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Biomedical subjects

D Sawamura

Publications and source records attributed to D Sawamura.

At least 19 recordsLinked to original sources
PubMed2006

Epidermolysis bullosa simplex in Japanese and Korean patients: genetic studies in 19 cases.

BACKGROUND: Epidermolysis bullosa simplex (EBS) comprises a group of hereditary bullous diseases characterized by intraepidermal blistering caused by mutations in either keratin gene, KRT5 or KRT14. Significant correlation between the position of mutations within these proteins and the clinical severity of EBS has been noted. A recent report showed EBS cases in Israel had unique genetic features compared with European or U.S.A. associated families, which suggests that the ethnic and geographical features of EBS patients may be different. OBJECTIVES: To assess the possibility that EBS may present with certain specific features in Japanese and Koreans and to identify additional EBS mutations for genotype/phenotype correlation. METHODS: EBS was clinically diagnosed and confirmed by transmission electron microscopic examination of a skin biopsy. Mutation analysis of KRT5 and KRT14 was performed by direct sequencing in 17 Japanese and two Korean EBS patients. RESULTS: We have identified six novel KRT5 missense mutations (V143D, D158V, V186M, Q191P, R352S, G517D). R352S is the first mutation in the 2A domain. Most of these novel mutations changed amino acids that were evolutionarily conserved. Eight including all five mutations in EBS-Dowling-Meara patients have been previously reported. We were unable to detect mutations in five sporadic EBS-Koebner patients. The proportion of mutations in KRT5 (11 of 14; 78%) is higher than that for KRT14 mutations (3 of 14; 21%) in these Japanese and Korean EBS patients. CONCLUSIONS: Japanese and Korean patients with EBS showed very similar phenotype and genotype correlations with patients from Western countries. Whether the higher proportion of KRT5 mutations is a definite characteristic of Japanese and Korean patients with EBS or not, requires further research into mutations in Japanese and Korean people.

Adult↗
PubMed2006

Childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type VII collagen: case report and review of the literature.

Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies to type VII collagen, a major component of anchoring fibrils. Most patients with EBA are adult and develop autoantibodies to the noncollagenous (NC) 1 domain of type VII collagen. We describe a 4-year-old Japanese boy presenting pruritic vesicles and tense blisters over his whole body. Immunofluorescence studies revealed linear IgG/C3 deposits along the dermal-epidermal junction of the patient's skin, and circulating IgG autoantibodies mapping to the dermal side of 1 M NaCl-split skin. By immunoblotting analysis using dermal extracts as a substrate, the patient's IgG antibodies labelled a 290-kDa protein corresponding to type VII collagen. Immunoblotting studies using recombinant proteins demonstrated that the patient's circulating autoantibodies recognized not only the NC1 but also the NC2 domain of type VII procollagen. Review of the previously reported cases and the present case suggested that patients with EBA with autoantibodies to regions other than the NC1 domain are all children younger than 10 years of age with clinical features of an inflammatory phenotype.

Autoantibodies↗
PubMed2006

Two cases of folliculosebaceous cystic hamartoma.

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed of dilated folliculosebaceous units associated with mesenchymal elements. Two cases of FSCH with typical histopathological features are reported. Patient 1 was a 60-year-old man presented with a normal skin-coloured asymptomatic nodule on his scalp. Patient 2 was a 70-year-old man with an asymptomatic nodule on his right auricle that had persisted for the previous 15 years. In all, 34 cases of FSCH have been reported in the English literature. Clinically, the lesions are asymptomatic, usually rubbery to firm in consistency, and usually occur on or above the neck (> 90%). Most lesions do not exceed 25 mm in diameter (> 90%). Histopathologically, FSCH shares several similar features to sebaceous trichofolliculoma, but it is usually possible to differentiate these two tumours.

Aged↗
PubMed2006

Development of lichen planus and psoriasis on lesions of vitiligo vulgaris.

This paper reports a unique case of coexistence of vitiligo vulgaris, lichen planus and psoriasis vulgaris in a 53-year-old man. Five years after the onset of vitiligo, lichen planus developed on his lower lip. Another 4 years after the onset of lichen planus, he also exhibited psoriasis on his upper arms and trunk. Both the lichen planus and psoriasis occurred on lesions of the preceding vitiligo vulgaris. We discuss potential mechanisms for association of these three dermatoses, including Koebner phenomenon and photodamage.

Humans↗
PubMed2005

Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9.

BACKGROUND: Direct injection of naked DNA into skin can be efficiently used to transfer genes into keratinocytes in vivo. However, bacterial DNA is known to be a potent stimulus for vertebrate immune cells and immune systems. Towards the clinical use of this method, this study examined whether the application of plasmid DNA by direct injection induces any adverse skin effects. METHODS: Several plasmid preparations were prepared and directly injected into rat and human skin. Migration, IL-6 production, and reactive oxygen production assays were performed to determine the type of the primary cells responsible for the reaction. Involvement of toll-like receptor (TLR) 9 was examined by experiments using TLR9-knockout mice. RESULTS: Injection of several plasmid preparations into rat and human skin resulted in an inflammatory reaction at the treated site. Contamination by endotoxin in the plasmid preparation was shown to worsen this skin inflammation reaction. Immunohistochemical analysis showed that the infiltrating cells in the skin lesions were predominantly monocytes and neutrophils. Further experiments examining migration, IL-6 production, and reactive oxygen production indicated that the primary responsible cells were monocytes rather than neutrophils. Since it was recently shown that cytosine-guanosine dinucleotide (CpG) motif is critical for immune reaction induction in bacterial DNA and cellular responses were mediated by TLR9, we injected plasmids into the ear skin of TLR9-knockout mice. A decrease in ear swelling was noted in the knockout mice, compared to controls, suggesting that plasmid-DNA-induced dermatitis was mediated mostly by TLR9. CONCLUSIONS: This study demonstrates that injection of plasmid DNA induces skin inflammation initiated by monocyte activation via TRL9. We should therefore attempt to counteract this dermatitis during the clinical use of the naked DNA injection method in skin.

Animals↗
PubMed2005

Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases.

Animals↗
PubMed2005

Detection of 1733insC mutations in an Asian family with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients. OBJECTIVES: This study reports the first Asian family that has been demonstrated to carry a BHD mutation. PATIENTS/METHODS: The proband was a 26-year-old Japanese man with multiple asymptomatic, soft skin-coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle. RESULTS: Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight-cytosine tract (nucleotides 1733-1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots. CONCLUSIONS: This study is the first to find the same hot-spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.

Adult↗
PubMed2005

Leuprorelin acetate granulomas: case reports and review of the literature.

Leuprorelin acetate, an agonist of gonadotropin-releasing hormone (GnRH), is indicated in the treatment of prostate cancer. Recently, depot formulations of leuprorelin acetate have been widely used. We report three patients who showed a granulomatous reaction after treatment using a leuprorelin acetate 3-month depot formulation. These patients presented with 5-6-cm subcutaneous nodules at injection sites, which developed after the depot type was changed from a 1-month to a 3-month formulation. Skin biopsy showed epithelioid cells and foreign body giant cells containing round, translucent microspheres which formed sarcoidal granulomas. Changing to other GnRH agonists resulted in no further problems. We have reviewed the previous reports of leuprorelin acetate-induced granuloma formation. The formation of such granulomas may be related to the polymers that allow slow release after injection, or leuprorelin acetate itself may be responsible. The depot injection methods using leuprorelin also seem to have a causal effect in granuloma formation. Dermatologists need to know that depot leuprorelin acetate may cause a granulomatous reaction which produces a subcutaneous nodule that might be misdiagnosed as a malignant tumour.

Aged↗
PubMed2005

Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing.

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.

Adult↗
PubMed2004

Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability.

BACKGROUND: Darier disease (DD), an autosomal dominant genodermatosis characterized by warty papules and plaques over seborrhoeic areas, is caused by mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase type 2 isoform (SERCA2). While markedly different clinical severity within DD-affected family members is known, the pathomechanism has not been elucidated. OBJECTIVES: Based on the hypothesis that multiple ATP2A2 mutations might contribute to the pathomechanism, we have analysed two DD families in which the clinical severity differs markedly within a single pedigree, and, as controls, eight DD families without differing clinical severity. METHODS: All the exons and intron-exon borders of ATP2A2 were directly sequenced from the genomic DNA extracted from all the subjects. RESULTS: We identified the heterozygous mutations, G233R in pedigree 1 and C318R in pedigree 2, respectively, whereas no other ATP2A2 mutations in any of severely affected individuals were found. In eight DD pedigrees as control, we have found M1V, N39D, L180R, A838P and 2170 insertion G in each of five pedigrees, but no mutation was found in three DD pedigrees. CONCLUSIONS: Our results together with previous data indicate that the distribution of mutations is scattered over the entire ATP2A2 without any, as yet, discernible 'hotspots'. The mutations in pedigrees 1 and 2 with intrafamiliar clinical differences occurred around the Ca(2+)-binding sites on SERCA2, which might be associated with differences in clinical severity. These variations in ATP2A2 mutations alone cannot account for the clinical heterogeneity within DD pedigrees.

Adolescent↗