Event-Related Alpha-Band Power Changes During Self-reflection and Working Memory Tasks in Healthy Individuals.

Dysfunctional attentional control is observed in patients with mental disorders. However, there is no established neurophysiological method to assess attention in such patients. We showed a discrepancy in alpha-band power in the tasks that evoked internal and external attention event-related alpha-band power changes in healthy subjects during self-reflection (SR) and working memory (WM) tasks in a preliminary study.

Dopamine-induced functional activation of Gα mediated by dopamine D-like receptor in rat cerebral cortical membranes.

Although multiple roles of dopamine through D-like (D and D) and D-like (D, D, and D) receptors are initiated primarily through stimulation or inhibition of adenylyl cyclase via G or G, respectively, there have been many reports indicating diverse signaling mechanisms that involve alternative G protein coupling. In this study, dopamine-induced Gα activation in rat brain membranes was investigated. Agonist-induced Gα activation was assessed by increase in guanosine-5'--(3-[S]thio)triphosphate ([S]GTPγS) binding to Gα determined by [S]GTPγS binding/immunoprecipitation assay in rat brain membranes.

Functional activation of Gα protein via α -adrenoceptor in rat cerebral cortical membranes.

Although it is recognized that α -adrenoceptors are coupled to diverse intracellular signalling pathways, its primary transduction mechanisms are evoked by activating phospholipase C in the cell membrane through Gα , resulting in production of inositol 1,4,5-trisphosphate and diacylglycerol. However, there have been few studies that indicate directly the involvement of Gα proteins in this signalling pathway in the central nervous system. In the current study, we tried to pharmacologically characterize (-)-adrenaline-stimulated [ S]GTPγS binding to Gα in rat brain membranes.

Optimization and pharmacological characterization of receptor-mediated G activation in postmortem human prefrontal cortex.

The biochemical abnormalities in transmembrane signal transduction mediated through G protein-coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist-induced [ S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [ S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl and NaCl concentrations in assay buffer, incubation period and effect of white matter contamination.

Chimeric Mice With Humanized Livers Demonstrate Human-Specific Hepatotoxicity Caused by a Therapeutic Antibody Against TRAIL-Receptor 2/Death Receptor 5.

The activation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2)/death receptor 5 (DR5) induces apoptosis in various tumor cells but not in normal human cells. Because some therapeutic antibodies targeting TRAIL-R2 have demonstrated severe hepatotoxicity in clinical applications, novel in vivo models reflecting clinical hepatotoxicity are now required. In this study, we investigated the hepatotoxicity caused by KMTR2, an anti-human TRAIL-R2 monoclonal antibody, in chimeric mice with humanized livers (PXB-mice).

Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole.

Background: KW-2450 is an oral dual insulin-like growth factor-1 receptor/insulin receptor tyrosine kinase inhibitor. We investigated the and preclinical activity of KW-2450 plus lapatinib and letrozole and conducted a phase I trial of the triple-drug combination in one male and 10 postmenopausal female patients with advanced/metastatic hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Methods: A series of and animal studies was undertaken of KW-2450 in combination with lapatinib and hormonal agents.

Functional coupling between adenosine A receptors and G-proteins in rat and postmortem human brain membranes determined with conventional guanosine-5'-O-(3-[S]thio)triphosphate ([S]GTPγS) binding or [S]GTPγS/immunoprecipitation assay.

Adenosine signaling plays a complex role in multiple physiological processes in the brain, and its dysfunction has been implicated in pathophysiology of neuropsychiatric diseases such as schizophrenia and affective disorders. In the present study, the coupling between adenosine A receptor and G-protein was assessed by means of two [S]GTPγS binding assays, i.e.

Functional activation of Gα coupled to 5-HT receptor and M muscarinic acetylcholine receptor in postmortem human cortical membranes.

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) play a pivotal role in a wide range of signal transduction pathways, and receptor/G-protein coupling has been implicated in the pathophysiology of mental disorders. In this study, guanosine-5'-O-(3-[S]thio)triphosphate ([S]GTPγS) binding/immunoprecipitation assay for Gα was applied to postmortem human brains. After its optimization for human prefrontal cortical membranes, we selected 5-hydroxytryptamine (5-HT) and carbachol as efficient agonists for subsequent experiments.

Brain structure differences among male schizophrenic patients with history of serious violent acts: an MRI voxel-based morphometric study.

Background: The biological underpinnings of serious violent behaviors in patients with schizophrenia remain unclear. The aim of this study was to identify the characteristics of brain morphometry in patients with schizophrenia and a history of serious violent acts, who were being treated under relatively new legislation for offenders with mental illness in Japan where their relevant action should be strongly associated with their mental illness. We also investigated whether morphometric changes would depend on types of serious violent actions or not.

Adenosine A1( )receptors are selectively coupled to Gα(i-3) in postmortem human brain cortex: Guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding/immunoprecipitation study.

By means of guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding assay combined with immunoprecipitation using anti-Gα subunit antibody, we recently reported 5-HT2A receptor- and M1 muscarinic acetylcholine receptor-mediated Gαq activation in rat cerebral cortical membranes (Odagaki et al., 2014). In the present study, this method has been applied to postmortem human brains, with focusing on adenosine receptor-mediated G-protein activation.

[Chaotic use of depression-related medical terms: how should it be settled?].

Along with the marked increase of depressive patients, psychiatric terms related to depression have come to be exposed to many lay people in recent years. As a result, various psychiatric terms formerly interpreted and used correctly by psychiatrists have been simplified too much into only a few words such as "utsu", which are often used in an inappropriate way. The new word "utsu" was originally a fragment of words such as "utsu-shoujou" (= depressive symptom),"utsu-joutai" (= depressive state), or "utsu-byou" (= depressive illness).

RhoC and guanine nucleotide exchange factor Net1 in androgen-unresponsive mouse mammary carcinoma SC-4 cells and human prostate cancer after short-term endocrine therapy.

Background: Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen-dependent and androgen-unresponsive SC-3 and SC-4 cells.

Methods: Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC-4 and SC-3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay.

Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.

We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age.

[Visual presentation of psychiatric clinical decision-making by "graphic assessment sheet for diagnoses and treatments"].

Psychiatrists often have to treat patients even when the clinical information is insufficient to make a definite diagnosis. This is the case especially when we are treating first-visit outpatients or inpatients who have just been admitted. One of the causes of information insufficiency is a delay in obtaining clinical information on the patient, and another is a lack of characteristic manifestations of the disease because of an immature developmental stage.

Direct generation of induced pluripotent stem cells from human nonmobilized blood.

The use of induced pluripotent stem cells (iPSCs) is an exciting frontier in the study and treatment of human diseases through the generation of specific cell types. Here we show the derivation of iPSCs from human nonmobilized peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) by retroviral transduction of OCT3/4, SOX2, KLF4, and c-MYC. The PB- and BM-derived iPSCs were quite similar to human embryonic stem cells with regard to morphology, expression of surface antigens and pluripotency-associated transcription factors, global gene expression profiles, and differentiation potential in vitro and in vivo.

Establishment of a novel monoclonal antibody against LGR5.

LGR5 is an orphan G-protein-coupled receptor (GPCR) that is expressed on the cell surface membrane. LGR5 is reported to be overexpressed in colon, liver, and ovary tumor compared to normal tissue. However, a specific ligand for LGR5 has not yet been determined, and the function is still not clear.

Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs).

Mood profile evaluation by families, young physicians and experienced psychiatrists in an actual clinical practice setting.

The purpose of this study was to explore differences in mood profile evaluation between raters with different backgrounds. Special emphasis was placed on expertise factor, influence of mood categories, and patient heterogeneity in a clinical setting. We administered Profile of Mood Scale (POMS) to patients' families, residents, and experienced psychiatrists as well as the patients, asking them to make an evaluation based on their image of the patients' subjective mood experience.

Complete sequencing and characterization of 21,243 full-length human cDNAs.

As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding.