Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 667 records · Page 37Linked to original sources

PubMed1998

Adenosine stimulates stellation of cultured rat cortical astrocytes.

We investigated the effect of adenosine on astrocyte morphology by using cell cultures prepared from the cerebral cortices of neonatal rats. Cultured rat cortical astrocytes exhibited flattened, polygonal morphology in the absence of stimulation, but differentiated into process-bearing stellate cells in response to adenosine (1-1000 microM). Adenosine-induced astrocyte stellation was abolished by treatment with microtubule inhibitors, colchicine and paclitaxel, indicating the involvement of cytoskeletal elements. The effect of adenosine was mimicked by other adenosine receptor agonists, and blocked by adenosine receptor antagonists and guanosine 5'-O-(2-thiodiphosphate), indicating that the effect of adenosine is mediated by G protein-coupled adenosine receptors. Although adenosine receptors are known to be linked to adenylate cyclase or phospholipase C, adenosine did not change intracellular cyclic AMP level nor intracellular Ca2+ concentration in astrocytes. Alternatively, adenosine-induced stellation was abolished by tyrosine phosphatase inhibitors, orthovanadate and phenylarsine oxide, suggesting that adenosine causes astrocyte stellation through tyrosine dephosphorylation. Adenosine may function as a factor regulating astrocyte differentiation.

Adenosine↗

PubMed1998

IL-4-producing NK1.1+ T cells are resistant to glucocorticoid-induced apoptosis: implications for the Th1/Th2 balance.

To elucidate the mechanisms by which glucocorticoids promote Th2-type responses, we investigated the influence of dexamethasone (DEX) on both cytokine production and viability of NK1.1+ T cells. The in vivo administration of DEX enhanced the IL-4 production of spleen cells and liver mononuclear cells in wild-type mice, but not in beta2m-deficient mice. DEX reduced the cellularity of conventional T cells, but not that of NK1.1+ T cells, in both spleen and liver, suggesting an increased proportion of NK1.1+ T cells. Moreover, the proportion of IL-4-producing NK.1 + T cells increased in the DEX-injected mice. These results suggest that DEX induced IL-4 production through the preferential survival of IL-4-producing NKI.1+ T cells. In investigating the reason for the preferential survival of NK1.1+ T cells, we found that NK1.1+ T cells were resistant to DEX-induced apoptosis and expressed a higher level of intracellular Bcl-2 compared with conventional NKI.1- T cells. In addition, splenic and hepatic NK1.1+ T cells were resistant to radiation-induced apoptosis. Collectively, our findings revealed an important role for NK1.1+ T cells in the regulation of Th1/Th2 balance by glucocorticoids and their possible functions under various apoptotic stimuli.

Animals↗

PubMed1998

Tardive dyskinesia and debrisoquine 4-hydroxylase (CYP2D6) genotype in Japanese schizophrenics.

Previous studies have shown that many neuroleptics are metabolized by debrisoquine 4-hydrolase (CYP2D6), which exhibits genetic polymorphisms. In Oriental populations, poor metabolizers (PMs) with a lack of CYP2D6 activity are rare, although the CYP2D6*10 allele, which is associated with decreased CYP2D6 activity, is commonly found. The authors examined the relationship between tardive dyskinesia (TD) and CYP2D6 polymorphisms, including the CYP2D6*10 allele. Subjects consisted of 100 Japanese schizophrenics. TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Genotyping for the presence of the CYP2D6*3, CYP2D6*4 and CYP2D6*10 alleles was performed using allele-specific PCR amplification and endonuclease digestions. The frequency of the CYP2D6*10 allele was 0.52, and only one allele showed the PM genotype. There was a significant difference in the allelic distribution of CYP2D6*10 between subjects with and without TD. We also found significant genotypic and allelic associations with dichotomized total AIMS scores of 6 or more (moderate or severe abnormal movements) and with scores of less than 6 (mild or no movements). After these associations were adjusted for confounding variables (gender, age, duration of illness and neuroleptic dose) by regression analysis, the CYP2D6*10 genotype showed significant association with the total AIMS score, and a modest association with TD occurrence. These results indicate that the CYP2D6*10 genotype may play a role in the development of moderate or severe abnormal movements.

Alleles↗

PubMed1998

Identification of two alpha-subunit species of GTP-binding proteins, Galpha15 and Galphaq, expressed in rat taste buds.

We cloned cDNAs for two G protein alpha-subunits belonging to the Galphaq family, each capable of activating PLCbeta, from rat tongue. One is a Galphaq in the narrow sense, and the other, termed rat Galpha15, is a rat counterpart of mouse Galpha15, sharing an amino acid sequence similarity of 94%. RT-PCR and Northern blot analysis demonstrated that rat Galpha15 and Galphaq were distinctly expressed in tongue epithelia containing taste buds. Immunostaining also showed that rat Galpha15, together with the Galphaq, was localized mainly in taste buds. These studies suggest the possibility that these two Galpha proteins function for taste signal transduction in sensory cells.

Amino Acid Sequence↗

PubMed1998

Inductions of hepatocyte growth factor and its activator in rat brain with permanent middle cerebral artery occlusion.

Hepatocyte growth factor (HGF) is a potent pleiotrophic peptide which has a trophic role for neuronal cells. As it exerts its effect only after a conversion to its heterodimeric active form, the activation step, which is catalyzed by an enzyme serine protease named HGF activator (HGFA), is of great importance. HGF activated by HGFA may act as a protecting agent in injured brain. In the present study, we investigated expression of immunoreactive HGF and HGFA in rat brain after permanent middle cerebral artery (MCA) occlusion. By immunohistochemical analysis, HGF and HGFA were normally expressed only in ependymal cells and choroid plexus. At 1 h after MCA occlusion, neurons in the ischemic penumbra region of the cerebral cortex slightly expressed immunoreactive HGFA. HGF was not induced at that time. At 3 h of ischemia, however, immunoreactive HGF as well as HGFA became detectable in neurons of the ischemic cerebral cortex and caudate. Immunoreactivity for HGF continued to increase until 24 h, while that for HGFA remained almost constant from 3 to 24 h. No glial or vascular endothelial cells expressed HGF nor HGFA. By Western blot analysis for HGF, a single band of molecular weight (MW) 34 kDa became apparent at 24 h, corresponding to the light chain of the active form HGF. The present study suggests that HGF and HGFA were induced in neurons under permanent ischemia with slightly different temporal profiles. Through activation by HGFA, the active form of HGF could serve as a neurotrophic factor in ischemic brain.

Animals↗

PubMed1998

Role of the endogenous production of interleukin 12 in immunotherapy.

Previous studies demonstrated that injecting mice with the cytokine interleukin 12 (IL-12) could significantly suppress the growth of a number of tumors, including murine B16 melanoma. In this report, the persistence of the antitumor effects of IL-12 is investigated. The i.p. injection of IL-12 (0.1 microg) on days 14, 16, 18, 20, and 22 was found to significantly suppress the growth of s.c. inoculated B16 melanoma for up to 2 weeks after the last injection of IL-12. Interestingly, the IL-12 serum level 4 days after the last injection of IL-12 was significantly elevated in tumor-bearing mice compared with that of IL-12-treated normal mice. The in vivo depletion of either CD4+ or CD8+ T cells abrogated the antitumor activity of IL-12 and diminished the apparent autocrine stimulation of IL-12 release seen after IL-12 treatment. Resection of the tumor-draining lymph nodes (LNs) but not of the spleen abrogated the antitumor effect of IL-12 treatment as well as the elevation of serum IL-12. Expression of mRNA encoding IL-12 as well as CD40 ligand (CD40L) was detected in the tumor-draining LNs but not in the spleen of tumor-bearing mice after IL-12 treatment. Furthermore, the antitumor activity observed after IL-12 treatment was diminished by the in vivo administration of either anti-IL-12 or anti-CD40L monoclonal antibodies. Collectively, these results suggest that the endogenous production of IL-12 resulting from the CD40-CD40L interaction between antigen-presenting cells and CD4+ T cells in the tumor-draining LNs may play a role in the persistence of the antitumor effects seen after IL-12 treatment.

Animals↗

PubMed1998

Early impairment and late recovery of synaptic transmission in the rat dentate gyrus following transient forebrain ischemia in vivo.

Ischemic stroke causes various functional deficits in the brain such as memory impairment, and clinical reports have shown that the impaired brain functions may partially recover. However, there has been no experimental model suitable for studying cellular mechanisms of functional recovery following brain ischemia. Therefore, we investigated the long-term influence of transient forebrain ischemia on excitatory synaptic transmission in the rat dentate gyrus, a brain region relatively resistant to ischemia. Fifteen minutes of transient forebrain ischemia produced no apparent histological damage in dentate granule cells, but caused a significant reduction of basal synaptic potentials evoked by perforant path stimulation. Field excitatory postsynaptic potential remained reduced for at least 1 month after ischemia, while population spike recovered to control level in 1 month. The induction of long-term potentiation was also impaired after ischemia, but it showed faster recovery than basal synaptic potentials. In conclusion, we found that synaptic transmission in the dentate gyrus of the rat is impaired following transient forebrain ischemia, but has a potential to recover. These results may provide a good model for studying the mechanisms of impairment and recovery of brain function after transient ischemia.

Animals↗

PubMed1998

Isolation and characterization of cDNA encoding rat heart type acetyl-CoA carboxylase.

We isolated and characterized cDNA clones encoding the entire open reading frame (ORF) of a protein consisting of 2456 amino acids with a molecular mass of 276069 Da from rat heart. As the deduced amino acid sequence showed 85% homology with that of human type 2 acetyl-CoA carboxylase (ACC2), we concluded that the cDNA clones encode rat heart type ACC2. Using the identified cDNA fragments and the reported cDNA fragment of rat type 1 ACC (ACC1), we determined the steady state transcript levels of ACC1 and ACC2 in various rat tissues quantitatively by Northern blot analysis. The transcript level of ACC2 was high in heart, skeletal muscle and brown adipose tissue, which require high energy and mainly metabolize fatty acids, whereas that of ACC1 was high in white adipose tissue, which stores fatty acids.

Acetyl-CoA Carboxylase↗

PubMed1998

Delayed selective motor neuron death and fas antigen induction after spinal cord ischemia in rabbits.

The mechanism of spinal cord injury has been thought to be related with tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model for spinal cord ischemia. Using this model, cell damage was histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7 days of the reperfusion. Time course expression of Fas antigen, identified as a apoptosis-regulating molecules, was also assessed in rabbit spinal cord following transient ischemia. Spinal cord sections from animals sacrificed at 8 h, 1 day, 2 days, and 7 days following 15-min ischemia were immunohistochemically evaluated using monoclonal antibodies for Fas antigen. Following 15-min ischemia, the majority of motor neuron showed selective cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunoreactivity of Fas antigen were induced at 8 h to 1 day of reperfusion selectively in motor neuron cells. The expression of Fas antigen may be related to the activation of apoptosis signal in motor neuron cells after spinal cord ischemia in rabbits.

Animals↗

PubMed1998

Medial amygdala stimulation produces a long-lasting excitatory postsynaptic potential/spike dissociation in the dentate gyrus in vivo.

We have previously found that high-frequency stimulation of the medial amygdala (MeA) induces long-term potentiation (LTP) of the population spike in the perforant path-dentate granule cell synapses of anesthetized rats. In the present study, we investigated the influence of MeA stimulation on the relationship between the population excitatory postsynaptic potential (pEPSP) and population spike in the dentate gyrus. High-frequency stimulation of the MeA produced a leftward shift of the E-S curve, in which population spike amplitude was plotted against pEPSP slope at various stimulus intensities. MeA-induced population spike LTP was also observed under blockade of GABAergic inhibition with picrotoxin. These results suggests that MeA stimulation leads to a long-lasting change in the internal firing characteristics of the dentate granule cells.

Action Potentials↗

PubMed1998

5-HT1A receptor-mediated inhibition of long-term potentiation in rat visual cortex.

We investigated the effect of 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on the induction of long-term potentiation in rat visual cortex slices. Perfusion of 8-OH-DPAT (0.1-10 microM) did not affect layer II/III field potentials evoked by test stimulation of layer IV, but significantly reduced long-term potentiation induced by tetanic stimulation. The inhibitory effect of 8-OH-DPAT was blocked by the 5-HT1A receptor antagonist, pindolol (10 microM), but not by the 5-HT2,7 receptor antagonist, ritanserin (100 microM), nor by the 5-HT3,4 receptor antagonist, MDL72222 (100 microM). These results suggest that the rat visual cortex long-term potentiation is inhibited by 5-HT1A receptor stimulation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

Expression of adenovirus-mediated E. coli lacZ gene in skeletal muscles and spinal motor neurons of transgenic mice with a mutant superoxide dismutase gene.

A replication-defective recombinant adenoviral vector containing E. coli lacZ gene was injected into the right biceps brachii muscles of transgenic mice carrying mutant human Cu/Zn superoxide dismutase (SOD1) gene and non-transgenic wild-type mice at 27 weeks of age. Although the transgenic mice showed remarkable neurogenic muscular changes and a marked motor neuron loss in the anterior horn of spinal cord, the lacZ gene was widely expressed in all the injected muscles of transgenic mice as well as of wild-type mice at 7 days after the injection. In one transgenic and two wild-type mice, the lacZ gene expression was first detected in a few motor neurons of right lower cervical cord (C5-C6). These results demonstrate that an adenovirus-mediated foreign gene is transferred and expressed in skeletal muscles both of normal and transgenic mice model for familial amyotrophic lateral sclerosis (FALS), and also, in the spinal motor neurons, may be transferred by retrograde transport from innervated muscles.

Adenoviridae↗

PubMed1998

Effects of S-8510, a novel benzodiazepine receptor partial inverse agonist, on basal forebrain lesioning-induced dysfunction in rats.

We investigated the effects of a novel benzodiazepine partial inverse agonist, S-8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo [4,5-d] pyrano [4,3-b] pyridine monophosphate monohydrate), on the impairment of spatial memory, decreased high-affinity choline uptake and acetylcholine release in basal forebrain-lesioned rats. S-8510 (3 and 5 mg/kg, p.o. 30 min before each training session) significantly ameliorated the basal forebrain-lesion-induced impairment of spatial memory in water maze task. In vivo brain microdialysis studies showed that systemic administration of S-8510 at 3 and 10 mg/kg significantly increased the release of acetylcholine in the front-parietal cortex in basal forebrain-lesioned rats. Further, repeated administration of S-8510 (3 and 10 mg kg(-1) day(-1) for 5 days) reversed the decrease in cortical high-affinity choline uptake induced by basal forebrain lesion. Thus, S-8510 improved the spatial memory impairment induced by lesion of the basal forebrain in rats. In addition, it increased acetylcholine release and high-affinity choline uptake from the cortex, a region closely associated with memory, in basal forebrain-lesioned rats. These results indicate that S-8510 has cognition enhancing and cholinergic-activating effects in the basal forebrain-lesioned rats, suggesting that this agent may be useful for the treatment of mild to moderate senile dementia including Alzheimer's disease.

Acetylcholine↗

PubMed1998

Medical amygdala-induced spike potentiation in the rat dentate gyrus is dependent on N-methyl-D-aspartate receptors and subcortical afferents.

We have previously found that high-frequency stimulation of the medial amygdala (MeA) produces a long-lasting potentiation of the population spike at medial perforant path-granule cell synapses in the dentate gyrus of anesthetized rats. The present study was performed to determine whether this novel form of potentiation requires activation of N-methyl-D-aspartate (NMDA) receptors and subcortical afferents. The MeA-induced spike potentiation was completely blocked by the NMDA receptor antagonist 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (3.5 mg/kg, i.p). When the fimbria-fornix, a major pathway of subcortical afferents, was lesioned, the early phase of MeA-induced spike potentiation remained intact, but the late phase of potentiation was abolished. These results suggest that the NMDA receptor is essentially required for the induction of MeA-induced spike potentiation, while subcortical afferents contribute to the establishment of potentiation.

Afferent Pathways↗

PubMed1998

Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG trinucleotide expansion and clinical characteristics.

We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2,000,000), and documented the clinical and molecular properties correlated with the CAG repeat expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8+/-4.8 (mean+/-S.D., n=13) and 22+/-0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.

Adolescent↗

PubMed1998

Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease.

We investigated the changes in water diffusion in the hippocampus and the temporal white matter (the temporal stem) in eight patients with possible Alzheimer's disease (AD), 10 patients with probable AD, and 10 age-matched controls, using coronal diffusion-weighted magnetic resonance (MR) imaging. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes and an index of diffusion anisotropy (IDA = ADC(max-min)/ADC(mean)) was then calculated. Although no significant differences were found in ADC and IDA values in the hippocampal body between controls and patients, vertical (superior-inferior) ADC values and ADC(mean) values in the temporal stem of patients with AD were significantly higher than those in controls, and IDA values were therefore significantly lower in patients with possible or probable AD than those in controls. Moreover, IDA values in the temporal stem were significantly correlated with the clinical severity. These results suggest that decreased fiber density, such as the disruption and loss of axonal membranes or myelin, occur early in the temporal stem, probably due to secondary degeneration related to grey matter pathology including the medial temporal lobe.

Aged↗

PubMed1998

Identification of alternative splicing forms of GLT-1 mRNA in the spinal cord of amyotrophic lateral sclerosis patients.

The glutamate transporter plays an essential role in regulating glutamate levels in the synaptic cleft. It has been postulated that the dysfunction of GLT-1, one subtype of glutamate transporter, may be etiologically related to amyotrophic lateral sclerosis (ALS). Two alternative splicing forms of GLT-1 messenger RNA (mRNA) were found in the cervical spinal cord of five ALS patients and three controls. Analysis with reverse transcription-polymerase chain reaction (RT-PCR) showed that the shorter mRNA was a result of exon 8 skipping. A truncated transcript containing an intronic sequence at the 3' end of exon 7 was also demonstrated. However, the incidence of both alternative mRNAs was not different between the five ALS patients and three controls. Interestingly, the mRNA were also found in the cerebral cortex of a control subject. These results suggest that alternative splicing forms of GLT-1 mRNAs do not play a pathogenetic role in ALS but rather a physiological one in the normal spinal cord and brain.

ATP-Binding Cassette Transporters↗

PubMed1998

Structure and transcriptional function of the 5'-flanking region of rat thromboxane receptor gene.

We cloned a cDNA for rat TX receptor, and observed its expression in the kidney, including vascular smooth muscle. The aim of the present study was to clone the 5'-flanking region (5'-FL) of rat TX receptor gene, and to examine its transcriptional gene expression regulation. The 5'-FL was cloned by a PCR method, and the nucleic acid structure of 5'-FL (approximately 1 Kb) was disclosed. The transcription initiation site was shown to be 63 bases upstream of the 5' end of the cDNA by the primer extension. In the 5'-FL, putative AP-1 binding sites, glucocorticoid-responsive elements, NF-kappa B binding sites, GATA box, and shear stress-responsive elements were identified. The 5'-FL was then fused upstream of firefly luciferase cDNA in an expression vector, and we examined its transcriptional activity in transiently transfected cultured vascular smooth muscle cells (VSMC). Luciferase expression was dependent on the length of 5'-FL, and it was significantly stimulated by phorbol 12-myristate 13-acetate (PMA), dexamethasone (Dex), tumor necrosis factor-alpha, and interleukin (IL). By a semi-quantitative RT-PCR method, TX receptor mRNA was shown to be induced by Dex, IL-6, and PMA in cultured VSMC. In conclusion, we have revealed the structure of transcription regulatory region of TX receptor. Expression of TX receptor gene is possibly up-regulated by activation of protein kinase C, glucocorticoid excess, and IL-6, in vascular smooth muscle.

Animals↗