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K Kato

Publications and source records attributed to K Kato.

At least 289 records · Page 16Linked to original sources

Neurotoxic effect of high dose methamphetamine administration on the hippocampal formation of adult mice: morphometric study using image analyzer.

The volume of the hippocampal formation was measured after repeated methamphetamine (MAP) administration. MAP (30 mg/kg, i.p.) or an equivalent volume of saline (SAL) was administered once daily for 5 days to adult male BALB/c mice. The animals were perfused 7 days after the last injection, and brain sections were stained with cresyl violet and studied with a computer-assisted image analyzer. The volume of the molecular layer at the ventral position of the dentate gyrus of MAP-treated animals was significantly decreased (77% of control, p < 0.001). In contrast, the volumes of the molecular layers at the dorsal and midseptal positions of the dentate gyrus did not change after MAP administration. Similarly, repeated MAP treatment did not affect the volumes of the granular layer and hilus at the dorsal, midseptal or ventral positions of the dentate gyrus. The present results are the first to document a persistent neurotoxic effect of high dose MAP administration on the hippocampal volume of adult mice.

Animals↗

Impaired learning with enhanced hippocampal long-term potentiation in PTPdelta-deficient mice.

Protein tyrosine phosphatase delta (PTPdelta) is a receptor-type PTP expressed in the specialized regions of the brain including the hippocampal CA2 and CA3, B lymphocytes and thymic medulla. To elucidate the physiological roles of PTPdelta, PTPdelta-deficient mice were produced by gene targeting. It was found that PTPdelta-deficient mice were semi-lethal due to insufficient food intake. They also exhibited learning impairment in the Morris water maze, reinforced T-maze and radial arm maze tasks. Interestingly, although the histology of the hippocampus appeared normal, the magnitudes of long-term potentiation (LTP) induced at hippocampal CA1 and CA3 synapses were significantly enhanced in PTPdelta-deficient mice, with augmented paired-pulse facilitation in the CA1 region. Thus, it was shown that PTPdelta plays important roles in regulating hippocampal LTP and learning processes, and that hippocampal LTP does not necessarily positively correlate with spatial learning ability. To our knowledge, this is the first report of a specific PTP involved in the regulation of synaptic plasticity or in the processes regulating learning and memory.

Animals↗

Establishment and usefulness of an anti-human CD57 IgG1 monoclonal antibody.

In the present study we established a new monoclonal antibody, JNK-1, which recognizes all cells recognized by CD57/HNK-1 mAb. JNK-1 and CD57 mAbs inhibited the binding of each other, suggesting that the molecules they recognize are either identical or sufficiently close to cause steric hindrance in the binding assay. JNK-1 mAb detected the 110-kDa protein, which is identical to the protein recognized by CD57/HNK-1 mAb in Western immunoblot analysis combined with immunoprecipitation. Therefore, JNK-1 mAb appears to recognize homogeneous molecules identified by the currently available CD57 mAb. Notably, JNK-1 mAb is composed of mouse IgG1 heavy chains, and thus can be used easily in immunoprecipitation, which cannot easily be performed with the available CD57 mAb because it is an IgM isotype. Thus, JNK-1, which is an IgG isotype, may present a useful tool to elucidate the CD57 protein.

Animals↗

Pairing of oligosaccharides in the Fc region of immunoglobulin G.

The Fc portion of immunoglobulin G (IgG) expresses paired oligosaccharides with microheterogeneities, which are associated with efficiencies of effector functions and with pathological states. A comparison of electrospray ionization mass spectrometry data obtained using a variety of Fc fragments derived from human and mouse IgG that do and do not retain the inter-chain disulfide bridge(s) revealed that (1) the Fc portion can be asymmetric as well as symmetric with respect to glycosylation and (2) the ratios of the individual glycoforms are different from what is expected from the random pairing.

Animals↗

Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor.

Membrane potential recordings, made from the circular smooth muscle layer of the gastric antrum taken from mutant mice which lacked the inositol trisphosphate (InsP3) type 1 receptor, were compared with those obtained from the stomach of control (wild-type) mice. Immunostaining of gastric muscles indicated that the distribution and form of c-kit positive cells were similar in wild-type and mutant mice. Smooth muscles from wild-type mice generated slow waves that in turn initiated spike potentials, while those from mutant mice were either quiescent or generated irregular bursts of spike potentials. In the presence of nifedipine, slow waves with reduced amplitude were generated in wild-type mice, while all electrical activity was abolished in mutant mice. Acetylcholine depolarized and sodium nitroprusside hyperpolarized the membrane in muscles from both types of mice, being more effective in wild-type mice. Noradrenaline produced similar hyperpolarizations in both types of mice. Transmural nerve stimulation evoked inhibitory junction potentials (IJPs) in both wild-type and mutant mice. In wild-type mice, the IJPs were reduced in amplitude by nitroarginine and converted to a cholinergic excitatory junction potential (EJP) by apamin. In mutant mice, the IJPs were unaffected by nitroarginine or atropine but were abolished by apamin. It is concluded that in antral smooth muscle, the expression of InsP3 type 1 receptors may be causally related to the generation of slow waves but not to the generation of action potentials. A lack of InsP3 receptors attenuates cholinergic excitatory and nitrergic inhibitory responses but does not alter the response to noradrenaline.

Acetylcholine↗

Quantum phase transition of the randomly diluted heisenberg antiferromagnet on a square lattice

Ground-state magnetic properties of the diluted Heisenberg antiferromagnet on a square lattice are investigated by means of the quantum Monte Carlo method with the continuous-time loop algorithm. It is found that the critical concentration of magnetic sites is independent of the spin size S, and equal to the two-dimensional percolation threshold. However, the existence of quantum fluctuations makes the critical exponents deviate from those of the classical percolation transition. Furthermore, we found that the transition is not universal, i.e., the critical exponents significantly depend on S.

Journal Article↗

Differential profiles of nitric oxide and norepinephrine releases in the paraventricular nucleus region in response to mild footshock in rats.

The purpose of this study was to determine whether the application of mild intermittent footshock stress can cause changes in the nitric oxide (NO) and norepinephrine (NE) releases in the hypothalamic paraventricular nucleus (PVN) region and medial prefrontal cortex (mPFC). Extracellular levels of NO metabolites and NE in the PVN region and mPFC were determined using an in vivo brain microdialysis technique in conscious rats. In the PVN region, we demonstrated that perfusion of N-methyl-D-aspartate through a microdialysis probe resulted in a dose-dependent increase in NO metabolite levels, whereas intraperitoneal administration of N(G)-nitro-L-arginine methyl ester produced a dose-dependent reduction in the levels of NO metabolites. The levels of NO metabolites in the PVN region increased after intraperitoneal administration of interleukin-1beta in a dose-dependent manner, as we previously reported. This increase in NO metabolite levels was abolished 60 min after systemic administration of N(G)-nitro-L-arginine methyl ester compared to the vehicle-treated control group. Twenty minutes of intermittent footshock induced NE release but did not induce NO release in the PVN region. On the contrary, in the mPFC, 20 min of intermittent footshock induced both NO and NE releases. The present results reveal different patterns and time courses in NO and NE releases between the PVN region and the mPFC in response to mild intermittent footshock stress. These findings are likely to have helpful suggestions for our understanding of the hypothalamic-pituitary-adrenal axis and the limbic forebrain system response to different kinds of stress.

Animals↗

Order and maximum incorporation of N-acetyl-D-galactosamine into threonine residues of MUC2 core peptide with microsome fraction of human-colon-carcinoma LS174T cells.

Mucin 2 (MUC2) is the major intestinal mucin. O-glycans are attached to MUC2 in a potentially diverse arrangement, which is crucial for their interaction with endogeneous and exogeneous lectins. In the present report, five oligopeptides [PTTTPITTTT(K), ITTTTTVTPT(K), TVTPTPTPTG(K), PTPTGTQTPT(K) and TQTPTTTPIT(K)] corresponding to portions of the MUC2 tandem repeat domain were synthesized, and incubated with UDP-N-acetyl-D-galactosamine (UDP-GalNAc) and detergent-soluble microsomes, prepared from the human colon carcinoma cell line LS174T. The products were fractionated by reverse-phase HPLC and characterized by matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. Oligopeptides with GalNAc residues derived from PTTTPITTTT(K), containing consecutive threonine residues, were found to be glycosylated with 1-7 GalNAc residues per single peptide. The sequences of all glycopeptides were determined. The results indicated that the predominant sites of the first through to the sixth GalNAc incorporation were Thr(3), Thr(6), Thr(5), Thr(2), Thr(4) and Thr(1), respectively. An exception was the presence of a glycopeptide with three GalNAc residues at Thr(1), Thr(4) and Thr(5). Oligopeptides containing alternating threonine residues [TVTPTPTPTG(K) and PTPTGTQTPT(K)] were not fully glycosylated under the same conditions or even after prolonged incubations. Thus, the preferential order and maximum number of GalNAc incorporation into threonine residues of MUC2 core peptides depends on the peptide sequence, when the microsome fraction of LS174T cells is used as a source of N-acetyl-D-galactosaminyltransferases.

Acetylgalactosamine↗

Development and validation of a liquid chromatographic-tandem mass spectrometric method for the determination of pibutidine in human urine.

A liquid chromatographic-tandem mass spectrometric method for the rapid quantitative determination of pibutidine, an H2-receptor antagonist, in human urine has been developed and validated over the concentration range 0.1-25.6 microg ml(-1). Urine samples were prepared based on a simple dilution with 0.05% acetic acid, followed by reversed-phase liquid chromatographic separation. Pibutidine and its internal standard (2H10-pibutidine) were ionized using an electrospray ionization interface and detected by tandem mass spectrometry in the selected reaction-monitoring mode. Completed validation demonstrated the method to be robust, accurate, precise and specific for the direct quantification of pibutidine in human urine. This method has enabled investigation of the urinary excretion of pibutidine following oral administration of pibutidine hydrochloride to healthy subjects.

Adult↗

High Ca(2+)/low Mg(2+) solution induces long-term depression in rat CA1 pyramidal neurons.

Inducing long-term depression (LTD), one type of synaptic plasticity, typically requires electrical stimulation. Using rat hippocampal slices, we show that increasing the Ca(2+) of the extracellular solution to 4 mM and decreasing the Mg(2+) to 0.1 mM induced LTD in the CA1 region in the absence of electrical stimulation. The ionically-induced-LTD occluded electrical stimulation-induced LTD and was not blocked by application of 50 microM D-2-amino-5-phosphonopentanoic acid (an N-methyl-D-aspartate receptor antagonist) or by 1 mM (RS)-alpha-methyl-4-carboxyphenylglycine (a metabotropic glutamate receptor antagonist) alone. However, LTD was not ionically induced in the presence of both inhibitors. Our findings suggest that altering tissue excitability by changing the ionic environment mimics electrical stimulation in the induction of LTD.

2-Amino-5-phosphonovalerate↗

During pain-avoidance neurons activated in the macaque anterior cingulate and caudate.

Lesions in either the anterior cingulate cortex (ACC) or the caudate nucleus (CN) impair avoidance behavior from noxious somatic stimuli, so these two areas may play a similar role in pain-avoidance behavior. To test this hypothesis, we recorded single neuronal activities in the ACC and in the CN of a monkey while it was performing a pain-avoidance task. Ten of 136 ACC and eleven of 160 CN neurons responded selectively during pain-avoidance behavior. We found little difference in the population distribution or in the response latency and duration. Our present findings are in accordance with previous lesion and anatomical studies which suggest that these two regions could function as one module in pain-avoidance behavior.

Animals↗

Lobe specific effects of testosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis.

We have previously shown that chronic administration of a pharmacological dose of testosterone propionate (TP) after treatment with the carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB), results in development of invasive and metastatic adenocarcinomas arising from the dorso-lateral and anterior prostate, as well as the seminal vesicles. Co-administration of ethinyl estradiol (EE) with TP increased the yield of carcinomas in the lateral and anterior lobes. In the present experiment, male F344 rats were treated with DMAB for 20 weeks and then co-administered a pharmacological dose of TP together with various doses of EE for 40 weeks. Without hormone(s) administration, carcinomas were confined to the ventral prostate and all were of intra-acinar type. TP administration suppressed development of the ventral prostate carcinomas but caused invasive carcinomas of the lateral and anterior lobes and of seminal vesicles and intra-acinar carcinomas in the dorsal prostate. The appearance of carcinomas in the lateral and anterior prostate was increased by co-administration of EE in a dose-related fashion but carcinomas of the seminal vesicles were inversely reduced. The suppressive influence of TP on ventral carcinoma development was overcome by only the highest dose of EE. It is concluded that estrogen can modify the enhancing effects of TP on induction of rat prostate and seminal vesicle carcinomas in a dose-related fashion with lobe specificity.

Aminobiphenyl Compounds↗

An immunocytochemical study of mitochondrial manganese-superoxide dismutase in the rat hippocampus after kainate administration.

We examined the immunocytochemical distribution of mitochondrial Mn-superoxide dismutase (SOD-2) in the rat hippocampus after systemic injection of kainic acid (KA), in order to understand SOD-2-responsible antioxidant defense mechanism during the neurodegenerative process. SOD-2 immunostaining was more intense in CA3 pyramidal neurons than in CA1 neurons in the normal hippocampus. The immunoreactivity in region CA1 was reduced without significant neuronal losses within 12 h of KA injection. The CA1 and CA3 neurons lost their immunoreactivity, whereas SOD-2-positive glia-like cells proliferated, mainly throughout the CA1 sector, and had intense immunoreactivity 3 and 7 days after KA injection. This immunocytochemical distribution of SOD-2-positive non-neuronal elements was similar to that of glial fibrillary acidic protein (GFAP) and S-100 protein-positive cells. Activated microglial cells selectively marked with lectin occurred in the areas affected by the KA-induced lesion. Double-labeling immunocytochemistry showed the co-localization of SOD-2-positive non-neuronal cells and GFAP or S-100 protein-like immunoreactivity in the same cells. This suggests that astroglial cells mobilized to synthesize of SOD-2 protein in a response to KA toxicity designed to reduce the oxidative damage.

Animals↗

Cardiac type cGMP-inhibited phosphodiesterase (PDE3A) gene structure: similarity and difference to adipocyte type PDE3B gene.

Phosphodiesterase type 3 isoforms, PDE3A and 3B, are expressed primarily in cardiovascular and adipose tissues, respectively. We previously reported a shorter transcript of 4.4-kb PDE3A which is predominantly transcribed in human placenta, whereas a full-length 7. 6-kb transcript corresponding to the cardiac PDE3A cDNA has not been characterized. Due to unfortunate circumstances created by changes in PDE3 nomenclature, PDE3B gene structure previously reported used PDE3A in its title. Here, we describe PDE3A gene structure, which comprises 16 exons spanning over 130 kb on chromosome 12p12. Two PDE3 isoforms share similar gene organization, but localize to different chromosomes. The most distal transcription initiation site of the PDE3A gene is approximately 1071 bases upstream of the ATG site, suggesting that exon 1 consists of 1071 and 960 bp of untranslated and translated sequences, respectively. The proximal 5'-flanking region, which does not contain TATA-like sequences, exhibited weak but significant promoter activity. Results suggest potential involvement of distal promoter/enhancer and translational regulation for expression of the 7.6-kb transcript.

3',5'-Cyclic-AMP Phosphodiesterases↗

Expression of coxsackievirus and adenovirus receptor in hearts of rats with experimental autoimmune myocarditis.

The expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcription-polymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.

Aging↗

DNA binding mode of the Fab fragment of a monoclonal antibody specific for cyclobutane pyrimidine dimer.

Monoclonal antibodies specific for the cyclobutane pyrimidine dimer (CPD) are widely used for detection and quantification of DNA photolesions. However, the mechanisms of antigen binding by anti-CPD antibodies are little understood. Here we report NMR analyses of antigen recognition by TDM-2, which is a mouse monoclonal antibody specific for the cis - syn -cyclobutane thymine dimer (T[ c, s ]T). (31)P NMR and surface plasmon resonance data indicated that the epitope recognized by TDM-2 comprises hexadeoxynucleotides centered on the CPD. Chemical shift perturbations observed for TDM-2 Fab upon binding to d(T[ c, s ]T) and d(TAT[ c, s ]TAT) were examined in order to identify the binding sites for these antigen analogs. It was revealed that d(T[ c, s ]T) binds to the central part of the antibody-combining site, while the CPD-flanking nucleotides bind to the positively charged area of the V(H)domain via electrostatic interactions. By applying a novel NMR method utilizing a pair of spin-labeled DNA analogs, the orientation of DNA with respect to the antigen-binding site was determined: CPD-containing oligonucleotides bind to TDM-2 in a crooked form, draping the 3'-side of the nucleotides onto the H1 and H3 segments, with the 5'-side on the H2 and L3 segments. These data provide valuable information for antibody engineering of TDM-2.

Animals↗

Changes of hippocampal Cu/Zn-superoxide dismutase after kainate treatment in the rat.

In order to evaluate the putative role of Cu,Zn-superoxide dismutase (SOD-1) in the antioxidant defense mechanism during the neurodegenerative process, we examined the level of mRNA, the specific activity and immunocytochemical distribution for SOD-1 in the rat hippocampus after systemic injection of kainic acid (KA). Hippocampal SOD-1 mRNA levels were significantly increased by the seizure intensity 3 and 7 days after KA. These enhanced mRNA levels for SOD-1 were consistent with the increased specific activities for SOD-1, suggesting that the superoxide radical generated in neurotoxic lesion, induced SOD-1 mRNA. The CA1 and CA3 neurons lost their SOD-1-like immunoreactivity, whereas SOD-1-positive glia-like cells mainly proliferated throughout the CA1 sector and had an intense immunoreactivity at 3 and 7 days after KA. This immunocytochemical distribution for SOD-1-positive non-neuronal elements was similar to that for glial fibrillary acidic protein (GFAP)-positive cells. Each immunoreactivity for SOD-1-positive non-neuronal cell or GFAP in the layers of CA1 and CA3 disappeared 3 and 7 days after a maximal stage 5 seizure. On the other hand, activated microglial cells as selectively marked with the lectin occurred in the areas affected by KA-induced lesion. Double-labeling immunocytochemical analysis demonstrated the co-localization of SOD-1-positive glia-like cells and reactive astrocytes as labeled by GFAP or S-100 protein immunoreactivity. This finding suggested that the mobilization of astroglial cells for the synthesis of SOD-1 protein is a response to the KA insult designed to decrease the neurotoxicity induced by oxygen-derived free radicals. Therefore, these alterations might reflect the regulatory role of SOD-1 against oxygen-derived free radical-induced neuronal degeneration after systemic KA administration.

Animals↗

G protein betagamma subunits induce stress fiber formation and focal adhesion assembly in a Rho-dependent manner in HeLa cells.

In fibroblasts, the G protein alpha subunits Galpha(12) and Galpha(13) stimulate Rho-dependent stress fiber formation and focal adhesion assembly, whereas G protein betagamma subunits instead exert a disruptive influence. We show here that the latter can, however, stimulate the formation of stress fibers and focal adhesions in epithelial-like HeLa cells. Transient expression of beta(1) with gamma(2), gamma(5), gamma(7), and gamma(12) in quiescent HeLa cells induced stress fiber formation and focal adhesion assembly as did expression of the constitutively active Galpha(12). Co-expression of betagamma with Galpha(i2) and the C-terminal fragment of the beta-adrenergic receptor kinase, both of which are known to bind and sequester free betagamma, blocked betagamma-induced stress fiber and focal adhesion formation. Inhibition was also noted with co-expression of a dominant negative mutant of Rho. Botulinum C3 exoenzyme, which ADP-ribosylates and inactivates Rho, and a Rho-associated protein kinase inhibitor, Y-27632, similarly inhibited betagamma-induced stress fiber and focal adhesion assembly. These results indicate that G protein betagamma subunits regulate Rho-dependent actin polymerization in HeLa cells.

3T3 Cells↗