論文 - 田中　謙二

Recurrent episodes of perceptual alteration in patients treated with antipsychotic agents

Uchida Hiroyuki, Suzuki Takefumi, Tanaka Kenji F., Watanabe Koichiro, Yagi Gohei, Kashima Haruo

Journal of Clinical Psychopharmacology 23 （ 5 ） 496 - 499 2003年10月

ISSN  0271-0749

　概要を見る

<p>Antipsychotics have been sporadically reported to induce the brief recurrent episodes characterized by hypersensitivity of the visual perception, which is known as paroxysmal perceptual alteration (PPA) mainly in Japan. PPA is characterized by hypersensitivity of perception mainly in visual modalities, which could occur in patients treated with antipsychotics. PPA is occasionally known to be accompanied by an oculogyric crisis (OGC). In this study, we examine the prevalence and the characteristics of patients with PPA. Three hundred thirty-eight patients who were treated with antipsychotics and diagnosed with schizophrenia, mood disorders, or neurotic disorders (International Classification of Disease, or ICD-10) were interviewed. We compared the characteristics between subjects with and without PPA. The mean overall prevalence of PPA was 3.25%, which was higher among patients treated with high-potency antipsychotics (3.91%) than in subjects treated with mid-potency or low-potency drugs (1.16%). PPA occurred simultaneously with OGC at the rate of 36.4%. We also found much similarity between PPA and OGC in terms of phenomenology. We suggest that PPA could manifest itself as an undesirable effect of antipsychotics, especially those of high potency. PPA and OGC may a share common underlying mechanism.</p>

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Preservation of hematopoietic properties in transplanted bone marrow cells in the brain

Ono Kenji, Yoshihara Ken, Suzuki Hiromi, Tanaka Kenji F., Takii Takemasa, Onozaki Kikuo, Sawada Makoto

Journal of Neuroscience Research 72 （ 4 ） 503 - 507 2003年05月

ISSN  0360-4012

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<p>Recent studies have described the possible transdifferentiation of bone marrow cells (BMC) into neurons and glia when they migrate to the brain. However, we have reported that some immature BMC migrating into the brain parenchyma after bone marrow transplantation express early hematopoietic markers but not neural or glial markers. The present study further characterizes transplanted BMC that migrate to the brain. Double immunolabeling confirmed that BMC migrating to the brain expressed hematopoietic but not neural markers, such as nestin, microtubule-associated protein-2 and glial fibrillary acidic protein, even 4 and 18 weeks after bone marrow transplantation. BMC that expressed green fluorescent protein also expressed hematopoietic but not neural markers when cultured with mixed brain cells according to double immunolabeling and single-cell dissection using a laser. Analysis of the DNA content indicated that most of the migrated BMC were arrested at the G0/G1 phase, and aneuploidy or tetraploidy was undetectable. Thus, BMC that migrate to the brain probably have preserved hematopoietic properties under physiological conditions. © 2003 Wiley-Liss, Inc.</p>

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Existence of functional β₁- and β₂-adrenergic receptors on microglia

Tanaka Kenji F., Kashima Haruo, Suzuki Hiromi, Ono Kenji, Sawada Makoto

Journal of Neuroscience Research 70 （ 2 ） 232 - 237 2002年10月

ISSN  0360-4012

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<p>We examined the expression and function of β-adrenergic receptor (β-AR) subtypes in both isolated primary rat microglia and a rat microglial cell line. RT-PCR analyses revealed that microglia expressed β₁- and β₂-ARs but not β₃-ARs, whereas rat primary peritoneal macrophages expressed only β₂-ARs. Stimulation of β-ARs on microglia by norepinephrine (NE) resulted in an increase in the level of intracellular cAMP and the subsequent expression of interleukin-1β mRNA. These effects were prevented by propranolol. Similar results were obtained with other selective β₁-AR agonists and antagonists. β₂-ARs on microglia were also functional. It is possible that noradrenergic innervations participate in the control of microglial functions via β₁-ARs on microglia in the brain, because NE has high affinity for β₁- and β₃-ARs but little or no affinity for β₂-ARs. It seems physiologically significant that microglia can be controlled by NE, which predominates over epinephrine in the brain, whereas macrophages in peripheral tissues can be controlled by epinephrine, which is at higher levels in peripheral tissues. © 2002 Wiley-Liss, Inc.</p>

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Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats

Huotari M., Passlin M., Nordberg H. L., Forsberg M., Kotisaari S., Tuomisto L., Shintani F., Tanaka K. F., Reenilä I., Laitinen K., Männistö P. T.

Journal of Neuroscience Methods 109 （ 1 ） 47 - 52 2001年08月

ISSN  0165-0270

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<p>6-Nitronoradrenaline, a bioactive compound recently identified in the brain, is known to inhibit catechol-O-methyltransferase. To study its effect on dopamine metabolism, it was administered into rat striatum via a microdialysis probe. Other nitrated catechols (6-nitrodopamine, 6-nitro-DOPAC and 5-nitro-HVA) were studied for comparison. Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Both 6-nitronoradrenaline and tolcapone increased striatal extracellular dopamine levels during the perfusion (at 100 μM concentration but not at 10 μM) and decreased the efflux of homovanillic acid. Tolcapone, but not other nitrated catechols, increased 3,4-dihydroxyphenylacetic acid efflux. None of the compounds inhibited MAO-B activity at 100 μM or lower. At 1 mM, 6-nitrodopamine inhibited MAO-B by 60%. Compared to tolcapone, other nitrated catechols were very weak COMT inhibitors in vitro. Neither tolcapone nor 6-nitronoradrenaline modified the metabolism of L-dopa which was given peripherally. In binding studies, both 6-nitronoradrenaline and other nitrocatechols failed to affect the dopamine transporter even at high μmolar concentrations. In conclusion, exogenous 6-nitronoradrenaline can act as a COMT inhibitor in the striatum and elevate striatal dopamine levels without inhibiting dopamine reuptake. Whether endogenous 6-nitronoradrenaline can be formed also in vivo in the striatum and act as a regulator of dopaminergic tone remains to be determined</p>

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Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metaolism in anesthetized rats

Huotari M, Passlin M, Nordberg HL, Forsberg M, Kotisaari S, Tuomisto L, Shintani Futoshi, Tanaka Kenji, F Reenila I, Laitinen K, Mannisto PT

Journal of Neuroscience Methods 109 （ 1 ） 47-52 2001年08月

研究論文（学術雑誌）, 共著

Elevated serum levels of interleukin-18 in schizophrenia

Shintani Futoshi, Tanaka Kenji, Fujii Yasuo, Yagi Gohei, Asai Masahiro

Psychiatry and Clinical Neuroscience 54 （ 6 ） S5-55 2000年12月

研究論文（学術雑誌）, 共著

Switching Neuroleptics polypharmacy into monopharmacy in Chronic schizophrenic patients

Watanabe Koichiro, Tanaka Kenji, Arai Tatsuyoshi, Hosogane Nana, Oda Kenichi, Tsunoda Kenichi, Uchida Hiroyuki, Inagaki Ataru, Yagi Gouhei

International Clinical Psychopharmacology 15 （ 6 ） 374 2000年11月

研究論文（学術雑誌）, 共著

Serum interleukin-18 levels are elevated in schizophrenia

Tanaka Kenji F., Shintani Futoshi, Fujii Yasuo, Yagi Gohei, Asai Masahiro

Psychiatry Research 96 （ 1 ） 75 - 80 2000年09月

ISSN  0165-1781

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<p>Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P = 0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia. (C) 2000 Elsevier Science Ireland Ltd.</p>

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Serum interleukin-18 levels are elevated in schizophrenia

Tanaka Kenji, Shintani Futoshi, Fujii Yasuo, Yagi Gohei, Asai Masahiro

Psychiatry Research 96 （ 1 ） 75-80 2000年09月

研究論文（学術雑誌）, 共著

脳内インターロイキン―1受容体アンタゴニストによるストレス反応の調節機構の解明

新谷太，田中謙二，脇田哲矢，八木剛平，浅井昌弘

精神薬研究年報 32   30-32 2000年03月

研究論文（学術雑誌）, 共著

精神分裂病の慢性重症例に対する抗精神病薬療法と血中モノアミン代謝産物の変動

八木剛平，田中謙二

臨床薬理 31 （ 1 ） 47-48 2000年01月

研究論文（学術雑誌）, 共著

Awakenings（めざめ現象）と非定型抗精神病薬への切り替え

田中謙二，藤井康男

臨床精神薬理 2 （ 8 ） 859-866 1999年08月

研究論文（学術雑誌）, 共著