Japanese guidelines for diagnosis and treatment of junctional and dystrophic epidermolysis bullosa.
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Epidermolysis Bullosa Dystrophica↗
Biomedical subjects
Hideoki Ogawa
Publications and source records attributed to Hideoki Ogawa.
Generalized pustular psoriasis: strategy for identification of psoriasis susceptibility gene.
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Genetic Predisposition to Disease↗
History of the establishment and revision of diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan.
We summarize the process of establishing and revising the diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan (including the results of a nationwide survey regarding these guidelines). We also summarize the content and present an evaluation of the utility of these guidelines. Due to the publication of these documents throughout the Japanese medical community, it appears that patients with pemphigus have recently begun to receive appropriate treatment, dramatically improving their quality of life and prognosis. Continuous examination of these criteria by means of follow-up studies of patients treated according to the guidelines is necessary to determine the long-term efficacy of treatment. To this end, it is hoped that these guidelines will be more extensively disseminated among the medical community.
History, 20th Century↗
Regulation of cell type-specific mouse Fc epsilon RI beta-chain gene expression by GATA-1 via four GATA motifs in the promoter.
The FcR beta-chain, a subunit of two related multisubunit receptor complexes, the FcepsilonRI and FcgammaRIII, amplifies the mast cell response and is necessary for the cell surface expression of FcepsilonRI in mouse. The transient reporter assay indicated that -69/+4 region is required for cell type-specific transcriptional regulation of mouse beta-chain gene. EMSA using Abs against transcription factors or competitive oligonucleotides demonstrated that -58/-40 region (containing overlapping three GATA-1 sites, -53/-48, -46/-51, and -42/-47) and -31/-26 region (containing one GATA-1 site) are recognized by GATA-1. The promoter activity of beta-chain was decreased by nucleotide replacements of the GATA-1 sites in mouse mast cell line PT18. Furthermore, exogenously produced GATA-1 up-regulated the promoter activity in CV-1 cells, which are negative in the beta-chain production and the up-regulation was apparently suppressed by GATA-1 site mutations. These results indicate that cell type-specific transcription of mouse beta-chain gene is regulated by GATA-1.
Amino Acid Motifs↗
TGF-beta/Smad signaling inhibits IFN-gamma and TNF-alpha-induced TARC (CCL17) production in HaCaT cells.
BACKGROUND: A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocytes, is implicated in the development of atopic dermatitis by recruiting CLA(+)CCR4(+) lymphocytes into lesional skin and its expression was induced by proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). However, it remains unknown how TARC expression is negatively regulated in keratinocytes. OBJECTIVE: We sought to determine whether transforming growth factor-beta 1 (TGF-beta 1) regulated TARC expression in keratinocytes. METHODS: The effect of TGF-beta 1 on mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in a human keratinocyte cell line, HaCaT cells, was evaluated by using RT-PCR and ELISA. Adenovector-mediated gene transfer was used to determine the effect of Smad proteins on TARC expression in HaCaT cells. RESULTS: TGF-beta 1 inhibited mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in HaCaT cells. The inhibitory effect of TGF-beta 1 on the TARC expression was suppressed by overexpression of Smad7, a major inhibitory regulator of Smad pathway for transforming growth factor-beta (TGF-beta) signaling, but not by PD98059, an inhibitor for ERK/mitogen-activated protein kinase (MAPK) pathway. In addition, overexpression of Smad2 or Smad3, major signal transducing Smads, was sufficient to inhibite the IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells. CONCLUSION: TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3, suggesting that modulation of TGF-beta/Smad signaling pathway may be beneficial for the treatment of atopic dermatitis.
Cell Line↗
IFN-gamma fails to antagonize fibrotic effect of TGF-beta on keloid-derived dermal fibroblasts.
BACKGROUND: Interferon-gamma (IFN-gamma) has been noted as a potential therapeutic agent for various fibrotic disorders, in part, through its antagonistic effect on a fibrogenic cytokine, transforming growth factor-beta (TGF-beta). Keloid is a fibrotic skin disorder that results in an excessive deposition of extracellular matrix, which is associated with altered-expression of or -responses to TGF-beta in dermal fibroblasts. OBJECTIVE: We sought to determine whether IFN-gamma antagonized TGF-beta-mediated fibrotic response in keloid-derived dermal fibroblasts. METHODS: Type I collagen production, fibroblast contractile activity, and alpha-smooth muscle actin (alpha-SMA) expression were assessed by using Western blotting, an in vitro type I collagen gel contraction assay, and immunofluorescence study in normal and keloid-derived human dermal fibroblasts in the presence or absence of IFN-gamma and/or TGF-beta. RESULTS: In contrast to normal dermal fibroblasts, IFN-gamma did not inhibit TGF-beta-induced type I collagen production, contractile activity, and alpha-SMA expression in keloid-derived dermal fibroblasts. In addition, keloid-derived dermal fibroblasts constitutively expressed type I collagen and alpha-SMA with increased capacity to contract a collagen matrix. CONCLUSION: IFN-gamma failed to antagonize TGF-beta-mediated fibrotic response in keloid-derived dermal fibroblasts. Thus, IFN-gamma may not be therapeutically useful for keloid and clarification of the molecular mechanisms underlying the IFN-gamma resistance should be investigated for therapeutic application of IFN-gamma for keloid.
Actins↗
Up-regulation of interleukin-13 receptor alpha1 on human keratinocytes in the skin of psoriasis and atopic dermatitis.
BACKGROUND: Interleukin (IL)-13 is a pleiotropic cytokine, which shares many biological functions with IL-4. The receptor subunits of IL-13 consist of IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2. The regulatory mechanisms of the IL-13Ralpha expression in the keratinocytes of certain skin disease have not been known. OBJECTIVE: To clear the roles of IL-13 and the regulatory mechanisms of its receptor in atopic dermatitis (AD) and psoriasis. METHOD: The expression of IL-13Ralpha1 in the skin of AD and psoriasis was investigated by immunohistochemistry. The regulation of IL-13Ralpha mRNA in the skin and human primary keratinocyte (HPK) was investigated by quantitative PCR. The secretion of IL-6 and RANTES from HPK was measured by ELISA. RESULTS: The expression of IL-13Ralpha1 was more prominent on the suprabasal keratinocytes in the skin of AD and striking increase of staining was observed on all layers of keratinocyte in the skin of psoriasis. The mRNA of IL-13Ralpha1, but not of IL-13Ralpha2 was overexpressed in both skin of AD and psoriasis. In vitro experiment using HPK demonstrated that IFN-gamma, IL-13 but not IL-4 could up-regulate the mRNA expression of IL-13Ralpha1. In contrast, IL-13Ralpha2 mRNA expression was up-regulated by IFN-gamma plus IL-4. Furthermore, the stimulation of HPK with IFN-gamma plus IL-13 and/or IL-4 resulted in significant enhancement of IL-6 and RANTES secretion. CONCLUSION: These findings indicate that IL-4 and IL-13 have different regulatory effects on the expression of IL-13Ralpha1 and alpha2, and the overexpression of IL-13Ralpha1 may play some roles in the pathogenesis of chronic stage of AD or psoriasis.
Cells, Cultured↗
Linear polarized infrared irradiation using Super Lizer is an effective treatment for multiple-type alopecia areata.
BACKGROUND: Super Lizer trade mark is a linear polarized light instrument, which has been used with good effect in orthopedics and anesthesiology to treat arthralgia and neuralgia with a high output of infrared radiation. AIM: To test Super Lizer trade mark 's efficacy for the treatment of alopecia areata. METHODS: Fifteen patients over 18 years of age, diagnosed with alopecia areata and displaying symptoms of patchy hair loss, were topically irradiated with infrared radiation using the Super Lizer trade mark. The patients were irradiated intermittently for an interval of 3 min once every week or every 2 weeks. RESULTS: Seven of 15 (46.7%) of the irradiated areas showed hair regrowth 1.6 months earlier than the nonirradiated areas (chi2 official approval, P = 0.003). With regard to adverse effects caused by Super Lizer trade mark treatment, only one patient complained of a sensation of heat in the irradiated area. CONCLUSIONS: These findings suggest that Super Lizer trade mark, with its noninvasive properties, is a useful apparatus for the treatment of mild forms of alopecia areata.
Adult↗
Phototrichogram analysis of Japanese female subjects with chronic diffuse hair loss.
Hair growth patterns of 101 Japanese female subjects with diffuse, chronic hair loss and 58 healthy Japanese female volunteers were categorized into subgroups using noninvasive quantitative methods after determining the key parameters of hair growth. Phototrichogram was performed at 0 and 48 h after clipping hairs in the parietal region of the scalp. Shaft diameters of the excised hairs were then measured. Multiple regression analysis indicated that hair densities, hair diameters, short hair ratios, and hair growth rates, but not anagen hair ratios, were significant, in order of decreasing importance, for grading female diffuse alopecia. Using cluster analysis, hair growth patterns among subjects complaining of diffuse hair loss were divided into six abnormal groups (n=60), two borderline groups (n=21), and one normal group (n=20). The control subjects judged to be normal by macroscopic observation, actually included two subjects with borderline hair growth patterns and one abnormal subject. Most of the abnormal groups shared features of female androgenetic alopecia. Hair patterns showing a decrease in hair density but without vellus hair change, however, emerged as the most prevalent and distinct pattern of chronic diffuse hair loss among the Japanese female subjects. The phototrichogram, combined with the measurement of hair diameters, is an accurate tool for assessing hair growth patterns, especially in detecting the slight changes indicative of the early phase of diffuse alopecia.
Adolescent↗
Mutations in ATP2A2 in patients with Darier's disease.
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Amino Acid Substitution↗
Regulation of human FcepsilonRI beta chain gene expression by Oct-1.
The beta chain, a component of the high-affinity receptor for IgE (FcepsilonRI), plays an important role in IgE-mediated allergic reaction. The beta chain accelerates the function of FcepsilonRI by amplification of its surface expression and of signal transduction in effector cells such as mast cells and basophils. Two regulatory regions, +60/+66 and +70/+76, for the human beta chain gene that are required for the cell-type-specific transcriptional activation were identified by transient reporter assay. Electrophoretic mobility shift assay demonstrated that Oct-1 binds both the regions, among which the +70/+76 Oct-1 motif was critical for the transactivation of the beta promoter responsive to Oct-1 overexpression. Regulation of beta chain gene expression is discussed.
5' Flanking Region↗
Smad7 suppresses the inhibitory effect of TGF-beta2 on corneal endothelial cell proliferation and accelerates corneal endothelial wound closure in vitro.
PURPOSE: The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation. METHODS: The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 on the wound-healing process in vitro. RESULTS: Overexpression of Smad7 abolished the inhibitory effect of TGF-beta2 or aqueous humor on the proliferation of cultured rabbit corneal endothelial cells associated with the inhibition of phosphorylation of Smad2 and downregulation of p27kip1. Smad7-overexpressing cultured rabbit corneal endothelial cells exhibited shorter wound closure time in the presence of aqueous humor than LacZ-expressing cells. CONCLUSION: Overexpression of Smad7 suppressed the inhibitory effect of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation and accelerated corneal endothelial wound closure in vitro. Modification of Smad7 expression in corneal endothelial cells may thus have applicability in the treatment of wounded corneal endothelium.
Adenoviridae↗
A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions.
Multiple hair follicle nevi are an extremely rare condition. In 1998, a case of unilateral multiple hair follicle nevi, ipsilateral alopecia and ipsilateral leptomeningeal angiomatosis of the brain was first reported from Japan. Very recently, hair follicle nevus in a distribution following Blaschko's lines has also been reported. In this paper, we observed a congenital case of unilateral, systematized linear hair follicle nevi associated with congenital, ipsilateral, multiple plaque lesions resembling epidermal nevi but lacking leptomeningeal angiomatosis of the brain. These cases implicate the possibility of a novel neurocutaneous syndrome. Additional cases should be sought in order to determine whether this condition is pathophysiologically distinct.
Epidermis↗
Recurrent E413K mutation of hHb6 in a Japanese family with monilethrix.
Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. This disorder has been reported to be caused by mutations in the helix termination motif of two type II cortex keratins, hHb1 and hHb6. Here we describe a Japanese monilethrix family that has the most frequent mutation, the E413K mutation in hHb6, so far found in 26 families. Genotype/phenotype correlation was not obvious in our case or in the previously reported cases.
Child, Preschool↗
Involvement of p300 in TGF-beta/Smad-pathway-mediated alpha2(I) collagen expression in mouse mesangial cells.
BACKGROUND: Transforming growth factor beta 1 (TGF-beta1) induces alpha2(I) collagen gene (COL1A2) expression in mesangial cells through physical and functional cooperation of Smad proteins and Sp1. A transcriptional coactivator, p300, is also suggested to play an important role in TGF-beta1/Smad signal transduction. However, the role of p300 in TGF-beta1/Smad-pathway-mediated transcriptional activation of the COL1A2 gene in mesangial cells is still obscure. METHODS: Endogenous p300 expression and its modulation by TGF-beta1 were evaluated by Western blotting and immunofluorescence. The physical interaction of p300 with Smad2/3 was examined by immunoprecipitation followed by Western blotting. The functional role of p300 in TGF-beta1/Smad-pathway-mediated COL1A2 transcription was investigated in cotransfection experiments using a COL1A2 promoter-luciferase reporter gene construct and p300 expression plasmids. RESULTS: TGF-beta1 induced COL1A2 gene expression in cultured mouse mesangial cells which was blocked by overexpression of inhibitory Smad7. In addition, TGF-beta1-induced nuclear export of endogenous Smad7 was observed in mouse mesangial cells. Endogenous p300 was expressed in the nucleus of the cells. TGF-beta1 induced interaction of endogenous p300 with Smad2/3, and a dominant negative construct of p300 inhibited the TGF-beta1-induced COL1A2 expression in cultured mouse mesangial cells. CONCLUSIONS: p300 may be involved in TGF-beta1/Smad-pathway-mediated type I collagen gene transcription in mouse mesangial cells. Our findings would reveal a molecular basis of TGF-beta1-induced type I collagen gene transcription in mouse mesangial cells.
Animals↗
Molecular cloning of rat transcription factor YY1.
YY1 is a ubiquitously expressed multifunctional transcription factor that is involved in both positive and negative regulation of gene expression as well as initiation of transcription. Here, we isolated cDNA encoding a full-length open reading frame (ORF) of rat YY1. Rat YY1 is composed of 411 amino acid residues and its amino acid sequence is 97.6% identical to that of mouse YY1 and 97.8% identical to that of human YY1. The transactivating abilities of wild-type rat YY1 and four truncated mutant forms of YY1 were examined by transient reporter assays. When residues 114-193, which sequence includes a portion of the activation region and most of the Gly/Lys-rich region, were lacking, transactivation activity decreased somewhat, but the further deletion in the activation region (of residues 56-113) did not cause further decrease of the activity. On the other hand, N-terminus of the activation region (1-78/100-106) did not have transactivation activity by itself as well as synergistic activity with an erythroid specific transcription factor GATA-1.
Amino Acid Sequence↗
Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells.
Antibacterial peptides function as effectors for defense in innate immunity. In mammals, they are implicated in the barrier protection of epithelia where their expression can be induced during infection and inflammation. Over a dozen of antibacterial peptides have been identified in humans. Among these, defensins and cathelicidins have been well characterized. Two types of defensins (alpha- and beta-defensins) are recognized based on the presence of their conserved six cysteine residues, whereas cathelicidins are characterized by a homologous cathelin sequence in the pro-region and a variable antibacterial C-terminal sequence. Human beta-defensins and cathelicidin hCAP18/LL-37 are mainly expressed in epithelial tissues where mast cells are present. Here we review the structure of human beta-defensins and cathelicidin, and describe their multiple activities on mast cells to induce chemotaxis, degranulation and prostaglandin D(2) production, acting through receptors coupled to G-protein-phospholipase C pathway. Thus, in addition to their bactericidal activities, epithelial cell-derived antibacterial peptides may modulate the inflammatory responses by recruiting mast cells to inflammation foci and inducing the degranulation as well as prostaglandin production from this cell population.
Amino Acid Sequence↗
[A short-term treatment of tinea corporis and tinea cruris with oral terbinafine].
We studied the effectiveness of short-term treatment of tinea corporis and tinea cruris with oral terbinafine at 250 mg/day for 2-3 days. The treatment on an open study basis consisted of two groups: the first group (n=17) was given 250 mg/day for two consecutive days, and the second group (n=24) was given the same dose for three consecutive days. No patient was treated topically. Effectiveness was evaluated at the end of the second week both clinically and mycologically (KOH examination and culture). In the two-day group, five cases showed an excellent response, three had a good response and nine had a fairly good response. Patients with good response or better comprised 47.1% of the total, while those with excellent response stood at 29.4%. The negative mycological examination ratio was 47.1%. In the three-day group, 12 cases showed an excellent response, four a good response while eight had a fairly good response. Patients with a good response or better comprised 66.7% of the group, while cases with an excellent response comprised 50.0%. The negative mycological examination ratio stood at 66.7%. The overall effectiveness evaluation showed no statistically significant difference between the two treatment groups in the Wilcoxon's rank sum test. No side effect was observed in either group. These findings showed that terbinafine therapy of tinea cruris is effective even with a short-term treatment of 2-3 days at a small dose.
Administration, Cutaneous↗