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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukoedema is a white or whitish-gray edematous lesion of the buccal and labial oral mucosa. The lesions may be diffuse or patchy, and are usually asymptomatic. Leukoedema may be confused with leukoplakia, Darier's disease, white sponge nevus, pachyonychia congenita, or candidal infection. The condition is seen most frequently among black men. The histologic appearance simulates that of white sponge nevus. Symptomatic leukoedema seems to respond to topical application of tretinoin.
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PMID:Leukoedema of the oral mucosa. Possibly an acquired white sponge nevus. 740 18

It has recently been demonstrated that genetic defects in keratin genes cause a number of different skin disorders, including epidermolysis bullosa simplex (EBS), epidermolytic hyperkeratosis (EH), the EH form of epidermal nevi, epidermolytic and non-epidermolytic forms of palmoplantar keratoderma (EPPK and PPK) and pachyonychia congenita (PC). In this review, I describe the research that led to this discovery.
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PMID:JSID Tanioku Memorial Lecture 1996. Genetic disorders of keratins and their associated proteins. 902

Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodermatoses.
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PMID:Human keratin diseases: hereditary fragility of specific epithelial tissues. 902 91

An increasing number of syndromes with palmoplantar keratoderma (PPK) with associated diseases are being identified, representing a wide spectrum of distinct entities. At present only one case report has described the combination of marked anogenital leukokeratosis with diffuse PPK evolving in a collodion baby. We report a patient with a diffuse, nonprogressive PPK in combination with an intermittently pruritic, slowly progressive anogenital leukokeratosis. Hyperkeratosis of the perineal area was most pronounced and extended to the distal portion of the anal mucosa. The opalescent lesion was also visualized at the margin of the major labia. Vulvar structures were not otherwise involved or dystrophic. There were no signs or symptoms of ectodermal dysplasia. Specifically, the nails were normal and showed no signs of pachyonychia congenita. Other differential diagnoses included dyskeratosis congenita and white sponge nevus, which may be associated with anogenital leukokeratosis, but a keratoderma is not associated with these entities. Keratin immunocytochemistry showed marked expression of suprabasal K17 and absence of K6 and K16. Further examination of the initial case described by Itin and Rufli demonstrated the same expression pattern and supports the contention that these two cases represent the same entity.
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PMID:Palmoplantar keratoderma and leukokeratosis anogenitalis: the second case of a new disease. 981 42

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.
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PMID:Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation. 1035 17

Keratins are the type I and II intermediate filament proteins which form a cytoskeletal network within all epithelial cells. They are expressed in pairs in a tissue- and differentiation-specific fashion. Epidermolysis bullosa simplex (EBS) was the first human disorder to be associated with keratin mutations. The abnormal keratin filament aggregates observed in basal cell keratinocytes of some EBS patients are composed of keratins K5 and K14. Dominant mutations in the genes encoding these proteins were shown to disrupt the keratin filament cytoskeleton resulting in cells that are less resilient and blister with mild physical trauma. Identification of mutations in other keratin genes soon followed with attention focussed on disorders showing abnormal clumping of keratin filaments in specific cells. For example, in bullous congenital ichthyosiform erythroderma, clumping of filaments in the suprabasal cells led to the identification of mutations in the suprabasal keratins, K1 and K10. Mutations have now been identified in 18 keratins, all of which produce a fragile cell phenotype. These include ichthyosis bullosa of Siemens (K2e), epidermolytic palmoplantar keratoderma (K1, K9), pachyonychia congenita (K6a, K6b, K16, K17), white sponge nevus (K4, K13), Meesmann's corneal dystrophy (K3, K12), cryptogenic cirrhosis (K8, K18) and monilethrix (hHb6, hHb1).In general, these disorders are inherited as autosomal dominant traits and the mutations act in a dominant-negative manner. Therefore, treatment in the form of gene therapy is difficult, as the mutant gene needs to be inactivated. Ways of achieving this are actively being studied. Reliable mutation detection methods from genomic DNA are now available. This enables rapid screening of patients for keratin mutations. For some of the more severe phenotypes, prenatal diagnosis may be requested and this can now be performed from chorionic villus samples at an early stage of the pregnancy. This review article describes the discovery of, to date, mutations in 18 keratin genes associated with inherited human diseases.
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PMID:The molecular genetics of keratin disorders. 1268 39

Diseases caused by mutations in gene encoding keratin intermediate filaments (IF) are characterized by a loss of structural integrity in the cells expressing those keratins in vivo. This is manifested as cell fragility, compensatory epidermal hyperkeratosis, and keratin filament aggregation in some affected tissues. Keratin disorders are a novel molecular category including quite different phenotypes such as epidermolysis bullosa simplex (EBS), bullous congenital ichthyosiform erthroderma (BCIE), pachyonychia congenital (PC), steatocystoma multiplex, ichthyosis bullosa of Siemens (IBS), and white sponge nevus (WSN) of the orogenital mucosa.
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PMID:The keratins and their disorders. 1545 38

Josef Jadassohn was a pioneering dermatologist who influenced the development of his specialty in many ways. He introduced the patch test for detection of hypersensitivity reactions, gave original descriptions of several entities, such as nevus sebaceous, granulosis rubra nasi, and pachyonychia congenita, and edited the Handbuch der Haut- und Geschlechtskrankheiten, the most comprehensive textbook of dermatology ever published. Moreover, Jadassohn left a phalanx of distinguished students, including Felix Lewandowsky, Wilhelm Lutz, Max Jessner, Hans Biberstein, Hermann Pinkus, and Marion B. Sulzberger.
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PMID:Josef jadassohn--an appreciation on the occasion of his 150th birthday. 2392 55

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the non-neuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNTs. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. non-neuronal cells. The non-neuronal cells that express one or more BoNT/A-binding proteins, and/or cleavage target synaptosomal-associated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT/A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an anti-ageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anticancer properties. BoNTs have a much wider range of applications than originally understood, and the individual cellular responses to the cholinergic impacts of BoNTs could provide fertile ground for future studies.
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PMID:The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond. 2978 14

A large number of disorders may affect the oral cavity, including genetic diseases, infections, cancers, blood diseases, skin diseases, endocrine and metabolic disorders, autoimmune and rheumatologic diseases, local lesions, to name a few. Oral mucosa shows a considerable variation in its normal structure and a wide range of conditions may affect it. Such conditions are often harmless or minor and could be primary or secondary to systemic disease. Several of them are quite rare and, hence, the diagnosis is not easy. Clinically, lesions may appear as ulcers, discoloration of the oral mucosa and alterations in size and configuration of oral anatomy. Genetic disorders have specific manifestations and can be caused by a derangement of one or more components of the tissue. Many of them follow the skin or systemic signs of the underlying genetic disease, but in a few cases oral signs could be the first manifestation of the disorder. Among them genodermatoses are prominent. They are inherited disorders characterized by a multisystem involvement. This review describes chondro-ectodermal dysplasia, dyskeratosis congenita, Ehlers-Danlos syndrome, hereditary benign intraepithelial dyskeratosis, keratosis follicularis, lipoid proteinosis, multiple hamartoma syndrome, pachyonychia congenita, Peutz-Jeghers syndrome, tuberous sclerosis and white sponge nevus. Other genetic disorders not included in the genodermatosis group and reported in the present review are: acanthosis nigricans, angio-osteo-hypertrophic syndrome, encephalotrigeminal angiomatosis, familial adenomatous polyposis, focal dermal hypoplasia, focal palmoplantar and oral mucosa hyperkeratosis syndrome, gingival fibromatosis, Maffucci's syndrome, neurofibromatosis (type 1) and oro-facial-digital syndrome (type 1). Disorders during embryonic development might lead to a wide range of abnormalities in the oral cavity; some of them are quite common but of negligible concern, whereas others are rare but serious, affecting not only the oral mucosa, but also other structures of the oral cavity (ie palate, tongue and gingiva). Fordyce's granules, leukoedema, cysts of the oral mucosa in newborns, retrocuspid papilla, geographic tongue, fissured tongue, median rhomboid glossitis, hairy tongue, lingual varices and lingual thyroid nodule are described. This review may help dentists, dental hygienists, but also general internists and pediatricians to diagnose different disorders of the oral mucosa, to understand the pathogenesis and to schedule a treatment plan.
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PMID:Genetic and developmental disorders of the oral mucosa: Epidemiology; molecular mechanisms; diagnostic criteria; management. 3109 Jan 39


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