Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
34 巻, 2 号
April
選択された号の論文の7件中1~7を表示しています
Full Papers
  • Masataka KITADATE, Toshishige SHIBAMOTO, Mikihiro TSUTSUMI, Hisao TONA ...
    2013 年 34 巻 2 号 p. 61-68
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    Hepatic venoconstriction occurs in rat anaphylactic hypotension. However, the exact venoconstrictive site remains unknown, and we therefore attempted to determine its location by using hepatic venography and histology. Anaphylaxis was induced in anesthetized Sprague-Dawley rats by i.v. administration of ovalbumin antigen. Venography of the portal vein (n = 8) was obtained at baseline and maximal hepatic venoconstriction. We separately examined photomicrographs of the liver sections. Along with systemic hypotension, portal venous pressure increased to a peak of 28 ± 3 cm- H2O at 2 min after antigen injection. Post-antigen portal venography revealed that 40% of portal venuls (76 vessels/total 188 vessels) with diameters from 160 to 300 μm were not visualized, suggesting that stenosis or obliteration occurred distally. The corresponding upstream portal vessels exhibited markedly bulging. Stenosis was also observed in some portal branches with diameters from 180 to 420 μm (9%; 17 vessels/total 188 vessels). Light microscopically, most portal venules with an estimated baseline diameter less than 110 μm showed stenosis, but statistically significant stenosis was found in those with baseline diameters of 20-70 μm. In conclusion, anaphylactic hepatic venoconstriction occurs over a wide range of portal veins with diameters less than 420 μm, and occurs markedly in portal venules with diameters less than 70 μm in anesthetized rats.
  • Toshiharu WAGURI, Toshinao GODA, Nobuhiko KASEZAWA, Kimiko YAMAKAWA-KO ...
    2013 年 34 巻 2 号 p. 69-74
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    Obesity is a complex multifactorial disorder resulting from the action and interaction of many genetic factors and environmental factors. Recently, it has become clear that inflammation is a key feature of obesity. Long-chain ω-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects, and the G protein-coupled receptor GPR120 was reported to mediate the anti-inflammatory effects of ω-3 PUFAs. In addition, it was reported that GPR120 is involved in the development of obesity in mice and humans. In this study, we investigated whether common genetic variants of the GPR120 gene could influence the risk of obesity in a Japanese population. Our data suggest that the combination of common genetic variations in the GPR120 gene and dietary fat intake is a possible determinant of body mass index.
  • Jianmin LI, Hiroshi SASAKI, Hiroki FUJIWARA, Hiroshi KATO, Kenya KANEK ...
    2013 年 34 巻 2 号 p. 75-85
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    We studied the synaptic plasticity of hippocampal CA1 neurons and spatial learning behavior in gerbils that had been loaded with a transient cerebral ischemia caused by 5 min or 10 min occlusion of the bilateral carotid arteries. The stimulus threshold to elicit the field responses after a transient cerebral ischemia was not different from that in controls, but there was a significant decrease in the magnitude of synaptic responses, which might result from the observed loss of neurons. Long-term potentiation (LTP) and depotentiation after a 10 min cerebral ischemia expressed as a percentage of the pre-tetanus or pre-low frequency stimulation value were almost the same as those in controls, although the actual magnitude of the LTP and depotentiation was lower than in controls. Gerbils that were loaded with a 10 min cerebral ischemia showed impairment in a spatial learning test when this was started 10 days after the cerebral ischemia, but not when it was started 20 days after the same cerebral ischemia. These results suggest that the changes in electrophysiological properties of hippocampal CA1 neurons seen at 10 days after a 10 min cerebral ischemia contribute to the impairment of spatial learning of gerbils seen at this time, and that the extra-CA1 regions might be involved in the recovery of spatial learning seen at 20 days after cerebral ischemia.
  • Shinnosuke YONAIYAMA, Yoshikazu TOYOKI, Satoko MOROHASHI, Shingo SAKUR ...
    2013 年 34 巻 2 号 p. 87-95
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas exhibit a wide range of histopathological variation. Epithelial cell adhesion molecule (EpCAM) is a 40 kDa type I membrane protein that is known to be highly expressed in epithelial carcinomas. In this study, we examined immunohistochemical expression of EpCAM in the pancreatic IPMNs in order to clarify its clinicopathological significance. We analyzed 51 cases of surgically resected IPMNs: 32 cases of adenoma; 6 cases of non-invasive carcinoma; 8 cases of minimally invasive carcinoma; and 5 cases of invasive carcinoma. Additionally, these 51 cases were classified into four phenotypes (gastric, intestinal, pancreatobiliary and oncocytic). EpCAM overexpression was found in 16 (31.4%) of the tumor samples. We found five predictive factors of malignancy using the univariate analysis as follows; serum CA19-9 level, main pancreatic duct diameter, presence of mural nodule, phenotype and EpCAM overexpression. In the multivariate analysis, only EpCAM overexpression was identified to be independently associated as a predictive factor for malignancy (odds ratio, 11.039; 95% confidence interval, 1.877-64.919; P-value, 0.008). Our study is the first report to demonstrate that EpCAM overexpression is an independent factor for malignancy; therefore, EpCAM overexpression is thought to be a novel predictor of malignant IPMNs.
  • Yoshiyuki KURODA, Kosuke KASAI, Naoki NANASHIMA, Hiroyuki NOZAKA, Mana ...
    2013 年 34 巻 2 号 p. 97-103
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    The effect of 4-methylumbelliferone (MU), a hyaluronan synthase-suppressor, on O-linked β-Nacetylglucosaminylation (O-GlcNAcylation) was investigated in cultured human skin fibroblasts, and we found that MU stimulated O-GlcNAcylation of the cellular proteins. Since O-GlcNAcylation affects protein phosphorylation via Ser/Thr kinases, we examined the effect of MU on both the phosphorylation of hyaluronan synthase 2 (HAS2) and hyaluronan production. The cells were cultured in the presence or absence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and MU independently or in combination. The protein fraction of each cell culture was extracted and divided into 2 parts-phosphorylated and non-phosphorylated fractions-by immobilized metal-affinity chromatography. The hyaluronan level in the medium was determined by an ELISA-like assay. Addition of MU decreased the level of hyaluronan in the medium and that of HAS2 in the phosphorylated protein fraction. On the contrary, the addition of TPA increased the levels of both of them. Interestingly, the combination of TPA and MU lowered the levels of them in treated cells as compared to those in untreated control cells. These results suggest that TPA activated protein kinase C (PKC), which stimulates the phosphorylation of HAS2, and increased hyaluronan production. Further, MU may inhibit the phosphorylation of HAS2 by PKC through the stimulation of O-GlcNAcylation.
  • Soh KATSUYAMA, Kazuma SATO, Tomomi YAGI, Yukinaga KISHIKAWA, Hitoshi N ...
    2013 年 34 巻 2 号 p. 105-111
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it frequently causes peripheral neuropathy. Milnacipran, a serotonin/noradrenaline reuptake inhibitor and fluvoxamine, a selective serotonin reuptake inhibitor, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of paclitaxel-induced mechanical allodynia in mice by milnacipran and fluvoxamine. Paclitaxel was administered once per day (2 mg/kg, intraperitoneally (i.p.)) for 5 days to mice. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In paclitaxel-treated mice, mechanical allodynia was observed on days 3-15 of paclitaxel administration. A single administration of milnacipran (20 mg/kg, i.p.) or fluvoxamine (40 mg/kg, i.p.) had no effect on paclitaxel- induced mechanical allodynia. However, repeated administration of milnacipran (10, 20 mg/kg, once per day, i.p.) for 5 days significantly reduced paclitaxel-induced mechanical allodynia. In contrast, repeated fluvoxamine administration (40 mg/kg, once per day, i.p.) for 5 days resulted in a weak attenuation of paclitaxel-induced mechanical allodynia. These results suggest that chronic paclitaxel administration induces mechanical allodynia, and that repeated milnacipran administration may be an effective therapeutic approach for the treatment of neuropathic pain caused by paclitaxel treatment for cancer.
  • Yutaka MASUDA, Toshihiro SUGIYAMA
    2013 年 34 巻 2 号 p. 113-117
    発行日: 2013年
    公開日: 2013/04/16
    ジャーナル フリー
    Mouse memory impairment induced by repeated daily dosing of lipopolysaccharide from Escherichia coli 044 was investigated using a passive avoidance method. One dose of 25 mg/kg or 8 repeated daily doses of 2.5 mg/kg of the lipopolysaccharide impaired the memory of 6-week-old male ddY mice. The chemical structure of the lipopolysaccharide was polymannoses Galβ1-3GalNAc-lipid A. Humoral polymannose-lipid reactivity was not found in lipopolysaccharide or in control mice receiving repeated daily doses of physiological saline. Humoral glycolipid with Galβ1-3GalNAc reactivity was found in the mice repeatedly treated with the lipopolysaccharide but not in the control mice repeatedly treated with physiological saline. Intraperitoneal injection of the humoral glycolipid did not impair memory in the normal mice, but mice treated beforehand with the glycolipid showed memory impairment after a subsequent single injection of 2.5 mg/kg of the lipopolysaccharide. These findings suggest that the polymannose component of the lipopolysaccharide is closely associated with the memory impairment effect and that the humoral glycolipid is a subsidiary metabolite of the lipopolysaccharide.
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