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Kimihiro Kiyokane

Publications and source records attributed to Kimihiro Kiyokane.

4 recordsLinked to original sources
PubMed2003

Downregulation of TGFbeta isoforms and their receptors contributes to keratinocyte hyperproliferation in psoriasis vulgaris.

BACKGROUND: Psoriasis vulgaris is a chronic inflammatory disorder characterized by epidermal hyperproliferation. Transforming growth factor beta (TGFbetas) have a major antiproliferative action in epidermis. OBJECTIVE: We evaluated the distribution and levels of expression of TGFbeta isoforms and their receptors in psoriatic versus normal skin with the goal of discovering potential alterations in TGFbeta signal transduction associated with psoriasis. METHODS: Expression of TGFbeta isoforms and their receptors was analyzed in normal and psoriatic skin using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. Furthermore, DNA synthesis was measured in normal keratinocytes transfected with a dominant-negative TGFbeta receptor II (TbetaRII) vector that eliminated most of the cytoplasmic TbetaRII domain. RESULTS: Marked elevations in DNA synthesis, as assessed by BrdU incorporation and proliferating cell nuclear antigen (PCNA) immunoreactivity, were confirmed in psoriatic epithelial cells. Using immunohistochemistry and RT-PCR analysis, expression of TGFbeta2 and 3 was diminished in the psoriatic epidermis as compared with those observed in normal skin. With respect to TGFbeta receptors, expression of TbetaRI and II was markedly decreased in the psoriatic epidermis. In addition, levels of Smad2 mRNA were also decreased in psoriatic skin. Transfection of normal keratinocytes with the dominant-negative TbetaRII vector significantly elevated DNA synthesis as compared with keratincoytes transfected with control vector (under condition of TGFbeta addition), suggesting that the dominant-negative TbetaRII mutant inhibits the antiproliferative effects of TGFbeta. CONCLUSION: The present investigation strongly suggest that the TGFbeta signaling pathway is downregulated in psoriatic skin and this situation leads to abnormal cell proliferation due to a functional decrease in growth regulation.

Adult↗
PubMed2003

A case of syringocystadenocarcinoma papilliferum in situ occurring partially in syringocystadenoma papilliferum.

We report a case of syringocystadenocarcinoma papilliferum in situ associated with syringocystadenoma papilliferum. The patient was a 64-year-old man with a red tumor that arose on top of his head two years before he consulted our department. The histological findings revealed a papillomatous growth on the epidermis forming several invaginations. Numerous papillary projections, lined by a two-layered epithelium with a benign appearance and decapitations on the luminal surface of the cells, extended into the lumens of the invaginations. Some projections showed a disorderly arrangement of multilayered cells with atypical nuclei. No differences between findings in the syringocystadenocarcinoma papilliferum in situ and those in the syringocystadenoma papilliferum were observed histochemically (PAS) or immunohistochemically (cytokeratin, CEA, CA 19-9, S-100, gross cystic disease fluid protein, lysozyme and Leu M1).

Cystadenocarcinoma, Papillary↗
PubMed2002

Characterization of nociceptin/orphanin FQ-induced pain responses by the novel receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride.

At the spinal level, nociceptin/orphanin FQ (Noc/OFQ) produces pronociceptive and allodynic effects at low doses (picogram range), while causing antinociceptive effects at high doses (microgram range). The discrepancy of pain modulation by Noc/OFQ at low and high doses raised a question whether Noc/OFQ exerted actions through the same Noc/OFQ receptor. In the present study, we examined the involvement of the Noc/OFQ receptor in pain responses with the novel nonpeptide antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride (JTC-801). Allodynia and hyperalgesia evoked by intrathecal administration of Noc/OFQ (50 pg/mouse) were dose dependently blocked by simultaneous administration of JTC-801 with IC(50) values of 32.2 and 363 pg, respectively. JTC-801 did not induce allodynia by itself. Subcutaneous injection of formalin into a hindpaw evoked biphasic pain behaviors such as flinching and biting in mice. Noc/OFQ at 10 pg increased the second-phase pain behaviors evoked by 1% formalin, whereas it strongly inhibited both the first-phase and second-phase pain evoked by 2% formalin at 1 microg. Although the pronociceptive effect by 10 pg of Noc/OFQ was dose dependently blocked by JTC-801 with an IC(50) value of 4.58 pg, the antinociceptive effects by 1 microg of Noc/OFQ were not antagonized by JTC-801. Furthermore, both phases of 2% formalin-induced pain behaviors were relieved by JTC-801. These results demonstrate that pronociceptive responses induced by a low dose of Noc/OFQ may be mediated through the Noc/OFQ receptor in the spinal cord and that JTC-801 can be a useful antagonist to examine the involvement of endogenous Noc/OFQ and mediation of the Noc/OFQ receptor under physiological and pathophysiological conditions including pain.

Aminoquinolines↗