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The Journal of Dermatology 01/2013; · 1.49 Impact Factor
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The Journal of Dermatology 03/2012; · 1.49 Impact Factor
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The Journal of Dermatology 02/2012; · 1.49 Impact Factor
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Annals of Dermatology 02/2012; 24(1):112-4. · 0.53 Impact Factor
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ABSTRACT: The relationship between the two coexpressed differentiation markers, profilaggrin and loricrin, is not clear right now. In this study, we explored the interaction of profilaggrin N-terminal domain (PND) with loricrin in keratinocytes and epidermis. Confocal immunofluorescence microscopic analysis of human epidermis showed that PND colocalized with loricrin. Loricrin nucleofected into HaCaT cells colocalized with PND in the nucleus and cytoplasm. The PND localizes to both the nucleus and cytoplasm of epidermal granular layer cells. Nucleofected PND also colocalized with keratin 10 (K10) in the nucleus and cytoplasm. Immunoelectron microscopic analysis of human epidermis confirmed the findings in nucleofected keratinocytes. Yeast two-hybrid assays showed that the B domain of human and mouse PND interacted with loricrin. The glutathione S-transferase (GST) pull-down analysis using recombinant GST-PND revealed that PND interacted with loricrin and K10. Knockdown of PND in an organotypic skin culture model caused loss of filaggrin expression and a reduction in both the size and number of keratohyalin granules, as well as markedly reduced expression of loricrin. Considering that expression of PND is closely linked to keratinocyte terminal differentiation, we conclude that PND interacts with loricrin and K10 in vivo and that these interactions are likely to be relevant for cornified envelope assembly and subsequent epidermal barrier formation.
Journal of Investigative Dermatology 01/2012; 132(4):1206-14. · 6.31 Impact Factor
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ABSTRACT: Juvenile xanthogranulomas are benign histiocytic cell tumors that develop mainly in infancy and early childhood and then spontaneously regress. We report a 2-year-old boy who presented with generalized eruption of a mixture of micronodular and macronodular juvenile xanthogranuloma with a large number of widely distributed lichenoid papules. Light microscopic and immunocytochemical analyses of the lesion were consistent with juvenile xanthogranuloma. Abdominal ultrasonography did not detect any visceral lesions, and brain magnetic resonance imaging did not detect any mass lesions. We decided to observe the course without treatment in this case because there are no internal masses of juvenile xanthogranuloma. Regular follow up has therefore been scheduled. To our knowledge, this is the third report of a case demonstrating juvenile xanthogranuloma with lichenoid appearance. Future analyses of various cytokines such as granulocyte-macrophage colony-stimulating factor and/or tumor necrosis factor-α in juvenile xanthogranuloma lesions should be of great help in elucidating the pathogenesis of this disease.
The Journal of Dermatology 10/2011; 39(5):462-5. · 1.49 Impact Factor
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The Journal of Dermatology 09/2011; 39(3):316-8. · 1.49 Impact Factor
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European journal of dermatology: EJD 06/2011; 21(4):616-7. · 2.53 Impact Factor
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ABSTRACT: The epidermal cornified cell envelope is a complex protein-lipid composite that replaces the plasma membrane of corneocytes and is crucial for epidermal barrier function. Loricrin is a major constituent of the epidermal cornified cell envelope, contributing approximately 70% by mass. In order to explore novel function of wild-type (WT) loricrin other than the major component of the epidermal cornified cell envelope, we transiently expressed construct encoding human WT and mutant loricrin (730insG) in HaCaT keratinocytes. HaCaT cells transfected with WT or mutant loricrin were at differentiation level. WT loricrin in the transfected cells was seen diffusely in the cytoplasm and nuclei. Positive transferase deoxytidyl uridine end labeling staining was observed in the nuclei of WT loricrin-transfected HaCaT keratinocytes. Data from the DNA fragmentation assay showed that only WT loricrin induced DNA ladders compared with that of mutant loricrin. WT loricrin-transfected HaCaT keratinocytes were susceptible to programmed cell death (PCD). Activation of caspase-14 was also seen. In contrast, PCD or activation of caspase-14 did not occur in mutant loricrin-transfected HaCaT cells. These results suggest that the expression of WT loricrin facilitates induction of PCD in HaCaT keratinocytes.
The Journal of Dermatology 11/2010; 37(11):956-64. · 1.49 Impact Factor
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The Journal of Dermatology 09/2010; 37(9):827-9. · 1.49 Impact Factor
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ABSTRACT: Loricrin is a major constituent of the epidermal cornified cell envelope. Recently, heterozygous loricrin gene mutations have been identified in two dominantly inherited skin diseases, Vohwinkel syndrome with ichthyosis and progressive symmetric erythrokeratoderma, collectively termed loricrin keratoderma. We generated stable HaCaT cell lines that express wild-type (WT) loricrin and a mutant form found in Vohwinkel syndrome with ichthyosis, using an ecdysone-inducible promoter system. The cells expressing the mutant loricrin grew more rapidly than those expressing WT loricrin after induction for 5 days. Confocal immunofluorescence microscopy revealed that phospho-Akt occurred in the nucleolus where the mutant loricrin was also located. The level of activity of Akt kinase was about nine times higher in cells with the mutant than in those with WT loricrin. ERK1/2, the epidermal growth factor receptor, vascular endothelial growth factor (VEGF) receptor 2 and Stat3 were all phosphorylated in cells with the mutant loricrin. The docking proteins, Gab1 and c-Cbl, were also tyrosine-phosphorylated in these cells. Furthermore, chromatin immunoprecipitation assays showed that Stat3 protein bound to the VEGF promoter in cells with the mutant. Thus, this study suggests that VEGF release and the subsequent activation of VEGF receptor 2 link loricrin gene mutations to rapid cell proliferation in a cellular model of loricrin keratoderma.
Journal of Biological Chemistry 03/2010; 285(21):16184-94. · 4.77 Impact Factor
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Fumiya Miyamura,
Shinichi Kako,
Hiroko Yamagami,
Ken Sato,
Miki Sato,
Kiriko Terasako,
Shun-Ichi Kimura,
Hideki Nakasone,
Satoko Aoki,
Shinya Okuda,
Rie Yamazaki,
Kumi Oshima,
Kentaro Yoshinaga,
Takakazu Higuchi,
Junji Nishida, Toshio Demitsu,
Akihiro Kakehashi,
Yoshinobu Kanda
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ABSTRACT: Only some carriers of human T cell lymphotropic virus type I (HTLV-1) develop adult T cell leukemia/lymphoma (ATLL) after a long latency period, and an association has been reported between chronic refractory eczema, known as infective dermatitis, and young-onset ATLL. A 25-year-old female developed ATLL and underwent allogeneic hematopoietic stem cell transplantation (HSCT) in non-remission. She had chronic refractory eczema and corneal injury at the onset of ATLL. Remission of ATLL was achieved, and the HTLV-1 proviral load decreased after HSCT. In addition, her pre-existing eczema and corneal injuries almost disappeared. More than a year has passed since the transplantation was performed, and she has had no recurrence of either ATLL or lesions in the skin and eye. Her clinical course suggests a possible association between skin and eye lesions and HTLV-1 infection. Changes in the immunological condition after HSCT might play a key role. Special attention is needed when HTLV-1 carriers develop eye or skin lesions.
International journal of hematology 09/2009; 90(3):397-401. · 1.17 Impact Factor
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ABSTRACT: A 15-year-old, woman, Crohn's disease patient, who carried the TPMT *3C heterozygous mutant, complained of alopecia 3 days after starting 6-mercaptopurine (6-MP) and then developed severe myelosuppression 6 weeks after starting 6-MP. The alopecia involved scalp hair only (body hair preserved) and was dominant in the temporal region. Following these side effects, transient remission of Crohn's disease occurred. Myelosuppression due to 6-MP is a rare but life-threatening side effect that is difficult to predict despite continuous monitoring of complete blood cell counts. In the present case, 6-MP-induced alopecia preceded myelosuppression and progressed rapidly as the myelosuppression worsened.
Internal Medicine 02/2009; 48(9):693-5. · 0.94 Impact Factor
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ABSTRACT: A 70-year-old-male had suffered from non-pruritic, erythematous eruptions on the trunk for 3 months without any general symptoms. The individual lesions lasted for several days. Laboratory investigation showed marked elevation of serum immunoglobulin A (2235 mg/dL) with monoclonal gammopathy (IgA k-type). Monoclonal gammopathy of undetermined significance was diagnosed. Histopathological examination of the eruption revealed diffuse neutrophilic infiltration with leukocytoclasia in the dermis. There was no vasculitis. Treatment with antihistamines alone was not effective. Diaphenyl sulfone (DDS) at 75 mg/day dramatically improved the skin lesions. A similar case of urticarial erythema associated with IgA myeloma has been previously reported. We suggest that neutrophilic, urticaria-like erythema associated with IgA monoclonal gammopathy may be regarded as a new entity.
The Journal of Dermatology 06/2008; 35(5):293-6. · 1.49 Impact Factor
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Hideto Yokokura, Toshio Demitsu,
Maki Kakurai,
Naoka Umemoto,
Ryuichi Azuma,
Tomoko Yamada,
Masayuki Suzuki,
Yoshinori Jimbu,
Kozo Yoneda,
Norito Ishii,
Takashi Hashimoto
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ABSTRACT: A 58-year-old Japanese male visited us with painful lesions on the lower lip, oral mucosa and genital region of an 8-month duration. Histological features of the genital lesion were almost consistent with lichenoid tissue reaction. A few intraepidermal acantholytic keratinocytes were also seen in the suprabasal clefts. Direct immunofluorescence exhibited cell surface immunoglobulin (Ig)G deposition and linear deposition of fibrinogen at the dermoepidermal junction. IgG anti-desmoglein (Dsg)3 antibody, but not anti-Dsg1 antibody, was detected in the patient's serum by enzyme-linked immunosorbent assay. Immunoblotting using normal human epidermal extract detected the 210-kD envoplakin, 190-kD periplakin and 130-kD Dsg3. The diagnosis of paraneoplastic pemphigus (PNP) was made. Subsequent investigation revealed a large space-occupying lesion in the liver. Histological findings from liver biopsy specimen were consistent with hepatocellular carcinoma. The patient has been alive 38 months after the diagnosis of PNP was made, although the liver mass has slowly enlarged. Our case is clinically and histologically similar to erosive mucosal lichen planus. Immunological studies confirmed the diagnosis of PNP. The results of negative Dsg1 and positive Dsg3 were consistent with clinical features showing severe mucosal involvement without cutaneous erosion. In PNP, the association with non-hematological solid tumor is extremely rare.
The Journal of Dermatology 01/2007; 33(12):842-5. · 1.49 Impact Factor
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The Journal of Dermatology 06/2006; 33(5):386-7. · 1.49 Impact Factor
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The Journal of Dermatology 03/2006; 33(2):158-9. · 1.49 Impact Factor
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Journal of Dermatological Science 11/2005; 40(1):65-7. · 3.72 Impact Factor
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ABSTRACT: Familial occurrence of sporotrichosis is rare. We report two patients, a husband and wife, with sporotrichosis. A 67-year-old man and a 63-year-old woman, who were farmers, had erythematous plaques and nodules on their faces and his forearm. They had noticed their cutaneous lesions during nearly the same period without any traumatic history. Fragments of biopsy specimens from both of them were submitted for mycological cultures and yielded pure cultures of Sporothrix schenckii (S. schenckii). Restriction fragment length polymorphisms in the mitochondrial DNA of the S. schenckii isolated from the biopsy specimens of their lesions were investigated. The isolates were identified as type 5, which is comparatively abundant in the Kanto area in Japan. The husband was treated with potassium iodide and itraconazole. His wife was treated with itraconazole alone. We failed to isolate a causative fungus from the soil. Our case is the second case in the literature of sporotrichosis in a husband and wife during the same period.
The Journal of Dermatology 08/2005; 32(7):569-73. · 1.49 Impact Factor
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ABSTRACT: A 75-year-old Japanese male visited us with bullous eruptions on the extremities. Physical examination revealed large bullae on the hands, lower legs and feet. The oral mucosa was also involved. Histology disclosed subepidermal blister with inflammatory cell infiltrates in the dermis. Direct immunofluorescence showed deposits of IgG and IgA at the cutaneous basement membrane zone. Indirect immunofluorescence on 1 M NaCl-split human skin sections demonstrated that the patient's IgG antibodies reacted with the dermal side of the split, while IgA antibodies reacted with the epidermal side. Immunoblotting showed that the patient's serum reacted with the NC1 domain of type VII collagen (290-kDa epidermolysis bullosa acquisita antigen) as well as the 120-kDa linear IgA bullous dermatosis antigen, LAD-1. Systemic prednisolone resulted in a favorable response. From the clinicopathological findings, the present case is not consistent with either epidermolysis bullosa acquisita or IgA bullous dermatosis. Therefore, we regarded the case as mixed bullous disease of epidermolysis bullosa acquisita and linear IgA bullous dermatosis. Such a case has not been previously reported.
Dermatology 02/2005; 211(2):146-8. · 2.05 Impact Factor
