Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
31 巻 , 5 号
選択された号の論文の8件中1~8を表示しています
Full Papers
  • Satoshi Hagiwara, Hideo Iwasaka, Hironori Koga, Akira Hasegawa, Kyousu ...
    2010 年 31 巻 5 号 p. 263-271
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    The dysregulated metabolism associated with diabetes mellitus (DM) impairs membrane trafficking events in the liver, including the process of autophagy, which is an essential ongoing cellular process that is highly regulated by nutrients, endocrine factors, and signaling pathways. Highmobility group box 1 (HMGB1) is a nuclear protein with a known role in systemic inflammation and the related various organ injuries. However, its relationship to autophagy is not well understood. The aim of this study was to investigate the effects of inflammation injury on autophagy in the liver in a rat model of DM. DM was induced in animals with streptozotocin, followed four weeks later by induction of inflammation by LPS injection. At 12 h after LPS administration, autophagy was assessed by immunohistochemistry and Western blot analysis of microtubuleassociated protein light chain 3 (LC3)-II, as well as transmission electron microscopy. Expression of HMGB1 was also examined by immunohistochemistry and Western blot analysis. Western blot analysis of liver tissue revealed that levels of LC3-II and HMGB1 protein increased in DM rats subjected to LPS-induced inflammation compared with non-DM rats. Autophagy was particularly enhanced in DM rats. Thus, autophagy might be related to progression to organ injury in patients with DM, and inflammation in these patients might be associated with over-induction of autophagy and increased HMGB1 expression.
  • Yuji Kasukawa, Naohisa Miyakoshi, Shigeto Maekawa, Koji Nozaka, Hideak ...
    2010 年 31 巻 5 号 p. 273-279
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    Vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall prevention are still unclear. The purpose of this study was to investigate the effects of alfacalcidol [1α(OH)D3] on muscle strength, muscle fatigue, and bone mineral density (BMD) in ovariectomized rats. Seven-month-old female Wistar rats were orally administered 1α(OH)D3 or its vehicle everyday for 4 weeks after ovariectomy (OVX) or sham operation. Calf muscle strength and fatigue were evaluated by electrical stimulation of the sciatic nerve under general anesthesia. 1α(OH)D3 administration significantly increased the maximum muscle strength in the sham-operated (P < 0.01) and the OVX (P < 0.01) groups compared to their respective control groups. However, 1α(OH)D3 administration did not significantly affect muscle fatigue in these groups. The BMD of the femur in the 1α(OH)D3-treated OVX group was significantly higher than that in the vehicle-treated OVX group (P = 0.04). These results suggested that 1α(OH)D3 increases muscle strength but does not affect muscle fatigue in this rat model. The effectiveness of activated vitamin D in preventing bone fractures may be partly owing to its effect on muscle strength in addition to its known effect on bone metabolism.
  • Akira Hozumi, Makoto Osaki, Kazutaka Sakamoto, Hisataka Goto, Tatsuya ...
    2010 年 31 巻 5 号 p. 281-286
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    Several studies have demonstrated the association of plasminogen activator inhibitor-1 (PAI-1) with osteonecrosis, but the underlying mechanism of osteonecrosis and its relationship with local PAI-1 is not clear. The objective of this study was to evaluate PAI-1 production by primary human bone marrow adipocytes and the effects of glucocorticoid administration. Bone marrow was obtained from 25 individuals during prosthetic insertion. Mature adipocytes were cultured for 24 h with or without dexamethasone. PAI-1, adiponectin, tumor necrosing factor-α (TNFα) expression were measured by latex photometric immunoassay or RT-PCR. Adiponectin, TNFα and PAI-1 were detected in all culture media. PAI-1 expression was significantly increased by treatment with 10-6 mol/L dexamethasone up to 24 h in protein and mRNA levels, while the levels of other adipokines did not change by dexamethasone. These results suggest that bone marrow adipocytes may play important roles for the development of glucocorticoid-induced osteonecrotic diseases by enhancing PAI-1 expression.
  • Tadashi Okabe, Chiyo Sato, Atsuhiro Sakamoto
    2010 年 31 巻 5 号 p. 287-292
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    Some reports have shown that electroconvulsive shock therapy (ECT) is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. We have previously shown that electroconvulsive shock (ECS) improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of these rats. In this study, we examined changes in the expression of NPY in the spinal cord of a CCI model. The rat model of CCI was established by ligating the left sciatic nerve. ECS was administered to the rats once daily for six days on days 7-12 after the operation using an electrical stimulator. RT-PCR was used to measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on the 14th day after the operation. NPY gene expression was decreased in the dorsal spinal cords after ECS; however, no differences in NPY expression were observed between the right and left side of dorsal spinal cords, suggesting that the effect of changes in NPY expression after ECS on the improvement of neuropathic pain is not directly related to the spinal cord, but mainly to the upper central nerves.
  • Ming-Yu Guo, Keitaro Satoh, Bing Qi, Takanori Narita, Osamu Katsumata- ...
    2010 年 31 巻 5 号 p. 293-299
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    In parotid acinar cells, the activation of β-adrenergic receptors induces the accumulation of intracellular cAMP, and consequently provokes the exocytotic release of amylase, a digestive enzyme. The cellular redox status plays a pivotal role in regulating various cellular functions. Cellular redox imbalance caused by the oxidation of cellular antioxidants, as a result of oxidative stress, induces significant biological damage. In this study, we examined the effects of diamide, a thioloxidizing reagent, on amylase release by rat parotid acinar cells. In cells treated with diamide, the formation of cAMP and the release of amylase induced by the β-agonist isoproterenol (IPR) were partially reduced. The inhibitory effect of diamide on the IPR-induced release of amylase could be abrogated by reduced glutathione or dithiothreitol. Diamide had no effect on the amylase release induced by forskolin, an adenylate cyclase activator, or by mastoparan, a heterotrimeric GTPbinding protein activator. In cells treated with diamide, the binding affinity for [3H]DHA, but not the number of binding sites, was reduced. These results suggest that β-adrenergic receptor function is reduced by thiol-oxidation, which inhibits amylase secretion by parotid acinar cells.
  • Einosuke Mizuta, Manabu Shirai, Keita Arakawa, Kyoko Hidaka, Junichiro ...
    2010 年 31 巻 5 号 p. 301-305
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    We investigated the distribution of T-type Ca2+ channel mRNAs in the mouse embryonic heart. Cav3.2, but not Cav3.1, was expressed in the E8.5 embryonic heart along with cardiac progenitor markers (Nkx2.5, Tbx5, Isl-1) and contractile proteins (alpha and beta MHC). In the E10.5 heart, the distribution of Cav3.1 mRNA was confirmed in the AV-canal and overlapped with that of MinK or Tbx2. Cav3.2 mRNA was observed not only in the AV-canal but also in the outflow tract, along with MinK and Isl-1, indicating the expression of Cav3.2 in the secondary heart field. Thus, Cav3.2 may contribute to the development of the outflow tract from the secondary heart field in the embryonic heart, whereas Cav3.1 may be involved in the development of the cardiac conduction-system together with Cav3.2.
  • Hideo Masuki, Minqi Li, Tomoka Hasegawa, Reiko Suzuki, Guo Ying, Liu Z ...
    2010 年 31 巻 5 号 p. 307-318
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    In order to define the osteocytic function in accelerated bone remodeling, we examined the distribution of the osteocytic lacunar-canalicular system (OLCS) and osteocyte-secreting molecules-dentin matrix protein (DMP) 1 and sclerostin-in the epiphyses and cortical bones of osteoprotegerin deficient (OPG-/-) mice. Silver impregnation visualized a well-arranged OLCS in the wild-type epiphyses and cortical bone, whereas OPG-/- mice had an irregular OLCS in the epiphyses, but well-arranged canaliculi in the cortical bone. DMP1-positive osteocytes were evenly distributed throughout the wild-type epiphyses and cortical bone, as well as the OPG-/- cortical bone. However, OPG-/- epiphyses revealed weak DMP1-immunoreactivity. Thus, osteocytes appear to synthesize more DMP1 as the OLCS becomes regular. In contrast, sclerostin-immunoreactivity was significantly diminished in the OPG-/- epiphyses and cortical bone. In OPG-/- epiphyses and cortical bone, triple staining demonstrated few sclerostin-positive osteocytes in the periphery of a thick cell layer of alkaline phosphatase-positive osteoblasts and many tartrate resistant acid phosphatasepositive osteoclasts. Summarizing, the regular distribution of OLCS may affect DMP1 synthesis, while the cellular activities of osteoclasts and osteoblasts rather than the regularity of OLCS may ultimately influence sclerostin synthesis.
  • Hiroyuki Harahashi, Tomoomi Odajima, Tsuneyuki Yamamoto, Masamitsu Kaw ...
    2010 年 31 巻 5 号 p. 319-328
    発行日: 2010年
    公開日: 2010/11/10
    ジャーナル フリー
    This study evaluates the effects of three kinds of periodontal surgery using statistical analyses of histological and immunohistochemical indices. Dehiscence defects were made on roots of maxillary teeth in monkeys. Surgically exposed roots were untreated, etched with EDTA, or treated with Emdogain® after EDTA etching. Paraffin sections were stained with hematoxylin and eosin or immunostained for bone sialoprotein (BSP) or osteopontin (OPN) and analysed using several indices. The relative length of regenerated cementum and of BSP/OPN-immunoreactive lines on dentin defect showed no differences among the three groups. Regenerated cementum area was larger in the etching-Emdogain group than in the etching group.The attached regenerated cementum in the untreated group was shorter than in the etching groups. Thickness of immunolabeling on detached cementum was larger than that on attached cementum in all of the groups. These findings suggest that etching reinforces the attachment of regenerated cementum, and that BSP and OPN are associated with the attachment, where they exercise strong adhesion within a certain level of thickness.
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