Nobuyuki Sato

S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.

Extracellular calcium ions (Ca2+) are important in regulating the differentiation of keratinocytes and squamous epithelial cells. To clarify the mechanisms involved in the differentiation of human esophageal epithelial cells (EECs), we used the primary culture of human EECs, which can be differentiated by increasing the concentration of extracellular Ca2+, and tried to reveal the extracellular Ca2+ inducible genes using a differential display (DD) method. We found that the calcium‐binding protein S100P showed a Ca2+‐inducible expression in the EECs. Our immunohistochemical study demonstrated that differentiated large EECs expressing S100P overlie immature proliferating cells which lack S100P immunoreactivity. S100P was detected in vivo in the suprabasal layers of the epithelium. These findings indicate that S100P expression is closely associated with differentiation of human EECs. We also investigated the expression of other S100 proteins, including S100A2, S100A6, and CAAF1 (S100A12), in human EECs. Most of the immature EECs were positive for S100A2 and S100A6, whereas the S100A12‐producing cells were similar to the S100P‐producing cells. In vivo, S100A12 was strongly detected on all epithelial cells except for basal and proliferating cells. S100A2 was detected on all of the epithelial cells. S100A6 was preferentially seen in the cells of basal layers. These findings suggest that within EECs S100 proteins might play important roles in cell differentiation during specific stages. Among them, S100P expression is unique in that this protein is transiently expressed during the early stage of differentiation. Anat Rec 267:60–69, 2002.

Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules

Background  Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal‐type‐related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation.

A sporadic case of epidermolytic hyperkeratosis caused by a novel point mutation in the keratin 1 gene

lesions have been documented in patients with known cutaneous lymphoma. However, in these cases, histological and immunohistochemical examination revealed CTCL rather than PG. In contrast, our patient had a clinical diagnosis of PG (supported by histology) made more then 2 months prior to the onset of subsequent CTCL, a finding we believe not previously reported. The exact nature of PG and its relationship with haematological disease remains to be elucidated. Several authors have commented upon the altered immune competence of PG patients and have drawn attention to immune dysfunctions such as the in vitro inhibition of neutrophil function and decreased neutrophil chemotaxis and delayed migration, coupled with abnormal bactericidal activity. The role of abnormal humoral or cell-mediated immunity in PG has also been explored. An abnormal ratio of T-helper cells (reduced) to T-suppressor cells (elevated) has been reported by Check et al. It has been suggested that many of the immunological abnormalities seen in PG may have an excess of T-suppressor function (or reduced T-helper function) as their underlying cause. Indeed abnormal T-helper to T-suppressor cell ratios may account for the association of PG with CTCL (ultimately due to expansion of a clone of malignant T cells) seen in our patient. The delay in presentation between PG and CTCL thus serves as a reminder of the correlation of PG and systemic disease. The apparent absence of concomitant systemic disease at presentation should not therefore dissuade the clinician from maintaining a high index of suspicion of an associated underlying disease process when assessing patients with PG.

A Missense Mutation in the Death Domain of EDAR Abolishes the Interaction with EDARADD and Underlies Hypohidrotic Ectodermal Dysplasia

Background: Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal-dominant or autosomal-recessive inheritance trait. X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms are caused by mutations in either EDAR or EDARADD genes. Methods: We analyzed the DNA from a Japanese patient with HED through direct sequencing, and also performed functional studies for the mutation. Results: We identified a homozygous missense mutation c.1073G>A (p.R358Q) in the EDAR gene of the patient, which was a nonconservative amino acid substitution within the death domain of EDAR protein. We demonstrated that the p.R358Q mutant EDAR protein lost its affinity to EDARADD, leading to reduced activation of the downstream NF-ĸB. Conclusion: Our data further suggest the crucial role of the EDAR signaling in development of hair, teeth, and sweat gland in humans.

Hypohidrotic ectodermal dysplasia caused by a missense mutation in the EDA gene

ejd.2011.1460 Auteur(s) : Atsushi Fujimoto1,2, Muhammad Farooq2, Nobuyuki Sato1, Yukiko Masui1, Hiroki Fujikawa1,2, Masaaki Ito1, Yutaka Shimomura2 yshimo@med.niigata-u.ac.jp 1 Division of Dermatology 2 Laboratory of Genetic Skin Diseases, Niigata University Graduate School, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by abnormal development of hair, teeth, and sweat glands. In most cases, HED shows an X-linked [...]

A case of myxoid malignant fibrous histiocytoma

A 66-year-old woman had noticed a nodule on her light groin 15 years ago. The nodule was excised two times because of recurrence. She came to our hospital because of a 3rd recurrence occurred. The nodule was widely excised with 5cm margins. Histopathologically, the tumor was mainly composed of spindle-shaped cells. In some areas of the lesion, the tumor cells were arranged in a storiform pattern, and in other areas myxoid changes were seen. Immunohistochemical study revealed that the tumor cells were positive for vimentin, factor XIII a, but negative for keratin, α-SMA, tdesmin, S-100, factor VIII, CD34 and EMA. Ultrastructurally, the tumor cells had a fibroblastic phenotype. Thus we diagnosed this tumor as malignant fibrous histiocytoma, myxoid type. Subsequently, a nodule had appeared on her forehead 2 years after the operation. Histopathologically, the nodule was diagnosed as myxoma, whereas the tumor which recurred about l year after the first operation was diagnosed as myxoid-MFH. One year later the tumor has recurred again; no systemic metastasis was detected. Recently it has been emphasized that, in most cases originally diagnosed as MFH, a specific line of differentiation is evident, and relatively few cases have to be classified as MFH or not otherwise specified. We assume that this case is myxofibrosarcoma rather than myxoid-MFH, because ultrastracturally, the tumor cells of this case were composed of only fibroblastic phenotype, and generally MFH reveals a more aggressive course than this case. [Skin Cancer (Japan) 2003; 18: 259-265]