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T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 91 records · Page 5Linked to original sources
PubMed2001

[The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica (Ephedraceae))].

We investigated false-positive reactions obtained from a drug screening test using a Triage panel. We detected 2 cases giving false-positive reaction for AMP (amphetamine, methamphetamine) during the screening of 187 normal subjects. Subsequent follow up testing by high-performance liquid chromatography (HPLC), showed both to be false-positive reactions. As both cases have a history of ingesting the herbal drug, Ma-huang (Ephedra sinica (Ephedraceae)), containing ephedrine, we examined the relationship between false-positive reactions on Triage and Ma-huang. All urine samples collected from 7 healthy volunteers following administration of Ma-huang indicated AMP positive on Triage. Also a high ratio of AMP positives was observed in the patients who were administered Ma-huang-containing drugs at the hospital. However, none of them were identified as true-positives by HPLC or gas chromatography mass spectrometry (GC/MS) analysis. The extract of Ma-huang contained in herbal drugs, which otherwise contain neither amphetamine nor its derivatives, gives (AMP) positive indications on Triage. We speculate that unidentified components of Ma-huang cause the false-positive reactions. We suggest that follow-up tests by GC/MS or HPLC are needed wherever a positive result is obtained from a screening test by Triage. Furthermore, it will be established to continue collecting information on prescribed and non-prescribed drugs.

Adult↗
PubMed2000

Molecular characterization and nuclear localization of rat timeless-like gene product.

Among three period genes (per1, per2, per3) in mammals, only per2 gene was shown to be involved in the core clock mechanism. To elucidate the molecular function of rat PERIOD2 (rPER2), we searched for binding proteins to the PAS domain of rPER2. We isolated a binding protein to this domain and identified it as a TIMELESS-like protein (TLP) on the basis of mass analyses. Then, we isolated a rat TLP cDNA from the rat hypothalamus library. RNA blot analysis and in situ hybridization indicates that rTLP mRNA was expressed in all rat tissues from whole brain, the suprachiasmatic nucleus, eye, lung, heart, liver, kidney, placenta, and testis. When rTLP gene product was expressed in COS-1 cells, nuclear localization of rTLP was detected in 99.6% of transfected cells. These results suggest that the interaction of rPER2 with rTLP may influence the regulation of circadian clock components in nucleus after rPER2 is translocated into the nucleus.

Amino Acid Sequence↗
PubMed2000

Phosphorylation of tau is regulated by PKN.

For the phosphorylation state of microtubule-associated protein, tau plays a pivotal role in regulating microtubule networks in neurons. Tau promotes the assembly and stabilization of microtubules. The potential for tau to bind to microtubules is down-regulated after local phosphorylation. When we investigated the effects of PKN activation on tau phosphorylation, we found that PKN triggers disruption of the microtubule array both in vitro and in vivo and predominantly phosphorylates tau in microtubule binding domains (MBDs). PKN has a catalytic domain highly homologous to protein kinase C (PKC), a kinase that phosphorylates Ser-313 (= Ser-324, the number used in this study) in MBDs. Thus, we identified the phosphorylation sites of PKN and PKC subtypes (PKC-alpha, -betaI, -betaII, -gamma, -delta, -epsilon, -zeta, and -lambda) in MBDs. PKN phosphorylates Ser-258, Ser-320, and Ser-352, although all PKC subtypes phosphorylate Ser-258, Ser-293, Ser-324, and Ser-352. There is a PKN-specific phosphorylation site, Ser-320, in MBDs. HIA3, a novel phosphorylation-dependent antibody recognizing phosphorylated tau at Ser-320, showed immunoreactivity in Chinese hamster ovary cells expressing tau and the active form of PKN, but not in Chinese hamster ovary cells expressing tau and the inactive form of PKN. The immunoreactivity for phosphorylated tau at Ser-320 increased in the presence of a phosphatase inhibitor, FK506 treatment, which means that calcineurin (protein phosphatase 2B) may be involved in dephosphorylating tau at Ser-320 site. We also noted that PKN reduces the phosphorylation recognized by the phosphorylation-dependent antibodies AT8, AT180, and AT270 in vivo. Thus PKN serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

Amino Acid Sequence↗
PubMed2000

T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma.

Bone resorption is regulated by the immune system, where T-cell expression of RANKL (receptor activator of nuclear factor (NF)-kappaB ligand), a member of the tumour-necrosis factor family that is essential for osteoclastogenesis, may contribute to pathological conditions, such as autoimmune arthritis. However, whether activated T cells maintain bone homeostasis by counterbalancing the action of RANKL remains unknown. Here we show that T-cell production of interferon (IFN)-gamma strongly suppresses osteoclastogenesis by interfering with the RANKL-RANK signalling pathway. IFN-gamma induces rapid degradation of the RANK adapter protein, TRAF6 (tumour necrosis factor receptor-associated factor 6), which results in strong inhibition of the RANKL-induced activation of the transcription factor NF-kappaB and JNK. This inhibition of osteoclastogenesis is rescued by overexpressing TRAF6 in precursor cells, which indicates that TRAF6 is the target critical for the IFN-gamma action. Furthermore, we provide evidence that the accelerated degradation of TRAF6 requires both its ubiquitination, which is initiated by RANKL, and IFN-gamma-induced activation of the ubiquitin-proteasome system. Our study shows that there is cross-talk between the tumour necrosis factor and IFN families of cytokines, through which IFN-gamma provides a negative link between T-cell activation and bone resorption. Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown.

Animals↗
PubMed2000

Pharmacological characterization of [3H]-JTH-601, a novel alpha1-adrenoceptor antagonist: binding to recombinant human alpha1-adrenoceptors and human prostates.

Several alpha1-adrenoceptor (AR) selective antagonists are now widely used to improve lower urinary tract symptoms in benign prostatic hyperplasia patients. However, these drugs often result in orthostatic hypotension, because of their poor uroselectivity; the blockade of alpha1-AR not only in prostate but also in vasculature. Here we have investigated uroselectivity of JTH-601, a newly developed antagonist, in radioligand binding experiment using recombinant human alpha1-AR subtypes and human prostate. In saturation experiments, [3H]-JTH-601 showed subtype selectivity: high affinity to alpha1a-AR (pKd; 9.88+/-0.09), lower affinity to alpha1b-AR (pKd; 8.96+/-0.17) and no specific binding at concentrations up to 3000 pM to alpha1d-AR. In competition experiments, JTH-601 and its metabolic compound (JTH-601-G1) also showed alpha1a-AR selectivity, exhibiting approximately 5 times higher affinity for alpha1a-AR than for alpha1b-AR, 10 to 20 times higher affinity than for alpha1d-AR, respectively. [3H]-JTH-601 also bound to human prostate membranes in monophasic manner with high affinity constant (pKd; 9.89+/-0.12, Bmax=123.6+/-16 fmol/mg protein). JTH-601 is a unique alpha1-AR antagonist that shows high affinity and selectivity for human recombinant alpha1a- and human prostate. This new compound is useful for understanding alpha1-AR pharmacology and may have a therapeutic value.

Adrenergic alpha-Antagonists↗
PubMed2000

Effects of hypoxia on cholesterol metabolism in human monocyte-derived macrophages.

We assessed the metabolism of low density lipoprotein (LDL) of human monocyte-derived macrophages under hypoxia. The specific binding and association of 125I-labeled LDL (125I-LDL) were not changed under hypoxia compared to normoxia. However, the degradation of 125I-LDL under hypoxia decreased to 60%. The rate of cholesterol esterification under hypoxia was 2-fold greater on incubation with LDL or 25-hydroxycholesterol. The cellular cholesteryl ester content was also greater under hypoxia on incubation with LDL. Secretion of apolipoprotein E into the medium was not altered under hypoxia, suggesting that apolipoprotein E independent cholesterol efflux may be reduced under hypoxia. Thus, hypoxia affects the intracellular metabolism of LDL, stimulates cholesterol esterification, and enhances cholesteryl ester accumulation in macrophages. Hypoxia is one of the important factors modifying the cellular lipid metabolism in arterial wall.

Apolipoproteins E↗
PubMed2000

Aryl hydrocarbon receptor nuclear translocator is induced by kainic acid in rat hippocampal glial cells.

The localization and function of aryl hydrocarbon receptor nuclear translocator (ARNT) in the brain are still unclear. In this study, we examined changes of ARNT protein in rat hippocampus, by immunoblotting and immunohistochemical analysis using anti-ARNT antibody. Treatment of kainic acid (KA) induced marked increase in ARNT protein in both cytosolic and organellar fractions. ARNT immunoreactivity was markedly increased, predominantly in microglia and partly in astrocytes, similar to the immunoreactivity of heme oxygenase-1. In contrast, protein level of dioxin receptor did not change and hypoxia-inducible factor-1alpha protein was undetectable. These results suggest that ARNT expression in glial cells may participate in KA-induced episodes in the hippocampus.

Animals↗
PubMed2000

Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function.

The common cytokine receptor gamma chain (gammac), a shared component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development and function of lymphocytes. The cytoplasmic domain of gammac consists of 85 aa, in which the carboxyl-terminal 48 aa are essential for its interaction with and activation of the Janus kinase, Jak3. Evidence has been provided that Jak3-independent signals might be transmitted via the residual membrane-proximal region; however, its role in vivo remains totally unknown. In the present study, we expressed mutant forms of gammac, which lack either most of the cytoplasmic domain or only the membrane-distal Jak3-binding region, on a gammac null background. We demonstrate that, unlike gammac or Jak3 null mice, expression of the latter, but not the former mutant, restores T lymphopoiesis in vivo, accompanied by strong expression of Bcl-2. On the other hand, the in vitro functions of the restored T cells still remained impaired. These results not only reveal the hitherto unknown role of the gammac membrane-proximal region, but also suggest the differential requirement of the cytoplasmic subregions of gammac in T cell development and function.

Animals↗
PubMed2000

Prognostic significance of reverse transcriptase-polymerase chain reaction measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and peripheral blood of patients with colorectal carcinoma.

BACKGROUND: The objective of this study was to assess the prognostic value of detecting circulating tumor cells in the tumor drainage blood and peripheral blood of patients with colorectal carcinoma. METHODS: A total of 53 patients with advanced colorectal carcinoma were studied. Tumor drainage blood and peripheral blood samples that were obtained during surgery were examined for carcinoembryonic antigen (CEA) mRNA using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In spiking experiments, the assay indicated a sensitivity limit of 1 carcinoma cell per 10(6) cells. CEA mRNA was detected in the tumor drainage blood of 36 of 53 patients (68%) and in the peripheral blood of 18 of 53 patients (34%). The rate of detection in both tumor drainage blood and peripheral blood was significantly higher in patients with lymph node metastasis, lymphatic invasion, or vascular invasion (P < 0.05). Among those patients who underwent potentially curative resection, the 2-year disease free survival rate of patients whose tumor drainage or peripheral blood was negative for CEA mRNA was significantly better than that of patients who showed CEA mRNA positivity of either sample (tumor drainage blood: 100% vs. 57%; P < 0.05; peripheral blood: 74% vs. 50%; P < 0.01), although the follow-up thus far has been only 9-30 months. CONCLUSIONS: The presence of CEA mRNA in the blood is a useful indicator of circulating tumor cells, and it is one of the determinant prognostic factors for patients with colorectal carcinoma. Moreover, the absence of CEA mRNA in tumor drainage blood was found to be a superior marker for disease free survival compared with that in peripheral blood.

Adult↗
PubMed2000

Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and hippocampus by the antiparkinsonian drugs, talipexole and pramipexole.

Treatment of rats for 4 days with the antiparkinsonian drugs, talipexole and pramipexole, markedly increased Bcl-2 immunoreactivity in neuronal dendritic processes in both cerebral cortex and hippocampus, but treatment for 1 day with either of these drugs did not. Repeated administration of talipexole or pramipexole may have neuroprotective effect in neurodegenerative disorders.

Animals↗
PubMed2000

Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase.

A novel gene, Reprimo, in which induction in cells exposed to X-irradiation is dependent on p53 expression, has been isolated. Ectopic p53 expression results in the induction of its mRNA. Reprimo is a highly glycosylated protein and, when ectopically expressed, it is localized in the cytoplasm and induces G(2) arrest of the cell cycle. In the arrested cells, both Cdc2 activity and nuclear translocation of cyclin B1 are inhibited, suggesting the involvement of Reprimo in the Cdc2.cyclin B1 regulation pathway. Thus, Reprimo may be a new member involved in the regulation of p53-dependent G(2) arrest of the cell cycle.

Amino Acid Sequence↗
PubMed2000

Rapamycin and FK506 induce long-term potentiation by pairing stimulation via an intracellular Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

Immunophilin-CsA and -FK506 complexes bind to calcineurin (CaN) and inhibit its phosphatase activity leading to enhancement of neuronal activities. However, inhibition of CaN activity is not the mediator of modulatory activity for IP3 and ryanodine receptors and does not mediate the neurotrophic actions of FK506. FK506 binding protein (FKBP)-12 also binds rapamycin, another immunosuppressant which does not affect CaN activity. Using whole-cell patch clamp techniques, excitatory postsynaptic currents (EPSCs) were recorded and we analyzed the effect of immunosuppressants on the synaptic potentiation induced by pairing weak presynaptic stimulation with postsynaptic depolarization in CA1 neurons of rat hippocampal slices. We found that postsynaptic application of rapamycin or FK506, at low concentrations, but not cyclosporin A, in conjunction with weak pairing stimulation, induced NMDA-dependent long-term potentiation (LTP). The rapamycin-induced LTP was blocked by chelating intracellular Ca(2+) or by inhibiting the intracellular Ca(2+) release. Thus, Ca(2+) release from intracellular Ca(2+) stores is required for the induction of LTP by weak pairing stimulation in the presence of rapamycin or FK506 at postsynaptic sites. We propose that postsynaptic FKBP-12 regulates synaptic transmission by stabilizing the postsynaptic Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

Animals↗
PubMed2000

Charge-density-wave transitions in the local-moment magnet Er5Ir4Si10

We report the observation of a new type of charge-density wave (CDW) in the large magnetic-moment rare-earth intermetallic compound, Er5Ir4Si10, which then orders magnetically at low temperatures. Single crystal x-ray diffraction shows the development of a 1D incommensurate CDW at 155 K, which then locks into a purely commensurate state below 55 K. The well-localized Er3+ moments are antiferromagnetically ordered below 2.8 K. We observe very sharp anomalies in the specific heat at 145 and 2.8 K, signifying the bulk nature of these transitions. Our data suggest the coexistence of strongly coupled CDW with local-moment antiferromagnetism in Er5Ir4Si10.

Journal Article↗
PubMed2000

Interleukin-4-inhibited mRNA expression in mixed rat glial and in isolated microglial cultures.

Interleukin-4 (IL-4) likely is one of the key players in the concert of immunosuppressive factors in brain. Therefore, influences of the cytokine on mRNA expression of endogenous mediators of inflammation, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interferon-inducible protein 10 (IP-10), interleukin-3 receptor-beta (IL-3R-beta), and of another antiinflammatory cytokine, IL-10, have been evaluated in the present study by semi-quantitative RT-PCR. Primary rat mixed glial cultures and isolated microglial cells, the resident immunocytes of the brain, have been used as rich sources of these mRNAs in response to the bacterial cell wall component lipopolysaccharide (LPS). Time-course studies showed peak levels of LPS-increased mRNAs at approximately 4 h. Interestingly, IL-10 mRNA was elevated also upon the LPS-stimulus. IL-4, given 30 min before LPS, inhibited increases of all mRNAs significantly, including IL-10 mRNA. IL-4, however, induced peroxisome proliferator-activated receptor (PPAR)-gamma in cultured microglia. This induction was completely inhibited by simultaneous administration of LPS. The data confirms IL-4 as an important antiinflammatory cytokine and gives some idea of cross-talk between intracellular signaling evoked by pro- and antiinflammatory substances.

Aged↗
PubMed2000

Cross talk between interferon-gamma and -alpha/beta signaling components in caveolar membrane domains.

Definition of cellular responses to cytokines often involves cross-communication through their respective receptors. Here, signaling by interferon-gamma (IFN-gamma) is shown to depend on the IFN-alpha/beta receptor components. Although these IFNs transmit signals through distinct receptor complexes, the IFN-alpha/beta receptor component, IFNAR1, facilitates efficient assembly of IFN-gamma-activated transcription factors. This cross talk is contingent on a constitutive subthreshold IFN-alpha/beta signaling and the association between the two nonligand-binding receptor components, IFNAR1 and IFNGR2, in the caveolar membrane domains. This aspect of signaling cross talk by IFNs may apply to other cytokines.

Animals↗
PubMed2000

A Concise Route to (+)-Estrone.

A concise route to the Torgov diene, the key intermediate of estrone, has been devised using a chiral dioxycyclopentenone as the starting material by employing a sequence of five steps of reactions involving a Lewis acid-mediated Diels-Alder reaction with Dane's diene.

Journal Article↗