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Biomedical subjects

Shin-ichi Niwa

Publications and source records attributed to Shin-ichi Niwa.

9 recordsLinked to original sources
PubMed2006

Establishment and characterization of the transformants stably-expressing MDR1 derived from various animal species in LLC-PK1.

PURPOSE: Stable transformants expressing human multidrug resistance 1 (MDR1), monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b in LLC-PK1 were established to investigate species differences in P-glycoprotein (P-gp, ABCB1) mediated efflux activity. METHODS: The seven cDNAs of MDR1 from five animals were cloned, and their transformants stably expressing the series of MDR1 in LLC-PK1 were established. Transport studies of clarithromycin, daunorubicin, digoxin, erythromycin, etoposide, paclitaxel, propranolol, quinidine, ritonavir, saquinavir, verapamil, and vinblastine were performed by using these cells, and efflux activity was compared among the species. RESULTS: Except for propranolol, all compounds showed efflux activity in all transformants, and were judged to be substrates of P-gp. There were slight interspecies and interisoforms differences in the substrate recognition. However, the efflux ratio among the series of the MDR1 stably expressing cells showed good correlation as represented between human and monkey MDR1, and poor correlation as represented between human MDR1 and mouse mdr1a, and human and canine MDR1. CONCLUSIONS: Results in the present study indicate that all MDR1 stably expressing cells have efflux activity for various P-gp substrates, and that interspecies differences and similarities of the P-gp substrate efflux activity may exist.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation.

The limited number of genome-wide transcriptome analyses using the postmortem brains of bipolar disorder sufferers has not produced a clear consensus on the molecular pathways affected by the disorder. To expand the knowledge in this area, we examined the expression levels of more than 12 000 genes in Brodmann's Area (BA), 46 (dorsolateral prefrontal cortex) from bipolar I disorder and control samples using Affymetrix GeneChips. This analysis detected 108 differentially expressed genes in bipolar brains. Validation studies using quantitative RT-PCR on the two original diagnostic cohorts plus tissue from schizophrenic subjects, confirmed the differential expressions of eight genes (RAP1GA1, SST, HLA-DRA, KATNB1, PURA, NDUFV2, STAR and PAFAH1B3) in a bipolar-specific manner and one gene (CCL3) which was downregulated in both bipolar and schizophrenic brains. Of these, protein levels of RAP1GA1 (RAP1 GTPase activating protein 1) showed a trend of increase in BA46 from bipolar brains, in keeping with mRNA transcript levels. Transmission disequilibrium analysis of the nine genes using 43 single nucleotide polymorphisms (SNPs) in 229 National Institute of Mental Health bipolar trios exposed nominal SNP association and modest empirical haplotypic association (P=0.033) between SST (somatostatin) and disease. Finally, gene network analysis using the currently obtained expression data highlighted cellular growth and nervous system development pathways as potential targets in the molecular pathophysiology of bipolar disorder.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Expression of human neuronal protein 22, a novel cytoskeleton-associated protein, was decreased in the anterior cingulate cortex of schizophrenia.

Human neuronal protein 22 (hNP22) is a novel neuron-specific protein featuring numerous motifs previously described in cytoskeleton-associating and signaling proteins. Because previous studies have supported abnormalities in neuronal cytoarchitecture and/or development in the schizophrenia brain, we examined the expression of hNP22 in the anterior cingulate cortex, the hippocampus and the prefrontal cortex of schizophrenic and normal control postmortem brains using high-sensitive immunohistochemistry. Seven schizophrenic and seven age- and sex-matched control brains were examined. The ratio of hNP22-immunopositive cells/total cells was significantly reduced in layer V (p=.020) and layer VI (p=.022) of the anterior cingulate cortex of schizophrenic brain compared with controls. In contrast, there were no significant changes observed in the hippocampus and the prefrontal cortex. These results suggest that altered expression of hNP22 may be associated with modifications in neuronal cytoarchitecture leading to dysregulation of neural signal transduction in the anterior cingulate cortex of the schizophrenia brain.

Actins↗
PubMed2005

Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases.

We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines.

Benzodiazepines↗
PubMed2003

Different effects of phencyclidine and methamphetamine on firing activity of medial prefrontal cortex neurons in freely moving rats.

The purpose of this study was to compare the effects of systemically administered MAP with those of phencyclidine (PCP), both of which induced comparable locomotor activity, on firing activity of medial prefrontal cortex (mPFC) neurons in freely moving rats. The results show that, unlike PCP, acutely administered MAP produced little changes in firing activity of mPFC neurons.

Animals↗
PubMed2003

Expression of hNP22 is altered in the frontal cortex and hippocampus of the alcoholic human brain.

BACKGROUND: Human neuronal protein (hNP22) is a gene with elevated messenger RNA expression in the prefrontal cortex of the human alcoholic brain. hNP22 has high homology with a rat protein (rNP22). These proteins also share homology with a number of cytoskeleton-interacting proteins. METHODS: A rabbit polyclonal antibody to an 18-amino acid epitope was produced for use in Western and immunohistochemical analysis. Samples from the human frontal and motor cortices were used for Western blots (n = 10), whereas a different group of frontal cortex and hippocampal samples were obtained for immunohistochemistry (n = 12). RESULTS: The hNP22 antibody detected a single protein in both rat and human brain. Western blots revealed a significant increase in hNP22 protein levels in the frontal cortex but not the motor cortex of alcoholic cases. Immunohistochemical studies confirmed the increased hNP22 protein expression in all cortical layers. This is consistent with results previously obtained using Northern analysis. Immunohistochemical analysis also revealed a significant increase of hNP22 immunoreactivity in the CA3 and CA4 but not other regions of the hippocampus. CONCLUSIONS: It is possible that this protein may play a role in the morphological or plastic changes observed after chronic alcohol exposure and withdrawal, either as a cytoskeleton-interacting protein or as a signaling molecule.

Adult↗
PubMed2002

The effect of the destruction of the caudate-putamen on the development of amygdaloid kindling and kindled seizures.

To elucidate the possible roles of the caudate-putamen (CP) on the development of amygdala (AM) kindling and AM-kindled seizures, the bilateral CP were destroyed by intra-CP injection of ibotenic acid (0.5 or 1.0 microg per side) before the AM kindling or after completion of the AM kindling. Prior destruction of the CP, especially by 0.5 microg ibotenic acid injection, caused a significant delay in seizure development. However, after completion of the AM kindling, bilateral destruction of the CP significantly suppressed AM-kindled seizures in proportion to lesion size, however, all animals reached a stage 5 seizure by additional stimulations and established AM kindling. These findings suggest that the intact CP modulates the development of the AM kindling and the generalization and/or expression of the kindled AM seizures, and that the CP plays an important role in the generalization and/or expression of the kindled AM seizures.

Amygdala↗