Hiroshi Tamura

Disruption of CXC Motif Chemokine Ligand-14 in Mice Ameliorates Obesity-induced Insulin Resistance

In obese individuals, white adipose tissue (WAT) is infiltrated by large numbers of macrophages, resulting in enhanced inflammatory responses that contribute to insulin resistance. Here we show that expression of the CXC motif chemokine ligand-14 (CXCL14), which targets tissue macrophages, is elevated in WAT of obese mice fed a high fat diet (HFD) compared with lean mice fed a regular diet. We found that HFD-fed CXCL14-deficient mice have impaired WAT macrophage mobilization and improved insulin responsiveness. Insulin-stimulated phosphorylation of Akt kinase in skeletal muscle was severely attenuated in HFD-fed CXCL14+/- mice but not in HFD-fed CXCL14-/- mice. The insulin-sensitive phenotype of CXCL14-/- mice after HFD feeding was prominent in female mice but not in male mice. HFD-fed CXCL14-/- mice were protected from hyperglycemia, hyperinsulinemia, and hypoadiponectinemia and did not exhibit increased levels of circulating retinol-binding protein-4 and increased expression of interleukin-6 in WAT. Transgenic overexpression of CXCL14 in skeletal muscle restored obesity-induced insulin resistance in CXCL14-/- mice. CXCL14 attenuated insulin-stimulated glucose uptake in cultured myocytes and to a lesser extent in cultured adipocytes. These results demonstrate that CXCL14 is a critical chemoattractant of WAT macrophages and a novel regulator of glucose metabolism that functions mainly in skeletal muscle.

Effect of potassium and phosphorus on the hydrogenation of CO over alumina-supported ruthenium catalyst

Abstract The effects of additives such as K, B, and P to Ru Al 2 O 3 catalysts were investigated with regard to the adsortion and the catalytic hydrogenation of CO. Thermal desorption of CO and infrared bands of CO adsorbed indicated that the addition of K increased the strength of CO adsorption, by enhancing the back-donation from Ru to CO. As for the catalytic hydrogenation of CO, the addition of K significantly increased the olefin/paraffin ratios in product hydrocarbons and suppressed the methane formation, while the catalytic activity decreased by the addition. On the other hand, the addition of P or B brought about opposite changes in both CO adsorption and CO hydrogenation. The relationships between the electronic state of Ru and the activity and selectivity for this reaction have been interpreted on the basis of the inhibiting effect of strongly adsorbed CO for the hydrogenation.

Cyclotron resonance of positive holes in AgBr

Abstract The first observation of cyclotron resonance of holes in AgBr is reported. Measurements have been made at 34 GHz and 1.7 K. It is shown that the energy surfaces for the hole polaron consist of a set of spheroids oriented along the [111] directions with the mass parameters m ∗ l = (1.71±0.06)m 0 and m ∗ t =(0.79±0.01)m 0 . The mobility of the hole polaron is determined to be about 1.5 × 10 5 cm 2 Vsec at 1.7 K.

Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM-CSF) during follicular growth and luteinization in gonadotropin-primed immature rodents

To obtain clues as to whether granulocyte-macrophage colony-stimulating factor (GM-CSF) is related to ovarian physiology, the sites, the gene expression and the production of GM-CSF in the ovary during follicular development and luteinization were studied in equine CG (eCG)-primed immature mice and rats. During follicular development, the expression of GM-CSF mRNA was localized in theca-interstitial tissues, oocytes and granulosa cells of small developing follicles in mice. In the mouse ovary after ovulation, luteal tissues as well as the above components had intense signals for GM-CSF mRNA. Mast cells, which were present mainly in the ovarian medulla, also expressed mRNA for GM-CSF in rats. Immunohistochemical analyses with two different antibodies against murine GM-CSF revealed that GM-CSF-like immunoreactivity was detectable mainly in theca-interstitial, luteal tissues, oocytes and mast cells. Intense GM-CSF positive cells in theca-interstitial and luteal tissues were stained with anti-CD11b antibody in mice. Messenger RNAs for GM-CSF receptor subunits were expressed in mast cells of the medulla and in luteal tissues in rat ovary. The levels of GM-CSF released into the culture media by rat ovarian dispersed cells 1-2 days after eCG treatment were higher than those before the treatment, although no significant change in the levels of ovarian GM-CSF mRNA was detected by reverse transcription-polymerase chain reaction analysis. The secretion of GM-CSF was also increased by treatment of the cells with immune stimulators such as phorbol ester, interleukin-1 and lipopolysaccharide. These data indicate that ovarian macrophages and mast cells in addition to theca-interstitial cells, synthesize and release GM-CSF during ovarian cycles, and that ovarian GM-CSF secreting capacity is enhanced during early stages of follicular development in rodents.

Cyclotron resonance of electrons and of holes in thallium chloride and in thallium bromide

Abstract Cyclotron resonance both of electrons and of holes has been studied in TlCl and in TlBr by the carrier-heating technique. The electron resonances are isotropic. The hole resonances are anisotropic with (1, 0, 0) or Δ-type symmetry, the longitudinal polaron effective mass being less than the transverse polaron effective mass.

In vivo differentiation of stem cells in the aorta-gonad-mesonephros region of mouse embryo and adult bone marrow.

OBJECTIVEnHematopoietic stem cells (HSCs) are thought to be generated from hemangioblasts, the common precursor cells for blood and endothelial cells, in the aorta-gonad-mesonephros (AGM) region of the mouse embryo. The genetic program of HSCs was recently demonstrated to be plastic, but the potential for AGM-region hemangioblasts to be transplanted and to differentiate in vivo has not been well described. Here we examined the fate of donor cells in mice transplanted with CD45(-) AGM cells, which presumably include hemangioblasts.nnnMATERIALS AND METHODSnCD45(-) cells in the AGM region of embryos at 11.5 days post coitum or CD45(+)CD34(-) side population (SP) of cells in adult bone marrow (BM) derived from enhanced green fluorescent protein transgenic mice were transplanted into the liver of busulfan-treated neonatal mice. Two to 6 months after injection of the cells, the contribution of donor-derived cells in the hematopoietic compartment and in various organs was analyzed by flow cytometry and confocal microscopy.nnnRESULTSnCD45(-) cells from the AGM region not only generated peripheral blood cells but also differentiated into endothelial and other nonhematopoietic cells in liver, kidney, lung, small intestine, and uterus in transplanted mice. A similar engrafting pattern was observed in the small intestine of mice transplanted with BM SP/CD45(+) cells, secondary BM-transplanted mice, and lethally irradiated adult mice that received intravenous injections of BM cells.nnnCONCLUSIONnA CD45(-) fraction of the AGM region and CD45(+) BM stem cells share the same in vivo potential to differentiate into hematopoietic, endothelial, smooth muscle, and stroma-like cells when transplanted in mice.

Long-term effects of peroxisome proliferators on the balance between hydrogen peroxide-generating and scavenging capacities in the liver of Fischer-344 rats

In order to clarify whether peroxisomal hydrogen peroxide (H2O2) plays an important role in peroxisome proliferator-induced hepatocarcinogenesis, we examined the change in metabolism of peroxisomal H2O2 in vivo and in vitro using male Fischer-344 rats fed clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP) for up to 78 weeks. Hepatic peroxisomal fatty acyl-CoA oxidase activity increased 12-20-fold after 2 or 4 weeks treatment; later this level gradually decreased toward controls, and at 78 weeks activity was 3-10-times of control. Although hepatic H2O2 levels were increased slightly by clofibrate, bezafibrate and DEHP, the changes did not correlate with the changes in peroxisomal fatty acyl-CoA oxidase activity. In isolated hepatocytes, the rate of leakage of peroxisomal H2O2 from peroxisomes into the cytosol and the hepatocellular H2O2 content was measured. The rate of leakage of peroxisomal H2O2 into cytosol increased 2.5-4-fold when peroxisomal beta-oxidation activity was induced by peroxisome proliferators, and the increases in this rate corresponded with changes in the peroxisomal beta-oxidation activity. In contrast, the hepatocellular H2O2 contents were not affected by induced peroxisomal beta-oxidation. These data show that H2O2 leaking from peroxisome into cytosol would be quickly decomposed, and thus peroxisomal H2O2 does not appear to play an important role in hepatocarcinogenesis by such an oxidative stress mechanism after the long-term treatment with peroxisome proliferators.

INNOVATION AND CREATIVITY SUPPORT VIA CHANCE DISCOVERY, GENETIC ALGORITHMS, AND DATA MINING

Creativity protocols and methodologies tend to be time consuming if applied manually. This paper presents how information technologies can support innovation and creativity for collaborative scenario creation and discussion. The fusion of change discovery, genetics algorithms, data mining, and computer-supported collaborative tools provide computational models of innovation and creativity. The proposed technology allows groups of participants in a creative processes to have pervasive access to the analysis of the current scenario in real time. This paper introduces such innovation technologies gathered in the DISCUS project, and summarizes the usage of DISCUS on marketing research workshops.

Lack of induction of hepatic DNA damage on long-term administration of peroxisome proliferators in male F-344 rats

In order to evaluate the relationship between hydrogen peroxide (H2O2) generation and subsequent DNA damage caused by peroxisome proliferation, we examined DNA damage and changes in peroxisomal beta-oxidation activity in rat liver. Male F-344 rats were given orally clofibrate, bezafibrate or di(2-ethylhexyl)phthalate (DEHP) for up to 78 weeks. In rats fed DEHP for 52 or 78 weeks hepatocarcinomas or neoplastic nodules were found. In rats treated for 2 weeks with peroxisome proliferators, peroxisomal beta-oxidation activity was increased 10-17 times over control levels. After long-term treatment (20-78 weeks), the level of peroxisomal beta-oxidation activity remained 3-13-times higher in each group. When single strand DNA breaks were measured by a DNA-alkaline elution technique, no increase in DNA damage was observed in livers from rats fed peroxisome proliferators for 2, 40 or 78 weeks. In rats bearing hepatocarcinomas induced by DEHP, the hepatic DNA showed significant breaks; the rate of DNA-alkaline elution was found to increase approximately 5-fold. No significant increase in hepatic lipid peroxide level was observed in each group. These results show that although prolonged treatment with peroxisome proliferators induces markedly peroxisomal beta-oxidation activity, the active oxygen species from peroxisomal beta-oxidation are not enough to give rise to significant DNA damage. Moreover, the change in the activity of peroxisomal beta-oxidation may not relate to hepatocarcinogenesis induced by peroxisome proliferators.

Temperature dependence of polaron cyclotron resonance in AgBr

Abstract Cyclotron resonance of a polaron in AgBr is studied at 9.4 and 48 GHz over the temperature range 1.7–25K. The absorption peak is observed to shift with increasing temperature toward higher magnetic fields by (2.1 ± 0.6) per cent between 17 and 23 K. The energy dependence of the cyclotron mass of a polaron deduced from the experimental data is compared with theoretical predictions; reasonable agreement with Hagas theory is found.