Background: Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti- Ted- H- 1 monoclonal antibody (mAb), but not with antifilag...Background: Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti- Ted- H- 1 monoclonal antibody (mAb), but not with antifilaggrin mAb or antiloricrin polyclonal antibody (pAb). This finding indicated that the Ted- H- 1 antigenic protein is a haematoxylin- stainable protein in KHG. Objectives: To clarify the identity of the major component protein of the large KHG in solar keratosis, another disorder in which large KHG are observed. Methods An enzyme immunohistochemical study was performed using antifilaggrin mAb, anti- Ted- H- 1 mAb and antiloricrin pAb. Immunofluorescent double staining and immunoelectron microscopic analyses were performed using anti- Ted- H- 1 mAb and antiloricrin pAb. Results: Antifilaggrin mAb, anti- Ted- H- 1 mAb and antiloricrin pAb reacted with normal KHG in nonlesional skin of solar keratosis, while only anti- Ted- H- 1 mAb reacted with the large KHG in the lesions of solar keratosis. Antifilaggrin mAb did not react with large KHG. Antiloricrin pAb reacted with the cell membrane of the stratum granulosum, but not with large KHG. Conclusions: These findings suggest that the haematoxylin- stainable protein in the large KHG would be a Ted- H- 1 antigen protein which was neither filaggrin nor loricrin.展开更多
目的观察大翅蓟属植物提取物对皮肤屏障相关蛋白的表达的影响,探讨其屏障修复作用。方法通过使用胶带黏贴的方法,对离体培养的皮肤造成皮肤屏障功能损伤模型,每隔2 d涂抹大翅蓟属植物提取物,7 d后评估损伤皮肤的淋巴上皮Kazal型相关抑...目的观察大翅蓟属植物提取物对皮肤屏障相关蛋白的表达的影响,探讨其屏障修复作用。方法通过使用胶带黏贴的方法,对离体培养的皮肤造成皮肤屏障功能损伤模型,每隔2 d涂抹大翅蓟属植物提取物,7 d后评估损伤皮肤的淋巴上皮Kazal型相关抑制因子(Lympho-epithelial Kazal type related inhibitor,LEKTI),兜甲蛋白(Loricrin,LOR),内披蛋白(Involucrin,INV)丝聚合蛋白(Filaggrin,FLG)的表达情况。结果正常皮肤和受损皮肤的LEKTI,LOR,INV,FLG染色均有增强,受损皮肤增强更为明显。结论大翅蓟属植物提取物可以提高皮肤FLG、LOR、INV、LEKTI的表达,进而提高皮肤屏障功能。展开更多
Background: Atopic dermatitis (AD)- specific genes have not yet been clarified. Objectives To identify gene expression specific to active atopic skin lesions. Methods: We analysed 23 000 genes in skin biopsy samples f...Background: Atopic dermatitis (AD)- specific genes have not yet been clarified. Objectives To identify gene expression specific to active atopic skin lesions. Methods: We analysed 23 000 genes in skin biopsy samples from 17 patients with AD and four normal controls using Affymetrix oligonucleotide arrays. Results Four of the 10 genes with the greatest differences in expression between patients and controls, S100A8 and S100A7 (upregulated), and loricrin and filaggrin (downregulated), were epidermal differentiation genes located on 1q21, a locus previously reported to have a genetic linkage with AD. Conclusions: Our results, showing downregulation of the cornified envelope genes and upregulation of the alternative keratinization pathway, are the first to suggest abnormal epidermal differentiation and defective defences as key abnormalities in AD.展开更多
We describe a Dutch man suffering from a previously undescribed erythrokeratoderma associated with palmoplantar keratoderma and circular constrictions of the fingers. No mutations were identified in the genes encoding...We describe a Dutch man suffering from a previously undescribed erythrokeratoderma associated with palmoplantar keratoderma and circular constrictions of the fingers. No mutations were identified in the genes encoding loricrin, connexin 26, 30, 30.3, 31 and 31.1, and ARS/complex B. There are some similarities between the disorder described here and other palmoplantar keratodermas and erythrokeratodermas, but assignment to a particular disease category is not possible. Hence wepropose that we have delineated a novel type of keratoderma.展开更多
Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immuno...Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.展开更多
Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a...Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for Cx26 mutations with negative results, presented the mtDNA A7445G point mutation in the homoplasmic form. To our knowledge, this is the fifth family in whom inherited NEPPK and hearing loss are related to this mitochondrial mutation.展开更多
Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) despite large differences in the phenotype between these conditions. ...Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) despite large differences in the phenotype between these conditions. In some of these indi viduals, defective cornified envelopes (CEs) have been reported by light or elec tron microscopic examination in epidermal scale, nail and/or hair. These finding s suggest that assessment of such defects could have a diagnostic utility in dis tinguishing TGM1-deficient versus non-deficient cases of autosomal recessive i chthyosis (ARI) . Present work (a) examines the integrity of CEs in epidermal sc ale and appendages in a case of TGM1-deficient CIE, (b) assesses the utility of hair/nail versus scale analysis in the diagnosis of TGM1 deficiency in vivo and (c)-helps characterize the consequences of the V518M mutation in TGM1, about w hich conflicting reports have appeared. To this end, epidermal scale or callus, nail and hair samples from a patient with TGM1-deficient CIE, his asymptomatic family members and control subjects were extracted vigorously in sodium dodecyl sulfate and dithiothreitol and examined by light (phase contrast) and electronmi croscopy. Both epidermal scale and nail from the index case lacked the prominent cell borders that were visible by phase contrast microscopy after detergent ext raction of control samples. (By contrast, abundant envelope structures were visi ble in extracted epidermal scale from patients with ichthyosis vulgaris, loricri n keratoderma and epidermolytic hyperkeratosis.) Electronmicroscopy confirmed th e paucity of intact CEs, and revealed further that hair cuticle cells from the s ame subject also lacked the marginal bands that are visible in control hair samp les. Such aberrations were evident neither in the samples from asymptomatic rela tives of the index case nor in the hair-cuticle cells of numerous normal indivi duals, evidence that this defect is not a common polymorphism. These studies ext end our prior work on TGM1-deficient LI to the full spectrum of TGM1-deficient patients, showing that the CIE phenotype, when attributable to a V518M heterozy gous mutation in TGM1 in combination with an inactive allele, confers a cross-l inking deficiency in a variety of keratinizing epithelia, as previously shown fo r TGM1-negative LI. These results further suggest that a non-invasive assessme nt of scale, nail and hair could be of diagnostic utility in distinguishing pati ents across a full range of phenotypes with deficiency in TGM1-encoded transglu taminase activity from other causes of ARI.展开更多
文摘Background: Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti- Ted- H- 1 monoclonal antibody (mAb), but not with antifilaggrin mAb or antiloricrin polyclonal antibody (pAb). This finding indicated that the Ted- H- 1 antigenic protein is a haematoxylin- stainable protein in KHG. Objectives: To clarify the identity of the major component protein of the large KHG in solar keratosis, another disorder in which large KHG are observed. Methods An enzyme immunohistochemical study was performed using antifilaggrin mAb, anti- Ted- H- 1 mAb and antiloricrin pAb. Immunofluorescent double staining and immunoelectron microscopic analyses were performed using anti- Ted- H- 1 mAb and antiloricrin pAb. Results: Antifilaggrin mAb, anti- Ted- H- 1 mAb and antiloricrin pAb reacted with normal KHG in nonlesional skin of solar keratosis, while only anti- Ted- H- 1 mAb reacted with the large KHG in the lesions of solar keratosis. Antifilaggrin mAb did not react with large KHG. Antiloricrin pAb reacted with the cell membrane of the stratum granulosum, but not with large KHG. Conclusions: These findings suggest that the haematoxylin- stainable protein in the large KHG would be a Ted- H- 1 antigen protein which was neither filaggrin nor loricrin.
文摘目的观察大翅蓟属植物提取物对皮肤屏障相关蛋白的表达的影响,探讨其屏障修复作用。方法通过使用胶带黏贴的方法,对离体培养的皮肤造成皮肤屏障功能损伤模型,每隔2 d涂抹大翅蓟属植物提取物,7 d后评估损伤皮肤的淋巴上皮Kazal型相关抑制因子(Lympho-epithelial Kazal type related inhibitor,LEKTI),兜甲蛋白(Loricrin,LOR),内披蛋白(Involucrin,INV)丝聚合蛋白(Filaggrin,FLG)的表达情况。结果正常皮肤和受损皮肤的LEKTI,LOR,INV,FLG染色均有增强,受损皮肤增强更为明显。结论大翅蓟属植物提取物可以提高皮肤FLG、LOR、INV、LEKTI的表达,进而提高皮肤屏障功能。
文摘Background: Atopic dermatitis (AD)- specific genes have not yet been clarified. Objectives To identify gene expression specific to active atopic skin lesions. Methods: We analysed 23 000 genes in skin biopsy samples from 17 patients with AD and four normal controls using Affymetrix oligonucleotide arrays. Results Four of the 10 genes with the greatest differences in expression between patients and controls, S100A8 and S100A7 (upregulated), and loricrin and filaggrin (downregulated), were epidermal differentiation genes located on 1q21, a locus previously reported to have a genetic linkage with AD. Conclusions: Our results, showing downregulation of the cornified envelope genes and upregulation of the alternative keratinization pathway, are the first to suggest abnormal epidermal differentiation and defective defences as key abnormalities in AD.
文摘We describe a Dutch man suffering from a previously undescribed erythrokeratoderma associated with palmoplantar keratoderma and circular constrictions of the fingers. No mutations were identified in the genes encoding loricrin, connexin 26, 30, 30.3, 31 and 31.1, and ARS/complex B. There are some similarities between the disorder described here and other palmoplantar keratodermas and erythrokeratodermas, but assignment to a particular disease category is not possible. Hence wepropose that we have delineated a novel type of keratoderma.
文摘Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.
文摘Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for Cx26 mutations with negative results, presented the mtDNA A7445G point mutation in the homoplasmic form. To our knowledge, this is the fifth family in whom inherited NEPPK and hearing loss are related to this mitochondrial mutation.
文摘Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) despite large differences in the phenotype between these conditions. In some of these indi viduals, defective cornified envelopes (CEs) have been reported by light or elec tron microscopic examination in epidermal scale, nail and/or hair. These finding s suggest that assessment of such defects could have a diagnostic utility in dis tinguishing TGM1-deficient versus non-deficient cases of autosomal recessive i chthyosis (ARI) . Present work (a) examines the integrity of CEs in epidermal sc ale and appendages in a case of TGM1-deficient CIE, (b) assesses the utility of hair/nail versus scale analysis in the diagnosis of TGM1 deficiency in vivo and (c)-helps characterize the consequences of the V518M mutation in TGM1, about w hich conflicting reports have appeared. To this end, epidermal scale or callus, nail and hair samples from a patient with TGM1-deficient CIE, his asymptomatic family members and control subjects were extracted vigorously in sodium dodecyl sulfate and dithiothreitol and examined by light (phase contrast) and electronmi croscopy. Both epidermal scale and nail from the index case lacked the prominent cell borders that were visible by phase contrast microscopy after detergent ext raction of control samples. (By contrast, abundant envelope structures were visi ble in extracted epidermal scale from patients with ichthyosis vulgaris, loricri n keratoderma and epidermolytic hyperkeratosis.) Electronmicroscopy confirmed th e paucity of intact CEs, and revealed further that hair cuticle cells from the s ame subject also lacked the marginal bands that are visible in control hair samp les. Such aberrations were evident neither in the samples from asymptomatic rela tives of the index case nor in the hair-cuticle cells of numerous normal indivi duals, evidence that this defect is not a common polymorphism. These studies ext end our prior work on TGM1-deficient LI to the full spectrum of TGM1-deficient patients, showing that the CIE phenotype, when attributable to a V518M heterozy gous mutation in TGM1 in combination with an inactive allele, confers a cross-l inking deficiency in a variety of keratinizing epithelia, as previously shown fo r TGM1-negative LI. These results further suggest that a non-invasive assessme nt of scale, nail and hair could be of diagnostic utility in distinguishing pati ents across a full range of phenotypes with deficiency in TGM1-encoded transglu taminase activity from other causes of ARI.
