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Biomedical subjects

H Yasuno

Publications and source records attributed to H Yasuno.

At least 19 recordsLinked to original sources
PubMed1998

Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase).

The stratum corneum of the skin serves as an effective barrier for maintenance of the internal milieu against the external environment. At the cell periphery of the stratum corneum is the cell envelope, a highly insoluble membranous structure composed of precursor proteins cross-linked by epsilon-(gamma-glutamyl)lysine bonds. Transglutaminase 1 (TGase 1; keratinocyte TGase), a membrane-bound isozyme of the TGase family, has been proposed to catalyze this process of assembly. Deficient cross-linking of the cell envelope in some patients with the autosomal recessive skin disorder lamellar ichthyosis (LI) and several mutations of the TGase 1 gene that have been identified in families with LI suggest the importance of this gene in production of the cell envelope. In this study, we generated mice lacking the TGase 1 gene, and we report that they have erythrodermic skin with abnormal keratinization. In their stratum corneum, degradation of nuclei and keratohyalin F-granules was incomplete and cell envelope assembly was defective. The skin barrier function of TGase 1-null mice was markedly impaired, and these mice died within 4-5 h after birth. These results clearly demonstrate that the TGase 1 gene is essential to the development and maturation of the stratum corneum and to adaptation to the environment after birth. Thus, these TGase 1 knockout mice may be a useful model for severe cases of LI.

Absorption↗
PubMed1998

Virus-associated haemophagocytic syndrome caused by rubella in an adult.

Haemophagocytic syndrome is a systemic clinicopathological entity characterized by systemic proliferation of benign haemophagocytic histiocytes, fever, cytopenia, abnormal liver function and, frequently, coagulopathy and hepatosplenomegaly. Its occurrence has been documented in association with viral, bacterial, fungal and parasitic infections, a wide spectrum of malignant neoplasms, autoimmune diseases and drugs. We report a case of rubella virus-associated haemophagocytic syndrome in a previously healthy 29-year-old woman. Blood tests showed cytopenia, especially severe thrombocytopenia, liver dysfunction, hyperferritinaemia and hypercytokinaemia. Bone marrow examination showed many mature histiocytes with active haemophagocytosis. A skin biopsy from the rash revealed perivascular lymphohistiocytic infiltrates with haemophagocytic histiocytes in the upper and mid-dermis. The patient was treated with antibiotics and immunoglobulin, and by supportive measures including platelet transfusion, and recovered completely.

Adult↗
PubMed1998

Oral and epicutaneous desensitization in urushiol contact dermatitis in guinea pigs sensitized by 2 methods of different sensitizing potency.

This investigation was conducted to study the relationship between the different intensities of sensitization to urushiol induced by the maximization test method (MT) or by the ear-flank method (EF) in guinea pigs, and hyposensitization induced by repeated oral and/or epicutaneous administration of the allergen, and to compare the immune tolerance achieved between these routes of dosing. During the observation period of 10 weeks, both oral and epicutaneous administration produced hyposensitization to urushiol after weak sensitization by EF; however, only combined administrations via the oral and epicutaneous routes achieved hyposensitization after potent sensitization, while inadequate tolerance was induced by oral dosing and none by epicutaneous dosing. Thus, it is indicated that difficulty in establishing immune tolerance may increase with increasing intensity of primary sensitization, and that hyposensitizing potency tends to increase in the order epicutaneous, oral and combined (e.p.+p.o.) administrations of urushiol.

Administration, Cutaneous↗
PubMed1998

Recurrent malignant proliferating trichilemmal tumour: local management with ethanol injection.

We report a 59-year-old woman who exhibited a recurrent malignant proliferating trichilemmal tumour on the scalp for 1 5 years. The tumour was recalcitrant to conventional treatments such as chemotherapy, radiation or hyperthermia and we performed intratumoral ethanol injection as an alternative means of reducing tumour mass and obtaining haemostasis. Biopsy specimens obtained after the ethanol injection revealed oedema, haemorrhage in the dermis and degeneration of the tumour cells, showing vacuolization with pyknotic nuclei. For cases of recurrent skin tumours and for patients in poor clinical condition, intratumoral ethanol injection is likely to be a therapeutic alternative to surgery or other conventional treatments.

Anemia↗
PubMed1997

Calcium channel blockers suppress the contact hypersensitivity reaction (CHR) by inhibiting antigen transport and presentation by epidermal Langerhans cells in mice.

Since Langerhans cells (LC) are the principal antigen-presenting cells among epidermal cells, treatments suppressing LC function may inhibit CHR. Although calcium channel blockers (CCB) have been shown to suppress the functions of several immunologically active cells, little is known about their effect on LC. In this study we show that pretreatment with topical 1% nifedipine or verapamil HCl significantly suppressed both the sensitization and elicitation phases of a CHR in mice. We then investigated whether CCB affected LC. Flow cytometric analysis of regional lymph node cells obtained 24 h after applying FITC demonstrated that topical CCB treatment significantly reduced the percentage of FITC+ NLDC-145+ cells, suggesting that CCB had suppressed antigen transport by LC. In vitro treatment with nifedipine or verapamil significantly suppressed the antigen-presenting capacity of LC in a dose-dependent manner. In addition, in vitro CCB treatment reduced the percentage of class II MHC antigen-positive epidermal cells and significantly suppressed class II MHC and B7-1 levels in LC, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction, whereas surface expression of B7-2 and mRNA was only weakly reduced. Neither expression of CD45 nor the percentage of CD45+ cells were affected, suggesting that the effects of CCB on LC were not due to cytotoxicity. Our results suggest that CCB inhibit CHR, at least in part, by suppressing the functions of LC.

Animals↗
PubMed1997

Activation of the human transglutaminase 1 promoter in transgenic mice: terminal differentiation-specific expression of the TGM1-lacZ transgene in keratinized stratified squamous epithelia.

Transglutaminase 1 (TGase 1) is a tissue-specific enzyme which is expressed in the keratinized stratified squamous epithelia and which catalyzes straightepsilon-(gamma-glutamyl) lysine cross-links of proteins to form the cell envelope at the periphery of cornified cells. A transient expression assay using a luciferase reporter gene linked to the 2.5 kb 5' upstream region of the human TGase 1 gene (TGM1) showed phorbol ester-responsive promoter activity in cultured normal human keratinocytes. To assess its promoter activity in vivo, we generated transgenic mice expressing the Escherichia coli beta-galactosidase gene (lacZ) directed by the 5' upstream region. beta-Galactosidase histochemistry revealed that the TGM1-lacZ transgene was expressed in terminally differentiating keratinocytes in upper layers of stratified squamous epithelia in embryonic, neonatal and adult transgenic mice. The expression pattern was similar to that of endogenous TGase 1 mRNA detected by in situ hybridization. Furthermore, topical application of a phorbol ester to adult tail skin enhanced expression of the transgene as well as TGase 1 mRNA in the epidermis. Thus, the 2.5 kb 5' upstream sequence of TGM1 includes elements regulating tissue- and terminal differentiation-specific gene expression in stratified squamous epithelia.

Animals↗
PubMed1997

Merkel cell carcinoma with partial spontaneous regression: an immunohistochemical, ultrastructural, and TUNEL labeling study.

We report a case of Merkel cell carcinoma that partially regressed after biopsy. A 76-year-old woman presented with an 1 month history of a rapidly enlarging nodule on her left cheek. After biopsy, the nodule reduced to almost half the size and was excised 1 month later. The excised specimen showed a dense cluster of lymphocytes and fibrosis around the tumor nests. In addition, lymphocytes showed apposition with tumor cells. An immunohistologically dense, even infiltration of CD4+ and CD8+ cells was found around the tumor nests, and more CD8+ cells than CD4+ cells were seen in the tumor nests. By electron microscopy (EM), apoptosis of tumor cells and lymphocytes was observed. Many apoptotic cells were also detected by in situ nick end-labeling (TUNEL) of DNA-breaks, especially in the marginal area of tumor nests surrounded by dense lymphocytic infiltrates. It seems likely that T-cell immunity, which induces apoptosis of tumor cells, may have been involved in tumor regression.

Aged↗
PubMed1997

Protein expression of fibroblast growth factor receptor-1 in keratinocytes during wound healing in rat skin.

Fibroblast growth factors have been shown to play important roles in wound healing. To define their sites of action, we examined the expression of fibroblast growth factor receptor-1 (FGFR-1) during burn wound healing in rat skin by immunohistochemistry and western blot analysis. In cryostat sections of intact skin, little or no staining was observed. After a burn, however, staining for FGFR-1 was found in newly forming epidermis. The suprabasal layer of such epidermis, composed mostly of regenerating keratinocytes, was stained intensely, whereas keratinocytes in newly forming hair follicles were devoid of staining. Staining gradually decreased week by week after wound closure and was hardly visible 10 weeks after the burn, when the thickness of the epidermis had returned to the normal level. Staining was also found in small blood vessels and capillaries of granulation tissues of the dermis. Western blot analysis using the same antiserum was performed in the newly forming epidermis 10 d after the burn. A single band was detected with an apparent molecular weight of 120 kDa, corresponding to the short membrane-bound form of rat FGFR-1. Our study indicates that FGFR-1 is expressed during wound healing, mainly in regenerating epidermis and to some extent in blood vessels of the dermis. Fibroblast growth factors may affect the proliferation and differentiation of epidermal keratinocytes as well as angiogenesis in the dermis via the FGFR-1 expressed during wound healing.

Animals↗
PubMed1997

Acute cutaneous barrier perturbation induces maturation of Langerhans' cells in hairless mice.

Perturbation of the cutaneous water permeability barrier has been shown to result in many physiological events in keratinocytes, including upregulation of proinflammatory cytokine production. However, little is known about the effect of barrier disruption on Langerhans' cells (LC). In the present study, we examined whether acute barrier perturbation by acetone treatment or tape stripping affects the phenotypes and functions of LC in male hairless mice. Both procedures resulted in a two- to five-fold increase in the expression of MHC class II antigens, B7-2 and intercellular adhesion molecule-1 on LC, whereas no significant changes were detected in levels of B7-1. Levels of intracellular interleukin-1 beta, as determined by flowcytometry, were also increased 1 h after acetone treatment or tape stripping. LC obtained from barrier-disrupted mice induced a significant increase in syngeneic and allogeneic T-cell proliferation, compared to those from saline-treated mice. These results indicate that LC play a crucial role in maintaining cutaneous homeostasis against increasing exposure to external substances resulting from barrier disruption.

Acetone↗
PubMed1997

Angiosarcoma of the scalp associated with renal transplantation.

A case of cutaneous angiosarcoma occurring in a 51-year-old male renal transplant patient is reported. Multiple violaceous nodules surrounded by poorly demarcated red to purple discoloration were found on his scalp. Immunosuppressants consisting of azathioprine and prednisolone had been administered during the 12-year period since the renal transplantation. We diagnosed the lesion clinically as a cutaneous angiosarcoma and performed a wide surgical excision. The histopathological findings confirmed the diagnosis and showed tumour cells in the peripheral margin. Postoperatively, the patient started immunotherapy with systemic administration of recombinant interleukin-2 (rIL-2), but he refused to continue it because of the acute rejection of the transplanted kidney induced by the rIL-2. Instead he received radiation therapy (total 7000 rad) of the scalp. Although no recurrence was noticed for 15 months after the completion of radiation, he died due to lung metastasis from angiosarcoma. We review the seven cases, including ours, of angiosarcoma after renal transplantation that are reported in detail in the literature.

Fatal Outcome↗
PubMed1997

Verruciform xanthoma in association with a vulval fibroepithelial polyp.

We report the clinical, light microscopic, immunohistochemical and ultrastructural features of a verruciform xanthoma that developed in association with a vulval fibroepithelial polyp. To our knowledge, this is the first time that this association has been reported. Immunohistochemical findings confirmed that the xanthoma cells were of a monocyte/macrophage lineage. In addition to typical histological characteristics, prominent vascular ectasias were detected in the deep dermis at the periphery of this lesion. The ectasias may play a part in pathogenesis.

Female↗
PubMed1996

The eta isoform of protein kinase C mediates transcriptional activation of the human transglutaminase 1 gene.

Transglutaminase 1 (TGase 1) is expressed during the terminal differentiation of keratinized squamous epithelium to form cornified cell envelope in differentiated keratinocytes by the epsilon-(gamma-glutamyl) cross-linking reaction. The gene for human TGase 1 is responsible for autosomal recessive lamellar ichthyosis, a severe hereditary keratinizing disorder of the skin. We examined the transcriptional activity of the gene in FRSK, rat keratinocytic cells, transfected with the luciferase reporter gene under control of the 5' upstream region of human TGase 1 gene. Transfection of the reporter gene with an expression vector for the eta isoform of novel protein kinase C (nPKCeta), as well as exposure to 12-0-tetradecanoylphorbol-13-acetate, markedly increased the luciferase activity in FRSK, but not in HT-1080 fibrosarcoma cells, although exogenous nPKCeta was expressed in both. The induction was suppressed by deleting the TGase 1 upstream sequence from -95 to -67 and by deleting the kinase domain from exogenous nPKCeta. In comparison with other PKC isoforms, nPKCeta most effectively induced the luciferase activity. We suggest that nPKCeta, an epithelium-specific isoform of PKC, mediates the activation of the TGase 1 transcription.

Animals↗