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Biomedical subjects

Tsuyoshi Araki

Publications and source records attributed to Tsuyoshi Araki.

At least 19 recordsLinked to original sources

Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development.

GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed.

Animals↗

Auditory P300 latency prolongation with age in schizophrenia: gender and subcomponent effects.

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N=108) and controls (N=70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho=0.214, P=0.026) and in male patients with schizophrenia (rho=0.260, P=0.049) whereas, it did not reach significance in female patients with schizophrenia (rho=0.174, P=0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.

Adult↗

The effect of perospirone on auditory P300 in schizophrenia: a preliminary study.

The present study was performed to determine the effect of perospirone, a novel antipsychotic drug with D(2)/5-HT(2A) antagonist and partial 5-HT(1A) agonist properties, on auditory P300 in eight patients with chronic schizophrenia. Switching to an equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in the negative symptoms of the positive and negative syndrome scale (PANSS). The change in P300 amplitude following a switch to perospirone correlated significantly with the improvement of general psychopathology symptoms, as well as with the change in scores on items of delusions, hallucinatory behavior, emotional withdrawal, depression, poor attention, and disturbance of volition. These results suggest that clinical improvement in response to perospirone in some patients may, at least in part, be mediated through cognitive change indexed by P300 in chronic schizophrenia.

Adult↗

Regulation of Dictyostelium prestalk-specific gene expression by a SHAQKY family MYB transcription factor.

PstA and pstO cells are the two major populations in the prestalk region of the Dictyostelium slug and DIF-1 is a low molecular weight signalling molecule that selectively induces pstO cell-specific gene expression. The two cell types are defined by their differential use of spatially separated regions of the ecmA promoter. Additionally, there are anterior-like cells (ALCs) scattered throughout the rear, prespore region of the slug. They, like the pstO cells, use a cap-site distal ecmA promoter segment termed the ecmO region. When multimerised, a 22-nucleotide subsegment of the ecmO region directs expression in pstA cells, pstO cells and ALCs. It also directs DIF-inducible gene expression. The 22-nucleotide region was used to purify MybE, a protein with a single MYB DNA-binding domain of a type previously found only in a large family of plant transcription factors. Slugs of a mybE-null (mybE-) strain express an ecmAO:lacZ fusion gene (i.e. a reporter construct containing the ecmA and ecmO promoter regions) in pstA cells but there is little or no expression in pstO cells and ALCs. The ecmA gene is not induced by DIF-1 in a mybE-strain. Thus, MybE is necessary for DIF-1 responsiveness and for the correct differentiation of pstO cells and ALCs.

Amino Acid Sequence↗

The Dictyostelium bZIP transcription factor DimB regulates prestalk-specific gene expression.

The ecmA gene is specifically expressed in prestalk cells and its transcription is induced by the chlorinated hexaphenone DIF-1. We have purified a novel bZIP transcription factor, DimB, by affinity chromatography on two spatially separated ecmA promoter fragments. Mutagenesis of the cap-site proximal DimB-binding site (the -510 site) greatly decreases ecmA expression in the pstO cells, which comprise the rear half of the prestalk zone, and also in the Anterior-Like Cells, which lie scattered throughout the prespore region. However, DimB is not essential for normal expression of the ecmA gene, instead it spatially limits its expression; ecmA is relatively highly expressed in the subset of prestalk cells that coats the prestalk zone, but in slugs of a DimB-null strain, ecmA is highly expressed throughout the prestalk zone. Because the -510 site is required for correct ecmA expression, we posit a separate activator protein that competes with DimB for binding to the -510 site. DimB rapidly accumulates in the nucleus when cells are exposed to DIF-1, and ChIP analysis shows that, in the presence of extracellular cAMP, DIF-1 causes DimB to associate with the ecmA promoter in vivo. Thus, DIF-1 regulates DimB activity to generate a gradient of ecmA expression in the prestalk zone of the slug.

Amino Acid Sequence↗

Comparison between mismatch negativity amplitude and magnetic mismatch field strength in normal adults.

The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing.

Adult↗

Perospirone in the treatment of schizophrenia: effect on verbal memory organization.

The present study was performed to determine if perospirone, a novel antipsychotic drug with D2/5-HT2A antagonist and partial 5-HT1A agonist properties, would improve memory organization in twelve patients with chronic schizophrenia. Switching to equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in indices of verbal memory organization of the Auditory Verbal Learning Test. Negative symptoms and extrapyramidal side effects were also ameliorated after switching to perospirone. The distinct cognitive enhancement profile of perospirone may be attributable to its partial 5-HT1A agonist action.

Adult↗

Confirmation of a relationship between reduced auditory P300 amplitude and thought disorder in schizophrenia.

We have previously reported an association between reduced amplitude of auditory P300 event-related potential and severity of positive thought disorder as assessed by the Comprehensive Index of Positive Thought Disorder in a sample of patients with chronic schizophrenia. Here we replicate those findings using a different measure, Thought Disorder Index (TDI), in a new larger sample of 55 patients. The auditory P300 amplitude showed a significant negative correlation with scores on TDI. This correlation was relatively more pronounced in the left temporal region than in the right temporal region. These results further suggest that electrophysiological abnormalities of information processing may underlie positive thought disorder in schizophrenia.

Adult↗

Electrophysiological indices associated with social functioning outcome in schizophrenia: a 5-year follow-up study.

We previously demonstrated that event-related potentials (ERPs), such as N1/N2b amplitudes in an auditory selective attention task, were significantly associated with communication skills of schizophrenia. The present study investigated the relationship between N1/N2b amplitudes and the quality of life (QOL) 5 years after ERP measurement. QOL of 15 patients with schizophrenia was assessed using the quality of life scale (QLS). Correlational analyses revealed a significant relationship between N2b, but not N1, amplitude and specific domains of QOL. N2b amplitude, an electrophysiological index of orienting response, may be associated with longitudinal social functioning outcome in schizophrenia.

Acoustic Stimulation↗

Association between lower P300 amplitude and smaller anterior cingulate cortex volume in patients with posttraumatic stress disorder: a study of victims of Tokyo subway sarin attack.

Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities.

Adult↗

Brain electric activity for active inhibition of auditory irrelevant information.

We applied high resolution event-related potentials (ERPs) to assess brain activities associated with inhibition of irrelevant information processing during auditory selective attention. Ten healthy subjects performed an auditory selective attention task. ERPs in response to standard stimuli delivered to the unattended ear (irrelevant stimuli) and those delivered to the attended ear (relevant stimuli) were evaluated using temporally sequential scalp current density (SCD) mappings. For the irrelevant stimuli, current sources were located in the mid-frontal regions at 140-220 ms post-stimuli, and these SCD values were significantly larger than those for the relevant stimuli. These results suggest that auditory selective attention process involves not only focusing attention on relevant information, but also inhibitory processing of irrelevant information mediated by the frontal cortex.

Adult↗

Season of birth effect on personality in a general population.

Seasonality of births in schizophrenia and other mental disorders has been consistently observed. This may be through effects of unknown environmental factors that seasonally fluctuate on the brain development. The effects may affect cognitive function of the brain and behavioral characteristics that might be correlated with the development of personality not only in patients with mental disorders but also in healthy subjects. We, therefore, investigated the effects of season of birth on personality traits in healthy Japanese adults (n = 397). Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during winter (December to February) than other subjects was observed (P = 0.036, after correction for the multiple testing, multiple regression analysis adjusting for age and sex). Other major factors of the NEO PI-R, including Neuroticism, Extraversion, Openness and Conscientiousness, were not affected by season of birth. Further studies may be recommended to confirm the results, considering the relatively limited sample size. Evaluation of cognitive functions and behaviors using other measures including event-related potentials and functional MRI may also help the interpretation of the present result.

Adult↗

Effects of corollary discharge on event-related potentials during selective attention task in healthy men and women.

Corollary discharge is a brain electrical activity associated with self-monitoring, which distinguishes self from others in thoughts or behaviors. Corollary discharge can be non-invasively assessed using event-related potential (ERP) recordings in humans. Previous studies have revealed that the amplitude of the N100 component elicited during an "odd-ball" task is reduced while a healthy subject is vocalizing, which may index the effect of corollary discharge on auditory ERPs. In this study, we attempted to assess the effect of vocalization on ERP components including N100, mismatch negativity (MMN), negative difference wave (Nd), and P300 during a selective attention task in 22 healthy adults. We also evaluated the possible contribution of gender to these effects. N100 amplitudes elicited by unattended standard stimuli were reduced under the vocalization condition compared with those under the baseline condition. However, there were no significant effects of vocalization on MMN, Nd or P300. Moreover, there was no significant effect of gender to the corollary discharge. These results suggest that the effect of corollary discharge on auditory ERPs is limited to the perceptual stage of information processing in healthy men and women.

Acoustic Stimulation↗

GSK3 is a multifunctional regulator of Dictyostelium development.

Glycogen synthase kinase 3 (GSK3) is a central regulator of metazoan development and the Dictyostelium GSK3 homologue, GskA, also controls cellular differentiation. The originally derived gskA-null mutant exhibits a severe pattern formation defect. It forms very large numbers of pre-basal disc cells at the expense of the prespore population. This defect arises early during multicellular development, making it impossible to examine later functions of GskA. We report the analysis of a gskA-null mutant, generated in a different parental strain, that proceeds through development to form mature fruiting bodies. In this strain, Ax2/gskA-, early development is accelerated and slug migration greatly curtailed. In a monolayer assay of stalk cell formation, the Ax2/gskA- strain is hypersensitive to the stalk cell-inducing action of DIF-1 but largely refractory to the repressive effect exerted by extracellular cAMP. During normal development, apically situated prestalk cells express the ecmB gene just as they commit themselves to stalk cell differentiation. In the Ax2/gskA- mutant, ecmB is expressed throughout the prestalk region of the slug, suggesting that GskA forms part of the repressive signalling pathway that prevents premature commitment to stalk cell differentiation. GskA may also play an inductive developmental role, because microarray analysis identifies a large gene family, the 2C family, that require gskA for optimal expression. These observations show that GskA functions throughout Dictyostelium development, to regulate several key aspects of cellular patterning.

Agar↗

[Neuroanatomy and neurophysiology in schizophrenia].

Advances in neuroimaging and neurophysiological techniques have enabled detailed investigations of the brain pathophysiology of schizophrenia. In this article, we first overviewed neuroanatomical and neurophysiological studies of the superior temporal gyrus and anterior cingulate cortex in patients with schizophrenia, using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), event-related potentials (ERPs) and magnetoencephalography (MEG). Next, we discussed several key points for future research in psychiatric neuroimaging, such as disease specificity, heterogeneity, utility as endophenotype markers, relationship to psychosocial outcome, and application to clinical purposes. Finally, we described important issues, in terms of the infrastructure and system, which need to be improved in clinical psychiatry research in Japan.

Brain↗

Smoking habits in Japanese patients with schizophrenia.

Studies from North America and Western Europe have observed a marked increase of smoking in schizophrenia. This preliminary study investigated smoking habits in Japanese patients with schizophrenia (n=137). The prevalence of smokers (34%) was not higher than in the general Japanese population (37%). Variables associated with smoking were also different from those reported in the Western literature. Different cultural backgrounds may underlie the differing results in Western and Japanese populations.

Adult↗

A STAT-regulated, stress-induced signalling pathway in Dictyostelium.

The Dictyostelium stalk cell inducer differentiation-inducing factor (DIF) directs tyrosine phosphorylation and nuclear accumulation of the STAT (signal transducer and activator of transcription) protein Dd-STATc. We show that hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc. Hyperosmotic stress is known to elevate intracellular cGMP and cAMP levels, and the membrane-permeant analogue 8-bromo-cGMP rapidly activates Dd-STATc, whereas 8-bromo-cAMP is a much less effective inducer. Surprisingly, however, Dd-STATc remains stress activatable in null mutants for components of the known cGMP-mediated and cAMP-mediated stress-response pathways and in a double mutant affecting both pathways. Also, Dd-STATc null cells are not abnormally sensitive to hyperosmotic stress. Microarray analysis identified two genes, gapA and rtoA, that are induced by hyperosmotic stress. Osmotic stress induction of gapA and rtoA is entirely dependent on Dd-STATc. Neither gene is inducible by DIF but both are rapidly inducible with 8-bromo-cGMP. Again, 8-bromo-cAMP is a much less potent inducer than 8-bromo-cGMP. These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway and the pharmacological evidence, at least, is consistent with cGMP acting as a second messenger.

Active Transport, Cell Nucleus↗