bromochloroacetic-acid and Hair-Diseases

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

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

The mammalian hair follicle (HF) is an active skin appendage which operates hair cycles throughout life. Recent advances in molecular genetics have led to the identification of many genes expressed in the HF. Furthermore, mutations in some of these genes have been shown to underlie congenital hair loss disorders in humans. Patients with congenital hair loss disorders can show various hair shaft anomalies, such as woolly hair and monilethrix. In the Japanese populations, most patients with congenital woolly hair/hypotrichosis possess common founder mutations in the lipase H (LIPH) gene. Identification of the causative genes for hair loss disorders directly demonstrates crucial roles of these genes in HF morphogenesis, development and/or hair growth in humans.

Topics: Cadherins; Desmosomes; Hair Diseases; Humans; Hypotrichosis; Keratins; Lipid Metabolism; Transcription Factors

The identification of causative genes carries the promise of new and innovative therapeutic strategies for both inherited and acquired hair disorders. Moreover, the delineation of the relationships between similar phenotypes, resulting from mutations affecting seemingly distinct regulatory pathways, paves the way to improved diagnosis and treatment. Finally, understanding the biological processes governing HF development and maintenance may have implications for more general disease processes in the skin, such as inflammation and cancer.

Topics: Hair Diseases; Hair Follicle; Humans; Keratins

The term 'keratin' is generally accepted to refer to the epithelial keratins of soft and hard epithelial tissues such as: skin, cornea, hair and nail. Since their initial characterization, the total number of mammalian keratins has increased to 54, including 28 type I and 26 type II keratins. Inherited defects that weaken the keratin load-bearing cytoskeleton produce phenotypes characterized by fragility of specific subsets of epithelial tissues. The vast majority of mutations are either missense or small in-frame in-del mutations and disease severity often relates to the position of the mutation in relation to the rod domain. The most complex epithelial structure in humans, the hair follicle, contains trichocyte ('hard') keratin filaments and approximately half of the 54 functional human keratin genes are trichocyte keratins. So far, only four of these have been linked to human genetic disorders: monilethrix, hair-nail ectodermal dysplasia, pseudofolliculitis barbae and woolly hair, while the majority of the hair keratins remain unlinked to human phenotypes. Keratin disorders are a classical group of dominant-negative genetic disorders, representing a large healthcare burden, especially within dermatology. Recent advances in RNA interference therapeutics, particularly in the form of small-interfering RNAs, represent a potential therapy route for keratin disorders through selectively silencing the mutant allele. To date, mutant-specific siRNAs for epidermolysis bullosa simplex, pachyonychia congenita and Messmann epithelial corneal dystrophy-causing missense mutations have been developed and proven to have unprecedented specificity and potency. This could herald the dawn of a new era in translational medical research applied to genetics.

Topics: Animals; Ectodermal Dysplasia; Genetic Therapy; Hair Diseases; Humans; Keratins; Mutation; RNA, Small Interfering

Elucidation of the genes encoding structural proteins of the human hair follicle has advanced rapidly during the last decade, complementing nearly three previous decades of research on this subject in other species. Primary among these advances was both the characterization of human hair keratins, as well as the hair keratin associated proteins (KAPs). This review describes the currently known human KAP families, their genomic organization, and their characteristics of expression. Furthermore, this report delves into further aspects, such as polymorphic variations in human KAP genes, the role that KAP proteins might play in hereditary hair diseases, as well as their modulation in several different transgenic mouse models displaying hair abnormalities.

Topics: Amino Acid Sequence; Animals; Chromosome Mapping; Gene Expression Regulation; Hair; Hair Diseases; Hair Follicle; Humans; Keratins; Molecular Sequence Data; Multigene Family; Phylogeny; Polymorphism, Genetic; Sulfur

We report the case of a 57-year-old immunocompromised man with a pilomatrix carcinoma in his left forearm. Pilomatrix carcinoma is the rare malignant counterpart of pilomatrixoma. It has a potential for local recurrence and can metastasise to distant sites. We discuss the differential diagnosis of this rare tumour, and the difficulty in distinguishing this lesion from an atypical proliferating pilomatrixoma. Ultrastructural features of pilomatrix carcinoma are also discussed.

Topics: Carcinoma; Desmosomes; Diagnosis, Differential; Hair Diseases; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Mucin-1; Pilomatrixoma; Skin Neoplasms

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

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

Monilethrix is an inherited hair dystrophy in which affected, fragile, hairs have an unique beaded morphology. Ultrastructural studies suggest a defect in filament structure in the cortex of the hair, and the hard keratins of hair and nail are thus candidate genes. In several families with autosomal dominant monilethrix, the disorder has been linked to the type II keratin gene cluster at chromosome 12q13. Recently, causative mutations in the critical helix termination motif in the 2B domain of the human hair basic keratin 6 (hHb6) have been identified. We now report the results of sequencing this domain in 13 unrelated families or cases with monilethrix. Five of the 13 had the same mutation as previously found, a G to A transversion leading to a lysine for glutamic acid substitution (E413K) in the 2B domain (residue 117 of the 2B helix) of hHb6. The mutation was confirmed by a restriction fragment length polymorphism assay developed for this purpose, and, as this mutation is evidently a common cause of the syndrome, for use in screening other cases. In eight families or cases, however, including three in whom linkage data are consistent with a defect at the type II keratin locus, no mutation was found in this domain of hHb6.

Topics: Family Health; Hair Diseases; Humans; Keratins; Pedigree; Polymorphism, Restriction Fragment Length; Protein Structure, Tertiary

The importance of wool in the textile industry has inspired extensive research into its structure since the 1960s. Over the past several years, however, the hair follicle has increased in significance as a system for studying developmental events and the process of terminal differentiation. The present chapter seeks to integrate the expanding literature and present a broad picture of what we know of the structure and formation of hair at the cellular and molecular level. We describe in detail the hair keratin proteins and their genes, their structure, function and regulation in the hair follicle, and also the major proteins and genes of the inner and outer root sheaths. We discuss hair follicle development with an emphasis on the factors involved and describe some hair genetic diseases and transgenic and gene knockout models because, in some cases, they stimulate natural mutations that are advancing our understanding of cellular interactions in the formation of hair.

Topics: Amino Acid Sequence; Animals; Animals, Genetically Modified; Biomechanical Phenomena; Cytokines; Gene Expression Regulation; Hair; Hair Diseases; Hair Follicle; Humans; Intermediate Filament Proteins; Keratins; Mice; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Protein Precursors; Proteins; Sequence Homology, Amino Acid; Sheep; Terminology as Topic

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

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

In 1984, Zaun described a new type of pilary dysplasia characterized by easily pluckable hair. We were able to observe three patients with this anomaly, and this paper is an attempt at reviewing the subject on the basis of these new cases compared with those previously published. Clinical features. The major sign of the anomaly is that hairs can be pulled off in tufts easily and painlessly, and promptly grow again (our cases). In all cases reported so far the hair was blond or dark-blond; in some patients it is described as scintillating (our cases). The hair shaft is usually thin (one of our cases), but it may be of normal caliber (two of our patients). In the occipital region the hairs are entangled, dry and short (our cases). They are implanted wide apart or at normal intervals (our patients); areas of alopecia are sometimes encountered (our cases). Hair growth may be slow (one of our cases) or of normal speed (two of our cases). The eyelashes and eyebrows, as well as other body hairs, are normal in all patients (fig. 1). Microscopy. The trichogram is exclusively composed of anagenic and dystrophic roots (our cases). Pathological examination by biopsy of the scalp is characteristic: transverse and oblique sections of the follicles show that the hairs are oval, triangular or trapezoidal in shape (fig. 7). Alterations of the inner epithelial sheath are also present, including keratinization and early decomposition (fig. 8), lack of complementation (fig. 7) and fissures between the cuticle of the inner epithelial sheath and of the hair, in the keratogenic area (fig. 9). (ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alopecia; Child; Child, Preschool; Epithelium; Female; Hair; Hair Diseases; Humans; Keratins; Male; Microscopy, Electron, Scanning; Microscopy, Polarization

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

A controlled randomized double-blind study was carried out in 72 female patients to compare tolerance and efficacy of two therapeutic agents containing vitamins of the B-group and L-cystine in different compositions versus a placebo in diffuse effluvia and hair structure lesions. Hair swelling as a criterion of hair quality and frontal and parietal anagen rates in trichograms as criteria of hair growth were determined before and after 4 months of therapy. Treatment with active medication 1 was statistically significantly superior to treatment with the placebo according to these criteria. Treatment with active medication 2 was superior to treatment with the placebo but inferior to treatment with active medication 1. The overall evaluation of efficacy by investigator and patient was in good agreement with these results. The additional active ingredients contained in active medication 1 but not contained in active medication 2 contribute to the efficacy of the medication. They cannot be compensated by the higher amounts of L-cystine contained in active medication 2. Given their good tolerance, no adverse effects were observed with the two active medications.

Topics: 4-Aminobenzoic Acid; Administration, Oral; Adult; Cysteine; Cystine; Double-Blind Method; Drug Combinations; Female; Hair; Hair Diseases; Hair Preparations; Humans; Keratins; Pantothenic Acid; Thiamine; Yeast, Dried

Growth and quality of hair was studied after treatment with Pantogar, another prescription (Verum-2) and placebo for four months in 60 patients with diffuse effluvium capillorum and agnogenic structural alternations of hair. Efficacy was assessed by measurements of swelling, dye-binding and thickness for hair-quality and evaluation of hair-density and trichograms for hair-growth. Statistical analysis of swelling properties and trichogram data indicated that Pantogar was effective, the second preparation improved quality of hair and retarded hair loss. Placebo was ineffective judged by the used parameters. Tolerance of the treatment was good and adverse effects could not be substantiated.

Topics: 4-Aminobenzoic Acid; Alopecia; Aminobenzoates; Calcium; Cysteine; Cystine; Double-Blind Method; Drug Combinations; Female; Hair Diseases; Humans; Keratins; Male; Pantothenic Acid; Thiamine; Yeast, Dried

The final shape of a head hair is predetermined through a variety of factors during its formation in the follicle. These are genetic pathways, specific growth factors, cell differentiation and segregation, etc, with spatial as well as chronological dynamics. The cortex of hair consists of two major cell groups. These are characterized by parallel (para-type) or roughly helical arrangements (ortho-type) of the intermediate filaments (IF). There are also cell-specific differences in the disulphide content, that is, of the cross-link density of the IF-associated matrix proteins. Given the current state of the academic discussion, we consider it as timely to support and broaden the view that, the structural differences of the cell types together with their lateral segregation are the main driving factor of curl formation. The mechanical effects, which derive thereof, are triggered in the transition zone of the follicle, that is, upon formation of the mature hair shaft. Furthermore, an irregular, "flat" cross section of the hair shaft is shown to be a synergistic but not determining factor of curl formation. The degree of cell type segregation along the mature hair shaft together with dynamic changes of the location of the plane of segregation, namely in a non-circular cross section can account for very complex curl patterns. Against the background of these views, we argue that contributions to hair curl are implausible, if they relate to physical mechanisms which are active below the transition zone from the living to the mature (dead) hair.

Topics: Animals; Biomechanical Phenomena; Cell Differentiation; Cell Separation; Hair; Hair Diseases; Hair Follicle; Humans; Intermediate Filament Proteins; Keratins; Models, Biological; Scalp

Topics: Animals; Cardiomyopathies; Cell Line, Tumor; Desmin; Desmoplakins; Epidermis; Hair Diseases; HEK293 Cells; Humans; Keratins; Mice; Mice, Knockout; Protein Binding; Protein Domains; Protein Folding; Skin Diseases, Genetic

A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.

Topics: Animals; Dermis; Diagnosis, Differential; Dog Diseases; Dogs; Female; Hair Diseases; Hair Follicle; Immunohistochemistry; Keratins; Skin Neoplasms

Pili torti is an extremely rare hair phenotype characterized by short length of hairs with hair shafts being easily broken. However, the mechanism of fragility in pili torti is unclear. In this study, we examined the underlying morphological features responsible for pili torti formation using transmission electron microscopy (TEM). We used pili torti samples from a patient with Björnstad syndrome and normal hairs from a healthy subject as a comparison. The macroscopic morphological features of the samples agreed with the results of a previous study showing that pili torti is twisted, flattened, thin and with partial trichorrhexis. Young's modulus of the samples was lower than that of normal hairs. Because the cross-sectional area of the pili torti samples was also smaller than that of normal hairs, it was clarified that the tensile strength of pili torti is 2.1-times lower than that of normal hair. Assessment of morphological features by TEM showed that the cuticle layers of the samples had wavy shapes with different thicknesses. Additionally, the cortex in the samples showed loose keratin intermediate filaments (IF). Our results suggested that these abnormalities in pili torti had already occurred below the infundibulum. Thus, the weakness of pili torti in tensile strength is thought to result from loose IF because of dysformation of disulfide bonds.

Topics: ATPases Associated with Diverse Cellular Activities; Child, Preschool; Electron Transport Complex III; Female; Hair Diseases; Hair Follicle; Hearing Loss, Sensorineural; Humans; Infant; Intermediate Filaments; Keratins; Microscopy, Electron, Transmission; Mitochondrial Diseases; Mutation; Scalp

Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions.. Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, β-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy.. The CKs, CD138, β-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor.. Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied.

Topics: beta Catenin; Craniopharyngioma; Epithelial Cells; fas Receptor; Glucose Transporter Type 1; Hair Diseases; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Microscopy, Electron, Scanning; Neprilysin; Odontogenic Cyst, Calcifying; Odontogenic Tumors; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms; Syndecan-1

Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth factor-β1 (TGF-β1) and four-and-a-half LIM domain protein 2 (FHL2) in pilomatricoma in synopsis with their expression patterns in human anagen hair. Human anagen hair showed TGF-β1 and nuclear FHL2 expression in the outer root sheath layer separated from nuclear β-catenin staining, which was observed in cells of matrix and inner root sheath layers. Correspondingly, 41 out of 50 pilomatricomas showed co-labelling of TGF-β1 and nuclear FHL2 in tumour cells, which mostly lacked nuclear β-catenin expression. Tumoural proliferation (ki67) was associated with nuclear β-catenin staining but not with expression of nuclear FHL2. In early pilomatricomas, TGF-β1 expression was observed in few peripheral tumour cells showing absent or faint nuclear FHL2 co-staining. TGF-β1 expression extended in growing tumours going along with strong nuclear FHL2 co-labelling as well as progressive keratin 14 and keratin 1 expression. In vitro, cultured human keratinocytes showed weak to marked autocrine TGF-β1 expression; in case of enhanced TGF-β1 expression associated with keratin 10 staining. TGF-β1-treatment of cultured human keratinocytes induced nuclear and cytoplasmatic FHL2 staining as well as keratin 14 staining. Accordingly, siRNA-mediated FHL2 knockdown of TGF-β1-stimulated keratinocytes reduced keratin 14 staining. In conclusion, tumoural TGF-β1 secretion seems to induce nuclear translocation of co-factor FHL2 mediating progressive keratin expression in pilomatricoma.

Topics: Active Transport, Cell Nucleus; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Hair Diseases; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; LIM-Homeodomain Proteins; Male; Middle Aged; Muscle Proteins; Pilomatrixoma; Skin Neoplasms; Transcription Factors; Transforming Growth Factor beta1; Young Adult

We herein report two cases of cystic trichoblastoma with an immunohistochemical study. The histopathological findings in these cases included new information, namely, their being composed of two and three cysts, the cystic components had features of a steatocystoma and a hybrid cyst in one case, and there were projections of an aggregation of trichoblastoma, as well as papillary projections of follicular germinative cells, from the cyst walls. The follicular germinative cells observed in the papillary projections and in the aggregations of trichoblastoma expressed cytokeratin-15 (clone C8/144B) and PHLDA1, markers of follicular stem cells. Cystic trichoblastoma is a unique type of trichoblastoma, which originates from the cyst walls of an infundibular cyst (usually) or steatocystoma/hybrid cyst (rarely). In some cases, a trichoblastic infundibular cyst is considered to be a minor form (or possibly a primitive stage) of cystic trichoblastoma.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Follicular Cyst; Hair Diseases; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Transcription Factors

Topics: Animals; Chromosomes, Mammalian; Cytoskeleton; Gene Expression Profiling; Hair Diseases; Hair Follicle; Intermediate Filament Proteins; Keratins; Mice; Mice, Transgenic; Oligonucleotide Array Sequence Analysis; STAT3 Transcription Factor

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

Topics: Aged; Cell Proliferation; Epidermal Cyst; Epithelial Cells; Female; Follicular Cyst; Hair Diseases; Humans; Keratins

Pilomatricoma is a common benign neoplasm of the skin characterized by a solid cutaneous nodule of hair matrix origin. The anetodermal or lymphangiectatic variant of pilomatricoma is rare, and its bullous appearance is often associated with attenuated collagen and elastic fibrils and dilated lymphatic vessels in the overlying dermis. However, the tumors of anetodermic pilomatricoma have never been characterized at the molecular level, and the exact mechanism for their development is unknown. In this study, we evaluated histological and molecular features of a bullous pilomatricoma along with 5 control tumors and determined that tumors of both anetodermic and control pilomatricoma comprise similar molecular features, such as nuclear lymphoid enhancer binding factor 1 (LEF1) localization and the expression of keratins. In addition, we associated the development of the anetodermic pilomatricoma with mechanical trauma, scar tissue formation, and increased numbers of blood and lymphatic vessels. This study suggests that the development of the anetodermic form of pilomatricoma is unlikely to be associated with the intrinsic properties of the tumor but with the mechanical trauma that disrupts the dermal integrity and vascular microenvironment.

Topics: Adolescent; Adult; Biomarkers, Tumor; Blister; Blood Vessels; Female; Fluorescent Antibody Technique; Hair Diseases; Humans; Immunohistochemistry; Keratins; Lymphatic Vessels; Lymphoid Enhancer-Binding Factor 1; Male; Middle Aged; Pilomatrixoma; Skin Neoplasms; Stress, Mechanical; Young Adult

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

Topics: Epidermal Cyst; Filaggrin Proteins; Hair Diseases; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Pilomatrixoma; Skin Neoplasms; Young Adult

Hair cortex comedo was described originally in an article detailing 2 cases of a comedo-like clinical lesion that was histologically a keratinous plug with cornification similar to the cortex of the hair shaft. We have collected retro- and prospectively a series of 34 cases of hair cortex comedo. In our series, there was a slight female predominance (Male:Female of 1:1.4), and the mean patient age was 28.8 years. All lesions were solitary, distributed mainly on the head and neck or trunk, and were described clinically as a blue subcutaneous papule or nodule with "cyst" as the most common clinical differential diagnosis. Histologic examination showed a solitary, vertically oriented, uniformly sized oval nodule of compact laminated corneocytes sitting in a patulous invagination lined by epithelium similar to the infundibulum, isthmus, or combinations of them; rarely matrical epithelium was identified. Entrapped melanin (30/34 cases), shadow cells (16/34 cases), and calcification (12/34 cases) were identified commonly. Remnants of a surrounding follicle were noted in 15 cases, with infundibular epithelium in 9 of the cases, isthmic epithelium in 3, and matrical or supramatrical epithelium (or both) in 3. There was an associated dense granulomatous infiltrate in the majority of the cases (25/34). Although hair cortex comedo was thought originally to be a variant of dilated pore of Winer, we believe that these distinctive lesions, which are characterized histopathologically by a uniformly sized vertically oriented dermal plug of laminated corneocytes with entrapped melanin and surrounding granulomatous inflammation, are likely derived from matrical or supramatrical cells (or both).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcinosis; Child; Child, Preschool; Diagnosis, Differential; Epithelial Cells; Female; Granuloma; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Melanins; Middle Aged; Missouri; Predictive Value of Tests; Prospective Studies; Retrospective Studies; Young Adult

Pilomatricoma is believed to differentiate towards the hair matrix and hair cortex. To elucidate the origin of differentiation in pilomatricoma, we studied the expression of epithelial keratin (K) and filaggrin (filament aggregating protein) in pilomatricoma. An immunohistochemical study has been made of 53 cases of pilomatricoma using 10 monospecific anti-keratin antibodies and anti-filaggrin antibody. Basophilic cells, transitional cells and shadow cells did not react with epithelial keratins and filaggrin antibodies as well as hair matrix and hair cortex. Instead, infundibular-type epithelium was positive for K1, K10 and filaggrin. Epithelium showing trichilemmal keratinization was positive for K14 and K16. The hair bulge-like structure was positive for K19. The differentiation of pilomatricoma is diversified, and is heterogeneous in epithelial keratin and filaggrin expression. Our results for keratin and filaggrin expression suggested that pilomatricoma can differentiate not only towards hair matrix and hair cortex, but also follicular infundibulum, outer root sheath and hair bulge.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Filaggrin Proteins; Hair; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pilomatrixoma; Skin; Skin Neoplasms

A case of distinctive benign follicular neoplasm previously reported under the designation of trichogerminoma is described. A 45-year-old man presented with an asymptomatic nodule on the scalp since 3 years. Histologically, the lesion corresponded to a well-organized, symmetrical dermal nodule made up of basophilic lobules included in a fibrocytic stroma. The lesion had the characteristics of hair germ tumors; however, most lobules depicted a distinctive pattern of rounded nests of concentrically arranged clear cells. Small follicle bulb-like basophilic structures, foci of sebaceous differentiation, and areas of infundibulocystic, isthmic, and outer sheath keratinization were also seen. This neoplasm and the other tumors with hair germ differentiation such as trichoblastoma and panfolliculoma seem to represent the same spectrum of hair follicle neoplasms only distinguishable by their degree of differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Scalp; Skin Neoplasms

Origin of basal cell carcinoma (BCC) is still unclear. We studied the cytokeratin (CK) profile in BCC using monoclonal antibodies against 12 CKs to further investigate the suggested origin of the tumor from follicular matrix cells or from follicular outer root sheath cells and to determine if BCC subtypes can be identified on the basis of their CK profiles. Cases of pilomatricoma and samples of fetal skin served as controls to establish the CK profile in matrical cells and developing follicles during intrauterine life, that of the epidermis and cutaneous adnexa in adult life having been determined in a previous study. The most significant findings were as follows: (a) CK 5 and CK 17 positivity in all the BCCs studied; (b) CK 7, CK 8, CK 18, and CK 19 positivity in 30/52, 33/52, 42/52, and 14/52 BCCs, respectively; (c) CK 14 negativity in almost all the BCCs studied; and (d) lack of CK 1 expression only in 2/2 morpheiform BCCs and 4/10 nodular BCCs. The study suggests a tumorous differentiation toward follicular outer root sheath cells and, in most cases, also toward the glandular components of the pilosebaceous-apocrine unit. No significant difference in the CK profile among the BCC subtypes studied was found.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Fetus; Gestational Age; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Pilomatrixoma; Skin; Skin Neoplasms

We report a case of primary sarcoma of the skin with a biphasic histological pattern, being composed of areas of mixed mesenchymal-epithelial cell proliferation and areas of purely sarcomatous growth. The tumor occurred in the posterior cervical region of a 93-year-old man, and its history was marked by sudden, rapid enlargement after many years of stable duration. The excised lesion was about 4 cm in diameter, had a firm consistency and was covered by intact skin. Histological examination showed a multifocal proliferation of follicular germinative cells arranged in corymbiform and petaloid shapes with an overall retiform growth pattern. Epithelial cords and strands were composed of cytologically uniform cells with bland nuclear features and were surrounded by a prominent, fibroblast-rich stroma reminiscent of a perifollicular sheath. In many areas of the tumor the stroma showed abrupt transition into a pleomorphic proliferation of large sarcomatous cells with frequent and often atypical mitoses. Multinucleated neoplastic cells infiltrated the epithelial structures to cause their partial or total obliteration in many fields of the lesion. Immunohistochemically, the epithelial cells displayed expression of various keratins, with a particularly intense staining for 34betaE12, and were partly positive for the CD10 antigen. A strong immunostaining for this antigen was also observed in malignant-appearing stromal areas, where no expression of cytokeratins was detected. Moreover, nuclear positivity for p53 protein was seen in sarcomatous cells, whereas it resulted in total lack of epithelial elements. Our case emphasizes that high-grade sarcoma may occur in the spectrum of trichoblastic tumors and that it may share some features of other noncutaneous biphasic neoplasms, such as mammary cystosarcoma phyllodes.

Topics: Aged, 80 and over; Cell Proliferation; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Neprilysin; Sarcoma; Skin Neoplasms; Stromal Cells; Tumor Suppressor Protein p53

To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament-aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.

Topics: Adult; Filaggrin Proteins; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Sebaceous Gland Diseases

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

Ectodermal dysplasias (ED) are developmental disorders affecting tissues of ectodermal origin including hair, nail, teeth and sweat glands. To date, four different types of ectodermal dysplasias involving only hair and nails have been described. In an effort to understand the molecular basis of ED of hair and nails, a Pakistani family with multiple affected individuals was studied. Linkage analysis was carried out by genotyping eight members of the family (five normal and three affected) using microsatellite markers linked to the related phenotype. The diseased phenotype was mapped to chromosome 12p11.1-q21.1 (Zmax=3.1). DNA sequence analysis of the coding exons and splice sites of six hair keratin genes, located in the linkage interval, failed to detect any pathogenic mutation in the affected individuals of the family. Failure to detect a mutation in the epithelial keratin genes suggests that the mutation lies either in the regulatory region of one of the keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.

Topics: Chromosome Mapping; Chromosomes, Human, Pair 12; Ectodermal Dysplasia; Female; Genes, Recessive; Genotype; Hair; Hair Diseases; Humans; Keratins; Male; Mutation; Nails; Nails, Malformed; Pakistan; Pedigree; Phenotype

The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.

Topics: Alleles; Amino Acid Sequence; Child, Preschool; Desmogleins; DNA Mutational Analysis; Female; Hair; Hair Diseases; Heterozygote; Humans; Hypotrichosis; Keratins; Microscopy, Electron, Scanning; Molecular Sequence Data; Mutation; RNA Stability; Transcription, Genetic

We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co-expression of the LEF1/beta-catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078).. Formalin-fixed paraffin sections of the tumor were examined using a panel of mono- and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and beta-catenin.. Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co-expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/beta-catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co-expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls.. Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co-expression and disrupted hHa1/beta-catenin-LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor.

Topics: Aged, 80 and over; beta Catenin; Biomarkers, Tumor; Epithelial Cells; Hair; Hair Diseases; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Lymphoid Enhancer-Binding Factor 1; Male; Pilomatrixoma; Skin Neoplasms; Transcription Factors

AP-2 transcription factors have been implicated in epidermal biology, but their functional significance has remained elusive. Using conditional knockout technology, we show that AP-2alpha is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking AP-2alpha exhibits elevated expression of the epidermal growth factor receptor (EGFR) in the differentiating layers, resulting in hyperproliferation when the receptors are activated. Chromatin immunoprecipitation and promoter activity assays identify EGFR as a direct target gene for AP-2alpha repression, and, in the absence of AP-2alpha, this is manifested primarily in excessive EGF-dependent phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto unrecognized repressive role for AP-2alpha in governing EGFR gene transcription as cells exit the basal layer and withdraw from the cell cycle. These results provide insights into why elevated AP-2alpha levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2alpha and elevated EGFR proteins.

Topics: Animals; Animals, Newborn; Calcium; Caspase 3; Caspases; Cell Proliferation; Chromatin Immunoprecipitation; Chromones; Dermis; DNA; Embryo, Mammalian; Enzyme Inhibitors; Epidermal Cells; Epidermal Growth Factor; Epidermis; ErbB Receptors; Gene Expression; Gene Expression Regulation; Hair Diseases; Integrases; Keratinocytes; Keratins; Ki-67 Antigen; MAP Kinase Signaling System; Mice; Mice, Transgenic; Morpholines; Phosphorylation; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; Quinazolines; Signal Transduction; Skin; Skin Abnormalities; Tetradecanoylphorbol Acetate; Transcription Factor AP-2; Transforming Growth Factor alpha; Tyrphostins

Ectodermal dysplasias are developmental disorders affecting tissues of ectodermal origin. To date, four different types of ectodermal dysplasia involving only hair and nails have been described. In an effort to understand the molecular bases of this form of ectodermal dysplasia, large Pakistani consanguineous kindred with multiple affected individuals has been ascertained from a remote region in Pakistan.. To identify the gene underlying the phenotype.. Microsatellite markers were genotyped in candidate regions and two point and multipoint parametric linkage analysis carried out.. The disease locus was mapped to a 16.6 centimorgan region on chromosome 12q12-q14.1 (Zmax = 8.2), which harbours six type II hair keratin genes. DNA sequence analysis revealed a homozygous missense mutation in the hair matrix and cuticle keratin KRTHB5, leading to histidine substitution of a conserved arginine residue (R78H) located in the head domain.. This report provides the first direct evidence relating to the molecular pathogenesis of pure hair-nail ectodermal dysplasias.

Topics: Arginine; Chromosome Mapping; Chromosomes, Human, Pair 16; Conserved Sequence; Ectodermal Dysplasia; Hair Diseases; Homozygote; Humans; Keratins; Keratins, Hair-Specific; Keratins, Type II; Microsatellite Repeats; Mutation, Missense; Nail Diseases

To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard alpha-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard alpha-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components. Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.

Topics: Animals; Biomarkers, Tumor; Blotting, Western; Cells, Cultured; Craniopharyngioma; Hair; Hair Diseases; Humans; Hybridomas; Immunoenzyme Techniques; Jaw Neoplasms; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Neoplasms; Odontogenic Cyst, Calcifying; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms

A 4-year-old Caucasian girl with pili trianguli et canaliculi had distinctive findings. These included unique ultrastructural alterations consisting of tonofilament-desmosomal detachment and tonofilament clumping within inner root sheath cells. We believe that the hair anomaly in this condition may be due to a compromised cytoskeleton with subsequent configurational changes of the inner root sheath. Despite these configurational changes keratinization of the inner root sheath occurs. As inner root sheath keratinization typically precedes keratinization of the hair shaft, the abnormally configured inner root sheath determines the surface characteristics of the hair shaft in pili trianguli et canaliculi.

Topics: Child, Preschool; Female; Hair; Hair Diseases; Humans; Immunohistochemistry; Keratins; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission

Topics: Adenoma; Cell Differentiation; Female; Hair Diseases; Humans; Keratins; Middle Aged; Skin Neoplasms

We report a congenital follicular dysplasia in five coatis from four different litters of the same parents born between 1996 and 2001. These coatis were born apparently alopecic with the entire body covered by very short dark hairs, with secondary lichenification of the skin, crusting and scaling. The main histopathological feature consisted of premature cornification of the cortical cells of the hair shaft. Cells were already fully cornified below the Adamson's fringe, leading to a disorganized, fragmented and constricted hair shaft. Based on the history of the animals and the nature of the lesions, a genetic defect in hair shaft keratinization was suspected.

Topics: Alopecia; Animals; Animals, Zoo; Female; Hair Diseases; Hair Follicle; Immunohistochemistry; Keratins; Male; Procyonidae

Human hair follicles exhibit a complex pattern of sequential hair keratin expression in the hair matrix, cuticle, and cortex. In pilomatricomas, that is, benign skin tumors thought to arise from germinative matrix cells of the hair follicle and retaining morphological signs of cortical differentiation, this differential hair keratin pattern has been shown to be faithfully preserved in the lower and upper transitional cell compartments of the tumors. Here we show that also the co-expression of hair keratin hHa5 with its regulatory nuclear homeoprotein HOXC13 in matrix cells of the hair follicle is maintained in lower transitional cells of pilomatricomas. In contrast, the nuclear co-expression of LEF1 and beta-catenin, which in the hair follicle has been postulated to initiate cortex cell differentiation through the induction of hair keratin hHa1 expression (Merill et al, Genes Dev 15:1688-1705, 2001), is not preserved in upper transitional cells of pilomatricomas. Although these cells correctly express hHa1, they are completely devoid of LEF1 and nuclear LEF1/beta-catenin co-expression is shifted to a subpopulation of hair keratin-free basaloid cells of the tumors. These data imply that unlike the normal hair follicle, cortical differentiation in pilomatricomas is not under the control of the canonical Wnt signaling pathway.

Topics: beta Catenin; Cytoskeletal Proteins; DNA-Binding Proteins; Hair Diseases; Hair Follicle; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lymphoid Enhancer-Binding Factor 1; Pilomatrixoma; Signal Transduction; Skin Neoplasms; Trans-Activators; Transcription Factors

Recent genetic investigations support the idea that basal cell carcinoma (BCC) is trichoblastic carcinoma. However, it is generally thought that clear cell basal cell carcinoma is a result of degeneration rather than tricholemmal differentiation.. We report a case of BCC, with clear cell components, that developed within seborrheic keratosis, with histopathological and immunohistochemical findings.. The clear cell components in the present case showed the following four characteristics: (i) at the periphery of the aggregations, columnar clear cells were aligned in a palisade along a well-defined basement membrane; (ii) the nuclei of the columnar clear cells were at the pole opposite the basement membrane; (iii) the clear cells contained glycogen; (iv) in the aggregations with clear cell components, there was diffuse positive staining for cytokeratin 7 (CK7) (OV/TLR/30), but only the inner region stained positive for CK17. These four characteristics are comparable to those of the lower portion of normal outer root sheath. In addition, the BCC in the present case was partly composed of squamous cells that contained glycogen and were selectively positive for CK17 - features similar to those of squamous cells in normal outer root sheath.. Some clear cell BCCs are simply the result of degenerative change, but other clear cell BCCs may be the result of tricholemmal (at the lower portion) differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin Neoplasms

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair resulting from periodic thinning of the shaft (MIM 158000). The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoded region in two hair-specific keratins (hHb1 and hHb6) have been identified as responsible for this disorder. We investigated two unrelated families from Russia and Colombia with monilethrix and found two missense mutations in hHb6. In the Russian family, we found a G to A transition at the first base of codon 402, resulting in a lysine substitution (GAG to AAG), designated E402K. In the Colombian family, affected patients carried a missense mutation of codon 413, involving a transition from G to A causing a lysine substitution (GAG to AAG), designated E413K. These two mutations have been identified in other monilethrix families from Europe. Our findings extend the body of evidence implicating recurrent hHb6 and hHb1 mutations in monilethrix families from around the world.

Topics: Colombia; DNA Mutational Analysis; Female; Glutamic Acid; Hair Diseases; Humans; Keratins; Lysine; Male; Mutation, Missense; Pedigree; Russia

Within stratified squamous epithelia, such as the epidermis, desmogleins are generally expressed in a differentiation-specific manner. Similar to the epidermis, the hair follicle is compartmentalized into a hierarchy of cell types based on their level of differentiation. Relatively undifferentiated stem cells in the bulge can generate epidermis, sebaceous gland, and hair bulb matrix cells. The latter give rise to at least six different cell types that keratinize as they move up the hair shaft and inner root sheath. Here, we examined expression patterns of the desmoglein isotypes, desmogleins 1, 2, and 3 in the cutaneous epithelium, and discovered that desmoglein 1 and 2 expression correlated with the state of differentiation of defined populations within the hair follicle. Desmoglein 2 was highly expressed by the least differentiated cells of the cutaneous epithelium, including the hair follicle bulge of the fetus and adult, bulb matrix cells, and basal layer of the outer root sheath. In contrast, desmoglein 1 defined more differentiated cell populations, and was expressed in epidermal suprabasal cells, the inner root sheath, and the innermost layers of the outer root sheath. We found that the expression pattern of desmoglein 3 correlated with different types of keratinization. In areas of trichilemmal keratinization in the follicle, and in cysts arising from these areas, desmoglein 3 was expressed throughout all layers of the outer root sheath and cyst wall. In areas of epidermal-like keratinization, such as in the infundibulum and in epidermal inclusion cysts, desmoglein 3 expression was limited mainly to the basal layer. We conclude that desmoglein expression patterns define compartments of cells in similar states of differentiation within the cutaneous epithelium, and reveal a hierarchy of differentiation among these compartments.

Topics: Adult; Cadherins; Cell Differentiation; Cytoskeletal Proteins; Desmoglein 1; Desmoglein 2; Desmoglein 3; Desmogleins; Desmoplakins; Fetus; Follicular Cyst; Hair Diseases; Hair Follicle; Humans; Keratins

The histogenesis of trichilemmoma remains unclear.. To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression.. In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively.. CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent.. These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Cell Differentiation; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms

Mutations in the hair keratins hHb1 and hHb6 have been recently reported to cause monilethrix, an autosomal dominant hair shaft disorder, characterized by variable degrees of hair fragility and follicular hyperkeratosis. We found 10 families with monilethrix in whicn the parents were not clinically affected, and sequenced the hair keratin hHb1, hHb2 and hHb6 genes in seven patients. In five patients no mutations were found, while in two patients we identified de novo germline missense mutations at the helix termination motif: E402K (hHb6) and E413K (hHb1).

Topics: Amino Acid Motifs; DNA Mutational Analysis; Exons; Genotype; Hair Diseases; Heterozygote; Homozygote; Humans; Hyperkeratosis, Epidermolytic; Keratins; Lysine; Microsatellite Repeats; Mutation; Pedigree; Phenotype; Protein Structure, Tertiary; Sequence Analysis, DNA

Carcinomas that arise in a proliferating trichilemmal cyst (PTC) have been described under a variety of names. Monoclonal antibodies (mAbs) indicating follicular differentiation have become available and were used here in two rare tumors with uncommon biologic behavior. To further elucidate the histogenesis of carcinomas arising in a PTC, mAbs to hair follicle stem cells and to hair follicle differentiation-specific cytokeratins (mAbs to cytokeratin [CK] 7, CK8, CK18, and CK19 as well as mAbs to CD8/CK15 and CD34) were studied on paraffin-embedded sections of two cases of carcinoma arising in a PTC, one anaplastic carcinoma, and one poorly differentiated squamous cell carcinoma (SCC). For comparison, concurrent PTCs and trichilemmal cysts as well as four SCCs from controls were studied. The anaplastic carcinoma showed expression of CK7, indicating a fetal hair root phenotype, and expression of CD34, indicating trichilemmal differentiation. In contrast, the poorly differentiated SCCs as well as the control SCCs stained negative for most of the mAbs applied. Expression of fetal and trichilemmal hair follicle phenotypes suggests differentiation from hair stem cells and might explain differences in biologic behavior.

Topics: Aged; Biomarkers; Carcinoma, Squamous Cell; Cell Division; Epidermal Cyst; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Phenotype; Scalp; Skin Neoplasms

To report the clinical features of the loose anagen hair syndrome and to test the hypothesis that the typical gap between the hair and the inner root sheath may result from hereditary defects in the inner root sheath or the apposed companion layer.. Case series.. A pediatric dermatology unit (referral center).. A consecutive sample of 17 children (13 girls). For 9 of them and their first-degree relatives, molecular analyses were performed in the K6HF gene with 50 appropriate controls.. Minoxidil therapy (5% lotion) in 11 patients for 1 to 12 months.. Clinical and follow-up features and determination of mutations in the K6HF gene.. Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients seldom cut their hair, and 4 had unmanageable hair. One patient had hypodontia. Two patients had an additional clinical phenotype of diffuse partial woolly hair. The family history was positive for loose anagen hair syndrome in 5 patients. Marked improvement was noted after treatment with 5% minoxidil lotion in 7 of the 11 patients treated. Polymerase chain reaction analysis of the gene segments encoding the alpha-helical 1A and 2B subdomains of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In 3 of these 9 families, a heterozygous glutamic acid and lysine mutation, E337K, was identified in the L2 linker region of K6HF.. Diffuse partial woolly hair can be associated with loose anagen hair syndrome. A keratin mutation, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type I partner of K6hf, could be responsible for loose anagen hair syndrome in other patients, or the gene involved may be a minor gene.

Topics: Child; Child, Preschool; Female; Hair Diseases; Humans; Keratins; Male; Syndrome

Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours.. To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin.. We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17.. While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas.. These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.

Topics: Carcinoma, Basal Cell; Hair Diseases; Hair Follicle; Humans; Keratins; Neoplasm Proteins; Neoplasms, Basal Cell; Pilomatrixoma; Skin Neoplasms

The murine genome is known to have two keratin 6 (K6) genes, mouse K6 (MK6)a and MK6b. These genes display a complex expression pattern with constitutive expression in the epithelia of oral mucosa, hair follicles, and nail beds. We generated mice deficient for both genes through embryonic stem cell technology. The majority of MK6a/b-/- mice die of starvation within the first two weeks of life. This is due to a localized disintegration of the dorsal tongue epithelium, which results in the build up of a plaque of cell debris that severely impairs feeding. However, approximately 25% of MK6a/b-/- mice survive to adulthood. Remarkably, the surviving MK6a/b-/- mice have normal hair and nails. To our surprise, we discovered MK6 staining both in the hair follicle and the nail bed of MK6a/b-/- mice, indicating the presence of a third MK6 gene. We cloned this previously unknown murine keratin gene and found it to be highly homologous to human K6hf, which is expressed in hair follicles. We therefore termed this gene MK6 hair follicle (MK6hf). The presence of MK6hf in the MK6a/b-/- follicles and nails offers an explanation for the absence of hair and nail defects in MK6a/b-/- animals.

Topics: Animals; Epithelial Cells; Gene Deletion; Hair Diseases; Hyperplasia; Isomerism; Keratins; Mice; Mice, Knockout; Microscopy, Electron; Molecular Sequence Data; Mouth Diseases; Nail Diseases; Phenotype; Sequence Homology, Amino Acid; Skin; Starvation; Tongue; Wound Healing

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.

Topics: Animals; Cell Differentiation; Hair; Hair Diseases; Hair Follicle; Keratins; Membrane Proteins; Mice; Mice, Transgenic; Phenotype; Receptor, Notch1; Receptors, Cell Surface; Transcription Factors

An otherwise healthy 24-year-old woman presented with persistent asymptomatic skin-coloured papular lesions on her trunk which had appeared over 18 months, gradually increasing in number, size and the extent of the skin surface area involved. Physical examination revealed multiple flesh - to whitish - coloured papules, 2 to 5 mm in diameter, located on her neck, anterior chest wall, axillae and upper abdomen (Fig. 1). The lesions were smooth, painless on palpation and not grouped. Laboratory investigations only showed normal results. Histopathological examination of a papular lesion from the upper abdomen revealed a cystic structure in the mid-dermis lined by four to five layers of squamous epithelium with a discrete granular layer. Laminated keratinous material and multiple transversely or obliquely cut vellus hairs were present within the cyst, while sebaceous elements were lacking in the vicinity or within the cyst wall (Fig. 2a, b). Polaroscopic examination demonstrated double refractile vellus hairs in the cyst.

Topics: Adult; Diagnosis, Differential; Female; Follicular Cyst; Hair Diseases; Humans; Keratins

Since the first description by Hashimoto et al., there have been only a few case reports of rippled-pattern tricogenic tumor. In addition, there are no reports on detailed immunohistochemical analyses of this rare neoplasm. We describe here an additional case of rippled-pattern trichogenic tumor with a special reference to its immunohistochemical features.. A nodule arising on the occipital area of a 62-year-old Japanese woman was histologically and immunohistochemically investigated.. Histopathologically, the lesion contained various-sized lobular nests, which consisted of oval to elliptical shaped basaloid cells without any atypia and were embedded in the collagenous stroma. Some elongated basaloid cells were arranged in a palisading fashion forming parallel rows of epithelial ribbons in a rippled-pattern. Cytokeratin (CK) immunohistochemistry showed constant expressions of CK1/5/ 10/14, CK5/8, CK14 and CK7, and focal expressions of CK17 and CK19 in the basaloid cells, suggesting a keratin phenotypical similarity to the cells in small nodular type trichoblastoma.. The present tumor is a variant of trichoblastoma, and considered to be in close association with the outer root sheath and/ or follicular germinative cells.

Topics: Biomarkers, Tumor; Female; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Proteins; Neoplasms, Basal Cell; Skin Neoplasms

TTD is a rare human genetic disease caused by mutations in XPB and XPD, two subunits of the transcription/repair factor TFIIH, and whose outstanding clinical characteristic is a lack of most human UHS proteins resulting in sulfur-deficient brittle hair. In an attempt to understand this transcription defect, we report here the genomic cloning of two highly related UHS keratin genes specifically expressed in follicular and epidermal cells. In addition to a high degree of nucleotide homology (87%), both genes also have a similar 90-nt promoter sequence. In-vivo and in-vitro studies allowed us to specify the position of the start sites, the TATA-boxes and some regulatory regions. Results indicate that both genes present common features in the regulation of their transcription and suggest that control of their expression might be affected by mutations in TFIIH subunits.

Topics: Amino Acid Sequence; Cloning, Molecular; DNA Repair; Gene Expression Regulation; Hair Diseases; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Promoter Regions, Genetic; Restriction Mapping; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Transcription Factor TFIIH; Transcription Factors; Transcription Factors, TFII; Transcription, Genetic

Hard keratins are expressed in normal hair and nails, and are characterized by a higher cysteine content than cytokeratins. Previous studies have suggested a coexpression of hard keratins and cytokeratins in pilomatrixoma, a benign follicular tumour which could originate from the hair matrix. Human hair keratin basic 1 (hHb1) is a newly characterized hair keratin which is expressed specifically by cortical cells of the normal hair shaft. A preliminary study has suggested that hHb1 could be expressed in pilomatrixoma. In order to confirm this hypothesis, we have studied a series of 128 pilomatrixomas by in situ hybridization, using a 35S-labelled hHb1-specific probe. The anti-sense probe was used as a negative control. Among these pilomatrixomas, six were early cases, 60 were classified into the intermediate stage (either fully developed or early regressive cases) and 62 were late regressive tumours made of shadow cells only. Forty-seven tumours showed hHb1 expression (37%), all being intermediate stage pilomatrixomas. The areas positively stained by the probe were band-like structures made of transitional cells only, which were very close to cells showing tricholemmal keratinization features. Neither the basophilic matrix cells nor the shadow cells expressed hHb1. Our results suggest that pilomatrixomas can differentiate towards cortical cells during their maturation process, as this keratin is specifically expressed in the cortex of the normal hair shaft. These data are consistent with previous studies which showed the expression of a hard keratin group in transitional cells by immunohistochemistry. The histogenesis of basophilic cells of pilomatrixoma is controversial, but it is likely that transitional cells represent an equivalent of the hair cortex.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Female; Hair Diseases; Humans; In Situ Hybridization; Infant; Keratins; Male; Middle Aged; Pilomatrixoma; Skin Neoplasms

Many reports exist of pigmented adnexal tumors containing dendritic melanocytes such as pigmented basal cell carcinomas and pigmented pilomatricomas. Correspondingly, melanocytes are a known component of the bulbs of anagen follicles. The phenomenon of melanization of adnexal tumors highlights the interrelationship between melanocytes and adnexal epithelium and may represent normal melanocytes colonizing a neoplastic proliferation. We report on two cases of a unique tumor composed of neoplastic matrical cells with a significant component of melanocytes. Both cases presented as pigmented papules in older men (66 and 80 years, forearm and pectoral region, respectively). Histologically, these were well-defined nodular proliferations composed of variably melanized, pleomorphic, and mitotically active matrical and supramatrical cells forming clusters of "shadow cells." Admixed with the epithelial cells were numerous melanized dendritic melanocytes. Shadow cells expressed keratin 13, and a subpopulation of S-100 protein-positive dendritic cells were evident. No recurrence of any type was found after reexcisions 4 months and 2 years later. We propose the name of melanocytic matricoma for these two heretofore unreported cases of a unique neoplasm composed of matrical cells and melanocytes recapitulating epithelial-melanocyte interaction in the follicular anagen bulb. Although their small size, circumscription and clinical course suggest a benign nature, melanocytic matricomas' cytologic atypia disclose the potential for malignant behavior.

Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Melanocytes; Neoplasms, Adnexal and Skin Appendage; Pilomatrixoma; S100 Proteins; Skin Neoplasms; Treatment Outcome

Monilethrix, a rare human hair disorder with autosomal dominant transmission, can be caused by mutations in hair keratins. Up to now, causative mutations have only been found in two type II cortex keratins, hHb6 and hHb1. In these hair keratins, the helix termination motif, HTM, was the only site in which mutations were located. The most frequent mutation, which has been found in 22 cases, was a Glu413Lys substitution in hHb6, whereas other mutations, i.e., hHb6 Glu413Asp, hHb1 Glu413Lys, and hHb1 Glu402Lys, have been reported in a distinctly lower number of cases. In this study, we describe the equivalent of the hHb1 Glu402Lys mutation in the HTM of cortex keratin hHb6. The mutation occurred in an American family in which it could only be detected in one clinically affected individual. Thus the underlying G-->A transition represents a spontaneous germ-line mutation in the hHb6 gene. This new mutation indicates that both the hHb6/hHb1 Glu413Lys substitution and the hHb6/hHb1 Glu402Lys substitution, represent mutational hotspots in the HTM of type II cortex keratins. However, we also describe a monilethrix-causing mutation in the helix initiation motif, HIM, of the cortex keratin hHb6. The critical Asn114Asp substitution was only found in affected members of a large Swedish three-generation family. Considering that since childhood, half of the affected individuals suffer from complete baldness and follicular keratosis, the new HIM mutation seems to be associated with a rather severe disease phenotype. In conclusion, our data strongly suggest that monilethrix is a disease of the hair cortex, whose etiology is interesting in that causative mutations seem to be restricted to type II hair keratins.

Topics: Amino Acid Sequence; Animals; Base Sequence; Female; Hair Diseases; Helix-Turn-Helix Motifs; Humans; Keratins; Male; Pedigree; Point Mutation

Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.

Topics: Amino Acid Sequence; Codon; Female; Genotype; Hair Diseases; Humans; Keratins; Male; Molecular Sequence Data; Mutation; Phenotype; Polymorphism, Restriction Fragment Length; Protein Structure, Secondary

Extensive epidermal necrosis in newborn infants is an unusual event of heterogeneous cause.. The objective of this article is to describe what seems to be a previously unrecognized lethal disease.. The clinical and histopathologic features of three premature infants, two of them nonidentical twins, and the autopsy findings of one of them were analyzed.. Intrauterine lethal epidermal necrosis with hair follicle calcification, except for the face, hands, feet, elbows, and knees, was present in all three patients. Some histopathologic features were suggestive of epidermal apoptosis.. We propose that the clinicopathologic alterations in our patients represent a new condition that may be caused by massive epidermal apoptosis.

Topics: Apoptosis; Calcinosis; Collagen; Diseases in Twins; Elbow; Epidermis; Face; Fatal Outcome; Female; Fetal Diseases; Foot; Hair Diseases; Hair Follicle; Hand; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Keratinocytes; Keratins; Knee; Necrosis; Skin; Skin Abnormalities; Twins, Dizygotic

Bsk (bare skin) is an autosomal dominant mutation linked to the Krt 1 (type 1 keratin) locus of mouse chromosome 11. The adult Bsk mouse manifests hair loss and corneal opacity. To identify and characterize the keratin genes involved in this mutation, we examined the hypothesis proposing that the Bsk mutation might involve a recombination event between cornea-specific (K12) and hair-specific (mHa 1, 2, 3 and 4) type I keratin genes.. The Bsk phenotype was examined by histochemical analysis, using light and electron microscopy. RFLP was used for their genotyping, and possible keratin gene expression was examined by immunohistochemical staining, Western analysis, RT-PCR and Northern hybridization.. Northern hybridization, RT-PCR and Western blot analysis revealed that mHa 1, 2, 3 and 4 keratins are expressed in the skin, but not in cornea, whereas the expression of K12 is limited to the corneas of the Bsk mice. These data ruled out the hypothesis that Bsk phenotype results from a recombination event between K12 and mHa 1, 2, 3 and 4. Ultrastructural and biochemical analyses also indicated that Bsk does not involve negative dominant mutations of keratin 12, mHa 1, 2, 3 and 4, epidermal-specific keratin 10, or basal cell-specific keratin 14. Expression of an acidic 50 kD keratin, recognized by monoclonal antibody AK 2, was up-regulated in the injured corneas of normal mice as well as Bsk corneas.. The gene linked to the Bsk mutation remains unknown. The pathological changes in the skin and corneas may be secondary to the loss of protecting hairs and lashes by an unknown mechanism.

Topics: Animals; Blotting, Northern; Blotting, Western; Cornea; Corneal Opacity; DNA Primers; DNA, Complementary; Hair Diseases; Keratins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Recombination, Genetic; Skin

Monilethrix is a rare human hair disorder with autosomal dominant transmission that can be caused by mutations in hair keratins. Up until now, pathogenic mutations in the type II hair cortex keratins hHb6 and hHb1 were restricted to a highly conserved glutamic acid residue Glu413 (Glu117 of the 2B subdomains) in the EIATYRRLLEGEE helix termination motif of the two keratins. The critical glutamic acid residue was substituted either by a lysine or, less frequently, by an aspartic acid residue. Here we report a novel mutation in a French monilethrix family, which again consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1. Family members bearing the hHb1 Glu402Lys mutation exhibit a particularly variable disease phenotype. The pedigree comprises two infant members, one with pronounced dystrophic alopecia, follicular keratosis, and clear-cut moniliform hair, and one with no hair loss at all and moniliform hair detectable only by electron microscopy, as well as an adult individual without any clinically or electron microscopically detectable symptoms, but with clear historical proof of the disease.

Topics: Adult; Child, Preschool; Female; Glutamic Acid; Hair Diseases; Humans; Keratins; Lysine; Phenotype; Point Mutation

Monilethrix is a rare autosomal dominant disease characterized by hair fragility and hyperkeratotic papules. Mutations in type-II hair specific keratins hHb6 and hHb1 have recently been reported. We describe a large family with a E410D mutation in the evolutionary conserved helix termination motif of keratin hHb6 that was variably expressed among 12 heterozygous members, and severely expressed among 3 homozygous members. These 3 patients had essentially complete lack of scalp hair since the age of 2 months with no improvement over time as well as follicular keratotic involvement extensively expressed over the scalp and large body areas. The variability seen in heterozygous patients, along with seasonal and pregnancy-related improvement suggest that other genetic or environmental factors may modify keratin gene expression. This represents the first report of a co-dominant keratin hHb6 mutation resulting in severe disease.

Topics: Base Sequence; DNA Mutational Analysis; Female; Gene Expression; Genes, Dominant; Genetic Testing; Hair Diseases; Humans; Keratins; Male; Mutation; Pedigree; Reference Values

Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias in which the main phenotypic characteristic is hypertrophic nail dystrophy. In the Jackson-Lawler form (PC-2), pachyonychia is accompanied by multiple pilosebaceous cysts, natal teeth, and hair abnormalities. By direct sequencing of genomic PCR products, we report heterozygous K17 missense mutations in the same conserved protein motif in a further five PC-2 families (K17 N92S in one familial and three sporadic cases; K17 Y98D in one familial case) confirming that mutations in this gene are a common cause of PC-2. We also show heterozygous missense mutations in K17 (N92H and R94H) in two families diagnosed as steatocystoma multiplex. Mild nail defects were observed in some but not all of these patients on clinical re-evaluation of these families. All the K17 mutations reported here were shown to co-segregate with the disease in the pedigrees analyzed and were excluded from 100 unaffected, unrelated chromosomes by restriction enzyme analysis of K17 genomic PCR products. We conclude that phenotypic variation is observed with K17 mutations, as is the case with other keratin disorders.

Topics: Cysts; Ectodermal Dysplasia; Female; Hair Diseases; Humans; Keratins; Male; Mutation; Nail Diseases; Pedigree; Phenotype

Using in situ hybridization, human hair keratin basic 1 (hHb1) gene expression was investigated in human normal scalp. hHb1 transcripts were specifically detected in the cortical cells of hair shaft but neither in the outer and inner root sheaths, nor in the hair cuticle or the medulla. hHb1 expression was detected strongly in cortical cells located from the beginning of the keratogenous zone up to the isthmus. These data specify the localization of hHb1 expression. Furthermore, neoplasms with follicular differentiation, including trichoblastoma, trichoepithelioma, pilomatricoma, pilar carcinoma and basal-cell carcinoma, were analysed for hHb1 gene expression. One of the 4 pilomatricoma specimens examined exhibited a very high level of hHb1 transcripts. Interestingly, this labeling was specifically associated to a transitional cell layer en route to trichocytic differentiation, providing evidence that in pilomatricoma, epithelial germ cells can differentiate towards hair shaft keratinocytes before evolving in ghost cells.

Topics: Carcinoma, Basal Cell; Cell Differentiation; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Neoplasm Proteins; Pilomatrixoma; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms

Pathogenic mutations in a large number of human epithelial keratins have been well characterized. However, analogous mutations in the hard alpha-keratins of hair and nail have not yet been described. Monilethrix is a rare autosomal dominant hair defect with variable expression. Hairs from affected individuals show a beaded structure of alternating elliptical nodes and constrictions (internodes). These internodes exhibit a high prospensity to weathering and fracture. Strong evidence that trichocyte keratin defects might underlie this hair disorder was provided by genetic linkage analyses that mapped this disease to the type-II keratin gene cluster on 12q13. All affected individuals from a four-generation British family with monilethrix, previously linked to the type-II keratin gene cluster, as well as three unrelated single monilethrix patients, exhibited a heterozygous point mutation in the gene for type-II hair cortex keratin hHb6, leading to lysine substitution of a highly conserved glutamic acid residue in the helix termination motif (Glu 410 Lys). In a three-generation French family with monilethrix of a milder and variable phenotype, we detected another heterozygous point mutation in the same glutamic acid codon of hHb6, which resulted in a conservative aspartic acid substitution (Glu 410 Asp). These mutations provide the first direct evidence for involvement of hair keratins in hair disease.

Topics: Adolescent; Child; Female; Glutamic Acid; Hair Diseases; Heterozygote; Humans; Keratins; Lysine; Male; Middle Aged; Mutation; Pedigree

We report the apparent first case of a trichilemmal cyst presenting intraorally. Trichilemmal cysts are cysts of epithelial origin with a distinctive keratinization pattern that simulates that of the human anagen hair follicle between bulge and sebaceous gland and in the sac surrounding catagen hairs. This type of keratinization of outer root sheath epithelium occurs when it is freed from its internal cover of inner root sheath. This particular case showed evidence of mild epithelial proliferation and slight foci of "metaplastic" epidermoid keratinization, possibly related to mild trauma. The rarity of intraoral hairs undoubtedly accounts for the lack of reported cases of trichilemmal cysts in oral or perioral locations.

Topics: Adult; Epidermal Cyst; Hair Diseases; Hair Follicle; Humans; Keratins; Lip Diseases; Male; Sex Ratio

Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular-keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies; non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax = 6.34 at theta = 0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.

Topics: Alopecia; Chromosome Mapping; Chromosomes, Human, Pair 12; Female; Hair Diseases; Humans; Keratins; Lod Score; Male; Microsatellite Repeats; Pedigree; Phenotype

Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.

Topics: Amino Acid Sequence; Base Sequence; Female; Germany; Hair; Hair Diseases; Humans; Keratins; Male; Molecular Sequence Data; Mutation; Pedigree; Polymerase Chain Reaction; Sequence Analysis, DNA

Topics: Cyclosporine; Eye Diseases; Eyelashes; Hair Diseases; Humans; Immunosuppressive Agents; Keratins; Kidney Transplantation; Male; Microscopy, Electron, Scanning; Middle Aged

An alternative to using hair specimens for the study of inherited hair shaft defects has been to explore protein compositions in the context of hair formation. Hair follicles were obtained from patients with a hair disorder and the presumptive hair shaft (PHS) separated by microdissection for protein solubilization and electrophoretic experiments aimed at providing a new basis to help explain the mechanism of hair shaft defects. Two-dimensional electrophoresis (fluorographs) of labelled extracts was used to examine the major hair structural proteins and other polypeptide(s) found associated with PHS extracts in normal and aberrant specimens. Changes in either the intermediate filaments (IFs) or matrix polypeptides were not normally found in defective PHS specimens. The polypeptides showing greatest variation were associated with a PHS-specific component which was recently found in normal specimens. The variation in this polypeptide was manifested as multiple spots of different molecular weights. An investigation of the role of PHS-associated polypeptides as a likely part of the hair cross-linking mechanisms, involved examination of a PHS extract from a Menkes' patient. The observations suggest that formation of hair fibre shaft defects may be related to the status of PHS-associated polypeptides which could in turn be influenced by the presence of copper in the hair follicle.

Topics: Electrophoresis, Polyacrylamide Gel; Female; Hair Diseases; Hair Follicle; Humans; Hydrogen-Ion Concentration; Keratins; Male; Pedigree

We report on an 11-year-old female patient with anhidrotic ectodermal dysplasia (AED) showing the following characteristics: (1) reduced number of hair follicles and incomplete formation of sweat glands; (2) disturbed hair growth with shortening of anagen and anhidrosis; (3) disturbed cytokeratin expression pattern of CK 13, 14, 19 (follicular epithelium) and of CK 18 (eccrine sweat glands); (4) reduction of cystine and increase in sulphonic cysteine acid. Thus, we demonstrated pathological differentiation on the immunomorphological and on the biochemical level, leading to disturbed keratinization that could be visualized by transmission and scanning electron microscopical studies of the hair shafts. According to these findings AED is a developmental defect that involves not only incomplete formation of hair follicles and sweat glands but also a disordered differentiation and follicular keratinization with disturbed cytokeratin pattern and pathological amino acid composition of the terminal hairs produced.

Topics: Antibodies, Monoclonal; Cell Differentiation; Child; Ectodermal Dysplasia; Female; Hair; Hair Diseases; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron, Scanning; Scalp; Sweat Gland Diseases; Sweat Glands; Tooth Abnormalities

The expression of cytokeratins and involucrin varies greatly in different epithelia, and this raises the possibility that detailed analysis of these epidermal proteins might provide a means of identifying various skin tumours. The present study was conducted to determine the immunohistochemical distribution of cytokeratins and involucrin in calcifying epithelioma of Malherbe, in order to elucidate the nature and differentiation of this tumour. To correlate the immunohistochemical profile with the most frequent histological patterns, we categorized the basophilic, transitional, shadow, and squamoid cells, and the shreds of keratin. Comparative studies with normal skin showed that the shadow and transitional cells corresponded to hair cortex cells, the squamoid cells to the outer root sheath, the basophilic cells adjacent to the stroma to the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the follicles, and the basophilic cells adjacent to the transitional cells to the hair matrix. The expression of cytokeratins in most shreds of keratin was similar to that in squamoid cells. Calcifying epithelioma was, therefore, shown to be composed of tumour cells differentiating into both the hair cortex and outer root sheath. These tumour cells were differentiated from basophilic cells, which showed the same staining patterns as the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the hair follicles, supporting the hypothesis that the keratinocytes in the outermost cell layer can differentiate into the transitional portion of the follicle and anagen hair.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Hair Diseases; Humans; Immunohistochemistry; Infant; Keratins; Middle Aged; Pilomatrixoma; Protein Precursors; Skin; Skin Neoplasms

The authors report on a laboratory model for continuous production of human hair during long periods of time. This study shows that the amino acid composition of hairs collected in situ from human scalp was similar to that of terminal hairs produced by the donors' scalp follicles grafted and maintained onto nude mice. A similar experiment was performed with scalp samples from a foetus with trichothiodystrophy (TTD). The amino acid analysis of TTD lanugo hairs and of the TTD shafts produced by grafted scalp specimens was consistent with findings published in the literature: severe decrease of cys (< 50% of control values) and moderate decrease of thr and pro (80% of control values or less) with an increase of ala-asp-ile-leu-lys-met-phe (120% of control values or more). These changes indicate a decrease of high sulphur proteins (HSP) and consequently a relative increase of keratins. Furthermore, when foetal scalp samples were grafted, the lanugo hairs transformed into terminal hairs along with normal initiation of melanisation. Hence, keratin and HSP gene expression and regulation of melanogenesis in the normal and genetically defective TTD human hair follicle grafts appear to be independent of systemic host-related factors, at least during a 6 months follow-up period after grafting. The present experimental evidence further supports conclusions gained from previous assays with normal and TTD variant scalp grafts, i.e. that the nude mouse bearing human scalp specimens may serve as a clinically relevant laboratory model for evaluating regulation of normal and abnormal gene expression in the hair follicle under well controlled experimental conditions.

Topics: Adult; Amino Acid Sequence; Amino Acids; Animals; Female; Fetal Tissue Transplantation; Gene Expression; Hair; Hair Diseases; Humans; Keratins; Male; Mice; Mice, Nude; Models, Biological; Molecular Sequence Data; Proteins; Sulfur; Transplantation, Heterologous

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

Topics: Cysts; Epidermal Cyst; Hair Diseases; Humans; Keratins; Skin Diseases

We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasms occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudoencapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or "cell balls" resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice.

Topics: Adolescent; Adult; Aged; Epidermis; Epithelium; Female; Hair Diseases; Humans; Keratins; Male; Middle Aged; Skin Neoplasms

Topics: Adenocarcinoma; Aged; Esophageal Neoplasms; Etretinate; Hair Diseases; Humans; Keratins; Male; Paraneoplastic Syndromes

Topics: Animals; Gene Expression Regulation; Hair Diseases; Keratins; Mice; Mice, Transgenic; Sheep

A hair matrix tumor showing an unusual tumor cell arrangement was found at the base of a solitary trichoepithelioma. Coexisting with solid epithelial islands and immature hair follicle-like stroma resembling the Verocay bodies of neurilemmoma or "ripplemarks" on waves were found. In other areas myxomatous degeneration of the stroma changed the rippling into a cribriform pattern. In some parts of the tumor there was a dense melanin pigment associated with MEL5 stained melanocytes. S-100 and CD1 (OKT6) antigen stains demonstrated Langerhans cells scattered in the parenchyma and less frequently in the stroma. The majority of tumor cells were considered immature pilar cortical cells because of the following: 1. HKN-6 was strongly positive; 2. a large number of melanocytes were associated with tumor cells in some foci; 3. ultrastructurally immature tumor cells, which had electron-dense tonofilaments and many desmosomes, were transformed without production of trichohyalin granules into semikeratinized cells which showed nuclear degeneration and loss of electron density in tonofilaments. This tumor, however, has not attained the degree of differentiation observed in trichoblastoma (1) another example of an immature cortical cell tumor. Squamous eddy-like or horn pearl-like foci of incomplete keratinization and large keratin-filled cysts were also present within the immature parenchyma, indicating that some immature cells were differentiating toward non-cortical cells, as found in the outer sheath. We would like to designate this tumor "rippled pattern trichomatricoma", a new entity.

Topics: Adult; Antibodies, Monoclonal; Biopsy; Cell Differentiation; Facial Neoplasms; Female; Hair Diseases; Humans; Immunohistochemistry; Keratins; Langerhans Cells; Microscopy, Electron

We present an unusual case of hair casts occurring after psychological trauma. These pseudonits must be correctly differentiated from pediculosis capitis.

Topics: Child; Diagnosis, Differential; Female; Hair Diseases; Humans; Keratins; Lice Infestations; Stress, Psychological

The hair casts are infrequent condition. There are two distinct groups: idiopathic and secondary. Idiopathic hair casts are described in three girls aged 3, 5 and 13 years. They are cousins, indicating a possible hereditary influence. It's a illness without systemic affection, with pathophysiology yet unknown. It is important to know, overall for differential diagnosis, specially nits. The only treatment is removal of casts by careful and repeated combing.

Topics: Adolescent; Child, Preschool; Diagnosis, Differential; Female; Hair Diseases; Humans; Keratins; Lice Infestations

A case of hair casts in an 8-year-old girl is described. The disorder is rare, the first description dating back to 1897 with a total of only 31 cases reported in the literature since then. The results of research conducted using the optic and electron microscopes (transmission and scanning) are recorded. These studies show that the typical lesion consists of two concentric layers of keratinized cells of differing structure: one resembling the inner layer of Huxley's sheath and the outer layer resembling Henle's layer.

Topics: Child; Female; Hair; Hair Diseases; Humans; Keratins; Microscopy, Electron; Microscopy, Electron, Scanning

We report a patient who developed a proliferating trichilemmal cyst on his shin. Histological examination revealed the typical features of this lesion. Proliferating trichilemmal cysts characteristically occur on the scalp and occasionally on the upper trunk. We describe the first example of this uncommon condition on the leg.

Topics: Aged; Cell Division; Cysts; Epithelium; Hair Diseases; Humans; Keratins; Leg; Male

There are two types of hair cast. The common type is found frequently in association with parakeratotic scalp disorders. They have features allowing specific identification. They occur in children and adults of either sex. It is suggested they be called parakeratotic hair casts, as this name reflects the cause and composition of the casts. The uncommon type has specific features that are different from the common type. They are not usually associated with diseases of the scalp and have only been reported in female subjects. It is suggested they be called peripilar keratin casts, as this is the name frequently used for them. The proposed nomenclature should avoid confusion between two distinct types of hair casts that have often inappropriately been regarded as the same disorder, and which have not been previously differentiated by specific names.

Topics: Female; Hair Diseases; Humans; Keratins; Male; Parakeratosis; Scalp Dermatoses; Terminology as Topic

Topics: Epidermal Cyst; Female; Fluorescent Antibody Technique; Hair Diseases; Humans; Keratins; Middle Aged; Scalp Dermatoses

Topics: Brain Diseases; Hair; Hair Diseases; Humans; Keratins; Syndrome

Topics: Alopecia; Brain Neoplasms; Cobalt Radioisotopes; Facial Dermatoses; Forehead; Glioma; Hair Diseases; Humans; Keratins; Male; Middle Aged; Scalp Dermatoses; Skin Pigmentation

The mixture at equal volumes of a 0.1 p. 100 solution of rhodamine B in distilled water and of a 0.25 p. 100 solution of toluidine blue in Walpole's pH 4.4 buffer dyes each pilar sheath differently. At the level of the medulla, the granules fix rhodamine B, so do the cortical cells at the level of the keratogenic zone. Once they are keratinized, however, cortical cells remain colorless. Concerning the cells of the inner root sheath, on the other hand, their trichohyaline granules are dyed by rhodamine B, whereas the keratinized cells turn dark blue under the effect of toluidine blue. The trichilemmal keratin both of the isthmus of the anagen hair and of the follicular sac becomes light red. This technique, which can be easily applied to the trichogram, allows us to identify more or less mature pilar anlages in in adnexal tumors, to differentiate keratinizing cysts and to trace various pathological keratins. Thanks to a chemical study, it was shown that the mixture rhodamine B-toluidine blue is only a mechanical mixture which works through its acide-bases properties.

Topics: Carcinoma, Basal Cell; Cysts; Diagnosis, Differential; Epidermis; Hair; Hair Diseases; Histocytochemistry; Humans; Keratins; Rhodamines; Skin Neoplasms; Xanthenes