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Biomedical subjects

K Nagaoka

Publications and source records attributed to K Nagaoka.

At least 19 recordsLinked to original sources

Spatially dependent inelastic tunneling in a single metallofullerene.

We have measured the elastic and inelastic tunneling properties of isolated Gd@C(82) molecules on Ag(001) using cryogenic scanning tunneling spectroscopy. We find that the dominant inelastic channel is spatially well localized to a particular region of the molecule. Ab initio pseudopotential density-functional theory calculations indicate that this channel arises from a vibrational cage mode. We further show that the observed inelastic tunneling localization is explained by strong localization in the molecular electron-phonon coupling to this mode.

Journal Article↗

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Journal Article↗

Association between nasal respiratory obstruction and vertical mandibular position.

Vertical mandibular position is considered to have an effect on the patency of the upper airway, because mouth opening is associated with a backward and downward displacement of the mandible and tongue. This study was conducted to investigate the nature of mandibular displacement at rest and to determine whether or not different respiration modes and body postures influence the mandibular position. The mandibular position was measured by use of a newly developed system with magnets and magnetic sensors placed on the upper and lower first molars, respectively. Vertical mandibular position was significantly affected by the degree of nasal airway obstruction. The proportion of the duration of mouth opening from 0 to 2.5 mm was about 80% in the sitting and lateral recumbent positions and 55% in the supine position. The amount and duration of vertical mandibular displacement were thus significantly increased by experimentally induced nasal respiratory obstruction. Furthermore, it was demonstrated that the amount and duration of mouth opening were significantly greater in the supine posture than in the sitting and lateral recumbent positions. It is thus shown that nasal respiratory disturbance may be a key determinant for mouth opening and breathing and the resultant vertical mandibular displacement.

Adult↗

Effects of activator on masticatory muscle activity during daytime and sleep.

The purpose of this study was to investigate masticatory muscle activity with and without the use of an activator during daytime and sleep, and further to focus on the changes in muscle activity produced by the daytime use. The subjects in this study were 10 healthy males (mean age: 27.6 years). A portable electromyogram (EMG) recording device was used to record the activity from the right temporal, masseter and digastric muscles. After recording, the integrated EMG values (microV s) were measured. The muscle activity was lower during sleep than during daytime, irrespective of the use of the activator. In sleep-time, temporal and digastric muscle activity was significantly decreased, although masseter muscle activity presented no significant differences. With the activator in use, the digastric muscle activity tended to increase in comparison with the elevator muscles during daytime and sleep. Although the activity of both elevator muscles was diminished by use of the activator during sleep in all subjects, some subjects showed an increase during daytime. These results suggested that the activator should be used, if possible, not only during sleep, but also during daytime and clenched on consciously to obtain the adaptation and development of the masticatory muscles for the 're-training of the muscles' at a new favourable mandibular position.

Adult↗

Mechanisms responsible for increase in circulating inhibin levels at the time of ovulation in mares.

In female mammals, inhibin is secreted by the granulosa cells and selectively inhibits secretion of FSH. Although circulating immunoreactive (ir)-inhibin levels decrease after ovulation as a result of the disappearance of its main source, they abruptly increase at the time of ovulation in mares. To investigate the mechanisms responsible for this increase, 50 ml of equine follicular fluid (eFF) was administered into the abdominal cavity of mares during the luteal phase (eFF, n = 4). One hour after treatment, plasma levels of ir-inhibin and inhibin pro-alphaC (but not estradiol-17beta) were significantly higher in eFF-treated mares than in control mares (n = 4). The hormone profiles in eFF-treated mares were similar to those in mares with the spontaneous or hCG induced ovulations. The present study demonstrates that the release of follicular fluid into the abdominal cavity when the follicle ruptures is responsible for the ovulatory inhibin surge in the mare. These findings also suggest that circulating inhibin pro-alphaC may be useful for determining the time of ovulation in the mare.

Animals↗

Temperature dependence of a single Kondo impurity.

Recent advances in scanning tunneling microscopy have allowed the observation of the Kondo effect for individual magnetic atoms. One hallmark of the Kondo effect is a strong temperature-induced broadening of the Kondo resonance. In order to test this prediction for individual impurities, we have investigated the temperature dependent electronic structure of isolated Ti atoms on Ag(100). We find that the Kondo resonance is strongly broadened in the temperature range T = 6.8 K to T = 49.0 K. These results are in good agreement with theoretical predictions for Kondo impurities in the Fermi liquid regime, and confirm the role of electron-electron scattering as the main thermal broadening mechanism.

Journal Article↗

Enhancer regions of ovine interferon-tau gene that confer PMA response or cell type specific transcription.

Interferon-tau (IFNtau), produced by the trophectoderm of peri-implantation conceptuses in ruminant ungulates, attenuates the uterine production of a luteolytic factor, prostaglandin F(2alpha), resulting in the maintenance of corpus luteum function. However, molecular mechanisms regulating the temporal/spatial expression of IFNtau gene are not clearly understood. The 5'-upstream region of the sheep IFNtau (oIFNtau) gene was examined for its transcriptional regulation in two different cell types; JEG3 cells supported the transactivation of oIFNtau-reporter construct, but HeLa cells did not. In a heterologous SV40 enhancer-oIFNtau promoter or oIFNtau enhancer-SV40 promoter systems, elements required for such cell specific transactivation were localized between -654 and -555 bases, the enhancer, but not the basal promoter region of the oIFNtau gene. In these combinations, high degrees of transactivation were observed in JEG3 cells and the activity was further enhanced by the addition of phorbol 12-myristate 13-acetate (PMA), while those responses were absent in HeLa cells. To identify nucleotide sequences responsible for cell specific expression, transient transfection studies with sequential point mutations in the enhancer elements were executed. Transactivation of oIFNtau enhancer-reporter constructs was primarily regulated by three regions containing AP-1 site, GATA like sequence and site(s) unidentified. In gel mobility shift assays (GMSAs), the AP-1 site located in the enhancer region was recognized by nuclear extracts from both cell types. However, one of the GMSA probes containing GATA-like sequence exhibited different DNA-protein complex patterns in JEG3 and HeLa cells. Observations, in which the same upstream sequence behaved differently due possibly to kinds of nuclear factors available in these cell lines, suggest that such a sequence may be involved in cell specific transactivation of the oIFNtau gene. Furthermore, the same enhancer sequences were also recognized by nuclear extracts from sheep trophoblasts, suggesting that the enhancer sequences between -654 and -555 bases of oIFNtau gene may be functioning in vivo.

Animals↗

Methanoculleus chikugoensis sp. nov., a novel methanogenic archaeon isolated from paddy field soil in Japan, and DNA-DNA hybridization among Methanoculleus species.

A strictly anaerobic, irregularly coccoid, methanogenic archaeon, strain MG62T (= JCM 10825T = DSM 13459T), was isolated from paddy field soil in Chikugo, Fukuoka, Japan. The cells stained gram-negative, were 1.0-2.0 microm in diameter, were lysed by SDS and hypotonic solutions and were flagellated. Motility was not observed. The strain was able to use H2/CO2, 2-propanol/CO2, formate, 2-butanol/CO2 and cyclopentanol/CO2 as substrates for methanogenesis, but did not utilize acetate, ethanol, methanol or methylamines. The optimum temperature and pH were 25-30 degrees C and 6.7-7.2. Analysis of lipid component parts (core lipids, phospholipid polar head groups and glycolipid sugar moieties) showed the characteristic pattern of members of the family Methanomicrobiaceae except for the absence of glucose as a glycolipid sugar moiety. The G+C content of the DNA was 62.2 mol %. Sequence analysis of the 16S rDNA revealed that the strain belonged to the genus Methanoculleus. The strain had DNA-DNA hybridization values of less than 50% with type strains of Methanoculleus species. On the basis of phenotypic, genotypic and phylogenetic characteristics, the name Methanoculleus chikugoensis sp. nov. is proposed for strain MG62T (= JCM 10825T = DSM 13459T). The DNA hybridization study also revealed the close relationships of three species, Methanoculleus olentangyi, Methanoculleus bourgensis and Methanoculleus oldenburgensis, among Methanoculleus species.

Base Composition↗

An essential role for NF-kappa B in IL-18-induced IFN-gamma expression in KG-1 cells.

IL-18 is a multifunctional cytokine playing various regulatory roles in the immune system including induced cytokine production. As a part of our ongoing studies on the molecular mechanisms of IL-18-induced IFN-gamma production, we have examined the transcriptional regulation of the IFN-gamma gene by IL-18 in a human myelomonocytic cell line, KG-1. On the basis of DNA/protein binding, we have determined an IL-18-inducible NF-kappa B binding site located at -786 to -776 of the IFN-gamma gene regulatory region (designated KBBsite). Transient transfection of promoter-reporter gene constructs revealed that the KBBsite is required for full IL-18-induced activation of the IFN-gamma gene transcription induced by IL-18. In addition, stable transformants of a dominant-negative form of the I kappa B alpha showed an inhibition of IL-18-dependent I kappa B alpha degradation, NF-kappa B activation, and expression of IFN-gamma. These results are the first to show the actual significance of the NF-kappa B pathway in the regulation of IFN-gamma gene expression by IL-18.

Binding Sites↗

A selective increase in circulating inhibin and inhibin pro-alphaC at the time of ovulation in the mare.

The relationship between a selective increase in circulating immunoreactive (ir)-inhibin and the time of ovulation was investigated in mares. Concentrations of plasma ir-inhibin were measured every 4 h during the periovulatory period. Inhibin pro-alphaC, a precursor protein of the inhibin alpha-subunit, was also measured. The changes in ir-inhibin and inhibin pro-alphaC in circulation were parallel. Concentrations of both ir-inhibin and inhibin pro-alphaC in the plasma increased at the same time when ovulatory follicles ruptured, and the peak levels of circulating ir-inhibin and inhibin pro-alphaC were maintained for 4-8 h. There was no selective increase in plasma concentrations of estradiol-17beta during the process of ovulation. These results suggest that the selective increase in ir-inhibin and inhibin pro-alphaC was caused by the absorption of follicular fluid after the rupture of ovulatory follicles. These results also suggest that the measuring of plasma concentrations of ir-inhibin or inhibin pro-alphaC in mares might be a useful method for detecting the time of ovulation.

Animals↗

[Splenic lymphoma with villous lymphocytes expressing chromosomal abnormalities].

An 88-year-old Japanese woman with splenomegaly, but without lymphadenopathy, was admitted because of epigastric distress. Laboratory data disclosed an RBC of 310 x 10(4)/microliter, Hb of 10.1 g/dl, Ht of 30.6%, Plt count of 9.8 x 10(4)/microliter, and WBC of 4,470/microliter with 38% abnormal lymphocytes. Peripheral blood films revealed lymphocytes with thin, short cytoplasmic villi, condensed nuclear chromatin, and small nucleoli. The lymphocytes stained negative for tartrate-resistant acid phosphatase. Also, immunophenotyping was positive for expression of the cell surface markers CD19, CD20, IgG, kappa and HLA-DR, but not for CD5, CD10, CD11c, CD23, CD25, CD38, or CD103 antigens. Chromosomal analysis of peripheral blood cells disclosed the 46, XX, del(7), (q32) aberration. A splenectomy was performed simultaneously with partial colon resection because of a mucinous carcinoma found in the transverse colon. Histologic examination of resected spleen tissues revealed a distinctive pattern of white pulp infiltration by lymphoma cells. The histologic findings and clinical data were consistent with the features of splenic lymphoma with circulating villous lymphocytes. Our patient exhibited a relatively benign clinical course, and was being followed on an outpatient basis with no additional therapy.

Aged↗

Establishment of the cells useful for murine interleukin-18 bioassay by introducing murine interleukin-18 receptor cDNA into human myelomonocytic KG-1 cells.

We genetically engineered human myelomonocytic KG-I cells by introducing cDNA of murine interleukin-18 receptor (MuIL-18R) and established human cells which were capable of responding to MuIL-18. These cells expressed larger number of MuIL-18R (> 13,000 sites/cell) than intrinsic human IL-18 receptor (HuIL-18R) (< 2,500 sites/cell). And the cells responded to MuIL-18 as well as to HuIL-18 in a dose-dependent manner, and produced large amounts of interferon-gamma (IFN-gamma). We could estimate the amount of murine IL-18 based on the amounts of IFN-gamma produced by these cells. The stoichiometry was observed up to 150 ng/ml of MuIL-18. By using these cells, a large amount of MuIL-18 (448 +/- 89.2 ng/ml) was detected in sera of Propionibacterium acnes (P. acnes)/lipopolysaccharide (LPS)-treated endotoxic mice (the same conditions in which IL-18 was first identified). These cells provide us with a useful tool for determining the bioactivity of MuIL-18.

Animals↗

Identification of genes affecting lycopene formation in Escherichia coli transformed with carotenoid biosynthetic genes: candidates for early genes in isoprenoid biosynthesis.

Although isopentenyl diphosphate is a precursor of isoprenoids in Escherichia coli, the genes and enzymes involved in its biosynthesis have not been identified. Thus, we tried to isolate E. coli mutants deficient in the biosynthesis and their complementary genes by use of an artificial phenotypic screening system employing three carotenoid biosynthetic genes, crtE, crtB, and crtI. Cells were mutagenized with ethylmethanesulfonate, then transformed with a plasmid for expression of the carotenogenic genes. Mutants deficient in biosynthesis of isopentenyl diphosphate were expected to form white colonies, because they are unable to produce enough lycopene, whereas wild-type cells form red colonies. Among large numbers of red colonies, we identified 117 white colonies. Next, we transformed each mutant with an E. coli genomic library. Twenty-nine complementary genes that restore red color of host colonies were isolated. A homology search and further complementation study using subcloned genes revealed that the true complementary genes encode isopentenyl diphosphate isomerase, subunits of ATP synthase, enzymes of the Krebs cycle, some aldehyde dehydrogenases, phosphate acetyltransferase, and enzymes which relate to the biosynthesis of ubiquinones and menaquinones. Two unknown genes were also found, designated elb1 and 2, which may be involved in the early steps of isoprenoid biosynthesis.

Carotenoids↗

Inhibin secretion in the mare: localization of inhibin alpha, betaA, and betaB subunits in the ovary.

To determine the source of circulating inhibin and estradiol-17beta during the estrous cycle in mares, the cellular localization of the inhibin alpha, betaA, and betaB subunits and aromatase in the ovary was determined by immunohistochemistry. Concentrations of immunoreactive (ir-) inhibin, estradiol-17beta, progesterone, LH, and FSH in peripheral blood were also measured during the estrous cycle in mares. Immunohistochemically, inhibin alpha subunits were localized in the granulosa cells of small and large follicles and in the theca interna cells of large follicles, whereas inhibin betaA and betaB subunits were localized in the granulosa cells and in the theca interna cells of large follicles. On the other hand, aromatase was restricted to only the granulosa cells of large follicles. Plasma ir-inhibin concentrations began to increase 9 days before ovulation; they remained high until 2 days before ovulation, after which they decreased when the LH surge was initiated. Thereafter, a further sharp rise in circulating ir-inhibin concentrations occurred during the process of ovulation, followed by a second abrupt decline. After the decline, plasma concentrations of ir-inhibin remained low during the luteal phase. Plasma estradiol-17beta concentrations followed a profile similar to that of ir-inhibin, except during ovulation, and these two hormones were positively correlated throughout the estrous cycle. Plasma FSH concentrations were inversely related to ir-inhibin and estradiol-17beta. These findings suggest that the dimeric inhibin is mainly secreted by the granulosa cells and the theca cells of large follicles; granulosa cells of small follicles may secrete inhibin alpha subunit, and estradiol-17beta is secreted by the granulosa cells of only large follicles in mares.

Animals↗

Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine, which is a potent inducer of IFN-gamma production and plays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-human IL-18 monoclonal antibodies and characterized them. 7 murine anti-human IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2/0 myeloma cells. These antibodies were classified into 4 groups according to competitive binding ELISAs to the human IL-18 molecule. 1 murine mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-18. A specific human IL-18 ELISA was developed using two neutralizing mAbs (#125-2H and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-denatured human IL-18. The ELISA does not show any cross-reactivity with other cytokines. Using this assay, human IL-18 was measurable in the plasma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 producing cells.

Adult↗