tumor, and this is, to our knowledge, the first reported case occurring perianally. Topics: Adult; Anus Neoplasms; Cytoplasm; Diagnosis, Differential; Epidermal Cyst; Epithelium; Female; Humans; Keratins; Skin Diseases; Sweat Gland Neoplasms; Syringoma | 1995 |
'Milia en plaque' in the supraclavicular area.
'Milia en plaque' is an unusual skin disease. Up to date only 6 cases have been reported, and all of them were located in the retro-auricular area. We report herein the first case of milia en plaque developed in the supraclavicular area. The absence of a known aetiologic factor in contrast to the previously published cases suggests that the present case belongs to the group of primary milia. Topics: Adult; Clavicle; Diagnosis, Differential; Epidermal Cyst; Humans; Keratins; Male; Skin Diseases | 1995 |
Epidermal disease: faulty keratin filaments take their toll.
Topics: Epidermolysis Bullosa Simplex; Humans; Hyperkeratosis, Epidermolytic; Keratins; Keratoderma, Palmoplantar; Mutation; Skin Diseases | 1994 |
Filaggrin immunoreactive composite keratohyalin granules specific to acrosyringia and related tumours.
The luminal cell layer of acrosyringia contains heterogeneous globular keratohyalin granules, some of which contain basophilic and eosinophilic components. Using immunoelectron microscopy we found that the majority of the granules, which are basophilic, are strongly reactive to an anti-filaggrin antibody, while the minority, which are eosinophilic, are not. Similar heterogeneous keratohyalin granules were observed in syringomas and in an eccrine syringofibroadenoma. Since such granules are not normally observed in other human cutaneous epithelia, it is suggested that these composite keratohyalin granules with partial filaggrin immunoreactivity might serve as a useful marker for acrosyringial differentiation in both normal and pathological material. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cytoplasmic Granules; Eccrine Glands; Epidermis; Extremities; Female; Fibroadenoma; Filaggrin Proteins; Humans; Hyalin; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Microscopy, Immunoelectron; Middle Aged; Skin Diseases; Sweat Gland Neoplasms; Syringoma | 1994 |
Increased expression of keratin 16 causes anomalies in cytoarchitecture and keratinization in transgenic mouse skin.
Injury to epidermis and other stratified epithelia triggers profound but transient changes in the pattern of keratin expression. In postmitotic cells located at the wound edge, a strong induction of K6, K16, and K17 synthesis occurs at the expense of the keratins produced under the normal situation. The functional significance of these alterations in keratin expression is not known. Here, we report that overexpression of a wild-type human K16 gene in a tissue-specific fashion in transgenic mice causes aberrant keratinization of the hair follicle outer root sheath and proximal epidermis, and it leads to hyperproliferation and increased thickness of the living layers (acanthosis), as well as cornified layers (hyperkeratosis). The pathogenesis of lesions in transgenic mouse skin begins with a reorganization of keratin filaments in postmitotic keratinocytes, and it progresses in a transgene level-dependent fashion to include disruption of keratinocyte cytoarchitecture and structural alterations in desmosomes at the cell surface. No evidence of cell lysis could be found at the ultrastructural level. These results demonstrate that the disruption of the normal keratin profile caused by increased K16 expression interferes with the program of terminal differentiation in outer root sheath and epidermis. They further suggest that when present at sufficiently high intracellular levels, K16, along with K6 and K17, appear capable of inducing a reorganization of keratin filaments in the cytoplasm of skin epithelial cells. Topics: Acantholysis; Amino Acid Sequence; Animals; Cell Adhesion; Cytoskeleton; Desmosomes; Epidermis; Female; Gene Expression Regulation; Hair; Humans; Keratinocytes; Keratins; Male; Mice; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Phenotype; Skin Diseases | 1994 |
A functional "knockout" of human keratin 14.
The importance of keratins and other intermediate filaments in the maintenance of tissue structure is emphasized by the discovery that many hereditary skin-blistering diseases are caused by mutations in keratin genes. Here, we describe a situation in which keratin 14 (K14) is missing altogether in the epidermis: A homozygous 2-nucleotide deletion in exon I of the K14 gene causes premature termination of the mRNA transcripts upstream from the start of the rod domain and results in a K14 null phenotype. In this individual no keratin intermediate filaments are visible in basal epidermal cells, although filaments are present in the upper layers of the epidermis. No compensating keratin expression is detected in vivo, and K14 mRNA is down-regulated. The individual, diagnosed as Köbner (generalized) EBS, suffers from severe widespread keratinocyte fragility and blistering at many body sites, but although the phenotype is severe, it is not lethal. This K14-/- phenotype confirms that only one K14 gene is expressed in human epidermis and provides an important model system for examining the interdependence of different keratin filament systems and their associated structures in the skin. Topics: Amino Acid Sequence; Base Sequence; Biopsy; Cells, Cultured; Consanguinity; DNA Primers; Epidermolysis Bullosa Simplex; Female; Gene Expression; Homozygote; Humans; In Situ Hybridization; Infant; Keratinocytes; Keratins; Male; Molecular Sequence Data; Pedigree; Polymerase Chain Reaction; RNA, Messenger; Sequence Deletion; Skin; Skin Diseases | 1994 |
Tricholemmal carcinoma. A clinicopathologic study of 13 cases.
We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous adnexal neoplasm. The patients were nine men and four women. In general, the tumors presented as slow-growing epidermal papules, indurated plaques, or nodules showing predilection for sun-exposed, hair-bearing skin. The lesions were most frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they showed a variegation of growth patterns including solid, lobular, and trabecular; they were characterized by a proliferation of epithelial cells with features of outer root sheath differentiation, including abundant glycogen-rich, clear cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells with subnuclear vacuolization. Because of their variable growth pattern, overt cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal spread, and brisk mitotic activity, these tumors may pose difficulties for diagnosis and be confused with other malignant skin tumors with clear cell changes. Despite the seemingly malignant cytological appearance of these lesions, clinical follow-up in 10 cases showed no recurrence or metastasis over a period of 2-8 years. Thus, conservative surgical excision with clear margins appears to be the treatment of choice for these neoplasms. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Diagnosis, Differential; Epidermal Cyst; Epithelium; Female; Follow-Up Studies; Glycogen; Hair Diseases; Humans; Keratins; Male; Middle Aged; Mitosis; Neoplasms, Basal Cell; Skin Diseases; Skin Neoplasms; Vacuoles | 1994 |
Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma.
Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response. Topics: Aged; Aged, 80 and over; Antigens, CD; Carcinoma, Squamous Cell; CD3 Complex; CD36 Antigens; CD4 Antigens; Epidermis; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Keratoacanthoma; Lymphocyte Activation; Middle Aged; Platelet Membrane Glycoproteins; Receptors, Interleukin-2; Remission, Spontaneous; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1994 |
[Cutaneous cysts and pseudocysts. I].
Topics: Cysts; Epidermal Cyst; Hair Diseases; Humans; Keratins; Skin Diseases | 1994 |
Keratin 17 expression as a marker for epithelial transformation in viral warts.
The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors. Topics: Biomarkers; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cell Transformation, Viral; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Skin; Skin Diseases; Skin Neoplasms; Warts | 1993 |
Concurrence between the molecular overlap regions in keratin intermediate filaments and the locations of keratin mutations in genodermatoses.
By analysis of the existing available data, we have found that the locations of disease-causing mutations in epidermal keratin genes are distributed in a non-random manner. Most occur in exons 1 and 7 which encode the highly conserved 1A and 2B rod domain sequence regions of the keratin chains. Recent structural studies have suggested these sequences define an important overlap between neighboring molecules in keratin intermediate filaments. In order to better map the extent of these overlap sequences and concurrently to identify those sequences likely to be sensitive to mutations, we have used a series of synthetic peptides in an established filament disassembly assay. Thus residue positions 7-16 of the 1A and positions 107-117 of the 2B rod domain segments describe the extent of the molecular overlap window wherein mutations in keratin (and perhaps other) intermediate filaments are most likely to alter filament stability and lead to abnormalities. Topics: Amino Acid Sequence; Chromosome Mapping; Humans; Intermediate Filaments; Keratins; Male; Molecular Sequence Data; Point Mutation; Skin; Skin Diseases | 1993 |
Transcriptional regulators of expression of K#16, the disease-associated keratin.
In most malignant and benign skin diseases, the normal pattern of keratin expression is altered. Among other phenotypic changes, the expression of hyperproliferation- and activation-associated keratins K#16 and K#6 is induced. Because the molecular mechanisms and the nuclear regulators involved in this induction are unknown, we have characterized the transcriptional regulators of expression of the keratin K#16 promoter. Our previous studies have shown that the transcription of K#16 is strongly and specifically induced in epidermal keratinocytes by epidermal growth factor (EGF), through the EGF-responsive element (RE). In the present work, using an electrophoretic mobility-shift assay, we have found several nuclear protein binding sites that have been identified as an Sp1 site, an AP2 site, the EGF-RE, and an enhancer element. The function of each site was assessed in transfection assays using specific deletions. Both the Sp1 and EGF-RE sites are essential for K#16 promoter activity. The site that functions as an independent enhancer, E, was found adjacent to and interacting with a sequence recognized by the AP2 transcription factor. This knowledge of the nuclear regulators of expression of the disease-associated K#16 keratin provides insight into the molecular parameters that might be important in skin diseases. Topics: Base Sequence; Binding Sites; Cell Line; DNA; DNA-Binding Proteins; Enhancer Elements, Genetic; Epidermal Growth Factor; Gene Expression Regulation; HeLa Cells; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Promoter Regions, Genetic; Sequence Deletion; Skin Diseases; Sp1 Transcription Factor; Transcription Factor AP-2; Transcription Factors | 1993 |
Familial elastosis perforans serpiginosa.
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 | 1993 |
Etretinate therapy for psoriasis and other keratinizing disorders: a 10-year retrospective study in Singapore.
Etretinate, a second generation retinoic acid, has been reported to be useful in the treatment of psoriasis and other keratinizing disorders. The effectiveness of etretinate for these disorders are studied in a 10-year retrospective study of all patients treated with etretinate in a skin clinic in Singapore.. The case records of 190 cases of psoriasis and other keratinizing disorders treated with etretinate were analyzed. Information collected included demographic data, dosage of etretinate taken, response and side effects, clinical follow-up, and relapse.. Most of the cases (72.6%) had psoriasis (138/190). The others had different keratinizing disorders. The dose of etretinate used was 0.15 to 1 mg/kg/day (median 0.36 mg/kg/day), and the duration of the treatment varied from 1 to 120 months (median 6 months). Etretinate was coadministered with UVB (ReUVB) or PUVA (RePUVA) in 89 (46.8%) patients. In psoriasis, the response to treatment was excellent in 41.3% (57/138), good in 36.2% (50/138), fair in 15.9% (22/138), and poor in 6.5% (9/138) of the cases. Patients with plaque-type psoriasis did better with combination therapy than with monotherapy. Those with keratinizing disorders showed excellent, good, fair, and poor responses in 32.7% (17/52), 32.7% (17/52), 25.0% (13/52), and 9.6% (5/52) respectively. Adverse effects were noted in 102 (53.7%) cases and were generally mild and tolerable. Etretinate was discontinued in 24 (12.6%) patients due to significant toxicity.. Etretinate is effective for treating psoriasis and other keratinizing disorders. Combination therapy is preferred in chronic plaque psoriasis. Adverse effects are common, but mild and tolerable. Topics: Adolescent; Adult; Child; Etretinate; Female; Humans; Keratins; Male; Middle Aged; Psoriasis; Retrospective Studies; Skin Diseases | 1993 |
Should you throw away this issue?
Topics: DNA; Forecasting; Humans; Keratins; Molecular Biology; Periodicals as Topic; Polymerase Chain Reaction; RNA, Ribosomal; Skin Diseases | 1993 |
Alu polymorphism in the human type I Keratin (KRT14) gene.
Topics: Base Sequence; Chromosome Mapping; Chromosomes, Human, Pair 17; Epidermolysis Bullosa Simplex; Humans; Introns; Keratins; Molecular Sequence Data; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; Skin Diseases | 1992 |
Ultrastructural changes in acquired perforating dermatosis.
We performed ultrastructural studies of skin lesions in seven adults with acquired perforating dermatosis. Three of the patients had diabetes mellitus and two were undergoing hemodialysis. Lesions in an early stage showed exocytosis of inflammatory cells and alteration of elastic fibers. Lesions in an intermediate stage featured discontinuities of the basement membrane and aggregates of electron-dense material lateral to the perforated focus, together with dermal edema, scattered macrophages, and densely aggregated collagen fibers that focally filled the papillary dermis. Later-stage lesions showed fibroblasts in the dermis and degenerated elastic fibers within transepidermal channels. In most cases there was a single large epidermal channel lined by flattened epithelial cells, and containing a variety of cellular and extracellular materials. Small "secondary" channels without abnormal keratinization were also observed within the epidermis. The findings suggest that altered keratinization is limited to the immediate vicinity of well-formed transepidermal channels, and that exocytosis of inflammatory cells and alterations of elastica are early and possibly key changes in lesion development. The unexpected discovery of hair fragments in one case suggests that curled hairs may play a role in the pathogenesis of some cases of acquired perforating dermatosis. Topics: Adult; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Skin; Skin Diseases | 1992 |
Scarring alopecia in discoid lupus erythematosus.
The clinicopathological features of the scarring alopecia of discoid lupus erythematosus (DLE) were studied. Scarring alopecia was present in 34% of 89 patients with DLE and was associated with a prolonged disease course. More than half these patients had scalp involvement at the onset of the disease. There was a significant reduction in size of sebaceous glands in affected scalp. Perifollicular lymphocytic inflammation was maximal around the mid-follicle at the level of the sebaceous gland, which seems to be an important functional level in the follicle. There are changes in the expression of the matrix molecules, the proteoglycans, in the connective tissue sheath and the keratin intermediate filaments in the outer root sheath cells at this level in normal scalp and in diseased scalp. Loss of a population of mid-follicular stem cells may be important in the pathogenesis of scarring alopecia in DLE. Topics: Adolescent; Adult; Aged; Alopecia; Chronic Disease; Female; Humans; Immunohistochemistry; Keratins; Lupus Erythematosus, Discoid; Male; Middle Aged; Scalp; Sebaceous Glands; Skin Diseases | 1992 |
Cell kinetics in skin disorders with disturbed keratinization.
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 | 1992 |
Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease.
To explore the relationship between keratin gene mutations and genetic disease, we made transgenic mice expressing a mutant keratin in the basal layer of their stratified squamous epithelia. These mice exhibited abnormalities in epidermal architecture and often died prematurely. Blistering occurred easily, and basal cell cytolysis was evidence at the light and electron microscopy levels. Keratin filament formation was markedly altered, with keratin aggregates in basal cells. In contrast, terminally differentiating cells made keratin filaments and formed a stratum corneum. Recovery of outer layer cells was attributed to down-regulation of mutant keratin expression and concomitant induction of differentiation-specific keratins as cells terminally differentiate, and the fact that these cells arose from basal cells developing at a time when keratin expression was relatively low. Collectively, the pathobiology and biochemistry of the transgenic mice and their cultured keratinocytes bore a resemblance to a group of genetic disorders known as epidermolysis bullosa simplex. Topics: Animals; Epithelium; Humans; Intermediate Filament Proteins; Keratins; Mice; Mice, Transgenic; Mutation; Phenotype; Skin; Skin Diseases | 1991 |
Idiopathic scrotal calcinosis is idiopathic.
The appearance of calcific masses within the dermis of scrotal skin is generally referred to as idiopathic scrotal calcinosis. There has been some debate about the pathogenesis of these calcium deposits. This debate centers on the question of whether the calcium deposition is truly idiopathic or whether it occurs as a result of preexisting epidermal cysts. We have performed immunohistochemical staining for keratin in nine patients with apparent idiopathic scrotal calcinosis and have found no evidence of keratin in the dermal tissue immediately adjacent to the calcium deposits. We conclude that idiopathic scrotal calcinosis is idiopathic. Topics: Adolescent; Adult; Aged; Calcinosis; Epidermal Cyst; Genital Diseases, Male; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Scrotum; Skin Diseases | 1991 |
Cutaneous trichilemmal cysts in three dogs.
Cutaneous trichilemmal cysts were recognized in 3 dogs. The lesions were multiple, asymptomatic, and occurred over the dorsal lumbar, lateral thoracic, dorsal neck, and cranial carpal regions. These cysts were not accompanied by other disease processes, and did not recur following surgical excision. Histologically, the trichilemmal cyst is characterized by trichilemmal differentiation of the entire cyst wall, and the formation of a predominantly amorphous and nonlaminated keratin in the cyst cavity. Topics: Animals; Cysts; Dog Diseases; Dogs; Female; Keratins; Male; Skin Diseases | 1991 |
Tenascin expression in human dermis is related to epidermal proliferation.
The extracellular matrix glycoprotein tenascin is sparsely distributed in normal human dermis. The authors have shown that in a number of skin diseases (psoriasis, skin tumors), tenascin expression is strongly increased. In this immunohistochemical study, using polyclonal and monoclonal antisera, we have tested the hypothesis that tenascin expression in vivo is linked to epidermal proliferation. Using the sellotape stripping model in normal human skin, which causes a rapid recruitment of keratinocytes into the cell cycle, induction of tenascin expression was found in the upper dermis within 24 hours after stripping. In contrast, in normoproliferative monogenic disorders of keratinization (X-linked recessive ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar ichthyosis), no increase in tenascin expression was found compared with normal skin. These findings demonstrate a relationship between epidermal proliferation and metabolic alterations in the dermal compartment. Topics: Cell Adhesion Molecules, Neuronal; Cell Division; Epidermal Cells; Epidermis; Extracellular Matrix; Extracellular Matrix Proteins; Fibronectins; Gene Expression; Humans; Ichthyosis; Immune Sera; Immunohistochemistry; Keratinocytes; Keratins; Skin Diseases; Tenascin | 1991 |
Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.
The promoter region of the suprabasal keratin 10 gene has been used to direct expression of a mutant human Harvey-ras oncogene to the differentiating cells of the mouse epidermis. Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo. Papillomas subsequently develop on the skin surface, initially at sites subject to biting or scratching such as the base of the tail or behind the ears. The results suggest that the "second event" involved in tumor development in these transgenic animals is the local induction of a mild wounding stimulus. Furthermore, because the H-ras transgene is expressed in suprabasal cells, it appears that cells which have left the stem cell compartment can be induced to form at least benign tumors in vivo. Topics: Animals; Chromosome Mapping; Cloning, Molecular; Epidermis; Gene Expression; Genes, ras; Keratins; Mice; Mice, Transgenic; Papilloma; Promoter Regions, Genetic; Skin; Skin Diseases; Skin Neoplasms; Stomach; Wound Healing | 1990 |
The sweat gland in graft versus host disease.
Sweat gland abnormalities occur much more frequently than hitherto described in cutaneous graft versus host disease (GVHD). Two patterns of abnormalities were identified in 80 per cent of cases of acute GVHD: a cytopathic pattern consisting of a combination of basal vacuolopathy with or without lymphocytic infiltration and basal cell degeneration, and a proliferative pattern consisting of basal cell hyperplasia. In chronic GVHD, complete sweat gland destruction with fibrosis was commonly observed. Squamous metaplasia and dilation of the sweat glands were less frequently identified. Ki67 immunostaining confirmed proliferative activity in the basal cells of the distal duct. HLA-DR antigens were expressed on the basal cells of the duct and secretory glands in acute GVHD but not in normal skin. Langerhans cells were absent in both normal and abnormal sweat glands. The role of HLA-DR or Langerhans cells in the initiation of GVHD is questioned in the light of the new data and the primary involvement of proliferating cells is confirmed. Topics: Acute Disease; Adolescent; Adult; Aged; Cell Survival; Child; Child, Preschool; Chronic Disease; Female; Graft vs Host Disease; Humans; Hyperplasia; Keratins; Male; Middle Aged; Skin Diseases; Sweat Glands | 1990 |
Papules in the auricular concha: lichen amyloidosus in a case of biphasic amyloidosis.
We present a patient with lichen amyloidosus on the ears and macular amyloidosis on the back. These diagnoses were supported by histological, histochemical and immunohistochemical studies. This is to the best of our knowledge the first reported case of a biphasic form of amyloidosis whose lichenoid counterpart consists of papules on the ears. This suggests that primary cutaneous localized amyloidosis may have peculiar clinical manifestations depending on the location of the lesion. Topics: Amyloidosis; Ear Diseases; Ear, External; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Skin Diseases | 1990 |
Proliferating trichilemmal cyst with spindle cell carcinoma.
We report a 58-year-old woman with proliferating trichilemmal cyst (PTC), from which a spindle cell carcinoma arose. The tumor on her scalp had been removed at another hospital. Histological examination had revealed almost typical features of PTC. However, the case showed a partial transformation to spindle cell carcinoma, and transition zones between squamous epithelium and spindle cells were present. Three months after histologic examination, the patient came to us for the treatment of recurrent tumor. Despite surgical resection, the patient died as a result of distant metastases. Histologically, the recurrent tumor was composed of only spindle-shaped tumor cells. We describe the first example of this uncommon condition. Topics: Carcinoma; Diagnosis, Differential; Epidermal Cyst; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Skin Diseases; Skin Neoplasms | 1990 |
An investigation of cytokeratin expression in skin epithelial cysts and some uncommon types of cystic tumours using chain-specific antibodies.
The differentiation state of skin epithelial cysts and some uncommon types of epithelial skin tumours was investigated by immunohistochemical staining, mainly using cytokeratin (CK) polypeptide-specific monoclonal antibodies. Samples of interfollicular epidermis, hair follicles and eccrine sweat glands were included as reference tissues. The CK reactivity in epidermoid cysts and milia is not restricted to CKs involved in epidermal-type differentiation, i.e. CK1, 5, 10 and 14, but in addition CK16, a hyperproliferative keratinocyte marker is suprabasally expressed. CK1 and 10 are other prominent suprabasal markers, while CK14 seems to be preferentially expressed in the basal cell layer. Of the non-epidermal CKs, only CK4 was focally or more extensively detected in about 50% of the cases. In terms of CK reactivity, keratinization of trichilemmal cysts corresponds to the keratinization of the anagen-phase hair follicle in the isthmus. The CK reactivity is again restricted to CK1, 5, 10, 14 and 16. However, the CK1 as well as CK10 reactivity is subject to serious limitations, since both CKs were only convincingly observed in foci of terminal differentiation. Eccrine hydrocystoma obligatorily expresses a complex CK set, including CK7, 8, 14, 18 and 19. This CK set perfectly corresponds to the CK composition observed in acini of eccrine sweat glands. In addition, a discontinuous CK4 and 16 reactivity was seen in about 50% of the sites, while CK1 and 10 displayed a strictly focal appearance. On the other hand, syringoma produces in its distinct structures, a CK pattern reminiscent of the one observed in eccrine sweat gland ducts and includes CK1, 5, 10, 14, 16 and 19.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Antibodies, Monoclonal; Antibody Specificity; Cysts; Epidermal Cyst; Epithelium; Gene Expression; Humans; Immunohistochemistry; Keratins; Peptides; Skin; Skin Diseases; Skin Neoplasms | 1990 |
Characterization of keratinocyte plasminogen activator inhibitors and demonstration of the prevention of pemphigus IgG-induced acantholysis by a purified plasminogen activator inhibitor.
To investigate the mechanisms by which cutaneous plasminogen activator (PA) may be regulated, we have tested cultured keratinocytes for the presence of PA inhibitors. Using biosynthetic labeling experiments with 35S-methionine in conjunction with specific antibody precipitation, we have shown that human keratinocytes in culture synthesized and secreted both PA inhibitor 1 and PA inhibitor 2. PA inhibitor 1 was present in conditioned media in the inactive form, but it could be detected with reverse phase autography. PA inhibitor 2 was detected by its ability to form complexes with 125I-uPA. Potential therapeutic relevance for cutaneous PA inhibitor 2 was suggested in skin organ culture experiments which demonstrated that purified PA inhibitor 2 from human placenta was able to prevent the acantholytic changes induced by pemphigus IgG. Topics: Acantholysis; Cells, Cultured; Culture Techniques; Epidermal Cells; Epidermis; Glycoproteins; Humans; Immunoglobulin G; Keratins; Pemphigus; Plasminogen Activators; Plasminogen Inactivators; Skin Diseases; Urokinase-Type Plasminogen Activator | 1989 |
Focal acantholytic dyskeratosis in condyloma acuminata.
Focal acantholytic dyskeratosis (FAD) is considered an incidental histological finding of unknown etiology. It has been described in association with only few pathological conditions. To the best of our knowledge, we report the first case of focal acantholytic dyskeratosis occurring in condyloma acuminata. Topics: Acantholysis; Adult; Biopsy; Condylomata Acuminata; Genital Diseases, Male; Humans; Keratins; Male; Skin Diseases | 1989 |
Focal acantholytic dyskeratosis occurring in pityriasis rubra pilaris.
Focal acantholytic dyskeratosis (FAD) is a distinctive histologic pattern characterized by suprabasilar clefts surrounding dermal papillae (villi), acantholytic and dyskeratotic cells at all levels of the epidermis, hyperkeratosis, and parakeratosis. The features of FAD are typically seen in Darier's disease, warty dyskeratoma, and transient acantholytic dermatosis; they are also present in a variety of cutaneous neoplastic and nonneoplastic lesions. FAD, however, has not been previously described in lesions of inflammatory dermatoses. We report a case of FAD occurring in lesions of pityriasis rubra pilaris (PRP). To the best of our knowledge, this is the first reported case of this kind. We also review the pertinent literature. Topics: Acantholysis; Epidermal Cells; Humans; Keratins; Male; Middle Aged; Pityriasis Rubra Pilaris; Skin Diseases | 1989 |
In vivo binding site of pemphigus vulgaris antibodies and their fate during acantholysis.
Ultrastructural localization of pemphigus vulgaris antigen-antibody complexes and their fate during acantholysis were studied in epidermal sheets obtained from the area surrounding the bullae and in acantholytic cells in blister fluid. The distribution of pemphigus vulgaris antibodies already bound to the keratinocytes in early acantholytic lesions was detected with ferritin-conjugated goat antihuman IgG. Ferritin particles were observed on the surface of keratinocytes with particular affinity for desmosomal structures. The acantholytic cells in the blister fluid bound only a small number of ferritin particles on their surface. During incubation at 37 degrees C, pemphigus vulgaris antigen-antibody complexes on the surface of separated desmosomes were internalized and recognized in cytoplasmic vesicles. Endocytosis of separated desmosomes also was observed in vivo when freshly obtained epidermal sheets were immediately processed for routine electron microscopic study. These findings suggest that pemphigus vulgaris antibodies are densely located on desmosomes and that the antigen-antibody complexes, together with other serum proteins on the keratinocyte surface, are internalized by a process of endocytosis. Topics: Acantholysis; Binding Sites, Antibody; Epidermis; Humans; Keratins; Pemphigus; Skin Diseases | 1989 |
Seborrheic keratosis with focal acantholysis.
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 | 1989 |
Altered keratin expression in benign and malignant skin diseases revealed with monoclonal antibodies.
We studied keratin expression in benign epidermal skin diseases, and in Bowen's disease by using three monoclonal cytokeratin antibodies. In adult normal skin, these antibodies bind only to the follicular epithelium (PKK1), the basal keratinocytes (PKK2), or the suprabasal cells in interfollicular epidermis (KA5). Additionally, in fetal epidermis, the PKK1 antibody reacts with basal keratinocytes. In psoriasis and lichen planus, the PKK2 antibody distinctly revealed all epidermal cell layers by immunostaining. However, a negative basal cell-like layer was revealed in both lesions with the KA5 antibody. In pityriasis rubra pilaris, the basal cell layer was uniformly stained with the PKK2 antibody, but only some keratinocytes in upper cell layers showed fluorescence and, in chronic eczema, the 3-4 lowest epidermal cell layers were reactive. The PKK1 antibody did not stain interfollicular keratinocytes in any of the benign proliferative skin diseases studied. In Bowen's disease, a heterogeneous staining pattern with varying intensity among individual cells was seen with all of the antibodies used. Our results suggest different changes in keratin expression in chronic benign and malignant epidermal diseases that may reflect the mechanisms behind these changes. Topics: Antibodies, Monoclonal; Bowen's Disease; Carcinoma, Squamous Cell; Epidermal Cells; Fluorescent Antibody Technique; Humans; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms | 1989 |
Stereotyped distribution of proliferating keratinocytes in disorders affecting the epidermis.
We used the technique of autoradiography after incorporation of tritiated thymidine (3H-TdR) to evaluate keratinocyte proliferation in basal, epibasal, and other epidermal layers in 30 diseases affecting the epidermis. The number and proportion of 3H-TdR-labeled keratinocytes were counted in the different layers of the epidermis. Significant correlations were found between the proliferative indices of the different epidermal layers. Such links indicate that the epidermis responds in a rather stereotyped way to various pathological conditions. There exists some regulation in the distribution, number, and proportion of 3H-TdR-labeled keratinocytes in the various layers of the epidermis. Topics: Epidermal Cells; Humans; Keratins; Reference Values; Skin Diseases; Statistics as Topic; Thymidine; Tritium | 1989 |
The use of retinoic acid to probe the relation between hyperproliferation-associated keratins and cell proliferation in normal and malignant epidermal cells.
When cells from normal human epidermis and from the human squamous cell carcinoma line SCC-13 were seeded on floating rafts of collagen and fibroblasts, they stratified and underwent terminal differentiation. Although the program of differentiation in SCC-13 cells was morphologically abnormal, the cultures resembled normal epidermal raft cultures by expressing the terminal differentiation-specific keratins, K1/K10, and by restricting their proliferative capacity to the basal-like cells of the population. In addition, the differentiating cells of both normal and SCC-13 raft cultures expressed keratins K6 and K16, which are not normally expressed in epidermis, but are synthesized suprabasally during wound-healing and in various epidermal diseases associated with hyperproliferation. While the behavior of normal and SCC-13 rafts was quite similar when they were cultured over normal medium, significant biochemical differences began to emerge when the cultures were exposed to retinoic acid. Most notably, while the SCC-13 cultures still stratified extensively, they showed a marked inhibition of both abnormal (K6/K16) and normal (K1/K10) differentiation-associated keratins, concomitantly with an overall disappearance of differentiated phenotype. Surprisingly, the reduction in K6/K16 in retinoid-treated SCC-13 cultures was not accompanied by a decrease in cell proliferation. Using immunohistochemistry combined with [3H]thymidine labeling, we demonstrate that while the expression of K6 and K16 are often associated with hyperproliferation, these keratins are only produced in the nondividing, differentiating populations of proliferating cultures. Moreover, since their expression can be suppressed without a corresponding decrease in proliferation, the expression of these keratins cannot be essential to the nature of the hyperproliferative epidermal cell. Topics: Blotting, Northern; Carcinoma, Squamous Cell; Cell Division; DNA; Electrophoresis, Gel, Two-Dimensional; Epidermal Cells; Epidermis; Gene Expression Regulation; Humans; Hyperplasia; Keratins; Molecular Weight; Skin Diseases; Tretinoin; Tumor Cells, Cultured | 1989 |
Eruptive infundibulomas. A distinctive presentation of the tumor of follicular infundibulum.
Hundreds of asymptomatic pale erythematous lesions, 2 to 15 mm in diameter, with complex angulated shapes in a mantle distribution over the upper portion of the chest and back and the shoulders, developed in two unrelated young men. Actinic porokeratosis, discoid lupus erythematosus, pityriasis versicolor, and acne scars were considered as possible diagnoses, but none of these appeared appropriate. Multiple skin biopsy specimens from both patients showed tumors of follicular infundibulum (infundibulomas), benign platelike proliferations of the external root sheath that were outlined by a prominent brushlike elastic network. This presentation of the tumor of follicular infundibulum can be recognized by its unusual clinical pattern and histopathology. Topics: Adult; Biopsy; Diagnosis, Differential; Elastic Tissue; Etretinate; Humans; Keratins; Male; Pigmentation Disorders; Skin; Skin Diseases; Sunlight | 1989 |
Keratinocyte expression of OKM5 antigen in inflammatory cutaneous disease.
Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness. Topics: Adult; Antigens, Differentiation; CD36 Antigens; Dermatitis, Atopic; Epidermis; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Lymphoma; Monocytes; Psoriasis; Skin Diseases; Skin Neoplasms | 1989 |
Distribution patterns of the OKM 5 antigen in normal and diseased human epidermis.
The distribution of OKM 5-positive dendritic cells in the epidermis was investigated in 75 cases of inflammatory dermatoses and in 14 cases of normal human skin by immunohistochemical and morphometric methods. Furthermore 6 cases of normal human skin, 14 cases of nevocellular nevi, 26 cases of malignant melanoma, 7 cases of contact dermatitis and 6 cases of mycosis fungoides have been examined with special emphasis on the expression of OKM 5 antigen on keratinocytes. OKM 5-positive dendritic cells were present in normal human epidermis at a density of 46 +/- 3.4 cells/mm2 section area. However, there was a significant increase in cutaneous drug eruptions (166 +/- 17.2 cells/mm2; U-test: p less than or equal to 0.05). Concerning OKM 5-positive keratinocytes, a mean percentage of 10.2% +/- 5.0% OKM 5-positive keratinocytes was found in nevocellular nevi, compared to 0.5% +/- 0.5% in the adjacent skin. The corresponding values for malignant melanomas were 52.5% +/- 3.4% (lesional epidermis) and 7.1% +/- 2.2% (adjacent epidermis). There were significant differences of both lesional and adjacent epidermis between nevi and melanomas (U-test: p less than or equal to 0.05). Our cases of contact dermatitis revealed a mean percentage of 19.3% +/- 6.7% OKM 5-positive keratinocytes, whereas in mycosis fungoides the corresponding value represents 42.7% +/- 6.2%. The differences between the percentage of OKM 5-positive keratinocytes in normal epidermis and contact dermatitis as well as mycosis fungoides were significant (U-test).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Antibodies, Monoclonal; Antigens, Surface; Dendritic Cells; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Skin Diseases | 1989 |
[X-linked dyskeratosis congenita with aplastic anemia--genetic and hematologic studies].
Two brothers in a Chinese family were affected with dyskeratosis congenita (DC). The proband's stepbrother died of pancytopenia and rectal adenocarcinoma. The proband with progressive pancytopenia was studied in genetics and hematology. Family investigations suggest that the disorder was inherited as an X-linked recessive transmission. No specific chromosome aberrations were detected in both peripheral blood and bone marrow cells. Bone marrow biopsy revealed markedly hypocellular marrow without prominent reticulin fibers. Hematopoiesis was assessed by assay of granulomonocytic (CFU-GM) colonies and clusters in vitro. Numbers of CFU-GM were profoundly reduced in marrow cultures from our patient. Although a defect in the stromal microenvironment and lymphocyte mediated suppression could not be excluded. It is possible that the defect is intrinsic to the hematopoietic stem cells. The familial disease described by this paper favors that the dyskeratosis congenita is X-linked with constitutional aplastic anemia. It is believed that the pancytopenia with hypocellular marrow in DC is an inherited rather than an acquired condition. Topics: Adolescent; Anemia, Aplastic; Genetic Linkage; Hematopoiesis; Humans; Keratins; Male; Skin Diseases; X Chromosome | 1989 |
Are hyperlinear palms and dry skin signs of a concomitant autosomal ichthyosis vulgaris in atopic dermatitis?
In 30% to 40% of cases atopic dermatitis (AD) is believed to be associated with autosomal dominant ichthyosis vulgaris (ADI). The diagnosis of ADI can be proved by the ultrastructural demonstration of a defective keratohyalin (KH) synthesis, resulting in minute granules of crumbly appearance in only one layer of granular cells. To investigate the suggested frequent association of ADI with AD, ultrastructural examination of dry skin of 49 AD patients was performed. Only in 2 patients abnormal KH was demonstrated by electron microscopy. 17 patients, including the 2 patients with abnormal KH, showed hyperlinear palms. The present study shows that hyperlinear palms and dry skin are in most cases a phenotypic marker of AD alone and not a sign of concomitant ADI. A histologically one-layered or absent stratum granulosum may occur in the dry skin of patients with only AD and does not indicate a manifestation of concomitant ADI in all cases. Topics: Adolescent; Adult; Dermatitis, Atopic; Female; Foot Dermatoses; Hand Dermatoses; Humans; Hyalin; Ichthyosis; Keratins; Male; Skin; Skin Diseases | 1989 |
Keratosis punctata palmaris et plantaris as an expression of focal acantholytic dyskeratosis.
An 11-year-old girl affected by keratosis punctata palmaris et plantaris, histologically showing focal acantholytic dyskeratosis, is described. This case demonstrates that keratosis punctata palmaris et plantaris may represent a new clinical expression of persistent multiple focal acantholytic dyskeratosis. Topics: Acantholysis; Biopsy; Child; Female; Humans; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Skin; Skin Diseases | 1989 |
A unique phospholipase A2 in human epidermis: its physiologic function and its level in certain dermatoses.
It is now well established that epidermis, like many other tissues, contains a phospholipase A2 that is responsible for the initiation of the arachidonic acid cascade. Here we report that human epidermis also contains a second, quite distinct enzyme of the phospholipase A2 group, which is unique in its extreme activity against phospholipids in true solution. It also differs from the classic cutaneous enzyme in that (a) its activity is not reduced by pretreatment of the skin with corticosteroids in vivo nor by treatment of the epidermal homogenate with alkaline phosphatase in vitro, and (b) its activity is reduced, rather than increased, in the lesions of inflammatory diseases such as psoriasis. The enzyme seems to occur mainly in fully differentiated keratinocytes, its level being low in the basal cell layer of epidermis and in keratinocytes cultured in vitro. On the basis of these observations, we suggest that this new phospholipase A2 is responsible for the degradation of phospholipids that accompanies the terminal keratinization process. Topics: Alkaline Phosphatase; Cells, Cultured; Clobetasol; Eczema; Epidermis; Humans; Keratins; Lichen Planus; Phospholipases; Phospholipases A; Phospholipases A2; Psoriasis; Skin Diseases; Trypsin | 1988 |
Reaction of human keratinocytes with the monoclonal antibody anti-Leu-11: an immunohistologic study.
Biopsy specimens from skin of 99 patients with 26 different dermatoses and 17 specimens from normal skin were labeled with regard to the reactivity of keratinocytes with the monoclonal natural killer-associated antibody anti-Leu-11b by means of the avidin-biotin-peroxidase complex method. Reactivity occurred in 64.7% of the preparations from normal skin and in 84.8% of the preparations from diseased skin. The membranes of the subcorneal keratinocyte layers were labeled regularly. In some of the preparations cytoplasmic reactivity and labeling of the basement membrane zone occurred in addition. Most labeled preparations and the highest labeling intensities were shown in the skin tumors and in the infectious dermatoses. The biologic significance of this finding is discussed. Topics: Antibodies, Monoclonal; Antigens, Surface; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Killer Cells, Natural; Lymphocyte Function-Associated Antigen-1; Skin Diseases; Skin Diseases, Infectious; Skin Neoplasms | 1988 |
Sulfur revisited.
Sulfur is a time-honored therapeutic agent useful in a variety of dermatologic disorders. Its keratolytic action is due to formation of hydrogen sulfide through a reaction that depends upon direct interaction between sulfur particles and keratinocytes. The smaller the particle size, the greater the degree of such interaction and the greater the therapeutic efficacy. When applied topically, sulfur induces various histologic changes, including hyperkeratosis, acanthosis, and dilatation of dermal vasculature. One study showed that sulfur was comedogenic when applied onto human and rabbit skin, findings that were not reproduced in other studies. About 1% of topically applied sulfur is systemically absorbed. Adverse effects from topically applied sulfur are uncommon and are mainly limited to the skin. In infants, however, fatal outcome after extensive application has been reported. Topics: Acne Vulgaris; Chemical Phenomena; Chemistry; Dermatitis, Seborrheic; Epidermis; Humans; Keratins; Skin Diseases; Sulfur | 1988 |
[ELISA in the detection of autoantibodies to epidermal cytokeratins].
Topics: Autoantibodies; Autoimmune Diseases; Enzyme-Linked Immunosorbent Assay; Humans; Keratins; Skin; Skin Diseases | 1988 |
Perforating lichen striatus.
A case of lichen striatus with transepidermal elimination of clusters of necrotic keratinocytes is reported. On the basis of the morphologic findings, we suggest that transepidermal elimination may be a mechanism of healing in some cutaneous lichenoid eruptions. Topics: Biopsy; Child; Epidermal Cells; Female; Humans; Keratins; Necrosis; Skin; Skin Diseases | 1988 |
Dyskeratosis and the dyskeratoses.
Darier first described dyskeratotic cells as infectious agents, but he later wrote that they were caused by abnormal keratinization. He grouped various inflammatory, infectious, and neoplastic skin diseases under the term "dyskeratoses." It is argued herein that the dyskeratotic cell and the so-called dyskeratoses have not been defined in a consistent manner because Darier's concepts were incorrect. Darier's dyskeratotic cell is classified here as one type of necrotic keratinocyte. Some conditions in which dyskeratotic and necrotic keratinocytes occur are described. Topics: Acantholysis; Cell Survival; Darier Disease; Epidermis; France; History, 19th Century; History, 20th Century; Keratins; Skin Diseases; Skin Neoplasms; Terminology as Topic | 1988 |
Recent observations regarding interferon, keratinocytes and lymphocytes in vitro and in vivo.
Topics: Cells, Cultured; Epidermal Cells; Epidermis; HLA-DR Antigens; Humans; Interferons; Keratins; Lymphocytes; Recombinant Proteins; Skin; Skin Diseases | 1988 |
Acantholytic acanthoma.
This article describes 31 examples of acantholytic acanthoma, a newly recognized, solitary, benign cutaneous tumor. Acantholytic acanthoma was typically an asymptomatic, keratotic papule or nodule. Patients ranged in age from 32 to 87 years (median 60 years); the ratio of men to women was 2:1; the most frequent clinical diagnosis was keratosis; and half of the growths were on the trunk of the body. Histologically, the lesions showed hyperkeratosis, papillomatosis, and acanthosis. Acantholysis was an outstanding finding in all cases; the patterns resembled pemphigus vulgaris, pemphigus vegetans, superficial pemphigus, or Hailey-Hailey disease, but no patient had evidence of any of these disorders. The term acantholytic is used because acantholysis is the outstanding histologic feature in these neoplasms; acanthoma was chosen because the growths are benign tumors of epidermal keratinocytes. The relationship of acantholytic acanthoma to acantholytic blistering disease is similar to that of solitary lichen planus-like keratosis to lichen planus and epidermolytic acanthoma to bullous congenital ichthyosiform erythroderma. Topics: Acantholysis; Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Middle Aged; Papilloma; Skin Diseases; Skin Neoplasms | 1988 |
Pagetoid dyskeratosis: a selective keratinocytic response.
Pale cells that resemble those of Paget's disease have been found within apparently normal epidermis in a variety of benign papules. Although they have been considered an artifact, they show characteristic premature keratinization. In contrast to other dyskeratotic processes they mature into orthokeratotic squamae. The histopathologic, ultrastructural and immunocytochemical features of these cells are illustrated, and the differential diagnosis is reviewed. Topics: Adolescent; Adult; Child; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Paget Disease, Extramammary; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1988 |
[Marking disorders of keratinization by means of lectins. II. Keratosis pilaris, lichen spinulosus, porokeratosis, lichen striatus and pityriasis rubra pilaris].
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 | 1988 |
Differential expression of major histocompatibility complex class II antigens on human keratinocytes.
Skin biopsies from 136 patients with 30 different dermatoses and eight biopsies of normal skin were investigated with the avidin-biotin-peroxidase complex method with regard to the expression of major histocompatibility complex class II antigens human leukocyte antigen (HLA) HLA-DR, HLA-DQ, HLA-DP on keratinocytes. In normal skin the expression of these antigens was restricted to acrosyringia and Langerhans cells. In the dermatoses investigated HLA-DR was found in 51.5% (70 of 136), HLA-DQ in 24.3% (33 of 136), and HLA-DP in 20.5% (8 of 39). In 37 cases (27.2%) only HLA-DR could be detected, whereas in 33 cases (24.3%) HLA-DR was expressed jointly with HLA-DQ. Coexpression of HLA-DR and HLA-DQ was found especially often in cutaneous T cell lymphomas, skin tumors, and inflammatory dermatoses. Topics: Epidermis; HLA-D Antigens; HLA-DP Antigens; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Skin Diseases | 1988 |
Warty dyskeratoma appearing in a patient with Darier's disease.
Topics: Acantholysis; Adult; Darier Disease; Epidermis; Female; Humans; Keratins; Skin Diseases | 1988 |
HLA-DR-positive keratinocytes are associated with suppressor lymphocyte epidermotropism. A biomathematical study.
The expression of HLA-DR antigen on keratinocytes has recently been described as a frequent finding in various dermatologic disorders without restriction to a particular entity or a peculiar histologic reaction pattern, except for the association with a mononuclear dermal infiltrate. To determine the relationship of HLA-DR+ keratinocytes and T lymphocyte epidermotropism in human disease in vivo, 82 skin specimens were investigated by immunohistologic and stereologic methods and by two- and three-dimensional linear regression analysis. In randomly selected cases of various dermatoses, HLA-DR+ keratinocytes were associated with T lymphocyte epidermotropism. Furthermore, HLA-DR+ keratinocytes correlated particularly with the proportion of epidermotropic suppressor/cytotoxic cells. Our findings demonstrate that HLA-DR+ keratinocytes are associated with a particular pattern of epidermotropism, which may suggest an interaction of keratinocytes and T suppressor/cytotoxic cells in vivo. Topics: Antibodies, Monoclonal; Epidermal Cells; Epidermis; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Models, Theoretical; Regression Analysis; Skin; Skin Diseases; T-Lymphocytes, Regulatory | 1988 |
Keratinocyte proliferation in wound healing and skin diseases.
Topics: Cell Division; Epidermal Cells; Epidermis; HLA-DR Antigens; Humans; Keratins; Models, Biological; Skin Diseases; Wound Healing | 1988 |
Etretinate for keratin disorders and isotretinoin for acne and not the other way around.
Topics: Acne Vulgaris; Etretinate; Humans; Isotretinoin; Keratins; Papillon-Lefevre Disease; Skin Diseases; Tretinoin | 1987 |
Characterization of two monoclonal antibodies to human epidermal keratohyalin: reactivity with filaggrin and related proteins.
Two monoclonal antibodies (AKH1 and AKH2) were elicited with partially purified human filaggrin and characterized by immunohistochemistry on normal and abnormal skin biopsies, immunoblotting techniques, and antigen purification. Both antibodies react strongly with the granular cell layer consistent with the distribution of keratohyalin and show a more diffuse reaction with the stratum corneum in normal skin biopsies. Reaction in cultured human keratinocytes is limited to immunofluorescent granules in flattened, well-differentiated cells in confluent cultures, in which we have previously demonstrated keratohyalin. On immunoblots AKH1 reacts with filaggrin (37 kD) and profilaggrin (400 kD), while AKH2 primarily stains bands of 150 and 300 kD. The AKH2 antigens were identified in the cationic protein fraction used for immunization and were purified by gel permeation and high-performance liquid chromatography. Amino acid composition of these proteins differs only slightly from filaggrin. Immunohistochemical staining patterns of the two antibodies are very similar in the genetic disorders of keratinization tested, except for ichthyosis vulgaris, and reflect the presence and distribution of keratohyalin. In ichthyosis vulgaris, AKH1 staining is weak, consistent with the morphology and with biochemical absence of profilaggrin/filaggrin; however, AKH2 staining is positive, although weaker than normal, suggesting the presence of the AKH2 antigens even when keratohyalin is absent or abnormal. Antibodies AKH1 and AKH2 may be useful as differentiation markers for keratinization in tissues and for cells in culture. Antibody AKH1 can be used specifically for detection of profilaggrin/filaggrin in tissues, cultured keratinocytes, and extracts. Topics: Antibodies, Monoclonal; Antigens; Cells, Cultured; Epidermis; Filaggrin Proteins; Histocytochemistry; Humans; Immunochemistry; Infant, Newborn; Intermediate Filament Proteins; Keratins; Male; Proteins; Skin Diseases | 1987 |
Arrested epidermal morphogenesis in three newborn infants with a fatal genetic disorder (restrictive dermopathy).
Two sibs and one unrelated infant were born prematurely with taut, shiny, restrictive skin that was abnormal in structure, organization, biochemistry, and state of differentiation. Prominent abnormalities in all regions of the skin were recognized by light and electron microscopy, immunohistochemistry, and biochemistry. The epidermis was hyperplastic, hyperkeratotic, and parakeratotic. Keratohyaline granules were abnormal in structure, but the keratohyalin-derived protein filaggrin was apparently normal in quantity and biochemistry. The epidermal cells contained less than the expected quantity of high-molecular-weight, differentiation-specific keratins and the tissue stained with antikeratin antibodies in an aberrant pattern. Additional 48 and 56 kD keratin polypeptides, indicative of a hyperproliferative state, were expressed. The dermal-epidermal junction was remarkably flat and the dermis was thinner than normal. The connective tissue appeared stretched and was oriented like tendon rather than dermis. Collagen fiber bundles and fibrils were smaller in diameter than normal. The nails were normal but other epidermal appendages such as the pilosebaceous structures and the eccrine sweat glands were underdeveloped, suggesting that morphogenesis of these structures was arrested at an early stage in utero. The subcutaneous fat was at least twice the thickness of the dermis. The skin abnormalities appeared to be the cause of the flexion contractions, characteristic facies, and inability to survive because of restricted respiratory movements. The structural and biochemical abnormalities in the skin of affected infants may serve as markers for prenatal and postnatal diagnosis of the disorder, and may provide insight into the basic mechanism of the disease. Topics: Filaggrin Proteins; Genes, Lethal; Histocytochemistry; Humans; Immunochemistry; Infant, Newborn; Intermediate Filament Proteins; Keratins; Microscopy, Electron; Microscopy, Electron, Scanning; Proteins; Skin; Skin Diseases | 1987 |
Kerosis and comedos without prominent elastosis in Favre-Racouchot disease.
Favre-Racouchot disease often is reported to be characterized by the association of cysts and comedos with prominent solar elastosis. Our histological study of patients who rarely exposed themselves to solar irradiation revealed no association between these signs. We detected only the presence of kerosis, as well as closed and open comedos. There were no true cysts. Actinic damage to the epidermis was absent, and solar elastosis was moderate to discrete. Therefore, the characteristic follicular alterations in Favre-Racouchot disease appear to be independent of and not secondary to solar elastosis. Topics: Adult; Elastic Tissue; Facial Dermatoses; Humans; Keratins; Male; Middle Aged; Sebaceous Glands; Skin Diseases; Sunlight | 1987 |
Immunologic detection of markers of keratinocyte differentiation.
Topics: Epidermis; Humans; Keratins; Keratoacanthoma; Skin Diseases | 1987 |
[Anti-keratin filament autoantibodies].
IgG anti-keratin-filament autoantibodies occur in all human sera and reach high titres in the sera of patients with various cutaneous and non-cutaneous diseases. At indirect immunofluorescence, these autoantibodies may, depending on their titre, appear as 'upper-cytoplasmic' antibodies or 'stratum-corneum' antibodies. In vitro, IgG anti-keratin-filament autoantibodies significantly enhance (as opsonins) the phagocytosis of keratin-filament aggregates by human monocytes and polymorphonuclear leucocytes. They may therefore, also in vivo, play a role in the removal of insoluble extracellular keratin-filament aggregates generated by necrotic or apoptotic cell death. Keratin (Civatte) bodies and deposits of localized cutaneous amyloid are examples of such keratin-filament aggregates that are found in various skin diseases but are also regularly present in large amounts in normal human skin. IgM anti-keratin-filament autoantibodies, which may, at indirect immunofluorescence, appear as 'general cytoplasmic' antibodies, also occur in all human sera and reach high titres in the sera of patients with various diseases. The regular presence of IgM in keratin bodies or deposits of localized cutaneous amyloid therefore probably represents the binding of IgM anti-keratin-filament autoantibodies to their respective antigens. To what extent these in vivo-bound autoantibodies prevent any further damaging reaction by the immune system in response to the liberation of keratin-filament autoantigen is as yet unclear. Topics: Amyloid; Autoantibodies; Autoimmune Diseases; Humans; Immunoglobulins; Keratins; Opsonin Proteins; Phagocytosis; Skin Diseases | 1987 |
A clinicopathological study of Flegel's disease (hyperkeratosis lenticularis perstans).
The clinical and histopathological features of 12 female patients with Flegel's disease were studied. The onset of this dermatosis was delayed until adulthood. The eruption consisted of scaly papules 1-5 mm in diameter which developed principally on the lower legs, upper arms and pinnae. Histopathologically there were discrete foci of hyperkeratosis with some parakeratosis over an attenuated and partially spongiotic epidermis. A genetic influence in this disorder was suggested by its occurrence in sisters in two families and in a mother and daughter. Immunohistochemical and biochemical studies suggested that there is a disorder of keratinocyte proliferation in the disease. Topics: Adolescent; Adult; Epidermis; Female; Humans; Hypertrophy; Keratins; Middle Aged; Skin Diseases | 1987 |
Abnormal keratinization in restrictive dermopathy.
Topics: Antibodies, Monoclonal; Female; Fetal Diseases; Filaggrin Proteins; Histocytochemistry; Humans; Immunochemistry; Infant, Newborn; Intermediate Filament Proteins; Keratins; Male; Pregnancy; Prenatal Diagnosis; Skin Diseases | 1987 |
Keratinocyte grafting: covering of skin defects by separated autologous keratinocytes in a fibrin net.
Topics: Epidermal Cells; Epidermis; Humans; Keratins; Skin Diseases; Transplantation, Autologous | 1987 |
Immunohistochemical study of epidermal Langerhans cells and dermal dendritic cells in benign and malignant skin lesions characterized by a dermal lymphoid infiltrate consisting either of B-cells or T-cells.
Skin biopsies from 43 patients with a rather dense dermal lymphoid infiltrate of either inflammatory or neoplastic nature have been investigated. We studied the number, distribution and immunophenotype of epidermal Langerhans cells and dermal dendritic cells. As previously reported, differences in epidermal Langerhans cell and dermal dendritic cell numbers between skin biopsies with a B-cell infiltrate and skin biopsies with a T-cell infiltrate were found, dendritic cells being more numerous in the latter. The main finding of this study was an uneven distribution of epidermal Langerhans cells and dermal dendritic cells in skin biopsies with a T-cell infiltrate: in skin lesions with an inflammatory lymphoid infiltrate, small clusters of epidermal and dermal dendritic cells admixed with T-lymphocytes (predominantly T-helper/inducer cells) and small blood vessels were present at areas of exocytosis. In skin lesions with a neoplastic lymphoid infiltrate larger, more loosely arranged aggregates of dendritic cells and T-cells were seen. These cell aggregations composed of activated (inflammatory or neoplastic) T-cells and dendritic cells may represent the cutaneous homologue of the secondary T-nodule in the lymph node. Both types of cell aggregates may correspond to the dendritic cell-T cell clusters observed in in vitro induced immune responses. Topics: B-Lymphocytes; Dendritic Cells; Histocytochemistry; HLA-DR Antigens; Humans; Immunochemistry; Keratins; Langerhans Cells; Lymphocytes; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1987 |
[Involucrin. Biological properties and expression in normal and pathological tissues].
Topics: Cell Differentiation; Epidermal Cells; Epidermis; Humans; Keratins; Protein Precursors; Skin Diseases | 1987 |
Rosette-formation in herpes simplex and herpes zoster lesions as demonstrated in Tzanck smears.
Topics: Cytotoxicity Tests, Immunologic; Epidermis; Granulocytes; Herpes Simplex; Herpes Zoster; Humans; Keratins; Lymphocytes; Rosette Formation; Skin Diseases; Skin Diseases, Vesiculobullous | 1987 |
[New methods of treating dermatoses with disordered keratinization processes].
Topics: Drug Evaluation; Etretinate; Humans; Keratins; Lichen Planus; Psoriasis; PUVA Therapy; Retinoids; Skin; Skin Diseases; Time Factors | 1987 |
A monoclonal anti-keratin antibody reactive with amyloid deposit of primary cutaneous amyloidosis.
Topics: Aged; Amyloid; Amyloidosis; Antibodies, Monoclonal; Antibody Specificity; Humans; Immunohistochemistry; Keratins; Male; Skin; Skin Diseases | 1987 |
Keratinocyte HLA-DR expression: the relationship to dermal lymphocytic infiltration.
Topics: Adult; Epidermis; HLA-DR Antigens; Humans; Keratins; Skin Diseases; T-Lymphocytes | 1987 |
Keratoacanthoma and squamous cell carcinoma of the skin: immunohistochemical localization of involucrin and keratin proteins.
Fifteen keratoacanthomas and fifteen squamous cell carcinomas of the skin were examined by immunoperoxidase methods for involucrin and both 45- and 63-kilodalton keratins. Keratoacanthomas showed a relatively homogeneous staining pattern for involucrin; all cells except basal cells stained with mild to moderate intensity. Squamous cell carcinomas disclosed a highly irregular involucrin staining pattern with marked variation in staining intensity from cell to cell. Staining patterns for keratin proteins did not appear to distinguish between keratoacanthomas and squamous cell carcinomas. The 45-kilodalton keratin pattern showed diffuse staining within both keratoacanthomas and squamous cell carcinomas, and the 63-kilodalton keratin pattern consisted of focal staining, mostly of dyskeratotic cells. These results suggest that involucrin may serve as a diagnostic aid in differentiating between squamous cell carcinomas and keratoacanthomas. In addition, other lesions in the differential diagnosis of keratoacanthoma and squamous cell carcinoma were also examined for involucrin. Topics: Adult; Aged; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratoacanthoma; Middle Aged; Neoplasm Proteins; Protein Precursors; Sebaceous Glands; Skin Diseases; Skin Neoplasms; Sweat Glands | 1986 |
Expression of HLA-DR and T6 antigens on keratinocytes and dendritic cells. A comparative immunohistochemical study.
The number, morphology, and distribution of cells with dendritic processes in the epidermis and dermis, as well as the expression of HLA-DR and T6 antigen on keratinocytes in 66 skin biopsy specimens have been studied. In the epidermis, OKT6+ cells with slender dendritic processes predominated in the upper layers and outnumbered OKIa1+ cells with dendritic processes, which were only fragmentarily stained and present throughout all layers. In the dermis, OKIa1+ cells with dendritic processes outnumbered OKT6+ cells with dendritic processes. Cases showing keratinocytic positivity for OKIa1 contained very few epidermal OKIa1+ cells with dendritic processes; cases showing surface staining of keratinocytes with OKT6 contained high numbers of epidermal OKT6+ cells with dendritic processes. We suggest that OKT6 and OKIa1 label distinctive subpopulations of epidermal and dermal dendritic cells and, as such provide complementary data. Topics: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Epidermal Cells; Epidermis; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Skin Diseases | 1986 |
HLA-DR expression on keratinocytes is a common feature of diseased skin.
Biopsy specimens from 185 patients with 52 different skin disorders were investigated by indirect immunofluorescence staining for the presence of HLA-DR bearing keratinocytes and their association with an underlying inflammatory infiltrate and in particular with activated (HLA-DR-positive, Leu-4-positive) T lymphocytes. HLA-DR expression on keratinocytes was demonstrated in 38 dermatoses, including lymphocytic vasculitis, lupus erythematosus, morphea, vitiligo, lichen planus, cutaneous T-cell lymphoma, various infectious dermatoses, allergic contact dermatitis, granulomatous dermatoses, Sweet's syndrome, lichen sclerosus and erythema nodosum. In 27 of these this had not previously been reported. Occurrence of HLA-DR on keratinocytes was invariably linked to the presence of a lymphocytic infiltrate containing numerous activated T-cells (Leu-4 +, HLA-DR +) whereas such infiltrates were not accompanied by HLA-DR expression on keratinocytes in all the dermatoses investigated, as in pseudolymphoma and erythema anulare centrifugum. However, HLA-DR positive keratinocytes were consistently absent in skin disorders lacking any significant lymphocytic infiltration (e.g. leukocytoclastic vasculitis, bullous autoimmune dermatoses, genodermatoses and mastocytosis). Although it has been suggested that HLA-DR-positive keratinocytes are involved in various immune responses of the skin, their exact functional significance is, as yet, unknown. Topics: Epidermis; Fluorescent Antibody Technique; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Keratins; Lymphocyte Activation; Skin; Skin Diseases; T-Lymphocytes | 1986 |
Comparative effects of growth inhibitors on DNA replication, DNA repair, and protein synthesis in human epidermal keratinocytes.
Cultured human epidermal keratinocytes were used as a model system for testing compounds with potential therapeutic effect against hyperproliferative skin disorders. We have investigated whether each test compound caused direct damage to the DNA or inhibited DNA repair and/or seminconservative replication of DNA, as well as its effect on the overall rate of protein synthesis and on expression of specific keratin genes. The following compounds were studied: (a) inhibitors of DNA polymerase alpha [aphidicolin and its derivative aphidicolin glycine], (b) inhibitors of topoisomerases [novobiocin, nalidixic acid, teniposide, etoposide, and 4'-(9-acridylamine) methanesulfon-m-anisidide], (c) modifiers of chromatin structure [sodium butyrate, 3-aminobenzamide, and nicotinamide], (d) inhibitors of calmodulin activation and protein kinase C [chlorpromazine and trifluoperazine]; and (e) drugs used in clinical dermatology [anthralin, fluocinolone acetonide, ketoconazole, and hydroxyurea]. The compounds were tested at concentrations at which they were known from the literature to be effective in their respective actions. Among the groups of compounds studied, the topoisomerase inhibitors were particularly interesting since they caused no detectable damage to DNA but exhibited maximal inhibitory effect on replication combined with minimal inhibition of DNA repair. In addition most of the topoisomerase inhibitors, particularly novobiocin, changed the pattern of gene expression by inhibiting the synthesis of certain keratins and inducing a Mr 67,000 protein in the prekeratin fraction. These properties combined with minimal systemic side effects may encourage the clinical exploration of some topoisomerase inhibitors for antiproliferative therapy of skin disorders. Topics: Anthralin; Aphidicolin; Cells, Cultured; Diterpenes; DNA Repair; DNA Replication; Etoposide; Growth Inhibitors; Humans; Keratins; Molecular Weight; Nalidixic Acid; Novobiocin; Protein Biosynthesis; Skin; Skin Diseases; Topoisomerase II Inhibitors | 1986 |
Reactivity of T lymphotropic retrovirus antibody (12/1-2) in man: comparison of epidermis with other epithelial cells.
The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen. Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens; Carcinoma, Basal Cell; Deltaretrovirus; Epithelium; Humans; Keratins; Lymphoma; Palatine Tonsil; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Thymus Gland | 1986 |
Colloid keratosis. Morphologic characterization of a nonspecific reaction pattern of squamous epithelium.
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 | 1986 |
GP37 expression in normal and diseased human epidermis: a marker for keratinocyte differentiation.
An antiserum prepared against a glycoprotein (GP37) extracted from the upper epidermal layers, was used to stain frozen sections of human oral mucosa, normal and abnormal skin by an indirect immunofluorescence technique. On normal human epidermis, this antiserum mainly reacted with the cytoplasm of granular cells, whereas on buccal mucosa the recognized antigen was observed as scattered dots limited to the upper epithelial layers. In epidermal diseases, alterations in the staining pattern were observed. In psoriasis, the labelling was markedly diminished; in contrast, in lichen planus it was intense and present on the 3-6 uppermost cellular layers. Basal cell epitheliomas were almost negative, except around horn cysts. In Bowen's disease dyskeratotic cells were strongly labelled. In squamous cell carcinomas a clear-cut staining was observed in squamous nests. On cultures, GP37 expression could be induced by growing epidermal cells in vitamin A-depleted medium. The biological significance of the observed staining patterns remains to be precised. Nevertheless, GP37 represents a sensitive marker of epidermal differentiation and may be useful in skin pathology and in in vitro studies. Topics: Animals; Carcinoma, Squamous Cell; Epidermal Cells; Fluorescent Antibody Technique; Glycoproteins; Humans; In Vitro Techniques; Keratins; Lichen Planus; Macaca; Mice; Psoriasis; Rabbits; Skin Diseases; Skin Neoplasms | 1986 |
Restrictive dermopathy: a newly recognized autosomal recessive skin dysplasia.
A brother and sister from consecutive pregnancies had rigid and tightly adherent skin in association with generalized contractures, unusual facies, pulmonary hypoplasia, an abnormal placenta, and a short umbilical cord. Both died shortly after birth. Pathologic examination of the skin by light and electron microscopy showed structural abnormalities of the epidermis, dermis, and subcutaneous fat. An abnormal pattern of keratin proteins was determined biochemically using extracted epidermal proteins. Autopsy showed a normal spinal cord and muscle histology. It is postulated that the defective skin severely restricted movement and secondarily led to the other abnormalities. Familial occurrence is most consistent with autosomal recessive transmission. These patients and the primary skin defect are discussed within the framework of the Fetal Akinesia or Hypokinesia Deformation Sequence. Topics: Abnormalities, Multiple; Arthrogryposis; Female; Genes, Lethal; Genes, Recessive; Humans; Infant, Newborn; Keratins; Male; Skin; Skin Diseases | 1986 |
Immunologic aspects of acute cutaneous graft-versus-host disease: decreased density and antigen-presenting function of Ia+ Langerhans cells and absent antigen-presenting capacity of Ia+ keratinocytes.
Cutaneous graft-versus-host disease (GVHD) provides a unique model for studying the pathogenesis of several important lymphocyte-mediated skin diseases. Morphologic studies have suggested that Ia antigen (Ia)-bearing epidermal Langerhans cells (LC) may be specific targets for destruction in these conditions. Keratinocytes synthesize and express Ia in GVHD and some other lymphocyte-mediated skin disorders; Ia+ keratinocytes, constitutively able to secrete epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1, may possess antigen-presenting capacity, thus leading to enhanced cutaneous immune responses and disease chronicity. We therefore investigated the fate of Ia+ LC, and the potential antigen-presenting capacity of Ia+ keratinocytes, in a murine model of GVHD. Lethally irradiated C3H/He (H-2k) mice developed acute cutaneous GVHD, and expressed keratinocyte Iak, 8 days after injection of BALB/c (H-2d) bone marrow and spleen cells. Immunofluorescence studies showed a progressive decrease in the density of Ia+ epidermal LC during the evolution of GVHD. This decrease was paralleled by a progressive reduction in the allostimulatory capacity of GVHD epidermal cells (EC) in the allogeneic EC-lymphocyte reaction (ELR). The fall in the density of Ia+ LC, and in EC allostimulatory capacity in both primary and secondary ELRs, was consistently greater in GVHD mice than in mice treated only with x-irradiation. The allostimulatory capacity of GVHD and x-irradiated EC could not be restored by addition of indomethacin or exogenous ETAF to ELR cultures. The decreased allostimulatory capacity was not the result of inhibition of the ELR, since EC from GVHD and x-irradiated mice did not cause suppression when added to control ELR cultures. The capacity of EC to present ovalbumin, purified protein derivative of tuberculin, 2,4,6-trinitrobenzenesulfonic acid coupled to EC, and native cytochrome c (CYTc) to antigen-specific T-cell lines, clones, or hybridomas was reduced in x-irradiated mice and markedly decreased in GVHD mice. The capacity of EC from x-irradiated and GVHD mice to present CYTc fragment 81-104, which does not require further processing or catabolism by accessory cells, was similarly decreased. Taken together, the results indicate that: the function of LC is markedly and progressively impaired in acute GVHD; LC function is also decreased, but to a lesser extent, following x-irradiation alone; and Ia+ keratinocytes from lethally irradiated mice Topics: Acute Disease; Animals; Antigen-Presenting Cells; Epidermis; Female; Fluorescent Antibody Technique; Graft vs Host Disease; Histocompatibility Antigens Class II; Isoantigens; Keratins; Langerhans Cells; Lymphocytes; Mice; Mice, Inbred Strains; Skin Diseases | 1986 |
Involucrin expression in epithelial tumors of oral and pharyngeal mucosa and skin.
Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL1. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Papilloma; Pharyngeal Neoplasms; Protein Precursors; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1986 |
Zinsser-Cole-Engman syndrome (dyskeratosis congenita) with cataract--a rare association.
A 26-year-old male patient with dermatological and systemic features suggestive of dyskeratosis congenita is reported with an unusual associated ocular feature of bilateral cataract. Topics: Adult; Cataract; Humans; Keratins; Male; Pedigree; Skin Diseases; Syndrome | 1986 |
Epithelioid sarcoma and isolated necrobiotic granuloma: a comparative immunocytochemical study.
Epithelioid sarcoma (ES) occasionally may be confused, both clinically and histologically, with isolated necrobiotic granulomas (ING), leading to misdiagnosis and potential mismanagement of these conditions. We studied 11 cases of ES and 11 of ING (6 examples of deep granuloma annulare and 5 of rheumatoid nodule) immunohistochemically, in an attempt to determine whether they could be diagnostically separated by such means. Monoclonal antibodies to cytokeratin polypeptides (CK), epithelial membrane antigen (EMA), and leukocyte common antigen (LCA) were applied to formalin-fixed, paraffin-embedded sections in each case, using the avidin-biotin-peroxidase complex technique. All ES cases stained positively for CK, and 6 expressed EMA, while examples of ING were non-reactive for these antigens. Conversely, the large epithelioid histiocytic cells in cases of ING were immunoreactive with anti-LCA, whereas no case of ES displayed this determinant in tumor cells. In the latter lesions, reactive peritumoral inflammatory cells were LCA-positive, but were readily distinguished from neoplastic cells on morphological grounds, as well as by their negativity with anti-CK and anti-EMA. Based on these data, it is concluded that immunohistologic stains for epithelial and hematopoietic antigens are valuable in the conclusive diagnostic separation of epithelioid sarcoma and necrobiotic granulomas. Topics: Adolescent; Adult; Aged; Antigens, Surface; Child; Child, Preschool; Diagnosis, Differential; Epithelium; Female; Granuloma; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Sarcoma; Skin Diseases; Skin Neoplasms | 1986 |
Expression of T6 antigen on the epidermal keratinocytes in various dermatoses.
Topics: Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Epidermis; Humans; Keratins; Skin Diseases | 1986 |
Reactive perforating collagenosis: light, ultrastructural and immunohistological studies.
Reactive perforating collagenosis is an uncommon disorder and few accounts refer to ultrastructural features. This report includes a study by light and transmission electron microscopy of serially sectioned biopsies from early lesions in two patients. Immunohistological investigations utilizing antibodies to basement membrane, laminin, collagen and cytokeratin were also done. Collagen and elastin were demonstrated within the centre of the lesions and there was a defect in the basal lamina at the base of the lesion. The collagen, cytokeratin and the basal lamina in the lesions were antigenically similar to those in the surrounding normal skin. These results are compared with previous findings and discussed in the light of the current views on the pathogenesis of this disorder. Topics: Basement Membrane; Child; Child, Preschool; Collagen; Collagen Diseases; Elastin; Epidermis; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Laminin; Male; Microscopy, Electron; Skin Diseases | 1986 |
Cytochemical expression of epidermal peroxidase and cytochrome oxidase activities in pathological skin conditions of man.
The cytochemical expression of epidermal peroxidase and cytochrome oxidase activity was recently well documented in normal human skin. We report here its expression in basal and squamous cell carcinomas, actinic keratoses, psoriasis, allergic contact dermatitis, seborrheic keratoses, and autosomal dominant ichthyosis vulgaris. The two enzyme activities were evaluated using the diaminobenzidine method. If present, the two enzymes were always localized in the same organelles as in normal epidermis: endogenous peroxidase in the nuclear envelope and endoplasmic reticulum, and cytochrome oxidase in mitochondria. In basal and squamous carcinomas, actinic keratoses and psoriasis, the keratinocytes lost their peroxidase activity, but maintained their cytochrome oxidase activity. In seborrheic keratoses, allergic contact dermatitis and ichthyosis vulgaris, the cytochrome oxidase activity was greatly reduced or abolished in keratinocytes, Langerhans' cells, and melanocytes, whereas the peroxidase activity was present as in normal epidermis. These results indicate that the two peroxidatic enzymes studied are not interrelated and alternatively suppressed by different cellular dysfunctions. Topics: 3,3'-Diaminobenzidine; Biopsy; Electron Transport Complex IV; Epidermal Cells; Humans; Keratins; Langerhans Cells; Peroxidases; Skin; Skin Diseases; Skin Neoplasms | 1986 |
[Ano-sacral cutaneous amyloidosis--dylon positive material does not react with monoclonal antikeratin antibody EKH4].
Topics: Aged; Amyloid; Amyloidosis; Anal Canal; Antibodies, Monoclonal; Coloring Agents; Humans; Keratins; Male; Organic Chemicals; Sacrococcygeal Region; Skin; Skin Diseases; Staining and Labeling | 1986 |
Immunodiagnosis in dermatopathology.
Topics: Antibodies, Monoclonal; Dermatitis; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Hypersensitivity, Delayed; Immunochemistry; Keratins; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1985 |
The characterization of two monoclonal anti-keratin antibodies and their use in the study of epithelial disorders.
The present paper describes the production and characterization of two monoclonal antibodies, K20 and K92. Immunohistological staining showed these two antibodies to be specific for keratinizing epithelium. However, whereas K20 stained all layers of the epidermis K92 reacted with only the suprabasal epidermal layers. Immunoblotting studies with preparations of keratins from both the non-cornified (i.e. the basal, spinous and granular layers) and cornified (stratum corneum) layers of epidermis showed that K20 recognized the 46, 48, 50, 55, 56, 56.5, 59, 61, 62, 64, 65, 66 and 67 kd bands, of which the 50 and 46 kd bands appeared to be masked in tissue sections. In contrast, antibody K92 was more restricted in its activity, recognizing only the 55 and 56 kd bands strongly. These antibodies were used in the study of various epithelial disorders and revealed alterations in the epithelial intermediate filament expression in both benign and malignant disease processes. Topics: Animals; Antibodies, Monoclonal; Cell Line; Dipodomys; Epithelium; Heel; Histocytochemistry; Humans; Immunochemistry; Immunoenzyme Techniques; Keratins; Kidney; Skin Diseases | 1985 |
Infundibular and trichilemmal keratinization of a pilar tumor.
Microscopic examination of a cystic epithelial tumor removed from the elbow of a 52-year-old man showed islands of epithelium undergoing keratinization without formation of a visible granular cell layer, as occurs within the follicular isthmus, in trichilemmal cysts, and in pilar tumors (proliferating trichilemmal cysts). Other areas showed keratinization with the formation of a distinct, even prominent, granular cell layer, as seen within the follicular infundibulum and in epidermal cysts. Possible modes of origin and relationships among these tumors and epidermal cysts are presented. Topics: Epidermal Cyst; Hair; Humans; Keratins; Male; Middle Aged; Skin Diseases | 1985 |
Epidermal calmodulin and skin disease.
Topics: Calmodulin; Cell Division; Humans; Keratins; Psoriasis; Skin; Skin Diseases | 1985 |
[Filaggrins].
It has been shown in recent studies that a group of histidine-rich proteins play a significant role--as interfilamentous matrix proteins--in keratin formation in the epidermis of man and other species. These proteins have been termed filaggrins in reference to their ability to aggregate in vitro reconstituted keratin filaments to macrofibrils with a striking similarity to the ultrastructural keratin pattern. Filaggrins derive from high molecular weight precursor proteins--profilaggrins--which are synthesized in the keratohyaline granules and break down rapidly into filaggrins when the granular cells undergo transition into corneocytes. Further metabolic breakdown of filaggrins leads to the formation of other compounds which subserve physiological functions: e.g. urocanic acid, which is possibly a natural sunscreen, and free amino acids, which are thought to contribute to the hygroscopic character of the horny layer and to its barrier function. Alterations of filaggrin metabolism have been recognized in a number of pathological states of the skin and may be responsible for disturbed epidermal differentiation. Topics: Amino Acids; Animals; Epidermis; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Molecular Weight; Protein Precursors; Skin Diseases; Urocanic Acid | 1985 |
Characterization of UV induced keratoacanthoma-like lesions in HRA/Skh-1 mice and their comparison with keratoacanthomas in man.
UV induced keratoacanthoma-like lesions in mice were studied grossly, light microscopically and electron microscopically. The tumours varied in their degree of cell organization and keratinization but all exhibited downward growth and had a continuous basement membrane. Ultrastructurally, the keratinocytes displayed villous distortion of their plasma membranes, and at times the basal lamina of the epidermal-dermal junction showed focal discontinuation. The keratoacanthoma-like lesions in mice had similarities of appearance to keratoacanthoma in man but showed no regression and regularly progressed to squamous cell carcinoma. This clinical course is dissimilar to that of keratoacanthoma in man which suggests that the use of the term is inappropriate for these UV induced tumours. Moreover, in the context of our experimental system and a dynamic picture of tumour development where tumour types can be seen as stably arising and continuing entities or, a progressive sequence for which squamous cell carcinoma represents an end stage, it is not appropriate to view the keratoacanthoma-like lesion in mice as an entity distinct from the spectrum of UV induced tumours progressing from benignity to malignancy. Topics: Animals; Carcinoma, Squamous Cell; Epidermis; Humans; Keratins; Keratoacanthoma; Mice; Mice, Hairless; Microscopy, Electron; Neoplasms, Radiation-Induced; Skin; Skin Diseases; Skin Neoplasms; Ultraviolet Rays | 1985 |
Brittle fingernails.
In this review an attempt has been made to clarify the etiology, pathogenesis, and therapy of brittle fingernails. Hopefully, this discussion will enable the clinician to better understand, evaluate and manage patients with this disorder. Topics: Anemia, Hypochromic; Calcium; Cosmetics; Fingers; Humans; Keratins; Nail Diseases; Nails; Skin Diseases; Sulfur; Toes; Water | 1985 |
Alterations in the expression of two epidermal differentiation antigens in human epidermal disorders.
The expression of an epidermal keratin subunit and a specific antigen of the keratinocyte membrane, two differentiation antigens in normal human epidermis, was studied in benign and malignant epidermal lesions by use of monoclonal antibodies KL1 (anti 55-57 Kd keratins) and KL3 (anti keratinocyte membrane antigen). In normal human epidermis, KL1 labelled all keratinocytes from the suprabasal layers, KL3 stained the intercellular spaces in all epidermal layers with a fluorescence intensity increasing from the basal to the more upper layers and recognized a keratinocyte membrane antigen as demonstrated in electron microscopy. Frozen or deparaffinized sections of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) malignant melanomas, warts, and skin biopsies from benign lesions (psoriasis, lichen planus, bullous pemphigoid, lupus erythematodes, pemphigus, vasculitis) were tested with either KL1 or KL3 by indirect immunofluorescence and/or immunoperoxidase. Benign and malignant lesions in which modifications of the keratinization process and cell differentiation are known to occur (BCC, SCC, warts, psoriasis) showed the most severe alterations as compared to normal epidermis. With KL1 we observed an irregular staining of basal cells; a reorganization of keratin filaments and variable staining intensities within tumoral cells which did not express high MW keratins. With KL3 drastic alterations in the epidermal intercellular patterns and loss of reactivity of tumoral cells were noted. Conversely, the positivity of epidermal basal cells with KL1, in some cases, was the only modification noted in other skin lesions. Topics: Antibodies, Monoclonal; Antigens, Surface; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Skin; Skin Diseases; Skin Neoplasms | 1985 |
Histologic distribution of staining by a monoclonal antibody (psi-3) in psoriasis and occurrence of psi-3 antigen in other cutaneous diseases.
psi-3 is a monoclonal antibody that recognizes a 135,000 molecular weight structural component of maturing keratinocytes in psoriasis (the psi-3 antigen) but fails to bind to any constituent of keratinocytes in normal epidermis. This paper describes the occurrence of the psi-3 antigen in a variety of dermatopathologic conditions using immunoperoxidase (biotin-avidin-peroxidase) and immunofluorescence methods which show excellent concordance. In 35 of 36 specimens of psoriasis vulgaris, psi-3 antibody consistently immunolabels the cytoplasm of keratinocytes above the basal layer. At the edges of psoriatic plaques, psi-3 antibody staining extends for a variable distance into lesion-free epidermis. A similar pattern has been found in a certain number of other conditions described in the paper, including squamous cell carcinoma and condyloma acuminatum, but not Darier's disease, basal cell carcinoma, nor lamellar ichthyosis. In all but one condition, the outermost or basal layer of cells is never stained. The only disease in which the lowermost cell layer is stained is a lichen planus-like lesion. The occurrence of psi-3 antigen cannot be correlated with any histologic feature of psoriasis such as acanthosis, loss of the granular layer, or hyperproliferation. The antigen appears to be a unique keratinocyte constituent which is expressed in certain pathologic conditions and which is not detected by any other histologic or immunophenotyping method. It is a potentially valuable addition to the panel of antibodies available for characterizing epithelial cells. Topics: Antibodies, Monoclonal; Antigens; Biopsy; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1985 |
A monoclonal antibody labelling the keratinocyte membrane: a marker of epidermal differentiation.
A murine hybridoma secreting an IgM monoclonal antibody (KL3) was produced by cell fusion of mouse myeloma cells with spleen cells from mice immunized with human epidermal keratins. On normal human epidermis KL3 stained the intercellular spaces from the stratum germinatum to the stratum granulosum with a fluorescence intensity increasing from the basal layer to the upper layers. Basal cells were not stained on the side facing the basement membrane. About 90% of free keratinocytes isolated after trypsinization were labelled by KL3 in a punctate staining. Immunoelectron microscopy allowed us to show that the antigen recognized by KL3 was exclusively localized on the keratinocyte membrane especially in the desmosomal plaques. KL3 reactivity was not modified by preincubation of skin sections with lectins showing a selective intercellular labelling of upper layers of epidermis or pemphigus antisera, nor by adsorption of the antibody on NP40 soluble proteins of the epidermis. Though KL3 reactivity was completely abolished after adsorption of purified keratins, no immunological reactivity of KL3 was detected with epidermal keratin polypeptides blotted on nitrocellulose paper. In psoriatic epidemis and epidermal tumors KL3 reactivity was drastically modified. These results suggest that KL3 recognized a keratinocyte membrane antigen implied in the epidermal differentiation process. Topics: Animals; Antibodies, Monoclonal; Antigens, Surface; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Membrane; Epidermal Cells; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Macaca fascicularis; Mice; Psoriasis; Rabbits; Skin; Skin Diseases; Skin Neoplasms; Warts | 1985 |
Colloid milium: a final degeneration product of actinic elastoid.
Serum amyloid P component (SAP) is present not only in all types of cutaneous amyloidosis, but also in the normal dermal elastic fibers as well as abnormal elastic fibers, such as elastotic degeneration of elastic fibers in actinic keratosis. It was previously postulated that the colloid substance in colloid milium is a final degeneration stage of actinic elastosis. In a lesion of colloid milium SAP was intensely positive with an indirect immunofluorescence method using rabbit antiserum to human SAP. Electron microscopy of the colloid lesion revealed components of normal elastic fibers as well as those of actinic elastoid as seen in actinic elastosis. It is concluded that the colloid substance derives, at least in major part, from elastic fibers through actinic degeneration. Topics: Aged; Amyloid; Biopsy; Colloids; Elastic Tissue; Fluorescent Antibody Technique; Humans; Keratins; Male; Microscopy, Electron; Serum Amyloid P-Component; Skin; Skin Diseases; Sunlight | 1985 |
Monoclonal antikeratin antibody: production, characterization, and immunohistochemical application.
A monoclonal antikeratin antibody, EKH4, was produced from a hybridoma cell line which was established by fusing P3X63SAg8 mouse myeloma cells with spleen cells of mice immunized with human trichilemmoma cells. Immunoblot analysis showed that EKH4 antibody reacts predominantly with 50 kilodalton keratin polypeptide in normal epidermis. By indirect immunofluorescence and immunoperoxidase techniques, EKH4 antibody reacted with the lower 2-3 cell layers of the epidermis as well as most cells of pilosebaceous follicle of human and animal skin. Tumor cells of human basal cell epitheliomas and squamous cell carcinomas were also stained with this antibody. The staining was much more regular and intense compared with an available monoclonal antikeratin antibody, AE1. In the lesion of epidermal proliferative disorders, such as psoriasis and actinic keratosis, the entire epidermis instead of the lower layers was stained with EKH4 antibody. Normal skin overlying or adjacent to epithelial tumors also showed positive staining in the entire epidermis. By using indirect immunoperoxidase technique, EKH4 also stained alcohol-fixed, paraffin-embedded tissue sections. Topics: Animals; Antibodies, Monoclonal; Cell Line; Collodion; Electrophoresis, Polyacrylamide Gel; Epidermis; Fluorescent Antibody Technique; Histocytochemistry; Humans; Hybridomas; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Paper; Skin Diseases | 1985 |
The keratinocyte has become the subject of intensive investigation.
Topics: Animals; Cells, Cultured; Desmosomes; Epidermal Cells; Humans; Keratins; Mice; Mice, Nude; Skin; Skin Diseases | 1984 |
Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes.
The polypeptide composition of epidermal keratin varies in disease. To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies. The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes. Specifically, a 50-kilodalton (kd) (AE1-positive) and a 58-kd (AE3-positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes. A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology. A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para- or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a nonhyperproliferative disease. These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis-specific and may represent markers for hyperproliferative keratinocytes in general. In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events. Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, disease-specific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases. Topics: Antibodies, Monoclonal; Antigen-Antibody Complex; Cells, Cultured; Humans; Keratins; Molecular Weight; Skin; Skin Diseases; Skin Neoplasms | 1984 |
Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.
As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells. Topics: Epidermis; Fluorescent Antibody Technique; Graft vs Host Disease; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Keratins; Lichen Planus; Lymphoma; Skin Diseases; T-Lymphocytes | 1984 |
Lichen amyloidosus. Ultrastructure and pathogenesis.
The ultrastructure of six cases of lichen amyloidosus was studied with special attention to epidermal keratinocytes and the role of tonofilaments as precursors of fibrils of amyloid. Through the process of apoptosis, keratinocytes undergo degeneration and become filamentous cells and then filamentous masses or Civatte bodies. These bodies then drop into the dermis through a damaged basement membrane. In the papillary dermis, islands of amyloid become closely associated with Civatte bodies. In some cases, conversion to straight nonbranching filaments, characteristic of fibrils of amyloid, was found within whorled, densely packed filamentous masses. The transformation into fibrils of amyloid was not observed in keratinocytes or Civatte bodies situated in the epidermis. This final step of conversion may be aided by dermal fibroblasts that are frequently lodged around deposits of amyloid. Topics: Adult; Amyloidosis; Female; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases | 1984 |
[Immunofluorescent staining properties of amyloid substance in primary localized cutaneous amyloidosis using anti-keratin antibody].
Topics: Amyloid; Amyloidosis; Antibodies; Fluorescent Antibody Technique; Humans; Keratins; Skin Diseases; Staining and Labeling | 1984 |
Expression of HLA-DR (Ia like) antigen on epidermal keratinocytes in human dermatoses.
Ia antigen (HLA-DR in man) has been demonstrated in keratinocytes in graft versus host disease. This study investigates the occurrence of HLA-DR in keratinocytes in the following dermatoses: eczematous dermatitis, discoid lupus erythematosus, with immunoglobulin and non-exposed skin from cases of systemic lupus erythematosus with immunoglobulin deposits, lichen planus, lichen simplex, bullous pemphigoid, pemphigus vulgaris, 'toxic erthema', tuberculid and chillblain. Keratinocyte staining was found in a variety of conditions. The unifying features of the instances of its occurrence was lymphoid infiltration and usually some focal evidence of keratinocyte damage. Thus in eczema the staining was mid-epidermal, while in discoid lupus erythematosus and lichen planus it was basal. HLA-DR staining was absent in bullous pemphigoid and pemphigus vulgaris, which is consistent with the hypothesis that in these conditions the damage is mediated by autoantibodies and complement in the absence of cellular immune attack. Topics: Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunity, Cellular; Keratins; Palatine Tonsil; Skin; Skin Diseases | 1984 |
Differential staining of cytoid bodies and skin-limited amyloids with monoclonal anti-keratin antibodies.
The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids. Topics: Amyloid; Amyloidosis; Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1984 |
Comparative investigation of epidermal markers on cells freshly isolated from from normal and wart epidermis.
Topics: Antigens, Viral; Basement Membrane; Cell Differentiation; Fluorescent Antibody Technique; Humans; Keratins; Skin; Skin Diseases; Warts | 1984 |
HLA-DR antigen expression on the keratinocyte surface in dermatoses characterized by lymphocytic exocytosis (e.g. pityriasis rosea).
We have investigated the immunoperoxidase staining pattern of the epidermis in several dermatoses characterized by exocytosis of mononuclear cells into the epidermis. We found that HLA-DR antigens showed an intercellular distribution in localized areas of the epidermis in nine of ten cases of pityriasis rosea, and in all four cases of spontaneously regressing flat warts, two cases of pityriasis lichenoides chronica, two of Schamberg's disease, and one case of lichen striatus. Lichen planus and mycosis fungoides cases were used as positive controls. OKT6 antigen was recognized only on the dendritic cells of the epidermis in all these cases. Judging from the distribution of Langerhans cells, the epidermal intercellular HLA-DR antigen seems to be expressed on the keratinocytes in such diseases, and this feature was confirmed by immunoelectron microscopy. These findings support the hypothesis that the expression of HLA-DR antigen on keratinocytes in these dermatoses is linked to cellular immune reactions involving the epidermis. Topics: Cell Membrane; Epidermis; Exocytosis; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Lymphocytes; Microscopy, Electron; Pigmentation Disorders; Pityriasis; Skin Diseases; Warts | 1984 |
Antibodies to Merkel cells in human sera. Incidence and significance.
Antibodies to Merkel cells (MC) are not known to occur in human sera. Using a newly described technic, we looked for the presence of antibodies directed against skin structures in sera from 2,300 patients with various dermatologic and hematologic disorders, as well as graft-versus-host disease (GVHD). Three of these sera (0.1%) were found to react with MC. One monoclonal IgM antibody was present in serum obtained from a patient with chronic cold agglutinin disease, the second from a patient with GVHD, and the third from a patient with pemphigus vulgaris. The present inadequate knowledge about normal MC function and the absence of described symptoms of MC dysfunction preclude analysis of the pathogenic significance of these MC antibodies in human sera. Topics: Aged; Anemia, Hemolytic, Autoimmune; Animals; Antibodies, Monoclonal; Epithelial Cells; Female; Fluorescent Antibody Technique; Graft vs Host Disease; Humans; Immunoglobulin M; Keratins; Rabbits; Skin; Skin Diseases | 1984 |
Proliferating trichilemmal cyst: an ultrastructural study.
A 73-year-old woman had a walnut-sized tumor in the occipital region for 10 years. The growth consisted of multiple small and large cystic epithelial masses. The cyst wall exhibited trichilemmal keratinization. Numerous squamous eddies as well as many glycogen-rich cells were present in the cyst wall. Some small round keratohyalin granules were observed in the cells below the horny layer. The desmosomes and masses of lipid droplets were seen in the horny layer. The findings described above are similar to those observed in the follicular isthmus and the follicular infundibulum. Other interesting findings include the presence of intranuclear inclusions of tonofilament-like material and/or keratohyalin-like granules within the cells near the mid-layer of the cyst wall. Topics: Aged; Cysts; Female; Humans; Keratins; Microscopy, Electron; Skin Diseases | 1984 |
Trichilemmal horn.
Topics: Aged; Female; Hair; Humans; Keratins; Skin Diseases | 1984 |
Xerodermoid induced by photochemotherapy.
Photochemotherapy induces alterations in the skin that resemble those in xeroderma pigmentosum. Acute responses may be distinguished from late, chronic, and delayed responses to PUVA. All of the types of cells present in the skin are affected by photochemotherapy. The structure of the epidermis and of the superficial dermis are altered and, possibly as a consequence, neoplasms may ensue. Topics: Bibliographies as Topic; Epidermis; Humans; Keratins; Photochemotherapy; PUVA Therapy; Skin Diseases | 1984 |
Polyarthritis with atypical keratotic nodular dermatosis or polyarthritis with multiple keratoacanthoma. A case report.
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 | 1984 |
Amyloidogenesis in organ-limited cutaneous amyloidosis: an antigenic identity between epidermal keratin and skin amyloid.
Epidermal keratin was extracted and antibody against this protein was produced in rabbits. Various forms of organ-limited cutaneous amyloidosis (lichenoid, macular, and nodular amyloidosis, and basal cell epithelioma) and primary systemic amyloidosis were immunohistochemically examined to test the identity between epidermal keratin and skin amyloid. Amyloids in lichenoid and macular amyloidoses, and in basal cell epithelioma had an identical antigenicity with epidermal keratin, whereas amyloids in nodular amyloidosis and systemic amyloidosis did not have this identity. In addition, amyloid in lichen amyloidosis contained disulfide bonds as in keratin. Connective tissue components including filaments of fibroblasts and vascular endothelial cells did not react with this antikeratin antibody. It was concluded that at least some of the amyloid substance in organ-limited cutaneous amyloidosis is derived from degenerated epidermal keratinocytes through filamentous degeneration or apoptosis. Topics: Amyloid; Amyloidosis; Epitopes; Fluorescent Antibody Technique; Humans; Keratins; Skin; Skin Diseases | 1983 |
Immunofluorescence and histochemical studies of localized cutaneous amyloidosis.
Lichen amyloidosus (LA) and macular amyloidosis (MA) are two forms of localized cutaneous amyloidosis in which the amyloid occurs as larger and smaller deposits respectively in the papillary dermis. The histogenesis of the amyloid of these conditions is unknown. By using an indirect immunofluorescence technique we showed that LA and MA do not react with antibodies against different previously characterized amyloid fibril proteins. These results indicate that the amyloid of LA and MA is different from other known types of amyloid. Protein AP, which was demonstrated in amyloid of MA and LA, is known to be present in all forms of amyloid and is of unknown significance. Antiserum against keratin did not react with the larger homogeneous amyloid bodies, but showed a weak reaction with some small deposits. Histochemical staining failed to show keratin in any of the tissues containing LA or MA. Topics: Adult; Aged; Amyloid; Amyloidosis; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases | 1983 |
Trichilemmal keratosis (horn): a light and electron microscopic study.
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 | 1983 |
Epidermal lipids, barrier function, and desquamation.
Based on recent morphologic, histochemical, and biochemical data, we propose a heterogeneous two-compartment model of the stratum corneum that ascribes a special role for intercellular lipids in the regulation of stratum corneum barrier function and desquamation. The evidence in favor of the model and several predictions based on the model are surveyed in this review. Topics: Ceramides; Fatty Acids, Nonesterified; Histocytochemistry; Humans; Keratins; Lipid Metabolism; Lipids; Protein Precursors; Skin; Skin Diseases; Staining and Labeling; Sterols; Steryl-Sulfatase; Sulfatases | 1983 |
The use of monoclonal antibody to keratin in human epidermal disease: alterations in immunohistochemical staining pattern.
A monoclonal antikeratin antibody, designated AEl, was used to stain frozen sections of normal and abnormal human skin by the immunofluorescence and peroxidase-antiperoxidase techniques. In normal human epidermis and ichthyosis vulgaris, a nonproliferative epidermal disease, this antibody selectively stained epidermal basal cells. Very different staining patterns were observed in various other epidermal diseases. A suprabasal staining pattern was observed in psoriasis (16 cases), verruca (9), seborrheic keratosis (5), actinic keratosis (2), as well as the epidermis adjacent to certain epidermal neoplasms (4). Basal cell carcinoma (7) showed weak, homogeneous staining. In contrast, a disorganized pattern consisting of cells with various staining intensities was observed in Bowen's disease (2) and squamous cell carcinoma (4). Although the biochemical basis for these altered staining patterns remains to be elucidated, these results provide further evidence that epidermal keratin expression can be affected by various disease states. Moreover, our data suggest that a common alteration in keratin expression, as defined by the suprabasal AEl staining pattern, exists in psoriasis and a number of other benign hyperproliferative epidermal diseases. Topics: Animals; Antibodies, Monoclonal; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Skin Diseases | 1983 |
Monoclonal antibodies to normal and abnormal epithelial antigens.
Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cultures were expanded and recloned. Two cloned antibodies of interest are DUX 5.2 and DUX 1.1.3. DUX 5.2 is the mouse IgG1 subclass and reacts with the membranes of ME-180 cells and the human skin epidermal basement membrane zone as shown by direct immunofluorescent microscopy. Ultrastructural localization using electron microscopic immunoperoxidase techniques showed localization of the DUX 5.2 antigen to be beneath the lamina densa; the reaction product may include the anchoring fibrils. Although DUX 5.2 reacts with the normal human basement membrane zone and the basement membrane zone in several diseases, there is no reactivity in the normal, never-blistered skin of patients with dystrophic epidermolysis bullosa (DEB). This suggests that the increased collagenase in the disease may be destroying antigenicity of the antigen recognized by DUX 5.2 or that the antigen may not be present in DEB. This antibody will thus allow early neonatal and prenatal diagnosis in DEB and allow isolation of the structural moiety which is deficient in DEB. DUX 1.1 is an IgM mouse immunoglobulin specific for the cytoplasm of human basal cells. Its reactivity with upper epidermis is significantly less than that seen in the basal layer. All cells of the basal layer stain uniformly. The slight amount of staining in upper cells probably represents dilution of antigen which is not synthesized beyond the basal layer. Basal cells of hair follicles and sweat glands are stained to some degree. Topics: Animals; Antibodies, Monoclonal; Cell Fusion; Clone Cells; Epithelium; Female; Fluorescent Antibody Technique; Immunoglobulin G; Immunoglobulin M; Keratins; Mice; Mice, Inbred BALB C; Multiple Myeloma; Skin; Skin Diseases | 1983 |
[Observation of primary cutaneous amyloidosis by an immunoenzyme technic (PAP method)--negative anti-keratin antibody reaction of amyloid].
Topics: Amyloid; Amyloidosis; Antibodies; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Skin Diseases | 1983 |
Dyskeratosis congenita: radiologic features.
Three males with the X-linked disorder dyskeratosis congenita are described. Each suffered femoral fractures after minimal trauma with poor healing. Long bones showed coarse trabecular patterns of the metaphyses and small lucency areas in the diaphyses. Two of the males were retarded brothers who additionally showed intracranial calcifications. Topics: Adolescent; Bone and Bones; Bone Diseases; Calcinosis; Female; Fractures, Bone; Humans; Intellectual Disability; Keratins; Male; Osteoporosis; Radiography; Sex Chromosome Aberrations; Skin Diseases; Skull; Syndrome; X Chromosome | 1982 |
Epidermal origin of the amyloid in localized cutaneous amyloidosis.
A case of localized cutaneous amyloidosis which developed after a lichen planus-like skin reaction is reported. The amyloid consisted of amyloid fibrils enveloped by heparan sulphate granules. These amyloid fibrils reacted to anti-human keratin antibody, indicating an epidermal origin for the fibrils. Topics: Aged; Amyloid; Amyloidosis; Antibodies; Heparitin Sulfate; Humans; Keratins; Male; Skin; Skin Diseases | 1982 |
Cutaneous and mucosal warts. Clinical and histopathological criteria for classification.
The clinical and histopathological study of cutaneous and mucosal warts demonstrates divergences between clinical and histopathological diagnoses among the group of myrmecias, mosaics, acrodigitate, and common warts. There is correlations criteria (when considered separately), such as hyperkeratosis and absence of keratohyaline granules in flat warts, and in ano-genital vegetations. The existence of clinical and histological overlaps emphasizes that it is not clear whether these cases are rare clinical varieties caused by as yet unknown types of human papillomaviruses, or rather by differences in the degree of keratinization at different sites in the body. Topics: Humans; Keratins; Papillomaviridae; Skin Diseases; Warts | 1982 |
Colloid bodies in dermatoses other than lichen planus.
In a previous study on lichen planus the morphology and significance of the colloid bodies were discussed (13). In the present study a description is given of 30 dermatoses with colloid bodies, observed among unselected patients. The colloid bodies develop as a result of damage to the epithelium caused by circulatory disorders with subsequent hypo- or anoxia. Lichenoid cell infiltration into the connective tissue--nearly always present--aggravates the process. Dyskeratosis, pyknosis and fibrinoid necrosis of the damaged cells occur and the nuclei disintegrate. The resultant colloid bodies may coalesce or scatter or be expelled from the epithelium according to the principles of apoptosis (6, 7). Besides circulatory disorders, purely local damage and pathological processes involving the tissues should be regarded as important factors. Although the colloid bodies are characteristic for various skin diseases, they do not have an absolutely clear diagnostic significance. In doubtful cases their presence may nevertheless be considered a valuable contribution and supplement to the diagnosis. Topics: Amyloid; Darier Disease; Erythema Multiforme; Humans; Keratins; Lupus Erythematosus, Systemic; Skin Diseases; Skin Diseases, Vesiculobullous; Staining and Labeling | 1982 |
Fractionation and characterization of the human epidermal stratum corneum in keratinization disorders.
Topics: Amino Acids; Chemical Fractionation; Electrophoresis; Humans; Keratins; Skin; Skin Diseases | 1982 |
Retinoids. Therapeutic use in dermatology.
Topics: Acne Vulgaris; Humans; Isotretinoin; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A | 1982 |
Pigmented follicular cysts.
This report deals with seven examples of an epithelial cyst for which we have found no proper designation in the classification of epithelial skin cysts. Clinically, the lesion is often hyperpigmented, located in mid-dermis and shows epidermoid keratinization. The cyst contains laminated keratin, many pigmented hair shafts and the cyst wall displays one or two growing hair follicles. Topics: Adult; Cysts; Female; Hair; Humans; Keratins; Male; Middle Aged; Skin Diseases | 1982 |
[Etretinate (Tigason). A drug for skin diseases with disturbances in keratinization].
Topics: Dermatologic Agents; Humans; Keratins; Skin Diseases; Tretinoin | 1982 |
The effect of increased tissue turnover on the keratinization of human epidermis.
Topics: Cytoskeleton; Humans; Keratins; Molecular Weight; Protein Precursors; Psoriasis; Skin; Skin Diseases | 1981 |
Spongiosis.
Topics: Edema; Humans; Keratins; Osmotic Pressure; Skin; Skin Diseases | 1981 |
Cod liver oil and skin disease.
Topics: Adolescent; Cod Liver Oil; Female; Fish Oils; Humans; Keratins; Pityriasis Rubra Pilaris; Skin Diseases | 1981 |
Immunofluorescence studies on civatte bodies and dyskeratotic cells with anti-keratin antibody.
So-called Civatte bodies and dyskeratotic cells were investigated in some skin disorders by using indirect immunofluorescence techniques with anti-human keratin antibody. In the disorders with lichenoid tissue reaction such as lichen planus and DLE, Civatte bodies were observed in the lower epidermis and upper dermis and they reacted distinctly to the anti-keratin antibody. In malignant skin tumors which show dyskeratotic cells in the epidermis, such as basal cell epithelioma and Bowen's disease, dyskeratotic cells were more clearly reacted to the antibody than other keratinocytes. These observations present additional new evidence for the hypothesis that Civatte bodies are derived from tonofilaments of keratinocytes. Topics: Adolescent; Aged; Animals; Antibodies; Female; Fluorescent Antibody Technique; Guinea Pigs; Humans; Keratins; Male; Microbodies; Microscopy, Electron; Middle Aged; Molecular Weight; Organoids; Rats; Skin; Skin Diseases; Skin Neoplasms | 1981 |
Amyloid in localized cutaneous amyloidosis: immunofluorescence studies with anti-keratin antiserum especially concerning the difference between systemic and localized cutaneous amyloidosis.
Amyloid of localized cutaneous amyloidosis and systemic amyloidosis were subjected to study with an indirect immunofluorescence technique using anti-keratin antiserum. Anti-keratin antiserum was prepared ad modum Sun & Green. Amyloid of localized cutaneous amyloidosis was positively stained for the antiserum, whereas amyloid of systemic amyloidosis (primary and multiple myeloma-associated) was negative. There was no difference between primary localized cutaneous amyloidosis (lichen amyloidosus and macular amyloidosis) and secondary localized cutaneous amyloidosis (amyloidosis associated with skin tumor). These results indicate that amyloid of localized cutaneous amyloidosis contains components derived from epidermal fibrous protein, probably tonofilaments of keratinocytes. Topics: Amyloid; Amyloidosis; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Multiple Myeloma; Skin; Skin Diseases | 1981 |
Phosphorylation of epidermal keratins.
When human and rat epidermis are exposed to 32P-orthophosphoric acid, labeled phosphate is incorporated into several proteins. The pattern of phosphorylation is identical whether the isotope is delivered in vivo or in vitro. The predominant phosphorylated proteins are insoluble in Tris-HCl buffer but soluble in SDS-beta-mercaptoethanol. They migrate in SDS-polyacrylamide gels with apparent molecular weights between 45,000 and 65,000. When analyzed by two-dimensional gel electrophoresis, the labeled phosphoproteins co-migrate with keratins isolated from human callus. Serine is the phosphate acceptor in these proteins. The pattern of phosphorylation of these SDS-beta-mercaptoethanol soluble epidermal proteins is not changed in basal cell carcinoma, icthyosis vulgaris, Kyrle's disease or Netherton's syndrome. The pattern is altered in psoriasis. Others have demonstrated that a 63,000 molecular weight protein is absent from active psoriatic lesions. We have found that a 63,000 molecular weight phosphoprotein is present in uninvolved skin but absent in the psoriatic plaques. Topics: Animals; Bony Callus; Electrophoresis, Agar Gel; Epidermis; Humans; In Vitro Techniques; Keratins; Molecular Weight; Phosphorylation; Psoriasis; Rats; Skin Diseases | 1980 |
Rhodamin B stain for keratin: evaluation of its specificity and its application in dermal pathology.
We used Rhodamin B stain in sections of normal skin, benign and malignant epithelial tumors and dermatoses. Keratin staining was uneven and showed variation in different lesions. While trichohyalin of the anagen hair follicle stained with intensity, keratohyalin granules failed to show similar reaction. Topics: Humans; Keratins; Rhodamines; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling; Xanthenes | 1980 |
Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization.
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 | 1980 |
[Study of normal and pathological keratinization using anti-keratin polypeptide sera (author's transl)].
Anti-keratin polypeptide sera were obtained against the different bands of polyacrylamide gel electrophoresis of fibrous proteins of stratum corneum derived from normal human epidermis. The sera were tested by indirect immunofluorescence of immunoperoxidase techniques. It was demonstrated that antibodies against P1 and P2 polypeptides, of MW 67,000 and 62,000 daltons respectively, were directed towards cytoplasmic antigens of keratinocytes of the upper Malpighian layers, while no labelling could be detected in the basal cell layer. Anti-P3 polypeptide sera and the anti-whole keratin serum labelled the whole epidermis, including the basal cell layer. Ultrastructural immuno-labelling performed on free epidermal cells obtained after trypsinization demonstrated that receptors for anti-P1 polypeptide sera were tonofilaments. These results showed that some keratin components (P1 and P2 polypeptides) might be absent in basal cell tonofilaments. This in in favour of various differentiation stages of the keratinizing cells. Keratin polypeptide 1 could be a useful marker of keratinization. According to preliminary studies, the expression of this keratin antigens was markedly disturbed in tumors such as basal and squamous cell carcinoma, in warts and in ichthyosis. Topics: Antibodies; Epidermis; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Peptides; Skin Diseases | 1980 |
Structural changes of human epidermal alpha-keratin in disorders of keratinization.
The chemistry and structure of the epidermal alpha-keratin extracted from the skin of patients with a variety of disorders of keratinization have been investigated using biochemical, biophysical, and electron microscopic techniques developed for the characterization of normal mammalian epidermal keratin. Generally, the alpha-keratin polypeptides of the diseased epidermis differed from those of uninvolved epidermis or of normal volunteers in having varying numbers of polypeptide components of lower molecular weights, numerous free amino acids, higher contents of alpha-helix, and only limited facility for polymerization in vitro into native-type epidermal keratin filaments. As the alpha-helix-enriched fragments, which represent up to two-thirds of the polypeptide chains, isolated after limited tryptic digestion of the keratin filaments of normal, uninvolved, and involved epidermis, were physicochemically identical, it seems that the end-terminal non-alpha-helical regions of the polypeptides of diseased epidermis are abnormal. These differences may be a result of degradation or of altered protein synthesis. Topics: Amino Acid Sequence; Callosities; Cytoskeleton; Epidermis; Humans; Keratins; Microscopy, Electron; Molecular Weight; Protein Conformation; Psoriasis; Skin Diseases | 1980 |
Two siblings with epidermodysplasia verruciformis with large clear cells in the epidermis: electron microscope and immunological findings.
In two Arab brothers presenting the characteristic clinical picture of epidermodysplasia verruciformis (EV), histological examination revealed large clear cells in the granular layer and uppermost part of the prickle cell layer of the epidermis. The report of this histological picture in two cases by other authors in the past had aroused considerable discussion as to the true diagnosis. The finding of large clear cells in our two confirmed cases of EV supports the opinion that this does not necessarily contradict the diagnosis of EV. Electron microscope investigation revealed groups of particles in the nuclei of a few keratinocytes in the granular layer which were compatible with papova virus particles. The changes seen in the clear cells support the theory of the viral etiology of EV. Ehe immunological studies showed intact humoral immunity but impaired cellular immunity. Topics: Adolescent; Epidermis; Humans; Keratins; Male; Papillomaviridae; Polyomaviridae; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Syndrome | 1979 |
Trichilemmal horn: cutaneous horn showing trichilemmal keratinization.
A unique and distinctive clinicopathological entity occurred in nineteen patients who ranged in age from 16 to 72 (median 50) years. Clinically, these were solitary cutaneous horns. Nine were on the limbs, four on the back, two on the face, three on the scalp, and in one the site was not known; the median duration was 2 years. Histologically, there was a benign picture with a protrusion of massive horn and trichilemmal keratinization at the base. This tumour, which I have named trichilemmal horn, must be differentiated from other lesions that show trichilemmal keratinization (trichilemmal cyst, proliferating trichilemmal cyst, keratoacanthoma) and from other cutaneous horns, including trichilemmomal horn (cutaneous horn overlying trichilemmoma). Topics: Adolescent; Adult; Aged; Cysts; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases; Skin Neoplasms | 1979 |
Fibrous proteins of normal and abnormal human epidermis.
Keratin proteins of human epidermis have been isolated from normal and abnormal tissues. The normal proteins whether removed from living layers (prekeratin) or from the stratum corneum (keratin) are shown to consist of three chains, molecular weights 65,000 (A), 60,000 (B) and 52,000 (C). When compared with the epidermal proteins isolated from abnormal tissues, differences can be detected in the electrophoretic pattern of the subunits. In general, relative amounts of the individual chains are altered and in specific cases or two of the polypeptides found normally are missing. All the alpha-fibrous proteins extracted are found to be very similar in amino acid composition. Topics: Amino Acids; Electrophoresis, Polyacrylamide Gel; Epidermis; Humans; Keratins; Molecular Weight; Skin; Skin Diseases; Spectrophotometry, Ultraviolet | 1979 |
Histogenesis of primary localized cutaneous amyloidosis: sequential change of epidermal keratinocytes to amyloid via filamentous degeneration.
Two cases of lichen amyloidosus and 8 cases of macular amyloidosis were examined by electron microscopy. Epidermal keratinocytes showed variable degrees of focal degeneration in the basal or lower Malpighian layer. The primary change was seen in cells which contain fibrillar (30 nm in thickness) cytoplasmic inclusion. The following developments seemed to lead to filamentous degeneration (colloid bodies): (1) aggregation of tonofilaments within the granular or fibrillar cytoplasm, (2) filamentous cells, which are composed of bundles of 7-nm thick filaments surrounded by cell membrane and desmosomes, and (3) filamentous masses composed of bundles or whorls of tightly packed 7-nm thick filaments in the intercellular spaces. At the dermo-epidermal junction, some of the filamentous masses were surrounded by the basal lamina of the epidermis and others were dropping into the dermis. Occasionally, loosened filaments (similar to amyloid filaments) were about to drop into the dermis. Early formation of amyloid islands consisted of electron-dense and electron-light parts. They were located directly beneath the epidermis. In the deeper postion of the papillary dermis and in the upper reticular dermis, the majority were electron-light masses. Electron dense parts were the densely packed 7-nm thick filaments, whereas electron-light parts were the typical straight amyloid filaments. Small tubular filaments were seen in common in the filamentous cells, filamentous masses, and amyloid islands. It is concluded that some of the amyloid substance in primary localized forms of cutaneous amyloidoses derive from the epidermal cells through filamentous degeneration. Topics: Adult; Amyloid; Amyloidosis; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Skin Diseases; Time Factors | 1979 |
[Dermatologic diagnosis].
Topics: Hair; Humans; Keratins; Melanocytes; Sebaceous Glands; Skin Diseases | 1979 |
Submicroscopic aspects of the keratinization, dyskeratinization and acantholysis of fogo selvagem.
Histopathological, cytomorphological and electron microscopic analyses in a case of fogo selvagem are reported. Contradictory to the light microscopical findings, the acantholysis as seen with the electron microscope involves the basal layer but not the subcorneal layers--at least not the most superficial part of the granular layer. A conspicuous disintegration of the tonofilament-desmosome complexes give rise to the concomitant dyskeratosis. This aberrant process, including an association between retracing tonofilaments and defective Odland bodies, results in the terminal stage of monstrous defective and specific keratohyalin. In cytoplasm, target-like structures similar to virions of the herpes virus group were observed. The dynamics of the pathological process is discussed. Topics: Acantholysis; Aged; Cytoplasm; Epidermis; Humans; Keratins; Male; Microscopy, Electron; Skin; Skin Diseases; Skin Diseases, Vesiculobullous | 1978 |
[Viral acanthomas and specialized forms of keratinosome "membrane coating granules" (author's transl)].
In the case of viral acanthomas, the stratum spinosum and granulosum presents ballooned cells which contain all transitional stages from multivesicular bodies (MVB) to keratinosomes. A particularity in condylomata acuminata are the "wagon-wheel" bodies. These structures are typical for the non keratinazed squamous epithelium. The participation of intercellular extruded "wagon-wheel" bodies, MVB and atypical keratinosomes on an irregular baso-apical diffusion-barrier in the epidermis of cases with viral acanthomas has been discussed. On the basis of the relation seen between MVB and the Golgi-apparatus, their transition to partially atypical keratinosomes in cases of viral acanthomas and their "expulsion" into the intercellular space could indicate that in keratinozytes the enzymatically regulated feed-back between the cellular surface and the capability to synthesize is changed by viral agents. The interference appears to manifest itself in the Golgi-apparatus and also appears to be "specified" by the terrain present. Topics: Animals; Condylomata Acuminata; Cytoplasmic Granules; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Microscopy, Electron; Papilloma; Skin Diseases; Skin Neoplasms; Tumor Virus Infections; Warts | 1978 |
[Rare intracytoplasmic membranous structures of some dermatoses (author's transl].
Rare intracytoplasmic membranous structures were observed in keratinocytes, histiocytes, Langerhans cells and in metastatic cells of several dermatoses. The morphological study is not conclusive of their functional activity. They seem related to the cellular activity, and with no diagnostic value. Topics: Cell Membrane; Endoplasmic Reticulum; Histiocytes; Humans; Keratins; Langerhans Cells; Neoplasms; Skin Diseases | 1978 |
Multinucleate epidermal cells in non-neoplastic dermatoses.
Multinucleate epidermal cells (MEC) originated from keratinocytes were observed histologically in 92 of 197 cases of non-neoplastic dermatoses, such as lupus erythematosus (26 of 70), lichenoid eruptions (26 of 47), Hailey-Hailey disease (5 of 5), psoriasis vulgaris (20 of 49) and so on. Most of these cells had two nuclei, and a few had three nuclei. MEC usually showed perinuclear bands of eosinophilic material which also showed positive staining for epidermal fibres (tonofilaments). In all cases of Hailey-Hailey disease, close correlation between formation of MEC and dyskeratotic tendency was observed. From these findings, it is concluded that the mechanism of formation of MEC in these dermatoses may be similar to that of Bowen's disease, in which dyskeratotic tonofilaments become entangled with the spindles of the mitotic apparatus so that normal cell division cannot take place. It seems likely that MEC are a manifestation not only of malignant dyskeratosis but also of benign one. Topics: Cell Nucleus; Humans; Keratins; Mitosis; Skin; Skin Diseases | 1978 |
Nodular grouped milia.
A young girl had a distinctive nodule with white spherules. Histologically, the lesion was composed of multiple small keratotic cysts. Topics: Cysts; Female; Humans; Infant; Keratins; Skin Diseases | 1977 |
Mechanisms involved in elimination of organisms from experimental cutaneous Candida albicans infections in guinea pigs.
Experimental cutaneous Candida albicans infections were produced in guinea pigs either by using occlusive dressings over the organisms or by applying them to the shaved skin directly without occlusive dressings. In either model there was clearance of the infecting organisms from the skin by a process involving profuse scaling of the keratinized layer in which they were confined. However, for each type of infection the mechanisms producing this scaling seemed to involve different parts of the host defense system. Infections produced under occlusive dressings were characterized by a rapid accumulation of polymorphonuclear leukocytes (PMN) in the epidermis and formation of thick crusts in which organisms were trapped. Sloughing of the crust removed the organisms. In this model, evolution of the lesions and the rate of clearance of the organisms did not depend on prior immunity to Candida. Two possible mechanisms for attraction of PMN into the lesions were direct activation of the alternative complement pathway by the organisms in the lesions and direct chemotactic activity in components of Candida albicans. In contrast, infections produced without occlusive dressings showed only minimal epidermal PMN infiltration, but also underwent profuse scaling of the keratinized layer. This response appeared to depend on cell-mediated immunity. Only animals with previously-acquired delayed hypersensitivity to Candida antigens could undergo this type of scaling, and indeed, this response was transferable to nonimmue animals with peritoneal exudate cells from Candida-immune animals. Clearance of the infecting organisms from this type of infection was significantly faster in immune than in nonimmune animals. It is postulated that a lymphokine released from lymphocytes in the upper epidermis acts on epidermal cells to increase the rate of keratin turnover either by the mitotic rate of the germinal cells or by increasing their rate of keratinization. Topics: Animals; Antigens, Fungal; Ascitic Fluid; Candida albicans; Candidiasis; Chemotaxis; Complement System Proteins; Guinea Pigs; Immunity, Cellular; Immunization, Passive; Immunologic Memory; Keratins; Neutrophils; Occlusive Dressings; Skin; Skin Diseases | 1976 |
Sunlight and aging of the skin.
Topics: Aging; Connective Tissue; Humans; Keratins; Melanocytes; Skin; Skin Diseases; Skin Physiological Phenomena; Sunlight; Time Factors; Ultraviolet Rays | 1976 |
The keratin in dermatological diagnoses.
Topics: Humans; Keratins; Keratosis; Skin Diseases | 1976 |
Peripilar keratin casts in boys.
Peripilar keratin casts are reported in three boys. All previous reports of peripilar keratin casts in children have apparently been in girls. Topics: Adolescent; Child; Child, Preschool; Dermatitis, Seborrheic; Hair; Humans; Keratins; Male; Psoriasis; Skin Diseases | 1975 |
Second European Meeting on Electron Microscopy applied to Cutaneous Pathology.
Topics: Humans; Keratins; Microscopy, Electron; Pigmentation; Skin; Skin Diseases; Skin Diseases, Vesiculobullous; Skin Neoplasms | 1975 |
An unusual pattern of testosterone metabolism in tissue associated with a keratin-filled cutaneous cyst.
Testosterone metabolism was studied in tissues associated with a keratin-filled cutaneous cyst. Instead of the 5alpha-reduced metabolites usually associated with skin steroid metabolism, considerable amounts of 5beta-reduced steroids were found. These included 5beta-androstane-3,17-dione, 17beta-hydroxy-5beta-androstan-3-one, and 5beta-androstane-3beta,17beta-diol. This change in metabolic pattern is discussed. Topics: Adult; Androstane-3,17-diol; Androsterone; Cysts; Dihydrotestosterone; Etiocholanolone; Humans; In Vitro Techniques; Keratins; Ketosteroids; Male; Muscles; Skin; Skin Diseases; Testosterone | 1975 |
Aspects of skin biology pertinent to pharmacology.
Topics: Animals; Cell Division; Connective Tissue; Disease Models, Animal; Epithelial Cells; Humans; Keratins; Melanocytes; Pigmentation Disorders; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Vitiligo | 1974 |
Epidermal growth and renewal.
Topics: Humans; Keratins; Skin; Skin Diseases | 1974 |
Proceedings: Peripilar keratin casts.
Topics: Child; Female; Hair; Humans; Keratins; Skin Diseases | 1974 |
Peripilar keratin casts (pseudo nits) and psoriasis.
Topics: Child; Child, Preschool; Diagnosis, Differential; Female; Hair; Humans; Keratins; Lice Infestations; Psoriasis; Skin Diseases | 1974 |
Electron microscopy of spherical keratohyalin granules.
Topics: Animals; Dogs; Histological Techniques; Hyalin; Ichthyosis; Keratins; Mice; Microscopy, Electron; Skin; Skin Diseases | 1973 |
Diseases of the skin. Structure and function of skin in relation to therapy.
Topics: Cell Membrane Permeability; Collagen; Elastin; Epithelial Cells; Growth Inhibitors; Humans; Keratins; Langerhans Cells; Melanocytes; Mitosis; Skin; Skin Absorption; Skin Diseases; Skin Physiological Phenomena | 1973 |
Production of epidermal damage in mammalian skins by some simple aluminium compounds.
Topics: Abscess; Aluminum; Animals; Hydrogen-Ion Concentration; Hyperplasia; Inflammation; Keratins; Mice; Permeability; Phospholipids; Protein Binding; Protein Denaturation; Skin; Skin Diseases; Skin Ulcer; Sulfhydryl Compounds; Swine | 1973 |
Alkaline phosphatase activity in cholesteatoma epithelium and skin.
Topics: Alkaline Phosphatase; Cholesteatoma; Cysteine; Ear Diseases; Epithelium; Glycerophosphates; Histocytochemistry; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iodoacetates; Keratins; Phosphatidylcholines; Skin Diseases; Sulfhydryl Compounds | 1972 |
Neonatal dermatology.
Topics: Birth Injuries; Blister; Drug Eruptions; Epidermolysis Bullosa; Erythema; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Keratins; Listeria monocytogenes; Lupus Erythematosus, Systemic; Male; Maternal-Fetal Exchange; Miliaria; Nevus; Pregnancy; Pregnancy Complications; Rubella; Skin Diseases; Skin Diseases, Infectious; Stevens-Johnson Syndrome; Sucking Behavior; Syphilis, Congenital; Urticaria Pigmentosa | 1971 |
Lichen amyloidosus. Electron microscopic study of a typical case and a review.
Topics: Amyloid; Amyloidosis; Cytoplasm; Fibroblasts; Humans; Keratins; Leg; Male; Middle Aged; Skin; Skin Diseases | 1971 |
Reactive perforating collagenosis.
Topics: Adult; Collagen Diseases; Humans; Keratins; Male; Necrosis; Skin Diseases | 1971 |
Hair destroying growth of Corynebacterium tenuis in the so-called trichomycosis axillaris. New findings from scanning electron microscopy.
Topics: Adult; Axilla; Corynebacterium; Female; Hair; Humans; Infections; Keratins; Male; Microscopy, Electron, Scanning; Middle Aged; Mycoses; Skin Diseases; Species Specificity | 1971 |
Keratinocyte glycogen: an ultrastructural study of the epidermal response to galactosamine and glucose in organ culture.
Topics: Amylases; Chemical Phenomena; Chemistry; Cytoplasmic Granules; Galactose; Glucosamine; Glucose; Glycogen; Hexosamines; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Organ Culture Techniques; Skin; Skin Diseases; Stimulation, Chemical | 1971 |
The mechanical properties of hair. II. Chemical modifications and pathological hairs.
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 | 1971 |
The cutaneous amyloidoses. I. Localized forms.
Topics: Adult; Aged; Amyloid; Amyloidosis; Collagen; Diagnosis, Differential; Female; Forearm; Humans; Keratins; Leg Dermatoses; Lichen Planus; Lipidoses; Male; Melanins; Middle Aged; Pruritus; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1970 |
[Practical significance of histochemistry].
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 | 1970 |
Peripilar keratin casts.
Topics: Child; Diagnosis, Differential; Female; Hair; Humans; Keratins; Phthiraptera; Skin Diseases | 1970 |
Peripilar keratin casts.
Topics: Child, Preschool; Diagnosis, Differential; Female; Hair; Humans; Keratins; Phthiraptera; Skin Diseases | 1970 |
[Cosmetic problems on the horny layer of the skin].
Topics: Amino Acids; Collagen; Detergents; Elasticity; Elastin; Forearm; Hand; Humans; Keratins; Lipids; Skin; Skin Diseases; Sulfhydryl Compounds | 1970 |
Keratinophilic fungi isolated from humans and from soil in the city of Birmingham, England.
Topics: Arthrodermataceae; England; Hair; Humans; Keratins; Nails; Skin; Skin Diseases; Soil Microbiology | 1969 |
[Zinsser-Cole-Engman (Zinsser-Fanconi) syndrome].
Topics: Adolescent; Adult; Aged; Female; Humans; Keratins; Leukoplakia; Male; Mouth Diseases; Nails; Skin Diseases | 1969 |
Netherton's syndrome.
Topics: Hair; Humans; Hypersensitivity; Ichthyosis; Infant; Keratins; Male; Skin; Skin Diseases | 1968 |
Tinea incognito.
Fourteen cases are described in which the local application of corticosteroid preparations to ringworm infections of the skin have resulted in unusual clinical pictures. A kerion-like lesion due to Trichophyton rubrum, intertriginous infections simulating candidiasis and due to Epidermophyton floccosum, and pictures resembling poikiloderma, papular rosacea, and indeterminate leprosy are among the changes that were seen in these patients. Topics: Adolescent; Adult; Aged; Betamethasone; Diagnosis, Differential; Eczema; Epidermophyton; Female; Fluocinolone Acetonide; Glucocorticoids; Griseofulvin; Humans; Keratins; Male; Middle Aged; Skin Diseases; Tinea; Triamcinolone Acetonide; Trichophyton; Valerates | 1968 |
[On the embryology and histochemistry of the normal nail and ungual pathology].
Topics: Histocytochemistry; Humans; Keratins; Nails; Skin Diseases | 1968 |
Keratinous cysts of the skin. Identification and differentiation of pilar cysts from epidermal cysts.
Topics: Cysts; Epidermal Cyst; Humans; Keratins; Scalp; Skin Diseases | 1966 |
Keratin granulomas in irradiated squamous cell carcinoma of various sites.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Granuloma; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Radium; Skin Diseases; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms | 1966 |
Studies on a skin calcifying system.
Topics: Animals; Calcinosis; Calciphylaxis; Calcium; Cholecalciferol; Hair Removal; Keratins; Male; Microscopy, Electron; Phosphorus; Rats; Rickets; Skin Diseases | 1965 |
Histidine and keratinization.
Topics: Animals; Histidine; Histocytochemistry; Humans; Keratins; Mice; Radioisotopes; Rats; Skin Diseases; Skin Physiological Phenomena | 1965 |
Application of fluorescent dyes to dermatological investigation. IV. Flourescent microscopical study of keratin.
Topics: Adolescent; Adult; Aged; Child; Fluorescent Dyes; Humans; In Vitro Techniques; Keratins; Microscopy, Fluorescence; Middle Aged; Skin Diseases | 1965 |
ADHERENCE OF BATH OIL TO KERATIN.
Topics: Absorption; Baths; Emulsions; Humans; Keratins; Mineral Oil; Oils; Psoriasis; Skin Diseases | 1964 |
CHAPPING AND CHILBLAINS.
Topics: Adrenal Cortex Hormones; Altretamine; Antineoplastic Combined Chemotherapy Protocols; Chilblains; Cisplatin; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Drug Therapy; Frostbite; Humans; Keratins; Ointments; Sebum; Skin Diseases; Sweat; Vitamins | 1964 |