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Kiyoshi Maeda

Publications and source records attributed to Kiyoshi Maeda.

44 records · Page 3Linked to original sources

Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims.

A serotonergic dysfunction in the brain has been reported to be involved in suicidal behavior independently of the presence of a specific psychiatric disorder. Serotonin 1A (5-HT1A) receptors are known to be located on serotonergic nerve terminals and to be involved in the presynaptic regulation of serotonin release. Genetic factors partly explain the risks for suicide, and a suicide completion group is thought to be more uniform than a suicide attempt group. To explore the hypothesis that the 5-HT1A receptor-induced serotonergic dysfunction is implicated genetically in suicide, we focused on the structural polymorphisms, Pro16Leu and Gly272Asp, of the 5-HT1A receptor gene, and examined the association between suicide victims who completed suicide and these two polymorphisms. In both polymorphisms, we found no significant difference in genotype distribution or allele frequencies between suicide victims and controls. These findings suggest that neither of these two polymorphisms is associated with suicide victims and it is unlikely that the 5-HT1A receptor gene is implicated in the susceptibility to suicide.

Female↗

No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides.

Monoamine oxidase A (MAOA) has been implicated in the control of aggression and/or impulsivity in humans and been involved in suicide. This gene has a functional polymorphism in which there is a variable number tandem repeat (VNTR) in the upstream region (MAOA-uVNTR). We hypothesized that MAOA dysfunction due to this polymorphism was associated with suicide genetically through the disinhibition of aggression and/or impulsivity. We performed an association study between completed suicides and the MAOA-uVNTR polymorphism. No significant difference in genotype distribution or allele frequencies was found between completed suicides and comparison groups either in males or females. These results show no evidence of an association between the MAOA-uVNTR polymorphism and completed suicides and suggest that MAOA is not involved in the susceptibility to suicide.

Adult↗

Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.

Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients.

Adaptor Proteins, Signal Transducing↗

[The effects of daily physical activity on QOL in the elderly].

OBJECTIVE: To ascertain the meaning and the influence of daily physical activity on QOL among the elderly, we surveyed their lifestyle exercise habits, cross-sectionally and longitudinally. METHODS: The subjects of this study were all residents living in a certain suburb of Nagoya-city, aged 63, 68, 73, 78, 83 years of age. They answered questionnaires regarding their exercise, physical activity, and QOL with six categories. The same questionnaire survey was conducted again 3 years later, and 958 people who answered both of them were examined in this study. The three-year-trend for physical activities, exercise habits and QOL scores, were analyzed and a comparison of QOL was made between the first and third year data based on the primary physical-activity-scores. In addition we applied logistic regression analysis to investigate the influence of physical activity changes (independent variable) on maintaining or improving of QOL scores (dependent variable). RESULTS: Daily physical activities were well maintained, but the percentage of feasible activities decreased by 5-10% as the sample population aged. On the other hand, 20 to 30% of the subjects increased their physical activity. The more people moved, the higher the QOL scores they had in both cross-sectional and longitudinal analyses. According to the logistic regression analysis, baseline physical activity habits positively contributed to most QOL change, increase in exercise tending to maintain or improve the QOL scores. CONCLUSIONS: Daily physical activity was relatively well maintained among the sample population, and some increased their physical activity scores over the period studied. Those with high values had better physical conditions and a consistently high QOL. These results suggest that maintaining or increasing physical activity positively influences QOL in the elderly.

Activities of Daily Living↗

Differential changes in glutamatergic transmission via N-methyl-D-aspartate receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine.

We searched for changes in glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine (Meth). Prior to being given a challenge dose of Meth (2 mg/kg, s.c.), the rats were given Meth (4 mg/kg, s.c.) five times a week for 3 wk. Seven days after the challenge test, we examined glutamate (Glu) release from hippocampal and striatal slices evoked by 30 mm KCl, and NMDA-evoked dopamine (DA) release from striatal slices. We further immunoquantified NMDAR1, R2A and R2B receptors as well as the fodrin alpha-subunit, a 240 kDa cytoskeletal protein that is cleaved to form 150 kDa limited proteolytic fragments by NMDA receptor stimulation. In the study of KCl-evoked Glu release, Glu release from the hippocampus was 31% lower in the Meth-sensitized rats than in the control rats, while Glu release from the striatum was 34% higher in the Meth-sensitized rats. NMDAR1, R2A and R2B immunoreactivities in the striatum were significantly lower in the Meth-sensitized rats (by 12, 13 and 12%, respectively) than those in the control rats. However, no differences in the immunoreactivities were found for the hippocampus. Immunoquantification of the fodrin alpha-subunit in the hippocampus revealed that 150 kDa fragments were significantly lower (by 10%) in the Meth-sensitized rats than in the control rats. In contrast to the control rats, NMDA-evoked DA release from the striatum was diminished in the Meth-sensitized rats. These results indicate that the activity of the Glu system is functionally decreased in the hippocampus of Meth-sensitized rats, whereas the Glu system in the striatum of Meth- sensitized rats shows adaptive and functional changes in the receptors in response to the increased Glu release.

Journal Article↗

Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer.

Intercellular adhesion molecule-1 (ICAM-1) is a 90-kDa cell surface glycoprotein and is known to be a member of the immunoglobulin gene superfamily of adhesion molecules. It has been suggested that ICAM-1 expression on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system. We studied the correlation between the expression of ICAM-1 and clinicopathological factors, as well as infiltration of tumor infiltrating lymphocytes (TILs) in colorectal cancer. Resected specimens from 96 patients with colorectal carcinoma were investigated using immunohistochemical staining with a monoclonal antibody against ICAM-1. As a result, the incidence of lymph node or liver metastasis was significantly lower in patients with ICAM-1-positive tumors than in those with ICAM-1-negative tumors. Infiltration of TILs was more frequently observed in the ICAM-1-positive tumors than in the ICAM-1-negative tumors. The prognosis of the patients with ICAM-1-negative tumors was significantly poorer than that of those with ICAM-1-positive tumors. In conclusion, these findings suggested that ICAM-1 expression is closely associated with metastasis and may be a useful indicator of prognosis in patients with colorectal cancer.

Adult↗

Helicobacter pylori infection, but not mucosal atrophy, significantly affects serum pepsinogen level after gastric cancer surgery.

BACKGROUND/AIMS: Helicobacter pylori (Hp) infection is frequently observed in the remnant stomach after gastric cancer surgery, and is considered to play one of the important roles in chronic mucosal inflammation and cancer development. METHODOLOGY: Serum pepsinogen (PG) levels were measured in one hundred and eight patients after gastrectomy performed because of gastric cancer. The correlation between PG levels and the grade of mucosal inflammation in the remnant stomach was investigated together with the status of Hp infection. RESULTS: No statistical difference in serum PG level was found according to the severity of reflux gastritis, or grade of mucosal atrophy. Significantly higher serum PG II level and lower PG I/II ratio were found in cases with histologically severe mucosal inflammation than in those without inflammation. In Hp positive cases, PG I level stayed constant while PG II level scored a significantly higher value than those of negative cases. As a result, PG I/II ratio became significantly lower in cases with Hp infection than in those without infection. CONCLUSIONS: Hp infection and active mucosal inflammation, but not bile reflux or mucosal atrophy, significantly affect on the serum PG level in patients with remnant stomach after gastric cancer surgery. Serum PG level was suggested to indicate the grade of acute and chronic Hp-related inflammation in those patients.

Adult↗

Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus 5-FU-leucovorin in colorectal cancer.

BACKGROUND: 5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In addition, activation of 5-FU to form various nucleotides via three pathways requires phosphorylation by orotate phosphoribosyltransferase, thymidine phosphorylase and uridine phosphorylase, respectively. The aim of this study was to assess the predictive value of the expression of these genes in patients receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer. PATIENTS AND METHODS: Twenty-seven patients with metastatic, or recurrent colorectal cancer were studied. Enzyme gene expression was measured in primary tumors by the real-time reverse transcription PCR method. RESULTS: The TS mRNA level was significantly higher in the responders than in the non-responders (p=0.0409). CONCLUSION: The effect of IFL therapy may be determined by the extent of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for predicting the effect of intravenous regimens such as FOLFIRI.

Adult↗