EXPRESSION OF p38 MITOGEN-ACTIVATED PROTEIN(MAP) KINASE IN THE NEURONS AND THE GLIAL CELLS OF THE DORSAL MOTOR NUCLEUS OF THE VAGUS NERVE AND THE HYPOGLOSSAL NUCLEUS AFTER AXOTOMY

Mitogen－activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli. p38 MAP kinase is one of the MAP kinase family and is activated in response to various extracellular stimuli such as proinflammatory cytokines and environmental stresses. To obtain information about the role of the p38 MAP kinase in the neurons and the glial cells after axotomy, we nvestigated changes of p38 MAP kinase expression in the dorsal motor nucleus(DMN) of the vagus nerve and the hypoglossal nucleus after axotomy in adult rats using in situ hybridization and immunohistochemical techniques. Expression of p38 MAP kinase mRNA was observed in the cytoplasms of the neurons in control rats, and showed no marked changes after axotomy. Three days after axotomy, however, expression of p38 MAP kinase mRNA was observed in the cytoplasms of perineuronal microglias in both nuclei. Immunohistochemical analysis revealed expression of p38 MAP kinase in the cytoplasms and nuclei of neurons in both nuclei in control rats. The stronger expression of activated p38 MAP kinase was observed in the DMN ofthe vagus nerve than in the hypoglossal nucleus. After axotomy，the expression of p38 MAP kinase, inactive and active, was reduced in the nuclei of neurons in both nuclei, while perineuronal microglias showed increased expression in their cytoplasms and nuclei. These findings indicate that the reduction of the expression of p38 MAP kinase, inactive and active, influences the transcription factors, and plays an important role in retrograde neuronal reactions. Moreover, the increased expression of p38 MAP kinase in the perineuronal microglias may be related to microglial cell reactions and retrograde neuronal reactions

Clinical effect of terodiline hydrochloride on nervous pollakisuria or irritative bladder

神経性頻尿および刺激膀胱患者を対象とし, その頻尿, 尿失禁, 残尿感などの症状に対するTD-758の臨床効果を, 24 mgあるいは12 mg, 1日1回, 4週間投与を行って検討した.1)解析対象例は95例で, TD-758 24 mg/日と12 mg日との間の症例配分および患者の属性に偏りはみられなかった.2)昼間の排尿回数は4週間投与により24 mg/日で2.7回, 12 mg/日投与で1.3回減少し, 2週目より両投与群間に有意差がみられた.夜間排尿回数は両投与群とも約1回減少したが, 両者間に有意差はなかった.3)頻尿, 尿失禁, 残尿感の改善率はいずれにおいても24 mg/日が12 mg/日に比し上回っており, 特に昼間頻尿では両投与群間で有意差がみられた.4)全般改善度判定では, 24 mg/日が12 mg/日に比し有意に優れ, 改善例はそれぞれ37例(74%)および23例(51%)であった.5)安全度判定で「副作用あり」と判定された例は24 mg/日で8例(15%), 12 mg/日で7例(15%)と同様であり, その内容としては口渇, 便秘, 胸やけなどの消化器症状が主であった.臨床検査成績では特記すべき異常変動はみられなかった.6)有用度判定の結果, 24 mg/日投与は12 mg/日投与に比し有意に優れ, 有用例はそれぞれ37例(74%)および23例(51%)であった.7) 4週間の試験終了後, 継続投与を行った症例19例(最長11ヵ月)では, 継続期間中に特記すべき副作用, また臨床検査値の異常は認められなかった.TD-758は神経性頻尿や刺激膀胱患者の頻尿, 尿失禁, 残尿感に有用であり, 至適用量は1日24 mgであるThe clinical effect of terodiline hydrochloride (TD-758) was studied in 95 patients with nervous pollakisuria or irritative bladder. TD-758 was given per os randomly at a dose of 24 mg or 12 mg once a day for 4 weeks. The symptoms such as urinary frequency, urinary incontinence and sense of residual urine were improved in 74% of the patients taking 24 mg, and in 51% of the patients taking 12 mg. The difference was statistically significant. Side effects such as dry mouth, constipation and heart burn were observed in 15% of the patients in each group and were not serious. The results of this study indicate that TD-758 is useful for these patients and its optimal dosage is 24 mg once a day

ICUの環境を考える : 騒音調査から

Article信州大学医学部附属病院看護研究集録 1988: 184-187 (1988)departmental bulletin pape

大学医療情報ネットワーク(UMIN) で利用可能な薬剤情報データベースと今後の課題

平成10年度国立大学附属病院医療情報処理部門連絡会議論文集 36-39, 199

Angiotensin II enhances epithelial-to-mesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma

金沢大学医薬保健研究域医学系We previously reported that hepatic stellate cells (HSCs) activated by angiotensin II (AngII) facilitate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma (ICC). AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition (EMT) in renal epithelial cells, alveolar epithelial cells and peritoneal mesothelial cells. However, in the past, the relationship between AngII and stromal cell-derived factor-1 (SDF-1) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail. SDF-1 and its specific receptor, CXCR4, are now receiving attention as a mechanism of cell progression and metastasis. In this study, we examined whether activated HSCs promote tumor fibrogenesis, tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor (AT-1) and the SDF-1/CXCR4 axis. Two human ICC cell lines and a human HSC line, LI-90, express CXCR4. Significantly higher concentration of SDF-1αwas released into the supernatant of LI-90 cells to which AngII had been added. SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor. Furthermore, addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression, reduced E-cadherin expression, and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells. Co-culture with HSCs also enhanced the migratory capability of ICC cells. These findings suggest that SDF-1α, released from activated HSCs and AngII, play important roles in cancer progression, tumor fibrogenesis, and migration in autocrine and paracrine fashion by mediating EMT. Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma, tumor progression and metastasis of tumor cells expressing AT-1 and CXCR4.Embargo Period 6 month

<所内学術研究成果報告>H. 「環境保全・地球環境温暖化防止をターゲットとする新パルプ資源ケナフの栽培と利用に関する研究」

本研究は, エコマテリアルとしての非木材繊維資源に最も適切である一年生植物ケナフ(Hibiscus cannabinus L.)の栽培とその利用を目的に, 1993年より開始した研究である。従来の成果は, すでに本年報1992,\u2794,\u2795,\u2796,\u2797,\u2798,および\u2799年に報告した。特に従来のケナフ栽培の成果の総決算として, 1998年より平塚市および平塚ケナフ普及協会との共同研究が行われてきた。特に, 平塚市では休耕田対策としてケナフの栽培を推奨し, 現在, 栽培したケナフのパルプ化と紙製造を行って市政に還元している。この現状はさらに展開し, 平塚市のみならず日本全国にその輪が広がり大きな活動となっている。これらの栽培や利用は最も基礎的な指導と, より学術的な研究成果の提供が常に必要であり, この点を最も重要な課題としている。さらに, 環境教育に対する展開を学校, 公民館などを中心に行い, 2000年度は, 平塚キャンパスで市内6小学校の生徒28名のケナフ教育を行った。まお, 研究室内では, 栽培研究の他に, a)種子の発芽阻害実験, b)海水による阻害実験, c)生長に伴うクロロフィル量および水分量の測定実験, d)光合成測定実験, e)花の成分(色素)研究, f)葉など各器官の成分研究などを行っている。取り扱った種類も, ローゼル(H. sabdariffa L.)類も加えると30種に近い

DIFFERENT EXPRESSION OF C-JUN AMINO-TERMINAL KINASE ISOFORM IN THE DORSAL MOTOR NUCLEUS OF THE VAGUS NERVE AND THE HYPOGLOSSAL NUCLEUS

Mitogen-activated protein kinases (MAPKs)are important mediators of signal transduction from the cell surface to the nucleus. c-Jun amino-terminal kinase (JNK) is a member of the MAP kinase group. The JNK family of kinases is comprised of at least 3 isoforms, JNK 1, JNK 2 and JNK 3, and all of these kinases phosphorylate the transcription factor c-Jun in response to various stimulations. c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transection. It is reported that the dorsal motor nucleus of vagus nerve shows degenerative changes after axotomy while the hypoglossal nucleus shows regenerative changes. In order to elucidate c-Jun metabolism after axotomy, we investigated the expression of JNK 1, JNK 2 and JNK 3 mRNA and immunohistochemical expression of JNK 1, JNK 2 and JNK 3 protein following vagus and hypoglossal nerve transection. We found that JNK 1, JNK 2 and JNK 3 mRNA were positive in the cytoplasms of neuronal and microglial cells. JNK 1 and JNK 2 protein were distributed mainly in the cytoplasm of neurons and glial cells, while only the JNK 3 immunoreactivity was observed intensely in the nuclei of neuronal cells. These results indicate that the principal activity of JNKs in neurons is contributed largely by JNK 3 under both normal and axotomized conditions