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Biomedical subjects

I Yamashita

Publications and source records attributed to I Yamashita.

At least 19 recordsLinked to original sources

Semantic structure in schizophrenia as assessed by the category fluency test: effect of verbal intelligence and age of onset.

It has been reported that long-term memory function, including the semantic structure of category, is impaired in patients with schizophrenia. The present study was performed to determine: (1) whether the deficit in semantic structure in schizophrenia is independent of cultural backgrounds, and (2) the effect of age of onset and verbal intelligence on the degradation of semantic structure in these patients. Fifty-seven Japanese patients with schizophrenia and 33 normal control subjects entered the study. The semantic structure was derived by Multidimensional Scaling (MDS) analysis based on data from the ANIMAL category fluency test. The semantic structure was compared between: (1) schizophrenic patients as a whole vs. normal control subjects; (2) earlier onset (age of onset <20 years) vs. later-onset groups of patients; and (3) high Vocabulary score (score of the Vocabulary subtest from the WAIS-R>7) vs. low Vocabulary score patient groups. Normal control subjects demonstrated the domestic/size dimension in semantic structure, while no such dimension was obtained in patients with schizophrenia. The subgroup comparisons revealed that the later onset or the high Vocabulary score group maintained a relatively intact semantic structure compared with the earlier onset or the low Vocabulary score group, respectively. These findings suggest that the deficit in semantic structure in patients with schizophrenia is commonly observed irrespective of cultural backgrounds, and that age of onset and the level of verbal intelligence are closely related to severity of degradation of the semantic structure in schizophrenia.

Adult↗

Stability of exploratory eye movements as a marker of schizophrenia--a WHO multi-center study. World Health Organization.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Adult↗

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Adult↗

Mikimopine synthase (mis) gene on pRi1724.

By determination of the nucleotide sequence adjacent to the right border of T-DNA of the mikimopine-type Ri plasmid (pRi1724) in Agrobacterium rhizogenes, a new open reading frame (ORF) encoding 318 amino acids was found. A transcript of 1.35 kb derived from this ORF was observed in hairy roots of Ajuga reptans by northern blotting analysis. Including its own promoter and terminator, this ORF was isolated from the pRi1724 T-DNA and introduced into tobacco plants by the Agrobacterium-binary vector system. Since mikimopine, an opine and a stereoisomer of cucumopine, was accumulated in all organs of the transgenic tobacco plants, the new ORF was deduced to be the mikimopine synthase gene. For comparison, the nucleotide sequence of cucumopine synthase encoded on pRi2659 was also determined. No homology was found between mikimopine synthase and cucumopine synthase at the nucleotide, but partial homology was found at the amino acid level. Mikimopine synthase and cucumopine synthase produced by a protein expression system using E. coli catalyzed the synthesis of mikimopine and cucumopine from L-histidine and alpha-ketoglutaric acid, requiring NADH as a cofactor. These synthesized opines were identified by paper electrophoresis, TLC and HPLC analyses. The synthesized mikimopine or cucumopine could be degraded by A. rhizogenes strains harboring Ri plasmids encoding the respective catabolic enzyme.

Amino Acid Sequence↗

Induction of E-selectin after partial hepatectomy promotes metastases to liver in mice.

BACKGROUND: The liver is the most frequent site of tumor metastasis. It has been suggested that partial hepatectomy promotes liver metastasis of malignant disease and that expression of E-selectin, a cell adhesion molecule, plays roles in tumor metastasis. However, no reports are available concerning the expression of E-selectin after hepatectomy. METHODS: In the present study, we used BALB/c mice subjected to 30% partial hepatectomy after injection of 1 x 10(4) colon 26 cells to determine the effects of partial hepatectomy on tumor metastasis to liver. E-Selectin expression within the liver after partial hepatectomy was evaluated using reverse transcription polymerase chain reaction and Western blotting. In addition, we injected polyclonal antibody to E-selectin into mice in which partial hepatectomy had augmented liver metastasis. RESULTS: Mice subjected to partial hepatectomy had significantly increased numbers of liver metastases (sham operation, 1.5 +/- 2.0, vs partial hepatectomy, 35.5 +/- 19.3; P < 0.001). Expression of E-selectin mRNA within the liver was markedly increased 4 h after partial hepatectomy, but subsequently decreased at 24 h. E-Selectin protein was detected 8 h after hepatectomy, but subsequently decreased at 24 h as measured by Western blotting. Mice subjected to intraperitoneal injection of neutralizing antibody after operation had significantly decreased numbers of liver metastases (phosphate-buffered saline, 20.6 +/- 9.2, P < 0.05, and normal IgG, 18.0 +/- 8.0, P < 0.05, compared with polyclonal antibody to E-selectin, 5.6 +/- 4.8). CONCLUSION: Induction of E-selectin by partial hepatectomy promotes hematogenous liver metastasis. Our findings can be applied to surgical treatment of liver tumor to reduce the recurrence of liver metastasis after hepatectomy by inhibiting E-selectin-mediated adhesion using reagents to E-selectin.

Animals↗

Distinct structural changes detected by X-ray fiber diffraction in stabilization of F-actin by lowering pH and increasing ionic strength.

Lowering pH or raising salt concentration stabilizes the F-actin structure by increasing the free energy change associated with its polymerization. To understand the F-actin stabilization mechanism, we studied the effect of pH, salt concentration, and cation species on the F-actin structure. X-ray fiber diffraction patterns recorded from highly ordered F-actin sols at high density enabled us to detect minute changes of diffraction intensities and to precisely determine the helical parameters. F-actin in a solution containing 30 mM NaCl at pH 8 was taken as the control. F-actin at pH 8, 30 to 90 mM NaCl or 30 mM KCl showed a helical symmetry of 2.161 subunits per turn of the 1-start helix (12.968 subunits/6 turns). Lowering pH from 8 to 6 or replacing NaCl by LiCl altered the helical symmetry to 2.159 subunits per turn (12.952/6). The diffraction intensity associated with the 27-A meridional layer-line increased as the pH decreased but decreased as the NaCl concentration increased. None of the solvent conditions tested gave rise to significant changes in the pitch of the left-handed 1-start helix (approximately 59.8 A). The present results indicate that the two factors that stabilize F-actin, relatively low pH and high salt concentration, have distinct effects on the F-actin structure. Possible mechanisms will be discussed to understand how F-actin is stabilized under these conditions.

Actins↗

Clinical trial of acetazolamide in SCA6, with assessment using the Ataxia Rating Scale and body stabilometry.

OBJECTIVE: To investigate the effect of acetazolamide on spinocerebellar ataxia type 6 (SCA6). METHODS: Acetazolamide (250-500 mg/day) was administered orally for 88 weeks to 6 patients with SCA6, and its effect was quantitatively monitored using the Ataxia Rating Scale (ARS) and body sway analysis by stabilometry. RESULTS: During administration of acetazolamide, the ARS score and the amplitude of body sway were significantly reduced compared with before administration. However, the response became weaker after 1 year of treatment. CONCLUSION: Although this was an open trial, the results suggested that acetazolamide can temporarily reduce the severity of symptoms during the progression of SCA6.

Acetazolamide↗

Magnetic resonance imaging study of the cavum septi pellucidi in patients with schizophrenia.

OBJECTIVE: High-resolution magnetic resonance imaging was used to evaluate the prevalence of the cavum septi pellucidi (CSP) in 79 normal subjects and 86 patients with schizophrenia. METHOD: The CSP was assessed by counting the number of consecutive coronal 1-mm slices containing the CSP. A CSP equal to or greater than 6 mm in length was defined as large. RESULTS: The CSP was found in 74.4% of the patients and 74.7% of the normal subjects, a nonsignificant difference. No difference between groups was found in the prevalence of a large CSP. CONCLUSIONS: The findings support the idea that a small CSP is a normal anatomical variant. More cases of a large CSP are needed to elucidate the implications of this abnormality in schizophrenia.

Adult↗

Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment.

OBJECTIVE: The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia. METHOD: Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group. CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.

Antipsychotic Agents↗

Ventricular enlargement in schizophrenia spectrum patients with prodromal symptoms of obsessive-compulsive disorder.

We hypothesized that male patients with schizophrenia spectrum disorders who have prodromal symptoms of obsessive-compulsive disorder (OCD) have ventricular enlargement compared with non-psychotic OCD patients, and that the difference in the ventricular size would offer a clue to the early detection of schizophrenia spectrum disorders. The ventricle-brain ratios (VBRs) in eight male patients with schizophrenia or schizotypal personality disorder (SPD) who had prodromal symptoms of OCD were compared with eight male patients with non-psychotic OCD and 14 normal male comparison subjects using three-dimensional magnetic resonance imaging (MRI). The VBR of the schizophrenia spectrum group was significantly larger than those of the OCD group or comparison subjects. Even the minimum VBR in the schizophrenia spectrum group was larger than the maximum VBR in the OCD group. These results may suggest the usefulness of three-dimensional MRI for early detection of patients with schizophrenia spectrum disorders who manifest OCD symptoms early in the course of the illness.

Adolescent↗

A transcriptional autoregulatory loop for KIN28-CCL1 and SRB10-SRB11, each encoding RNA polymerase II CTD kinase-cyclin pair, stimulates the meiotic development of S. cerevisiae.

Alkalization of the medium is associated with and required for the cellular development to meiosis and sporulation in the yeast Saccharomyces cerevisiae. To elucidate the molecular mechanisms for the significance of external alkalization, we isolated mutants defective in division arrest at G1 phase under an alkaline condition. The mutants obtained had recessive alleles of SRB10 encoding the cyclin (SRB11)-dependent protein kinase that phosphorylates the CTD domain of the largest subunit of RNA polymerase II and negatively regulates the transcriptional initiation of certain genes. A delta srb11 deletion mutant showed the same cell cycle defect. When shifted to alkali, wild-type cells decreased transcript levels of G1-cyclin genes (CLN1 to CLN3) and KIN28-CCL1 (encoding another CTD kinase-cyclin pair which, in contrast, stimulates the promoter clearance and transcriptional elongation in most genes), resulting in the accumulation of G1 cells and the hypophosphorylated form of RNA polymerase II and in an increase in cell size. However, under the same conditions, a delta srb10 mutant was defective in these events, except the downregulation of CLN1 and CLN2. The delta srb10 mutation also influenced on the transcript levels of meiosis-inducing genes called IME1 and IME2: the mutation elevated the transcript level of IME1 but reduced that of IME2, resulting in partial defects in premeiotic DNA synthesis and meiosis. Overexpression of KIN28 and CCL1 in wild-type cells impaired the alkali-induced G1 arrest and the rate of meiosis and elevated the transcript levels of SRB11 and IME1. These results indicate that a transcriptional autoregulatory loop for KIN28-CCL1 and SRB10-SRB11 is important for G1 arrest and meiosis. We also found that environmental conditions for meiosis finely regulate the transcript levels of KIN28 and CCL1, such that nitrogen starvation first elevates them but subsequent alkalization of medium decreases them.

Culture Media↗

Neural correlates of memory organization deficits in schizophrenia. A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task.

Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99mTc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.

Adult↗

Prevalence of triplet repeat expansion in ataxia patients from Hokkaido, the northernmost island of Japan.

Approximately 44% of cases of spinocerebellar ataxia (SCA) in Hokkaido, the northernmost island of Japan, were estimated to be inherited. To determine the prevalence of triplet repeat expansion in hereditary SCA patients, we genotyped seven genetically defined dominant SCAs in 349 patients, including 266 patients from 77 families, 78 probands from unrelated families with hereditary late-onset SCA, and five patients in whom a family history of SCA was not demonstrated. The frequency of each disorder in a total of 155 unrelated families was 23.9% for Machado-Joseph disease (MJD), 29.0% for SCA6, 9.7% for SCA1, 7.7% for SCA2, and 2.6% for dentatorubral-pallidoluysian atrophy. Abnormal expansion of triplet repeats for SCA7 and SCA8 was not detected. A total of 27.1% of the patients had still unknown SCA mutations. In addition, the GAA repeat in the frataxin gene was not abnormally expanded in 13 early-onset SCA patients with clinical features similar to those of Friedreich ataxia. Comparison of our results with those from other centers handling SCA showed that MJD is prevalent throughout Japan, but the frequencies of other dominant SCAs differ considerably even within Japan.

Family Health↗

Cyclic AMP regulates cell size of Schizosaccharomyces pombe through Cdc25 mitotic inducer.

Nutritional state modulates the cell size of the fission yeast Schizosaccharomyces pombe, such that cells grown in rich medium are larger in size than those in poor medium. This signal is transduced partly through the cyclic AMP-dependent protein kinase cascade. However, little is known about how cyclic AMP interacts with the central cell cycle machinery, Cdc2, the cyclin-dependent kinase that induces mitosis. We show here that cyclic AMP regulates mitosis and cell size, in part, through regulation of protein stability of the Cdc2-activating phosphatase, Cdc25. However, our analysis demonstrates that cyclic AMP can negatively regulate mitosis independently of dephosphorylation of Cdc2 at Tyr(15).

8-Bromo Cyclic Adenosine Monophosphate↗