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T Kishi

Publications and source records attributed to T Kishi.

At least 19 recordsLinked to original sources
PubMed2007

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.

Adult↗
PubMed2005

A study of the metabolism of methamphetamine and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in isolated rat hepatocytes.

The metabolism of methamphetamine (MA) and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in freshly isolated rat hepatocytes was investigated, and compared with in vivo results. A suspended hepatocyte culture, established from male Wistar rats using a collagenase perfusion technique, was incubated in the presence of MA or 2C-B. After enzymatic hydrolysis of the conjugated forms, the metabolites were extracted by liquid-liquid partition and analyzed by gas chromatography/mass spectrometry (GC/MS). Amphetamine, p-hydroxymethamphetamine and p-hydroxyamphetamine were detected in the culture fluids of the rat hepatocytes inoculated with MA. The alcohol derivative, carboxylic acid derivative, 2-O-desmethyl-2C-B, 2-O-desmethyl-N-acetyl-2C-B and 5-O-desmethyl-N-acetyl-2C-B were detected in the case of 2C-B. The major metabolite of MA in rat hepatocytes was p-hydroxymethamphetamine. This is in good agreement with the urinary excretion profile for rats that were fed MA. 2-O-Desmethyl-2C-B and the carboxylic acid derivative were the major recovered metabolites of 2C-B in the rat hepatocyte culture, a slight deviation from the in vivo findings, in which 5-O-desmethyl-N-acetyl-2C-B was found to be the main component. Metabolites with a hydroxy group were largely present in their conjugated forms in the culture fluids, except for 2-O-desmethyl-2C-B. Taking these results into consideration, a primary hepatocyte culture system has the potential to provide a quick and handy method for estimating the in vivo metabolic fate of abused drugs.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2005

Body weight is regulated by the brain: a link between feeding and emotion.

Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence.

Animals↗
PubMed2005

Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats.

The metabolism of 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a recently banned designer drug, in rats was studied by analysing its urinary metabolites. p-Hydroxy-TFMPP (p-OH-TFMPP) was isolated and identified as the main metabolite by using nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of TFMPP and p-OH-TFMPP in rats were investigated following a single intraperitoneal dosing of 5 mg kg(-1) TFMPP by using an optimized analytical procedure that combined solid-phase extraction and LC-ESI MS techniques. The cumulative amount of p-OH-TFMPP excreted within the first 48 h reached approximately 64% of the dose, of which 70% was the glucuronide conjugated form. The cumulative amount of parent TFMPP excreted was less than 0.7% of the dose. The results suggest that p-OH-TFMPP would be the most relevant metabolite to be detected for TFMPP exposure in the forensic and clinical analysis of human urine.

Animals↗
PubMed2004

Current clinical results of the Tsukuba BNCT trial.

Nine high grade gliomas (5 glioblastomas and 4 anaplastic astrocytomas) were treated with BSH-based intaoperative boron neutron capture therapy (IOBNCT). BSH (100 mg/kg body weight) was intravenously injected, followed by single fraction irradiation using the mixed thermal/epithermal beam of Japan Research Reactor 4. The blood boron level at the time of irradiation averaged 29.9 (18.8-39.5)microg/g. The peak thermal neutron flux as determined by post-irradiation measurements varied from 1.99 to 2.77x10(9) n cm(-2)s(-1). No serious BSH-related toxicity was observed in this series. The interim survival data in this study showed median survival times of 23.2 months for glioblastoma and 25.9 months for anaplastic astrocytoma, results which are consistent with the current conventional radiotherapy with/without boost radiation. Of the 4 residual tumors, 2 showed complete response (CR) and 2 showed partial response (PR) within 6 months following BNCT. No linear correlation was proved between the dose and the occurrence of early neurological events. The maximum boron dose of 11.7-12.2 Gy in the brain related to the occurrence of radiation necrosis. The clinical application of a mixed thermal/epithermal beam and JRR-4 facilities on BSH-based IOBNCT proved to be safe and effective in this series.

Adult↗
PubMed2002

Spin-polarized tunneling spectroscopy of co(0001) surface States.

Spin-polarized tunneling was studied on Co surfaces of exchange coupled Co/Cu/Co samples, using an Fe tip. A spin-polarized surface state of Co(0001) was found to exist at -0.43 eV relative to E(F), with FWHM of 0.23 eV in the spectra. The state exhibits negative magnetoresistance with an effective spin polarization of less than -23%, suggesting negatively high spin polarization of the surface state. Our first-principles calculations have supported the existence of the surface state. From the calculation, the state is identified as a minority spin Gamma-centered d(2)(z)-like surface state.

Journal Article↗
PubMed2001

Serine proteinase inhibitor 3 and murinoglobulin I are potent inhibitors of neuropsin in adult mouse brain.

Extracellular serine protease neuropsin (NP) is expressed in the forebrain limbic area of adult brain and is implicated in synaptic plasticity. We screened for endogenous NP inhibitors with recombinant NP (r-NP) from extracts of the hippocampus and the cerebral cortex in adult mouse brain. Two SDS-stable complexes were detected, and after their purification, peptide sequences were determined by amino acid sequencing and mass spectrometry, revealing that target molecules were serine proteinase inhibitor-3 (SPI3) and murinoglobulin I (MUG I). The addition of the recombinant SPI3 to r-NP resulted in an SDS-stable complex, and the complex formation followed bimolecular kinetics with an association rate constant of 3.4 +/- 0.22 x 10(6) M(-1) s(-1), showing that SPI3 was a slow, tight binding inhibitor of NP. In situ hybridization histochemistry showed that SPI3 mRNA was expressed in pyramidal neurons in the hippocampal CA1-CA3 subfields, as was NP mRNA. Alternatively, the addition of purified plasma MUG I to r-NP resulted in an SDS-stable complex, and MUG I inhibited degradation of fibronectin by r-NP to 24% at a r-NP/MUG I molar ratio of 1:2. Immunofluorescence histochemistry showed that MUG I localized in the hippocampal neurons. These findings indicate that SPI3 and MUG I serve to inactivate NP and control the level of NP in adult brain, respectively.

Animals↗
PubMed2001

Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulation of NK cell activity and subsets.

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets. METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies. RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre-infusion NK cell activity (mean + SD. 40.9 + 17.0%) at 4.4 +/- 0.5 weeks of gestation (GW) decreased to 15.0 +/- 7.90% at post-infusion status (5.4 +/- 0.5 GW). Pre-infusion percentages of CD56+ CD16- cells (3.5 +/- 2.1%) and CD56+ CD16- cells (16.8 +/- 8.8%) decreased to 3.0 +/- 2.2% and 11.1 +/- 6.9%, respectively, after MIVIg treatment. CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

Abortion, Habitual↗
PubMed2001

Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ.

1. We have already shown that the left ventricular (LV) end-systolic pressure-volume relationship (ESPVR) of rat hearts in situ is an upward convex curve and that LV end- systolic pressure (ESP(mLVV)) and the systolic pressure-volume area (PVA(mLVV)) at a mid-range LV volume (mLVV) sensitively reflect acute changes in LV contractility and work capability. Milrinone is a non-glycosidic, non-sympathomimetic drug that increases myocardial cAMP concentrations by selective inhibition of cardiac phosphodiesterase III. Therefore, milrinone could act on the entire cardiovascular system and cause an increase in inotropy, arterial vasodilatation and venodilatation. The aim of the present study was to investigate whether the approach we have recently instituted is able to detect the effects of milrinone on the entire cardiovascular system. 2. We measured simultaneously, in anaesthetized rats, continuous LV pressure using a catheter-tip micromanometer and LV volume by LV volumetry using a conductance catheter. We obtained steady state LV pressure-volume loops and intermittently obtained the LV ESPVR by gradual occlusion of the ascending aorta. We then evaluated LV function by assessing milrinone-induced changes in the ESPVR (i.e. ESP(mLVV) and PVA(mLVV)) and vasodilator actions by assessing milrinone-induced changes in ESP(ESV) and effective arterial elastance (Ea), defined as the ESP(ESV)/stroke volume ratio. 3. Milrinone (total dose 49.5 microg; infusion rate 3.3-6.7 microg/min, 7-10 microg/kg per min; blood concentration 53.9 ng/mL) largely shifted the ESPVR upwards and, thus, significantly increased end-systolic pressure (ESP(0.08)) and the systolic pressure-volume area (PVA(0.08)) at a mid-range LV volume (= 0.08 mL/g myocardium). Milrinone also significantly decreased LV ESP(ESV) and decreased Ea, although these decreases were not significant. 4. The results of the present study suggest that our own recently instituted approach to evaluate LV function by measuring LV pressure-volume loops and ESPVR succeeded in detecting a cardiotonic action of milrinone with arterial vasodilatation in normal rat hearts.

Animals↗
PubMed2001

Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.

We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA.

Diagnosis, Differential↗
PubMed2001

Adenovirus-mediated gene transfer into the NTS in conscious rats. A new approach to examining the central control of cardiovascular regulation.

The nucleus tractus solitarii (NTS) is an important site for the regulation of sympathetic nerve activity. It receives the signals through afferent fibers from arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other visceral receptors. Many studies have examined the role of nitric oxide (NO) in the NTS in cardiovascular regulation. However, most of these studies were conducted in an acute state with anesthesia. We have developed a novel technique of endothelial nitric oxide synthase (eNOS) gene transfer into the NTS in vivo. Adenovirus vectors encoding either the beta-galactosidase gene (Ad beta gal) or the endothelial nitric oxide synthase gene (AdeNOS) gene were transfected into the NTS. In the Ad beta gal-treated rats, the local expression of beta-galactosidase was confirmed by X-Gal staining, and beta-galactosidase activity was quantified using a colorimetric assay. In the AdeNOS-treated rats, the local expression of eNOS protein was confirmed by immunohistochemistry, and eNOS production was measured by in vivo microdialysis. Blood pressure and heart rate were monitored by a radiotelemetry system in a conscious state. The expression of each gene was observed from day 5 to day 10 after the gene transfer. In the AdeNOS-treated rats, blood pressure and heart rate significantly decreased from day 5 to day 10, and then thereafter gradually recovered over time. Our method may be useful in examining the local effect of a particular substance produced by a specific gene in the brain on cardiovascular function.

Adenoviridae↗
PubMed2001

Familial idiopathic hypoparathyroidism, sensorineural deafness and renal dysplasia.

We describe a 27-year-old woman with familial idiopathic hypoparathyroidism, bilateral sensorineural deafness and right renal aplasia. There was a family history of deafness in her father and two other family members with sensorineural deafness, one of whom had hypoparathyroidism. To our knowledge, there have been four previous reports of idiopathic hypoparathyroidism associated with sensorineural deafness and renal dysplasia. The clinical features were not identical to any of the four previous reports. Although no chromosome abnormalities were present in the patient using standard trypsin G-banding analysis, we speculate that some common genetic mutation caused hypoparathyroidism, sensorineural deafness and renal dysplasia.

Adult↗
PubMed2001

Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release.

In this study, we examine the role of NO located in the rostral ventrolateral medulla (RVLM) in the control of blood pressure and the activity of the sympathetic nervous system. To determine the effect of an increase in NO production in the RVLM on blood pressure in conscious rats, adenovirus vectors encoding either endothelial NO synthase (AdeNOS) or beta-galactosidase (Adbetagal) were transfected into the bilateral RVLM. The local expression of endothelial NO synthase (eNOS) protein in the RVLM was confirmed by immunohistochemical staining for the eNOS protein and by Western blot analysis. Mean arterial blood pressure (MAP) and heart rate, which were monitored using a radio-telemetry system, were significantly decreased in the AdeNOS-treated group from day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion was decreased on day 7 after the gene transfer in the AdeNOS-treated group. Microinjection of either N(G)-monomethyl-L-arginine (L-NMMA) or bicuculine, a gamma-amino butyric acid (GABA) receptor antagonist, into the RVLM at day 7 after the gene transfer increased MAP to significantly greater levels in the AdeNOS-treated group. However, microinjection of kynurenic acid into the RVLM on day 7 after the gene transfer did not alter MAP levels in either group. GABA and glutamate levels in the RVLM, when measured by in vivo microdialysis, were significantly increased in the AdeNOS-treated group. These results suggest that the increase in NO production caused by the overexpression of eNOS in the bilateral RVLM decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. Furthermore, these responses may be mediated by an increased release of GABA in the RVLM.

Adenoviridae↗
PubMed2000

CV-2619 protects cultured astrocytes against reperfusion injury via nerve growth factor production.

In this study, we examined the effect of the neuroprotective agent 2, 3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (CV-2619) on reperfusion injury in cultured rat astrocytes after exposure to hydrogen peroxide (H(2)O(2))-containing medium. CV-2619 (10 nM to 10 microM) significantly attenuated the reperfusion-induced decrease in cell viability. The compound showed an anti-apoptotic effect in this astrocyte injury model. Antioxidants such as ascorbic acid, alpha-tocopherol and reduced glutathione also inhibited H(2)O(2) exposure-induced cytotoxicity. CV-2619 did not affect the levels of reactive oxygen species, but it increased nerve growth factor (NGF) production. The effect of CV-2619 on H(2)O(2) exposure-induced cytotoxicity was blocked by cycloheximide and anti-NGF antibody. The protective effect of CV-2619 was antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor 2'-amino-3'-methoxyflavone and the phosphatidylinositol-3 kinase inhibitor wortmannin. These findings suggest that the effect of CV-2619 is mediated at least partly by NGF production in astrocytes and that ERK and phosphatidylinositol-3 kinases play a role in the downstream mechanism.

Animals↗
PubMed2000

Evidence for hypomethylation in two children with acute lymphoblastic leukemia and leukoencephalopathy.

BACKGROUND: The prognosis of patients with acute lymphoblastic leukemia (ALL) in childhood has improved with intensive chemotherapy. In particular, central nervous system (CNS) leukemia has been well controlled by the presymptomatic administration of intrathecal methotrexate (MTX), high dose systemic MTX, and irradiation. However, the prolonged intrathecal administration and/or the administration of high doses of systemic MTX, especially when combined with irradiation, can lead to leukoencephalopathy (LE), a serious CNS complication of such prophylaxis. Because the mechanisms by which MTX causes this complication have not been elucidated, the authors investigated the transmethylation status of the cerebrospinal fluid (CSF) in two children with ALL and LE to investigate the pathophysiology of that disorder. METHODS: The levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were measured in the CSF of 2 children with ALL and LE, 7 children with ALL only who were undergoing presymptomatic administration of MTX, and 18 reference children in whom diagnostic lumbar puncture was indicated for other reasons. A sensitive, high performance liquid chromatography (HPLC) method was used with fluorescence detection. RESULTS: The concentrations of SAM in the CSF were lower in the patients with ALL during treatment with MTX compared with the reference children. The SAM levels in the 2 patients with both ALL and LE were slightly lower than the levels in the 7 patients with ALL only. The SAH concentrations in the CSF were higher in the patients with ALL and LE compared with the patients with ALL only and the reference children. The mean concentration of SAH in the CSF was similar in the reference children to that found in the 7 patients with ALL only. The SAM-to-SAH ratios were lower in the 2 patients with ALL and LE and in the 7 patients with ALL only compared with the reference children. The ratios in the patients with ALL and LE were still lower than in those with ALL only, thus providing supporting evidence of hypomethylation in the 2 patients with ALL and LE. CONCLUSIONS: The data suggest that the treatment of children with ALL using MTX causes subclinical hypomethylation and that progressive hypomethylation in the CNS, as evidenced in the 2 patients with ALL and LE, may be responsible for the demyelination in the LE induced by MTX.

Child↗
PubMed2000

Topographical organization of projections from the subiculum to the hypothalamus in the rat.

The projections from the subiculum to the hypothalamus were comprehensively examined in the rat by using the anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde cholera toxin B subunit (CTb) methods. Tracing of efferents with PHA-L indicated that the medial preoptic region received projection fibers from the temporal two-thirds of the subiculum, whereas the anterior, tuberal, and mammillary regions received those from the full longitudinal extent of the subiculum. The subicular projections to the anterior and tuberal hypothalamic regions were also found to be organized in a topographical manner such that the temporal-to-septal axis of origin in the subiculum determined a ventromedial-to-dorsolateral axis of termination in the medial zone of the hypothalamus: Massive labeled fibers from the temporalmost part of the subiculum terminated in the subparaventricular zone and its caudal continuum around the dorsal and medial aspects of the ventromedial nucleus, and those from progressively more septal parts terminated in progressively more dorsolateral parts of the medial zone. In addition, the temporal-to-septal axis of origin in the subiculum tended to determine a medial-to-lateral axis of termination in the preoptic region as well as a ventral-to-dorsal axis of termination in the mammillary region. Furthermore, the temporal-to-septal axis of origin in the septal two-thirds of the subiculum corresponded to a ventrolateral-to-dorsomedial axis of termination in the medial mammillary nucleus. The topographical projections from the subiculum to the medial zone of the hypothalamus were confirmed by CTb experiments, representatively in the subicular projections to the anterior hypothalamic region. These results suggest that different populations of neurons existing along the longitudinal axis of the subiculum may exert their influences on the execution of different hypothalamic functions.

Animals↗