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Biomedical subjects

H Kamiya

Publications and source records attributed to H Kamiya.

At least 73 records · Page 4Linked to original sources
PubMed2001

The apolipoprotein E genotype influences the risk for vasospastic angina.

It has been suggested that people with the epsilon4 allele of the apolipoprotein E (apoE) polymorphism and the deletion (D) allele of the insertion (I/D) polymorphism of angiotensin-converting enzymes, are at a greater risk for coronary artery disease. However, only a few studies have examined the relationships between vasospastic angina (VSA) and genotype, especially with the apoE polymorphism. In the present study, 76 patients with VSA without significant fixed coronary artery stenosis, 149 patients with ischemic heart disease (IHD) who had 75% or more luminal diameter narrowing and 213 healthy subjects were enrolled. The odds ratio for VSA of the epsilon4 allele carriers relative to the epsilon3/3 allele subjects compared with subjects with IHD and control subjects combined was 0.44 (95% CI 0.21 to 0.93, P=0.021), and that compared with control subjects alone was 0.36 (95% CI 0.17 to 0.78, P=0.005), implying that the presence of the epsilon4 allele indicates resistance to the development of VSA. In contrast, people with the epsilon2 allele showed a tendency to develop VSA more frequently than did patients with IHD (P=0.009), although the frequency of the epsilon2 allele did not differ between patients with VSA and control subjects. On the other hand, no recessive and dominant effects of the D alleles on VSA were found. These findings suggest that the risk of the occurrence of VSA may be reduced by the epsilon4 allele and increased by the epsilon2 allele. The ApoE polymorphism may be associated with IHD and VSA, probably due to the modulation of lipid metabolism.

Adult↗
PubMed2001

Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.

BACKGROUND: Several studies have shown that calcineurin may play a critical role in the signalling of cardiac hypertrophy in various experimental models. OBJECTIVE: To elucidate whether calcineurin is involved in cardiac hypertrophy due to energy metabolic disorder by using the juvenile visceral steatosis (JVS) mouse, which is a murine model of systemic carnitine deficiency. METHODS AND RESULTS: Cardiac hypertrophy in JVS mice (C3H strain) progresses gradually after birth and is present until eight weeks of age. In this study, calcineurin activity in JVS mice increased significantly at four weeks of age (the developing stage of cardiac hypertrophy) compared with age-matched control mice. Treatment with calcineurin inhibitor FK506 (0.5 or 1.0 mg/kg/day) from the age of four to eight weeks attenuated cardiac hypertrophy without beneficially affecting cardiac function. Gene expression, accompanied by cardiac hypertrophy, was also suppressed by the FK506 treatment. CONCLUSIONS: The activation of calcineurin is involved in the development of cardiac hypertrophy in the JVS mouse, and calcineurin inhibition may be useful for reducing cardiac hypertrophy.

Animals↗
PubMed2001

Monoclonal antibodies reactive with dendritic cells of Mongolian gerbils.

Mongolian gerbils (Meriones unguiculatus) serve as an valuable model animal for several infectious diseases of medical and veterinary importance. Reagents available for characterization of the immune response of Mongolian gerbils are strictly limited. We describe three novel murine monoclonal antibodies (mAbs) to dendritic cells of Mongolian gerbils. These include HUSM-M.g.11 of IgG2b isotype, HUSM-M.g. 20 of IgG2a isotype, and HUSM-M.g.30 of IgG1 isotype. All of these mAbs had an identical profile of immunohistochemical reactions with various tissues taken from immune-naive Mongolian gerbils, and were intensively expressed on dendritic cells, including epidermal Langerhans cells, B-cell follicles, and the thymic reticulum. Positive reactions of the epidermis and intestinal mucosa with these mAbs were induced by cutaneous or intestinal infections with parasites. Competitive enzyme-linked immunosorbent assay and immunoblot analysis (western blotting) indicated that all of these mAbs recognize an identical peptide epitope on a molecule with approximate molecular mass of 29 kDa. These data suggest that the mAbs recognize major histocompatibility complex class-II molecules of gerbils. Use of described mAbs would facilitate characterization of immune responses as well as investigations on host responses to infections of medical and veterinary importance, using the gerbil model.

Animals↗
PubMed2000

Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus.

To investigate the mechanisms by which phorbol esters potentiate transmitter release from mossy fibre terminals we used fura dextran to measure the intraterminal Ca2+ concentration in mouse hippocampal slices. A phorbol ester, phorbol 12,13-diacetate (PDAc), potentiated the field excitatory postsynaptic potential (fEPSP) slope. PDAc also enhanced the stimulation-dependent increase of [Ca2+]i in the mossy fibre terminal (Delta[Ca2+]pre). The magnitude of the PDAc-induced fEPSP potentiation (463+/-57% at 10 microM) was larger than that expected from the enhancement of Delta[Ca2+]pre (153+/-5%). The Delta[Ca2+]pre was suppressed by omega-agatoxin IVA (omega-AgTxIVA, 200 nM), a P/Q-type Ca2+ channel-specific blocker, by 31%. The effect of PDAc did not select between omega-AgTxIVA-sensitive and -resistant components. The PDAc-induced potentiation of the fEPSP slope was partially antagonized by the protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIS-I, 10 microM), whereas the Delta[Ca2+]pre was completely blocked by BIS-I. Although the BIS-I-sensitive fEPSP potentiation was accompanied by a reduction of the paired-pulse ratio (PPR), the BIS-I-resistant component was not. Whole-cell patch clamp recording from a CA3 pyramidal neuron in a BIS-I-treated slice demonstrated that PDAc (10 microM) increased the frequency of miniature excitatory postsynaptic currents (mEPSCs, 259+/-33% of control) without a noticeable change in their amplitude (102+/-5% of control). These results suggest that PKC potentiates transmitter release by at least two distinct mechanisms, one Delta[Ca2+]pre dependent and the other Delta[Ca2+]pre independent. In addition, some phorbol ester-mediated potentiation of synaptic transmission appears to occur without activating PKC.

Action Potentials↗
PubMed2000

Role of rab GDP dissociation inhibitor alpha in regulating plasticity of hippocampal neurotransmission.

Rab GDP dissociation inhibitor alpha (Rab GDIalpha) is a regulator of the Rab small G proteins implicated in neurotransmission, and mutations of Rab GDIalpha cause human X-linked mental retardation associated with epileptic seizures. In Rab GDIalpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice. Furthermore, the Rab GDIalpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures. These results suggest that Rab GDIalpha plays a specialized role in Rab3A recycling to suppress hyperexcitability via modulation of presynaptic forms of plasticity.

Animals↗
PubMed2000

Two DNA polymerases of Escherichia coli display distinct misinsertion specificities for 2-hydroxy-dATP during DNA synthesis.

The insertion specificities of an oxidized dATP analogue, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), were determined using the alpha (catalytic) subunit of Escherichia coli DNA polymerase III and the exonuclease-deficient Klenow fragment of DNA polymerase I. In contrast to our previous observation that mammalian DNA polymerase alpha incorporated the oxidized nucleotide opposite T and C, these two E. coli DNA polymerases incorporated 2-OH-dATP opposite T and G on the DNA template. Steady-state kinetic studies indicated that the alpha subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite G. On the other hand, the incorporation of 2-OH-dATP opposite T by the exonuclease-deficient Klenow fragment was 2 orders of magnitude more efficient than that opposite G. These results indicate that the misinsertion specificity of 2-OH-dATP differs between replicative and repair-type DNA polymerases, and provide a biochemical basis for the mutations induced by 2-OH-dATP in E. coli.

Adenosine Triphosphate↗
PubMed2000

Methylglyoxal induces G:C to C:G and G:C to T:A transversions in the supF gene on a shuttle vector plasmid replicated in mammalian cells.

We previously reported that the majority of base-pair substitutions induced by an endogenous mutagen, methylglyoxal, were G:C-->T:A transversions and G:C-->A:T transitions in wild-type and nucleotide excision repair (NER)-deficient (uvrA or uvrC) Escherichia coli strains. To investigate the mutation spectrum of methylglyoxal in mammalian cells and to compare the spectrum with those detected in other experimental systems, we analyzed mutations in a bacterial suppressor tRNA (supF) gene in the shuttle vector plasmid pMY189. We treated pMY189 with methylglyoxal and immediately transfected it into simian COS-7 cells. The cytotoxicity and the mutation frequency (MF) increased according to the dose of methylglyoxal. In the mutants induced by methylglyoxal, multi-base deletions were predominant (50%), followed by base-pair substitutions (35%), in which 89% of the substitutions occurred at G:C sites. Among them, G:C-->C:G and G:C-->T:A transversions were predominant. The overall distribution of methylglyoxal-induced mutations detected in the supF gene was different from that for the spontaneous mutations. These results suggest that methylglyoxal may take part in causing G:C-->C:G and G:C-->T:A transversions in vivo.

Animals↗
PubMed2000

Cloning of the Microcystis aeruginosa M228 lectin (MAL) gene.

We have cloned and characterized the gene encoding Microcystis aeruginosa (strain M228) lectin (MAL). The gene contains 1551 nucleotides and an open reading frame for a protein of 517 amino acids with a predicted molecular weight of 55,159 Da. The carboxy-terminal region of MAL has three tandemly repeated homologous domains composed of 61 amino acids. These regions show similarity to the corresponding regions of the alpha-amylase of Clostridium beijerinckii (23% identity). The mal gene lies adjacent to an ORF that display homology to cytochrome P-450 and polyketide synthase. Southern hybridization showed that the genomic DNA of the strain M228 contained, in addition to MAL gene (mal), at least two other mal like gene.

Amino Acid Sequence↗
PubMed2000

The role of tachykinin NK-1 receptors in the area postrema of ferrets in emesis.

The role of tachykinin NK-1 receptors in the area postrema (AP) in emesis was examined in ferrets. Strong c-fos-like immunoreactivity was observed in the AP and nucleus tractus solitalius (NTS) in cisplatin (10 mg/kg, i.p.)-treated animals, but not in control animals. The number of the central emetogen morphine-induced vomits and retches was remarkably reduced (95%) and that of the peripheral emetogen copper sulphate-induced vomits was significantly (54%) reduced by AP lesion. Pretreatment with the tachykinin NK-1 receptor antagonists HSP-117 (1.0 microg) and CP-99,994 (7.5 microg) into the AP decreased the numbers of vomits and retches induced by morphine and copper sulphate. These results suggest that NK-1 receptors in the AP are involved in the mechanism of emesis induced by morphine and copper sulphate.

Animals↗
PubMed2000

2-Hydroxy-dATP is incorporated opposite G by Escherichia coli DNA polymerase III resulting in high mutagenicity.

Four kinds of oxidatively damaged DNA precursors, 8-hydroxydeoxyguanosine 5'-triphosphate (8-OH-dGTP), 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), 5-hydroxydeoxycytidine 5'-triphosphate (5-OH-dCTP) and 5-formyldeoxyuridine 5'-triphosphate (5-CHO-dUTP), were employed in in vitro gap-filling reactions of the supF gene conducted by the Escherichia coli DNA polymerase III holoenzyme, and these treated DNAs were transfected into various E.coli strains. When the manipulated DNAs were transfected into the repair-proficient strain, supF mutants were obtained much more frequently by the purine nucleotides than by the pyrimidine nucleotides (2-OH-dATP > 8-OH-dGTP >> 5-OH-dCTP approximately 5-CHO-dUTP). This result is in contrast to our previous observation that these four oxidatively damaged nucleotides induce chromosomal gene mutations with similar frequencies when incorporated directly into E.coli. 2-OH-dATP elicited G-->T transversions, indicating the formation of G*2-OH-dATP pairs. These results demonstrate that 2-OH-dATP was highly mutagenic in this assay system containing the in vitro DNA synthesis by the E.coli replicative DNA polymerase, in addition to in the in vivo assay system reported previously. Slight increases in the mutant frequencies were observed when alkA (for 8-OH-dGTP and 2-OH-dATP) and mutY (for 2-OH-dATP) strains were used as hosts. This is the first report that clearly shows the formation of G*2-OH-dATP pairs.

Adenosine Triphosphate↗
PubMed2000

Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice.

Subcutaneous injection of formalin into a paw of mice caused two distinct phases of licking and biting, first phase (1-5 min) and the second phase (7-30 min) after the injection. The muscarinic antagonist atropine (0.1-10 ng, i.t.) and the M(3) receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.1-20 ng, i.t.) inhibited the second phase of this response, whereas higher doses of atropine (20-100 ng, i.t.) did not cause inhibition. The M(1) muscarinic receptor antagonist pirenzepine (10-100 ng, i.t.) did not inhibit either the first or the second phase response, but a high dose of pirenzepine (1000 ng, i.t.) tended to inhibit the second phase response. On the other hand, the M(2) muscarinic receptor antagonist 11-¿(2-[(diethylamino)methyl]-1-piperidinyl¿acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one (AF-DX116; 10-1000 ng, i.t.) had no effect on either the first or the second phase of response. The opioid receptor antagonist naloxone did not affect the 4-DAMP-induced anti-nociceptive response. The i.t. injection of the acetylcholinesterase inhibitor neostigmine (25 ng) significantly inhibited only the second phase. The acetylcholine (ACh) depletor hemicholinium-3 (HC-3) (1 microg, i.t.) completely abolished the 4-DAMP-induced anti-nociceptive response. The ACh content of the spinal cord was significantly increased 14 min after formalin injection. This significant increase in the ACh content was inhibited by pretreatment with 4-DAMP (10 ng, i.t.). These results suggest that endogenous ACh in the spinal cord acts as a transmitter anti-nociception, and that ACh release regulated by presynaptic M(3) muscarinic receptors in the spinal cord is involved in the second phase of nociception induced by formalin.

Acetylcholine↗
PubMed2000

Kainate receptor-mediated presynaptic inhibition at the mouse hippocampal mossy fibre synapse.

1. The presynaptic action of kainate (KA) receptor activation at the mossy fibre-CA3 synapse was examined using fluorescence measurement of presynaptic Ca2+ influx as well as electrophysiological recordings in mouse hippocampal slices. 2. Bath application of a low concentration (0.2 microM) of KA reversibly increased the amplitude of presynaptic volley evoked by stimulation of mossy fibres to 146 +/- 6 % of control (n = 6), whereas it reduced the field excitatory postsynaptic potential (EPSPs) to 30 +/- 4 %. 3. The potentiating effect of KA on the presynaptic volleys was also observed in Ca2+-free solution, and was partly antagonized by (2S, 4R)-4-methylglutamic acid (SYM 2081, 1 microM), which selectively desensitizes KA receptors. 4. The antidromic population spike of dentate granule cells evoked by stimulation of mossy fibres was increased by application of 0.2 microM KA to 160 +/- 10 % of control (n = 6). Whole-cell current-clamp recordings revealed that the stimulus threshold for generating antidromic spikes recorded from a single granule cell was lowered by KA application. 5. Application of KA (0.2 microM) suppressed presynaptic Ca2+ influx to 78 +/- 4 % of control (n = 6), whereas the amplitude of the presynaptic volley was increased. 6. KA at 0.2 microM reversibly suppressed excitatory postsynaptic currents (EPSCs) evoked by mossy fibre simulation to 38 +/- 9 % of control (n = 5). 7. These results suggest that KA receptor activation enhances the excitability of mossy fibres, probably via axonal depolarization, and reduces action potential-induced Ca2+ influx, thereby inhibiting mossy fibre EPSCs presynaptically. This novel presynaptic inhibitory action of KA at the mossy fibre-CA3 synapse may regulate the excitability of highly interconnected CA3 networks.

Animals↗
PubMed2000

Pharmacological characterization of a novel AVP(4-9) binding site in rat hippocampus.

pGlu-Asn-Cys (Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)), a major metabolite C-terminal fragment of Arginine(8)-vasopressin (AVP), improves the disruption of the learning and memory, and is a far more potent in the mnemonic function than AVP. In this study, we pharmacologically characterized its putative binding site and mechanism of intracellular signaling. Radioligand binding assay showed that [35S]AVP(4-9) could detect specific binding sites in the rat hippocampus membrane preparations, and the binding site was specifically displaced by AVP(4-9) but not by either V(1) or V(2) antagonists. Furthermore, [35S]AVP(4-9) could not detect the cloned rat V(1a), V(1b) and V(2) vasopressin receptors. Even at a low doses (10-100 pM), AVP(4-9) caused an increase in both inositol(1,4, 5)-trisphosphate (Ins(1,4,5)P(3)) and intracellular calcium concentrations ([Ca(2+)](i)) in rat hippocampal cells. The AVP(4-9)-induced [Ca(2+)](i) increase was partially inhibited by the absence of Ca(2+) or by Ca(2+)-channel blocker, suggesting that AVP(4-9) caused the [Ca(2+)](i) increase via release from intracellular calcium store as well as influx from extracellular calcium. For the first time, this study provides evidence to show that AVP(4-9) activates Ins(1,4,5)P(3)/[Ca(2+)](i) pathway through a novel type of receptor in rat hippocampus, which might be potentially important in improving the mnemonic function.

Animals↗
PubMed2000

Survival of destrobilated adults of Taenia crassiceps in T-cell-depleted Mongolian gerbils.

In Mongolian gerbils (Meriones unguiculatus), prednisolone treatment induces the survival of strobilated Taenia crassiceps to sexual maturity followed by fecal release of gravid proglottides. The mechanism underlying the effects of prednisolone has not been elucidated in this taeniid/rodent model. Using a novel murine monoclonal antibody specific to a cell-surface determinant of gerbil T-cells (HUSM-M.g.15 of IgG2b isotype) for in vivo depletion of the cells, we examined the T-cell dependence of the following two phenomena: (1) elimination of strobilated T. crassiceps from the intestine of naive gerbils, and (2) depressed egg formation by the cestode in prednisolone-treated gerbils. In T-cell-depleted gerbils, only destrobilated adults were recovered from the intestine, although the recovery rate was comparable with that observed in prednisolone-treated animals. Egg formation by the cestode in T-cell-depleted, prednisone-treated gerbils did not differ from that seen in gerbils treated with prednisolone alone. We conclude that one of main effects of prednisolone can be ascribed to the suppression of T-cell functions that work to eliminate strobilated T. crassiceps from gerbils.

Animals↗
PubMed2000

Chemokine production by the BEAS-2B human bronchial epithelial cells: differential regulation of eotaxin, IL-8, and RANTES by TH2- and TH1-derived cytokines.

BACKGROUND: Bronchial epithelial cells produce many types of chemokines and may contribute to lung inflammation by recruiting inflammatory cells. The CC chemokine eotaxin is a potent, eosinophil-specific chemoattractant that has been detected in the bronchial epithelium of patients with asthma. OBJECTIVES: The aim of this study was to investigate the regulatory mechanisms of chemokine production from bronchial epithelium by inflammatory cytokines, especially T(H)2- and T(H)1-derived cytokines, in bronchial asthma. METHODS: BEAS-2B human bronchial epithelial cells were cultured with TNF-alpha, IL-4, IL-13, and IFN-gamma alone or in combination, after which supernatants were assayed for eotaxin, IL-8, and RANTES proteins with ELISA. Reverse transcription-PCR was also performed. RESULTS: TNF-alpha induced production of eotaxin, IL-8, and RANTES in a concentration-dependent manner. Both IL-4 and IL-13 synergistically enhanced TNF-alpha-induced eotaxin production, whereas IL-8 production induced by TNF-alpha was significantly down-regulated by the T(H)2-derived cytokines. IFN-gamma, a T(H)1 cytokine, counteracted the enhancing effects of IL-4 and IL-13 on eotaxin production. RANTES production by TNF-alpha was not affected by IL-4 and IL-13 but was markedly enhanced by IFN-gamma. CONCLUSIONS: These results suggest that T(H)2 cytokines are involved in preferential recruitment of eosinophils in bronchial asthma by enhancing eotaxin and reducing IL-8 production from bronchial epithelial cells and that T(H)1 cytokines counteract the effects of T(H)2 cytokines by reducing eotaxin production.

Bronchi↗