Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stratum corneum basic protein (SCBP) aggregates specifically with keratin filaments, forming macrofibrils in which the filaments are highly aligned. The appearance of the macrofibrils formed in vitro is similar to the keratin pattern in the intact stratum corneum, suggesting that SCBP is an interfilamentous matrix substance of epidermal keratin (Dale et all., Nature, 276: 729, 1978, see Ref. 13). Electron microscope and biochemical analyses were performed to determine the optimum molar ratio of SCBP and keratin filaments (average subunit molecular weight, 62,000). The optimum mixtures, in which all of the proteins were aggregated into macrofibrils, contained 1-2 moles of SCBP per 3 moles filament subunits. At ratios below this value, free filaments were observed by electron microscopy; above this value, excess SCBP was observed in the supernate by immunologic assay. The precursor of SCBP has been purified after extraction from keratohyalin granules in 1 M potassium phosphate. The precursor is immunologically similar to SCBP. Their amino acid compositions are essentially identical. However, in contrast to SCBP, the precursor is an insoluble, neutral protein which contains approximately 10 moles of phosphate per mole protein. This phosphate is covalently bound to the precursor and is not due to the presence of nucleic acid. During the conversion of a granular cell to a cornified cell, the precursor, present in keratohyalin granules, must be converted by proteolysis and/or dephosphorylation to active SCBP which aggregates with keratin filaments and forms the complex of filaments embedded in a matrix.
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PMID:Stratum corneum basic protein: an interfilamentous matrix protein of epidermal keratin. 616 25

A rabbit antiserum prepared against human keratins isolated from calluses was applied to sections of 108 neoplasms using indirect immunofluorescence and immunoperoxidase technics. The vast majority of epithelial neoplasms were strongly positive for keratin-type proteins, even in the absence of obvious keratinization or squamous differentiation as revealed by light microscopy. This keratin-positivity was invariably correlated with the identification of intermediate-sized filaments arranged in loose or dense bundles in the cytoplasm of neoplastic epithelial cells. Keratin-negative neoplasms included nevi, malignant melanomas, carcinoid tumors, malignant lymphomas, and a variety of connective-tissue tumors. Immunologic identification of keratin-type proteins was particularly helpful in establishing the epithelial nature of "undifferentiated" malignant tumors, including oat cell carcinomas.
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PMID:Immunohistochemical localization of keratin-type proteins in epithelial neoplasms. Correlation with electron microscopic findings. 618 89

The cytoskeletal intermediate filaments of pigmented nevi and malignant melanomas (nine cases of each) were evaluated using monospecific antibodies against intermediate filament proteins and immunofluorescence microscopy. Both pigmented nevi and cutaneous malignant melanomas showed only vimentin-type intermediate filaments, but not keratin, neurofilaments, desmin or glial fibrillary acidic protein. Thus, nevi and melanomas do not show neural characteristics in the cytoskeletal intermediate filament pattern although they appear to show other neural markers. Vimentin - content in melanomas versus keratin - content in carcinomas may be used as a differential diagnostic feature.
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PMID:Presence of fibroblast-type intermediate filaments (vimentin) and absence of neurofilaments in pigmented nevi and malignant melanomas. 619 Aug 49

We report our experience in Singapore with the use of the new oral Retinoid-etretinate (Tigason RO 10-9359) in 23 patients suffering from various congenital disorders of keratinisation. In this study the drug was administered to 8 patients with Darier's disease, 7 patients with congenital ichthyosis, 4 patients with palmar plantar keratoderma, 2 patients with systematised epidermal naevus and 2 patients with progressive symmetrical erythrokeratoderma. The best results were obtained in patients with ichthyosis where complete clearance was possible. All patients with Darier's except one showed significant improvement. Palmar plantar keratoderma except for one patient gave only fair to minimal improvement. Etretinate was useful in systematised epidermal naevus and progressive symmetrical erythrokeratoderma. Pruritus and cheilitis were the commonest side effect. In two patients (both with Darier's disease) treatment was stopped because of side effects. The side effects were dose related. The histology showed a reduction of the keratin layer but remnants of the original features of the pathology were still present.
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PMID:Oral retinoid (Tigason R etretinate) therapy in congenital disorders of keratinisation. 622 85

The Pityrosporum ovale (PO) is demonstrated in various percentages of the keratotic lesions of the seborrheic areas depending upon the techniques. The accumulation of horny material most probably enhances the multiplication of the yeast and makes its demonstration easier. The PAS technique prevails upon the mycological ones (77 p. 100 versus 50-65 p. 100). PO proliferates only in the keratin layer; there are isolated spores, small clusters or even large stratified colonies. On the other side the prevalence of PO does not differ significantly whatever the ultimate diagnosis of seborrheic keratosis, actinic keratosis, naevocellular nevus or vial wart. Its multiplication within the keratin layer of the lesions does not make any difference as far as the lymphocytic infiltration of the dermis is concerned.
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PMID:[Pityrosporum ovale in keratotic lesions of seborrheic areas]. 624 43

Solitary small very dark and papular pigmented nevi, less than 4 mm, are seen commonly in the second decade of life and have a distinctive histologic pattern. Microscopically these lesions show abundant intraepidermal melanin, included within the keratin layer, and proliferating single melanocytes or nevus cell nests. Prominent nucleoli in the melanocytic cells, occasional mitoses, and the invariable presence of moderate numbers of dermal melanophages and lymphocytes indicated the activity of the pathologic process. The benignity of the lesions in nine patients is supported by a benign course over a one- to three-year evaluation period after limited excisional biopsy procedures. The clinical and pathologic evidence of activity in these nevi suggests yet another possible precursor of malignant melanoma. The B-K mole syndrome and the dysplastic nevi syndrome differ from these cases both clinically and histologically.
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PMID:Solitary small active junctional nevi in juvenile patients. 684 62

Five cases are described of a distinctive histologic variant of benign spindle and epithelioid cell nevus characterized by extensive and prominent stromal hyalinization. The lesions consisted of a proliferation of spindle or epithelioid nevocytes scattered singly or in small clusters in the dermis and surrounded by abundant paucicellular hyalinized or collagenous stroma. Three patients were men and two were women. Their age range was 23 to 45 years (mean, 32). Two of the lesions were located in the head and neck region, two in the lower extremities, and one in the trunk. Immunohistochemical strains showed positive staining of the spindle or epithelioid cells with S-100 protein and vimentin; stains for keratin, EMA, CEA, actin, and desmin were all negative. Van Gieson and trichrome histochemical reaction demonstrated the collagenous nature of the hyalinized intercellular matrix; Congo red, crystal violet, and alcian blue stains were all negative. The etiology and pathogenesis of the intercellular hyalin deposits are unknown, but they probably represent a regressive phenomenon in longstanding or involuting lesions. Hyalinizing Spitz nevus must be included in the differential diagnosis of cutaneous lesions exhibiting a prominent hyalinized stroma and must be differentiated from other dermal neoplasms, particularly cutaneous metastases from occult internal malignancies and malignant melanoma.
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PMID:Hyalinizing spindle and epithelioid cell nevus. A study of five cases of a distinctive histologic variant of Spitz's nevus. 753 78

This study was undertaken to analyze keratin gene expression at both the mRNA and protein level in oral hairy leukoplakia (OHL). Comparisons were made with normal lingual epithelium from a similar site, tongue biting, normal buccal mucosa and another condition which disturbs oral epithelial differentiation, white sponge nevus. Combined immunocytochemical and in situ hybridization studies for keratins 14 and 19 were carried out on 2 specimens of OHL from HIV-positive males and one sample each of the other cases. Keratin 14 protein expression was uniform throughout all the epithelia. In normal epithelia and in lesions other than OHL, keratin 14 mRNA was most strongly expressed in basal cells with weaker but still significant amounts in the spinous cell layer. In both cases of OHL there was weaker basal cell expression of keratin 14 mRNA and frequent absence in koilocytoid cells. Keratin 19 protein expression was heterogeneous in the basal layer of all specimens with suprabasal staining of occasional groups of cells. Its mRNA was uniformly distributed in all cases. The findings indicate the keratin mRNA expression does not always parallel that of protein and that, in the case of keratin 14, expression may be influenced by the presence of EBV.
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PMID:Expression of keratin 14 and 19 mRNA and protein in normal oral epithelia, hairy leukoplakia, tongue biting and white sponge nevus. 768 26

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


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