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Kazuo Yamada

Publications and source records attributed to Kazuo Yamada.

89 records · Page 5Linked to original sources
PubMed2003

A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia.

Hypofunction of the N-methyl-D-aspartate (NMDA) receptor has been hypothesized to underlie the pathophysiology of schizophrenia, based on the observation that non-competitive antagonists of the NMDA receptor, such as phencyclidine, induce schizophrenia-like symptoms. Mice lacking the NR2A subunit of the NMDA receptor complex are known to display abnormal behaviour, similar to schizophrenic symptoms. The expression of NR2A starts at puberty, a period corresponding to the clinical onset of schizophrenia. This evidence suggests that the NR2A (GRIN2A) gene may play a role in the development of schizophrenia and disease phenotypes. In this study, we performed a genetic analysis of this gene in schizophrenia. Analysis of the GRIN2A gene detected four single nucleotide polymorphisms, and a variable (GT)(n) repeat in the promoter region of the gene. A case-control study (375 schizophrenics and 378 controls) demonstrated evidence of an association between the repeat polymorphism and the disease (P = 0.05, Mann-Whitney test), with longer alleles overly represented in patients. An in-vitro promoter assay revealed a length dependent inhibition of transcriptional activity by the (GT)(n) repeat, which was consistent with a receptor binding assay in postmortem brains. Significantly, the score of symptom severity in chronic patients correlated with repeat size (P = 0.01, Spearman's Rank test). These results illustrate a genotype-phenotype correlation in schizophrenia and suggest that the longer (GT)(n) stretch may act as a risk-conferring factor that worsens chronic outcome by reducing GRIN2A levels in the brain.

Adult↗
PubMed2003

Subarachnoid hemorrhage induces Na+/myo-inositol cotransporter in the rat brain.

Neurons and glial cells respond to extracellular hyperosmolarity by accumulating small organic solutes, called "osmolytes." Na+/myo-inositol is one of the major organic osmolytes in the brain and Na+/myo-inositol cotransporter (SMIT) regulates extracellular Na+/myo-inositol content. Subarachnoid hemorrhage (SAH) is an osmotic stress-inducing event of the brain. The expression of SMIT messenger ribonucleic acid (mRNA) and protein was investigated with in situ hybridization and immunohistochemistry in rat brains with SAH induced by endovascular perforation. SMIT riboprobe was raised from a 490-bp rat SMIT complementary deoxyribonucleic acid. Anti-SMIT antibody was raised in rabbits. SMIT mRNA was expressed strongly in the cortex, hippocampus, and hypothalamus of the perforated side at 6 to 24 hours after SAH. Mild upregulation was noted in the contralateral cortex, hippocampus, and hypothalamus. The ventral aspect of the pons showed mild upregulation. Microautoradiography and immunostaining showed SMIT expression mainly in the neurons, but also in some non-neural cells in the hippocampus. The present results indicate that diffuse osmotic stress occurs in the host brain after SAH.

Animals↗
PubMed2003

Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitor.

OBJECT: The phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a tumor suppressor by negatively regulating the growth/survival signals of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. The PI3-K/Akt pathway in PTEN-deficient tumors may be one of the key targets for anticancer therapy. The authors examined the effects of the PI3-K inhibitor 2-(4-morpholinyl)-8-phenylchromone (LY294002) on human malignant glioma cells, and compared these effects on PTEN-deficient cells with those on PTEN-wild-type (PTEN-wt) cells. METHODS: Using human malignant glioma cell lines, including the PTEN-deficient cells A172 and U87MG and the PTEN-wt cells LN18 and LN229, the effects of LY294002 on cell growth, apoptosis, and chemotherapeutic agent-induced cytotoxicity were evaluated. The LY294002 inhibited the growth of U87MG cells associated with reduced phosphatidylinositol 3,4,5,-trisphosphate and phosphorylated Akt, and also induced growth inhibition in three other cell lines. Although LY294002 caused apoptosis in all four cell lines, apoptosis seemed to contribute to only a small portion of growth inhibition induced by LY294002. There was no link between the status of PTEN and the median inhibitory concentration values for LY294002 or between the gene status and the extent of LY294002-induced apoptosis. The LY294002 significantly augmented the cytotoxicity induced by etoposide in PTEN-deficient cells, but not in PTEN-wt cells. Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea- and cisplatin-induced cytotoxicity by LY294002 was not linked to the status of PTEN. No marked difference in the amounts of phosphorylated Akt was found between PTEN-deficient and PTEN-wt cells. CONCLUSIONS: The findings show that PI3-K is a possible target for therapy in patients with gliomas, and PI3-K inhibitors in combination with chemotherapeutic agents could be potent therapeutic modalities for patients with malignant gliomas.

Apoptosis↗
PubMed2003

C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia.

The pericentromeric region of chromosome 18, especially 18p11.2, is described as a schizophrenia susceptibility locus. We had previously cloned two novel brain-derived transcripts from this region: the gene for a second human myo-inositol monophosphatase (IMPA2) and a gene of unknown function, C18orf1. Recently, we reported a distortion of transmission of the tandem repeat marker D18S852, embedded in the 3'-untranslated region of C18orf1, in schizophrenia, using a family-based association test. A subsequent case-control study also revealed a significant association between the haplotype constructed from D18S852 and the 6409T>C polymorphism located in C18orf1 and schizophrenia. In the present study, we screened the C18orf1 gene for mutations and identified a novel single nucleotide polymorphism (SNP), -96T>C in exon 2. This SNP showed significant genotypic (P = 0.048) and allelic association (P = 0.005) with schizophrenia in a case-control study. The distributions of haplotypes defined by D18S852 and -96T>C were different between control and schizophrenia groups (P = 0.021). These findings suggest that C18orf1 or a gene nearby may contribute to the overall genetic risk for schizophrenia.

Adult↗
PubMed2002

Frequency analyses of CSF flow on cine MRI in normal pressure hydrocephalus.

Our objective was to clarify intracranial cerebrospinal fluid (CSF) flow dynamics in normal-pressure hydrocephalus (NPH). Frequency analyses of CSF flow measured with phase-contrast cine MRI were performed. The CSF flow spectra in the aqueduct were determined in patients ( n=51) with NPH, brain atrophy or asymptomatic ventricular dilation (VD), and in healthy volunteers (control group; n=25). The changes in CSF flow spectra were also analyzed after intravenous injection of acetazolamide. Moreover, a phase transfer function (PTF) calculated from the spectra of the driving vascular pulsation and CSF flow in the aqueduct were assessed. These values were compared with the pressure volume response (PVR). The amplitude in the NPH group was significantly larger than that in the VD or control group because of a decrease in compliance. The phase in the NPH group was significantly different from that in either the VD or the control group, but no difference was found between the VD and control groups. The amplitude increased in all groups after acetazolamide injection. The PTF in the NPH group was significantly larger than in the control group, and a positive correlation was noted between PTF and PVR. Frequency analyses of CSF flow measured by cine MRI make it possible to noninvasively obtain a more detailed picture of the pathophysiology of NPH.

Acetazolamide↗
PubMed2002

Residential maze as a task for testing rats' maze learning ability: effects of hippocampal lesions and cholinergic receptor antagonists.

We investigated whether rats can learn mazes by a procedure in which rats were left in the maze (residential maze) in groups for 1 h a day. Water and food locations, which served as the start and goal boxes respectively in the test trial, were at the opposite ends of the maze. On the test trial conducted everyday before the residence period, animals put in the start box showed a significant decrease of the error response into the blind alleys and running time to reach the goal box. Systemic administration of scopolamine (0.25, 0.5 mg/kg), a muscarinic receptor antagonist, dose-dependently increased the number of errors, but mecamylamine, a nicotinic receptor antagonist, had no effect. Bilateral hippocampal lesions retarded both the acquisition and retention of this maze learning. The results suggest that this residential maze procedure is useful for testing maze learning ability in rats.

Animals↗
PubMed2002

Measurements of MTF and SNR(f) using a subtraction method in MRI.

A method was developed for accurate measurement of the modulation transfer function (MTF) and signal-to-noise ratio in the spatial frequency domain (SNR(f)) of magnetic resonance images (MRI). The MTF was calculated from the complex images of a line object which were obtained by the subtraction of two separately acquired data sets of a specially designed phantom with a sliding sheet. Moreover, the SNR(f) was calculated from the MTF and Wiener spectrum, both of which were determined using the same phantom configuration. The MTFs and SNR(f)s in the conventional spin-echo (SE) and turbo SE, in which the effective echo time was set to the first echo, were evaluated by changing the T2 of the phantom and the echo train length. The MTFs in the positive and negative frequencies indicated the effect of the k-space trajectory for each pulse sequence. SNR(f)s gave spatial frequency information that was not obtained with conventional methods. In this method, the influence of image nonuniformity and unwanted artefacts (edge and ghost) could be eliminated. An analysis of the MTF and the SNR in the spatial frequency domain provides additional information for the assessment of image quality in MRI.

Artifacts↗
PubMed2002

Intracerebral hemorrhage upregulates Na(+)/myo-inositol cotransporter in the rat brain.

We examined the expression of Na(+)/myo-inositol cotransporter (SMIT) in the rat brain after intrastriatal hemorrhage. The expression of SMIT messenger RNA (mRNA) increased around hematoma 3 days after hemorrhage and it returned to control level as hematoma was absorbed. The expression of SMIT mRNA also increased at ipsilateral substantia nigra without blood-brain barrier disruption 7 days after hemorrhage and remained high until 42 days after hemorrhage. Immunohistochemistry revealed that macrophages around hematoma and microglias at ipsilateral substantia nigra were SMIT-positive. These results suggest that the expression of SMIT must be regulated not only by osmolality but also by unknown factors.

Animals↗
PubMed2002

Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population.

We have recently identified a novel polymorphic short tandem repeat (STR) in the 5' upstream region of the cholecystokinin (CCK) gene and reported its association with panic disorder. A linkage study of affective disorder showed a modest linkage signal on the short arm of chromosome 3, the location of the CCK gene. Furthermore, clinical comorbidity of depression and anxiety disorders have been documented. In the present study, we examined a possible association of the CCK STR with mood disorders. We genotyped 165 subjects with mood disorders consisting of unipolar and bipolar disorders and 253 control samples. However, no significant allelic associations were detected between the STR and either the combined mood disorders (P = 0.885), the unipolar group (P = 0.296), or the bipolar group (P = 0.605). These data suggest that the CCK promoter STR is unlikely to have a major genetic effect on the development of mood disorders in the Japanese population.

Adult↗
PubMed2002

Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders.

Chromosome 16p13 has been shown to display modest linkage signals for mood disorders in a number of studies. An interesting candidate gene in this region is the adenylate cyclase (AC) type 9 gene (ADCY9). ACs are critical in neuronal signaling, and perturbation of brain AC activity has been reported in mood disorder postmortem brains. ACs may also act as targets of antidepressants. Two distinct length transcripts for the ADCY9 gene have been reported, but molecular mechanisms are unknown. To investigate the potential role of ADCY9 in mood disorders, we clarified alternative poly(A) sites for the two mRNA species, delineated the exon-intron structure, and screened the gene for genetic variants. The two transcripts encoded by ADCY9 shared the first 10 exons, but exon 11 was shorter in one of the mRNA species. Seven single nucleotide polymorphisms, including a missense mutation and one polymorphic microsatellite repeat in the 3'-UTR, were identified. However, a case-control study using the missense polymorphism, 2316A>G (Ile772Met), and the tetranucleotide repeat (TTTA)n showed no significant association with mood disorders in Japanese samples. The DNA polymorphisms detected in this study can be tested in other ethnic samples and/or other psychiatric diseases.

Adenylyl Cyclases↗
PubMed2002

Molecular forms of human brain natriuretic peptide in plasma.

BACKGROUND: Brain natriuretic peptide (BNP) is a vasoreactive peptide hormone, which is synthesized and secreted mainly from the heart ventricles. METHODS: Molecular forms of immunoreactive human brain natriuretic peptide (BNP) were examined. Chemically synthesized human BNP was added to whole blood samples from a healthy volunteer. The immunoreactive peptide was recovered by immunoaffinity chromatography followed by reversed-phase HPLC (RP-HPLC). Molecular form of immunoreactive BNP in plasma from heart failure patients was also examined. RESULTS: Sequential analysis and amino acid analysis of the peptide revealed that two amino acid residues were deleted from the amino terminus of BNP. When roughly classified according to molecular weight (MW), two forms of BNP (high-MW BNP and low-MW BNP) were observed. The estimated MW of high-MW BNP (36 kDa) was three times that of pro-BNP (12 kDa). CONCLUSIONS: Analysis of low-MW BNP by RP-HPLC revealed that a small amount of BNP 1-32 or des-SerPro-BNP (BNP 3-32) was contained in plasma from heart failure patients.

Amino Acid Sequence↗
PubMed2002

Hemodynamic flow patterns evaluated by transcranial color-coded duplex sonography after STA-MCA bypass for internal carotid artery occlusion.

Extracranial-intracranial (EC-IC) bypass surgery had been widely performed for the treatment of internal carotid artery occlusion. However, it is presently difficult to predict how the bypass flow will contribute to intracranial circulation. We examined intracranial hemodynamics by transcranial color-coded duplex sonography (TCCD) after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and retrospectively studied the relationship between the postoperative contribution of the bypass flow and the preoperative collateral circulation and cerebrovascular perfusion status in 10 patients. Hemodynamics in the MCA detected by TCCD were classified into three patterns. In pattern A, perfusion of the whole MCA area is completely dependent on the bypass flow. In pattern B, perfusion of the M2 segment is dependent on the bypass flow, but perfusion of the M1 segment is independent of the bypass flow. In pattern C, perfusion of the whole MCA area is supplied by collateral flow and the bypass does not function efficiently. Preoperative absence of collateral flow via anterior communicating artery and cerebral perfusion status type 3 (reduced regional cerebral blood flow and regional cerebral vasoreactivity) seems to predict hemodynamic usefulness of the bypass flow after surgery. TCCD is an easy and noninvasive method for evaluating intracranial cerebral circulation after EC-IC bypass surgery.

Carotid Artery, Internal↗
PubMed2002

[Neural transplantation for cerebral ischemia/infarction--the present situation and prospects].

Cerebral infarction results in multiple symptoms including hemiplegia and cognitive disturbances. The central nervous system has a limited capacity for self-repair, thus there is a great interest in the possibility of repairing the central nervous system by neural transplantation. Two different types of cerebral infarction model are well investigated for neural transplantation. Several kinds of donor cells have been used to try to restore the brain damage after ischemic insult. Reconstruction of neural circuits by transplantation is an ideal goal for the treatment of cerebral infarction, but trophic action of transplantation is also expected. Amelioration of ischemia-induced brain damage and recovery of neural dysfunction are documented. However, there are several factors and problems to be solved for clinical application.

Animals↗
PubMedDate not supplied

Preventive effect of neutropenia on carbon tetrachloride-induced hepatotoxicity in rats.

The preventive effect of neutropenia on carbon tetrachloride (CCl4)-induced hepatotoxicity was examined in rats. In rats treated once with CCl4 (1 ml kg(-1), i.p.), the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indices of liver cell damage, and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, increased at 6 h after the intoxication and further increased at 24 h. The liver of CCl4 -treated rats showed an increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration at 6 h after the intoxication followed by a further increase in TBARS concentration and further decreases in SOD activity and GSH concentration at 24 h with increased xanthine oxidase (XO) activity at 24 h. Neutropenic treatment with anti-rat neutrophil antiserum (2 ml kg(-1), i.p.) at 0.5 h after CCl4 intoxication attenuated the increases in serum ALT and AST activities and hepatic MPO activity and TBARS concentration and the decreases in hepatic SOD activity and GSH concentration found at 6 and 24 h after CCl4 intoxication and the increase in hepatic XO activity found at 24 h after the intoxication. This neutropenia reduced the necrotic and degenerative changes with inflammatory cell infiltration in the liver cell of CCl4 -treated rats. These results indicate that neutropenia prevents CCl4 -induced hepatotoxicity in rats by attenuating the disruption of hepatic reactive oxygen species metabolism mediated by neutrophils accumulating in the liver tissue.

Animals↗
PubMedDate not supplied

Effectiveness of Gorei-san (TJ-17) for treatment of SSRI-induced nausea and dyspepsia: preliminary observations.

Selective serotonin reuptake inhibitors (SSRIs) are apt to cause gastrointestinal adverse events such as nausea and dyspepsia. Gorei-san (TJ-17), which is composed of five herbs (Alismatis rhizoma, Atractylodis lanceae rhizoma, Polyporus, Hoelen, and Cinnamomi cortex), is a Japanese herbal medicine that has been used to treat nausea, dry mouth, edema, headache, and dizziness. The authors investigated the efficacy of TJ-17 for patients who experienced nausea or dyspepsia induced by SSRIs. Twenty outpatients who experienced nausea or dyspepsia induced by SSRIs were recruited for the study. Seventeen patients were female, three were male, and patient age ranged from 21 to 74 years (49.8 +/- 17.0 years). TJ-17 was added to the previous regimen. Nausea and dyspepsia disappeared completely in nine patients, decreased in four patients, decreased slightly in two patients, and did not change in five patients. No adverse events were associated with the addition of TJ-17 in any patient.

Adult↗