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Biomedical subjects

T Minami

Publications and source records attributed to T Minami.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗
PubMed2001

Lewis acid-promoted deoxygenative di[beta,beta-bis(ethylthio)]vinylation of aldehydes with trimethylsilylketene bis(ethylthio)acetal.

Silylketene dithioacetal 1 reacted with aldehydes 2a-o, 14, or cinnamaldehyde (11) in the presence of Lewis acid to give deoxygenative divinylation products, 3-substituted 1,4-pentadienes 3a-o, 15, or 5-phenyl-1,3,6-heptatriene 13b, in good to moderate yields. Similar reaction with 2-aminobenzaldehyde (16) or salicylaldehyde (17) produced quinoline 19 or chroman 20 in 40-58% yield. Treatment of 1 with alpha-diketones 22a-c or alpha-ketoester 24 led to tetrasubstituted furans 23a-c or allylic alcohol 25, respectively, in rather low yields. The formation mechanisms of these products are discussed.

Journal Article↗
PubMed2001

Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma.

BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.

Adult↗
PubMed2001

Observation of toroidal flow antiparallel to the drift direction in the hot electron mode plasmas in the compact helical system.

A toroidal flow antiparallel to the drift direction is observed in the hot electron mode plasmas when a large positive electric field and a sharp electron temperature gradient are sustained inside the internal transport barrier in the Compact Helical System. This toroidal flow reaches up to 5x10(4) m/s at the plasma center, and it is large enough to reverse the toroidal flow driven by a tangentially injected neutral beam. These observations clearly show the plasma favors flow in the minimum nablaB direction at the transport barrier.

Journal Article↗
PubMed2001

Characterization of the glutamatergic system for induction and maintenance of allodynia.

Glutamate is the main excitatory neurotransmitter in the central nervous system and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostaglandin (PG) E(2) and PGF(2 alpha) induced touch-evoked pain (allodynia) through the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters involved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allodynia. In addition to PGE(2) and PGF(2 alpha), N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were observed in NMDA receptor epsilon 4 (NR2D) subunit knockout (GluR epsilon 4(-/-)) mice, but not in epsilon 1 (NR2A) subunit knockout (GluR epsilon 1(-/-)) mice. Conversely, PGF(2 alpha)- and AMPA-induced allodynia were observed in GluR epsilon 1(-/-) mice, but not in GluR epsilon 4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon 2 (NR2B) antagonist CP-101,606 and neonatal capsaicin treatment. PGF(2 alpha)- and AMPA-induced allodynia were not affected by CP-101,606 and by neonatal capsaicin treatment. On the other hand, the glutamate transporter blocker DL-threo-beta-benzyloxyaspartate (DL-TBOA) blocked all the allodynia induced by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic system and suggest that the glutamate transporter is essential for the induction and maintenance of allodynia.

ATP-Binding Cassette Transporters↗
PubMed2001

Epistatic interactions between skin tumor modifier loci in interspecific (spretus/musculus) backcross mice.

The development of cancer is influenced both by exposure to environmental carcinogens and by the host genetic background. Epistatic interactions between genes are important in determining phenotype in plant and animal systems and are likely to be major contributors to cancer susceptibility in humans. Several tumor modifier loci have been identified from studies of mouse models of human cancer, and genetic interactions between modifier loci have been detected by genome scanning using recombinant congenic strains of mice (R. Fijneman et al., Nat. Genet., 14: 465-467, 1996; T. van Wezel et al., Nat. Genet., 14: 468-470, 1996; W. N. Frankel et al., Nat. Genet., 14, 371-373, 1996). We demonstrate here that strong genetic interactions between skin tumor modifier loci can be detected by hierarchical whole genome scanning of a complete interspecific backcross [outbred Mus spretus X Mus musculus (NIH/Ola)]. A locus on chromosome 7 (Skts1) showed a highly significant interaction with Skts5 on chromosome 12 (P < 10(-16)), whereas additional significant interactions were detected between loci on chromosomes 4 and 5, and 16 and 15. Some of these quantitative trait loci and their interactions, in particular the Skts1-Skts5 interaction, were confirmed in two completely independent backcrosses using inbred spretus strains (SEG/Pas and SPRET/Ei) and NIH/Ola. These results, therefore, illustrate the general use of interspecific crosses between Mus musculus and Mus spretus for the detection of strong genetic interactions between tumor modifier genes.

Animals↗
PubMed2001

Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain.

The REV1 protein is a member of the growing family of translesion DNA polymerases. A cDNA of the human REV1 gene that we had originally isolated encoded 1250 amino acids residues, which was one amino acid shorter than previously reported ones. The shorter form of REV1 was named REV1S. All individuals examined expressed equivalent amounts of REV1S and REV1 mRNA, suggesting that the REV1S mRNA is a splicing variant. We show that the REV1S protein also possesses deoxycytidyl transferase activity that inserts a dCMP opposite a DNA template apurinic/apyrimidinic site. Deletion and point mutation analysis of the REV1S protein revealed that the domain required for deoxycytidyl transferase and DNA binding activities of the REV1S protein are located in a conserved domain of translesion DNA polymerases. This result indicates that the structure of the catalytic site of the deoxycytidyl transferase closely resembles that of the translesion DNA polymerases. Therefore, the molecular mechanism of the dCMP transfer reaction of the REV1S protein and maybe also the REV1 protein might be the same as that of the dNTP transfer reaction of the translesion DNA polymerases.

Amino Acid Sequence↗
PubMed2001

Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia.

We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects.

Anemia, Aplastic↗
PubMed2001

Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin.

While acute pain has a fundamental role to operate a protective system, chronic pain associated with inflammation and nerve injury often outlasts its biological usefulness. Therefore, there has recently been great interest in the neurochemical mechanisms of hyperalgesia to noxious stimuli and tactile pain (allodynia) to innocuous stimuli with a hope to relieve persistent, intractable pain. Over several decades non-steroidal anti-inflammatory drugs and opioids have been employed for clinical management of pain. The introduction of molecular biology to pain research has enabled us to describe the mechanism of pain at the molecular level and to develop analgesics with selectivity for targets and with less adverse effects. This review focuses on current knowledge concerning mechanisms and pathways for pain induced by prostaglandins and their interactions with novel neuropeptides nociceptin/orphanin FQ and nocistatin derived from the same opioid precursor protein.

Analgesics↗
PubMed2001

2'-O,4'-C-Methylene bridged nucleic acid (2',4'-BNA): synthesis and triplex-forming properties.

For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance, there is only limited information available on the triplex-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide (TFO) significantly enhances the binding affinity towards target dsDNA. On Tm measurements, the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with deltaTm/modification of +4.3 to +5 degrees C at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2',4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-kappaB transcription factor (p50)-target dsDNA binding by forming a stable triplex at pH 7.0.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2001

Characterization of EP receptor subtypes responsible for prostaglandin E2-induced pain responses by use of EP1 and EP3 receptor knockout mice.

Prostaglandin E2 (PGE2) is known to be the principal pro-inflammatory prostanoid and play an important role in nociception. To identify PGE receptor (EP) subtypes that mediate pain responses to noxious and innocuous stimuli, we studied them by use of EP1 and EP3 knockout (EP1(-/-) and EP3(-/-)) mice. PGE2 could induce mechanical allodynia in EP1(+/+), EP3(+/+) and EP3(-/-) mice, but not in EP1(-/-) mice. N-methyl-D-aspartate (NMDA), the substrate of nitric oxide (NO) synthase L-arginine, or the NO donor sodium nitroprusside administered intrathecal (i.t.) could induce allodynia in EP3(-/-) and EP1(-/-) mice. Activation of EP1 receptors appears to be upstream, rather than downstream, of NMDA receptor activation and NO production in the PGE2-induced allodynia. Although PGE2 produced thermal hyperalgesia over a wide range of dosages from 50 pg to 0.5 microg kg(-1) in EP3(+/+) mice, it showed a monophasic hyperalgesic action at 5 ng kg(-1) or higher doses in EP3(-/-) mice. The selective EP3 agonist, ONO-AE-248, induced hyperalgesia at 500 pg kg(-1) in EP3(+/+) mice, but not in EP3(-/-) mice. Saline-injected EP1(-/-) mice showed hyperalgesia, which was reversed by i.t. PGE2 in a dose-dependent manner. There was no significant difference in the formalin-induced behaviours between EP1(-/-) or EP3(-/-) mice and the cognate wild-type mice. These results demonstrate that spinal EP1 receptors are involved in the PGE2-induced allodynia and that spinal EP3 receptors are involved in the hyperalgesia induced by low doses of PGE2. However, the formalin-induced pain cannot be ascribed to a single EP receptor subtype EP1 or EP3.

Animals↗
PubMed2001

Distinct regulatory mechanism for p70 S6 kinase beta from that for p70 S6 kinase alpha.

BACKGROUND: A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70beta), has a highly homologous amino acid sequence to that of p70/p85 S6 kinase (p70alpha). This includes the critical phosphorylation sites, Thr252, Ser394 and Thr412 in p70alpha1, which correspond to Thr241, Ser383 and Thr401 in p70beta1, respectively. However, the regulatory mechanism for p70beta remains to be elucidated. RESULTS: We report here the expression and the mechanism of in vivo regulation of p70beta. Two isoforms, p70beta1 and p70beta2, were expressed in a variety of tissues at a different level. p70beta1 was mainly targeted to the nucleus, whereas p70beta2 dispersed throughout the cytoplasm including nucleoplasm. The kinase activity of p70beta1 was less sensitive to the inhibition induced by rapamycin, wortmannin and amino acid withdrawal than that of p70alpha. The portion of p70beta activity inhibited by rapamycin was rescued by the rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR). Mutational analysis revealed that the phosphorylation of Thr241 and Thr401 in p70beta1 was indispensable for the kinase activity. In contrast, a p70beta1 mutant in which Ser383 was substituted with Gly (S383G) still retained nearly the half maximal activity. Sequential phosphorylation of wild-type and S383G mutant of p70beta1 with mTOR and 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro synergistically activated their kinase activities. CONCLUSION: These results indicate that p70beta is regulated by the mTOR- and PDK1-signalling pathways through a synergistic interaction between phosphorylated Thr241 and Thr401, while Ser383 plays minor role in their activation mechanism. Activated p70beta may be less sensitive to dephosphorylation mediated by putative phosphatases activated by rapamycin, amino acid withdrawal, and probably wortmannin.

Androstadienes↗
PubMed2001

The effects of capsaicin cream on prostaglandin-induced allodynia.

UNLABELLED: Although intradermal injection of capsaicin produces acute pain and secondary hyperalgesia, long-term topical application of capsaicin cream has been used as a medication for pain relief in various pain conditions. We previously reported that intrathecal administration of prostaglandin (PG) E(2) and PGF(2alpha) into mice induced touch-evoked pain (allodynia) through capsaicin-sensitive and capsaicin-insensitive afferent fibers, respectively. To clarify the mechanism of an analgesic effect by capsaicin cream, here we applied it to the tail and hind paws of mice and investigated its effects on PGE(2)- and PGF(2alpha)-induced allodynia. Twenty-four-hour pretreatment of mice with 0.025% or 0.05% capsaicin cream markedly alleviated allodynia induced by PGE(2), but not by PGF(2alpha). These results suggest that the topical application of capsaicin cream modulates capsaicin-sensitive afferents and ameliorates allodynia evoked by PGE(2) at the spinal level. IMPLICATIONS: Topical application of capsaicin cream alleviates touch-evoked pain induced by the intrathecal administration of prostaglandin E(2). This study may provide a rationale for the use of capsaicin cream as a therapeutic drug for pain relief.

Animals↗
PubMed2001

Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis in a new congenic strain, WKAH.C-Atp7b rats.

To examine whether Long-Evans Cinnamon (LEC) rats, a mutant rat model of Wilson's disease, have a susceptibility gene(s) to hepatocarcinogenesis in addition to the causative gene, Atp7b, we established a new congenic strain, WKAH.C-Atp7b rats, in which the Atp7b gene of the LEC rats is inserted into the normal Wistar-King Aptekman Hokkaido (WKAH) background. Hepatocellular tumors developed spontaneously in both sexes of WKAH.C-Atp7b rats, their incidence being slightly lower than that in LEC rats. Incidences of spontaneous liver tumors in LEC, WKAH.C-Atp7b and WKAH rats correlated with hepatic copper and iron concentrations. Medium-term liver bioassay showed that LEC rats were more susceptible to the induction of glutathione S-transferase placental form-positive preneoplastic foci than WKAH.C-Atp7b rats, and WKAH.C-Atp7b rats were more susceptible than WKAH rats. In an N-diethylnitrosamine (DEN)-induced long-term carcinogenicity study, 1) LEC rats were similarly or rather less susceptible to hepatocellular tumors than WKAH.C-Atp7b and WKAH rats, indicating that the progression of the preneoplastic foci to liver cancer in LEC rats was worse than that in WKAH.C-Atp7b and WKAH rats, 2) the incidences of kidney tumors in LEC and WKAH.C-Atp7b rats were higher than that in WKAH rats and high copper concentrations in the kidneys were observed in LEC and WKAH.C-Atp7b rats, 3) LEC rats were resistant to lung carcinogenesis. These data indicate that the susceptibility of LEC rats to liver and kidney carcinogenesis could be explained by Atp7b gene mutation and that the susceptibility to lung carcinogenesis is controlled by gene(s) other than Atp7b.

Adenosine Triphosphatases↗
PubMed2001

DNA methylation regulates placental lactogen I gene expression.

Expression of rat placental lactogen I is specific to the placenta and never expressed in other tissues. To obtain insight into the mechanism of tissue-specific gene expression, we investigated the methylation status in 3.4 kb of the 5'-flanking region of the rat placental lactogen I gene. We found that the distal promoter region of the rat placental lactogen I gene had more potent promoter activity than that of the proximal area alone, which contains several possible cis-elements. Although there are only 17 CpGs in the promoter region, in vitro methylation of the reporter constructs caused severe suppression of reporter activity, and CpG sites in the placenta were more hypomethylated than other tissues. Coexpression of methyl-CpG-binding protein with reporter constructs elicited further suppression of the reporter activity, whereas treatment with trichostatin A, an inhibitor of histone deacetylase, reversed the suppression caused by methylation. Furthermore, treatment of rat placental lactogen I nonexpressing BRL cells with 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, or trichostatin A resulted in the de novo expression of rat placental lactogen I. These results provide evidence that change in DNA methylation is the fundamental mechanism regulating the tissue-specific expression of the rat placental lactogen I gene.

Animals↗
PubMed2001

Selective accumulations of aluminum in five human arteries.

The aim of the present study was to determine variability of aluminum (Al) accumulation in human arteries and to observe the relationship between Al and five other elements (Ca, Fe, Mg, P, and Si) in the arteries. The Al contents in the thoracic aorta, basilar, coronary, femoral, and radial arteries of 26 human subjects were estimated by an inductively coupled plasma-atomic emission spectrometer and compared quantitatively to five elements. Al was detected in 88% of the cases in both the femoral and radial arteries, 73% in the coronary artery, 58% in the aorta, and 31% in the basilar artery. The average Al content was highest in the femoral artery (48.3 +/- 15.0 microg/g dry weight) and lowest in the basilar artery (8.1 +/- 3.6 microg/g). The Al had positive correlations with P, Ca, or Mg in both the aorta and femoral artery, and with Ca or P in the basilar artery. In the coronary artery, a correlation was found between Al and Si. No relationships were found between Al and each of the five elements in the radial artery. From these results, Al varied widely among the five arteries and accumulated more in the femoral and radial arteries but less in the basilar artery. These accumulations of Al were positively correlated with Ca or P in several arteries, but not sufficiently to explain the accumulation of Al. Further investigations are required to understand the mechanism of the variability of Al accumulation in the arteries.

Aged↗
PubMed2001

Relationship between meniscal degeneration and element contents.

The purpose of this study is to investigate the relationship between meniscal degeneration and element contents. The contents of elements (calcium, phosphorus, sulfur, and magnesium) in the menisci from 17 patients with osteoarthritis (OA) of the knee, 6 with rheumatoid arthritis (RA), and 2 who underwent the surgical operation for malignant tumors (control) were analyzed by inductively coupled plasma-atomic emission spectrometry, and the menisci were divided into four stages (Stage 0-3) of histological degeneration. The calcium contents of the menisci were 0.26 +/- 0.16 in Stage 0, 0.50 +/- 0.37 in Stage 1, and 0.69 +/- 0.66 in Stage 2, respectively (the values represent mg elements/g dry tissue). They increased with the progression of the stage. This tendency was found in the menisci with OA, but was not clear in those with RA. The calcium content in the control group was 0.17 +/- 0.09 mg/g. There was no significant relationship between the stage of degeneration and the contents of phosphorus, sulfur, or magnesium. The calcium content of the meniscus might indicate the degree of meniscal degeneration.

Adolescent↗