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Biomedical subjects

Takahiro Nemoto

Publications and source records attributed to Takahiro Nemoto.

17 recordsLinked to original sources
PubMed2007

Contribution of divergent thinking to community functioning in schizophrenia.

Fluency deficits have been associated with poor community functioning in patients with schizophrenia. In our previous study we demonstrated that the ability to generate higher-quality responses on tasks of divergent thinking as measured by several fluency tests was impaired in patients with schizophrenia. The purpose of the present study was to investigate the contribution of the deficits in divergent thinking to community dysfunction in schizophrenia. Forty Japanese outpatients with schizophrenia and 32 healthy control subjects were recruited for this study and assessed over a broad spectrum of the neurocognitive domain. Their capacity for divergent thinking was assessed by idea, design, and word fluency tests. Community functioning was assessed by using the Global Assessment of Functioning (GAF), the Life Assessment Scale for the Mentally Ill (LASMI), and the Social Functioning Scale (SFS). The results confirmed the qualitative deficits of divergent thinking in schizophrenia. Stepwise multiple regressions using neurocognitive and demographic/clinical variables as predictors revealed that the higher-quality response scores on the tasks of divergent thinking significantly contributed to community functioning. Moreover, the deficit on the verbal task of divergent thinking significantly contributed to impairment in the area of daily living, and the deficit on the nonverbal task of divergent thinking significantly contributed to impairment in the area of interpersonal relations. The results of this study reveal the importance and the possibility of cognitive remediation and cognitive training with strategies that target capacity for divergent thinking to improve community functioning in patients with schizophrenia.

Adult↗
PubMed2006

Both experimental and theoretical investigations of solid-state 17O NMR for L-valine and L-isoleucine.

We have presented an experimental investigation of the carboxyl oxygen NMR parameters for four distinct sites in l-valine and l-isoleucine. The carboxyl (17)O quadrupolar coupling constant, C(Q), and isotropic chemical shift, delta(iso), for these compounds are obtained by analyzing two-dimensional (17)O multiple-quantum magic-angle spinning (MQMAS) and/or 1D MAS spectra. The values of C(Q) and delta(iso) found to be in the range of 7.00-7.85 MHz, and 264-314 ppm, respectively. Extensive quantum chemical calculations at the density functional levels have been performed for a full cluster of l-valine molecules and a few theoretical models. The calculated results indicated that there was a correlation between the (17)O NMR parameters and C-O bond lengths, which was helpful for the spectral assignment. They also demonstrated that the torsion angle of l-valine plays an important role in determining the magnitudes of (17)O NMR parameters.

Isoleucine↗
PubMed2006

Ornithine decarboxylase overexpression enhances ERK and p38 phosphorylation and matrix metalloproteinase-2 expression.

In the present study, we investigated the relationship between ornithine decarboxylase, MAP kinase, and MMP-2 expression in vitro. Overexpression of ornithine decarboxylase cDNA induced MMP-2 expression both at mRNA and protein levels. Promoter analysis and gel shift assay showed that p53 and Ets-1 were involved in MMP-2 expression in ornithine decarboxylase overexpressing transfectants. Erk and p38 MAP kinase were significantly activated. Using specific inhibitors of MEK and p38, we clarified that MMP-2 expression was induced via both Erk and p38 MAP kinase signaling pathways. This is the first report showing the existence of a causal relationship between ornithine decarboxylase expression, Erk and p38 MAP kinase activation, and MMP-2 expression.

Animals↗
PubMed2006

2H Natural-abundance MAS NMR spectroscopy: an alternative approach to obtain 1H chemical shifts in solids.

(2)H NMR was examined as an approach to determine (1)H chemical shifts in solids. For high-resolution observation, the line width due to (2)H quadrupole interaction and chemical-shift anisotropy was removed by magic-angle spinning and that due to (1)H-(2)H dipolar interactions by (1)H decoupling. Further, we showed that the sensitivity can be enhanced by applying (1)H to (2)H cross polarization and by adding spinning-sideband spectra. These make it possible to obtain (2)H natural-abundance MAS spectra revealing highly resolved (2)H signals. The second-order quadrupole effects of (2)H are also examined.

Journal Article↗
PubMed2006

Growth hormone-releasing hormone (GHRH) neurons in the arcuate nucleus (Arc) of the hypothalamus are decreased in transgenic rats whose expression of ghrelin receptor is attenuated: Evidence that ghrelin receptor is involved in the up-regulation of GHRH expression in the arc.

GH secretagogue (GHS)/ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (Arc) of the hypothalamus. GHRH, somatostatin, and neuropeptide Y (NPY) in the hypothalamus are involved in the regulatory mechanism of GH secretion. We previously created transgenic (Tg) rats whose GHS-R expression is reduced in the Arc, showing lower body weight and shorter nose-tail length. GH secretion is decreased in female Tg rats. To clarify how GHS-R affects GHRH expression in the Arc, we compared the numbers of GHS-R-positive, GHRH, and NPY neurons between Tg and wild-type rats. Immunohistochemical analysis showed that the numbers of GHS-R-positive neurons, GHRH neurons, and GHS-R-positive GHRH neurons were reduced in Tg rats, whereas the numbers of NPY neurons and GHS-R-positive NPY neurons did not differ between the two groups. The numbers of Fos-positive neurons and Fos-positive GHRH neurons in response to KP-102 were decreased in Tg rats. Competitive RT-PCR analysis of GHRH mRNA expression in the cultured hypothalamic neurons showed that KP-102 increased NPY mRNA expression level and that NPY decreased GHRH mRNA expression level. KP-102 increased GHRH mRNA expression level in the presence of anti-NPY IgG. GH increased somatostatin mRNA expression. Furthermore, GH and somatostatin decreased GHRH mRNA expression, whereas KP-102 showed no significant effect on somatostatin mRNA expression. These results suggest that GHS-R is involved in the up-regulation of GHRH and NPY expression and that NPY, somatostatin, and GH suppress GHRH expression. It is also suggested that the reduction of GHRH neurons of Tg rats is induced by a decrease in GHS-R expression.

Animals↗
PubMed2006

Reducing the dose of antipsychotic agents ameliorates visual hypersensitivity attack: an ideal treatment option in terms of the adverse effect.

There are sporadic reports of antipsychotic-induced visual hypersensitivity attack (VHA). VHA is characterized by hypersensitivity of perception mainly in the visual modality and sometimes accompanied by an oculogyric crisis. However, some researchers regard VHA as a schizophrenia symptom. To determine whether VHA is an adverse effect of antipsychotic agents, we examined the effect of dose reduction on VHA. This was an open-label 36-week study. We randomized 34 patients with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures were the frequency and duration of VHA, assessed with patients' self-reports, and the Clinical Global Impressions (CGI). Assessment also included the Drug-induced Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric hospitals in Tokyo.VHA diminished in 16 patients (94.1%) in the reduced-dose group in the CGI score, the frequency (number of episodes per week), and the duration of the episodes (from 4.06 to 1.77, P < 0.001; from 2.59 to 0.82, P = 0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no changes in the fixed-dose group. There were no changes in the underlying illness as measured by the PANSS in both groups. Reducing the dose of antipsychotic agents ameliorates VHA and represents the ideal treatment option for patients with VHA.

Adolescent↗
PubMed2006

Relation between social functioning and neurocognitive test results using the Optional Thinking Test in schizophrenia.

The current study investigated the relationship between clinical evaluations of social functioning and neurocognitive test results, including various fluency tests for assessing divergent thinking, in patients with schizophrenia. The Optional Thinking Test (OTT) was used to measure the ability of individuals to conceive of alternatives. This test assesses alternative thinking, or the capacity to generate solutions to problems. The current study examined 36 schizophrenia patients and 25 normal subjects using the Mini-Mental State Examination (MMSE), the Rey Auditory Verbal Learning Test (RAVLT), the Letter Cancellation Test (LCT), the Letter and Category Fluency Tests, and the OTT for neurocognitive assessment, as well as the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), the Social Functioning Scale (SFS), and the Life Assessment Scale for the Mentally Ill - Interpersonal Relations (LASMI-I) for clinical measures. The schizophrenia patients had significantly poorer performances on the MMSE, RAVLT, LCT (time), fluency tests, and OTT than the controls. In the OTT, the proportions of classified strategies were indistinguishable between the schizophrenia patients and the controls. Alternative thinking, as measured by the OTT, was correlated with verbal fluency and attention but was not correlated with the social functioning scores (GAF, SFS, LASMI-I), whereas the Means-Ends Problem-Solving was correlated with the GAF in schizophrenia. Patients with schizophrenia could conceive of the same categories of alternatives as healthy people, but could not conceive as many alternatives.

Adult↗
PubMed2005

Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors.

AIM: To investigate the expressions of ornithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors. METHODS: ODC activity, MMP-2 expression, and mitogen-activated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively. RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels. CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

Antineoplastic Agents↗
PubMed2005

Urocortin 2 induces tyrosine hydroxylase phosphorylation in PC12 cells.

Urocotins (Ucns) are newly discovered members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn 2 is expressed in the adrenal medulla, and its receptor, CRF2 receptor, is also expressed in the adrenal gland. To predict the physiological significance of Ucn 2 expression in the adrenal medulla, we examined the effects of Ucn 2 on catecholamine secretion and intracellular signaling using PC12 cells, a rat pheochromocytoma cell line. PC12 cells were found to express CRF2 receptor, but not CRF1 receptor. Treatment with Ucn 2 increased noradrenaline secretion and induced phosphorylation of PKA and Erk1/2. Tyrosine hydroxylase (TH), a rate-limiting enzyme for catecholamine synthesis, was also phosphorylated by Ucn 2. Pretreatment with a PKA inhibitor blocked Ucn 2-induced NA secretion, and Erk1/2 and TH phosphorylation. Pretreatment with a MEK inhibitor did not block Ucn 2-induced noradrenaline secretion or PKA phosphorylation, although TH phosphorylation was blocked. Thus, Ucn 2 induces noradrenaline secretion and TH phosphorylation through the PKA pathway and the PKA-Erk1/2 pathway, respectively. These results suggest Ucn 2 in the adrenal gland may be involved in the regulation of catecholamine release and synthesis.

Animals↗
PubMed2005

Social cognitive problem-solving in schizophrenia: associations with fluency and verbal memory.

This study assessed the relationship between social functioning and neurocognitive function in individuals with schizophrenia. Social cognitive problem-solving (SCPS) is a significant contributor to social competence and is an aspect of information processing that is involved in the identification and resolution of interpersonal or social problems. We examined 49 schizophrenia patients and 28 healthy controls using the means-ends problem-solving procedure (MEPS) for SCPS, the Rey Auditory Verbal Learning Test (RAVLT), the Wisconsin Card Sorting Test (WCST), and a series of fluency tests for neurocognitive assessment, as well as the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Fluency tests can be used to evaluate divergent thinking, and a qualitative analysis was done of the fluency test responses. The results suggest that patients with schizophrenia have a significantly poorer MEPS performance than normal controls. In patients with normal RAVLT scores, MEPS scores were correlated with task-modified responses on the fluency test but not with any of the WCST scores. This suggests that SCPS is related to divergent thinking that requires concept flexibility and/or the conversion of viewpoint in patients with schizophrenia in whom verbal memory function is preserved.

Adult↗
PubMed2005

Qualitative evaluation of divergent thinking in patients with schizophrenia.

Patients with schizophrenia show deficits across a broad spectrum of neurocognitive domains. In particular, deficits in verbal fluency are common. Verbal fluency tests are neuropsychological tests that assess frontal lobe function or executive function but also assess divergent thinking. However, few studies have considered the impairment of verbal fluency from the viewpoint of divergent thinking. To consider the structure of divergent thinking, not only verbal assessments but also non-verbal assessments are indispensable. We administered several fluency tests, the idea fluency test, the design fluency test, and word (letter and category) fluency tests to 26 patients with schizophrenia and 26 healthy control subjects to evaluate divergent thinking in both groups and assessed their responses qualitatively. An acceptable minimal level of intelligence was maintained in the patient group. Although attention and executive functioning were relatively preserved in the subjects with schizophrenia, they demonstrated significant deficits in divergent thinking and had particular difficulty in producing ideas and designs requiring concept flexibility, a conversion of viewpoint, originality, or novelty. Research on deficits in divergent thinking in patients with schizophrenia may contribute to the development of cognitive and behavioral rehabilitation programs.

Adult↗
PubMed2004

Duration of untreated psychosis and pathways to psychiatric services in first-episode schizophrenia.

The aim of the present study was to examine the duration of untreated psychosis (DUP) in first-episode schizophrenia patients in Japan and to investigate the available pathways to psychiatric services. Eighty-three patients who visited Keio University Hospital (n = 54) or Oizumi Mental Hospital (n = 29) were evaluated retrospectively with regard to their DUP, living situation, social participation level, referral pathway, reason for seeking treatment, and their global assessment of functioning (GAF) score. The mean DUP was 13.7 months (median, 5.0 months) overall. No significant difference in DUP was found between subjects living alone and those living with others; however, employed patients had a significantly shorter DUP (8.1 months) than unemployed patients (18.7 months). Pathways to psychiatric services were totally different between the two institutions. Fifty-two subjects (62.7%) came to the services directly: 40 patients (74.1%) came to the university hospital and 12 patients (41.4%) came to the mental hospital. At the mental hospital, nine patients (31.0%) had been admitted because of a legal obligation, and six (20.7%) had been referred through public health centers. None of the patients had been referred to either of the services by general practitioners. The main reason for seeking treatment was psychiatric symptom aggravation (59.3%) at the university hospital and acting out (64.3%) at the mental hospital. Some universal psychosocial factors appear to influence the DUP but the characteristics of specific psychiatric services may also affect treatment delays.

Adolescent↗
PubMed2003

The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification.

Autophagy is a process for the bulk degradation of cytosolic compartments by lysosomes/vacuoles. The formation of autophagosomes involves a dynamic rearrangement of the membrane for which two ubiquitin-like modifications (the conjugation of Apg12p and the modification of a soluble form of MAP-LC3 to a membrane-bound form) are essential. In yeast, Apg10p is an E2-like enzyme essential for Apg12p conjugation. The isolated mouse APG10 gene product interacts with mammalian Apg12p dependent on mammalian Apg7p (E1-like enzyme), and facilitates Apg12p conjugation. The interaction of Apg10p with Apg12p is dependent on the carboxyl-terminal glycine of Apg12p. Mutational analysis of the predicted active site cysteine (Cys161) within mouse Apg10p shows that mutant Apg10pC161S, which can form a stable intermediate with Apg12p, inhibits Apg12p conjugation even in the presence of Apg7p, while overexpression of Apg7p facilitates formation of an Apg12p-Apg5p conjugate. Furthermore, the coexpression of Apg10p with Apg7p facilitates the modification of a soluble form of MAP-LC3 to a membrane-bound form, a second modification essential for autophagy. Mouse Apg10p interacts with MAP-LC3 in HEK293 cells, while no mutant Apg10pC161S forms any intermediate with MAP-LC3. Direct interaction between Apg10p and MAP-LC3 is also demonstrated by yeast two-hybrid analysis. The inability of mutant Apg10pC161S to form any intermediate with MAP-LC3 has ruled out the possibility that MAP-LC3 interacts with Apg10p as a substrate.

Amino Acid Sequence↗
PubMed2002

Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing.

A dynamic membrane rearrangement occurs in cells during autophagy to form autophagosomes. In this dynamic process, two ubiquitin-like modifications, Apg12p-conjugation and LC3-modification, are essential for the formation of autophagosomes. Apg7p and Apg10p catalyze the conjugation of Apg12p to Apg5p. The same Apg7p and Apg3p catalyze the processing of LC3 to a membrane-bound form, LC3-II. In this paper, we investigated whether Apg12p has an influence on the second LC3-modification system. A cross-linking experiment revealed that Apg3p interacts with the endogenous Apg12p.Apg5p conjugate. However, Apg3p itself interacts with free Apg12p more preferentially than the Apg12p.Apg5p conjugate, when free Apg12p exists. When Apg12p was overexpressed, LC3 processing was significantly enhanced in the presence of Apg7p. In contrast, when the Apg12p.Apg5p conjugate itself was accumulated by the overexpression of Apg12p and Apg5p, LC3 processing was dominantly inhibited, even in the presence of Apg7p. These results indicate that both Apg12p and the Apg12p.Apg5p conjugate are regulatory factors for LC3 processing.

Autophagy↗
PubMed2002

Coexpression of glucose transporter 1 and matrix metalloproteinase-2 in human cancers.

BACKGROUND: Cancer cells express higher levels of glucose transporter proteins (Gluts) than do normal cells. Glut-1 overexpression is associated with invasiveness. Because matrix metalloproteinase-2 (MMP-2) is also overexpressed in cancer cells and is associated with invasiveness, we tested the hypothesis that Glut-1 may regulate MMP-2 expression. METHODS: We transiently transfected Glut-1 complementary DNA (cDNA) or Glut-1 antisense oligonucleotides in the human rhabdomyosarcoma cell line RD and analyzed MMP-2 mRNA expression and cell invasiveness. Empty vector and sense oligonucleotides were used for controls. We analyzed MMP-2 promoter activity in transfectants with a luciferase reporter assay and with p53 and Ets-1 gel mobility shift assays. Eight human cancer cell lines and 80 human cancer specimens were analyzed for coexpression of Glut-1 and MMP-2 by western blot and immunohistochemical analyses, respectively. RESULTS: Overexpression of Glut-1 in RD cells increased MMP-2 expression 4.3-fold (95% confidence interval [CI] = 3.7-fold to 4.9-fold) and invasiveness 3.2-fold (95% CI = 2.6-fold to 3.8-fold) relative to control transfected cells. Conversely, suppression of Glut-1 expression by antisense oligonucleotides decreased MMP-2 expression by 71.5% (95% CI = 71.1% to 71.9%) and invasiveness by 53.0% (95% CI = 47.5% to 58.5%). Glut-1-mediated MMP-2 expression involved the binding of the transcription factor p53 but not Ets-1. All eight human cancer cell lines coexpressed Glut-1 and MMP-2 by western blotting, and 45 of 80 human tumor tissues coexpressed Glut-1 and MMP-2 by immunohistochemistry. CONCLUSIONS: MMP-2 expression and cell invasiveness are tightly associated with Glut-1 expression in human cancer cell lines. Because suppression of Glut-1 decreased MMP-2 expression and cancer cell invasion, Glut-1 could be a target for therapy of various cancers that overexpress Glut-1.

Blotting, Northern↗
PubMed2002

Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression.

Angiogenesis, an essential process for tumor growth, is regulated by endothelial proliferation factors and their inhibitors such as endostatin. Endostatin, a carboxyl-terminal fragment of type XVIII collagen, inhibits endothelial proliferation, angiogenesis, and tumor growth. Ornithine decarboxylase (ODC), a molecule that is overexpressed in various cancers, is associated with promoting tumor growth and angiogenesis. We found that ODC-overexpressing human cancer cells and breast cancer specimens showed suppressed expression of type XVIII collagen and endostatin. We hypothesized that ODC overexpression may facilitate angiogenesis in tumors by suppressing endostatin expression. ODC-overexpressing COS cells, which showed suppressed type XVIII collagen and endostatin expression, were established. Conditioned media derived from these cells, containing decreased levels of endostatin, induced significant endothelial proliferation. ODC-overexpressing cells, when transplanted into nude mice, suppressed type XVIII collagen expression and promoted neovascularization in vivo. Thus, overexpression of ODC facilitates endothelial proliferation by suppressing endostatin expression.

Animals↗