Spinocerebellar ataxia type 6 (SCA6): Clinical pilot trial with gabapentin

The clinical effect of the GABAergic drug gabapentin was evaluated in 11 patients with spinocerebellar ataxia type 6 (SCA6). The total period of gabapentin treatment was 4 weeks, and outcome measures were determined with the International Cooperative Ataxia Rating Scales (ICARS) and postural sway studies. At week 4, 5 patients showed a decrease of the ICARS values by more than 10% compared with the pretreatment baseline. Eight patients showed a more than 10% decrease of the sway area (SA) and/or sway path length (SPL) values in postural sway Studies. The ICARS values and SA/SPL values were not necessarily consistent in each patient, but 3 patients showed a more than 10% decrease in the ICRAS, SA, and SPL values at week 4 when compared to the pre-treatment baseline. As a whole, the efficacy of gabapentin was not statistically confirmed in the 4-week trial because of the variation in efficacy in each patient, but the data are indicative that some SCA6 patients could benefit from gabapentin treatment.ArticleJOURNAL OF THE NEUROLOGICAL SCIENCES. 278(1-2):107-111 (2009)journal articl

原発性肺癌切除例における肺癌細胞の腫瘍内多様性に関する研究 -増殖細胞核抗原と核DNA量の二重染色による同時定量的解析

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1375号, 学位授与年月日：平成8年3月6日,学位授与年：199

Photoelectrochemical properties of dye-dispersing allophane-titania composite electrodes

Dye-dispersing allophane-titania composite electrodes were prepared from titanium alkoxide sols containing dye and allophane. The photoelectric conversion properties of the electrodes were investigated by photoelectrochemical measurements. The photocurrent values in the UV range decreased with an increase in the allophane content, whereas those in the visible range were increased by adding 1.0% (Al/Ti ratio) allophane. As a small amount of allophane nanoparticles were highly dispersed in the titania electrodes, the dye molecules were dispersed in the electrodes without decreasing the efficiency of the electron injection from the dye to the titania conduction band. The dye molecules dispersed on the titania nanoparticle surface were capped with allophane nanoparticles which prevented desorption. The dye molecules strongly interacted with the titania nanoparticle surface and efficiently injected the excited electrons into the titania conduction band. (C) 2015 Elsevier B.V. All rights reserved.ArticleAPPLIED CLAY SCIENCE. 107:138-144 (2015)journal articl

Interleukin-1 inhibits voltage-dependent P/Q-type Ca2+ channel associated with the inhibition of the rise of intracellular free Ca2+ concentration and catecholamine release in adrenal chromaffin cells

Effects of interleukin (IL) on intracellular free Ca2+ concentration ([Ca2+]i) rise and catecholamine (CA) release were examined in isolated, cultured bovine adrenal chromaffin cells. IL-1α and IL-1β inhibited the rise of [Ca2+]i and CA release induced by acetylcholine (ACh) and excess KCl both in normal and in Ca2+-sucrose medium. IL-1 receptor antagonist, IL-1RA by pretreatment blocked the inhibitory actions of IL-1. IL-1α reduced CA release induced by veratridine in normal medium but not in the presence of diltiazem. Analysis using specific blockers for voltage-operated Ca2+ channels revealed that IL-1α specifically inhibited the P/Q-type Ca2+ channel to reduce [Ca2+]i rise induced by excess KCl. IL-1 did not affect [Ca2+]i rise induced either by bradykinin or caffeine in Ca2+- deprivated medium or via activation of store-operated Ca2+ channel. The inhibitory effects of IL-1 were blocked by pretreatments of cells with herbimycin A, U0126 and PD 98054, but not with SB202190, SP 600125 or pertussis toxin (PTX), inhibited the induction of the inhibitory action of IL-1.These results demonstrated that IL-1 inhibits stimulation-evoked [Ca2+]i rise and CA release in chromaffin cells by blocking voltage-operated P/O-type Ca2+ channels. The inhibitory action of IL-1 may be mediated through tyrosine kinase and MEK/ERK pathways

MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters

AbstractThe Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DATs demonstrated greater transport activity than the wild-type, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [3H]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity

MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters

AbstractThe Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DATs demonstrated greater transport activity than the wild-type, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [3H]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity

Transport of dopamine and levodopa and their interaction in COS-7 cells heterologously expressing monoamine neurotransmitter transporters and in monoaminergic cell lines PC12 and SK-N-SH

The present study investigated the effects of levodopa, a precursor of dopamine (DA) therapeutically used for the treatment of Parkinson's disease, on DA transport in the two different systems, COS-7 cells heterologously expressing rat monoamine transporter cDNA and in monoaminergic cell lines PC12 and SK-N-SH. Levodopa enhanced uptake of [3H]DA and [3H]norepinephrine (NE) but not [3H]serotonin in the transfected COS-7 cells in a concentration-dependent manner. On the other hand, in PC12 and SK-N-SH cells where NET is functionally expressed, levodopa enhanced [3H]DA and [3H]NE uptake at low concentrations and inhibited the uptake at higher concentrations. The effects of levodopa on catecholamine transporters in the opposite direction suggest a different mechanism at the intra- and extracellular sites in a levodopa transport-dependent and independent manner