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Volume 37 (2016)
- Issue 6 Pages 329-
- Issue 5 Pages 271-
- Issue 4 Pages 221-
- Issue 3 Pages 167-
- Issue 2 Pages 77-
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Volume 37, Issue 2
Displaying 1-9 of 9 articles from this issue
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Full Papers
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Hideaki HIRAI, Tadashi YOSHIZAWA, Satoko MOROHASHI, Toshihiro HAGA, Yu ...2016 Volume 37 Issue 2 Pages 77-84
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSPoorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients’ prognosis.View full abstractDownload PDF (5400K) -
Mitsuhiko YOSHIDA, Eun Young LEE, Takashi KOHNO, Tomoaki TANAKA, Masar ...2016 Volume 37 Issue 2 Pages 85-93
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSGlucose-6-phosphatase (G6Pase) is a key regulator of gluconeogenesis. We previously found that administration of glycerol, a substrate for gluconeogenesis, transactivates G6Pase in the mouse liver. To clarify its cell-autonomous transcriptional activation in hepatocytes, we examined the mechanism of expression of the gene G6pc, which encodes G6Pase, in rat hepatoma cell line FAO cells. Endogenous G6pc expression in FAO cells was increased by glycerol administration as well as by the fatty acid oleate. Luciferase reporter assay revealed that the ~2.0 kb mouse G6pc promoter contains the element(s) responsible for glycerol-stimulated G6pc transactivation. Using several deletion- or chimeric-constructs of G6pc promoter, we found that the DNA response element for hepatocyte nuclear factor 4α (HNF4α) (−77/−65) in the G6pc promoter is essential for transactivation by glycerol. Similarly to glycerol, oleate also increased G6pc expression through its action on the HNF4α element (−77/−65). Furthermore, the reporter activities were higher in the cells co-treated with glycerol plus oleate than in those singly treated with glycerol or oleate. In addition, the temporal profiles of G6pc expression differed between glycerol and oleate administration. Our present results suggest that glycerol and oleate induce G6pc expression both via the HNF4αelement (−77/−65) and also through other regulatory mechanisms.View full abstractDownload PDF (757K) -
Mitsunari NAKAJIMA, Minetaro OGAWA, Yoshiaki AMAKURA, Morio YOSHIMURA, ...2016 Volume 37 Issue 2 Pages 95-99
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSIn our previous studies, we reported anti-inflammatory functions of 3,5,6,7,8,3’,4’-heptamethoxyflavone (HMF), which is a polymethoxyflavone rich in various citrus fruits. Here, we investigated the immunomodulatory function of HMF in mice. HMF administration (50 mg/kg, i.p., 2 times/week) tended to reduce the production of antigen-specific IgE induced by ovalbumin in combination with aluminum hydroxide gel. Fluorescence-activated cell sorting analysis revealed the reduction of interleukin-4+CD4+ spleen cells and sustained presence of interferon-γ+CD4+ spleen cells in mice administered HMF, whereas the ratio of CD4+CD8− versus CD4−CD8+ spleen cells was not affected. Interleukin-4 release from CD3/CD28-stimulated spleen cells of mice administered HMF was reduced, whereas interferon-γ release was not affected. These results suggest that HMF has an immunomodulatory function via reduced interleukin-4 expression.View full abstractDownload PDF (889K) -
Masatoshi OKUBO, Yoh-ichi SATOH, Masato HIRAKAWA, Kana SASAKI, Kazuki ...2016 Volume 37 Issue 2 Pages 101-115
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESS5-hydroxytriptamine (5-HT: serotonin) is an important transmitter that causes vessel constriction, although few studies have examined the effect of 5-HT on venous smooth muscles. The intracellular Ca2+ concentration ([Ca2+]i) plays an essential role in stimulus-response coupling in numerous tissue/cells including vascular smooth muscle cells. The present study was performed to examine whether differences between arteries and veins in the response to 5-HT can be detected under confocal microscope with respect to [Ca2+]i dynamics. In posterior ciliary arteries of rats, 5-HT induced a [Ca2+]i increase. The 5-HT-induced responses were caused by both Ca2+ influx and mobilization. Agonist and antagonist experiments revealed that arterial smooth muscles possess 5-HT1a, 1b, 2 (Gprotein-coupled type) and 5-HT3 (ion channel type) receptors, and that 5-HT2 in particular plays a major role in these responses. For vorticose veins, the 5-HT-induced responses were also caused by both Ca2+ influx and mobilization. However, the cAMP dependent pathway (5-HT4-7) was found to be significant in vasocontraction with respect to 5-HT in these vessels. Thus, Ca2+ mobilization was induced by 5-HT2 and 5-HT4-7 in a vessel-dependent manner, whereas Ca2+ influx universally was induced by 5-HT3. These results indicate that the posterior ciliary arteries and vorticose veins in the same tissue might differ greatly in their responses to stimulus.View full abstractDownload PDF (3420K) -
Mika IKEGAME, Yoshiaki TABUCHI, Yukihiro FURUSAWA, Mariko KAWAI, Atsuh ...2016 Volume 37 Issue 2 Pages 117-126
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSMechanical stress promotes osteoblast proliferation and differentiation from mesenchymal stem cells (MSCs). Although numerous growth factors and cytokines are known to regulate this process, information regarding the differentiation of mechanically stimulated osteoblasts from MSCs in in vivo microenvironment is limited. To determine the significant factors involved in this process, we performed a global analysis of differentially expressed genes, in response to tensile stress, in the mouse cranial suture wherein osteoblasts differentiate from MSCs. We found that the gene expression levels of several components involved in bone morphogenetic protein, Wnt, and epithelial growth factor signalings were elevated with tensile stress. Moreover gene expression of some extracellular matrices (ECMs), such as cysteine rich protein 61 (Cyr61)/CCN1 and galectin-9, were upregulated. These ECMs have the ability to modulate the activities of cytokines and are known as matricellular proteins. Cyr61/CCN1 expression was prominently increased in the fibroblastic cells and preosteoblasts in the suture. Thus, for the first time we demonstrated the mechanical stimulation of Cyr61/CCN1 expression in osteogenic cells in an ex vivo system. These results suggest the importance of matricellular proteins along with the cytokine-mediated signaling for the mechanical regulation of MSC proliferation and differentiation into osteoblastic cell lineage in vivo.View full abstractDownload PDF (1939K) -
Saori YOSHIDA, Toshiyuki FUKUTOMI, Toru KIMURA, Hiroyuki SAKURAI, Ryo ...2016 Volume 37 Issue 2 Pages 127-139
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSEzrin is an actin binding protein which cross-links membrane proteins with cytoskeleton directly or indirectly via PDZ domain-containing scaffold proteins. It is mainly expressed at the brush border membrane (BBM) of gastrointestinal tracts, and is involved in the construction of microvilli structure and the functional expression of membrane protein complexes at the cell surface. To precisely study the roles of ezrin on the expression of membrane proteins at the cell surface, here we prepared the BBM fractions of ileums from the wild-type and ezrin-knockdown (Vil2kd/kd) mice, analyzed them by mass spectrometry, and compared their proteomic patterns. Totally 313 proteins were identified in the BBM fractions. Several transport proteins, cytoskeleton-associated proteins, and trafficking proteins were up- or down-regulated in the BBM fraction of the ileum in the Vil2kd/kd mice. Among them, the expressions of i) Na+/H+ exchanger regulatory factor 1 (a PDZ domain-containing scaffold protein), ii) sodium monocarboxylate transporter 1, which contains a PDZ domain-binding motif at their carboxy-terminal, and iii) chloride intracellular channel protein 5 were down-regulated at the BBM fraction of the ileum in the Vil2kd/kd mice, suggesting that ezrin is involved in their expression in the BBM.View full abstractDownload PDF (2909K) -
Zhusheng LIU, Tomomaya YAMAMOTO, Tomoka HASEGAWA, Hiromi HONGO, Kanako ...2016 Volume 37 Issue 2 Pages 141-151
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSWe employed a well-standardized murine rib fracture model to assess the distribution, in the cortical bone, of three important osteocyte-derived molecules—dentine matrix protein 1 (DMP1), sclerostin and fibroblast growth factor 23 (FGF 23). Two days after the fracture, the periosteum thickened, and up to the seventh day post-fracture, the cortical surfaces were promoting neoformation of two tissue types depending on the distance from the fracture site: chondrogenesis was taking place near the fracture, and osteogenesis distant from it. The cortical bones supporting chondrogenesis featured several empty lacunae, while in the ones underlying newly-formed woven bone, empty lacunae were hardly seen. DMP1-immunopositive osteocytic lacunae and canaliculi were seen both close and away from the fracture. In contrast, the region close to the fracture had only few sclerostin- and FGF23-immunoreactive osteocytes, whereas the distant region revealed many osteocytes immunopositive for these markers. Mature cortical bone encompassing the native cortical bone was observed at two-, three- and four-weeks post-fracture, and the distribution of DMP1, sclerostin and FGF23 appeared to have returned to normal. In summary, early stages of fracture healing seem to be important for triggering chondrogenesis and osteogenesis that may be regulated by osteocytes via their secretory molecules.View full abstractDownload PDF (4529K) -
Yoshie YAMAGUCHI, Katsunori YAMAMOTO, Yoshinori SATO, Shinjiro INOUE, ...2016 Volume 37 Issue 2 Pages 153-159
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSPlacental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.View full abstractDownload PDF (916K)
Communication
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Motoko TAKAHASHI, Kozo TANAKA, Toshifumi WAKAI, Toru HIROTA2016 Volume 37 Issue 2 Pages 161-165
Published: April 01, 2016
Released on J-STAGE: April 23, 2016
JOURNAL FREE ACCESSProtein phosphorylation is the prime post-translational modification to drive cell division. Identification of phosphorylated proteins and their related kinases has uncovered molecular networks underlying mitotic processes, including chromosome assembly. Here we aimed to identify phosphoproteins from a mitotic chromosome-enriched lysate biochemically using mass spectrometry. We employed the Polo-box domain (PBD) of Polo-like kinase to tether phosphorylated proteins in the lysate. Resulting candidates included a number of chromosomal proteins that would not be identified unless using chromosome-enriched fractions. Among them, we focused to a chromokinesin KIF4A which becomes concentrated along the longitudinal axis of mitotic condensed chromatids. We found that KIF4A is phosphorylated specifically during mitosis, depending on the activity of Cdk1 and Aurora B, which turned out to be required for KIF4A to interact with condensin I. The molecular link between KIF4A and condensin raises an interesting possibility that the interaction of two distantly related ATPases is triggered by mitotic phosphorylation.View full abstractDownload PDF (1056K)
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