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Biomedical subjects

Takuya Kojima

Publications and source records attributed to Takuya Kojima.

At least 19 recordsLinked to original sources

Cloning of two isoforms of soluble acid invertase of Japanese pear and their expression during fruit development.

Soluble acid invertase (S-AIV; EC 3.2.1.26) in Japanese pear fruit has an important role in accumulating hexoses during fruit enlargement and regulates the sucrose-to-hexose ratio in the vacuole. Full-length cDNA of PsS-AIV1 and PsS-AIV2 isoforms were cloned from Japanese pear fruit and their amino acid sequences share 40% identity; PsS-AIV1 was confirmed to code S-AIV isozyme purified previously. The roles of PsS-AIV1 and PsS-AIV2 genes throughout fruit development and in sugar composition were investigated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using specific primers of their transcripts. PsS-AIV1 transcript had a maximum level at 34 days after full bloom (DAFB) and decreased rapidly during fruit development; PsS-AIV2 transcript increased gradually during fruit growth from 34 DAFB, had its maximum level at 79 DAFB and remained high until 107 DAFB at active fruit enlargement. The activity of S-AIV was highest at 34 DAFB, decreased during fruit growth until 66 DAFB, remained almost the same during early fruit enlargement until 79 DAFB and then decreased again. Soluble sugars fructose and glucose began accumulating predominantly during fruit enlargement from 66 DAFB; sucrose began increasing rapidly during fruit maturation from 121 DAFB. High expression of PsS-AIV1 transcript and high enzyme activity in the young fruit stage seems to have an important role in supplying a lot of substrate for energy needed for cell division and growth by hydrolyzing sucrose to hexoses. Increasing PsS-AIV2 expression during fruit enlargement may lead to rapid cell expansion through increased osmotic pressure by accumulation of a large amount of hexose in the vacuole.

Amino Acid Sequence↗

Infrared study on annealing effect on conformation of zinc stearate.

The molecular conformation and thermal transition behavior of two zinc stearate specimens, unannealed one and annealed one, were compared. The unannealed specimen has one thermal transition at 134 degrees C. Annealing was made by increasing temperature to 150 degrees C and cooling to room temperature slowly. This annealed specimen has an exothermic peak at 103 degrees C, and endothermic shoulders and a peak at 118, 124 and 131 degrees C, respectively. The observed frequencies of all bands of the unannealed specimen at room temperature are assigned to the all-trans conformation. We found new bands at 858, 823, 793, 766, 688, and 604 cm-1 for the annealed specimen. Based on the normal mode analyses, these bands are assigned to the TGT conformation at the COO end, where T means trans and G means gauche. The annealed specimen consists of almost all-trans molecule but partial molecules have the TGT conformation.

Calorimetry, Differential Scanning↗

Direct effects of short-term psychoeducational intervention for relatives of patients with schizophrenia in Japan.

This study examined the direct effects of short-term psychoeducation on relatives of inpatients with schizophrenia, with the goal of introducing this type of support program into standard care. The subjects were 46 relatives of inpatients with schizophrenia who attended three or four sessions of psychoeducation. Levels of anxiety and subjective burden and distress were measured before and after sessions using self-administered rating scales. In addition, levels of expressed emotion were also measured. Results showed that both state and trait anxiety on the State-Trait Anxiety Inventory were significantly lower after psychoeducational intervention than before intervention. In addition, subjective burden and distress reported by the family significantly decreased on the subscales for family confusion resulting from a lack of knowledge of the illness and anxiety about the future, subjective burden and depression resulting from the patient's illness, and difficulties in the relatives' relationships with the patient. Comparison of high and low expressed emotion families showed that the intervention was almost equally effective for the two groups. However, its effectiveness with regard to the subjective burden and depression experienced by the families was significantly greater among high expressed emotion families. The present study confirmed that family psychoeducation during hospitalization, even for a short period, is effective for all families, whether high or low expressed emotion. Moreover, the results suggested that the intervention may have a greater effect on emotional factors in high expressed emotion families than in low expressed emotion families.

Adult↗

[Eye movement in patients with schizophrenia].

To clarify the cognitive function of schizophrenia, the exploratory eye movement was investigated using S-shaped figures in patients with schizophrenia and their relatives. As a result, the exploratory eye movement has been found to be a biological marker that reflects a specific and trait factor of schizophrenia. Using the exploratory eye movement combined with brain functional imaging, the pathology of schizophrenia that the neural network centering on thalamus was damaged is being clarified. Moreover, the disease gene of schizophrenia may be discovered especially on the chromosome 22 using the exploratory eye movement as an endophenotype. In addition, the exploratory eye movement can be given as a powerful candidate of diagnostic tool for schizophrenia.

Adult↗

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗

[Atypical depression in Japan--39 case series].

UNLABELLED: In Japan, relatively little attention has been paid to atypical depression, which is defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. The present study was undertaken to obtain detailed clinical information from patients with a diagnosis of atypical depression. We assessed clinical characteristics of each atypical feature, comorbidity of other psychiatric disorders, presence of a stressful life event, and underlying psychological stress in 39 psychiatric outpatients. We also examined the relationship of interpersonal sensitivity to each atypical feature. RESULTS AND DISCUSSION: Mean age of onset was 22 +/- 6, 74% were female, 20 patients (51%) had comorbid social phobia. Thirty (77%) had hyperphagia and 25 of these were women. Twenty (74%) had hypersomnia. Only seven patients reported daytime sleepiness and others (13) reported difficulty in staying awake due to lack of energy. Nineteen (49%) had leaden paralysis. Thirty-two patients (82%) had rejection sensitivity and this symptom correlated with scores of FNE (fears of negative evaluation), LSAS (Liebowits social anxiety scale) and Brief social phobia scale (BSPA). Seven patients reported disappointment in love as a stressful life event preceding the depressive episode. In patients with comorbid social phobia, loss of confidence due to hypersensitivity to rejection or criticism seemed to be the most important factor as a chronic psychologica stress. Seven patients met criteria for bipolar disorder and five out of seven had comorbid generalized social phobia. The clinical and theoretical implications of these findings were discussed.

Adult↗

Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks.

Antisaccade tasks require a subject to inhibit a saccade toward a briefly appearing peripheral target and instead to immediately generate a saccade to an equivalent point in the opposite hemifield. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks required to inhibit reflexive saccades and to voluntarily generate saccades. The results demonstrated that saccade and antisaccade tasks often bilaterally activate frontal, parietal and supplementary eye fields, lenticular nuclei and occipital cortex. Additional activation of bilateral dorsolateral prefrontal cortices, supramarginal gyri, anterior cingulate cortices and thalamus was observed during antisaccade tasks. These results indicate that fronto-parietal and fronto-striato-thalamo-cortical circuits are involved in antisaccade tasks. The fronto-parietal circuit is thought to be related to the planning of saccadic eye movements that involve attentional control, while the fronto-striato-thalamo-cortical circuits connect to cortical region as a feedback network. We speculate that the abnormalities in spatial attention and eye movement control observed in schizophrenia stem from dysfunctions in the fronto-parietal and fronto-striato-thalamo-cortical circuits.

Adult↗

Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families.

Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.

Alleles↗

Endogenous 5-HT inhibits firing activity of hippocampal CA1 pyramidal neurons during conditioned fear stress-induced freezing behavior through stimulating 5-HT1A receptors.

This study examines the activity of hippocampal CA, pyramidal neurons during conditioned fear stress (CFS)-induced freezing behavior in unanesthetized, unrestrained rats. The firing frequency of hippocampal CA1 pyramidal neurons was significantly decreased when conditioned rats exhibited freezing behavior. Firing frequency returned to the baseline after freezing behavior disappeared. The selective 5-hydroxytryptamine (5-HT)1A antagonists, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635), and N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2-phenylpropamide (WAY-100135) and 5-HT depletion with parachlorophenylalanine (PCPA) completely abolished the decrease in firing frequency during CFS-induced freezing behavior. These results suggested that endogenous 5-HT inhibited the firing activity of hippocampal CA1 pyramidal neurons during CFS-induced freezing behavior mainly through stimulating 5-HT1A receptors.

Animals↗

Significant linkage to chromosome 22q for exploratory eye movement dysfunction in schizophrenia.

A genome-wide scan for a locus responsible for exploratory eye movement (EEM), which is quantitative and can be disturbed in association with schizophrenia, was performed. A 10-cM resolution genome-wide linkage analysis of the EEM disturbance with 358 highly polymorphic microsatellite markers in 38 nuclear families with 122 members (38 probands, 47 sibs, and 37 parents) including 58 sib-pairs yielded the suggestive linkage to the GCT10C10 marker on chromosome 22q11.2 (LOD = 2.48). Dense mapping with additional markers around the GCT10C10 marker yielded evidence for significant linkage between EEM disturbance and markers D22S429 and D22S310 on chromosome 22q12.1 (LOD score of 4.63) with suggestive evidence for the chromosome region 22q11.2-q12.1. Our findings suggest that a relatively small number of loci may control the schizophrenia-related quantitative EEM trait. We believe that identifying gene(s) on chromosome 22q associated with the EEM phenotype may forward our understanding of the etiology of schizophrenia.

Adult↗

Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples.

BACKGROUND: A family based association study in a British sample found the NOTCH4 gene to be associated with schizophrenia; however, all six replication studies failed to confirm the finding. METHODS: We performed a family based association study of NOTCH4 and schizophrenia in 123 trios (16 Japanese and 107 Chinese). In addition to the original study's polymorphisms, we examined four new single nucleotide polymorphisms (SNPs)--SNPs_A, B, C and D--around SNP1 of the original study. We genotyped all samples for SNPs_A-D and for SNP1 and (CTG)n of the original study. RESULTS: We found no significant associations between NOTCH4 and schizophrenia or its subtypes for all polymorphisms, regardless of gender. The finding remained negative when the Chinese sample was analyzed separately. Exploratory analyses suggested that SNP_A may be associated with early-onset schizophrenia and that SNP1 may be associated with schizophrenia characterized by numerous negative symptoms. CONCLUSIONS: NOTCH4 is not a significant susceptibility gene for schizophrenia when clinical heterogeneity is ignored; however, NOTCH4 may be associated with early-onset schizophrenia or schizophrenia with many negative symptoms, but these findings should be interpreted cautiously.

Adult↗